Environmental Health Perspectives

About the journal

Publisher: ACS Publications
Published: 1972 to the present, United States
Language: English
ISSN: 0091-6765 (print), 1552-9924 (electronic)
Absorbed: EHP Toxicogenomics
Its record in the NLM Catalog

2020s

Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY). A. Olsson, L. Bouaoun, J. Schüz, et al. 2024;132(1):17005. PubMed · Publisher · Free full text

Abstract

Background: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents.

Objectives: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking.

Methods: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI).

Results: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8).

Discussion: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.
Invited Perspective: Eliminating Toxics to Prevent Disease: Asbestos Leads the Way. D. Kriebel, D.J. Myers. 2022;130(5):51305. Comment PubMed · Publisher · Free full text
The Ecological Association between Asbestos Consumption and Asbestos-Related Diseases 15 Years Later. E.M. Rath, M.L. Yuen, C.O. Odgerel, et al. 2022;130(5):57703. PubMed · Publisher · Free full text

Summary

This research letter updated the authors' 2007 international ecological analysis to see whether the associations between deaths from mesothelioma and asbestosis and historical asbestos consumption had changed. Deaths by sex and 5-year age group were taken from the WHO mortality database (ICD-10 codes C45.0 pleural mesothelioma, C45.1 peritoneal mesothelioma, C45 all mesothelioma, J61 asbestosis). They were age-standardized to the world standard population and averaged for 2010–2014. Asbestos consumption for 1970, 1975 and 1980 was taken from the U.S. Geological Survey and averaged. Log-transformed mortality rates were regressed on per-capita consumption. Slovenia was removed as an outlier because its consumption data were unreliable. The all-mesothelioma analyses covered 71 countries for men and 69 for women. Consumption was a highly significant predictor of all-mesothelioma mortality, with adjusted R2 of 0.39 for men and 0.30 for women (both p < 0.0001). Each 1 kg per capita increase in consumption was linked to a 2.4-fold (95% CI: 1.8, 3.0) increase in deaths in men and a 1.8-fold (95% CI: 1.4, 2.2) increase in women. Background rates were 0.56 and 0.35 deaths per million. Seven of eight disease–sex combinations showed significant positive associations; asbestosis in women did not. The authors concluded that the associations remained consistent with 2007, although somewhat reduced for mesothelioma, and that eliminating asbestos consumption must be a priority.

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2010s

Occupational Asbestos Exposure and Incidence of Colon and Rectal Cancers in French Men: The Asbestos-Related Diseases Cohort (ARDCo-Nut). C. Paris, I. Thaon, F. Hérin, et al. 2017;125(3):409-415. PubMed · Publisher · Free full text

Abstract

Background: The relationships between asbestos exposure and colorectal cancer remain controversial.

Objectives: We examined the association between asbestos exposure and colorectal cancer incidence.

Methods: Volunteer retired workers previously exposed to asbestos were invited to participate in the French ARDCo screening program between 2003 and 2005. Additional data on risk factors for colorectal cancer were collected from the ARDCo-Nut subsample of 3,769 participants in 2011. Cases of colon and rectal cancer were ascertained each year through 2014 based on eligibility for free medical care following a cancer diagnosis. Survival regression based on the Cox model was used to estimate the relative risk of colon and rectal cancer separately, in relation to the time since first exposure (TSFE) and cumulative exposure index (CEI) to asbestos, and with adjustment for smoking in the overall cohort and for smoking, and certain risk factors for these cancers in the ARDCo-Nut subsample.

Results: Mean follow-up was 10.2 years among 14,515 men, including 181 colon cancer and 62 rectal cancer cases (41 and 17, respectively, in the ARDCo-Nut subsample). In the overall cohort, after adjusting for smoking, colon cancer was significantly associated with cumulative exposure (HR = 1.14; 95% CI: 1.04, 1.26 for a 1-unit increase in ln-CEI) and ≥ 20-40 years since first exposure (HR = 4.67; 95% CI: 1.92, 11.46 vs. 0-20 years TSFE), and inversely associated with 60 years TSFE (HR = 0.26; 95% CI: 0.10, 0.70). Although rectal cancer was also associated with TSFE 20-40 years (HR = 4.57; 95% CI: 1.14, 18.27), it was not associated with ln-CEI, but these findings must be interpreted cautiously due to the small number of cases.

Conclusions: Our findings provide support for an association between occupational exposure to asbestos and colon cancer incidence in men. Citation: Paris C, Thaon I, Hérin F, Clin B, Lacourt A, Luc A, Coureau G, Brochard P, Chamming's S, Gislard A, Galan P, Hercberg S, Wild P, Pairon JC, Andujar P. 2017. Occupational asbestos exposure and incidence of colon and rectal cancers in French men: the Asbestos-Related Diseases Cohort (ARDCo-Nut). Environ Health Perspect 125:409-415; http://dx.doi.org/10.1289/EHP153.
Effects of Chrysotile Exposure in Human Bronchial Epithelial Cells: Insights into the Pathogenic Mechanisms of Asbestos-Related Diseases. G.R. Gulino, M. Polimeni, M. Prato, et al. 2016;124(6):776-84. PubMed · Publisher · Free full text

Abstract

Background: Chrysotile asbestos accounts for > 90% of the asbestos used worldwide, and exposure is associated with asbestosis (asbestos-related fibrosis) and other malignancies; however, the molecular mechanisms involved are not fully understood. A common pathogenic mechanism for these malignancies is represented by epithelial-mesenchymal transition (EMT), through which epithelial cells undergo a morphological transformation to assume a mesenchymal phenotype. In the present work, we propose that chrysotile asbestos induces EMT through a mechanism involving a signaling pathway mediated by tranforming growth factor beta (TGF-β).

Objectives: We investigated the role of chrysotile asbestos in inducing EMT in order to elucidate the molecular mechanisms involved in this event.

Methods: Human bronchial epithelial cells (BEAS-2B) were incubated with 1 μg/cm2 chrysotile asbestos for ≤ 72 hr, and several markers of EMT were investigated. Experiments with specific inhibitors for TGF-β, glycogen synthase kinase-3β (GSK-3β), and Akt were performed to confirm their involvement in asbestos-induced EMT. Real-time polymerase chain reaction (PCR), Western blotting, and gelatin zymography were performed to detect mRNA and protein level changes for these markers.

Results: Chrysotile asbestos activated a TGF-β-mediated signaling pathway, implicating the contributions of Akt, GSK-3β, and SNAIL-1. The activation of this pathway in BEAS-2B cells was associated with a decrease in epithelial markers (E-cadherin and β-catenin) and an increase in mesenchymal markers (α-smooth muscle actin, vimentin, metalloproteinases, and fibronectin).

Conclusions: Our findings suggest that chrysotile asbestos induces EMT, a common event in asbestos-related diseases, at least in part by eliciting the TGF-β-mediated Akt/GSK-3β/SNAIL-1 pathway.

Citation: Gulino GR, Polimeni M, Prato M, Gazzano E, Kopecka J, Colombatto S, Ghigo D, Aldieri E. 2016. Effects of chrysotile exposure in human bronchial epithelial cells: insights into the pathogenic mechanisms of asbestos-related diseases. Environ Health Perspect 124:776-784; http://dx.doi.org/10.1289/ehp.1409627.
Children's health in Latin America: the influence of environmental exposures. A. Laborde, F. Tomasina, F. Bianchi, et al. 2015;123(3):201-9. Review PubMed · Publisher · Free full text

Abstract

Background: Chronic diseases are increasing among children in Latin America.

Objective And Methods: To examine environmental risk factors for chronic disease in Latin American children and to develop a strategic initiative for control of these exposures, the World Health Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data.

Results: Industrial development and urbanization are proceeding rapidly in Latin America, and environmental pollution has become widespread. Environmental threats to children's health include traditional hazards such as indoor air pollution and drinking-water contamination; the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury, arsenic, and pesticides; hazardous and electronic waste; and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization, and socioeconomic forces.

Conclusions: To control environmental threats to children's health in Latin America, WHO, including PAHO, will focus on the most highly prevalent and serious hazards-indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children's environmental health (CEH), building a network of Collaborating Centres, promoting biomedical research in CEH, building regional capacity, supporting development of evidence-based prevention policies, studying the economic costs of chronic diseases in children, and developing platforms for dialogue with relevant stakeholders.
Current Research and Opportunities to Address Environmental Asbestos Exposures. D.J. Carlin, T.C. Larson, J.C. Pfau, et al. 2015;123(8):A194-7. PubMed · Publisher · Free full text

Abstract

Asbestos-related diseases continue to result in approximately 120,000 deaths every year in the United States and worldwide. Although extensive research has been conducted on health effects of occupational exposures to asbestos, many issues related to environmental asbestos exposures remain unresolved. For example, environmental asbestos exposures associated with a former mine in Libby, Montana, have resulted in high rates of nonoccupational asbestos-related disease. Additionally, other areas with naturally occurring asbestos deposits near communities in the United States and overseas are undergoing investigations to assess exposures and potential health risks. Some of the latest public health, epidemiological, and basic research findings were presented at a workshop on asbestos at the 2014 annual meeting of the Society of Toxicology in Phoenix, Arizona. The following focus areas were discussed: a) mechanisms resulting in fibrosis and/or tumor development; b) relative toxicity of different forms of asbestos and other hazardous elongated mineral particles (EMPs); c) proper dose metrics (e.g., mass, fiber number, or surface area of fibers) when interpreting asbestos toxicity; d) asbestos exposure to susceptible populations; and e) using toxicological findings for risk assessment and remediation efforts. The workshop also featured asbestos research supported by the National Institute of Environmental Health Sciences, the Agency for Toxic Substances and Disease Registry, and the U.S. Environmental Protection Agency. Better protection of individuals from asbestos-related health effects will require stimulation of new multidisciplinary research to further our understanding of what constitutes hazardous exposures and risk factors associated with toxicity of asbestos and other hazardous EMPs (e.g., nanomaterials).
The JPC-SE position statement on asbestos: a long-overdue appeal by epidemiologists to ban asbestos worldwide and end related global environmental injustice. W.K. Al-Delaimy. 2013;121(5):a144-5. Editorial PubMed · Publisher · Free full text
Importance of meta-analyses for evaluating carcinogens. M. Kogevinas, N. Pearce. 2012;120(4):A145; author reply A146-7. Letter · Comment PubMed · Publisher · Free full text
Mitochondria-derived reactive intermediate species mediate asbestos-induced genotoxicity and oxidative stress-responsive signaling pathways. S.X. Huang, M.A. Partridge, S.A. Ghandhi, et al. 2012;120(6):840-7. PubMed · Publisher · Free full text

Abstract

Background: The incidence of asbestos-induced human cancers is increasing worldwide, and considerable evidence suggests that reactive oxygen species (ROS) are important mediators of these diseases. Our previous studies suggested that mitochondria might be involved in the initiation of oxidative stress in asbestos-exposed mammalian cells.

Objective: We investigated whether mitochondria are a potential cytoplasmic target of asbestos using a mitochondrial DNA-depleted (ρ(0)) human small airway epithelial (SAE) cell model: ρ(0) SAE cells lack the capacity to produce mitochondrial ROS.

Methods: We examined nuclear DNA damage, micronuclei (MN), intracellular ROS production, and the expression of inflammation-related nuclear genes in both parental and ρ(0) SAE cells in response to asbestos treatment.

Results: Asbestos induced a dose-dependent increase in nuclear DNA oxidative damage and MN in SAE cells. Furthermore, there was a significant increase in intracellular oxidant production and activation of genes involved in nuclear factor κB and proinflammatory signaling pathways in SAE cells. In contrast, the effects of asbestos were minimal in ρ(0) SAE cells.

Conclusions: Mitochondria are a major cytoplasmic target of asbestos. Asbestos may initiate mitochondria-associated ROS, which mediate asbestos-induced nuclear mutagenic events and inflammatory signaling pathways in exposed cells. These data provide new insights into the molecular mechanisms of asbestos-induced genotoxicity.
Radiographic evidence of nonoccupational asbestos exposure from processing Libby vermiculite in Minneapolis, Minnesota. B.H. Alexander, K.K. Raleigh, J. Johnson, et al. 2012;120(1):44-9. PubMed · Publisher · Free full text

Abstract

Background: Community exposure to asbestos from contaminated vermiculite ore from Libby, Montana, occurred in many processing sites in the United States, including a densely populated urban residential neighborhood of Minneapolis, Minnesota.

Objective: We examined exposed community residents who never worked at the plant or never lived with a plant worker for radiographic evidence of lung changes consistent with asbestos exposure.

Methods: We obtained posteroanterior chest radiographs to identify the prevalence of pleural abnormalities consistent with pneumoconiosis, as determined by consensus of two National Institute for Occupational Safety and Health-certified B-reader radiologists. We estimated cumulative asbestos exposure (fibers per cubic centimeters × months) with air dispersion model data and activity-based modeled exposure estimates for vermiculite processing waste contact. We modeled associations between pleural abnormalities and asbestos exposure using multiple logistic regression to adjust for year of birth, sex, and potential occupational asbestos exposure.

Results: Radiographs were obtained for 461 participants. The prevalence of pleural abnormalities by B-reader consensus was 10.8%. A history of direct contact with the waste and ever playing in the waste piles was associated with pleural abnormalities {odds ratio [OR] 2.78 [95% confidence interval (CI): 1.26, 6.10] and 2.17 (95% CI: 0.99, 4.78), respectively, when adjusted for background exposure}. The regression coefficients for log-transformed measures (fibers per cubic centimeters × months) of background exposure and activity-based exposure were 0.322 (95% CI: 0.078, 0.567) and 0.063 (95% CI: -0.013, 0.139), respectively, when adjusted for each other, and 0.283 (95% CI: 0.104, 0.463) for cumulative exposure from all sources.

Conclusion: These results support the hypothesis that community exposure to asbestos-contaminated vermiculite originating from Libby, Montana, is associated with measurable effects based on radiographic evidence.
Subchronic pulmonary pathology, iron overload, and transcriptional activity after Libby amphibole exposure in rat models of cardiovascular disease. J.H. Shannahan, A. Nyska, M. Cesta, et al. 2012;120(1):85-91. PubMed · Publisher · Free full text

Abstract

Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species.

Objective: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be increasingly sensitive to Libby amphibole (LA)-induced subchronic lung injury.

Methods: Male healthy Wistar Kyoto (WKY), spontaneously hypertensive (SH), and SH heart failure (SHHF) rats were intratracheally instilled with 0.0, 0.25, or 1.0 mg LA (with saline as the vehicle). We examined bronchoalveolar lavage fluid (BALF) and histological lung sections after 1 week, 1 month, or 3 months for pulmonary biomarkers and pathology. SHHF rats were also assessed at 6 months for pathological changes.

Results: All animals developed concentration- and time-dependent interstitial fibrosis. Time-dependent Fe accumulation occurred in LA-laden macrophages in all strains but was exacerbated in SHHF rats. LA-exposed SHHF rats developed atypical hyperplastic lesions of bronchiolar epithelial cell origin at 3 and 6 months. Strain-related baseline differences existed in gene expression at 3 months, with persistent LA effects in WKY but not SH or SHHF rats. LA exposure altered genes for a number of pathways, including inflammation, immune regulation, and cell-cycle control. Cell-cycle control genes were inhibited after LA exposure in SH and SHHF but not WKY rats, whereas tumor suppressor genes were induced only in WKY rats. The inflammatory gene expression also was apparent only in WKY rats.

Conclusion: These data show that in Fe-overload conditions, progressive Fe accumulation occurs in fiber-laden macrophages within LA-induced lesions. Fe overload does not appear to contribute to chronic inflammation, and its role in hyperplastic lesion development requires further examination.
The traveling Libby legacy: Minnesota community exhibits nonoccupational health impacts consistent with asbestos damage. T. Tillett. 2012;120(1):A35. News · Comment PubMed · Publisher · Free full text
Use of meta-analyses by IARC Working Groups. K. Straif, L. Stayner, P.A. Demers, et al. 2012;120(9):A342-3. Letter · Comment PubMed · Publisher · Free full text
A meta-analysis of asbestos and lung cancer: is better quality exposure assessment associated with steeper slopes of the exposure-response relationships?. V. Lenters, R. Vermeulen, S. Dogger, et al. 2011;119(11):1547-55. Meta-analysis · Review PubMed · Publisher · Free full text

Abstract

Background: Asbestos is a well-recognized cause of lung cancer, but there is considerable between-study heterogeneity in the slope of the exposure-response relationship.

Objective: We considered the role of quality of the exposure assessment to potentially explain heterogeneity in exposure-response slope estimates.

Data Sources: We searched PubMed MEDLINE (1950-2009) for studies with quantitative estimates of cumulative asbestos exposure and lung cancer mortality and identified 19 original epidemiological studies. One was a population-based case-control study, and the others were industry-based cohort studies.

Data Extraction: Cumulative exposure categories and corresponding risks were abstracted. Exposure-response slopes [KL (lung cancer potency factor of asbestos)] were calculated using linear relative risk regression models.

Data Synthesis: We assessed the quality of five exposure assessment aspects of each study and conducted random effects univariate and multivariate meta-regressions. Heterogeneity in exposure-response relationships was greater than expected by chance (I2 = 64%). Stratification by exposure assessment characteristics revealed that studies with well-documented exposure assessment, larger contrast in exposure, greater coverage of the exposure history by exposure measurement data, and more complete job histories had higher meta-KL values than did studies without these characteristics. The latter two covariates were most strongly associated with the KL value. Meta-KL values increased when we incrementally restricted analyses to higher-quality studies.

Conclusions: This meta-analysis indicates that studies with higher-quality asbestos exposure assessment yield higher meta-estimates of the lung cancer risk per unit of exposure. Potency differences for predominantly chrysotile versus amphibole asbestos-exposed cohorts become difficult to ascertain when meta-analyses are restricted to studies with fewer exposure assessment limitations.
Global magnitude of reported and unreported mesothelioma. E.K. Park, K. Takahashi, T. Hoshuyama, et al. 2011;119(4):514-8. PubMed · Publisher · Free full text

Abstract

Background: Little is known about the global magnitude of mesothelioma. In particular, many developing countries, including some with extensive historical use of asbestos, do not report mesothelioma.

Objectives: We estimated the global magnitude of mesothelioma accounting for reported and unreported cases.

Methods: For all countries with available data on mesothelioma frequency and asbestos use (n=56), we calculated the 15-year cumulative number of mesotheliomas during 1994-2008 from data available for fewer years and assessed its relationship with levels of cumulative asbestos use during 1920-1970. We used this relationship to predict the number of unreported mesotheliomas in countries for which no information on mesothelioma is available but which have recorded asbestos use (n=33).

Results: Within the group of 56 countries with data on mesothelioma occurrence and asbestos use, the 15-year cumulative number of mesothelioma was approximately 174,300. There was a statistically significant positive linear relation between the log-transformed national cumulative mesothelioma numbers and the log-transformed cumulative asbestos use (adjusted R(2)=0.83, p<0.0001). Extrapolated to the group of 33 countries without reported mesothelioma, a total of approximately 38,900 (95% confidence interval, 36,700-41,100) mesothelioma cases were estimated to have occurred in the 15-year period (1994-2008).

Conclusions: We estimate conservatively that, globally, one mesothelioma case has been overlooked for every four to five reported cases. Because our estimation is based on asbestos use until 1970, the many countries that increased asbestos use since then should anticipate a higher disease burden in the immediate decades ahead.
Meeting report: mode(s) of action of asbestos and related mineral fibers. M.R. Gwinn, D. DeVoney, A.M. Jarabek, et al. 2011;119(12):1806-10. PubMed · Publisher · Free full text

Abstract

Background: Although asbestos in general is well known to cause a range of neoplastic and non-neoplastic human health effects, not all asbestos fiber types have the same disease-causing potential, and the mode of action (MOA) of specific types of asbestos and related fibers for various health outcomes are not well understood.

Objectives: A workshop was held to discuss the state of the science of the MOA for asbestos-related disease. The objective was to review the range of asbestos-induced health effects (including those at sites remote to the respiratory tract). We sought to identify existing knowledge gaps and define what research is needed to address these gaps and advance asbestos research.

Discussion: Discussions centered on areas of uncertainty in the field, including the ways asbestos is defined and characterized, the role of different fiber characteristics (e.g., length and mineralogy) in disease, and the impact of low-dose exposures on human health. Studying the dosimetry and mode of action of multiple fiber types would enhance our understanding of asbestos-related disease. To better elucidate the MOA of specific asbestos fibers, the risk assessor requires data as to specific characteristics of asbestos in determining fiber toxicity (e.g., surface area, mineral type), which may inform efforts to assess and control exposures and prevent adverse human health outcomes for the diverse range of fiber types. Specific research aims were defined for these topics and for overarching issues to be addressed, including the use of standardized terminology, test materials, and better experimental models to aid in data extrapolation to humans.

Conclusion: To resolve these and other issues, participants agreed that diverse scientific disciplines must coordinate to better understand the MOA leading to the various asbestos-related disease end points.
Occupational exposure to asbestos and ovarian cancer: a meta-analysis. M.C. Camargo, L.T. Stayner, K. Straif, et al. 2011;119(9):1211-7. Meta-analysis PubMed · Publisher · Free full text

Abstract

Objective: A recent Monographs Working Group of the International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence for a causal association between exposure to asbestos and ovarian cancer. We performed a meta-analysis to quantitatively evaluate this association.

Data Sources: Searches of PubMed and unpublished data yielded a total of 18 cohort studies of women occupationally exposed to asbestos.

Data Extraction: Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer.

Data Synthesis: All but one study reported standardized mortality ratios (SMRs) comparing observed numbers of deaths with expected numbers for the general population; the exception was a study that reported standardized incidence ratios. For simplicity, we refer to all effect estimates as SMRs. The overall pooled SMR estimate for ovarian cancer was 1.77 (95% confidence interval, 1.37-2.28), with a moderate degree of heterogeneity among the studies (I2 = 35.3%, p = 0.061). Effect estimates were stronger for cohorts compensated for asbestosis, cohorts with estimated lung cancer SMRs > 2.0, and studies conducted in Europe compared with other geographic regions. Effect estimates were similar for studies with and without pathologic confirmation, and we found no evidence of publication bias (Egger's test p-value = 0.162).

Conclusions: Our study supports the IARC conclusion that exposure to asbestos is associated with increased risk of ovarian cancer.
Pleural mesothelioma in New Caledonia: associations with environmental risk factors. F. Baumann, P. Maurizot, M. Mangeas, et al. 2011;119(5):695-700. PubMed · Publisher · Free full text

Abstract

Background: High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite.

Objectives: We studied the spatial and temporal variation of MM and its association with environmental factors.

Methods: We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space-time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses.

Results: The highest incidence was observed in the Houaïlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2-4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence.

Conclusions: Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia.
Where there is asbestos, there is mesothelioma: filling in the data blanks. R.C. Haynes. 2011;119(4):A177. Comment · News PubMed · Publisher · Free full text
A case-control study of lung cancer nested in a cohort of European asphalt workers. A. Olsson, H. Kromhout, M. Agostini, et al. 2010;118(10):1418-24. PubMed · Publisher · Free full text

Abstract

Background: We conducted a nested case-control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed.

Objective: We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers.

Methods: Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002-2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar.

Results: A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84-1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88-1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate.

Conclusions: We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role.
A repeat call for the banning of asbestos. L.S. Birnbaum, J.C. Schroeder, H.A. Tilson. 2010;118(7):A280-1. Comment · Editorial PubMed · Publisher · Free full text
A worn-out welcome: renewed call for a global ban on asbestos. R.C. Haynes. 2010;118(7):A298-303. Comment · News PubMed · Publisher · Free full text

Summary

This news feature reported on the Collegium Ramazzini's 2010 renewal of its 1999 call for a global ban on the mining and use of asbestos. It drew on published sources and interviews with occupational health experts, consultants and advocates. The article stated that global asbestos use was about 4.3–4.7 million metric tons per year when Iceland became the first country to ban most forms in 1983, and had fallen to 2.1 million metric tons twenty-five years later. Demand continued to rise in rapidly industrializing countries such as India and China. Chrysotile accounted for nearly all asbestos still mined. An estimated 125 million people were still exposed at work. The feature described the World Trade Organization ruling that upheld France's ban against Canada's challenge, Canada's continued chrysotile exports, widespread chrysotile use in India, and the 'Kubota Shock' that preceded Japan's phase-out. It noted one estimate of about 100,000 Japanese mesothelioma deaths over the next 40 years. In the United States, mining stopped in 2002, but 1,460 metric tons of chrysotile were imported in 2008. Efforts to pass a federal ban had repeatedly stalled. Alternatives were reported to cost 10–15% more. Interviewees said a U.S. and Canadian ban would have major worldwide influence and expected an eventual global ban.

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Are current or future mesothelioma epidemics in Hong Kong the tragic legacy of uncontrolled use of asbestos in the past?. L.A. Tse, I.T. Yu, W. Goggins, et al. 2010;118(3):382-6. PubMed · Publisher · Free full text

Abstract

Inhaled asbestos fibers may contribute to three-fourths of malignant mesotheliomas diagnosed in men and almost 40% of cases diagnosed in women. Bans on the manufacture and sale of amphibole asbestos fibers are expected to reduce the incidence of mesothelioma, but the long latency period from initial exposure to clinical disease means that people exposed before bans were enacted will continue to develop asbestos-related mesotheliomas as they age. Tse et al. (p. 382) used historical data on asbestos consumption and mesothelioma diagnoses to predict future mesothelioma trends in Hong Kong. Asbestos use peaked during a construction boom in the early 1960s and subsequently declined by > 90% following a ban on the sale and import of crocidolite and amosite asbestos in 1996, whereas mesothelioma diagnoses in men increased from a single case in 1972–1976 to 63 cases in 2002–2006 (corresponding to crude incidence rates of 0.09 and 3.86 cases/million men, respectively). Assuming an average latency of 42 years, the authors predict that incidence rates will peak in 2009 and that diagnoses will peak in 2014. However, they caution that ongoing use of chrysotile asbestos and the release of asbestos fibers from older buildings during demolition or renovation may slow the projected decline. [corrected]
Case report: Lung disease in World Trade Center responders exposed to dust and smoke: carbon nanotubes found in the lungs of World Trade Center patients and dust samples. M. Wu, R.E. Gordon, R. Herbert, et al. 2010;118(4):499-504. PubMed · Publisher · Free full text

Abstract

Context: After the collapse of the World Trade Center (WTC) on 11 September 2001, a dense cloud of dust containing high levels of airborne pollutants covered Manhattan and parts of Brooklyn, New York. Between 60,000 and 70,000 responders were exposed. Many reported adverse health effects.

Case Presentation: In this report we describe clinical, pathologic, and mineralogic findings in seven previously healthy responders who were exposed to WTC dust on either 11 September or 12 September 2001, who developed severe respiratory impairment or unexplained radiologic findings and underwent video-assisted thoracoscopic surgical lung biopsy procedures at Mount Sinai Medical Center. WTC dust samples were also examined. We found that three of the seven responders had severe or moderate restrictive disease clinically. Histopathology showed interstitial lung disease consistent with small airways disease, bronchiolocentric parenchymal disease, and nonnecrotizing granulomatous condition. Tissue mineralogic analyses showed variable amounts of sheets of aluminum and magnesium silicates, chrysotile asbestos, calcium phosphate, and calcium sulfate. Small shards of glass containing mostly silica and magnesium were also found. Carbon nanotubes (CNT) of various sizes and lengths were noted. CNT were also identified in four of seven WTC dust samples.

Discussion: These findings confirm the previously reported association between WTC dust exposure and bronchiolar and interstitial lung disease. Long-term monitoring of responders will be needed to elucidate the full extent of this problem. The finding of CNT in both WTC dust and lung tissues is unexpected and requires further study.
Chrysotile asbestos and mesothelioma. R.A. Lemen. 2010;118(7):A282. Comment · Letter PubMed · Publisher · Free full text
Exposure to asbestos-containing vermiculite ore and respiratory symptoms among individuals who were children while the mine was active in Libby, Montana. L.C. Vinikoor, T.C. Larson, T.F. Bateson, et al. 2010;118(7):1033-28. PubMed · Publisher · Free full text

Abstract

Background: Libby, Montana, was home to the largest vermiculite ore mine in the United States. The processing, use, and transport of the ore, which was contaminated with amphibole asbestos, led to generalized contamination of the community. The mine closed in 1990.

Objectives: We examined the prevalence of respiratory symptoms in 2000-2001 and their association with history of vermiculite exposure among people who were < or = 18 years of age when the mine closed.

Methods: Information on respiratory symptoms and exposure history was collected by questionnaire in 2000-2001, at which time participants were 10-29 years old. Logistic regression was used to model the associations between exposures and outcomes adjusted for age, sex, and tobacco smoke exposure.

Results: Of the 1,003 individuals included in the study, 10.8% reported usually having a cough, 14.5% reported experiencing shortness of breath when walking up a slight hill or hurrying on level ground, and 5.9% reported having coughed up bloody phlegm in the past year. These respiratory symptoms were positively associated with frequently handling vermiculite insulation compared with never handling vermiculite insulation. We found no association between vermiculite insulation in the house and respiratory symptoms. Respiratory symptoms were associated with other vermiculite exposures as well, and the number and frequency of these activities showed a positive trend with usually having a cough. We found no association between any of the activities and abnormal spirometry.

Conclusions: These data suggest that residents of Libby, Montana, who were children when the mine closed experienced some respiratory symptoms associated with asbestos-contaminated vermiculite exposure.
National use of asbestos in relation to economic development. G.V. Le, K. Takahashi, A. Karjalainen, et al. 2010;118(1):116-9. PubMed · Publisher · Free full text

Abstract

Background: National disparities in asbestos use will likely lead to an unequal burden of asbestos diseases.

Objectives: As economic status may be linked to asbestos use, we assessed, globally, the relationship between indicators of national economic development and asbestos use.

Methods: For the 135 countries that have ever used asbestos, per capita asbestos use (kilograms per capita per year) was compared with per capita gross domestic product (GDP) in 1990 Geary-Khamis dollars (GKD) for the period 1920-2003. Countries were grouped into three income levels (high, middle, and low) that were adapted from the 2003 World Bank categories.

Results: The historical pattern of asbestos use followed the environmental Kuznets curve in which use by high-income countries peaked when incomes attained 10,000-15,000 GKD and essentially ceased at income levels over 20,000 GKD. Currently, middle- and low-income countries are increasing their use of asbestos, closely following the paths once traced by higher income countries.

Conclusions: Developing countries have the opportunity to eliminate asbestos use sooner than high-income countries and thus reduce the future burden of asbestos diseases.
The case for a global ban on asbestos. J. LaDou, B. Castleman, A. Frank, et al. 2010;118(7):897-901. PubMed · Publisher · Free full text

Abstract

Background: All forms of asbestos are now banned in 52 countries. Safer products have replaced many materials that once were made with it. Nonetheless, many countries still use, import, and export asbestos and asbestos-containing products, and in those that have banned other forms of asbestos, the so-called "controlled use" of chrysotile asbestos is often exempted from the ban. In fact, chrysotile has accounted for > 95% of all the asbestos used globally.

Objective: We examined and evaluated the literature used to support the exemption of chrysotile asbestos from the ban and how its exemption reflects the political and economic influence of the asbestos mining and manufacturing industry.

Discussion: All forms of asbestos, including chrysotile, are proven human carcinogens. All forms cause malignant mesothelioma and lung and laryngeal cancers, and may cause ovarian, gastrointestinal, and other cancers. No exposure to asbestos is without risk. Illnesses and deaths from asbestos exposure are entirely preventable.

Conclusions: All countries of the world have an obligation to their citizens to join in the international endeavor to ban the mining, manufacture, and use of all forms of asbestos. An international ban is urgently needed. There is no medical or scientific basis to exempt chrysotile from the worldwide ban of asbestos.
XRCC1 deficiency sensitizes human lung epithelial cells to genotoxicity by crocidolite asbestos and Libby amphibole. J.R. Pietruska, T. Johnston, A. Zhitkovich, et al. 2010;118(12):1707-13. PubMed · Publisher · Free full text

Abstract

Background: Asbestos induces DNA and chromosomal damage, but the DNA repair pathways protecting human cells against its genotoxicity are largely unknown. Polymorphisms in XRCC1 have been associated with altered susceptibility to asbestos-related diseases. However, it is unclear whether oxidative DNA damage repaired by XRCC1 contributes to asbestos-induced chromosomal damage.

Objectives: We sought to examine the importance of XRCC1 in protection against genotoxic effects of crocidolite and Libby amphibole asbestos.

Methods: We developed a genetic model of XRCC1 deficiency in human lung epithelial H460 cells and evaluated genotoxic responses to carcinogenic fibers (crocidolite asbestos, Libby amphibole) and nongenotoxic materials (wollastonite, titanium dioxide).

Results: XRCC1 knockdown sensitized cells to the clastogenic and cytotoxic effects of oxidants [hydrogen peroxide (H₂O₂), bleomycin] but not to the nonoxidant paclitaxel. XRCC1 knockdown strongly enhanced genotoxicity of amphibole fibers as evidenced by elevated formation of clastogenic micronuclei. Crocidolite induced primarily clastogenic micronuclei, whereas Libby amphibole induced both clastogenic and aneugenic micronuclei. Crocidolite and bleomycin were potent inducers of nuclear buds, which were enhanced by XRCC1 deficiency. Libby amphibole and H₂O₂ did not induce nuclear buds, irrespective of XRCC1 status. Crocidolite and Libby amphibole similarly activated the p53 pathway.

Conclusions: Oxidative DNA damage repaired by XRCC1 (oxidized bases, single-strand breaks) is a major cause of chromosomal breaks induced by crocidolite and Libby amphibole. Nuclear buds are a novel biomarker of genetic damage induced by exposure to crocidolite asbestos, which we suggest are associated with clustered DNA damage. These results provide mechanistic evidence for the epidemiological association between XRCC1 polymorphisms and susceptibility to asbestos-related disease.

2000s

Asbestos burden predicts survival in pleural mesothelioma. B.C. Christensen, J.J. Godleski, C.R. Roelofs, et al. 2008;116(6):723-6. PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of <1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors.

Objective: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis.

Methods: We studied incident cases of MPM patients enrolled through the International Mesothelioma Program at Brigham and Women's Hospital in Boston, Massachusetts, using survival follow-up, self-reported asbestos exposure (n=128), and a subset of cases (n=80) with quantitative asbestos fiber burden measures.

Results: Consistent with the established literature, we found independent, significant associations between male sex and reduced survival (p<0.04), as well as between nonepithelioid tumor histology and reduced survival (p<0.02). Although self-reported exposure to asbestos was not predictive of survival among our cases, stratifying quantitative asbestos fiber burden [number of asbestos bodies per gram of lung (wet weight)] into groups of low (0-99 asbestos bodies), moderate (100-1,099), and high fiber burden (>1,099), suggested a survival duration association among these groups (p=0.06). After adjusting for covariates in a Cox model, we found that patients with a low asbestos burden had a 3-fold elevated risk of death compared to patients with a moderate fiber burden [95% confidence interval (CI), 0.95-9.5; p=0.06], and patients with a high asbestos burden had a 4.8-fold elevated risk of death (95% CI, 1.5-15.0; p<0.01) versus those with moderate exposure.

Conclusion: Our data suggest that patient survival is associated with asbestos fiber burden in MPM and is perhaps modified by susceptibility.
Grand rounds: asbestos-related pericarditis in a boiler operator. B.A. Abejie, E.H. Chung, R.W. Nesto, et al. 2008;116(1):86-9. Case report PubMed · Publisher · Free full text

Abstract

Context: Occupational and environmental exposures to asbestos remain a public health problem even in developed countries. Because of the long latency in asbestos-related pathology, past asbestos exposure continues to contribute to incident disease. Asbestos most commonly produces pulmonary pathology, with asbestos-related pleural disease as the most common manifestation. Although the pleurae and pericardium share certain histologic characteristics, asbestos-related pericarditis is rarely reported.

Case Presentation: We present a 59-year-old man who worked around boilers for almost 30 years and was eventually determined to have calcific, constrictive pericarditis. He initially presented with an infectious exacerbation of chronic bronchitis. Chest radiographs demonstrated pleural and pericardial calcifications. Further evaluation with cardiac catheterization showed a hemodynamic picture consistent with constrictive pericarditis. A high-resolution computerized tomography scan of the chest demonstrated dense calcification in the pericardium, right pleural thickening and nodularity, right pleural plaque without calcification, and density in the right middle lobe. Pulmonary function testing showed mild obstruction and borderline low diffusing capacity.

Discussion: Based on the patient's occupational history, the presence of pleural pathology consistent with asbestos, previous evidence that asbestos can affect the pericardium, and absence of other likely explanations, we concluded that his pericarditis was asbestos-related.

Relevance To Clinical Practice: Similar to pleural thickening and plaque formation, asbestos may cause progressive fibrosis of the pericardium.
Inhaled asbestos exacerbates atherosclerosis in apolipoprotein E-deficient mice via CD4+ T cells. N.K. Fukagawa, M. Li, T. Sabo-Attwood, et al. 2008;116(9):1218-25. PubMed · Publisher · Free full text

Abstract

Background: Associations between air pollution and morbidity/mortality from cardiovascular disease are recognized in epidemiologic and clinical studies, but the mechanisms by which inhaled fibers or particles mediate the exacerbation of atherosclerosis are unclear.

Objective And Methods: To determine whether lung inflammation after inhalation of a well-characterized pathogenic particulate, chrysotile asbestos, is directly linked to exacerbation of atherosclerosis and the mechanisms involved, we exposed apolipoprotein E-deficient (ApoE(-/-)) mice and ApoE(-/-) mice crossed with CD4(-/-) mice to ambient air, NIEHS (National Institute of Environmental Health Sciences) reference sample of chrysotile asbestos, or fine titanium dioxide (TiO(2)), a nonpathogenic control particle, for 3, 9, or 30 days.

Results: ApoE(-/-) mice exposed to inhaled asbestos fibers had approximately 3-fold larger atherosclerotic lesions than did TiO(2)-exposed ApoE(-/-) mice or asbestos-exposed ApoE(-/-)/CD4(-/-) double-knockout (DKO) mice. Lung inflammation and the magnitude of lung fibrosis assessed histologically were similar in asbestos-exposed ApoE(-/-) and DKO mice. Monocyte chemoattractant protein-1 (MCP-1) levels were increased in bronchoalveolar lavage fluid and plasma, and plasma concentrations correlated with lesion size (p < 0.04) in asbestos-exposed ApoE(-/-) mice. At 9 days, activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), transcription factors linked to inflammation and found in the promoter region of the MCP-1 gene, were increased in aortas of asbestos-exposed ApoE(-/-) but not DKO mice.

Conclusion: Our findings show that the degree of lung inflammation and fibrosis does not correlate directly with cardiovascular effects of inhaled asbestos fibers and support a critical role of CD4(+) T cells in linking fiber-induced pulmonary signaling to consequent activation of AP-1- and NF-kappaB-regulated genes in atherogenesis.
Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells. M. Pacurari, X.J. Yin, J. Zhao, et al. 2008;116(9):1211-7. PubMed · Publisher · Free full text

Abstract

Background: Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells.

Objective: Exposure to asbestos is the primary cause of malignant mesothelioma in 80-90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT.

Methods: In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor kappaB (NF-kappaB), and protein serine-threonine kinase (Akt).

Results: Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-kappaB, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure.

Conclusions: The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.
Recent mortality from pleural mesothelioma, historical patterns of asbestos use, and adoption of bans: a global assessment. K. Nishikawa, K. Takahashi, A. Karjalainen, et al. 2008;116(12):1675-80. PubMed · Publisher · Free full text

Abstract

Background: In response to the health risks posed by asbestos exposure, some countries have imposed strict regulations and adopted bans, whereas other countries have intervened less and continue to use varying quantities of asbestos.

Objectives: This study was designed to assess, on a global scale, national experiences of recent mortality from pleural mesothelioma, historical trends in asbestos use, adoption of bans, and their possible interrelationships.

Methods: For 31 countries with available data, we analyzed recent pleural mesothelioma (International Classification of Diseases, 10th Revision) mortality rates (MRs) using age-adjusted period MRs (deaths/million/year) from 1996 to 2005. We calculated annual percent changes (APCs) in age-adjusted MRs to characterize trends during the period. We characterized historical patterns of asbestos use by per capita asbestos use (kilograms per capita/year) and the status of national bans.

Results: Period MRs increased with statistical significance in five countries, with marginal significance in two countries, and were equivocal in 24 countries (five countries in Northern and Western Europe recorded negative APC values). Countries adopting asbestos bans reduced use rates about twice as fast as those not adopting bans. Turning points in use preceded bans. Change in asbestos use during 1970-1985 was a significant predictor of APC in mortality for pleural mesothelioma, with an adjusted R(2) value of 0.47 (p < 0.0001).

Conclusions: The observed disparities in global mesothelioma trends likely relate to country-to-country disparities in asbestos use trends.
Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy. D. Ferrante, M. Bertolotti, A. Todesco, et al. 2007;115(10):1401-5. PubMed · Publisher · Free full text

Abstract

Background: Family members of asbestos workers are at increased risk of malignant mesothelioma (MM). Although the hazard is established, the magnitude of the risk is uncertain, and it is unclear whether risk is also increased for other cancers. Few cohort studies have been reported.

Objective: The "Eternit" factory of Casale Monferrato (Italy), active from 1907 to 1986, was among the most important Italian plants producing asbestos-cement (AC) goods. In this article we present updated results on mortality and MM incidence in the wives of workers at the factory.

Methods: We studied a cohort of 1,780 women, each married to an AC worker during his employment at the factory but not personally occupationally exposed to asbestos. Cohort membership was defined starting from the marital status of each worker, which was ascertained in 1988 from the Registrar's Office in the town where workers lived. At the end of follow-up (April 2003), 67% of women were alive, 32.3% dead, and 0.7% lost to follow-up. Duration of exposure was computed from the husband's period of employment. Latency was the interval from first exposure to the end of follow-up.

Results: The standardized mortality ratio (SMR) for pleural cancer [21 observed vs. 1.2 expected; SMR = 18.00; 95% confidence interval (CI), 11.14-27.52] was significantly increased. Mortality for lung cancer was not increased (12 observed vs. 10.3 expected; SMR = 1.17; 95% CI, 0.60-2.04). Eleven incident cases of pleural MM were observed (standardized incidence ratio = 25.19; 95% CI, 12.57-45.07).

Conclusions: Household exposure, as experienced by these AC workers' wives, increases risk for pleural MM but not for lung cancer.
Modeling mesothelioma risk associated with environmental asbestos exposure. M.M. Maule, C. Magnani, P. Dalmasso, et al. 2007;115(7):1066-71. PubMed · Publisher · Free full text

Abstract

Background: Environmental asbestos pollution can cause malignant mesothelioma, but few studies have involved dose-response analyses with detailed information on occupational, domestic, and environmental exposures.

Objectives: In the present study, we examined the spatial variation of mesothelioma risk in an area with high levels of asbestos pollution from an industrial plant, adjusting for occupational and domestic exposures.

Methods: This population-based case-control study included 103 incident cases of mesothelioma and 272 controls in 1987-1993 in the area around Casale Monferrato, Italy, where an important asbestos cement plant had been active for decades. Information collected included lifelong occupational and residential histories. Mesothelioma risk was estimated through logistic regression and a mixed additive-multiplicative model in which an additive scale was assumed for the risk associated with both residential distance from the plant and occupational exposures. The adjusted excess risk gradient by residential distance was modeled as an exponential decay with a threshold.

Results: Residents at the location of the asbestos cement factory had a relative risk for mesothelioma of 10.5 [95% confidence interval (CI), 3.8-50.1), adjusted for occupational and domestic exposures. Risk decreased rapidly with increasing distance from the factory, but at 10-km the risk was still 60% of its value at the source. The relative risk for occupational exposure was 6.0 (95% CI, 2.9-13.0), but this increased to 27.5 (95% CI, 7.8-153.4) when adjusted for residential distance.

Conclusions: This study provides strong evidence that asbestos pollution from an industrial source greatly increases mesothelioma risk. Furthermore, relative risks from occupational exposure were underestimated and were markedly increased when adjusted for residential distance.
New insight into intrachromosomal deletions induced by chrysotile in the gpt delta transgenic mutation assay. A. Xu, L.B. Smilenov, P. He, et al. 2007;115(1):87-92. PubMed · Publisher · Free full text

Abstract

Background: Genotoxicity is often a prerequisite to the development of malignancy. Considerable evidence has shown that exposure to asbestos fibers results in the generation of chromosomal aberrations and multilocus mutations using various in vitro approaches. However, there is less evidence to demonstrate the contribution of deletions to the mutagenicity of asbestos fibers in vivo.

Objectives: In the present study, we investigated the mutant fractions and the patterns induced by chrysotile fibers in gpt delta transgenic mouse primary embryo fibroblasts (MEFs) and compared the results obtained with hydrogen peroxide (H2O2) in an attempt to illustrate the role of oxyradicals in fiber mutagenesis.

Results: Chrysotile fibers induced a dose-dependent increase in mutation yield at the redBA/gam loci in transgenic MEF cells. The number of lambda mutants losing both redBA and gam loci induced by chrysotiles at a dose of 1 microg/cm(2) increased by > 5-fold relative to nontreated controls (p < 0.005). Mutation spectra analyses showed that the ratio of lambda mutants losing the redBA/gam region induced by chrysotiles was similar to those induced by equitoxic doses of H2O2. Moreover, treatment with catalase abrogated the accumulation of y-H2AX, a biomarker of DNA double-strand breaks, induced by chrysotile fibers.

Conclusions: Our results provide novel information on the frequencies and types of mutations induced by asbestos fibers in the gpt delta transgenic mouse mutagenic assay, which shows great promise for evaluating fiber/particle mutagenicity in vivo.
Policy: chrysotile on ice. R. Renner. 2007;115(3):A130. News PubMed · Publisher · Free full text

Summary

This news report described the October 2006 decision by parties to the Rotterdam Convention, a group of more than 100 countries that share information about hazardous chemicals, not to add chrysotile asbestos to the convention's list of chemicals that require prior informed consent (PIC) before export. The 1998 convention required PIC for more than 30 chemicals. This was the second time the convention had declined to list chrysotile. Carl Smith of the Foundation for Advancements in Science and Education said that listing is not a ban, only an agreement to share information. He said chrysotile met all requirements for listing but remained economically important. The article reported that chrysotile products such as pipes and roof shingles were still widely used in the developing world, and that a Wall Street Journal estimate valued the trade at $600 million a year. A panel of 31 experts on the Chemical Review Committee had found that chrysotile met the listing criteria, and most meeting participants supported listing. Canada, Ukraine, Russia, Kyrgyzstan, India, Iran and Peru objected and blocked action. The Canadian government-funded Chrysotile Institute maintained that chrysotile is less toxic than amphibole asbestos. Other groups called controlled use a fallacy and noted that the WHO and other bodies classify chrysotile as a human carcinogen. Further consideration was deferred to 2008.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update of a cohort mortality study. P.A. Sullivan. 2007;115(4):579-85. PubMed · Publisher · Free full text

Abstract

Background: Vermiculite from the mine near Libby, Montana, is contaminated with tremolite asbestos and other amphibole fibers (winchite and richterite). Asbestos-contaminated Libby vermiculite was used in loose-fill attic insulation that remains in millions of homes in the United States, Canada, and other countries.

Objective: This report describes asbestos-related occupational respiratory disease mortality among workers who mined, milled, and processed the Libby vermiculite.

Methods: This historical cohort mortality study uses life table analysis methods to compare the age-adjusted mortality experience through 2001 of 1,672 Libby workers to that of white men in the U.S. population.

Results: Libby workers were significantly more likely to die from asbestosis [standardized mortality ratio (SMR) = 165.8; 95% confidence interval (CI), 103.9-251.1], lung cancer (SMR = 1.7; 95% CI, 1.4-2.1), cancer of the pleura (SMR = 23.3; 95% CI, 6.3-59.5), and mesothelioma. Mortality from asbestosis and lung cancer increased with increasing duration and cumulative exposure to airborne tremolite asbestos and other amphibole fibers.

Conclusions: The observed dose-related increases in asbestosis and lung cancer mortality highlight the need for better understanding and control of exposures that may occur when homeowners or construction workers (including plumbers, cable installers, electricians, telephone repair personnel, and insulators) disturb loose-fill attic insulation made with asbestos-contaminated vermiculite from Libby, Montana.
Nested case-control study of autoimmune disease in an asbestos-exposed population. C.W. Noonan, J.C. Pfau, T.C. Larson, et al. 2006;114(8):1243-7. Randomized trial PubMed · Publisher · Free full text

Abstract

Objective: To explore the potential association between asbestos exposure and risk of autoimmune disease, we conducted a case-control study among a cohort of 7,307 current and former residents of Libby, Montana, a community with historical occupational and environmental exposure to asbestos-contaminated vermiculite.

Methods: Cases were defined as those who reported having one of three systemic autoimmune diseases (SAIDs): systemic lupus erythematosus, scleroderma, or rheumatoid arthritis (RA). Controls were randomly selected at a 3:1 ratio from among the remaining 6,813 screening participants using frequency-matched age and sex groupings.

Results: The odds ratios (ORs) and 95% confidence intervals (CIs) for SAIDs among those >or=65 years of age who had worked for the vermiculite mining company were 2.14 (95% CI, 0.90-5.10) for all SAIDs and 3.23 (95% CI, 1.31-7.96) for RA. In this age group, exposure to asbestos while in the military was also an independent risk factor, resulting in a tripling in risk. Other measures of occupational exposure to vermiculite indicated 54% and 65% increased risk for SAIDs and RA, respectively. Those who had reported frequent contact with vermiculite through various exposure pathways also demonstrated elevated risk for SAIDs and RA. We found increasing risk estimates for SAIDs with increasing numbers of reported vermiculite exposure pathways (p<0.001).

Conclusion: These preliminary findings support the hypothesis that asbestos exposure is associated with autoimmune disease. Refined measurements of asbestos exposure and SAID status among this cohort will help to further clarify the relationship between these variables.
Assessment of autoimmune responses associated with asbestos exposure in Libby, Montana, USA. J.C. Pfau, J.J. Sentissi, G. Weller, et al. 2005;113(1):25-30. PubMed · Publisher · Free full text

Abstract

Systemic autoimmune responses are associated with certain environmental exposures, including crystalline particles such as silica. Positive antinuclear antibody (ANA) tests have been reported in small cohorts exposed to asbestos, but many questions remain regarding the prevalence, pattern, and significance of autoantibodies associated with asbestos exposures. The population in Libby, Montana, provides a unique opportunity for such a study because of both occupational and environmental exposures that have occurred as a result of the mining of asbestos-contaminated vermiculite near the community. As part of a multifaceted assessment of the impact of asbestos exposures on this population, this study explored the possibility of exacerbated autoimmune responses. Age- and sex-matched sets of 50 serum samples from Libby and Missoula, Montana (unexposed), were tested for ANA on HEp-2 cells using indirect immunofluorescence. Data included frequency of positive tests, ANA titers, staining patterns, and scored fluorescence intensity, all against known controls. Serum immunoglobulin A (IgA), rheumatoid factor, and antibodies to extractable nuclear antigen (ENA) were also tested. The Libby samples showed significantly higher frequency of positive ANA and ENA tests, increased mean fluorescence intensity and titers of the ANAs, and higher serum IgA, compared with Missoula samples. In the Libby samples, positive correlations were found between ANA titers and both lung disease severity and extent of exposure. The results support the hypothesis that asbestos exposure is associated with autoimmune responses and suggests that a relationship exists between those responses and asbestos-related disease processes.
Asbestos and international organizations. L. Tomatis. 2004;112(6):A336-7. Comment · Historical article · Letter PubMed · Publisher · Free full text
Asbestos-induced peritoneal mesothelioma in a construction worker. R. Fonte, S. Gambettino, M. Melazzini, et al. 2004;112(5):616-9. Case report PubMed · Publisher · Free full text

Abstract

Occupational and environmental asbestos exposure continues to represent a public health problem, despite increasingly restrictive laws adopted by most industrialized countries. Peritoneal mesothelioma is a rare and aggressive asbestos-related malignancy. We present the case of a 65-year-old man who developed recurrent ascites after having been exposed to asbestos in the building industry for > 40 years. Liver function and histology were normal. Abdominal computed tomography initially excluded the presence of expansive processes, and no abnormal cells were found in the ascitic fluid. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum. Histopathology of bioptic samples revealed epithelioid neoplastic proliferation with a tubulopapillary pattern, falsely suggesting metastatic adenocarcinomatosis. In consideration of the occupational history, and after further diagnostic procedures had failed to identify the hypothetical primitive tumor, immunostaining of the neoplastic tissue was performed. Results were negative for carcinoembrionary antigen and the epithelial glycoprotein Ber-EP4, whereas results were positive for the mesothelial markers cytokeratins, calretinin, epithelial membrane antigen, and HBME-1, thus leading to the correct diagnosis of peritoneal epithelial mesothelioma. The Italian Workers' Compensation Authority recognized the occupational origin of the disease. Cytoreductive surgery associated with continuous hyperthermic peritoneal perfusion (cisplatin at 42 degrees C, for 1 hr) was performed. The disease relapsed after 4 months and was later complicated by a bowel obstruction requiring palliative ileostomy. The patient died 23 months after diagnosis. This case illustrates the insidious diagnostic problems posed by peritoneal mesothelioma, a tumor which often simulates other malignancies (e.g., metastatic carcinomas) at routine histopathological examination. Occupational history and immunohistochemistry are helpful for the correct diagnosis, which, in turn, is important in relation to prognosis and treatment (adoption of new integrated procedures that seem to promise prolonged survival and increased quality of life), and in relation to medicolegal issues and occupation-related compensation claims following asbestos exposure.
Health and environmental consequences of the world trade center disaster. P.J. Landrigan, P.J. Lioy, G. Thurston, et al. 2004;112(6):731-9. Review PubMed · Publisher · Free full text

Abstract

The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperreactivity. Evaluation of 10,116 firefighters showed exposure-related increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on 11 September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster.
Monitoring for asbestos: U.S. EPA methods. K.C. Callahan. 2004;112(13):A728. Comment · Letter PubMed · Publisher · Free full text
Overstating the consequences of radiographic abnormalities. J.J. Flynn, S. Kardos, L. Yan. 2004;112(2):A84; author reply A84-5. Letter · Comment PubMed · Publisher · Free full text
Radiographic abnormalities and asbestos exposure: Libby, Montana. B. Price. 2004;112(2):A82-3, author reply A83. Letter · Comment PubMed · Publisher · Free full text
The asbestos cancer epidemic. J. LaDou. 2004;112(3):285-90. PubMed · Publisher · Free full text

Abstract

The asbestos cancer epidemic may take as many as 10 million lives before asbestos is banned worldwide and exposures are brought to an end. In many developed countries, in the most affected age groups, mesothelioma may account for 1% of all deaths. In addition to mesotheliomas, 5-7% of all lung cancers can be attributed to occupational exposures to asbestos. The asbestos cancer epidemic would have been largely preventable if the World Health Organization (WHO) and the International Labor Organization (ILO) had responded early and responsibly. The WHO was late in recognizing the epidemic and failed to act decisively after it was well under way. The WHO and the ILO continue to fail to address the problem of asbestos mining, manufacturing, and use and world trade of a known human carcinogen. Part of the problem is that the WHO and the ILO have allowed organizations such as the International Commission on Occupational Health (ICOH) and other asbestos industry advocates to manipulate them and to distort scientific evidence. The global asbestos cancer epidemic is a story of monumental failure to protect the public health.
The WTC disaster and asbestos regulations. J.H. Lange. 2004;112(11):A606-7; author reply A607. Comment · Letter PubMed · Publisher · Free full text
Environmental threats to children's health in Southeast Asia and the Western Pacific. W.A. Suk, K.M. Ruchirawat, K. Balakrishnan, et al. 2003;111(10):1340-7. Review PubMed · Publisher · Free full text

Abstract

The Southeast Asia and Western Pacific regions contain half of the world's children and are among the most rapidly industrializing regions of the globe. Environmental threats to children's health are widespread and are multiplying as nations in the area undergo industrial development and pass through the epidemiologic transition. These environmental hazards range from traditional threats such as bacterial contamination of drinking water and wood smoke in poorly ventilated dwellings to more recently introduced chemical threats such as asbestos construction materials; arsenic in groundwater; methyl isocyanate in Bhopal, India; untreated manufacturing wastes released to landfills; chlorinated hydrocarbon and organophosphorous pesticides; and atmospheric lead emissions from the combustion of leaded gasoline. To address these problems, pediatricians, environmental health scientists, and public health workers throughout Southeast Asia and the Western Pacific have begun to build local and national research and prevention programs in children's environmental health. Successes have been achieved as a result of these efforts: A cost-effective system for producing safe drinking water at the village level has been devised in India; many nations have launched aggressive antismoking campaigns; and Thailand, the Philippines, India, and Pakistan have all begun to reduce their use of lead in gasoline, with resultant declines in children's blood lead levels. The International Conference on Environmental Threats to the Health of Children, held in Bangkok, Thailand, in March 2002, brought together more than 300 representatives from 35 countries and organizations to increase awareness on environmental health hazards affecting children in these regions and throughout the world. The conference, a direct result of the Environmental Threats to the Health of Children meeting held in Manila in April 2000, provided participants with the latest scientific data on children's vulnerability to environmental hazards and models for future policy and public health discussions on ways to improve children's health. The Bangkok Statement, a pledge resulting from the conference proceedings, is an important first step in creating a global alliance committed to developing active and innovative national and international networks to promote and protect children's environmental health.
Phosphorylation of p53 protein in A549 human pulmonary epithelial cells exposed to asbestos fibers. M. Matsuoka, H. Igisu, Y. Morimoto. 2003;111(4):509-12. PubMed · Publisher · Free full text

Abstract

We examined effects of asbestos exposure on the phosphorylation of p53 protein in human pulmonary epithelial type II cells (A549), which express wild-type p53. In cells exposed to two different types of asbestos, chrysotile (approximately 1-6% iron content) and crocidolite (approximately 27% iron content) fibers, at the doses of 1, 5, and 10 microg/cm2 for 24 hr, the levels of p53 phosphorylated at Ser15 and p53 protein were correlated with the dose. On a per-weight basis, chrysotile was more potent in inducing Ser15 phosphorylation and accumulation of p53 protein than was crocidolite. After exposure to 10 micro g/cm2 chrysotile, the levels of p53 phosphorylated at Ser15 and of p53 protein increased after 18 hr. Among serines in p53 protein immunoprecipitated from A549 cells treated with chrysotile, only Ser15 was markedly phosphorylated. In contrast, no clear phosphorylation was observed at Ser6, Ser9, Ser20, Ser37, Ser46, or Ser392. Blocking of the extracellular signal-regulated protein kinase pathway with U0126 or inhibition of p38 activity with SB203580 did not suppress chrysotile-induced Ser15 phosphorylation. On the other hand, treatment with wortmannin, an inhibitor of DNA-activated protein kinase and ataxia-telangiectasia mutated, suppressed both chrysotile-induced Ser15 phosphorylation and accumulation of p53 protein. Treatment with either catalase or N-acetylcysteine failed to suppress chrysotile-induced Ser15 phosphorylation, suggesting that reactive oxygen species do not play a major role in the phosphorylation of p53 protein. The present results show that asbestos, particularly chrysotile, induces phosphorylation of p53 protein at Ser15 in A549 cells depending on a DNA damage-signaling pathway.
Radiographic abnormalities and exposure to asbestos-contaminated vermiculite in the community of Libby, Montana, USA. L.A. Peipins, M. Lewin, S. Campolucci, et al. 2003;111(14):1753-9. PubMed · Publisher · Free full text

Abstract

Mining, handling, processing, and personal or commercial use of asbestos-contaminated vermiculite have led to widespread contamination of the Libby, Montana, area. We initiated a medical testing program in response to reports of respiratory illness in the community. The purpose of this analysis was to identify and quantify asbestos-related radiographic abnormalities among persons exposed to vermiculite in Libby and to examine associations between these outcomes and participants' self-reported exposures. A cross-sectional interview and medical testing were conducted in Libby from July through November 2000 and from July through September 2001. A total of 7,307 persons who had lived, worked, or played in Libby for at least 6 months before 31 December 1990 completed the interview. Of those, 6,668 participants > or = 18 years of age received chest radiographs to assess the prevalence of pleural and interstitial abnormalities. We observed pleural abnormalities in 17.8% of participants and interstitial abnormalities in < 1% of participants undergoing chest radiography. We examined 29 occupational, recreational, household, and other exposure pathways in the analysis. The prevalence of pleural abnormalities increased with increasing number of exposure pathways, ranging from 6.7% for those who reported no apparent exposures to 34.6% for those who reported > or = 12 pathways. The factors most strongly associated with pleural abnormalities were being a former W.R. Grace worker, being older, having been a household contact of a W.R. Grace worker, and being a male. In addition to being a former W.R. Grace worker, environmental exposures and other nonoccupational risk factors were also important predictors of asbestos-related radiographic abnormalities.
Analysis of the biological and chemical reactivity of zeolite-based aluminosilicate fibers and particulates. E. Fach, W.J. Waldman, M. Williams, et al. 2002;110(11):1087-96. PubMed · Publisher · Free full text

Abstract

Environmental and/or occupational exposure to minerals, metals, and fibers can cause lung diseases that may develop years after exposure to the agents. The presence of toxic fibers such as asbestos in the environment plus the continuing development of new mineral or vitreous fibers requires a better understanding of the specific physical and chemical features of fibers/particles responsible for bioactivity. Toward that goal, we have tested aluminosilicate zeolites to establish biological and chemical structure-function correlations. Zeolites have known crystal structure, are subject to experimental manipulation, and can be synthesized and controlled to produce particles of selected size and shape. Naturally occurring zeolites include forms whose biological activity is reported to range from highly pathogenic (erionite) to essentially benign (mordenite). Thus, we used naturally occurring erionite and mordenite as well as an extensively studied synthetic zeolite based on faujasite (zeolite Y). Bioactivity was evaluated using lung macrophages of rat origin (cell line NR8383). Our objective was to quantitatively determine the biological response upon interaction of the test particulates/fibers with lung macrophages and to evaluate the efficacy of surface iron on the zeolites to promote the Fenton reaction. The biological assessment included measurement of the reactive oxygen species by flow cytometry and chemiluminescence techniques upon phagocytosis of the minerals. The chemical assessment included measuring the hydroxyl radicals generated from hydrogen peroxide by iron bound to the zeolite particles and fibers (Fenton reaction). Chromatography as well as absorption spectroscopy were used to quantitate the hydroxyl radicals. We found that upon exposure to the same mass of a specific type of particulate, the oxidative burst increased with decreasing particle size, but remained relatively independent of zeolite composition. On the other hand, the Fenton reaction depended on the type of zeolite, suggesting that the surface structure of the zeolite plays an important role.
Characterization of the dust/smoke aerosol that settled east of the World Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 September 2001. P.J. Lioy, C.P. Weisel, J.R. Millette, et al. 2002;110(7):703-14. PubMed · Publisher · Free full text

Abstract

The explosion and collapse of the World Trade Center (WTC) was a catastrophic event that produced an aerosol plume impacting many workers, residents, and commuters during the first few days after 11 September 2001. Three bulk samples of the total settled dust and smoke were collected at weather-protected locations east of the WTC on 16 and 17 September 2001; these samples are representative of the generated material that settled immediately after the explosion and fire and the concurrent collapse of the two structures. We analyzed each sample, not differentiated by particle size, for inorganic and organic composition. In the inorganic analyses, we identified metals, radionuclides, ionic species, asbestos, and inorganic species. In the organic analyses, we identified polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, pesticides, phthalate esters, brominated diphenyl ethers, and other hydrocarbons. Each sample had a basic pH. Asbestos levels ranged from 0.8% to 3.0% of the mass, the PAHs were > 0.1% of the mass, and lead ranged from 101 to 625 microg/g. The content and distribution of material was indicative of a complex mixture of building debris and combustion products in the resulting plume. These three samples were composed primarily of construction materials, soot, paint (leaded and unleaded), and glass fibers (mineral wool and fiberglass). Levels of hydrocarbons indicated unburned or partially burned jet fuel, plastic, cellulose, and other materials that were ignited by the fire. In morphologic analyses we found that a majority of the mass was fibrous and composed of many types of fibers (e.g., mineral wool, fiberglass, asbestos, wood, paper, and cotton). The particles were separated into size classifications by gravimetric and aerodynamic methods. Material < 2.5 microm in aerodynamic diameter was 0.88-1.98% of the total mass. The largest mass concentrations were > 53 microm in diameter. The results obtained from these samples can be used to understand the contact and types of exposures to this unprecedented complex mixture experienced by the surviving residents, commuters, and rescue workers directly affected by the plume from 11 to 12 September and the evaluations of any acute or long-term health effects from resuspendable dust and smoke to the residents, commuters, and local workers, as well as from the materials released after 11 September until the fires were extinguished. Further, these results support the need to have the interior of residences, buildings, and their respective HVAC systems professionally cleaned to reduce long-term residential risks before rehabitation.
Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species. A. Xu, H. Zhou, D.Z. Yu, et al. 2002;110(10):1003-8. PubMed · Publisher · Free full text

Abstract

Asbestos is an important environmental carcinogen in the United States and remains the primary occupational concern in many developing countries; however, the underlying mechanisms of its genotoxicity are not known. We showed previously that asbestos is a potent gene and chromosomal mutagen in mammalian cells and that it induces mostly multilocus deletions. Furthermore, reactive oxygen species (ROS) are associated with the mutagenic process. To evaluate the contribution of ROS to the mutagenicity of asbestos, we examined their generation, particularly hydrogen peroxide, and compared the types of mutants induced by crocidolite fibers with those generated by H(2)O(2 )in human-hamster hybrid (A(L)) cells. Using confocal scanning microscopy together with the radical probe 5,6 -chloromethy-2,7 -dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA), we found that asbestos induces a dose-dependent increase in the level of ROS among fiber-treated A(L) cells, which is suppressed by concurrent treatment with dimethyl sulfoxide. Using N-acetyl-3,7-dihydroxyphenoxazine (Amplex Red reagent) together with horseradish peroxidase, we further demonstrated that there was a dose-dependent induction of H(2)O(2) in crocidolite-treated A(L) cells. The amount of H(2)O(2 )induced by asbestos reached a plateau at a dose of 6 microg/cm(2). Concurrent treatment with catalase (1,000 U/mL) inhibited this induction by 7- to 8-fold. Mutation spectrum analysis showed that the types of CD59(-) mutants induced by crocidolite fibers were similar to those induced by equitoxic doses of H(2)O(2). These results provide direct evidence that the mutagenicity of asbestos is mediated by ROS in mammalian cells.
The environmental history in pediatric practice: a study of pediatricians' attitudes, beliefs, and practices. N. Kilpatrick, H. Frumkin, J. Trowbridge, et al. 2002;110(8):823-7. PubMed · Publisher · Free full text

Abstract

We conducted a mail survey of practicing pediatricians in Georgia to assess their knowledge, attitudes, and behaviors regarding recording patients' environmental histories. Of 477 eligible pediatricians, 266 (55.8%) responded. Fewer than one in five reported having received training in environmental history-taking. Pediatricians reported that they strongly believe in the importance of environmental exposures in children's health, and 53.5% of respondents reported experience with a patient who was seriously affected by an environmental exposure. Pediatricians agreed moderately strongly that environmental history-taking is useful in identifying potentially hazardous exposures and in helping prevent these exposures. Respondents reported low self-efficacy regarding environmental history-taking, discussing environmental exposures with parents, and finding diagnosis and treatment resources related to environmental exposures. The probability of self-reported history-taking varied with the specific exposure, with environmental tobacco smoke and pets most frequently queried and asbestos, mercury, formaldehyde, and radon rarely queried. The pediatricians' preferred information resources include the American Academy of Pediatrics, newsletters, and patient education materials. Pediatricians are highly interested in pediatric environmental health but report low self-efficacy in taking and following up on environmental histories. There is considerable opportunity for training in environmental history-taking and for increasing the frequency with which such histories are taken.
An unusual case of mixed-dust exposure involving a "noncommercial" asbestos. R.F. Dodson, J.L. Levin. 2001;109(2):199-203. Case report PubMed · Publisher · Free full text

Abstract

Our health center evaluated an individual for suspected pneumoconiosis, which had resulted from exposures in a foundry/metal reclamation facility. Appropriate consent forms were obtained for the procedures. Historically, individuals who work in foundries have been exposed to various types of dusts. The clinical findings in this case were consistent with silicosis with a suspicion of asbestos-induced changes as well. A sample from this individual, analyzed by electron microscopy, showed both classical and atypical ferruginous bodies. The uncoated fiber burden in this individual indicated an appreciable number of anthophyllite asbestos fibers. This finding, coupled with analysis of cores from ferruginous bodies and the presence of ferruginous bodies in areas of interstitial fibrosis, pathologically supported the diagnosis of asbestos-related disease. The unique factor associated with this case is that unlike in some settings in Finland where anthophyllite was mined and used commercially, this mineral fiber is not commonly found in commercially used asbestos products in the United States. Although the actual source of the asbestos exposure in this case is still being sought, it should be recognized that anthophyllite is a contaminant of many other minerals used in workplace environments, including foundries. The fiber burden indicates a unique type of exposure, differing from that usually construed as typical in occupational settings in the United States.
Effect of size of man-made and natural mineral fibers on chemiluminescent response in human monocyte-derived macrophages. M. Ohyama, T. Otake, K. Morinaga. 2001;109(10):1033-8. PubMed · Publisher · Free full text

Abstract

Fiber size is an important factor in the tumorigenicity of various mineral fibers and asbestos fibers in animal experiments. We examined the time course of the ability to induce lucigenin-dependent chemiluminescence (CL) from human monocyte-derived macrophages exposed to Japan Fibrous Material standard reference samples (glass wool, rock wool, micro glass fiber, two types of refractory ceramic fiber, refractory mullite fiber, potassium titanium whisker, silicon carbide whisker, titanium oxide whisker, and wollastonite). We determined how fiber length or width might modify the response of cells. We found that the patterns of time-dependent increase of CL (sigmoid type) were similar for each sample except wollastonite. We observed a strong correlation between geometric-mean length and ability to induce CL in seven samples > 6 microm in length over the time course (largest r(2) = 0.9760). Although we also observed a close positive correlation between geometric-mean width and the ability to induce CL in eight samples < 1.8 microm in width at 15 min (r(2) = 0.8760), a sample of 2.4 microm in width had a low ability to induce CL. Moreover, the relationship between width and the rate of increase in ability to induce CL had a negative correlation at 30-60 min (largest r(2) = 0.7473). Our findings suggest that the release of superoxide from macrophages occurs nonspecifically for various types of mineral fibers depending on fiber length.
Environmental aftermath. L. Claudio. 2001;109(11):A528-36. PubMed · Publisher · Free full text

Summary

This news feature described environmental health concerns after the 11 September 2001 terrorist attacks destroyed the World Trade Center in New York City. It drew on interviews with scientists, physicians, officials and local residents, and on early monitoring results. The article noted that 5,000 tons of asbestos-containing fireproofing had been sprayed up to the fortieth floor of one tower before New York City banned asbestos spraying in May 1970. The collapse released dust and smoke that may have contained asbestos, PCBs, dioxins, lead, particulate matter and other contaminants. Nearly 20,000 people lived within a half-mile of the site, and thousands of rescue workers worked there, sometimes without respirators. All 99 EPA samples taken in and around Ground Zero between October 12 and 15 showed asbestos below 70 structures per square millimeter, the AHERA school reentry standard, although at least 27 earlier readings had exceeded it. Chest X-rays had been taken for 350 of about 4,000 firefighters as a baseline. Daily PM2.5 averages fell below the EPA level of concern, but hourly peaks, often at night, exceeded it. Lead in dust ranged from 38 to 635 micrograms per gram. Experts differed on the asbestos risk to residents. The article concluded that long-term health effects could not yet be predicted and that communicating this uncertainty to the public was a major challenge.

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Increased risk of malignant mesothelioma of the pleura after residential or domestic exposure to asbestos: a case-control study in Casale Monferrato, Italy. C. Magnani, P. Dalmasso, A. Biggeri, et al. 2001;109(9):915-9. PubMed · Publisher · Free full text

Abstract

The association of malignant mesothelioma (MM) and nonoccupational asbestos exposure is currently debated. Our study investigates environmental and domestic asbestos exposure in the city where the largest Italian asbestos cement (AC) factory was located. This population-based case-control study included pleural MM (histologically diagnosed) incidents in the area in 1987-1993, matched by age and sex to two controls (four if younger than 60). Diagnoses were confirmed by a panel of five pathologists. We interviewed 102 cases and 273 controls in 1993-1995, out of 116 and 330 eligible subjects. Information was checked and completed on the basis of factory and Town Office files. We adjusted analyses for occupational exposure in the AC industry. In the town there were no other relevant industrial sources of asbestos exposure. Twenty-three cases and 20 controls lived with an AC worker [odds ratio (OR) = 4.5; 95% confidence interval (CI), 1.8-11.1)]. The risk was higher for the offspring of AC workers (OR = 7.4; 95% CI, 1.9-28.1). Subjects attending grammar school in Casale also showed an increased risk (OR = 3.3; 95% CI, 1.4-7.7). Living in Casale was associated with a very high risk (after selecting out AC workers: OR = 20.6; 95% CI, 6.2-68.6), with spatial trend with increasing distance from the AC factory. The present work confirms the association of environmental asbestos exposure and pleural MM, controlling for other sources of asbestos exposure, and suggests that environmental exposure caused a greater risk than domestic exposure.
Dielectric changes in membrane properties and cell interiors of human mesothelial cells in vitro after crocidolite asbestos exposure. E. Dopp, L. Jonas, B. Nebe, et al. 2000;108(2):153-8. PubMed · Publisher · Free full text

Abstract

Asbestos induces cytogenetic and genotoxic effects in cultured cell lines in vitro. For further investigations of the fiber-induced cellular changes, electrorotation (ROT) measurements can be used to determine early changes of surface properties and dielectric cellular changes. In the present study, human mesothelial cells (HMC) were exposed to nontoxic concentrations of crocidolite asbestos (1 microg/cm(2)) for 12, 24, 30, 50, and 72 hr, and were investigated for changes in dielectric properties, morphologic and biochemical changes using ROT measurements, electron microscopy, and flow cytometry, respectively. The results of ROT measurements revealed slightly increased internal conductivity and decreased membrane conductance of HMC during the first 12 hr of exposure to crocidolite. This may be due to functional changes of ion channels of the cellular membrane. However, after exposures of >= 30 hr, reduced internal conductivity and increased membrane conductance of HMC occurred. These effects may be caused by permeabilization of the cell membrane and the leakage of ions into the surrounding medium. The membrane capacitance of HMC is always decreased during exposure of cells to crocidolite fibers. This decreased membrane capacitance may result from the observed reduction in the number of microvilli and from the shrinkage of cells as observed by electron microscopy and flow cytometry. Changes in composition of the plasma membrane were also observed after the labeling of phosphatidylserines (PS) on the cell surface. These observed changes can be related to apoptotic events. Whereas during the first 50 hr of exposure only a small number of HMC with increased exposure of PS on the cell surface was detected by flow cytometry, the dielectric properties of HMC showed marked changes during this time. Our results show that surface property changes of the cellular membrane of HMC as well as interior dielectric changes occur after the exposure of cells to crocidolite fibers. The observed changes are discussed in terms of complex combined cellular effects after amphibole asbestos exposure.
Environmental malignant mesothelioma in southern Anatolia: a study of fifty cases. E.H. Zeren, D. Gümürdülü, V.L. Roggli, et al. 2000;108(11):1047-50. PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a highly aggressive tumor of the serous membranes, which in humans results from exposure to asbestos and asbestiform fibers. Although occupational malignant mesothelioma is still the most common form of this lesion, naturally contaminated soil can play an important role in the development of environmental malignant mesothelioma in some parts of the world. Fifty cases of malignant mesothelioma (MM) from southern Turkey with no occupational history of asbestos exposure were reviewed regarding pathologic and clinical features. A case of hyaline fibrous plaque of the pleura was also included in this series. Histologically the cases were classified as epithelial (36 cases); sarcomatous (7 cases); and biphasic (7 cases). One of the sarcomatous cases was desmoplastic. Ultrastructural examination of the tumor tissue in three cases revealed long-surface microvilli in epithelial cells. Interstitial cells of the lung in one case showed electron-dense asbestos fibers in the cytoplasm. Mineralogical analyses of the lung tissue in three cases of MM and the case of pleural plaque showed high amounts of asbestos fibers most consistent with tremolite and actinolite. The clinical and pathologic features of our cases support that the environmental inhalation of asbestos is still a major health problem in some parts of Turkey.
Government laboratory worker with lung cancer: comparing risks from beryllium, asbestos, and tobacco smoke. C. Steinmaus, J.R. Balmes. 2000;108(10):1003-6. Case report PubMed · Publisher · Free full text

Abstract

Occupational medicine physicians are frequently asked to establish cancer causation in patients with both workplace and non-workplace exposures. This is especially difficult in cases involving beryllium for which the data on human carcinogenicity are limited and controversial. In this report we present the case of a 73-year-old former technician at a government research facility who was recently diagnosed with lung cancer. The patient is a former smoker who has worked with both beryllium and asbestos. He was referred to the University of California, San Francisco, Occupational and Environmental Medicine Clinic at San Francisco General Hospital for an evaluation of whether past workplace exposures may have contributed to his current disease. The goal of this paper is to provide an example of the use of data-based risk estimates to determine causation in patients with multiple exposures. To do this, we review the current knowledge of lung cancer risks in former smokers and asbestos workers, and evaluate the controversies surrounding the epidemiologic data linking beryllium and cancer. Based on this information, we estimated that the patient's risk of lung cancer from asbestos was less than his risk from tobacco smoke, whereas his risk from beryllium was approximately equal to his risk from smoking. Based on these estimates, the patient's workplace was considered a probable contributing factor to his development of lung cancer.
Health effects of asbestos and nonasbestos fibers. O.Y. Osinubi, M. Gochfeld, H.M. Kipen. 2000;108 Suppl 4(Suppl 4):665-74. Review PubMed · Publisher · Free full text

Abstract

Exposures to asbestos and synthetic fibers remain areas of great concern in the field of occupational lung disease. Despite extensive study, the health effects associated with fibers remains an area of substantial controversy. In particular, effects of fibers at relatively low doses, particularly for mesothelioma, remain a matter of evolving opinion, especially when integrated with the divergence of opinion on relative pathogenicity of different fiber types. Mechanistic studies continue to provide a window into pathogenesis and some hope for understanding dose-response relationships at the lower levels seen in contemporary Western workplaces and the general environment. Changes in clinical assessment based on use of new chest imaging techniques beyond the traditional plain film are also an area of evolution and begin to challenge B-reading as the definitive tool for noninvasive assessment of disease. Public health concerns have to a great extent been transported to the developing world where there is a strong trend toward increased use of asbestos, although it has been virtually eliminated from commerce in most developed countries. For nonasbestos fibers, the major unsettled issues are their relative potencies as carcinogens for the human lung and mesothelium and the need to sort out the relation between physical and chemical properties of these fibers and their pathogenicity. The recent discovery of "flock worker's lung" due to synthetic fibers once again alerts us to emerging diseases associated with new technologies.
Inhaled crocidolite mutagenicity in lung DNA. B. Rihn, C. Coulais, E. Kauffer, et al. 2000;108(4):341-6. PubMed · Publisher · Free full text

Abstract

We used transgenic mice carrying the lacI reporter gene to study the mutagenesis potential of asbestos crocidolite. The animals were exposed by nose-only inhalation to an aerosol containing 5.75 mg/m(3) crocidolite dust for 6 hr/day and 5 consecutive days. After 1, 4, and 12 weeks, we examined four end points: the cytology of bronchoalveolar lavage, the lung load of crocidolite, the hydrophobic DNA adducts, and the mutations in the lacI reporter gene. Twelve weeks after exposure, nearly 10% of the inhaled fibers remained in the lung (227 +/- 103 ng/mg lung). There was evidence of a typical inflammatory response consisting of multinucleate macrophages at weeks 4 and 12, whereas immediately after the exposure, we observed numerous polymorphonuclear neutrophils. The mutant frequency significatively increased during the fourth week after the exposure: 13.5 [time] 10(-5) in the exposed group versus 6. 9 10(-5) in the control group. The induction factor, defined by the ratio of checked mutants of exposed mice to checked mutants of control mice, was 1.96. The mutation spectrum of control lung DNA and exposed lung DNA was similar, suggesting the possible involvement of a DNA repair decrease in crocidolite-treated animals. We used the (32)P-postlabeling method and did not detect any increase of either 5 mC or bulky adduct in treated mice. This is the first study that demonstrates asbestos mutagenicity in vivo after a nose-only inhalation.
Inorganic dust pneumonias: the metal-related parenchymal disorders. P. Kelleher, K. Pacheco, L.S. Newman. 2000;108 Suppl 4(Suppl 4):685-96. Review PubMed · Publisher · Free full text

Abstract

In recent years the greatest progress in our understanding of pneumoconioses, other than those produced by asbestos, silica, and coal, has been in the arena of metal-induced parenchymal lung disorders. Inhalation of metal dusts and fumes can induce a wide range of lung pathology, including airways disorders, cancer, and parenchymal diseases. The emphasis of this update is on parenchymal diseases caused by metal inhalation, including granulomatous disease, giant cell interstitial pneumonitis, chemical pneumonitis, and interstitial fibrosis, among others. The clinical characteristics, epidemiology, and pathogenesis of disorders arising from exposure to aluminum, beryllium, cadmium, cobalt, copper, iron, mercury, and nickel are presented in detail. Metal fume fever, an inhalation fever syndrome attributed to exposure to a number of metals, is also discussed. Advances in our knowledge of antigen-specific immunologic reactions in the lung are particularly evident in disorders secondary to beryllium and nickel exposure, where immunologic mechanisms have been well characterized. For example, current evidence suggests that beryllium acts as an antigen, or hapten, and is presented by antigen-presenting cells to CD4+ T cells, which possess specific surface antigen receptors. Other metals such as cadmium and mercury induce nonspecific damage, probably by initiating production of reactive oxygen species. Additionally, genetic susceptibility markers associated with increased risk have been identified in some metal-related diseases such as chronic beryllium disease and hard metal disease. Future research needs include development of biologic markers of metal-induced immunologic disease, detailed characterization of human exposure, examination of gene alleles that might confer risk, and association of exposure data with that of genetic susceptibility.
Reducing environmental risk associated with laboratory decommissioning and property transfer. R. Dufault, E. Abelquist, S. Crooks, et al. 2000;108 Suppl 6(Suppl 6):1015-22. PubMed · Publisher · Free full text

Abstract

The need for more or less space is a common laboratory problem. Solutions may include renovating existing space, leaving or demolishing old space, or acquiring new space or property for building. All of these options carry potential environmental risk. Such risk can be the result of activities related to the laboratory facility or property (e.g., asbestos, underground storage tanks, lead paint), or the research associated with it (e.g., radioactive, microbiological, and chemical contamination). Regardless of the option chosen to solve the space problem, the potential environmental risk must be mitigated and the laboratory space and/or property must be decommissioned or rendered safe prior to any renovation, demolition, or property transfer activities. Not mitigating the environmental risk through a decommissioning process can incur significant financial liability for any costs associated with future decommissioning cleanup activities. Out of necessity, a functioning system, environmental due diligence auditing, has evolved over time to assess environmental risk and reduce associated financial liability. This system involves a 4-phase approach to identify, document, manage, and clean up areas of environmental concern or liability, including contamination. Environmental due diligence auditing includes a) historical site assessment, b) characterization assessment, c) remedial effort and d) final status survey. General practice standards from the American Society for Testing and Materials are available for conducting the first two phases. However, standards have not yet been developed for conducting the third and final phases of the environmental due diligence auditing process. Individuals involved in laboratory decommissioning work in the biomedical research industry consider this a key weakness.

1990s

A healthy home environment?. J. Manuel. 1999;107(7):A352-7. PubMed · Publisher · Free full text

Abstract

Over the past seven years, the U.S. Environmental Protection Agency has consistently ranked indoor air pollution among the top five risks to public health. One of the most dangerous indoor air pollutants is carbon monoxide (CO). CO can be lethal, but perhaps more important, many people suffer ill health from chronic, often undetected exposure to low levels of this gas, resulting in fatigue, headache, dizziness, nausea, and vomiting. Another dangerous pollutant is volatile organic compounds (VOCs), which come from sources including building products, cleaning agents, and paints. One VOC, formaldehyde, can act as an irritant to the conjunctiva and upper and lower respiratory tract. Formaldehyde is also known to cause nasal cancer in test animals.
A retired shipyard worker with rapidly progressive pulmonary interstitial fibrosis. E.V. Moy, H. Hu, D.C. Christiani. 1999;107(4):321-7. Case report PubMed · Publisher · Free full text

Abstract

We present a case of progressive interstitial fibrosis in a retired shipyard worker who was exposed to asbestos during the postwar era of the late 1940s and 1950s, when asbestos exposures in the workplace were not regulated. Forty years later, at 63 years of age, the patient presented with restrictive lung disease. The patient was diagnosed with asbestos-related pleural disease and parenchymal asbestosis. He remained stable for the next 7 years, but then he began to manifest rapid clinical progression, which raised the possibility of an unusual variant of asbestosis, a concomitant interstitial process, or an unrelated disease. Lung biopsy was not undertaken because of the patient's low pulmonary reserve and limited treatment options. An empiric trial of oral steroids was initiated, but his pulmonary status continued to deteriorate and he died of pulmonary failure at 72 years of age. Many diseases result in pulmonary interstitial fibrosis. Ideally, open lung biopsy should be performed, but this procedure inevitably causes complications in many patients with end-stage restrictive lung disease. Furthermore, while the presence of asbestos bodies in tissue sections is a sensitive and specific marker of asbestos exposure, neither this finding nor any other charge is a marker indicative of asbestosis or the severity of asbestosis. With the enactment of the Asbestos Standard in the United States, asbestos exposures have been decreasing in this country. However, industries that produce asbestos products and wastes continue to expand in developing countries. Prevention of asbestos-related lung disease should be a global endeavor, and asbestos exposures should be regulated in both developed and developing countries.
Asbestos and cancer: An overview of current trends in Europe. M. Albin, C. Magnani, S. Krstev, et al. 1999;107 Suppl 2(Suppl 2):289-98. Review PubMed · Publisher · Free full text

Abstract

This review assesses the contribution of occupational asbestos exposure to the occurrence of mesothelioma and lung cancer in Europe. Available information on national asbestos consumption, proportions of the population exposed, and exposure levels is summarized. Population-based studies from various European regions on occupational asbestos exposure, mesothelioma, and lung cancer are reviewed. Asbestos consumption in 1994 ranged, per capita, between 0. 004 kg in northern Europe and 2.4 kg in the former Soviet Union. Population surveys from northern Europe indicate that 15 to 30% of the male (and a few percent of the female) population has ever had occupational exposure to asbestos, mainly in construction (75% in Finland) or in shipyards. Studies on mesothelioma combining occupational history with biologic exposure indices indicate occupational asbestos exposure in 62 to 85% of the cases. Population attributable risks for lung cancer among males range between 2 and 50% for definite asbestos exposure. After exclusion of the most extreme values because of methodologic aspects, most of the remaining estimates are within the range of 10 to 20%. Estimates of women are lower. Extrapolation of the results to national figures would decrease the estimates. Norwegian estimates indicate that one-third of expected asbestos-related lung cancers might be avoided if former asbestos workers quit smoking. The combination of a current high asbestos consumption per capita, high exposure levels, and high underlying lung cancer rates in Central Europe and the former Soviet Union suggests that the lung cancers will arise from the smoking-asbestos interaction should be a major concern.
Combined effect of cigarette smoke and mineral fibers on the gene expression of cytokine mRNA. Y. Morimoto, T. Tsuda, H. Hori, et al. 1999;107(6):495-500. PubMed · Publisher · Free full text

Abstract

To investigate which parameters are stimulated by mineral fibers and whether cigarette smoke enhanced a fiber-induced response, we examined the level of cytokine mRNA from alveolar macrophages (AMs) and lungs of rats exposed to mineral fibers and cigarette smoke in vivo. Male Wistar rats were given a single intratracheal instillation of 2 mg of Union Internationale Contre le Cancer chrysotile or refractory ceramic fiber (RF1). The animals then inhaled a side stream of smoke 5 days per week for 4 weeks. The expression of manganese superoxide dismutase, inducible nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF), interleukin-1[alpha] (IL-1[alpha]), interleukin-6 (IL-6), and tumor necrosis factor-[alpha] (TNF[alpha]) mRNA from lipopolysaccharide-stimulated AMs and lungs of rats exposed to mineral fibers and/or cigarette smoke were assessed using semiquantitative reverse-transcriptase polymerase chain reaction. Exposure only to cigarette smoke increased in IL-1[alpha] mRNA levels in AMs. Chrysotile stimulated the expression of IL-1[alpha], TNF[alpha], and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1[alpha] and TNF[alpha] in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile; IL-1[alpha] in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1[alpha], iNOS, and bFGF were increased in rats stimulated with mineral fibers, and the stimulating effects of mineral fibers were enhanced by cigarette smoke. Therefore, IL-1[alpha], iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers.
Comments on "Comparative hazards of chrysotile asbestos and its substitutes: a European perspective". H. Savastano. 1999;107(12):A596-7. Letter PubMed · Publisher · Free full text
Comparative hazards of chrysotile asbestos and its substitutes: A European perspective. P.T. Harrison, L.S. Levy, G. Patrick, et al. 1999;107(8):607-11. PubMed · Publisher · Free full text

Abstract

Although the use of amphibole asbestos (crocidolite and amosite) has been banned in most European countries because of its known effects on the lung and pleura, chrysotile asbestos remains in use in a number of widely used products, notably asbestos cement and friction linings in vehicle brakes and clutches. A ban on chrysotile throughout the European Union for these remaining applications is currently under consideration, but this requires confidence in the safety of substitute materials. The main substitutes for the residual uses of chrysotile are p-aramid, polyvinyl alcohol (PVA), and cellulose fibers, and it is these materials that are evaluated here. Because it critically affects both exposure concentrations and deposition in the lung, diameter is a key determinant of the intrinsic hazard of a fiber; the propensity of a material to release fibers into the air is also important. It is generally accepted that to be pathogenic to the lung or pleura, fibers must be long, thin, and durable; fiber chemistry may also be significant. These basic principles are used in a pragmatic way to form a judgement on the relative safety of the substitute materials, taking into account what is known about their hazardous properties and also the potential for uncontrolled exposures during a lifetime of use (including disposal). We conclude that chrysotile asbestos is intrinsically more hazardous than p-aramid, PVA, or cellulose fibers and that its continued use in asbestos-cement products and friction materials is not justifiable in the face of available technically adequate substitutes.
In situ microscopic analysis of asbestos and synthetic vitreous fibers retained in hamster lungs following inhalation. R.A. Rogers, J.M. Antonini, H. Brismar, et al. 1999;107(5):367-75. PubMed · Publisher · Free full text

Abstract

Hamsters breathed, nose-only, for 13 weeks, 5 days/week, 6 hr/day, either man-made vitreous fiber (MMVF)10a, MMVF33, or long amosite asbestos at approximately 300 World Health Organization (WHO) fibers/cc or long amosite at 25 WHO fibers/cc. [World Health Organization fibers are longer than 5 microm and thicker than 3 microm, with aspect ratio >3.] After sacrifice, fiber burden was estimated (left lungs) by ashing and scanning electron microscopy (ashing/SEM) or (right middle lobes) by confocal laser scanning microscopy (CLSM) in situ. In situ CLSM also provided three-dimensional views of fibers retained, undisturbed, in lung tissue. Fibers of each type were lodged in alveoli and small airways, especially at airway bifurcations, and were seen fully or partly engulfed by alveolar macrophages. Amosite fibers penetrated into and through alveolar septa. Length densities of fibers in parenchyma (total length of fiber per unit volume of lung) were estimated stereologically from fiber transsections counted on two-dimensional optical sections and were 30.5, 25.3, 20.0, and 81.6 mm/mm3 for MMVF10a, MMVF33, and low- and high-dose amosite, respectively. Lengths of individual fibers were measured in three dimensions by tracking individual fibers through series of optical sections. Length distributions of amosite fibers aerosolized, but before inhalation versus after retention in the lung were similar, whether determined by ashing/SEM or in situ CLSM. In contrast, the fraction of short MMVF10a and MMVF33 fibers increased and the geometric mean fiber lengths of both MMVFs decreased by approximately 60% during retention. Most likely due to fiber deposition pattern and differences in sampling, fiber burdens [MMVF10a, MMVF33, and amosite (high dose; 269 WHO fibers/cc)] determined by ashing/SEM were 1.4, 1. 5, and 3.5 times greater, respectively, than those calculated from in situ CLSM data. In situ CLSM is able to provide detailed information about the anatomic sites of fiber retention and also fiber lengths and burdens in good agreement with ashing/SEM results.
Occupational cancer in central European countries. E. Fabiánová, N. Szeszenia-Dabrowska, K. Kjaerheim, et al. 1999;107 Suppl 2(Suppl 2):279-82. Review PubMed · Publisher · Free full text

Abstract

The countries of central Europe, including Poland, the Czech Republic, Slovakia, Hungary, Romania, and Bulgaria, suffer from environmental and occupational health problems created during the political system in place until the late 1980s. This situation is reflected by data on workplace exposure to hazardous agents. Such data have been systematically collected in Skovakia and the Czech Republic since 1977. The data presented describe mainly the situation in the early 1990s. The number of workers exposed to risk factors at the workplace represent about 10% of the working population in Slovakia and 30% in Poland. In Slovakia in 1992 the percentage of persons exposed to chemical substances was 16.4%, to ionizing radiation 4.3%, and to carcinogens 3.3% of all workers exposed to risk factors. The total number of persons exposed to substances proven to be carcinogens in Poland was 1.3% of the employees; 2.2% were exposed to the suspected carcinogens. The incidence of all certified occupational diseases in the Slovak Republic was 53 per 100,000 insured employees in 1992. Cancers certified as occupational cancers are skin cancer caused by occupational exposure to carcinogens, lung cancer caused by ionizing radiation, and asbestosis together with lung cancer. Specific information on occupational cancers from Romania and Bulgaria was not available for this paper. It is difficult to predict a trend for future incidences of occupational cancer. Improved control technology, governmental regulatory activity to reduce exposure, surveillance of diseases and risk factors, and vigilant use of preventive measures should, however, ultimately reduce occupational cancer.
Occupational cancer in europe. P. Boffetta, M. Kogevinas. 1999;107 Suppl 2(Suppl 2):227. PubMed · Publisher · Free full text

Abstract

This monograph summarizes the current research on the epidemiology and prevention of occupational cancer in Europe. Eleven peer-reviewed articles offer a composite view of the current status and future perspectives of this discipline at a time of major economic and political changes in Europe. The monograph includes a brief history of occupational cancer research in Europe and the current burden of cancer from occupational exposure. A large portion of the monograph is devoted to reviews of occupational cancer in various European countries or groups of countries. The first two reviews describe those regions with the strongest tradition of research in the field: the Nordic countries and the United Kingdom. These countries are characterized by high-quality cancer registries and routinely collected information on occupation, e.g., on the occasion of censuses, allowing record linkage studies. Four articles address the situation in the remaining large Western European countries--France, Germany, Italy, and Spain. Although these countries have a strong tradition in occupational health research, with the possible exception of Spain, their epidemiologic research dates back only to the 1970s and 1980s; in recent years, however, research on occupational cancer has expanded considerably. The last two articles of the geographic overview describe the occupational cancer research in the Central European countries and the European territories of the Commonwealth of Independent States. The authors of these two articles critically review the available data on occupational cancer from former Socialist countries and provide reliable information on the extent and amount of occupational exposure to carcinogens. The two final articles of the monograph address specific thematic issues: the importance of asbestos as an occupational carcinogen in Europe and the use of routinely collected data to investigate occupational cancer in women, based on the experience in England and Wales. Despite the heterogeneity of these articles, which reflects to a large extent the differences in quality and completeness of the available data on occupational cancer, they represent an original attempt to provide a systematic overview of occupational cancer research in Europe. This publication is originally a partial result of two projects on occupational cancer in Europe funded by the European Commission, Directorate General XII (grants BMH1-CT92-1110 and BMH1-CT95-1100) and has been expanded to include non-European Union countries.
Occupational cancer in Germany. I. Brüske-Hohlfeld. 1999;107 Suppl 2(Suppl 2):253-8. Review PubMed · Publisher · Free full text

Abstract

As in probably mostly all other European countries, the incidence of occupational cancer in Germany increased steadily after World War II. In 1994 about 1,600 cases of occupational cancer were compensated--more than ever before. More than half of these cases were lung cancer, most caused either by asbestos (n=545) or by ionizing radiation ((italic)n(/italic)=306). Other frequent target organs of asbestos were the pleura and the peritoneum with 495 cases of mesotheliomas. Asbestos was the single most important risk factor for occupational cancer, causing more than 1000 deaths per year. All other malignant diseases, such as bladder cancer, leukemia, angiosarcoma of the liver, adenocarcinoma of the nose or nasal sinuses, and skin cancer, were comparatively rare. Although primary exposure to ionizing radiation in uranium ore mining occurred in the 1950s and attributable lung cancers seem to be on the decline, this is not true for asbestos, where the peak incidence in lung cancer and mesothelioma has not been reached yet.
Occupational cancer in Italy. E. Merler, P. Vineis, D. Alhaique, et al. 1999;107 Suppl 2(Suppl 2):259-71. Review PubMed · Publisher · Free full text

Abstract

This article is a discussion of occupational cancer in Italy. The introduction provides the necessary context of Italian industrialization and occupational health regulation. This is followed by a review of Italian epidemiologic studies of occupational cancer risks considered in terms of relative measures of risk and attributable risk of carcinogenic agents or exposure circumstances. We attempt to establish the number of workers exposed to carcinogens in Italy and the intensity of their exposures. Finally, the Italian system of compensation for occupational cancer is discussed. Several cohort and case-control studies have addressed the issue of occupational risks, mostly among male workers. The results of these studies suggest that the growing incidence of and mortality by mesothelioma is explained by the widespread and intense exposure to asbestos in some Italian industrial settings. A high attributable risk of lung tumors among male populations in industrial areas of northern Italy is explained by occupational exposures. However, insufficient data are available for clear definition of the extent and intensity of occupational exposure to carcinogenic substances. In Italy, we must prioritize and maximize resources in occupational cancer epidemiology and revitalize the role of national institutions. Recent legislation has established new regulations on the handling of carcinogenic substances in industrial settings, a new list of occupational diseases, and a national registry of mesothelioma linked to asbestos exposure. These legislative changes are expected to have positive effects.
Occupational cancer in the United Kingdom. D. Coggon. 1999;107 Suppl 2(Suppl 2):239-44. Review PubMed · Publisher · Free full text

Abstract

Most of the known occupational hazards of cancer have occurred in the United Kingdom. Over recent decades a contraction of manufacturing industry and legal controls on carcinogens have led to reductions in exposure, but cases continue to occur, often as a consequence of exposures 20 or more years ago. By far the most important occupational cause of cancer in the United Kingdom is asbestos, which currently accounts for some 600 cases of mesothelioma and perhaps 100 cases of bronchial carcinoma per year. Recent trends suggest that the number of mesothelioma cases attributable to asbestos will increase over the next few decades. Exposure to sunlight in outdoor work may cause several hundred cases of nonmelanomatous skin cancer per year, and occupational exposure to polycyclic aromatic hydrocarbons could be responsible for a similar number of skin and lung tumors. Other known occupational hazards of cancer are unlikely to account for more than 100 cases per year in total.
Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury. S. Zhu, M. Manuel, S. Tanaka, et al. 1998;106 Suppl 5(Suppl 5):1157-63. Review PubMed · Publisher · Free full text

Abstract

Recently, a second pathway for the generation of potential oxidants with the reactivity of the hydroxyl radical without the need for metal catalysis has been described. In response to various inflammatory stimuli, lung endothelial, alveolar, and airway epithelial cells, as well as activated alveolar macrophages, produce both nitric oxide (.NO) and superoxide anion radicals (O2.-). .NO regulates pulmonary vascular and airway tone and plays an important role in lung host defense against various bacteria. However, .NO may be cytotoxic by inhibiting critical enzymes such as mitochondrial aconitase and ribonucleotide reductase, by S-nitrosolation of thiol groups, or by binding to their iron-sulfur centers. In addition, .NO reacts with O2.- at a near diffusion-limited rate to form the strong oxidant peroxynitrite (ONOO-), which can nitrate and oxidize key amino acids in various lung proteins such as surfactant protein A, and inhibit their functions. The presence of ONOO- in the lungs of patients with acute respiratory distress syndrome has been demonstrated by measuring levels of nitrotyrosine, the stable product of tyrosine nitration. Various studies have shown that inhalation or intratracheal instillation of various respirable mineral dusts or asbestos fibers increased levels of inducible nitric oxide synthase mRNA. In this presentation, we review the evidence for the upregulation of .NO in the lungs of animals exposed to mineral particulates and assess the contribution of reactive nitrogen species in the pathogenesis of the resultant lung injury.
Crocidolite activates NF-kappa B and MIP-2 gene expression in rat alveolar epithelial cells. Role of mitochondrial-derived oxidants. K.E. Driscoll, J.M. Carter, B.W. Howard, et al. 1998;106 Suppl 5(Suppl 5):1171-4. PubMed · Publisher · Free full text

Abstract

Nuclear factor kappa B (NF-kappa B) is a transcription factor that regulates expression of several genes coding for inflammatory and immunoregulatory proteins including the neutrophil chemotactic cytokine MIP-2. In previous studies we found that crocidolite asbestos activates the nuclear translocation of NF-kappa B as well as MIP-2 gene expression in rat alveolar type II cells. Here we report that both crocidolite-induced NF-kappa B activation of MIP-2 gene expression can be attenuated by the antioxidant tetramethylthiourea, suggesting the dependence of these responses on oxidative stress. Crocidolite exposure of RLE-TN cells also increased production of H2O2, a response that was inhibited by the mitochondrial respiratory chain inhibitor thenoyltrifluoroacetone (TTFA). TTFA treatment of RLE-6TN cells also inhibited crocidolite-induced nuclear translocation of NF-kappa B and MIP-2 gene expression. These results indicate crocidolite exposure of rat alveolar type II cells results in increased production of mitochondrial-derived hydrogen peroxide and that mitochondrial-derived oxidants contribute to crocidolite activation of NF-kappa B and increases in MIP-2 gene expression.
Modulation of mitochondrial gene expression in pulmonary epithelial cells exposed to oxidants. Y.M. Janssen, K.E. Driscoll, C.R. Timblin, et al. 1998;106 Suppl 5(Suppl 5):1191-5. PubMed · Publisher · Free full text

Abstract

Oxidants are important in the regulation of signal transduction and gene expression. Multiple classes of genes are transcriptionally activated by oxidants and are implicated in different phenotypic responses. In the present study, we performed differential mRNA display to elucidate genes that are induced or repressed after exposure of rat lung epithelial (RLE) cells to H2O2 or crocidolite asbestos, a pathogenic mineral that generates oxidants. After 8 or 24 hr of exposure, RNA was extracted, reverse transcribed, and amplified by polymerase chain reaction with degenerate primers to visualize alterations in gene expression. The seven clones obtained were sequenced and encoded the mitochondrial genes, NADH dehydrogenase subunits ND5 and ND6, and 16S ribosomal RNA. Evaluation of their expression by Northern blot analysis revealed increased expression of 16S rRNA after 1 or 2 hr of exposure to H2O2. At later time periods (4 and 24 hr), mRNA levels of 16S rRNA and NADH dehydrogenase were decreased in H2O2-treated RLE cells when compared to sham controls. Crocidolite asbestos caused increases in 16S rRNA levels after 8 hr of exposure, whereas after 24 hr of exposure to asbestos, 16S rRNA levels were decreased in comparison to sham controls. In addition to these oxidants, the nitric oxide generator spermine NONOate caused similar decreases in NADH dehydrogenase mRNA levels after 4 hr of exposure. The present data and previous studies demonstrated that all oxidants examined resulted in apoptosis in RLE cells during the time frame where alterations of mitochondrial gene expression were observed. As the mitochondrion is a major organelle that controls apoptosis, alterations in expression of mitochondrial genes may be involved in the regulation of apoptosis.
Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis. V. Vallyathan, X. Shi, V. Castranova. 1998;106 Suppl 5(Suppl 5):1151-5. Review PubMed · Publisher · Free full text

Abstract

Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis.
Selected new developments in asbestos immunotoxicity. G.J. Rosenthal, E. Corsini, P. Simeonova. 1998;106 Suppl 1(Suppl 1):159-69. Review PubMed · Publisher · Free full text

Abstract

Research over the past three decades has shown that the mammalian immune system can be altered by the occupational exposure of asbestos. Early clinical studies generally focused on systemic observations of immune alteration such as the number and function of peripheral lymphocytes and monocytes. More recently as the regulatory influence of local immunity in health and disease becomes more defined, immunologic changes occurring in the lung, the primary target organ of asbestos, have been significant areas of investigation. This review will focus on recent studies that examine the influence of asbestos on pulmonary immunity as well as the role of host immune competence in asbestos-related disease.
Analyzing the genes and peptide growth factors expressed in lung cells in vivo consequent to asbestos exposure and in vitro. A.R. Brody, J.Y. Liu, D. Brass, et al. 1997;105 Suppl 5(Suppl 5):1165-71. Review PubMed · Publisher · Free full text

Abstract

Inhalation of fibrogenic particles causes injury to the bronchiolar-alveolar epithelium. Consequently, there is a rapid proliferative response as the epithelium recovers and interstitial mesenchymal cells divide and produce connective tissue. In our model of brief (5-hr) exposure to chrysotile asbestos (approximately 1000 fibers/cc) in rats and mice, these events result in focal scarring at the bronchiolar-alveolar duct junctions in a histopathologic pattern identical to that seen in asbestos-exposed individuals. After 3 consecutive days of exposure, these lesions persist for at least 6 months postexposure. We postulate that cell proliferation and production of extracellular matrix is mediated in large part by three peptide growth factors, transforming growth factors alpha and beta (TGF-alpha and -beta), and platelet-derived growth factor (PDGF) A- and B-chains. To test this hypothesis in part, we have asked whether the genes that code for these growth factor proteins are activated at sites of asbestos-induced lung injury. If these genes were not activated, it would be reasonable to suspect that other potent growth factors and cytokines released during lung injury could be the primary mediators of fibroproliferative lung disease. In the studies reported here, we show, by in situ hybridization (ISH) and immunohistochemistry, that the four genes and their concomitant proteins are expressed within 24 hr in the bronchiolar-alveolar epithelium and underlying mesenchymal cells. RNase protection assay and ISH showed that the PDGF gene was upregulated during the first 5 hr of exposure and all the gene products remained above control levels for at least 2 weeks postexposure. TGF-alpha is a potent mitogen for epithelial cells, whereas the PDGF isoforms are potent growth factors for mesenchymal cells. TGF-beta retards fibroblast growth but stimulates extracellular matrix synthesis. Further studies using gene knockouts, appropriate antibodies, or antisense technology will be necessary to prove whether any of the growth factors are playing a significant role in fibrogenic lung disease. In addition, we have carried out a series of studies using type II alveolar epithelial cells purified from adult mouse lungs and maintained for up to 8 weeks in serum-free culture. These cells exhibit high transepithelial resistance values and they release TGF-beta 1 and -beta 2. This cell type also has been cultured from TGF-alpha knockout mice, resulting in monolayers with increased transepithelial resistance. This combination of studies in vivo and in vitro will allow us to pursue the mechanisms through which growth factors mediate lung fibrosis.
Approaches to characterizing human health risks of exposure to fibers. V.T. Vu, D.Y. Lai. 1997;105 Suppl 5(Suppl 5):1329-36. Review PubMed · Publisher · Free full text

Abstract

Naturally occurring and man-made (synthetic) fibers of respirable sizes are substances that have been identified by the U.S. Environmental Protection Agency (U.S. EPA) as priority substances for risk reduction and pollution prevention under the Toxic Substances Control Act (TSCA). The health concern for respirable fibers is based on the link of occupational asbestos exposure and environmental erionite fiber exposure to the development of chronic respiratory diseases, including interstitial lung fibrosis, lung cancer, and mesothelioma in humans. There is also considerable laboratory evidence indicating that a variety of fibers of varying physical and chemical characteristics can elicit fibrogenic and carcinogenic effects in animals under certain exposure conditions. This paper discusses key scientific issues and major default assumptions and uncertainties pertaining to the risk assessment of inhaled fibers. This is followed by a description of the types of assessment performed by the U.S. EPA to support risk management actions of new fibers and existing fibers under TSCA. The scope and depth of these risk assessments, however, vary greatly depending on whether the substance under review is an existing or a new fiber, the purpose of the assessment, the availability of data, time, and resources, and the intended nature of regulatory action. In general, these risk assessments are of considerable uncertainty because health hazard and human exposure information is often incomplete for most fibers. Furthermore, how fibers cause diseases and what specific determinants are critical to fiber-induced toxicity and carcinogenicity are still not completely understood. Further research to improve our knowledge base in fiber toxicology and additional toxicity and exposure data gathering are needed to more accurately characterize the health risks of inhaled fibers.
Asbestos and silica-induced changes in human alveolar macrophage phenotype. A. Holian, M.O. Uthman, T. Goltsova, et al. 1997;105 Suppl 5(Suppl 5):1139-42. PubMed · Publisher · Free full text

Abstract

The mechanism by which fibrogenic particulates induce inflammation that can progress to lung fibrosis is uncertain. The alveolar macrophage (AM) has been implicated in the inflammatory process because of its function and reported release of inflammatory mediators when isolated from fibrotic patients. It has been recently shown that fibrogenic, but not nonfibrogenic, particulates are highly potent in inducing apoptosis of human AM. In this study, we tested the hypothesis that fibrogenic particulates could shift the phenotypic ratio of human AM to a more inflammatory condition. The macrophage phenotypes were characterized by flow cytometry targeting the RFD1 and RFD7 epitopes. Results demonstrated that chrysotile and crocidolite asbestos, as well as crystalline silica, but not titanium dioxide or wollastonite, increased the RFD1+ phenotype (inducer or immune activator macrophages) and decreased the RFD1+ RFD7+ phenotype (suppressor macrophages). These results provide a mechanistic explanation that may link apoptosis (namely, suppressor macrophages) to a shift in the ratio of macrophage phenotypes that could initiate lung inflammation.
Asbestos, asbestosis, and lung cancer: observations in Quebec chrysotile workers. B.W. Case, A. Dufresne. 1997;105 Suppl 5(Suppl 5):1113-9. PubMed · Publisher · Free full text

Abstract

One prospective epidemiologic study of asbestos cement workers with radiological small opacities has been cited as a rationale for attributing excess lung cancer to asbestosis. This approach could have considerable practical value for disease attribution in an era of decreasing exposure. However, a recent International Agency for Research on Cancer review concludes that the mechanism of production of asbestos-related lung cancer are unknown. Asbestosis, therefore, cannot be a biologically effective dose marker of lung cancer susceptibility. Asbestosis nonetheless would be useful in identifying asbestos-attributable lung cancer cases if it could be proven an infallible exposure indicator. In this study, we tested this hypothesis in the chrysotile miners and millers of Quebec, Canada. We examined exposure histories, autopsy records, and lung fiber content for 111 Quebec chrysotile miners and millers. If the hypothesis of an asbestosis requirement for lung cancer attribution were accurate, we would expect as asbestosis diagnosis to separate those with lung cancer and high levels of exposure from those with lower levels of exposure in a specific and sensitive manner. This is the first such study in which historical job-based individual estimates based on environmental measurements, lung fiber content, exposure timing, and complete pathology records including autopsies were available for review. We found significant excesses of lung tremolite and chrysotile and estimated cumulative exposure in those with lung cancer and asbestosis compared to those with lung cancer without asbestosis. However, when the latter were directly compared on a case-by-case basis, there was a marked overlap between lung cancer cases with and without asbestosis regardless of the measure of exposure. Smoking habits did not differ between lung cancer cases with and without asbestosis. In regression models, smoking pack-years discriminated between those with the without lung cancer, regardless of asbestosis status. Most seriously, the pathologic diagnosis of asbestosis itself seemed arbitrary in many cases. We conclude that although the presence of pathologically diagnosed asbestosis is a useful marker of exposure, the absence of this disease must be regarded as one of many factors in determining individual exposure status and disease causation.
Battling over asbestos in the third world. 1997;105(11):1178-80. News PubMed · Publisher · Free full text

Summary

This news feature described the debate over asbestos use in developing countries, where demand had grown as many developed countries phased it out. It summarized a report by Fernanda Giannasi and Annie Thebaud-Mony, published in the April-June 1997 issue of the International Journal of Occupational and Environmental Health, that described a "silent epidemic" of asbestos-related disease among workers in Brazil. At an Eternit asbestos cement plant in Osasco that closed in the early 1990s, four of the first 12 workers seen at one clinic had asbestosis, seven had pleural plaques, and one died of peritoneal cancer four months later. In an unpublished follow-up, Giannasi reported that 57.5% of 421 former workers examined had diseases that could be related to asbestos dust. The authors concluded that asbestos could not be used safely and that a ban was needed, especially in developing countries. Scott Houston of the industry-supported Asbestos Institute argued that chrysotile, which he said made up 90% of asbestos used worldwide, posed no public health risk with basic exposure controls, and that substitutes might be more dangerous. Joseph LaDou and Barry Castleman disputed this. Castleman said alternative materials existed. Both said industry groups had influenced the WHO and ILO through consultants presented as independent experts. Houston denied any misrepresentation.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Can microwave radiation at high temperatures reduce the toxicity of fibrous crocidolite asbestos?. M. Gulumian, Z.L. Nkosibomvu, K. Channa, et al. 1997;105 Suppl 5(Suppl 5):1041-4. PubMed · Publisher · Free full text

Abstract

Exposure of animals and humans to crocidolite asbestos fibers produces fibrosis and two types of cancers: bronchogenic carcinoma and mesothelioma. It is therefore desirable to reduce toxicity of these fibers without affecting their other characteristics. In this study, commercial crocidolite asbestos fibers were radiated with microwave radiation at different temperatures. Radiated fibers and nonradiated original fibers were then studied by Mössbauer spectroscopy to quantify the amount of ferric and ferrous ions present at structurally different sites in each crocidolite sample. They were also studied for their ability to initiate the peroxidation of linoleic acid to assess the effect of radiation on this process. Results showed that microwave radiation reduced the total Fe2+/Fe3+ ratio. This reduction produced a concomitant decrease in the ability of the radiated samples to peroxidize linoleic acid.
Cell signaling pathways elicited by asbestos. B.T. Mossman, S. Faux, Y. Janssen, et al. 1997;105 Suppl 5(Suppl 5):1121-5. PubMed · Publisher · Free full text

Abstract

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to asbestos fibers in vitro. These include nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) cascade important in regulation of the transcription factor, activator protein-1 (AP-1). Both NF kappa B and AP-1 bind to specific DNA sequences within the regulatory or promoter regions of genes that are critical to cell proliferation and inflammation. Unraveling the cell signaling cascades initiated by mineral dusts and pharmacologic inhibition of these events may be important for the control and treatment of mineral-associated occupational diseases.
Chemical characterization and reactivity of iron chelator-treated amphibole asbestos. J. Gold, H. Amandusson, A. Krozer, et al. 1997;105 Suppl 5(Suppl 5):1021-30. PubMed · Publisher · Free full text

Abstract

Iron in amphibole asbestos is implicated in the pathogenicity of inhaled fibers. Evidence includes the observation that iron chelators can suppress fiber-induced tissue damage. This is believed to occur via the diminished production of fiber-associated reactive oxygen species. The purpose of this study was to explore possible mechanisms for the reduction of fiber toxicity by iron chelator treatments. We studied changes in the amount and the oxidation states of bulk and surface iron in crocidolite and amosite asbestos that were treated with iron-chelating desferrioxamine, ferrozine, sodium ascorbate, and phosphate buffer solutions. The results have been compared with the ability of the fibers to produce free radicals and decompose hydrogen peroxide in a cell-free system in vitro. We found that chelators can affect the amount of iron at the surface of the asbestos fibers and its valence, and that they can modify the chemical reactivity of these surfaces. However, we found no obvious or direct correlations between fiber reactivity and the amount of iron removed, the amount of iron at the fiber surface, or the oxidation state of surface iron. Our results suggest that surface Fe3+ ions may play a role in fiber-related carboxylate radical formation, and that desferrioxamine and phosphate groups detected at treated fiber surfaces may play a role in diminishing and enhancing, respectively, fiber redox activity. It is proposed that iron mobility in the silicate structure may play a larger role in the chemical reactivity of asbestos than previously assumed.
Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results. T.W. Hesterberg, C. Axten, E.E. McConnell, et al. 1997;105 Suppl 5(Suppl 5):1223-9. PubMed · Publisher · Free full text

Abstract

The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups.
Crocidolite asbestos induces apoptosis of pleural mesothelial cells: role of reactive oxygen species and poly(ADP-ribosyl) polymerase. V.C. Broaddus, L. Yang, L.M. Scavo, et al. 1997;105 Suppl 5(Suppl 5):1147-52. PubMed · Publisher · Free full text

Abstract

Mesothelial cells, the progenitor cells of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known. We asked whether asbestos induced apoptosis in mesothelial cells and whether reactive oxygen species were important. Rabbit pleural mesothelial cells were exposed to crocidolite asbestos or control particles (1-10 micrograms/cm2) over 24 hr and evaluated for oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation. Asbestos fibers, not control particles, induced apoptosis in mesothelial cells by all assays. Induction of apoptosis was dose dependent; crocidolite (5 micrograms/cm2) induced apoptosis (15.0 +/- 1.1%, mean +/- SE; n = 12) versus control particles (< 4%), as measured by appearance of nuclear condensation. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen), deferoxamine, and 3-aminobenzamide (an inhibitor of the nuclear enzyme, poly(adenosine diphosphate-ribosyl) polymerase). We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species. We speculate that escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations.
Cytokines and particle-induced inflammatory cell recruitment. K.E. Driscoll, J.M. Carter, D.G. Hassenbein, et al. 1997;105 Suppl 5(Suppl 5):1159-64. Review PubMed · Publisher · Free full text

Abstract

The inflammatory response is a key component of host defense. However, excessive or persistent inflammation can contribute to the pathogenesis of disease. Inflammation is regulated, in part, by cytokines, which are small, typically glycosylated proteins that interact with membrane receptors to regulate cellular processes such as proliferation, differentiation, and secretion. During the past 10 years studies in humans and experimental animals have demonstrated that a cytokine called tumor necrosis factor alpha (TNF-alpha) plays a key role in the initiation of inflammatory responses in the lung and other tissues, including inflammation resulting from inhalation of noxious particles. There is now compelling evidence that one of the pathways by which inhaled particles stimulate the recruitment and subsequent activation of inflammatory cells is through the activation of lung macrophages to release TNF-alpha. TNF-alpha then acts via paracrine and autocrine pathways to stimulate cells to release other cytokines known as chemokines, which are directly chemotactic to leukocytes and other cells that participate in inflammatory and wound healing responses. In addition to a TNF-alpha-mediated pathway, there is growing evidence that some particles such as quartz and crocidolite can directly activate lung epithelial cells to release chemokines such as macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant, and interleukin-8. A direct stimulatory effect of particles on lung epithelium may represent an additional or alternate pathway by which inhaled particles may elicit inflammation in the lung. Recent studies have suggested that oxidative stress may be a component of the mechanism by which particles activate cytokine production in cells such as macrophages and epithelial cells. The contribution of oxidative stress to particle-induced cytokine gene expression appears to be mediated, at least in part, through activation of the transcription factor nuclear factor kappa B.
Demonstration of nitric oxide on asbestos and silicon carbide fibers with a new ultraviolet spectrophotometric assay. P. Leanderson, V. Lagesson, C. Tagesson. 1997;105 Suppl 5(Suppl 5):1037-40. PubMed · Publisher · Free full text

Abstract

Nitric oxide (NO) has a number of important functions in biological systems and may play a role in the toxicity of mineral fibers. We investigated whether NO might be present on the surface of mineral fibers and if crocidolite could adsorb NO from NO gas or cigarette smoke. NO was determined with a new gas chromatography-ultraviolet spectrophotometric technique after thermal desorption from the fiber surface and injection in a gas flow cell. NO was found in different amounts on chrysotile B, crocidolite, amosite, and silicon carbide whiskers. There was a strong correlation between the amount of NO and the specific surface area of these fibers (r = 0.98). NO could not be demonstrated on rockwool fibers [man-made vitreous fiber(s) (MMVF)21 and MMVF22] or silicon nitride whiskers. NO on crocidolite, amosite, and silicon carbide whiskers was readily desorbed from the fibers at increased temperature, while NO on chrysotile B seemed to be more firmly adsorbed to the fiber and required a longer period of time to be desorbed. The amount of NO bound to crocidolite increased from 34 micrograms/g fiber to 85 and 474 micrograms/g after exposing the fibers to cigarette smoke and NO gas, respectively. These findings indicate that a) NO adsorbs to fiber surfaces, b) some fibers adsorb more NO than others, c) some fibers adsorb NO more strongly than others, and d) the amounts of NO on fibers may be increased after exposure of the fiber to cigarette smoke or other sources of NO. The biological significance of NO on mineral fibers remains to be investigated.
DNA damage-inducible genes as biomarkers for exposures to environmental agents. N.F. Johnson, T.R. Carpenter, R.J. Jaramillo, et al. 1997;105 Suppl 4(Suppl 4):913-8. PubMed · Publisher · Free full text

Abstract

A biodosimetric approach to determine alpha-particle dose to the respiratory tract epithelium from known exposures to radon has been developed in the rat. Cytotoxicity assays have been used to obtain dose-conversion factors for cumulative exposures typical of those encountered by underground uranium miners. However, this approach is not sensitive enough to derive dose-conversion factors for indoor radon exposures. The expression of DNA damage-inducible genes is being investigated as a biomarker of exposure to radon progeny. Exposure of cultures of A549 cells to alpha particles resulted in an increase in the protein levels of the DNA damage-inducible genes, p53, Cip1, and Gadd45. These protein changes were associated with a transient arrest of cells passing through the cell cycle. This arrest was typified by an increase in the number of cells in the G1 and G2 phases and a decrease in the number of cells in the S phase. The effect of inhaled alpha particles (radon progeny) in rats was examined in the epithelial cells of the lateral well of the anterior nasal cavity. Exposures to radon progeny resulted in a significant increase in the number of cells in the G1 phase and a decrease in the number of cells in the S phase. These cell-cycle changes were concomitant with an increase in the number of cells containing DNA strand breaks. These results suggest a commonality between cell-cycle events in vitro and in vivo following exposure to ionizing radiation. In addition to ionizing radiation, A549 cells were exposed to 4-nitroquinoline-1-oxide, methyl methanesulphonate, crocidolite asbestos, and glass microfiber. These studies showed that physical and chemical agents induce different expression patterns of p53, Cip1, and Gadd153 proteins and they could be used to discriminate between toxic and nontoxic materials such as asbestos and glass microfiber. The measurement of gene expression in A549 cells may provide a means to identify a broad spectrum of physical and chemical toxicants encountered in the environment.
Dose-response relationship of fibrous dusts in intraperitoneal studies. M. Roller, F. Pott, K. Kamino, et al. 1997;105 Suppl 5(Suppl 5):1253-6. PubMed · Publisher · Free full text

Abstract

The relationship between the number of fibers injected intraperitoneally and the occurrence of peritoneal mesotheliomas in rats was investigated using data from a series of carcinogenicity studies with several fibrous dusts. Based on observed tumor incidences ranging between 10 and 90%, the hypothesis of a common slope of dose-response relationships (parallel probit lines in probit analysis) cannot be rejected. In general, parallelism of probit lines is considered an indication of a common mode of action. Analysis of the shape of the dose-response relationship, with one apparent exception, shows virtually linear or superlinear behavior, i.e., from these data, there is no indication of a decrease in carcinogenic potency of an elementary carcinogenic unit at lower doses.
Early mesothelial cell proliferation after asbestos exposure: in vivo and in vitro studies. I.Y. Adamson. 1997;105 Suppl 5(Suppl 5):1205-8. PubMed · Publisher · Free full text

Abstract

There is some evidence that proliferation of pleural mesothelial cells (MC) occurs soon after deposition of asbestos fibers. To study this effect, we instilled a single dose of 0.1 mg crocidolite into the lungs of mice for 1 and 6 weeks and counted labeled nuclei after 3H-thymidine (3HT) injection. Short fibers (< 1 micron) induced little change in the lung; they were mostly phagocytized and had a minimal effect on MC labeling. Long fibers up to 20 microns damaged the bronchiolar epithelium and were incorporated into connective tissue. Increased 3HT uptake was seen in fibroblasts and epithelial cells and also in MC, which peaked at 2% labeled at 1 week compared to near 0% labeling in controls. No fibers were found in or near labeled MC, which suggested that a cytokine generated in the lung during the early response phase might induce MC proliferation. To look for a cytokine effect in vitro, we instilled asbestos into rat lungs and, after 1 and 6 weeks, bronchoalveolar and pleural lavage fluids as well as macrophages were collected. Alveolar macrophages contained fibers, but pleural macrophages (PM) did not. After short-term culture, macrophage supernatants and the lavage fluids were tested on rat lung MC in culture. At 1 week, PM secreted growth factor(s) for MC, and the mitogenic effect was more pronounced with lavage fluids. No effects on MC were found using material prepared 6 weeks after asbestos. The early MC growth increase was not blocked by antibodies to cytokines, such as platelet-derived growth factor, fibroblast growth factors, or tumor necrosis factor, but was inhibited by anti-keratinocyte growth factor (anti-KGF). The results show that an early growth phase of MC after asbestos exposure appears unrelated to particle translocation to the pleura but is associated with cytokine release, most likely KGF, by lung cells.
Effects of mineral fibers on the expression of genes whose product may play a role in fiber pathogenesis. T. Tsuda, Y. Morimoto, H. Yamato, et al. 1997;105 Suppl 5(Suppl 5):1173-8. PubMed · Publisher · Free full text

Abstract

To determine which factors are useful for the risk assessment of man-made fibers, we examined the gene expression of proinflammatory cytokines, growth factors, manganese superoxide dismutase (MnSOD), and inducible nitric oxide synthase (iNOS) in mineral fiber-exposed rats by means of reverse transcription-polymerase chain reaction (RT-PCR). Male Wistar rats received a single intratracheal instillation of either saline (control) or two types of fibers (2 mg of Union Internationale Centre le Cancer (UICC) chrysotile or alumina silicate refractory ceramic fiber [RCF]). Expression of interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), platelet-deriving growth factor-A, (PDGF-A), platelet-deriving growth factor-B (PDGF-B), transforming growth factor beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), MnSOD, and iNOS mRNA from lung and lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM) were assessed by RT-PCR. Among these factors, IL-1 alpha, TNF-alpha, IL-6, bFGF, and iNOS would be the possible parameters for the risk assessment of fibers. In a follow-up study, we investigated the time course (3 days, 1 week, 1 month, and 3 months) of expression of IL-1 alpha and TNF-alpha by LPS-stimulated AM exposed to mineral fibers in vivo. Male Wistar rats were instilled intratracheally with saline or fibers (2 mg of Union Internationale Contre le Cancer UICC crocidolite or potassium octatitanate whisker [TW]). The expression of IL-1 alpha mRNA by fibers was greatest in TW, crocidolite, chrysotile, and RCF-instilled rat AM, in that order. The increase of IL-1 alpha and TNF-alpha mRNA in AM peaked at 1 month and 3 days after exposure to crocidolite or TW, respectively. The expression of IL-1 alpha by fibers (crocidolite, chrysotile, TW, and RCF) may be a good indicator of the pathologic potential of fibers.
Efflux of reduced glutathione after exposure of human lung epithelial cells to crocidolite asbestos. S.A. Golladay, S.H. Park, A.E. Aust. 1997;105 Suppl 5(Suppl 5):1273-7. PubMed · Publisher · Free full text

Abstract

This study investigated glutathione (GSH) homeostasis in human lung epithelial cells (A549) exposed to crocidolite. Exposure of A549 cells to 3 micrograms/cm2 crocidolite resulted in a decrease in intracellular reduced glutathione by 36% without a corresponding increase in GSH disulfide. After a 24-hr exposure to crocidolite, 75% of the intracellular GSH lost was recovered in the extracellular medium, of which 50% was in reduced form. Since the half-life of reduced GSH in culture medium was less than 1 hr, this suggests that reduced GSH was released continuously from the cells after treatment. The release of GSH did not appear to result from nonspecific membrane damage, as there was no concomitant release of lactate dehydrogenase or 14C-adenine from loaded cells after crocidolite treatment for 24 hr. Crocidolite exposure resulted in the formation of S-nitrosothiols but no increase in the level of GSH-protein mixed disulfides or GSH conjugates. Exposure of A549 cells to crocidolite for 24 hr decreased gamma glutamylcysteine synthetase (gamma-GCS) activity by 47% without changes in the activities of GSH reductase, GSH peroxidase, GSH S-transferase, or glucose-6-phosphate dehydrogenase. Treatment of cells with crocidolite pretreated with the iron chelator desferrioxamine B resulted in the same level of intracellular GSH depletion and efflux and the same decrease in gamma-GCS activity as treatment with unmodified crocidolite, which suggests that iron-catalyzed reactions were not responsible for the GSH depletion.
Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and cigarette smoke in vivo. Y. Morimoto, T. Tsuda, H. Nakamura, et al. 1997;105 Suppl 5(Suppl 5):1247-51. PubMed · Publisher · Free full text

Abstract

To determine the effect of mineral fibers and cigarette smoke on remodeling of lung tissues, we examined matrix metalloproteinase-1 (MMP-1), MMP-2, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-2, and types I and IV collagen mRNA levels from rat lungs exposed to mineral fibers and/or cigarette smoke in vivo. Male Wistar rats (10 weeks of age) were given a single intratracheal instillation of 2 mg of chrysotile or alumina silicate ceramic fibers (RCF). Animals were then exposed to cigarette smoke (side stream) 5 days per week for 4 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Exposure to cigarette smoke induced increases in MMP-1 and TIMP-1 mRNA levels and decreased TIMP-2 and type I collagen mRNA levels in lung. Chrysotile or RCF stimulated the expression of MMP-1 mRNA in the lung. The mineral fibers and cigarette smoke had more than additive effects on the expression of MMP-2 and TIMP-1 in the lung. These data suggest that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix may be associated with the remodeling of lung tissues induced by mineral fibers and/or cigarette smoke.
Fiber-specific molecular features of tumors induced in rat peritoneum. K. Unfried, M. Roller, F. Pott, et al. 1997;105 Suppl 5(Suppl 5):1103-8. PubMed · Publisher · Free full text

Abstract

Molecular markers such as mutational spectra or mRNA expression patterns may give some indication of the mechanisms of carcinogenesis induced by fibers and other carcinogens. In our study, tumors were induced by application of crocidolite asbestos or benzo[a]pyrene (B[a]P) to rat peritoneum. DNA and RNA of these tumors were subjected to analysis of point mutations and to investigation of mRNA expression patterns. With both assays we found typical features depending on the type of carcinogen applied. The analysis of point mutations in the tumor suppressor gene p53 revealed mutations in the B[a]P-induced tumors. However, in the tumors induced by crocidolite asbestos that were of the same tumor type as those induced by B[a]P, mutations in p53 were not detectable. Every mutation detected on the DNA level causes an amino acid substitution within one of the functional domains of the tumor suppressor protein. Therefore, these mutations seem to be of biological relevance for tumor progression and indicate a difference in the carcinogenesis regarding the type of the carcinogenic substance. An additional specificity of crocidolite-induced tumors was detectable by analyzing the mRNA expression of the tumor suppressor gene WT1, which is known to be expressed in human mesothelial and mesothelioma cells. A relatively high amount of WT1 mRNA was measured by quantitative competitive reverse transcription-polymerase using RNA extracted from crocidolite-induced tumors. However, WT1 seems to be expressed on a rather low level in tumors induced by B[a]P.
Fluorescence imaging of reactive oxygen metabolites generated in single macrophage cells (NR8383) upon phagocytosis of natural zeolite (erionite) fibers. J.F. Long, P.K. Dutta, B.D. Hogg. 1997;105(7):706-11. PubMed · Publisher · Free full text

Abstract

In this paper we address the phenomenon of reactive oxygen metabolite generation subsequent to phagocytosis of mineral fibers by macrophages. Natural erionite fibers were chosen because of their established toxicity. Macrophages (cell line NR8383) were loaded with the dye 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate and exposed to erionite particles by centrifuging cells and fibers together to effect adherence. Reactive oxygen metabolite generation was examined by monitoring the fluorescence of oxidized dye formed via the reaction with oxygen species produced during phagocytosis. Individual cells were repeatedly scanned for up to 2 hr to monitor the evolution of this fluorescence. It was found that erionite-exposed cells had a mean total fluorescence of three times that of controls during the first 35 min, declining to two times that of controls at 35-60 min and about the same level as that of controls at 60-80 min. Ultrastructural studies of similarly treated aliquots of cells showed marked variation in size and numbers of the phagocytized particles. This study demonstrates that intracellular oxidation can be monitored on a single cell basis over a period of time. Quantitative studies are in progress to establish the relationship between the phagocytized particulate load and the extent of fluorescence.
Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors. P.S. Gilmour, D.M. Brown, P.H. Beswick, et al. 1997;105 Suppl 5(Suppl 5):1313-7. PubMed · Publisher · Free full text

Abstract

We studied asbestos, vitreous fiber (MMVF10), and refractory ceramic fiber (RCF1) from the Thermal Insulation Manufacturers' Association fiber repository regarding the following: free radical damage to plasmid DNA, iron release, ability to deplete glutathione (GSH), and activate redox-sensitive transcription factors in macrophages. Asbestos had much more free radical activity than any of the man-made vitreous fibers. More Fe3+ was released than Fe2+ and more of both was released at pH 4.5 than at pH 7.2. Release of iron from the different fibers was generally not a good correlate of ability to cause free radical injury to the plasmid DNA. All fiber types caused some degree of oxidative stress, as revealed by depletion of intracellular GSH. Amosite asbestos upregulated nuclear binding of activator protein 1 transcription factor to a greater level than MMVF10 and RCF1; long-fiber amosite was the only fiber to enhance activation of the transcription factor nuclear factor kappa B (NF kappa B). The use of cysteine methyl ester and buthionine sulfoximine to modulate GSH suggested that GSH homeostasis was important in leading to activation of transcription factors. We conclude that the intrinsic free radical activity is the major determinant of transcription factor activation and therefore gene expression in alveolar macrophages. Although this was not related to iron release or ability to deplete macrophage GSH at 4 hr, GSH does play a role in activation of NF kappa B.
Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases. J. Jagirdar, T.C. Lee, J. Reibman, et al. 1997;105 Suppl 5(Suppl 5):1197-203. PubMed · Publisher · Free full text

Abstract

Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases.
Increased focal adhesion kinase- and urokinase-type plasminogen activator receptor-associated cell signaling in endothelial cells exposed to asbestos. A. Barchowsky, B.M. Lannon, L.C. Elmore, et al. 1997;105 Suppl 5(Suppl 5):1131-7. PubMed · Publisher · Free full text

Abstract

Exposure of low-passage endothelial cells in culture to nonlethal amounts of asbestos, but not refractory ceramic fiber-1, increases cell motility and gene expression. These changes may be initiated by the fibers mimicking matrix proteins as ligands for receptors on the cell surface. In the present study, 1- to 3-hr exposures of endothelial cells to 5 mg/cm2 of chrysotile asbestos caused marked cell elongation and motility. However, little morphological change was seen when chrysotile was added to cells pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI)-anchored receptors or with herbimycin A to inhibit tyrosine kinase activity. Affinity purification of GPI-anchored urokinase-type plasminogen activator receptor (uPAR) from chrysotile-exposed cells demonstrated that asbestos altered the profile of proteins and phosphoproteins complexed with this receptor. Tyrosine kinase activities in the complexes were also increased by asbestos. Immunoprecipitations with selective monoclonal antibodies demonstrated that both chrysotile and crocidolite asbestos increase kinase activities associated with p60 Src or p120 focal adhesion kinase (FAK). Further, chrysotile also changed the profile of proteins and phosphoproteins associated with FAK in intact cells. These data suggest that asbestos initiates endothelial cell phenotypic change through interactions with uPAR-containing complexes and that this change is mediated through tyrosine kinase cascades.
Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage. Y. Lim, S.H. Kim, K.A. Kim, et al. 1997;105 Suppl 5(Suppl 5):1325-7. PubMed · Publisher · Free full text

Abstract

Although asbestos stimulates oxygen radical generation in alveolar macrophages, the exact mechanism is still not clear. The purpose of this study was to compare the ability of three asbestos fibers (amosite, chrysotile, and crocidolite) to generate oxygen radicals in macrophages and examine the mechanism of this action. All asbestos fibers were able to induce chemiluminescence but chrysotile induced maximal chemiluminescence at higher concentrations than amosite and crocidolite. Protein kinase C (PKC) inhibitors (sphingosine and staurosporine) suppressed the ability of asbestos to induce oxygen radical generation. Phospholipase C (PLC) inhibitors (U73122 and neomycin) and protein tyrosine kinase (PTK) inhibitors (erbstatin and genistein) decreased oxygen radical generation of asbestos-stimulated alveolar macrophages. Oxygen radical generation was not suppressed by an adenylate cyclase activator (forskolin), a protein kinase A inhibitor (H-8), and a protein serine-threonine phosphatase inhibitor (okadaic acid). PLC and PTK inhibitors suppressed the increment of phosphoinositide turnover by amosite. These results suggest that asbestos fibers induce the generation of oxygen radicals through PTK, PLC, and PKC pathways in a dose-response pattern.
Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers. D.B. Warheit, S.I. Snajdr, M.A. Hartsky, et al. 1997;105 Suppl 5(Suppl 5):1219-22. PubMed · Publisher · Free full text

Abstract

This study compared pulmonary effects of para-aramid respirable-sized, fiber-shaped particles (RFP) (p-aramid fibrils) and chrysotile asbestos fiber exposures in rats. Additional p-aramid inhalation studies were conducted in hamsters to compare species responses. The hamster results are preliminary. The parameters studied were clearance/biopersistence of inhaled p-aramid RFP or size-separated asbestos fibers as well as pulmonary cell proliferation and inflammation indices after 2-week inhalation exposures. Rats were exposed nose only to chrysotile asbestos fibers at concentrations of 459 and 782 fibers/ml or to p-aramid RFP at 419 or 772 fibrils/ml. Hamsters were exposed whole body to p-aramid RFP at concentrations of 358 and 659 fibrils/ml. Subsequently, animals were assessed immediately (time 0) as well as 5 days (10 days for hamsters), 1, 3, 6, and 12 months postexposure. Lung burdens for the p-aramid-exposed rats were 4.8 x 10(7) and 7.6 x 10(7) fibrils/lung, with similar numbers of chrysotile fibers > 5 microns recovered from the lungs of asbestos-exposed rats. In comparison, 1.4 x 10(6) fibrils/lung were recovered in the high-dose hamster group. Biopersistence studies in p-aramid-exposed rats and hamsters demonstrated an initial increase (relative to time 0) in retained p-aramid fibrils during the first month postexposure, which indicated breakage or shortening of inhaled fibrils. This result was associated with a progressive reduction, and increased residence time in the lung, in the mean lengths of the fibrils, which signified biodegradability of inhaled p-aramid fibrils in both species. In contrast, clearance of short chrysotile asbestos fibers was rapid, but clearance of the long chrysotile fibers was slow or insignificant, as evidenced by a progressive increase over time in the mean lengths of fibers recovered from the lungs of exposed rats. Two-week, high-dose exposures to p-aramid in both rats and hamsters produced transient increases in pulmonary inflammatory and cell proliferative responses. In contrast, inhalation of size-separated chrysotile asbestos fibers in rats produced persistent increases in cell labeling indices of airway, alveolar, and subpleural cells measured through a period of 1 to 3 months postexposure. These results suggest that inhaled p-aramid RFP are biodegradable in the lungs of exposed rats and hamsters. In contrast, exposures to chrysotile asbestos fibers in rats resulted in a selective pulmonary retention of long chrysotile fibers.
Malignant transformation of immortalized human bronchial epithelial cells by asbestos fibers. T.K. Hei, L.J. Wu, C.Q. Piao. 1997;105 Suppl 5(Suppl 5):1085-8. PubMed · Publisher · Free full text

Abstract

Although asbestos is a well-established lung carcinogen, there currently is no suitable human cell model in which to examine the underlying cellular and molecular changes associated with fiber-mediated bronchial carcinogenesis. Using a recently established transformation model based on a human papillomavirus-immortalized human bronchial epithelial cell line, we successfully transformed these BEP2D cells after a single, 7-day treatment with a 20-microgram/ml (4 micrograms per cm2 area) dose of Union Internationale Contre le Cancer (UICC) Rhodesian chrysotile fibers. Asbestos treatment resulted in a surviving fraction of 0.18 compared to control cells. Transformed cells developed through a series of sequential steps, including altered growth kinetics, resistance to serum-induced terminal differentiation, and anchorage-independent growth, before becoming tumorigenic to form progressively growing tumors in nude mice. Seven tumorigenic cell lines were isolated and determined to be of human epithelial origin based on immunofluorescent staining of keratin and isozyme analysis. Analysis of tumor DNA revealed no mutations at either codon 12 or 13 in any the ras oncogenes. An independent role for K-ras mutation in fiber carcinogenesis, therefore, cannot be confirmed. This model provides a unique opportunity to study the cellular and molecular changes at the various stages in fiber-mediated neoplastic transformation of human bronchial epithelial cells.
Mechanism of asbestos-mediated DNA damage: role of heme and heme proteins. Q. Rahman, N. Mahmood, S.G. Khan, et al. 1997;105 Suppl 5(Suppl 5):1109-12. PubMed · Publisher · Free full text

Abstract

Several observations, including studies from this laboratory, demonstrate that asbestos generates free radicals in the biological system that may play a role in the manifestation of asbestos-related cytotoxicity and carcinogenicity. It has also been demonstrated that iron associated with asbestos plays an important role in the asbestos-mediated generation of reactive oxygen species. Exposure to asbestos leads to degradation of heme proteins such as cytochrome P450-releasing heme in cytosol. Our simulation experiments in the presence of heme show that such asbestos-released heme may increase lipid peroxidation and can cause DNA damage. Further, heme and horseradish peroxidase (HRP) can cause extensive DNA damage in the presence of asbestos and hydrogen peroxide/organic peroxide/hydroperoxides. HRP catalyzes oxidation reactions in a manner similar to that of prostaglandin H synthetase. Iron released from asbestos is only partially responsible for DNA damage. However, our studies indicate that DNA damage mediated by asbestos in vivo may be caused by a combination of effects such as the release and participation of iron, heme, and heme moiety of prostaglandin H synthetase in free radical generation from peroxides and hydroperoxides.
Mechanisms of fiber-induced genotoxicity. M.C. Jaurand. 1997;105 Suppl 5(Suppl 5):1073-84. Review PubMed · Publisher · Free full text

Abstract

The mechanisms of particle-induced genotoxicity have been investigated mainly with asbestos fibers. The results are summarized and discussed in this paper. DNA damage can be produced by oxidoreduction processes generated by fibers. The extent of damage yield depends on experimental conditions: if iron is present, either on fibers or in the medium, damage is increased. However, iron reactivity does not explain all the results obtained in cell-free systems, as breakage of plasmid DNA was not directly associated with the amount of iron released by the fibers. The proximity of DNA to the site of generation of reactive oxygen species (ROS) is important because these species have an extremely short half-life. Damage to cellular DNA can be produced by oxidoreduction processes that originate from cells during phagocytosis. Secondary molecules that are more stable than ROS are probably involved in DNA damage. Oxidoreduction reactions originating from cells can induce mutations. Genotoxicity is also demonstrated by chromosomal damage associated with impaired mitosis, as evidenced by chromosome missegregation, spindle changes, alteration of cell cycle progression, formation of aneuploid and polyploid cells, and nuclear disruption. In some of these processes, the particle state and fiber dimensions are considered important parameters in the generation of genotoxic effects.
Mineral properties and their contributions to particle toxicity. G.D. Guthrie. 1997;105 Suppl 5(Suppl 5):1003-11. Review PubMed · Publisher · Free full text

Abstract

It has been recognized since at least as early as the mid-1500s that inhaled minerals (i.e., inorganic particles) can pose a risk. Extensive research has focused on the biological mechanisms responsible for asbestos- and silica-induced diseases, but much less attention has been paid to the mineralogical properties and geochemical mechanisms that might influence a mineral's biological activity. Several important mineralogical characteristics control a mineral's reactivity in geochemical reactions and are likely to determine its biological reactivity. In addition to the traditionally considered variables of particle size and shape, mineralogical characteristics such as dissolution behavior, ion exchange, sorptive properties, and the nature of the mineral surface (e.g., surface reactivity) play important roles in determining the toxicity and carcinogenicity of a particle. Ultimately, a mineral's species (which provides direct information on a mineral's structure and composition) is probably one of the most significant yet most neglected factors that must be considered in studies of toxicity and carcinogenicity.
Oncogenes and tumor-suppressor genes in mesothelioma--a synopsis. J.F. Lechner, J. Tesfaigzi, B.I. Gerwin. 1997;105 Suppl 5(Suppl 5):1061-7. Review PubMed · Publisher · Free full text

Abstract

Invariably mesothelioma is diagnosed late in the development of the disease when treatment is no longer effective. Therefore, a key to reducing the mortality rate of this neoplasm is knowledge of the general sequence of genetic events between initiation of mesothelial cells and the emergence of the metastatic tumor cells. Unfortunately, relatively little is known about the early changes in the genesis of this disease. Of the known changes, the most frequent are in the tumor-suppressor genes p16INK4a and NF2 and possibly the SV40 virus large T-antigen oncogene. The molecular nature of the changes in these genes as well as other alterations are addressed in this overview.
p53, Cip1, and Gadd153 expression following treatment of A549 cells with natural and man-made vitreous fibers. N.F. Johnson, R.J. Jaramillo. 1997;105 Suppl 5(Suppl 5):1143-5. PubMed · Publisher · Free full text

Abstract

DNA damage induced by chemicals and ionizing radiation is associated with the expression of negative regulators of the cell cycle. The arrest of cells in G1 and G2 phases of the cell cycle provides time for DNA repair. Asbestos fibers are carcinogenic when inhaled by both humans and animals; however, the mechanism by which the fibers exert their effect is unknown. This work was undertaken to determine whether the expression of DNA damage-inducible genes differs between crocidolite, a fiber positive for lung tumors, and JM 100 glass microfiber, which is negative for lung tumors when inhaled by rats. Temporal and dose-related expressions of p53, Cip1, and Gadd153 proteins were determined in cultured A549 cells treated with either Union Internationale Contre le Cancer crocidolite or JM 100 for 20 hr and cultured in fresh media. Immunolabeled cells were analyzed by flow cytometry, and the increased number of protein-expressing cells was determined by subtracting the expression in unexposed cells from exposed cells. Crocidolite induced the expression of all three proteins with a maximum expression after approximately 18 hr in fresh media. At a similar time point, JM 100 did not markedly induce the three proteins. Crocidolite also induced a dose-dependent increase in the number of cells in the G2 phase of the cell cycle. These results show that asbestos behaves like ionizing radiation and genotoxic chemicals by inducing proteins associated with DNA damage and cell-cycle arrest. The clear difference in response between crocidolite and JM 100 may help elucidate the mechanism of action of toxic and nontoxic fibers.
Pleural macrophage recruitment and activation in asbestos-induced pleural injury. N. Choe, S. Tanaka, W. Xia, et al. 1997;105 Suppl 5(Suppl 5):1257-60. PubMed · Publisher · Free full text

Abstract

The pathogenesis of asbestos-induced pleural fibrosis is poorly understood. Moreover, there has been a long-standing controversy regarding the relative potential of different commercial types of asbestos to cause pleural disease. We postulated that inhaled asbestos fibers translocate to the pleural space where they stimulate the recruitment and activation of pleural macrophages. To test this hypothesis, and to determine whether there are differences between inhaled amphibole and serpentine asbestos, Fischer 344 rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 2 weeks) to either National Institute of Environmental Health Sciences (NIEHS) crocidolite (average concentration 7.55 mg/m3) or NIEHS chrysotile fibers (average concentration 8.51 mg/m3). Comparisons were made with sham-exposed rats. The rats were sacrificed at 1 and 6 weeks after the cessation of exposure. More pleural macrophages were recovered at 1 and 6 weeks after crocidolite and chrysotile exposure than after sham exposure. Small numbers of crocidolite fibers (approximately 1 per 4000 cells) were detected in the pleural cell pellet of one crocidolite-exposed rat by scanning electron microscopy. Pleural macrophage supernatants were assayed for production of nitric oxide (NO) (by the Griess reaction) and tumor necrosis factor alpha (TNF-alpha) (by an enzyme-linked immunosorbent assay method). Significantly greater amounts of NO as well as TNF-alpha were generated by pleural macrophages at 1 and 6 weeks after either crocidolite or chrysotile inhalation than after sham exposure. Conceivably, translocation of asbestos fibers to the pleural space may provide a stimulus for persistent pleural space inflammation, cytokine production, and the generation of toxic oxygen and nitrogen radicals. Enhanced cytokine secretion within the pleural space may in turn upregulate adhesion molecule expression and the synthesis of extracellular matrix constituents by pleural mesothelial cells. Thus, our findings may have significance for the development of asbestos-induced pleural injury.
Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E. S.P. Faux, P.J. Howden. 1997;105 Suppl 5(Suppl 5):1127-30. PubMed · Publisher · Free full text

Abstract

Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF-kappa B and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF-kappa B to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NF-kappa B DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF-kappa B DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF-kappa B to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events to NF-kappa B transcription factor induction by asbestos.
Pulmonary carcinogenicity of inhaled particles and the maximum tolerated dose. G. Oberdörster. 1997;105 Suppl 5(Suppl 5):1347-55. Review PubMed · Publisher · Free full text

Abstract

Chronic inhalation bioassays in rodents are used to assess pulmonary carcinogenicity for purposes of hazard identification and potentially for risk characterization. The influence of high experimental doses on tumor development has been recognized for some time and has led to the concept of maximum tolerated dose (MTD) for dose selection, with the highest dose being at the MTD. Exposure at the MTD should ensure that the animals are sufficiently challenged while at the same time the animal's normal longevity is not altered from effects other than carcinogenicity. A characteristic of exposure-dose-response relationships for chronically inhaled particles is that lung tumors are significantly increased only at high exposure levels, and that lung tumors are seen in rats only but not in mice or hamsters. This lung tumor response in rats is thought to be secondary to persistent alveolar inflammation, indicating that the MTD may have been exceeded. Thus, mechanisms of toxicity and carcinogenicity may be dose dependent and may not operate at lower doses that humans normally experience. Despite awareness of this problem, carcinogenicity bioassays that evaluate particulate compounds in rodents have not always been designed with the MTD concept in mind. This is due to several problems associated with determining an appropriate MTD for particle inhalation studies. One requirement for the MTD is that some toxicity should be observed. However, it is difficult to define what degree of toxic response is indicative of the MTD. For particle inhalation studies, various noncancer end points in addition to mortality and body weight gain have been considered as indicators of the MTD, i.e., pulmonary inflammation, increased epithelial cell proliferation, increased lung weight, impairment of particle clearance function, and significant histopathological findings at the end of a subchronic study. However, there is no general agreement about quantification of these end points to define the MTD. To determine whether pulmonary responses are indicative of the MTD, we suggest defining an MTD based on results of a multidose subchronic and chronic inhalation study with a known human particulate carcinogen, e.g., asbestos or crystalline silica. Quantification of effects in such a study using the noncancer end points listed above would identify a dose level without significant signs of toxicity at the end of the subchronic study. If this dose level still results in significant lung tumor incidence at the end of the chronic study. We will have a sound basis for characterizing the MTD and justifying its use in future particle inhalation studies. Also, a better understanding of cellular and molecular mechanisms of particle-induced lung tumors is needed to support the MTD concept.
Short-term inhalation and in vitro tests as predictors of fiber pathogenicity. R.T. Cullen, B.G. Miller, J.M. Davis, et al. 1997;105 Suppl 5(Suppl 5):1235-40. PubMed · Publisher · Free full text

Abstract

A wide range of fiber types was tested in two in vitro assays: toxicity to A549 epithelial cells, as detachment from substrate, and the production of the proinflammatory cytokine tumor necrosis factor (TNF) by rat alveolar macrophages. Three of the fibers were also studied in vivo, using short-term inhalation followed by a) bronchoalveolar lavage to assess the inflammatory response and b) measurement of cell proliferation in terminal bronchioles and alveolar ducts, using incorporation of bromodeoxyuridine (BrdU). The amount of TNF produced by macrophages in vitro depended on the fiber type, with the man-made vitreous fibers, and refractory ceramic fibers being least stimulatory and silicon carbide (SiC) whiskers providing the greatest stimulation. In the epithelial detachment assay there were dose-dependent differences in the toxicity of the various fibers, with long amosite being the most toxic. However, there was no clear relationship to known chronic pathogenicity. Fibers studied by short-term inhalation produced some inflammation, but there was no clear discrimination between the responses to code 100/475 glass fibers and the more pathogenic amosite and SiC. However, measurements of BrdU uptake into lung cells showed that amosite and SiC produced a greater reaction than code 100/475, which itself caused no more proliferation than that seen in untreated lungs. These results mirror the pathogenicity ranking of the fibers in long-term experiments. In conclusion, the only test to show potential as a predictive measure of pathogenicity was that of cell proliferation in lungs after brief inhalation exposure (BrdU assay). We believe that this assay should be validated with a wider range of fibers, doses, and time points.
Surface reactivity in the pathogenic response to particulates. B. Fubini. 1997;105 Suppl 5(Suppl 5):1013-20. Review PubMed · Publisher · Free full text

Abstract

The peculiar characteristics of dust toxicity are discussed in relation to the processes taking place at the particle-biological medium interface. Because of surface reactivity, toxicity of solids is not merely predictable from chemical composition and molecular structure, as with water soluble compounds. With particles having the same bulk composition, micromorphology (the thermal and mechanical history of dust and adsorption from the environment) determines the kind and abundance of active surface sites, thus modulating reactivity toward cells and tissues. The quantitative evaluation of doses is discussed in comparisons of dose-response relationships obtained with different materials. Responses related to the surface of the particle are better compared on a per-unit surface than per-unit weight basis. The role of micromorphology, hydrophilicity, and reactive surface cations in determining the pathogenicity of inhaled particles is described with reference to silica and asbestos toxicity. Heating crystalline silica decreases hydrophilicity, with consequent modifications in membranolytic potential, retention, and transport. Transition metal ions exposed at the surface generate free radicals in aqueous suspensions. Continuous redox cycling of iron, with consequent activation-reactivation of the surface sites releasing free radicals, could account for the long-term pathogenicity caused by the inhalation of iron-containing fibers. In various pathogenicities caused by mixed dusts, the contact between components modifies toxicity. Hard metal lung disease is caused by exposure to mixtures of metals and carbides, typically cobalt (Co) and tungsten carbide (WC), but not to single components. Toxicity stems from reactive oxygen species generation in a mechanism involving both Co metal and WC in mutual contact. A relationship between the extent of water adsorption and biopersistence is proposed for vitreous fibers. Modifications of the surface taking place in vivo are described for ferruginous bodies and for the progressive comminution of chrysotile asbestos fibers.
Susceptibility of p53-deficient mice to induction of mesothelioma by crocidolite asbestos fibers. J.M. Marsella, B.L. Liu, C.A. Vaslet, et al. 1997;105 Suppl 5(Suppl 5):1069-72. PubMed · Publisher · Free full text

Abstract

Exposure of mesothelial cells to asbestos fibers in vitro has been shown to induce DNA damage mediated by oxidants. An early cellular response to DNA damage is increased expression of the p53 protein. This protein induces transcription of genes that activate cell cycle checkpoints or induce apoptosis. A murine mesothelial cell line that spontaneously acquired a point mutation in the p53 gene shows increased sensitivity to DNA damage induced by crocidolite asbestos fibers. It is hypothesized that p53-deficient mice will show increased sensitivity to the genotoxic effects of asbestos and accelerated development of malignant mesotheliomas.
Talc and amosite/crocidolite preferentially deposited in the lungs of nonoccupational female lung cancer cases in urban areas of Japan. H. Yamada, H. Hashimoto, M. Akiyama, et al. 1997;105(5):504-8. PubMed · Publisher · Free full text

Abstract

To analyze the correlation between asbestos lung burden and lung cancer, lungs of 211 female cases with and without lung cancer were examined. Phase-contrast microscopic (PCM) counting of ferruginous (FBs) and uncoated fibers (UFs), which had length longer than 5 microns and aspect ratios greater than 3:1, revealed a significantly higher level of FBs plus UFs in urban lung cancer cases than urban non-lung cancer cases (1380.5 vs. 550.3; p < 0.001). No difference was noted between rural lung cancer and non-lung cancer cases. Analytical electron microscopic studies identified various kinds of mineral fibers with an aspect ratio greater than 3:1 in the lung tissue including chrysotile, actinolite/tremolite, amosite/crocidolite, fibrous talc, mica, silica, iron, wollastonite, chlorite, kaoline, and others. The most frequently detected fibers were thin, short chrysotile fibers, most of which could not be found by PCM, followed by relatively thick, long actinolite/tremolite fibers, fibrous talc, and in a smaller number, amosite/crocidolite of intermediate length and width. Amosite/crocidolite and fibrous talc counts in urban lung cancer cases were greater than those of urban non-lung cancer cases, rural lung cancer, and rural non-lung cancer cases; these findings were consistent with PCM analysis. Therefore, it is suggested that fibers detected in PCM observation may be mainly amosite/crocidolite with some parts fibrous talc and that fibrous talc in urban environments may be another candidate for carcinogenic or cocarcinogenic factors of female lung cancer.
The role of oxygen free radicals in occupational and environmental lung diseases. V. Vallyathan, X. Shi. 1997;105 Suppl 1(Suppl 1):165-77. Review PubMed · Publisher · Free full text

Abstract

Oxygen free radicals and their metabolites, collectively described as reactive oxygen species (ROS), have been implicated in the pathogenesis of many diseases. The pulmonary system is particularly vulnerable to ROS-induced injury because of its continuous exposure to toxic pollutants from a wide variety of sources in the ambient air. Additionally, lungs are exposed systemically to ROS generated from xenobiotic compounds and endogenous sources. This review describes the sources of endogenous and exogenous ROS generation in the lung. Special emphasis is given to major sources of ROS in occupational and environmental exposures to asbestos, crystalline silica, coal, chromium, herbicides, bleomycin, and cigarette smoke. ROS-induced lung injury at different target levels may contribute to similar patterns of cell injury and alterations at the molecular level by initiation, propagation, and autocatalytic chain reactions. Intracellular signalling, activation and inactivation of enzymes, stimulation, secretion, and release of proinflammatory cytokines, chemokines, and nuclear factor activation and alterations are also common events. Understanding the interactions of these intricate mechanistic events is important in the prevention and amelioration of lung injury that results from acute and chronic exposures to toxins in ambient air.
Drinking water and cancer. R.D. Morris. 1995;103 Suppl 8(Suppl 8):225-31. Review PubMed · Publisher · Free full text

Abstract

Any and all chemicals generated by human activity can and will find their way into water supplies. The types and quantities of carcinogens present in drinking water at the point of consumption will differ depending on whether they result from contamination of the source water, arise as a consequence of treatment processes, or enter as the water is conveyed to the user. Source-water contaminants of concern include arsenic, asbestos, radon, agricultural chemicals, and hazardous waste. Of these, the strongest evidence for a cancer risk involves arsenic, which is linked to cancers of the liver, lung, bladder, and kidney. The use of chlorine for water treatment to reduce the risk of infectious disease may account for a substantial portion of the cancer risk associated with drinking water. The by-products of chlorination are associated with increased risk of bladder and rectal cancer, possibly accounting for 5000 cases of bladder cancer and 8000 cases of rectal cancer per year in the United States. Fluoridation of water has received great scrutiny but appears to pose little or no cancer risk. Further research is needed to identify and quantify risks posed by contaminants from drinking-water distribution pipes, linings, joints, and fixtures and by biologically active micropollutants, such as microbial agents. We need more cost-effective methods for monitoring drinking-water quality and further research on interventions to minimize cancer risks from drinking water.
Mitotic disturbances and micronucleus induction in Syrian hamster embryo fibroblast cells caused by asbestos fibers. E. Dopp, J. Saedler, H. Stopper, et al. 1995;103(3):268-71. PubMed · Publisher · Free full text

Abstract

Asbestos and other mineral fibers have long been known to induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We investigated the occurrence of mitotic disturbances induced by asbestos (amosite, crocidolite, chrysotile) in an in vitro approach using Syrian hamster embryo (SHE) fibroblast cells. The following endpoints were investigated: micronucleus formation as a result of mitotic disturbances and characterization of the induced micronucleus population by kinetochore staining and visualization of the spindle apparatus. Supravital UV-microscopy was used to analyze changes in interphase chromatin structure, impaired chromatid separation, and blocked cytokinesis. All three asbestos fiber types induced a high frequency of micronucleus formation in SHE cells (> 200/2000 cells) in a dose-dependent manner (0.1-5.0 micrograms/cm2), with a maximum between 48 hr and 66 hr exposure time. At higher concentrations (more than 5.0 micrograms/cm2) the micronucleus formation decreased again as a result of increased toxicity. Kinetochore staining of micronuclei revealed that 48 +/- 2% of asbestos-induced micronuclei reacted positively with CREST (antikinetochore) serum. Furthermore, spindle apparatus deformations occurred in cells with disturbed metaphases and anaphases, while the spindle fiber morphology appeared unchanged. Our results show that asbestos fibers may cause both loss and breakage of chromosomes in the absence of direct interaction with spindle fibers.
Air pollution measurements in traffic tunnels. R. De Fré, P. Bruynseraede, J.G. Kretzschmar. 1994;102 Suppl 4(Suppl 4):31-7. PubMed · Publisher · Free full text

Abstract

Air pollution measurements during April 1991 are reported from the Craeybeckx highway tunnel in Antwerp, Belgium. The tunnel was used daily by an average of 45,000 vehicles, of which 60% were gasoline fueled passenger cars, 20% diesel cars, and 20% trucks. Of the gasoline cars, only 3% had three-way catalysts. Tunnel air concentrations of nitrogen oxides, sulphur dioxide, carbon dioxide, carbon monoxide, nonmethane hydrocarbons, volatile organic compounds, polycyclic aromatic hydrocarbons, and lead are presented. The traffic emissions in the tunnel are calculated by the carbon balance method, which uses the increase of the total carbon concentration in the tunnel air as the reference quantity. Division of the concentration of any pollutant by the total carbon concentration gives emission factors per kilogram of carbon. These emission factors can be converted directly to emissions relative to fuel consumption or per kilometer. The fraction of diesel used in the tunnel was derived from sulphur to carbon ratios in tunnel air. A calculation procedure with breakdown of emission factors according to vehicle categories was used to estimate countrywide emissions. The estimated emissions were compared to results from the Flanders Emissions Inventory [Emissie Inventaris Vlaamse Regio (EIVR)] and calculated emissions according to the emission factors proposed by the European Commissions CORINAIR Working Group. For NOx there is excellent agreement. For carbon monoxide and hydrocarbons, the tunnel data produced higher emissions than the CORINAIR model would predict but lower than the official EIVR statistics. The estimated lead emissions from traffic are found to be 22 to 29% of the lead in gasoline.
An experimental approach to the evaluation of the biopersistence of respirable synthetic fibers and minerals. D.M. Bernstein, R. Mast, R. Anderson, et al. 1994;102 Suppl 5(Suppl 5):15-8. PubMed · Publisher · Free full text

Abstract

The biopersistence of fibers and minerals in the respiratory tract is an important parameter in the toxicity of those materials. The biopersistence of respirable synthetic fibers and minerals in man can be most closely evaluated in an animal model. While acellular and in vitro systems are important for initial evaluation of solubility and durability, they cannot simulate the dynamics of inhalation deposition and clearance and the subsequent systemic reaction to fibers and minerals that occurs in the animal. To evaluate the biopersistence of synthetic fibers, male rats were exposed to a well defined rat respirable aerosol of man-made vitreous fibers (MMVF), 6 hr/day for 5 days. Following exposure, subgroups were sacrificed at intervals ranging from 1 hr to 52 weeks. Following sacrifice, the lungs were removed, weighed, and immediately frozen at 20 degrees C for subsequent digestion by low temperature plasma ashing. The number, size distribution, and chemical composition of the fibers in the aerosol and lung were determined. With this animal model the role of biopersistence in altering the geometry and clearance of fibers can be systematically evaluated. The model also can be applied for the evaluation of the biopersistence of nonfibrous minerals.
Asbestos and colon cancer: a weight-of-the-evidence review. J.F. Gamble. 1994;102(12):1038-50. Meta-analysis PubMed · Publisher · Free full text

Abstract

What is the evidence that exposure to asbestos causes colon cancer? This weight-of-evidence review considers epidemiologic evidence from cohort studies of asbestos-exposed workers, case-control studies of colon cancer, animal bioassays, and other corroborative evidence. The major evidence for a causal association at high exposure is a combined colorectal standardized mortality ratio (SMR) of 1.5 for asbestos cohorts where the lung cancer SMR was greater than twofold. However, misdiagnosis may spuriously elevate the SMR. The strongest evidence against a causal association between colon cancer and asbestos exposure is the lack of an exposure-response gradient in asbestos cohorts where trends for lung cancer are observed. Population-based case-control studies of colon cancer do not show any consistent risk associated with asbestos exposure. Long-term ingestion studies show no evidence of an increased incidence of colon cancer in animals by this route of exposure and do not provide biological plausibility for a causal association between asbestos exposure and colon cancer.
Asbestos: facts and fiction. B.T. Mossman. 1994;102(5):424-5. Letter · Review PubMed · Publisher · Free full text
Biopersistence of respirable synthetic fibers and minerals: point of view of the chest physician. P. De Vuyst. 1994;102 Suppl 5(Suppl 5):7-9. Review PubMed · Publisher · Free full text

Abstract

Problems of diagnosis related to the presence or absence of particles in lung and pleural tissues are discussed from the clinician's viewpoint. The advantage of applying mineralogical analytical techniques is considered.
Biopersistence of respirable synthetic fibers and minerals: the point of view of the epidemiologist. P. Boffetta. 1994;102 Suppl 5(Suppl 5):11-3. Review PubMed · Publisher · Free full text

Abstract

Biopersistence of fibers and minerals in human respiratory tissues is an important aspect of the toxicity of these agents. However, few data are available from human studies. Although a number of studies have measured the lung burden of asbestos and other minerals in exposed humans, few presented information relevant to biopersistence of these agents. The studies analyzing asbestos lung burden in workers at different intervals following cessation of exposure suggest a linear decrease in concentration over time, that is independent of duration of exposure. However, the available evidence on asbestos is too sparse to allow a firm conclusion; almost no data are available on other minerals.
Biopersistences of man-made vitreous fibers and crocidolite fibers in rat lungs following short-term exposures. R.P. Musselman, W.C. Miiller, W. Eastes, et al. 1994;102 Suppl 5(Suppl 5):139-43. PubMed · Publisher · Free full text

Abstract

Biopersistence of commercial man-made vitreous fibers (MMVF) and crocidolite were studied in Fischer 344 rats. MMVF used were size-selected to be rat-respirable, and rats were exposed nose-only 6 h/day for 5 days to gravimetric concentrations (30 mg/m3) of two fiber glass compositions--a rockwool, and a slagwool--or to 10 mg/m3 of long-fibered crocidolite, or to filtered air. Animals were sacrificed at 1 hr, 1, 5, 31, 90, 180, 270, 365, and 545 days after exposure stopped. Fibers were recovered from digested lung tissue to determine changes in concentrations (fibers/mg dry lung) and fiber retentions (expressed as percent of day 1 retention [PR]) for selected dimension categories. One-day average concentrations of lung-retained MMVF and crocidolite fibers, of diameter > or = 0.5 micron or > 20 microns in length, were nearly equal, permitting direct comparisons between MMVF and crocidolite. At 270 days average PR for MMVF > or = 0.5 micron in diameter were from 3 to 6 +/- 2% and 27 +/- 9% for crocidolite. For fibers > 20 microns, PR were 1 to 4 +/- 4% for MMVF and 37 +/- 20% for crocidolite. At 545 days, MMVF > 20 microns in length were at background level while concentration of crocidolite fibers > 20 microns in length remained at 2000 +/- 400 f/mg DL (dry lung), or 38 +/- 9% of day-1 retention. These results suggest strongly that MMVF dissolved or fractured in vivo whereas crocidolite fibers did not change.
Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence. J.C. Barrett. 1994;102 Suppl 5(Suppl 5):19-23. Review PubMed · Publisher · Free full text

Abstract

Carcinogenic agents can influence the carcinogenic process either by mutating critical target genes or by increasing the number of cells at risk for mutations. Cytogenetic and molecular studies of asbestos-related cancers indicate that inactivation or loss of multiple tumor suppressor genes occurs during lung cancer development. Aneuploidy and other chromosomal changes induced by asbestos fibers may be involved in genetic alterations in asbestos-related cancers. Furthermore, asbestos fibers may influence the carcinogenic process by inducing cell proliferation, free radicals, or other promotional mechanisms. Therefore, asbestos fibers may act at multiple stages of the carcinogenic process by both genetic and epigenetic mechanisms. Biopersistence is undoubtedly important in fiber carcinogenicity. However, the time required for a fiber to remain in the lung to exert a cancer-related effect is difficult to specify.
Chronic inhalation and biopersistence of refractory ceramic fiber in rats and hamsters. R.W. Mast, T.W. Hesterberg, L.R. Glass, et al. 1994;102 Suppl 5(Suppl 5):207-9. PubMed · Publisher · Free full text

Abstract

Lifetime "nose-only" inhalation studies were conducted in rats using four types of refractory ceramic fibers (FCF), 1 micron in diameter x 22 to 26 microns length: High Purity, Kaolin, Zirconia, and After-Service; and on hamsters using Kaolin RCF. For comparison, animals also were exposed to chrysotile fibers. Rats were exposed 6 hr/day, 5 days/week for 24 months to concentrations ranging between 3 and 30 mg/m3. Time- and dose-dependent lesions in the rat included the development of interstitial fibrosis, pleural fibrosis, pulmonary tumors, and mesothelioma. Exposure to 3, 9 or 16 mg/m3 produced no excess lung tumors; no fibrosis was seen at 3 mg/m3. A significant increase in lung tumors and interstitial fibrosis was observed at 30 mg/m3. A single mesothelioma was observed in rats exposed to 9 mg/m3, while two occurred at 30 mg/m3. Hamsters were similarly exposed to 30 mg/m3 Kaolin RCF for 18 months; no lung tumors were induced, but pulmonary and pleural fibrosis were observed and there was a 42% incidence of mesothelioma. Multiple interim sacrifices together with recovery animals allowed detailed assessment of the lung burden of RCF, which was found to be dose related and, at the high doses, exceeded 10(5) fibers/mg of dry lung. During the various recovery periods there was a clear reduction in fiber burden. Mathematical modeling of these data for deposition, clearance, and retention and for species is currently underway.
Chrysotile biopersistence in the lungs of persons in the general population and exposed workers. A.M. Langer, R.P. Nolan. 1994;102 Suppl 5(Suppl 5):235-9. PubMed · Publisher · Free full text

Abstract

Lung burden analysis was performed on 126 autopsy cases of persons who died in New York City from 1966 through 1968. Of the 126 cases, 107 were probably non-occupationally exposed, judging by occupational history and asbestos body content of lung. Fifty-three of the 107 cases contained short chrysotile fibers/fibrils, < 5 microns in length, present in 3-fold greater amounts than were found in laboratory background controls. The fiber concentrations ranged from 1.8 to 15.7 x 10(6) f/gm/dry lung tissue, and the proportion of fibers > or = 5 microns in length was only 0.34% of the total chrysotile population found. Other inorganic particles present included fragments of amphiboles. In contrast to these data, the lung parenchyma of persons occupationally exposed to asbestos commonly showed the presence of other fiber types, especially amosite and crocidolite, at very much higher concentrations and greater fiber length. Any chrysotile present would usually be in fiber bundle form, with both fibers and fibrils > 5 microns in length. Comparison of the lung fiber content of occupationally exposed persons with that of the general population showed marked qualitative and quantitative differences. Fibers are durable, and are retained in a range of concentrations. Their length and dose, among other factors, which control their biological potential are different in the two populations; the risk factors for chrysotile-induced disease are not the same.
Comparative investigations of the biodurability of mineral fibers in the rat lung. H. Muhle, B. Bellmann, F. Pott. 1994;102 Suppl 5(Suppl 5):163-8. PubMed · Publisher · Free full text

Abstract

The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates.
Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system. J.M. Arif, S.G. Khan, N. Mahmood, et al. 1994;102 Suppl 5(Suppl 5):181-3. PubMed · Publisher · Free full text

Abstract

This article reports the effect of coexposure to Indian chrysotile asbestos (5 mg/rat) and kerosene soot (5 mg/rat) on the pulmonary phase I and phase II drug-metabolizing enzymes 1, 4, 8, 16, 30, 90, and 150 days after a single intratracheal inoculation. Exposure to soot resulted in a significant induction of the pulmonary microsomal cytochrome P450 and the activity of dependent monooxygenase, benzo(a)pyrene (B[a]P) hydroxylase, and epoxide hydrase at all time intervals. On the other hand, the cytosolic glutathione S-transferase (GST) activity was induced at days 1, 4, 8, 16, and 30 after exposure, followed by inhibition in the enzyme activity. In contrast, chrysotile exposure depleted cytochrome P450, B[a]P hydroxylase, epoxide hydrase, and GST at initial stages, while all these parameters except GST were induced at later stages. However, coexposure to chrysotile and soot led to a significant inhibition in the cytochrome P450 levels, activities of B[a]P hydroxylase, epoxide hydrase, and GST at initial stages of exposure. At advanced stages, however, an additional increase in cytochrome P450, B[a]P hydroxylase, and epoxide hydrase but a decrease in GST was observed. These results clearly show that the intratracheal coexposure to high levels of asbestos and kerosene soot alters the metabolic activity of the lung, which is turn may retain toxins in the system for a longer period, resulting in adverse pathological disorders.
Environmental asbestotic pleural plaques in northeast Corsica: correlations with airborne and pleural mineralogic analysis. F. Rey, C. Boutin, J.R. Viallat, et al. 1994;102 Suppl 5(Suppl 5):251-2. PubMed · Publisher · Free full text

Abstract

We report a prevalence study of environmental pleural plaques in subjects over 50 years old from the northeastern Corsican village of Murato, built on asbestos surface deposits. The percentage of plaques was 41%, versus 7.5% in the control village of Vezzani. Although surface deposits contain both chrysotile and tremolite, airborne pollution and asbestos lung burden of exposed inhabitants consist essentially of tremolite as assessed by transmission electron microscopy (TEM). However, TEM analysis of the parietal pleura of three animals bred in exposed areas showed a predominance of short fibers of chrysotile. The respective roles of tremolite and chrysotile in inducing pleural plaques in Corsica should thus be considered.
Epidemiological significance of mineral fiber persistence in human lung tissue. J.C. McDonald. 1994;102 Suppl 5(Suppl 5):221-4. Review PubMed · Publisher · Free full text

Abstract

For the experimentalist, mineral fiber persistence may provide clues to disease mechanisms, for the epidemiologist, to the measurement of exposure. Qualitatively, this can be valuable when unsuspected exposures have been demonstrated as, for example, MMMF workers exposed to amosite or chrysotile workers to tremolite. Quantitatively, the potential of lung burden analyses to assess lifetime mineral fiber exposure has yet to be achieved with confidence. The difficulties are 2-fold, the first related to sampling and the second to the dynamics of biopersistence. Until some noninvasive method is found to identify and quantify numerically inorganic fibers in human tissue during life, epidemiological studies must depend on lung samples obtained at autopsy or thoracic surgery. This source is inevitably subject to seriously large and indefinable bias of various kinds. Of equal importance is the present uncertain state of knowledge concerning factors that determine what is present in the lung at any time. These determinants clearly include the dimensional features of airborne environmental particulates and characteristics that affect their durability in tissue.
Fiber levels and disease in workers from a factory predominantly using amosite. A.R. Gibbs, M.J. Gardner, F.D. Pooley, et al. 1994;102 Suppl 5(Suppl 5):261-3. PubMed · Publisher · Free full text

Abstract

The Cape Boards Plant at Uxbridge produced insulation board containing amosite asbestos between 1947 and 1973 with only small amounts of chrysotile. After 1973 only amosite was used. In this study we examined lung samples from 48 workers who had been employed at the plant and who had come to autopsy. The study investigated the fiber levels against the lung pathology including amount of interstitial fibrosis and numbers of ferruginous bodies. The degree of interstitial fibrosis and number of asbestos bodies were graded and the tissues were analyzed by transmission electron microscopy and energy dispersive X-ray analysis and the fibers counted and typed. The 48 cases included 5 mesotheliomas and 14 lung cancers. The mineral analysis results were dominated by the amosite fiber levels. The amounts of chrysotile were relatively small. There were higher levels in lung cancer cases than mesotheliomas and higher levels in mesothelioma cases than those who had died from nonasbestos related diseases. Analysis of the lung tissues showed a consistent pattern of high amosite levels, which confirms the impression that amosite was the predominant form of asbestos used and also indicates that the factory had been a very dusty one.
Gasoline, asbestos, and dioxin. 1994;102(2):146-7. News PubMed · Free full text
Human exposure to urban air pollution. C.E. Boström, J. Almén, B. Steen, et al. 1994;102 Suppl 4(Suppl 4):39-47. Review PubMed · Publisher · Free full text

Abstract

This study deals with some methods of making human exposure estimates, aimed at describing the human exposure for selected air pollutants in Sweden that are suspected carcinogens. Nitrogen oxides (NOx) have been chosen as an indicator substance for estimating the concentration of the urban plume. Earlier investigations have shown that the traffic in Swedish cities contributes around 85% to the measured NOx concentrations, and that most of the mutagenicity in urban air originates from traffic. The first section of this paper describes measurements in Stockholm of some unregulated light hydrocarbons, such as ethene, ethyne, propane, propene, butane, and isobutane. In addition, measurements of some volatile aromatic hydrocarbons are presented. Simultaneous measurements of carbon monoxide (CO) were made. The ratios between CO and the individual specific compounds were determined by linear regression analysis. By analysis of relationships between CO and NOx, NOx concentrations can be used as a tracer to describe the exposure for these specific compounds. NOx are considered to be a better tracer than CO, because NOx or NO2 values exist for many places over a long time, while CO is measured mostly in streets with high concentrations. At low concentrations, instruments that measure normal CO levels give no detectable signals. Through use of atmospheric dispersion models and models that describe how people live and work in urban areas it has been possible to describe the average exposure to NOx in cities of different sizes. The exposure to NOx for people living in the countryside has also been estimated. In this way, it has been possible to calculate the average exposure dose for NOx for the Swedish population. This figure is 23 micrograms/m3. By use of the relationships between NOx and specific compounds the average dose has been calculated for the following compounds: polyaromatic compounds (PAH); ethene, propene, and butadiene; benzene, toluene, and xylene; formaldehyde and actaldehyde; nickel, chromium (VI), arsenic, and cadmium; asbestos; and silicon.
Introduction: INSERM-IARC-CNRS workshop on biopersistence of respirable synthetic fibers and minerals. J. Bignon, R. Saracci, J.C. Touray. 1994;102 Suppl 5(Suppl 5):3-5. PubMed · Publisher · Free full text

Summary

This introduction to the proceedings of the INSERM-IARC-CNRS workshop on biopersistence of respirable synthetic fibers and minerals outlined the background to the meeting and summarized its sessions. The workshop was held at the International Agency for Research on Cancer in Lyon, France, in September 1992, and some 150 specialists attended. The authors reviewed earlier findings that fiber length and diameter influence carcinogenicity, and that the most biopersistent fibers appeared to have the highest fibrogenic or carcinogenic potential. They noted that in lung tissue from people who died with mesothelioma after exposure to mixed amphibole and chrysotile asbestos, amphibole fibers were usually retained in greater amounts, even when chrysotile had been dominant. Human mesothelioma was more often associated with amphibole exposure, whereas rat inhalation and cell culture studies found the two types about equally carcinogenic. They described processes affecting persistence, including deposition, clearance, translocation, breakage, splitting, leaching and dissolution, and uncertainty about pH in body fluids. The sessions covered three areas: in vitro tests, where dissolution rates for the same fiber differed between laboratories by as much as a factor of two; animal experiments and analytical techniques; and relevance to human disease. The authors called for a renewed hazard classification of synthetic fibers. They identified cellulose fibers used as asbestos substitutes as a research gap.

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Investigation of the biodurability of wollastonite and xonotlite. B. Bellmann, H. Muhle. 1994;102 Suppl 5(Suppl 5):191-5. PubMed · Publisher · Free full text

Abstract

The in vivo durability of wollastonite materials, coated and uncoated, and of xonotlite was tested. Wollastonite is an anhydrous natural silicate and xonotlite is a hydrated synthetic calcium silicate. UICC crocidolite was used as a positive control with high durability. Using a dry-sizing technique, fractions from the stock materials were prepared according to the definition of "thoracic particulate mass" and "respirable particulate mass" of the American Conference of Governmental Industrial Hygienists. Fibers were instilled intratracheally into female Wistar rats, and the evenness of their distribution in the lung was checked by scanning electron microscopy (SEM). After serial sacrifices at 2 and 14 days, 1, 3, and 6 months, and low temperature ashing of the lung, the fibers were analyzed by SEM. The number and size distribution of fibers were investigated. The total number of crocidolite fibers decreased with a half-time of 240 days, but the number of fibers > 5 microns in length was unchanged after 6 months. The elimination kinetics of wollastonite fibers from the lung were relatively fast, with half-times of 15 to 21 days. The coating of wollastonite in Wollastocoat had no effect on this elimination process. For the thoracic fraction of wollastonite, the elimination from the lung was as fast as for the respirable particulate fraction. The elimination kinetics of xonotlite from the lung was very fast. This material consisted of single crystals of acicular morphology with a median length of 1.3 micron and of agglomerates of these crystals. More than 99% of single crystals and about 85 to 89% of the agglomerates were already eliminated 2 days after instillation.
Investigation on the durability of man-made vitreous fibers in rat lungs. B. Bellmann, H. Muhle, O. Kamstrup, et al. 1994;102 Suppl 5(Suppl 5):185-9. PubMed · Publisher · Free full text

Abstract

Two types of sized stonewool with median lengths of 6.7 and 10.1 microns and median diameters of 0.63 and 0.85 microns, and crocidolite with fibers of median length of 4.8 microns and median diameter of 0.18 microns were instilled intratracheally into female Wistar rats. A single dose of 2 mg in 0.3 ml saline was used for the stonewool samples and 0.1 mg in 0.3 ml saline for crocidolite. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM). Five animals per group were sacrificed after 2 days, 1, 3, 6, and 12 months. After low-temperature ashing of the lungs about 200 fibers per animal were analyzed by SEM for length and diameter. The number and mass of fibers in the total lung were calculated. For the stonewool samples the decrease in the number of fibers in the lung ash followed approximately first order kinetics resulting in half-times of 90 and 120 days. The analysis of fiber number and diameter of different length fractions was used to estimate the contribution of three processes of fiber elimination: transport by macrophages for short fibers, breakage of fibers, and dissolution of fibers. (The process of transport by macrophages was found fastest for fibers with length < 2.5 microns). For the elimination of critical fibers with length > 5 microns, the breakage and dissolution were the most important processes. The breakage of fibers was predominant for one of the stonewool samples. The preferential type of the mechanism of fiber elimination is dependent on chemical composition and size distribution.
Lung content analysis of cases occupationally exposed to chrysotile asbestos. R.P. Nolan, A.M. Langer, J. Addison. 1994;102 Suppl 5(Suppl 5):245-50. PubMed · Publisher · Free full text

Abstract

The lung contents of six workers who had been occupationally exposed to chrysotile asbestos were examined. Five were lung cancer cases from Quebec, Canada. The sixth, an American worker who had developed pleural mesothelioma, was particularly interesting, with the lung content strikingly distinct from the Canadian cases; chrysotile, the predominant fiber in his lung, was present at a concentration 300 times that of the average total fiber content in the Canadian cases. The fiber length distribution of the chrysotile recovered from the U.S. mesothelioma case was indistinguishable from that of chrysotile specimens known to produce mesotheliomas in rats. It was also found that the characteristics of the calcium-magnesium-iron silicate fibers present in all six cases were not readily comparable to tremolite asbestos specimens known to induce mesotheliomas in animals.
Mechanisms associated with human alveolar macrophage stimulation by particulates. A. Holian, K. Kelley, R.F. Hamilton. 1994;102 Suppl 10(Suppl 10):69-74. PubMed · Publisher · Free full text

Abstract

Asbestos and silica are well-known fibrogenic dusts. However, there is no comprehensive understanding of the molecular and cellular events that lead to fibrosis as a consequence of asbestos or silica inhalation. Previous studies have shown that asbestos stimulates superoxide anion production in alveolar macrophages through the phospholipase C/protein kinase C pathway. In contrast, silica does not appear to activate this pathway nor stimulate superoxide anion production, but silica does stimulate cytokine release by some undetermined pathway. Therefore, using human alveolar macrophages isolated from normal healthy volunteers, we evaluated the potential involvement of intracellular calcium and tyrosine kinases as potential signal transduction pathways. In the absence of serum, crystalline silica, and to a lesser extent amorphous silica, caused a rapid and dose-dependent elevation of intracellular calcium coming from the extracellular space. However, in the presence of serum, which is required for silica-stimulated cytokine release, neither form of silica caused noticeable elevation of intracellular calcium. Silica, however, did increase the extent of tyrosine phosphorylation, most notably of proteins at approximately 46 and 50 kDa, suggesting activation of a tyrosine kinase pathway. Preincubation of alveolar macrophages for 24 hr with silica-primed human alveolar macrophages for enhanced interleukin-1 beta (IL-1 beta) release stimulated by endotoxin (LPS) that was dose dependent. The enhanced LPS-stimulated release of IL-1 beta correlated with enhanced mitogen-activated protein kinase activity. Taken together, these results indicate that a tyrosine kinase pathway is activated during silica stimulation of human alveolar macrophages.
Media and science: harmless dioxin, benign CFCs, and good asbestos. D.P. Rall. 1994;102(1):10. Editorial PubMed · Publisher · Free full text

Summary

In this editorial, the founder of Environmental Health Perspectives and former director of NIEHS argued that mass media had misled the public about three environmental hazards: dioxin, chlorofluorocarbons (CFCs), and chrysotile asbestos, which he stated makes up 95% of asbestos in place in the United States. On dioxin, he criticized a 15 August 1991 New York Times story reporting that its dangers had been exaggerated. He said the story ignored a January 1991 NIOSH report by Fingerhut et al. that workers exposed for more than 2 years and observed for at least 20 years had a 46% greater cancer death rate than expected, and he cited later confirming studies. On CFCs, he summarized data presented by Sherwood Rowland refuting critics' claims about ozone depletion. On asbestos, he stated that a 19 January 1990 Science report by Mossman and others, most associated with the asbestos industry, argued that chrysotile was less toxic and posed minimal risk at low doses. He said this account ignored human data on chrysotile carcinogenicity, including mesotheliomas among Canadians and among family members of exposed workers. He added that asbestos seldom appears in pure form, that no threshold has been found, and that rebuttal letters received little press coverage. He concluded that professional journals should review their editorial policies and publish balancing views and commentary in the same issue.

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One-year follow-up of the phagocytic activity of leukocytes after exposure of rats to asbestos and basalt fibers. M. Hurbánková. 1994;102 Suppl 5(Suppl 5):201-3. PubMed · Publisher · Free full text

Abstract

The phagocytic activity of leukocytes in peripheral blood was investigated after 2, 24, and 48 hr; 1, 2, 4, and 8 weeks; and 6 and 12 months following intraperitoneal administration of asbestos and basalt fibers to Wistar rats. Asbestos and basalt fibers differed in their effects on the parameters studied. Both granulocyte count and phagocytic activity of leukocytes during the 1-year dynamic follow-up in both dust-exposed groups of animals changed in two phases, characterized by the initial stimulation of the acute phase I, followed by the suppression of the parameters in the chronic phase II. Exposure to asbestos and basalt fibers led, in phase II, to impairment of the phagocytic activity of granulocytes. Asbestos fibers also significantly decreased phagocytic activity of monocytes. Exposure to basalt fibers did not affect the phagocytic activity of monocytes in phase II. Results suggest that the monocytic component of leukocytes plays an important role in the development of diseases caused by exposure to fibrous dusts, but basalt fibers have lesser biological effects than asbestos fibers.
Oxygen radicals and asbestos carcinogenesis. V.D. Moyer, C.A. Cistulli, C.A. Vaslet, et al. 1994;102 Suppl 10(Suppl 10):131-6. Review PubMed · Publisher · Free full text

Abstract

Asbestos fibers have been shown to generate reactive oxygen species using a variety of in vitro assays. It is hypothesized that these highly reactive metabolites mediate the development of malignant mesothelioma induced by asbestos fibers. DNA is a potential target of oxidant attack. Adaptive responses to oxidant injury have been described during exposure of mesothelial cells to asbestos fibers in vitro. Failure of these adaptive responses may lead to genetic instability and alterations in oncogenes and tumor suppressor genes that confer a proliferative advantage to emerging neoplastic mesothelial cells.
Oxygen radicals and asbestos-mediated disease. T.R. Quinlan, J.P. Marsh, Y.M. Janssen, et al. 1994;102 Suppl 10(Suppl 10):107-10. Review PubMed · Publisher · Free full text

Abstract

Asbestos fibers are potent elaborators of active oxygen species whether by reactions involving iron on the surface of the fiber, or by attempted phagocytosis of fibers by cell types resident in the lung. The link between production of active oxygen species and the pathogenesis of asbestos-mediated disease has been highlighted by studies outlined here exploring the use of antioxidant scavengers which inhibit the cytotoxic effects of asbestos both in vitro and in vivo. The use of antioxidant enzymes ameliorates the induction of certain genes necessary for cell proliferation, such as ornithine decarboxylase, implicating oxidants as causative factors in some abnormal cell replicative events. Based on these observations, antioxidant enzymes likely represent an important lung defense mechanism in response to oxidative stress. In addition, their gene expression in lung or in cells from bronchoalveolar lavage might be a valuable biomarker of chronic inflammation and pulmonary disease after inhalation of oxidants.
Persistence of long, thin chrysotile asbestos fibers in the lungs of rats. P.G. Coin, V.L. Roggli, A.R. Brody. 1994;102 Suppl 5(Suppl 5):197-9. Review PubMed · Publisher · Free full text

Abstract

The distribution of inhaled mineral fibers in the lung determines the site and severity of disease caused by the fibers. Some of our recent work has described the fate of inhaled asbestos fibers in rodents. After a brief inhalation exposure, asbestos fibers are deposited primarily at the first alveolar duct bifurcations, and fibrotic lesions are initiated. These sites of deposition occur as close to the visceral pleura as 220 micron. Several studies have suggested that short fibers are cleared from the lung more efficiently than long ones, and our data support this view. Our laboratory has shown that aerosolized chrysotile fibers longer than 16 microns can be deposited in the peripheral lung parenchyma of rats, and the measured clearance rate of these fibers is not significantly different from zero. Chrysotile, but no amphibole, fibers split longitudinally, so that the number of retained chrysotile fibers > or = 16 microns in length increases over time. We have not observed significant changes in chemical composition of chrysotile fibers up to 30 days post-deposition in the rat. Nor have we observed translocation of chrysotile fibers from the "central" regions of the lung toward the subpleural regions. However, 1 month after a single 3-hr exposure to chrysotile asbestos, the longest, most pathogenic fibers persist throughout the lung parenchyma. These retained fibers have the potential to cause disease in both parenchyma and pleura.
Persistence of natural mineral fibers in human lungs: an overview. A. Churg, J.L. Wright. 1994;102 Suppl 5(Suppl 5):229-33. Review PubMed · Publisher · Free full text

Abstract

Virtually all available data on persistence of naturally occurring mineral fibers in human lungs have been derived from studies of asbestos fiber loads. These studies indicate that, although both amphibole and chrysotile asbestos fibers are found in the lungs of the general population and exposed workers, amphibole fibers are universally present in disproportionately large and chrysotile fibers in disproportionately small amounts compared to their known abundance in the original inhaled dusts. Why this should be remains unclear. Most reports have shown that fiber accumulation is proportional to measured exposure for amphiboles, but this is not generally true for chrysotile. Very little information is available on actual fiber clearance rates from human lungs. For amosite and crocidolite, estimated clearance half-times are measured in years to decades, whereas for chrysotile the available, rather indirect, data suggest that the vast majority of fibers are cleared within months, although some fibers may be sequestered and very slowly cleared. Overall these studies suggest that the differences between amphibole and chrysotile fiber burdens in man reflect much faster clearance of chrysotile fibers, rather than a failure of chrysotile deposition. A variety of other naturally occurring fibers are commonly found in human lungs, but there are no data on their rates of accumulation or disappearance.
Regarding bias. J.B. Gee. 1994;102(5):425-6. Letter PubMed · Publisher · Free full text
Regulation of antioxidant enzymes in lung after oxidant injury. T. Quinlan, S. Spivack, B.T. Mossman. 1994;102 Suppl 2(Suppl 2):79-87. Review PubMed · Publisher · Free full text

Abstract

Studies have implicated active oxygen species (AOS) in the pathogenesis of various lung diseases. Many chemical and physical agents in the environment are potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat, etc. These agents produce AOS by different mechanisms, but frequently the lung is the primary target of toxicity, and exposure results in damage to lung tissue to varying degrees. The lung has developed defenses to AOS-mediated damage, which include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In this review, antioxidant defenses to environmental stresses in the lung as well as in isolated pulmonary cells following exposure to a number of different oxidants, are summarized. Each oxidant appears to induce a different pattern of antioxidant enzyme response in the lung, although some common trends, i.e., induction of MnSOD following oxidants inducing inflammation or pulmonary fibrosis, in responses to oxidants occur. Responses may vary between the different cell types in the lung as a function of cell-cycle or other factors. Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants may serve as a biomarker of AOS-mediated damage in the lung.
Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats. T.W. Hesterberg, W.C. Miiller, R. Mast, et al. 1994;102 Suppl 5(Suppl 5):133-7. PubMed · Publisher · Free full text

Abstract

This article describes the relationship between fiber biopersistence and the chronic toxicity of different chemical compositions of man-made vitreous fibers (MMVF) in the lung. Rats were exposed in "nose-only" inhalation chambers, 6 hr/day, 5 days/week, for 24 months to aerosol concentrations of 30 mg/m3 containing comparable fiber numbers and similar dimensions of fibrous glass (FG) or refractory ceramic fiber (RCF). Interim sacrifices were performed periodically to monitor fiber number and dimensions in the lung and the progression of pulmonary alterations. At each interim sacrifice, three to six recovery animals were removed from each exposure group and held until two years to determine the biopersistence of fibers after different exposure times. Fibers were recovered from the ashed lungs, counted, and measured using optical and scanning electron microscopy (SEM). Fiber chemistry was assessed in 91-week recovery lungs using energy dispersive spectroscopy (EDS) analysis. RCF induced lung fibrosis and an elevation in lung tumors and pleural mesotheliomas. FG exposure resulted in no lung fibrosis, no statistically significant increase in the lung tumor incidence, and no mesotheliomas. After two years of continuous exposure, the number of World Health Organization fibers per milligram dry lung recovered from RCF and FG exposed lungs was comparable. EDS analysis of recovery lungs showed that most of the alkalis and alkaline earths had leached from the FG fibers over time. A slight change in RCF chemistry was observed. These findings indicate that the change in the chemical composition of fibers may be an important determinant of the chronic toxicity of MMVFs.
Retention of asbestos fibers in the human body. A. Tossavainen, A. Karjalainen, P.J. Karhunen. 1994;102 Suppl 5(Suppl 5):253-5. PubMed · Publisher · Free full text

Abstract

The number, type, and size of retained asbestos fibers were measured by scanning electron microscopy (SEM) in lung tissues of 10 workers who had died from lung cancer or mesothelioma. The levels were 190-3000 x 10(6) fibers/g of dry tissue in three crocidolite sprayers, 6-39 x 10(6) fibers/g of dry tissue in two asbestos product workers and 13-280 x 10(6) fibers/g of dry tissue in five insulators exposed to anthophyllite. The duration of past exposure corresponding to the limit of 1 million fibers/g of dry tissue was 1 to 2 days in spraying, 3 to 10 days at the production plant and 1 to 4 months in insulation work. No long-term clearance of amphibole fibers, > 5 microns in length, could be demonstrated. In one of the sprayers the fiber concentrations of lung parenchyma, visceral and parietal pleura, hilar lymph nodes, and kidney cortex were orders of magnitude higher than in a series of unselected autopsies. The size and aspect ratio of crocidolite fibers in various tissues were similar, indicating that the translocation processes are rather unselective in respect to fiber dimensions.
Review of animal/in vitro data on biological effects of man-made fibers. S.A. Ellouk, M.C. Jaurand. 1994;102 Suppl 2(Suppl 2):47-61. Review PubMed · Publisher · Free full text

Abstract

This paper reviews the investigations with man-made fibers (MMF). Insulation woods: glasswool (GW), rockwool (RW), slagwool (SW), glass microfibers (GMF), glass filaments (GFiI), and refractory ceramic fibers (RCF) have been used in experimental animals and in in vitro cell systems. A large heterogeneous number of fibers, methods of fiber preparation, size selection, aerosolization, fiber size, and fiber burden measurement were noted, rendering difficult a comparison between results. By inhalation, RCF and asbestos used as positive controls produced a significant tumor increase. In some studies, a low tumor yield was found after inhalation of insulation wools; when all inhalation data were gathered, a significant tumor increase was found with GW. However, it is difficult to draw definitive conclusions on the potential of other fiber types because, in addition to the different compositions of the fibers, differences in fiber number and sizes existed, especially in comparison with asbestos. Moreover, experiments using inoculation, especially by the intraperitoneal route revealed a carcinogenic potential of all fibers types but GFiI and SW. In these two groups a small number of animals has been investigated and the fiber characteristics were sometimes irrelevant. So far, a relationship between the carcinogenic potency and fiber dimensions has been established. Other fiber parameters may be of importance (surface chemistry, biopersistence, fiber structure, for example) but further investigations are necessary to determine the correlations between these parameters and tumor incidence. In vitro experiments have emphasized the fiber characteristics identified in vivo as playing a role in the carcinogenic potency and should be developed as a better approach of the mechanistic effects of MMF.
Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies. F. Pott, M. Roller, K. Kamino, et al. 1994;102 Suppl 5(Suppl 5):145-50. PubMed · Publisher · Free full text

Abstract

At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS)
Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action. F.M. Kogan, O.V. Nikitina. 1994;102 Suppl 5(Suppl 5):205-6. PubMed · Publisher · Free full text

Abstract

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity.
The occupational physician's point of view: the model of man-made vitreous fibers. P. Brochard, J.C. Pairon, J. Bignon. 1994;102 Suppl 5(Suppl 5):31-6. PubMed · Publisher · Free full text

Abstract

This article gives a detailed description of the procedure the occupational physician uses in interpreting the available scientific data to provide useful information for prevention of pulmonary diseases related to man-made mineral fibers, particularly lung cancer and mesothelioma. As it is difficult to reach definite conclusions from human data on the toxicity of specific fibers, an experimental approach is needed. Concerning animal data, we emphasize that adequate inhalation studies are the "gold standard" for extrapolating to humans. However, experiments using intracavitary injection or cells in vitro may represent indicative tests for a possible carcinogenic effect. Such tests should be used to assess the intrinsic carcinogenicity of fibers, but they must be confirmed by adequate inhalation models. Despite the present uncertainties, a proposal is made that could make it possible to classify fibers according to their toxicologic potential, grading them in accordance with physicochemical parameters, in vitro testing, and animal experiments. This procedure may be applicable to nonvitreous fibers and to organic fibers.
Asbestos findings questioned. J.B. Gee. 1993;101(7):564-5. Comment · Letter PubMed · Publisher · Free full text
Asbestos-induced lung disease. A.R. Brody. 1993;100:21-30. Review PubMed · Publisher · Free full text

Abstract

This review attempts to deal with two major questions concerning asbestos-induced lung disease: How does inhaled asbestos cause cell proliferation and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the past 10 years, and there appear to be two hypothetical schemes which could explain, at least in part, the fibroproliferative effects of asbestos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first, but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple varieties of growth factors and cytokines that mediate the pathogenesis of asbestosis. There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor beta, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis. The challenge today is to establish which combinations of the many factors released actually are playing a role in disease pathogenesis. The issue of continued risk currently is more a question of policy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances under which asbestos in buildings constitutes an ongoing health hazard. The litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a complete carcinogen. It appears to be generally nongenotoxic, but all asbestos fiber types can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation.
Chemical agents and the immune response. M.I. Luster, G.J. Rosenthal. 1993;100:219-26. Review PubMed · Publisher · Free full text

Abstract

Our desire to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical-induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals has increased, in part, due to the fact that chemical companies are moving to larger and/or different markets. It has been estimated that 35 million Americans suffer from allergic disease, of which 2-5% are from occupational exposure. Although there is not yet a clear understanding of dose-response relationships or disease predisposition, there are many well-defined examples (isocyanates, anhydrides) of chemical sensitizers in humans and experimental animals. Evidence that chemicals suppress immune responses in humans is considerably less well established, although there is a public perception that chemicals generally cause immunosuppression. This perception has been fueled by highly publicized legal cases and scientific controversies within the academic and industrial communities. As a consequence of these public and scientific concerns, many of the regulatory agencies are developing immunotoxicity testing guidelines. At the present, however, there are limitations on adequate human methodology and data that allow the extrapolation of animal data to assess human risk. The potential for human immunosuppression remains of concern, however, because of a large database generated from animal studies that demonstrates immunosuppression as well as reports of immunosuppression in humans inadvertently (e.g., halogenated aromatic hydrocarbons) or occupationally (asbestos, benzene) exposed to xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS)
Chemical interaction: enhancement and inhibition of clastogenicity. W.A. Anwar. 1993;101 Suppl 3(Suppl 3):203-6. PubMed · Publisher · Free full text

Abstract

Most environmental exposures involve concurrent or sequential exposure to multiple chemicals in air, water, and food. Interactive effects in carcinogenesis have been described for certain combinations of agents. They are described in terms of enhancement or inhibition of carcinogenesis. Enhancement effects have been documented for cigarette smoking in combination with exposure to asbestos, radon, alcohol, or other exposures. A variety of inhibitors of carcinogenesis have also been described. They are classified into agents preventing formation of carcinogens; blocking agents; and suppressing agents. Assessment of risk from exposure to multiple agents can be derived either from epidemiological studies in relation to actual exposure or from laboratory studies after controlled exposure to different agents. Prediction of how toxic components of mixtures will interact should be based on an understanding of the mechanisms of such interactions. Compounds may interact chemically, yielding new toxic components or causing a change in the biological availability of the existing components or metabolites. In humans, great individual variability in response is to be expected because of genetic heterogeneity or acquired host susceptibility factors. Interaction is thus a key component in the risk assessment process. In this paper, the definition of interaction and the theoretical basis for different types of interaction in cancer causation are reviewed. Epidemiological and experimental studies showing interactive effects of two chemical carcinogens are also presented.
Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice. J.K. Haseman, A.M. Lockhart. 1993;101(1):50-4. PubMed · Publisher · Free full text

Abstract

We examined a database of 379 long-term carcinogenicity studies in rats and mice to evaluate sex and species correlations in site-specific carcinogenic responses. Within a species, most target sites showed a strong correlation between males and females. For example, chemicals producing forestomach or liver tumors in males were likely to produce these same types of tumors in females. There was also a significant correlation between species for certain site-specific carcinogenic effects, most notably tumors of the forestomach, liver, and thyroid gland. In contrast, adrenal pheochromocytoma, preputial/clitoral gland neoplasms, and lung tumors showed no significant interspecies correlation. Many chemicals produced a syndrome of carcinogenic effects involving tumors of the skin, Zymbal gland, preputial/clitoral gland, mammary gland, and/or oral cavity. Regarding different target sites, there appeared to be a correlation between thyroid and liver tumors both within and between species. Further, all chemicals producing mesotheliomas in male rats also produced mammary gland neoplasms in female rats. In contrast, kidney and urinary bladder tumors showed no significant association with any other tumor type in rats or mice. If a chemical produced a site-specific carcinogenic effect in female rats or mice, there was approximately a 65% probability that the chemical would also be carcinogenic at that same site in males. The interspecies correlation was somewhat lower: approximately 36% of the site-specific carcinogenic effects observed in one species (rats or mice) were also observed in the other species.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of mineral particles containing iron on primary cultures of rabbit tracheal epithelial cells: possible implication of oxidative stress. C. Guilianelli, A. Baeza-Squiban, E. Boisvieux-Ulrich, et al. 1993;101(5):436-42. PubMed · Publisher · Free full text

Abstract

Environmental mineral particles such as asbestos are responsible for numerous respiratory diseases. In addition to effects related to their geometry, particles are now assumed to act by triggering an oxidative stress process. Iron-containing particles, in particular, can produce oxygen-activated species by oxidizing their iron. To evaluate the involvement of iron-containing particles in respiratory diseases, three mineral particles (chrysotile, nemalite, and hematite) were tested in primary cultures of tracheal epithelium. Because of the ciliary beat, the three mineral particles were quickly concentrated at the periphery of the mucociliary epithelium, reconstituted in vitro where they induced cellular lesions. Endocytosis of the three types of particles was observed. Cytotoxicity studies have indicated that among the tested particles, the most cytostatic after 24 hr of treatment was the one that contained more Fe2+ available on the surface, nemalite. Moreover, the effect of nemalite was reduced by pretreatment with desferrioxamine. As mineral particles, especially asbestos, are suspected to induce squamous metaplasia, we chose to study two specific transformations of the epithelium: the expression of cytokeratin-13 and the formation of cross-linked envelopes. Under our culture conditions, nemalite and chrysotile increased the expression of the cytokeratin-13, a specific marker of squamous metaplasia, whereas nemalite was the only particle able to strongly induce the formation of cross-linked envelopes. Nemalite was the most cytostatic particle and the most efficient at inducing squamous metaplasia. Measures of oxidizing power by electron-spin resonance revealed that nemalite produced the most oxygen-activated species.(ABSTRACT TRUNCATED AT 250 WORDS)
Global problems from exposure to asbestos. A.L. Frank. 1993;101 Suppl 3(Suppl 3):165-7. Review PubMed · Publisher · Free full text

Abstract

Considerable human-derived data the health consequences of asbestos exposure are available. Usually, less information is available from laboratory models of asbestos-related health effects. Animal data mirror the experience in man, and cellular studies help in to understand the mechanistic changes related to asbestos. Although it is clearly carcinogenic, asbestos has shown much variability when examined for its mutagenic activity. Asbestos, a commercial term referring to a family of six naturally occurring mineral fibers, has been widely used around the world. Disease has been recognized into the last century, and at this time every occupational group that has been examined for possible asbestos-related disease has demonstrated it. Disease associated with asbestos makes no distinction based on race or geography, and wherever asbestos is handled it produces disease. With shifting global commercial patterns, disease patterns can be expected to shift also.
Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations. H. Vainio, K. Husgafvel-Pursiainen, S. Anttila, et al. 1993;101 Suppl 3(Suppl 3):189-92. PubMed · Publisher · Free full text

Abstract

To investigate the role of tobacco smoking and asbestos fibers in the etiology of human lung cancer, we examined the activating point mutations in the K-ras oncogene in DNA samples from 49 patients. Mutations were found more often in tissue from adenocarcinomas (12/21) than in tissue from tumors other than nonadenocarcinomas of the lung (3/28). Among the adenocarcinoma patients, asbestos exposure was predictive of K-ras mutation (odds ratio, 4.9; 95% confidence interval, 0.7-34.3); in patients with other types of lung cancer, the relation appeared to be an inverse one, but the numbers were small. The proportion of heavy smokers (over 50 pack-years) was 60% among people with K-ras mutations and 35% among the K-ras-negative subjects, suggesting that smoking causes K-ras mutations. If mutations in K-ras genes are caused by smoking, asbestos would act as a promoting agent by conferring selective growth conditions for clonal expansion on these mutated cells. Asbestos may favor recruitment of (initiated) K-ras mutation-positive cells in the multistage process of carcinogenesis by stimulating cellular growth.
Kidney cancer and hydrocarbon exposures among petroleum refinery workers. C. Poole, N.A. Dreyer, M.H. Satterfield, et al. 1993;101 Suppl 6(Suppl 6):53-62. PubMed · Publisher · Free full text

Abstract

To evaluate the hypothesis of increased kidney cancer risk after exposure to hydrocarbons, especially those present in gasoline, we conducted a case-control study in a cohort of approximately 100,000 male refinery workers from five petroleum companies. A review of 18,323 death certificates identified 102 kidney cancer cases, to each of whom four controls were matched by refinery location and decade of birth. Work histories, containing an average of 15.7 job assignments per subject, were found for 98% of the cases and 94% of the controls. To each job, industrial hygienists assigned semiquantitative ratings for the intensity and frequency of exposures to three hydrocarbon categories: nonaromatic liquid gasoline distillates, aromatic hydrocarbons, and the more volatile hydrocarbons. Ratings of "present" or "absent" were assigned for seven additional exposures: higher boiling hydrocarbons, polynuclear aromatic hydrocarbons, asbestos, chlorinated solvents, ionizing radiation, and lead. Each exposure had either no association or a weak association with kidney cancer. For the hydrocarbon category of principal a priori interest, the nonaromatic liquid gasoline distillates, the estimated relative risk (RR) for any exposure above refinery background was 1.0 (95% confidence interval [CI] 0.5-1.9). Analyses of cumulative exposures and of exposures in varying time periods before kidney cancer occurrence also produced null or near-null results. In an analysis of the longest job held by each subject (average duration 9.2 years or 40% of the refinery work history), three groups appeared to be at increased risk: laborers (RR = 1.9, 95% CI 1.0-3.9); workers in receipt, storage, and movements (RR = 2.5, 95% CI 0.9-6.6); and unit cleaners (RR = 2.3, 95% CI 0.5-9.9).
Lung cancer in the lower lobe is associated with pulmonary asbestos fiber count and fiber size. S. Anttila, A. Karjalainen, O. Taikina-aho, et al. 1993;101(2):166-70. PubMed · Publisher · Free full text

Abstract

We studied exposure to asbestos, pulmonary fibrosis, fiber count, and fiber size in relation to the lobar origin of lung cancer in 90 consecutive patients. Among the 32 patients with a history of occupational exposure to asbestos, 22 were construction workers. The proportion of lower-lobe tumors increased with the duration of exposure from 45% in those working less than 15 years to 82% in those working 15 years or more in the construction trade, as compared with 25% in patients who were probably not exposed. The location of the tumor in the lower lobe was explained by the high number of total fibers [odds ratio (OR) = 9.0, CI = 2.3-34.6), of fibers 3 microns and longer (OR = 22.1, CI = 3.9-125), and fibers of anthophyllite (OR = 14.6, CI = 2.4-83.4) and crocidolite (OR = 7.0, CI = 1.2-41.2) when the effect of smoking and fibrosis was adjusted in the logistic regression analysis. The location of the tumor did not correlate with fibrosis, pack-years smoked, or the number of short (< 3 microns) fibers. Our findings suggest that asbestos causes an excess of lower-lobe tumors at a relatively low exposure level, independently of pulmonary fibrosis.
Mechanisms of multistep carcinogenesis and carcinogen risk assessment. J.C. Barrett. 1993;100:9-20. Review PubMed · Publisher · Free full text

Abstract

Many different types of chemical exposures can increase the incidence of tumors in animals and humans, but usually a long period of time is required before the carcinogenic risk of an exposure is manifested. Both of these observations can be explained by a multistep/multigene model of carcinogenesis. In this model, a normal cell evolves into a cancer cell as the result of heritable changes in multiple, independent genes. The two-stage model of initiation and promotion for chemical carcinogenesis has provided a paradigm by which chemicals can act by qualitatively different mechanisms, but the process of carcinogenesis is now recognized as more complex than simply initiation and promotion. Even a three-stage model of initiation, promotion, and progression, which can be operationally defined, is not adequate to describe the carcinogenic process. The number of genes altered in a cancer cell compared to a normal cell is not known; recent evidence suggests that 3-10 genetic events are involved in common adult malignancies in humans. Two distinct classes of genes, protooncogenes and tumor-suppressor genes, are involved in the cancer process. Multiple oncogenes may be activated in a tumor, while multiple tumor-suppressor genes may be inactivated. Identification of the genes involved in carcinogenesis and elucidation of the mechanisms of their activation or inactivation allows a better understanding of how chemical carcinogens influence the process of neoplastic evolution. The findings of multiple genetic changes (including point mutations, chromosomal translocations, deletions, gene amplification, and numerical chromosome changes) in activated protooncogenes and inactivated tumor-suppressor genes provide experimental support for Boveri's somatic mutation theory of carcinogenesis. In addition to mutagenic mechanisms, chemicals may heritably alter cells by epigenetic mechanisms and enhance the clonal expansion of altered cells. Most chemical carcinogens operate via a combination of mechanisms, and even their primary mechanism of action may vary depending on the target tissues. The classification of chemicals by mechanism of action or by nongenotoxic or genotoxic activity has certain inherent difficulties because no classification of chemicals is exhaustive or definitive.
Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke. H.S. Sekhon, B. Keeling, A. Churg. 1993;101(4):326-30. PubMed · Publisher · Free full text

Abstract

The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of instilled fibrogenic particles on the clonal growth of murine pulmonary alveolar macrophages. Y. Oghiso, Y. Yamada, Y. Shibata. 1992;97:159-61. PubMed · Publisher · Free full text

Abstract

Murine pulmonary alveolar macrophages (PAM) form macrophage colonies in vitro with colony-stimulating factors, which stimulate the clonal growth of radioresistant alveolar colony-forming cells (AL-CFC). The toxic effects of fibrogenic mineral dust particles on AL-CFC were investigated after intratracheal instillation into mice. Exposure to either crocidolite asbestos or silica (Min-u-sil) induced a significant depletion of AL-CFC as well as a decrease in PAM recovery compared to either untreated or titanium dioxide-exposed animals. Such effects were also noted with different doses (50-200 micrograms/animal) of instilled particles. The plating efficiency of AL-CFC was depleted in PAM exposed to fibrogenic particles in vitro, but not when exposed to nonfibrogenic titanium dioxide particles. These results indicate the toxic effects of fibrogenic dust particles on the clonal growth of PAM, cells which play a role in the clearance of inhaled particles from the lung and in subsequent pathologic processes.
Influence of surfactant components and exposure geometry on the effects of quartz and asbestos on alveolar macrophages. J. Schimmelpfeng, E. Drosselmeyer, V. Hofheinz, et al. 1992;97:225-31. PubMed · Publisher · Free full text

Abstract

Bovine (BAM) and rat (RAM) alveolar macrophages were incubated in vitro with DQ12 quartz or UICC chrysotile asbestos either alone or in the presence of dipalmitoyl lecithin (DPL). The reaction of the cells of both species to the untreated dust particles was similar qualitatively and quantitatively, with a loss of viability and release of lactate dehydrogenase and N-acetyl-beta-glucosaminidase after 20 hr of incubation. In the presence of DPL, the toxicity of quartz to BAM disappeared completely, whereas the protective influence of the phospholipid was distinctly diminished in the case of RAM. The presence of lavage fluid was less effective than that of pure DPL. There was no protective influence of DPL with asbestos either for BAM or for RAM. The effects of phagocytizable, suspended quartz particles were compared with the effects of the same type of particles fixed on a glass surface to exclude the possibility of phagocytosis. The effect of the suspended particles on the viability and release of enzymes was more pronounced than that of the fixed particles. On the other hand, superoxide anion production was stimulated to a much higher degree by the fixed quartz particles. This could be explained by the continuing contact of the outer cell membrane with the silica surfaces, whereas free particles were rapidly phagocytized. The release of lysosomal enzymes induced by fixed quartz particles was a secondary phenomenon following cell death.
A case-control study of lung cancer with special reference to asbestos exposure. M. Minowa, S. Hatano, M. Ashizawa, et al. 1991;94:39-42. PubMed · Publisher · Free full text

Abstract

A case-control study of lung cancer was carried out in Yokosuka City, Kanagawa Prefecture, the location of a pre-war Japanese Imperial naval factory and present site of a U.S. naval base. Cytologically or pathologically confirmed male fatal cases of lung cancer during the period of 1978 to 1982 in Yokosuka Kyosai Hospital were compared with a control group in the same hospital. Controls who died from causes other than cancer, pneumoconiosis, accident, or suicide were matched by age to the cases. Information that included occupational and smoking history was obtained by interviews with the families of the 96 cases and 86 controls. Major results were as follows: a) The relative risks of lung cancer associated with asbestos exposure and suspected exposure were 2.41 (p less than 0.05) and 1.56, respectively, after controlling for age and smoking history, and the relative risk associated with smoking was 6.01 (p less than 0.05) after adjusting for age and asbestos exposure. b) The age- and smoking-adjusted relative risks of lung cancer associated with asbestos exposure were 3.40 (p less than 0.01) and 1.72 for Kreyberg groups I and II, respectively. Significantly elevated relative risk associated with smoking history was demonstrated for Kreyberg group I, but not for group II, after controlling for age and asbestos exposure.
Amphibole content of cosmetic and pharmaceutical talcs. A.M. Blount. 1991;94:225-30. PubMed · Publisher · Free full text

Abstract

Pharmaceutical and cosmetic-grade talcs were examined for asbestiform amphibole content using a new density-optical method. Talcs under the Food and Drug Administration are not regulated as to asbestos content; however, all talcs were well below the level mandated by the Occupational Safety and Health Administration for industrial talcs. Only one was found to contain an amphibole particle size distribution typical of asbestos.
Comparison of risks from outdoor and indoor exposure to toxic chemicals. L.A. Wallace. 1991;95:7-13. PubMed · Publisher · Free full text

Abstract

Environmental Protection Agency TEAM (Total Exposure Assessment Measurement) Studies have measured exposures of about 800 persons to 25 volatile organic compounds (VOCs) and exposures of about 300 persons to 32 pesticides. These persons were selected to represent more than 1 million residents of industrial manufacturing cities such as Bayonne and Elizabeth, New Jersey, and Los Angeles, California; cities with light industry, such as Greensboro, North Carolina, and Baltimore, Maryland; rural areas such as Devils Lake, North Dakota; and cities with high pesticide use such as Jacksonville, Florida, as well as low-to-moderate pesticide use such as Springfield, Massachusetts. The TEAM data provide an opportunity to estimate the risks from airborne exposure to a number of suspected carcinogens for a substantial number of persons residing in a wide variety of urban, suburban, and rural areas. Because all of the TEAM Studies measured outdoor concentrations near the homes of the participants, it is possible to apportion the risks between outdoor and indoor sources. Upper-bound lifetime risks of cancer are calculated for both indoor and outdoor sources of 12 VOCs and about 23 pesticides measured in the TEAM Studies. These risk calculations are supplemented by calculations based on other studies for some additional pollutants, including radon and environmental tobacco smoke. The relationship of these upper-bound risk estimates to "best-guess" values is discussed. Sharper estimates of risk based on identifying population subgroups exposed to major sources are also discussed. Important gaps in our knowledge of exposure measurements are identified, e.g., particulates (including polyaromatic hydrocarbons); 1,3-butadiene, asbestos, chromium, cadmium, arsenic, vinyl chloride, methylene chloride, and most polar organics.
Germinomas and teratoid siphon anomalies in softshell clams, Mya arenaria, environmentally exposed to herbicides. G.R. Gardner, P.P. Yevich, J. Hurst, et al. 1991;90:43-51. PubMed · Publisher · Free full text

Abstract

Seminomas and dysgerminomas are epizootic in softshell clams, Mya arenaria, from three Maine estuaries contaminated with herbicides. The first epizootic was discovered in 22% of clams collected as Searsport near Long Cove Brook and three culverts that conveyed heating oil and jet fuel spilled from a tank farm in 1971. Data from subsequent epizootiological studies and a series of long-term experimental exposures of softshell clams to no. 2 fuel oil, JP-4, and JP-5 jet fuel at the U.S. EPA, Environmental Research Laboratory in Narragansett, Rhode Island, and in the field did not support an etiology by these petroleum products. In the two recent epizootics reported here, the germinomas have been observed in 3% of the softshell clams collected from Roque Bluffs near Machiasport and from 35% of softshell clams collected from Dennysville. Mya collected at Dennysville had pericardial mesotheliomas and teratoid siphon anomalies in addition to gonadal neoplasms. Estuaries at Dennysville had been contaminated by herbicides in a 1979 accidental spray overdrift during aerial application of Tordon 101 to adjacent forests. Further investigation determined widespread use of the herbicides Tordon 101, 2,4-D,2,4,5-T, and other agrochemicals in an extensive forestry and blueberry industry in both the Roque Bluffs and the Dennysville areas. Herbicide applications at Searsport were confirmed for railroad property bordering Long Cove estuary and for Long Cove Brook adjacent to the estuary where a highway department reportedly cleans its spray equipment. Herbicide contamination is the only common denominator identified at all three sites where Mya have been found with gonadal neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)
Public inquiries about indoor air quality in California. J.M. Macher, S.B. Hayward. 1991;92:175-80. PubMed · Publisher · Free full text

Abstract

To identify the indoor air quality issues about which Californians most often sought advice from a health department or a public information agency and to evaluate how well these agencies met the public's needs, members of the California Interagency Working Group (IWG) on Indoor Air Quality kept records of inquiries they received over a 30-month period from mid-1985 through 1987. Members of the IWG answered calls from residents of a least 49 of California's 58 counties. IWG members received more public inquiries about residences than about offices, educational institutions, commercial buildings, or medical facilities. However, each call about a residence probably represented fewer people at risk of exposure to a real or a potential problem than did calls about other types of buildings. Homeowners themselves asked the majority of the questions about residences, whereas a large number of the inquiries about office buildings were made, not by affected office workers, but by building managers, contractors, consultants, or company health and safety officers. The leading topics of concern in the residences were asbestos, chemical and biological contamination, and radon. In offices, chemical contamination, the ventilation system, biological contamination, asbestos, and tobacco smoke were the most frequently mentioned sources of problems. Callers often reported experiencing headaches, allergy symptoms, nose or throat irritation, and respiratory tract problems in connection with their complaints. IWG members directed a third of the calls elsewhere, of which half were referred to consultants or testing laboratories. The IWG's experience in the State of California could help other health departments prepare to face the public's increasing concern about indoor air pollution.
Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts. R. Ebert, J.C. Barrett, R.W. Wiseman, et al. 1990;88:175-8. PubMed · Publisher · Free full text

Abstract

Carcinogen-induced point mutations resulting in activation of ras oncogenes have been demonstrated in various experimental systems such as skin carcinogenesis, mammary, and liver carcinogenesis. In many cases, the data support the conclusion that these point mutations are critical changes in the initiation of these tumors. The Syrian hamster embryo (SHE) cell transformation model system has been widely used to study the multistep process of chemically induced neoplastic transformation. Recent data suggest that activation of the Ha-ras gene via point mutation is one of the crucial events in the transformation of these cells. We have now cloned the c-Ha-ras proto-oncogene from SHE cDNA-libraries, and we have performed polymerase chain reaction and direct sequencing to analyze tumor cell lines induced by different chemical carcinogens for the presence of point mutations. No changes were detectable at codons 12, 13, 59, 61, and 117 or adjacent regions in tumor cell lines induced by diethylstilbestrol, asbestos, benzo(a)pyrene, trenbolone, or aflatoxin B1. Thus, it is not known whether point mutations in the Ha-ras proto-oncogene are essential for the acquisition of the neoplastic phenotype of SHE cells. Activation of other oncogenes or inactivation of tumor suppressor genes may be responsible for the neoplastic progression of these cells. However, in SHE cells neoplastically transformed by diethylstilbestrol or trenbolone, a significant elevation of the c-Ha-ras expression was observed. Enhanced expression of c-myc was detected in SHE cells transformed by benzo(a)pyrene or trenbolone.
Effects of fiber characteristics on lung deposition, retention, and disease. M. Lippmann. 1990;88:311-7. Review PubMed · Publisher · Free full text

Abstract

There is abundant epidemiologic evidence that asbestos fibers can cause lung fibrosis (asbestosis), bronchial cancer, and mesothelioma in humans, as well as limited evidence for such effects in workers exposed to slag and rockwool fibers. Epidemiological evidence for human disease from inhalation exposures to conventional fibrous glass is negative. While health concerns based on the morphological and toxicological similarities between man-made fibers and asbestos are warranted, it is important to note that most of the toxicological evidence for glass fiber toxicity in laboratory animals is based on nonphysiological exposures such as intratracheal instillation or intraperitoneal injection of fiber suspensions. Man-made fibers have produced lung fibrosis and mesotheliomas in such tests, albeit at much lower yields than asbestos. For all durable mineral fibers, critical length limits must be exceeded to warrant concern about chronic toxicity; i.e., 2 microns for asbestosis, 5 microns for mesothelioma, and 10 microns for lung cancer. Fiber width must be less than 0.1 microns for mesothelioma, and larger than this limit for asbestosis and lung cancer. The human health risks for most fibrous glass products are either low or negligible for a variety of reasons. First, most commercial fibrous glass products have mean fiber diameters of approximately 7.5 microns, which results in mean aero-dynamic diameters approximately 22 microns. Thus, most glass fibers, even if dispersed into the air, do not penetrate into the lung to any great extent. Second, the small fraction of smaller diameter fibers that do penetrate into the lungs are not persistent within the lungs for most fibrous glass products due to mechanical breakage into shorter lengths and overall dissolution.(ABSTRACT TRUNCATED AT 250 WORDS)
Historical developments and perspectives in inorganic fiber toxicity in man. I.J. Selikoff. 1990;88:269-76. Historical article · Review PubMed · Publisher · Free full text

Abstract

The first patient known to have died from asbestosis (1900) began work in 1885, approximately 5 years after the industrial use of asbestos began in Britain. Mineral particles were found in his lungs. No special comment was made of their fibrous nature then nor when the first case was reported in 1924. The various neoplasms attributed to asbestos in the next decades posed an additional question: What influence did the fibrous shape of the particles have on carcinogenic potential? The cogency of the problem was amplified by the identification in humans of asbestos-like neoplasms with a fiber other than asbestos (erionite) and by the production of such neoplasms in experimental animals with a variety of man-made inorganic fibers, often used as substitutes for asbestos. The lessons learned about asbestos may help guide us in evaluating current fiber problems.
Human disease consequences of fiber exposures: a review of human lung pathology and fiber burden data. V.L. Roggli. 1990;88:295-303. Review PubMed · Publisher · Free full text

Abstract

Inhalation of asbestos fibers results in a variety of neoplastic and nonneoplastic diseases of the respiratory tract. Some of these diseases, such as asbestosis, generally occur after prolonged and intensive exposure to asbestos, whereas others, such as pleural mesothelioma, may occur following brief exposures. Inhalation of nonasbestiform mineral fibers can occur as well, and these fibers can be recovered from human lung tissue. Thus, there has been considerable interest in the relationship between mineral fiber content of the lung and various pathologic changes. Techniques for fiber analysis of human tissues have not been standardized, and consequently results may differ appreciably from one laboratory to another. In all reported series, extremely high fiber burdens are found in the lungs of individuals with asbestosis. Although there is a correlation between the tissue concentration of asbestos fibers and the severity of pulmonary fibrosis, further studies of the mineralogic correlates of fiber-induced pulmonary fibrosis are needed. Mesothelioma may occur with fiber burdens considerably less than those necessary to produce asbestosis. More information is needed regarding the migration of fibers to the pleura and the numbers, types, and dimensions of fibers that accumulate at that site. Patients with asbestosis have a markedly increased risk for lung cancer, but the risk of lung cancer attributable to asbestos in exposed workers without asbestosis who also smoke is controversial. Combined epidemiologic-mineralogic studies of a well-defined cohort are needed to resolve this issue. In addition, more information is needed regarding the potential role of nonasbestos mineral fibers in the pathogenesis of lung cancer.
Human epidemiology: a review of fiber type and characteristics in the development of malignant and nonmalignant disease. J.A. Merchant. 1990;88:287-93. Review PubMed · Publisher · Free full text

Abstract

Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.
Human occupational and nonoccupational exposure to fibers. N.A. Esmen, S. Erdal. 1990;88:277-86. Review PubMed · Publisher · Free full text

Abstract

Human exposure to fibers in occupational and nonoccupational environments has been a health concern for nearly a century. In this review, selected results from the literature are presented to highlight the availability, limitations, and interpretive difficulties associated with the past and current human fiber exposure data sets. In the traditionally defined asbestos fibers, large amounts of the data available suffer from the diversity of sample collection and analysis methods. Two simple generalizations suggest that occupational exposures are several orders of magnitude higher than that of environmental exposures; and currently extant data and the current routine measurement practices present significant difficulties in the consistent interpretation of the data with respect to health effects. The data on the human exposures to man-made vitreous fibers are much more complete than the data on asbestos exposure, while exposure data on other man-made fibrous materials are lacking. The human exposure data to many minerals which, at times, exist in fibrous habit, are very scanty, and in view of the biological activity of some of these fibers, this lack may be of significant concern.
In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays. B.T. Mossman. 1990;88:319-22. Review PubMed · Publisher · Free full text

Abstract

In vitro studies employing organ cultures, primary cell cultures, cell lines, and bacterial systems have been used to assess the toxicity, mutagenicity, and carcinogenic potential of asbestos and nonasbestos fibers. These experiments have been useful in defining mechanisms contributing to the causation of fiber-associated lung diseases. Long (greater than 8 microns), thin asbestos fibers are more active in vitro than short (less than or equal to 2 microns) fibers or nonfibrous particles, an observation supporting the importance of fiber dimension in disease. Although in vitro bioassays cannot evaluate characteristics such as clearance and/or durability of fibers which may be critical determinants of fiber toxicity in lung, they can be used both to address dosimetry at the cellular level (i.e., number of fibers per cell that elicit a measurable biologic end point) and to evaluate preventive approaches to fiber-induced cell injury. Development of in vitro models employing target cells of the lung, i.e., mesothelial cells, tracheobronchial epithelial cells, and lung fibroblasts, as well as carefully characterized preparations of fibers and particles, will be necessary to evaluate whether in vitro bioassays are amenable to predicting the pathogenic potential of synthetic and naturally occurring fibers comparatively.
Interaction of amosite and surface-modified amosite with a V79-4 (Chinese hamster lung) cell line. E.A. Sara, R.C. Brown, C.E. Evans, et al. 1990;85:101-5. PubMed · Publisher · Free full text

Abstract

We have been examining a number of chemically modified mineral fibers, derived from amosite asbestos, by in vitro methods to clarify the role of the fiber surface in determining biological activity. The various fibers have identical size distributions but differ in their affinities for components of the cell membrane. They were treated with boiling toluene or chemically modified by treatment with alkyldimethylchlorosilanes (R = C8, C18) that react with free-surface hydroxyl groups to form the corresponding siloxanes. Fibers in MEM supplemented with 15% fetal calf serum were added to a suspension of V79-4 cells labeled with tritiated thymidine and the mixture was incubated. Aliquots of this mixture were spun down on a density gradient to determine the degree of cell-fiber interaction. At 37 degrees C native amosite (UICC standard) stuck to cells within 15 min of incubation, and the amount of sticking was maximum within 70 min. Decreasing the temperature decreased the amount of sticking, and at 20 degrees C no sticking was observable. The chemically modified amosite and the amosite treated with boiling toluene did not stick to the cells even after 70 min. Soaking the toluene-treated amosite with aqueous solutions at room temperature for 48 hr produced a material that had the same sticking properties as the original untreated fiber. These results indicate that the silanol content, and possibly the degree of hydration of the fiber surface, is important for a fiber to stick to a cell surface.
Modulating factors in the expression of radiation-induced oncogenic transformation. E.J. Hall, T.K. Hei. 1990;88:149-55. Review PubMed · Publisher · Free full text

Abstract

Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing alpha-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene.
The effects of acid precipitation runoff episodes on reservoir and tapwater quality in an Appalachian Mountain water supply. W.E. Sharpe, D.R. DeWalle. 1990;89:153-8. PubMed · Publisher · Free full text

Abstract

The aluminum concentration and Ryznar Index increased and the pH decreased in a small Appalachian water supply reservoir following acid precipitation runoff episodes. Concomitant increases in tapwater aluminum and decreases in tapwater pH were also observed at two homes in the water distribution system. Lead concentrations in the tapwater of one home frequently exceeded recommended levels, although spatial and temporal variation in tapwater copper and lead concentrations was considerable. Since source water and reservoir water copper and lead concentrations were much lower, the increased copper and lead concentrations in tapwater were attributed to corrosion of household plumbing. Tapwater copper concentration correlated well with tapwater pH and tapwater temperature. Asbestos fibers were not detected in tapwater. The asbestos-cement pipe in the water distribution system was protected by a spontaneous metallic coating that inhibited fiber release from the pipe. Several simultaneous reactions were hypothesized to be taking place in the distribution system that involved corrosion of metallic components and coating of asbestos-cement pipe components in part with corrosion products and in part by cations of watershed origin. Greater water quality changes might be expected in areas of higher atmospheric deposition.
The relationship between fibrosis and cancer in experimental animals exposed to asbestos and other fibers. J.M. Davis, H.A. Cowie. 1990;88:305-9. Review PubMed · Publisher · Free full text

Abstract

The association between occupational asbestos exposure and the development of both pulmonary fibrosis or asbestosis and pulmonary carcinomas is well documented. It has been suggested that the two pathological conditions are associated with asbestos-related carcinomas developing from areas of asbestosis and not occurring when exposure has been too low to produce this type of pulmonary scarring. Experimental inhalation studies so far published have not been designed to examine this association specifically, but many publications have reported that asbestos samples producing high levels of fibrosis is experimental animals are also very carcinogenic. Samples of asbestos or man-made fibers that produce little fibrosis also produce few tumors. These works are reviewed. In order to examine the association between fibrosis and tumor production in more detail, groups of animals with and without pulmonary tumors and with individual fibrosis measurements were assembled from a number of inhalation studies undertaken over a period of years at this Institute. It was found that animals with pulmonary tumors had almost double the amount of pulmonary fibrosis as animals of similar age that did not. In a few of the animals where tumors were found at an early stage of development, their origin from fibrotic areas could be confirmed, although in most cases where tumor deposits were widespread this was not possible. Experimental confirmation of the site of origin of most pulmonary tumors in asbestos-treated rats would require new studies with rats examined specifically at an age when early tumors would be expected.
Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen. Y. Kurokawa, A. Maekawa, M. Takahashi, et al. 1990;87:309-35. Review PubMed · Publisher · Free full text

Abstract

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.

1980s

Evidence supporting a role for active oxygen species in asbestos-induced toxicity and lung disease. B.T. Mossman, J.P. Marsh. 1989;81:91-4. Review PubMed · Publisher · Free full text

Abstract

Asbestos is an important occupational and environmental toxicant that affects several cell types in the respiratory tract. In an effort to understand how asbestos causes cell injury and/or altered proliferation and differentiation of cells, this laboratory has focused on reactive oxygen species as mediators of asbestos-induced biological effects. A compendium of experimental results reported by this laboratory and others supports this hypothesis. For example, scavengers of reactive oxygen metabolites and iron chelators (i.e., desferroxamine) prevent cytotoxicity after addition of asbestos to a variety of cell lines and macrophages in vitro. DNA strand breakage associated with toxicity of crocidolite asbestos in C3H10T 1/2 cells also is ameliorated with use of desferroxamine. All types of asbestos cause lipid peroxidation in mammalian cells and artificial membranes, a phenomenon that can be prevented by removal of catalytic iron. Last, asbestos causes generation of active oxygen species after interaction with leukocytes or by reduction of oxygen on the surface of the fibers.
Mass transfer rates of polycyclic aromatic hydrocarbons between micron-size particles and their environment--theoretical estimates. P. Gerde, P. Scholander. 1989;79:249-58. PubMed · Publisher · Free full text

Abstract

This paper presents a mathematical model of how rapidly polycyclic aromatic hydrocarbons (PAHs) adsorb onto initially clean micron-size particles in the ambient air and how fast these substances are likely to be desorbed from the particles after deposition on the surface lining layer of the lung. Results show that, on the one hand, the very low gas-phase concentrations of PAHs in the ambient air should result in a comparatively slow transfer of such compounds to micron-size particles, a process that may last from minutes to hours. On the other hand, the comparatively high solubilities of PAHs in the lining layer of the lung should promote an almost instantaneous release of PAHs onto nonporous particles, and a release within a matter of minutes of most PAHs reversibly adsorbed onto the interior surfaces of porous particles. Two important conclusions can be drawn from this. First, the PAHs in tobacco smoke do not have time enough to interact in the gas phase with other airborne particles before these agents are inhaled into the smoker's lungs. Therefore, adsorption in the gas phase of PAHs onto asbestos fibers can hardly be a characteristic parameter in the mechanism behind the synergistic effect between tobacco smoking and asbestos exposure for the induction of bronchial cancer. Second, the release rate of reversibly adsorbed PAHs from their carrier particles in the lung seems to be so fast that this cannot be a parameter of importance in directly influencing the residence times of such substances in the lung.
Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells. G. Cameron, C.D. Woodworth, S. Edmondson, et al. 1989;80:101-8. PubMed · Publisher · Free full text

Abstract

Within 1 to 4 weeks after exposure to asbestos, differentiated rodent and human tracheobronchial epithelial cells in organ culture undergo squamous metaplasia, a putative preneoplastic lesion characterized by conversion of mucociliary cell types to keratinizing cells. The exogenous addition of retinal acetate (RA) to culture medium of hamster tracheal organ cultures reverses preestablished, asbestos-induced squamous metaplasia, although data suggest that the effectiveness of RA decreases as the length of time between exposure to asbestos and initial application of RA increases. alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), inhibits squamous metaplasia caused by asbestos or vitamin A deficiency, whereas addition of methylglyoxal bis(guanylhydrazone) (MGBG), a structural analog of spermidine and inhibitor of S-adenosylmethionine decarboxylase, causes an enhancement of metaplasia under both circumstances. Basal cell hyperplasia and increased incorporation of 3H-thymidine by tracheal epithelial cells also are seen after addition of the polyamines, putrescine or spermidine, to tracheal organ cultures, an observation supporting the importance of polyamines in the development of this lesion. The use of retinoids and inhibitors of ODC could be promising as preventive and/or therapeutic approaches for individuals at high risk for development of asbestos-associated diseases.
Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers. J.C. Barrett, P.W. Lamb, R.W. Wiseman. 1989;81:81-9. Review PubMed · Publisher · Free full text

Abstract

Asbestos and other mineral fibers are carcinogenic to humans and animals but differ from many carcinogens in that they do not induce gene mutations. An understanding of these interesting human carcinogens, therefore, is an important problem in cancer research. Asbestos and other fibers induce predominantly two types of cancers: mesotheliomas and bronchogenic carcinomas. Fiber size is an important factor in the carcinogenic activity of these substances as has been shown for mesothelioma induction. For bronchogenic carcinomas, but not for mesotheliomas, a synergistic effect of asbestos exposure and cigarette smoke has been observed in humans. The mechanisms by which fibers alone versus fibers in concert with other carcinogens induce cancers are probably distinct. In addition to fiber dimensions, fiber durability and surface properties of fibers are important properties affecting carcinogenicity. Evidence exists that asbestos is a complete carcinogen, an initiator and a promoter. Multiple mechanisms must be operative to explain the diverse effects of mineral fibers. Although asbestos is inactive as a gene mutagen, there is now clear evidence that it induces chromosomal mutations (aneuploidy and aberrations) in a wide variety of mammalian cells including mesothelial cells. Asbestos also induces transformation of cells in culture including mesothelial cells and fibroblasts. A mechanism for cell transformation, which is dependent on fiber dimension, has been proposed. The fibers are phagocytized by the cells and accumulate in the perinuclear region of the cells. When the cell undergoes mitosis, the physical presence of the fibers interferes with chromosome segregation and results in anaphase abnormalities. The transformed cells show aneuploidy and other chromosome abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Proliferative lesions in the male reproductive system of F344 rats and B6C3F1 mice: incidence and classification. K. Mitsumori, M.R. Elwell. 1988;77:11-21. Review PubMed · Publisher · Free full text

Abstract

The incidences of all primary neoplasms in the testes and accessory reproductive organs of 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice were obtained from the pathology data base of more than 300 long-term toxicity/carcinogenicity studies performed for the National Toxicology Program. The overall incidence of reproductive system neoplasms in male F344 rats was 81.5%. The most common neoplasms were interstitial cell adenoma of the testis (76.6%), adenoma/carcinoma of the preputial glands (2.9%), mesothelioma of the tunica vaginalis (1.5%), and adenoma of the prostate gland (0.3%). The combined incidence (0.1%) of 59 other rare neoplasms consisted of 18 different types that occurred with a frequency of 4 or less. In contrast to the rats, male B6C3F1 mice had a low overall incidence (0.6%) of neoplasms in reproductive organs. The most common neoplasm was the interstitial cell adenoma (0.4%). Thirty additional types of neoplasms were identified. Each of these uncommon neoplasms occurred at a frequency of 12 or less with an overall combined incidence of 0.2%. Morphological features are described for neoplasms in the rat and mouse, and criteria are presented for differentiation of testicular interstitial cell adenoma, prostatic adenoma, and mesothelioma from hyperplastic changes.
Mesovarian leiomyomas in the rat. C. Gopinath, W.A. Gibson. 1987;73:107-13. PubMed · Publisher · Free full text

Abstract

Prolonged treatment with two chemically distinct beta-stimulants, Salbutamol and Terbutaline, resulted in mesovarian leiomyomas in Sprague-Dawley rats. Development of these tumors induced by Salbutamol was prevented by concurrent administration of the beta-blocker Propranolol. Mesovarian leiomyomas induced by Salbutomol did not show any regression or progression during a 44-week postdosing recovery period. This report also gives the first recorded incidence of spontaneous mesovarian leiomyomas in the rat.
Ovarian neoplasia in the Sprague-Dawley rat. D.J. Lewis. 1987;73:77-90. PubMed · Publisher · Free full text

Abstract

Macroscopic and microscopic characteristics of 210 spontaneous ovarian tumors from 7748 Sprague-Dawley rats are described. The tumors were classified as tubular adenoma, anaplastic adenocarcinoma, papillary cystadenoma, papillary cystadenocarcinoma, mesothelioma, sertoliform tubular adenoma, Sertoli's cell tumor, granulosa cell tumor, thecal cell tumor, polycystic sex cord/stromal tumor, and lipoid cell tumor. The histogenesis of the tumor types is discussed.
Report on cancer risks associated with the ingestion of asbestos. DHHS Committee to Coordinate Environmental and Related Programs. 1987;72:253-65. Review PubMed · Publisher · Free full text

Abstract

This report is an assessment of all available literature that pertains to the potential risk of cancer associated with ingestion of asbestos. It was compiled by a working group to assist policy makers in the Department of Health and Human Services determine if adequate information was available for a definitive risk assessment on this potential problem and evaluate if the weight of evidence was sufficient to prioritize this issue for new policy recommendations. The work group considered the basis for concern over this problem, the body of toxicology experiments, the individual epidemiologic studies which have attempted to investigate this issue, and the articles that discuss components of risk assessment pertaining to the ingestion of asbestos. In the report, the work group concluded: that no direct, definitive risk assessment can be conducted at this time; that further epidemiologic investigations will be very costly and only possess sufficient statistical power to detect relatively large excesses in cancers related to asbestos ingestion; and that probably the most pertinent toxicologic experiments relate to resolving the differences in how inhaled asbestos, which is eventually swallowed, is biologically processed by humans, compared to how ingested asbestos is processed. The work group believes that the cancer risk associated with asbestos ingestion should not be perceived as one of the most pressing potential public health hazards facing the nation. However, the work group does not believe that information was sufficient to assess the level of cancer risk associated with the ingestion and therefore, this potential hazard should not be discounted, and ingestion exposure to asbestos should be eliminated whenever possible.
Contribution of environmental fibers to respiratory cancer. G.S. Omenn, J. Merchant, E. Boatman, et al. 1986;70:51-6. PubMed · Publisher · Free full text

Abstract

This article reviews studies of the carcinogenicity of mineral fibers, notably asbestos, and presents seven major recommendations for further research. Mineral fibers represent the greatest cause--after cigarette smoke--of respiratory cancer due to air pollutants. Past asbestos exposure may currently account for 2000 mesothelioma deaths per year and 4000 to 6000 lung cancer deaths per year. All major commercial types of asbestos (crocidolite, amosite, and chrysotile) can cause each of the major asbestos-related respiratory diseases. Lung cancers in asbestos-exposed individuals probably do not have a different distribution of histological types from that of non-asbestos-related lung cancers. Nonoccupational exposures are likely to be associated with malignant disease outcomes qualitatively similar to those associated with occupational exposures. Further investigations of fibers are needed to characterize the relationships among physicochemical properties, patterns of migration and clearance, dose, and adverse health effects. Transmission electron microscopy has been found to be the preferred method of analysis of environmental fibers. Relations among time factors (e.g., age at first exposure), dose, and risk for adverse health effects require analyses of existing and new epidemiologic studies of exposed cohorts. Concomitant exposure, behavioral factors, and host factors affecting susceptibility to asbestos should be identified.
Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan. Y. Kurokawa, S. Takayama, Y. Konishi, et al. 1986;69:221-35. PubMed · Publisher · Free full text

Abstract

Long-term in vivo carcinogenicity tests of potassium bromate (KBrO3), sodium hypochlorite (NaClO), and sodium chlorite (NaClO2) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-week tests. Control animals were given distilled water. The carcinogenic potential of KBrO3 was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO3 at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. NaClO was administered to male and female rats, respectively, at doses of 1000 or 500 ppm and 2000 or 1000 ppm for 104 weeks. In mice, NaClO was given at doses of 1000 or 500 ppm to either sex for 103 weeks. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. NaClO2 was given to rats of both sexes at a dose of 600 or 300 ppm for 85 weeks. No statistically significant differences were observed in the incidences of tumor formation between NaClO2-treated and control groups of both sexes. NaClO2 was administered to mice at a concentration of 500 or 250 ppm for 85 weeks. In males, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls (p less than 0.05). However, these incidences in treated males were within the range of values of historical control data in our program. We concluded that KBrO3 was carcinogenic in rats of both sexes. NaClO was not carcinogenic in either rats and or mice under the conditions of the present studies. Although NaClO2 was shown to be noncarcinogenic in rats, the results for mice were evaluated as inconclusive. Also the results of two-stage mouse skin carcinogenesis using KBrO3, NaClO, and NaClO2 are presented. The necessity for further testing of oxidant chemicals to determine potential carcinogenic and/or promoting effects is suggested in view of the recently proposed role of active oxygen species in carcinogenesis.
Effects of asbestos on the random migration of rabbit alveolar macrophages. Q.N. Myrvik, E.A. Knox, M. Gordon, et al. 1985;60:387-93. PubMed · Publisher · Free full text

Abstract

The toxicity of sized and characterized chrysotile, crocidolite, and amosite preparations obtained from Dr. K. R. Spurny have been evaluated using alveolar macrophage (AM) migration inhibition assays and viability tests. These results have been compared with asbestos samples obtained from the National Institute of Environmental Health Sciences (NIEHS). These latter samples are designated chrysotile A (RT), crocidolite (RT), and amosite (RT). In addition, filter-isolated preparations of chrysotile A (RT) that consisted mainly of large nonphagocytosable fibers were also tested. Chrysotile (Spurny) and sonicated chrysotile A (RT) produced 50% migration inhibition at about 115 micrograms/mL. Spurny crocidolite produced 50% migration inhibition at about 340 micrograms/mL, whereas RT crocidolite produced 50% migration inhibition at about 230 micrograms/mL. RT amosite caused 50% migration inhibition at about 180 micrograms/mL, whereas Spurny amosite was inactive up to 500 micrograms/mL. The large nonphagocytosable chrysotile A (RT) fibers produced 50% migration inhibition at about 66 micrograms/mL. This indicates that fibers can be toxic for AM through extracellular membrane contact. In general the results from the viability studies paralleled the migration inhibition observations. None of the asbestos preparations induced a burst in the hexose monophosphate shunt of BCG-immune AM at 1 mg/mL. BCG-immune AM were more susceptible to cell death than normal AM when incubated with chrysotile A (RT), amosite (RT) and zymosan. Migration inhibition induced by asbestos fibers probably reflects toxicity of the asbestos preparations and could play an important role in blocking normal alveolar clearance of inhaled particles.
Health implications of environmental exposure to asbestos. J.C. McDonald. 1985;62:319-28. PubMed · Publisher · Free full text

Abstract

The health impact of environmental pollution resulting from the industrial use of asbestos can be assessed in three ways. First, there are the direct epidemiological surveys. These indicate that domestic exposure has been responsible for cases of mesothelioma and possibly lung cancer and radiological changes in family contacts of asbestos workers. Exposure in the neighborhood of crocidolite mines and factories has also resulted in cases of mesothelioma but no similar evidence exists for chrysotile or amosite. Neither air nor water pollution has been directly incriminated as a cause of either respiratory or digestive malignancies. Second, a few attempts have been made to extrapolate from exposure response findings in industrial cohorts. For several reasons, even for lung cancer, this approach is dubious: the observed gradients have a 100-fold range in slope; the equivalences of dust, fiber and gravimetric measures are largely guesswork; and the carcinogenic potential of mineral fibers, particularly for the pleura, varies enormously with fiber type and/or dimensions. No adequate exposure-response observations have been made for mesothelioma. A third approach makes use of the differing incidence of mesothelioma in men and women. Data from several countries indicate that, until the 1950s (i.e., 30-40 years after significant industrial use of asbestos began), the rates were similar in both sexes. Since then, the incidence in males has risen steeply--in the U.S. and U.K. at about 10% per annum. In females, on the other hand, there has been little or no convincing increase. These data suggest that the "background" level of mesothelioma in both sexes is and has been about 2 per million per annum and that--as at least some mesothelioma cases in females are directly or indirectly attributable to occupational exposure--there is little room left for any contribution from the general environment. It is recommended that mesothelioma surveillance, backed by appropriate epidemiological inquiries, offers an effective method of monitoring the health impact of asbestos air pollution.
Impact of effects of acid precipitation on toxicity of metals. G.F. Nordberg, R.A. Goyer, T.W. Clarkson. 1985;63:169-80. Review PubMed · Publisher · Free full text

Abstract

Acid precipitation may increase human exposure to several potentially toxic metals by increasing metal concentrations in major pathways to man, particularly food and water, and in some instances by enhancing the conversion of metal species to more toxic forms. Human exposures to methylmercury are almost entirely by way of consumption of fish and seafood. In some countries, intakes by this route may approach the levels that can give rise to adverse health effects for population groups with a high consumption of these food items. A possible increase in methylmercury concentrations in fish from lakes affected by acid precipitation may thus be of concern to selected population groups. Human exposures to lead reach levels that are near those associated with adverse health effects in certain sensitive segments of the general population in several countries. The possibility exists that increased exposures to lead may be caused by acid precipitation through a mobilization of lead from soils into crops. A route of exposure to lead that may possibly be influenced by acid precipitation is an increased deterioration of surface materials containing lead and a subsequent ingestion by small children. A similar situation with regard to uptake from food exists for cadmium (at least in some countries). Human metal exposures via drinking water may be increased by acid precipitation. Decreasing pH increases corrosiveness of water enhancing the mobilization of metal salts from soil; metallic compounds may be mobilized from minerals, which may eventually reach drinking water. Also, the dissolution of metals (Pb, Cd, Cu) from piping systems for drinking water by soft acidic waters of high corrosivity may increase metal concentrations in drinking water. Exposures have occasionally reached concentrations which are in the range where adverse health effects may be expected in otherwise healthy persons. Dissolution from piping systems can be prevented by neutralizing the water before distribution. Increased aluminum concentrations in water is a result mainly of the occurrence of Al in acidified natural waters and the use of Al chemicals in drinking water purification. If such water is used for dialysis in patients with chronic renal failure, it may give rise to cases of dialysis dementia and other disorders. A possible influence on health of persons with normal renal function (e.g., causing Alzheimer's disease) is uncertain and requires further investigation.(ABSTRACT TRUNCATED AT 400 WORDS)
Inhaled particles in human disease and animal models: use of electron beam instrumentation. A.R. Brody. 1984;56:149-62. Review PubMed · Publisher · Free full text

Abstract

The mineral pneumoconioses (lung disease caused by inhalation of inorganic dust) have been an important disease entity for centuries. In the last several decades, the electron microscope has been used to elucidate the distribution and identification of inhaled minerals, to aid in establishing etiologic factors, and less commonly, to determine the basic biologic mechanisms through which inhaled minerals cause lung disease. In this section, I review the instrumentation and tissue preparation currently used to address some modern problems in particle-induced lung disease. For example, human pneumoconioses of undetermined etiology can be clarified by electron microscopy and X-ray energy spectrometry. In addition, the initial deposition patterns of asbestos and silica are demonstrated in animal models, and the contributions of electron microscopy in establishing the initial lesions of asbestosis are described.
Particles causing lung disease. K.H. Kilburn. 1984;55:97-109. Review PubMed · Publisher · Free full text

Abstract

The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and quantify our preliminary picture of the pathogenesis of lung disease by particles, but a useful start has been made.
Pulmonary toxicology of silica, coal and asbestos. A.G. Heppleston. 1984;55:111-27. Review PubMed · Publisher · Free full text

Abstract

Mineral particles are customarily inhaled as mixtures, though one component may predominate and determine the response. Although the lesions often possess a characteristic structure, according to the main type of particle deposited, morphology affords little indication of pathogenesis. Being a major element in the evolution of dust lesions, macrophage behavior has been examined extensively in vitro after treatment with mineral particles, attention being directed to membrane and biochemical changes; however, no clear lead to the origin of the lesions has emerged. Pulmonary fibrosis, as one of the ultimate consequences of dust accumulation, required a direct in vitro approach in which the products of the macrophage-particle interaction were utilized to provoke collagen formation by fibroblasts in a two-phase system. By this means, silica and asbestos stimulated connective tissue formation and application of the technique to coal dusts appears promising. Coal workers may develop a peculiar type of emphysema in relation to lesions whose fibrous content is comparatively small. Type II alveolar epithelium is also stimulated by inhaled particles and lipid accumulation follows. Alveolar lipidosis interferes with the fibrotic response by preventing contact between macrophage and particles. This phenomenon may account in part for anomalies, apparent in coal workers, between epidemiological findings and dust composition. Carcinogenesis is a well-recognized feature of asbestos exposure, but, as with fibrosis, risk prediction on the basis of in vitro tests of cytotoxicity is premature and may not be valid.
Radionuclide injury to the lung. G.E. Dagle, C.L. Sanders. 1984;55:129-37. Review PubMed · Publisher · Free full text

Abstract

Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed.
A graphical analysis of the interrelationships among waterborne asbestos, digestive system cancer and population density. M.E. Tarter, R.C. Cooper, W.R. Freeman. 1983;53:79-89. PubMed · Publisher · Free full text

Abstract

Five statistical procedures were used to partial the correlation between waterborne asbestos and digestive site cancer for the putative effects of population density. These include: analysis based on a data subset with roughly homogeneous population density; standard residual analysis (partial correlation); conditional probability integral transformation; analysis based upon ranked data, and use of logarithmic transformation. Nonparametric regression graphical techniques are applied to examine the nature or shape of the asbestos-cancer dose-response curve. Evidence is presented that suggests that there is considerable difference between analyses involving nonhigh-density tracts and non-San Francisco tracts. Evidence is also presented that the modal-type nonparametric regression curve forks or bifurcates when adjustment is made for population density.
Accumulation of ingested asbestos fibers in rat tissues over time. K. Patel-Mandlik, J. Millette. 1983;53:197-200. PubMed · Publisher · Free full text

Abstract

With the use of the transmission electron microscope, asbestos fibers have been assessed in kidney cortex of four groups of rats previously exposed to intermediate-range feeding grade chrysotile asbestos. Newborn rats, from mothers gavaged with asbestos during pregnancy, were gavaged twice a week at the dose level of 50 mg/kg beginning at age day 7 until their natural death or sacrifice. The rats were divided into four groups by age: 0-200, 200-400, 400-600 and 600-800 days. Of the 20 rats comprising the four test groups, 17 were positive, average fiber recovery being 5.34 X 10(3)/mg dry weight. Average fiber level in control tissues was 0.23 X 10(3)/mg dry weight. Fiber recovery in tissues from control animals was shown to be significantly lower (p less than 0.005) than that from test tissues. Test groups showed highly significant differences (p less than 0.005) from each other in the fiber levels. Dose-response relationship was not significant (0.05 less than p less than 0.1). The length distribution and the alterations in morphology of the recovered fibers are described. This study is consistent with the passage of chrysotile asbestos across the gastrointestinal wall.
Additional comments on the study of the effect of population density on the results of the California Bay area study. P.M. Conforti. 1983;53:191-2. PubMed · Publisher · Free full text
Additional notes on the case-control study in western Washington on the cancer risk from asbestos in drinking water. L. Polissar, R.K. Severson, E.S. Boatman. 1983;53:189-90. PubMed · Publisher · Free full text
Additional notes on the use of quantitative analysis of urine to assess exposure to asbestos fibers in drinking water in the Puget Sound region. E.S. Boatman. 1983;53:195. PubMed · Publisher · Free full text
Additional thoughts on the review of epidemiologic studies related to ingested asbestos. G.M. Marsh. 1983;53:185-7. PubMed · Publisher · Free full text
An adherent cell perifusion technique to study the overall and sequential response of rat alveolar macrophages to toxic substances. G. Forget, M.J. Lacroix, A. Cadieux, et al. 1983;51:131-40. PubMed · Publisher · Free full text

Abstract

Essentially pure (97%) alveolar macrophages were isolated by bronchoalveolar lavage of rats with warm (37 degrees C) PBS solution. These cells were allowed to adhere to the inside walls of open-ended glass cylinders which were closed off at each end by three-way stopcocks. The adhering cells were perifused with RPMI-1640 medium supplemented with 5% fetal bovine serum for 18 hr at the rate of 1 mL/hr, and the effluent medium was collected automatically in 2-mL aliquots. Cell recoveries and viabilities did not differ from those found for Petri cultures treated similarly, indicating that the perifusion method under study offered an adequate milieu for short-term primary cultures. The alveolar macrophages in culture were subjected to the presence of particulate (chrysotile asbestos) and soluble (phorbol myristate) toxicants, and their response was monitored in the effluent medium by measuring the release of prostaglandins (PGE) by radioimmunoassay. A significant increase in the sequential release of PGE was observed in the presence of asbestos (100 micrograms/mL) or phorbol myristate (200 ng/mL). Treatment of the cells with indomethacin (20 microM) completely abolished the release of PGE stimulated with phorbol myristate. A cumulative response to the toxicants was also observed when cells were harvested manually from the chambers: asbestos caused a 2-fold increase in cell mortality relative to control, while phorbol myristate brought about a 3-fold increase in the number of dead cells. This effect was not prevented by the presence of indomethacin. Cell aggregation was also observed when cells were perifused in the presence of phorbol myristate, whether indomethacin was present or absent. Our results indicate that the cell perifusion system combines the advantages of conventional adherent cell cultures (viability, aggregation) with those of perifusion techniques (sequential metabolism studies).
Answers to some questions raised by the presentation on the graphical analysis of the interrelationships between waterborne asbestos, digestive system cancer and population density. M.E. Tarter. 1983;53:193-4. PubMed · Publisher · Free full text
Asbestos affects the in vitro uptake and detoxification of aromatic compounds. R.C. Brown, G.T. Fleming, A.I. Knight. 1983;51:315-8. PubMed · Publisher · Free full text

Abstract

A number of mineral dusts were tested for their ability to catalyze the transformation of benzo(a)pyrene from the microcrystalline state into lipid solution. The findings of Lakowicz and his co-workers, that fibrous dusts were more active than nonfibrous dusts, were confirmed. Macromolecular binding metabolites of BaP were formed in A549 cells to a similar extent whether the BaP was added in solution or adsorbed to fibers; however, the level of water-soluble metabolites was lower in cultures treated with adsorbed hydrocarbon. It was found that asbestos can also inhibit the accumulation of 1-naphthyl glucuronide in cultures treated with 1-naphthol. The significance of this in asbestos pathogenesis is briefly discussed.
Asbestos fibers, plasma and inflammation. J.A. Hamilton. 1983;51:281-5. PubMed · Publisher · Free full text

Abstract

Fibrin clots have been detected at sites of inflammation, and kinins have been implicated as mediators of the vascular phenomena of acute inflammation, systemic shock, and disseminated intravascular coagulation. It is now reported that both negatively and positively charged asbestos fibers shorten the partial thromboplastin time of human plasma, indicating coagulation of the plasma. A sample containing short (less than 5 micron in length) chrysotile fibers is ineffective. Only the negatively charged amphiboles (crocidolite and amosite) are able to activate factor XII (Hageman factor). This particular effect of the amphiboles is enhanced by high molecular weight kininogen and leads to kinin formation.
Asbestos in drinking water: a Canadian view. P. Toft, M.E. Meek. 1983;53:177-80. PubMed · Publisher · Free full text

Abstract

For several years now, public health professionals have been faced with evaluating the potential hazards associated with the ingestion of asbestos in food and drinking water. In Canada, this is a subject of particular concern, because of the widespread occurrence of chrysotile asbestos in drinking water supplies. The results of available Canadian monitoring and epidemiologic studies of asbestos in drinking water are reviewed and discussed in light of other published work. It is concluded that the risk to health associated with the ingestion of asbestos, at the levels found in municipal drinking water supplies, is so small that it cannot be detected by currently available epidemiologic techniques.
Asbestos in drinking water: a status report. J.A. Cotruvo. 1983;53:181-3. PubMed · Publisher · Free full text

Abstract

The conference is briefly reviewed in the light of its impact on future regulatory decisions regarding the possible control of asbestos fiber in drinking water. The results of animal feeding studies indicate that asbestos fails to demonstrate toxicity in whole-animal lifetime exposures. The epidemiologic evidence of risk from ingestion of water containing asbestos fibers is not convincing, and in view of the lack of confirmation by animal studies, the existence of a risk has not been proven; however occupational gastrointestinal cancer may indicate ingestion risk. Whether or not there is a risk from asbestos in drinking water, however, common sense tells us to deal with an undesirable situation by employing means that are commonly and economically available. Well-known methods can minimize the presence of asbestos fibers in finished drinking water. In the case of natural fiber in raw water, standard or augmented filtration practices are extremely effective. If the source of asbestos fiber is asbestos-cement pipe that is being attacked by corrosive water, then, there is more than sufficient economic reason to correct the corrosivity of the water.
Asbestos in water supplies of the United States. J.R. Millette, P.J. Clark, J. Stober, et al. 1983;53:45-8. PubMed · Publisher · Free full text

Abstract

The review of available data on the concentrations of asbestos in U.S. water supplies suggests that the majority of water consumers are not exposed to asbestos concentrations over 1 million fibers/Liter. A few populations, however, may be exposed to concentrations over 1 billion fibers/L. Of the 538 water supplies for which waterborne asbestos data are available, 8% have concentrations of fibers over 10 million fibers/L. The vast majority of asbestos fibers found in U.S. water supplies are under 5 micron in length.
Asbestos penetration of the gastrointestinal tract. W.H. Hallenbeck. 1983;53:153-4. PubMed · Publisher · Free full text

Summary

In this commentary, the author reviewed studies of whether asbestos taken in through the diet or by intubation can penetrate the gastrointestinal (GI) tract of humans and animals. Of three human studies of asbestos ingested in drinking water, one concluded that ingested asbestos could not be found in urine. The other two found evidence that it could penetrate the GI tract, migrate, and be recovered in urine and tissues. The author noted that these two positive studies were uncontrolled to the extent that inhaled asbestos may have contributed. Among at least 12 animal studies in rats and baboons, five rat studies and two baboon studies presented evidence of penetration and/or migration to tissues. Three rat studies and two baboon studies found little or no evidence of this. The author judged the positive animal findings not completely convincing because of small fiber numbers, qualitative data presentation, too few control data, and fiber counts not reported per grid opening. He judged the negative studies not completely convincing because the asbestos recovery of their methods was not demonstrated. He described two studies in progress in his laboratory. One compared three sample preparation methods and evaluated urine as an index of worker exposure to airborne asbestos. The other reevaluated earlier baboon tissues using the EPA provisional methodology, with documented recovery.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Assessment of studies on cancer risks from asbestos in Connecticut drinking water. J.W. Meigs. 1983;53:107-8. PubMed · Publisher · Free full text
Assessment of the epidemiological data relating lung cancer to air pollution. F.E. Speizer. 1983;47:33-42. Review PubMed · Publisher · Free full text

Abstract

The epidemiological data linking air pollution and lung cancer are derived from statistical associations concerning rates of cancer among urban and rural residents, migrant studies and studies of occupational groups exposed to effluents from fossil fuel combinations. Few, if any of these studies, are adequately adjusted for both relatively simple measures of cigarette smoking or the potentially more subtle effects of the duration of smoking. Because urbanization and industrial sources of air pollution correspond chronologically with the major increases in cigarette smoking, it is not likely that the specific attributable risk to each component can be adequately assessed. Interactions between cigarette smoking and specific air pollutants, similar to those seen between cigarette smoking and asbestos and or radiation, may be occurring. Considering the various estimates made over the last 25 years, it is likely that the effect of air pollution on lung cancer is something greater than zero; however, it is unlikely that the estimate exceeds 2% of all lung cancers or 5/100,000 cases in urban males. Thus, the effect on all cancers is likely to be less than 1% of all cases.
Biochemical components of bronchoalveolar lavage in early experimental asbestosis of the sheep: phospholipase A2 activity, prostaglandin E2 and proteins. P. Sirois, G. Drapeau, R. Bégin. 1983;51:293-8. PubMed · Publisher · Free full text

Abstract

Biochemical analyses of bronchoalveolar lavage (BAL) supernatants of sheep treated with weekly intratracheal instillations (for 6 months) of saline, 2 mg, or 128 mg of asbestos (chrysotile B; UICC) were performed. Our results showed that proteins (either total or its various components) and phospholipase A2 activity were unchanged in the low exposure group as compared to controls. However, in the high exposure group, with histopathological evidence of early asbestosis, there were significant increases in total proteins, albumin, alpha 2-globulin, beta- and gamma-globulins as well as phospholipase A2 activity of BAL fluid. Prostaglandin E2 activity was significantly increased in both low and high dose groups. These changes in protein and lipid components of BAL following asbestos exposure constitute early indices of lung inflammatory reactions which may contribute to the development of asbestosis.
Biochemical mechanisms in asbestos toxicity. Q. Rahman, B. Das, P.N. Viswanathan. 1983;51:299-303. PubMed · Publisher · Free full text

Abstract

The alarming hazardous nature of asbestos makes it the foremost among toxic fugitive dusts. The biochemical mechanisms responsible for the diverse biological effects of asbestos, such as fibrosis, asbestos bodies, pleural plaques, respiratory difficulty, cancer, and cytotoxicity, are being studied in this laboratory. As asbestosis progresses in guinea pigs, along with reticulum formation, lysosomal enzymes are released from membrane-bound latent state to active free form, initiating degradative changes. Considerable alterations take place in the pulmonary metabolic machinery. Mitochondria in lung cells were found to be important loci for the toxic effect of asbestos. A profile of mitochondrial activity, in control and asbestotic animals, revealed specific enzymic changes such as increased cytochrome c oxidase during the disease. The functional organization of mitochondria was also altered, since the organelles from asbestotic lungs were swollen as measured by spectrophotometry. Glutamate dehydrogenase activity of mitochondria became exposed in asbestosis. The maleate dehydrogenase shunt which is involved in transport of the redox potential across the membrane was enhanced in cytosol and mitochondria. The involvement of microsomal enzymes in asbestosis was indicated by alterations in glucose-6-phosphatase and tyrosine transaminase and aniline hydroxylase. Changes in the biotransformational capacity of lung, due to asbestos, could be an important aspect in toxicity, especially the carcinogenic effect. Considerable alterations were encountered in the levels of different phospholipids and in mucopolysaccharide constituents. On the basis of the above, the molecular mechanisms in asbestos toxicity are explained as an integrated model. Interactions of dust constituents with those of membranes and the ensuing metabolic adjustments are thus important in the etiology of asbestosis.
Biological in vitro and in vivo responses of chrysotile versus amphiboles. J. Bignon, M.C. Jaurand. 1983;51:73-80. Review PubMed · Publisher · Free full text

Abstract

Although all commercial forms of asbestos have been demonstrated to be carcinogenic in animals, so far epidemiological data are controversial concerning what asbestos types are the most carcinogenic and fibrogenic in humans. In order to understand the early cellular events induced by fibrous particles, different in vitro studies (hemolysis, release of enzymes by macrophages, assays on cell culture systems) have been carried out in several laboratories; most of these studies have shown that cell and subcellular in vitro responses were different depending on fiber types: chrysotile versus amphiboles. This presentation compares the results of different laboratories with our data obtained by using a model which modifies the chemistry of the fibers by acid treatment. The acid-leached chrysotile and acid-treated amphibole fibers showed different biological responses in several in vitro systems used in comparison to unleached fibers. These differences in the in vitro reactivity were related to the chemical state of the fibers and might explain the differences in their effects in animals after intrapleural injection as assessed by the percentage of mesothelioma, the latency period, the survival time and the degree of pleural fibrosis. The carcinogenic effect of the fibers is discussed in relation of their in vitro inflammatory or cytotoxic responses.
Cancer risk from asbestos in drinking water: summary of a case-control study in western Washington. L. Polissar, R.K. Severson, E.S. Boatman. 1983;53:57-60. PubMed · Publisher · Free full text

Abstract

We conducted a case-control, interview-based study of the risk of developing cancer from asbestos in drinking water. An area that included Everett, Washington, was selected for the study because of the unusually high concentration of chrysotile asbestos in drinking water from the Sultan River. Through a population-based tumor registry, 382 individuals with cancer of the buccal cavity, pharynx, respiratory system, digestive system, bladder, or kidneys, diagnosed between 1977 and 1980, were identified, and they or their next of kin were interviewed. We conducted validation checks of our interviews, including a comparison with secondary sources. Data on asbestos exposure were collected based on residence and workplace history, and on individual water consumption. Logistic regression was used to estimate cancer risk. We found no convincing evidence for increased cancer risk from imbibed asbestos. Confidence intervals for relative risks for almost all sites included unity. There were significantly elevated risks only for male stomach and male pharyngeal cancer, but these sex-inconsistent results, based on small numbers of cases, are probably due to other factors.
Cell-mediated cytotoxicity expressed by lymphoid cells from rats with asbestos-induced peritoneal mesothelioma towards rat fetal cell. R.H. Stevens, D.A. Cole, H.F. Cheng, et al. 1983;51:91-6. PubMed · Publisher · Free full text

Abstract

Cell-mediated immunity (CMI) directed towards rat fetal cells was evaluated in Fischer F344 young inbred male rats having asbestos-induced peritoneal mesothelioma. The tumors were induced by exposure to Canadian chrysotile B fibers and the CMI delineated by the injury and destruction brought about to 6- to 10-day-old primary fetal cell cultures by the so-called educated peripheral blood lymphoid-cells (PBLC) obtained from the cancer-bearing rats. A significant cytotoxicity was found to be expressed by the PBLCs, suggesting that during the development of mesothelioma, a cellular retrodifferentiation occurs, thereby educating the effectors to recognize a common determinant existing in both the tumor and fetal cells. Educated PBLCs were produced from rats having endodermal tissue cancers (adenocarcinomas of the small bowel, colon and pancreas) and were found to also be cytotoxic to the fetal cultures, yet no injury was apparently inflicted upon cultured mesothelioma target cells by these effectors. These results suggested that the tumor education was specific and that probably a unique and different fetal component was being recognized by the effector cells obtained from the rats with lesions arising either in the mesodermal or endodermal tissue. Further support for this concept was the failure of an antibody, specific to an oncofetal protein existing in endodermal lesions, to apparently recognize any common oncogenic proteins in the mesothelioma. Preliminary studies have also been accomplished which suggests the existence of natural killing immune responses existing to the mesothelioma target cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of cytotoxic effect of asbestos on normal human fibroblasts. M.J. Chang, N.P. Singh, A. Turturro, et al. 1983;51:237-9. PubMed · Publisher · Free full text

Abstract

Using viable cell counting and the incorporation of radioactive thymidine in cell TCA precipitate, we have attempted to separate the effects of asbestos on cell growth inhibition (reproductive failure) vs. cell killing. NIEHS crocidolite and NIEHS intermediate-sized chrysotile at a concentration of 10 micrograms/mL were studied. Cytotoxic effects were demonstrated with both types of asbestos. Thymidine incorporation expressed as cpm/viable cell was enhanced in the presence of either form of asbestos. It is concluded that both negatively charged crocidolite and positively charged chrysotile are toxic to human fibroblast cells in culture and exert their cell killing but not growth inhibition effect concurrently with a stimulation of DNA synthesis.
Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters. E.E. McConnell, A.M. Shefner, J.H. Rust, et al. 1983;53:11-25. PubMed · Publisher · Free full text

Abstract

Bioassays of amosite, short-range (SR), intermediate-range (IR) or intermediate-range chrysotile asbestos in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Syrian golden hamsters. Amosite and both forms of chrysotile asbestos were administered at a concentration of 1% in pelleted diet for the entire lifetime of the hamsters starting with mothers of the test animals. Group sizes varied from 125-254. There was no adverse effect on body weight gain or survival by either type of asbestos or by IR chrysotile asbestos in combination with DMH. A significant increase (p less than 0.05) in adrenal cortical tumors was observed in male hamsters exposed to SR and IR chrysotile asbestos and in females treated with IR chrysotile asbestos when compared to the pooled control groups. However, statistical significance (p less than 0.05) was lost when these dosed groups were compared with temporal control groups. Neither of the male or female amosite asbestos groups showed increased neoplasia in any tissue or organ compared to the control groups. The cocarcinogen studies using IR chrysotile asbestos and 1,2-dimethylhydrazine dihydrochloride were considered inadequate because there was no increase in intestinal neoplasia in the DMH group.
Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats. E.E. McConnell, H.A. Rutter, B.M. Ulland, et al. 1983;53:27-44. PubMed · Publisher · Free full text

Abstract

Carcinogenesis bioassays of blocky (nonfibrous) tremolite and amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Fischer 344 rats. The minerals were administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats starting with the dams of the test animals. One group of amosite rats also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250 animals. The offspring from mothers exposed to tremolite or amosite asbestos were smaller at weaning than those from untreated mothers and remained smaller throughout their life. The administration of dimethylhydrazine (DMH) did not affect body weight gain, either in amosite-exposed or nonexposed animals. Survival was comparable in the tremolite and control groups. The amosite-exposed rats showed enhanced survival compared to the untreated controls. DMH exposure reduced survival by approximately one year, although the amosite plus DMH groups survived slightly better than the DMH alone groups. No toxicity or increase in neoplasia was observed in the tremolite-exposed rats compared to the controls. Significant increases (p less than 0.05) in the rates of C-cell carcinomas of the thyroid and monocytic (mononuclear cell) leukemia in male rats were observed in amosite-exposed groups. However, the biological significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and the positive effect was not observed in the amosite plus preweaning gavage group. The biological significance of an increased incidence of mononuclear cell leukemia is questionable, because of a lack of statistical significance in the amosite group when evaluated using life table analysis, lack of significance when compared to the tremolite control group, and the fact that no toxic or neoplastic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high rate of (62-74%) of intestinal neoplasia in amosite and nonamosite-exposed groups. Neither an enhanced carcinogenic nor protective effect was demonstrated by exposure to amosite asbestos.
Comments on the California studies. R.C. Cooper. 1983;53:109-10. PubMed · Publisher · Free full text
Comparative toxicities of different forms of asbestos on rat pleural mesothelial cells. M.C. Jaurand, I. Bastie-Sigeac, A. Renier, et al. 1983;51:153-8. PubMed · Publisher · Free full text

Abstract

The effects of UICC crocidolite and chrysotile A, either oxalic acid-leached or unleached, on the viability, morphology and growth characteristics of rat pleural mesothelial cells (PMC) were examined; DQ12 quartz particles were also used. When asbestos fibers were added for 48 hr at the beginning of exponential growth, 20 or 50 micrograms/mL of chrysotile fibers were cytotoxic and no growth occurred; with 5 or 10 micrograms/mL a latent period was observed, and the mean population doubling time was increased. Chrysotile ingestion was associated with morphological changes (spreading, intense vacuolation); moreover, a large proportion of the cells was binucleated (more than 30% with 10 micrograms/mL). The oxalic acid-leached chrysotile inhibited growth at a concentration of 50 micrograms/mL; with 5 or 10 micrograms/mL, no spreading occurred, but a shrinkage of some cells was observed. A few large vacuoles were seen in the cytoplasm of the cells; there were fewer binucleated cells. Addition of 5 or 10 micrograms/mL of crocidolite, either leached or unleached, did not significantly change the growth rate, in spite of the presence of a large number of fibers inside the cells which persisted when the cells reached confluency. With 20 or 50 micrograms/mL, the mean population doubling time was increased in a dose-dependent manner. A slight vacuolation of the cells occurred. The sample of quartz did not modify the parameters studied in this report. The results confirm the different in vitro reactivities of the two kinds of unleached asbestos fibers. Leaching of chrysotile fibers decreased their reactivity; alternatively, leaching of crocidolite increased the effects on PMC.
Comparing epidemiologic studies of ingested asbestos for use in risk assessment. L.S. Erdreich. 1983;53:99-104. PubMed · Publisher · Free full text

Abstract

Epidemiologic data can be used in risk assessment in various ways: to calculate the dose-response relationship between exposure levels and adverse effects; to establish ranges of exposure known to be safe or unsafe; to verify an endpoint in humans derived from a route or species extrapolation; to support assumptions necessary for performing extrapolation procedures. These points are illustrated in the risk assessment for exposure to asbestos in drinking water. A previous risk assessment for asbestos, the EPA's Ambient Water Quality Criteria (AWQC) for Asbestos, was derived from cohort studies of inhalation exposure. Epidemiologic studies of ingested asbestos, all of geographical correlation design, were compared on the basis of their ability to add information in support of both the route extrapolation and low-dose extrapolation used in this risk assessment. Results of these ingestion studies were inconsistent due to variable ability to detect a risk from chronic low-level exposure. After preliminary comparisons of factors that determine scientific validity and statistical power, two ingestion studies were selected to determine if they had the potential to detect the risk predicted by the AWQC. This evaluation has shown that these studies do not offer quantitative data for estimating levels associated with a defined risk. Due to short exposure duration and limited power, clearly safe and clearly unsafe ranges could not be definitely identified. The most appropriate ingestion studies suggest, but do not prove, the endpoint derived from the route extrapolation in the AWQC.
Correlation of in vitro and in vivo methods by means of mass dose and fiber distribution for amosite and fibrous ferroactinolite. D.L. Coffin, L.D. Palekar, P.M. Cook. 1983;51:49-53. PubMed · Publisher · Free full text

Abstract

Oncogenesis and in vitro data (reported elsewhere in detail) are compared on the basis of relative activity by mass and by dimensional fiber parameters. When tumor induction is compared to the number of fibers of various lengths and aspect ratios in the dose in rats to the degree of tumor induction, a degree of difference with the long thin fiber concept of tumorigenesis by mineral fibers is noted. Consistency is re-established, however, when cognizance is taken of the change in the length and aspect ratio that took place during residence in the lung. This change resulted in a severalfold excess for ferroactinolite of all fiber lengths with high aspect ratios, produced as a result of longitudinal splitting of the introduced fibers. The response by mass in the in vitro procedures did not mimic oncogenesis. When mass was so adjusted that there were an equal number of mineral fibers, aspect ratio greater than 3, for dose for the two minerals, agreement was closer in both the rabbit alveolar macrophage toxicity test and the clonal cytotoxicity assay in Chinese hamster ovary cells. When activity was related to the number of mineral fibers, the same aspect ratio computed to have been contained in the mass dose, agreement with the relative induction of lung tumors was closer. In all cases, erythrocyte lysis was more active in reflecting the number of mineral fibers.
Critical review of epidemiologic studies related to ingested asbestos. G.M. Marsh. 1983;53:49-56. PubMed · Publisher · Free full text

Abstract

Thirteen epidemiologic studies of ingested asbestos conducted in five areas of the United States and Canada were reviewed and evaluated for the definitiveness and applicability regarding the development of ambient water quality standards. One or more studies found male or female associations between asbestos in water supplies and cancer mortality (or incidence) due to neoplasms of the esophagus, stomach, small intestine, colon, rectum, gallbladder, pancreas, peritoneum, lungs, pleura, prostate, kidneys, brain, and thyroid, and also due to leukemia. Several methodologic weaknesses and limitations were found in each study, leading to the determination that no individual study or aggregation of studies exist that would establish risk levels from ingested asbestos. A binomial probability analysis of the eight independent studies suggested that, while the level of male-female agreement was generally low, the number of observed positive associations in males and females for neoplasms of the esophagus, stomach, pancreas, and prostate was unlikely to have been generated by chance factors alone, and thus, may have a biological basis related to ingested asbestos. Cancers of the small intestine and leukemia were implicated to a lesser degree in this analysis. The patterns of integrated findings for most gastrointestinal cancers were somewhat consistent with patterns observed among asbestos-exposed occupational groups, whereas the patterns found for pancreatic cancer, kidney cancer, and leukemia were not consistent.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytotoxic action of mineral dusts on CHV 79 cells in vitro: factors affecting toxicity. S.O. Lock, M. Chamberlain. 1983;51:189-93. PubMed · Publisher · Free full text

Abstract

The cytotoxic action of a series of mineral dusts has been studied using Chinese hamster V79-4 cells obtained from three separate laboratories in the UK. The dusts which have been studied include samples of asbestos from the Union Internationale Contre le Cancer reference series and an internationally available sample of quartz (DQ12). Besides comparing results obtained with the three different cells, two alternative methods of exposing the cells to the dusts were also compared. The toxicity assay employed uses the inhibition of colony formation from a single cell suspension as a measure of toxicity. The numbers of colonies which grow in the presence of the various concentrations of the dusts are expressed as percentages of the colonies which grow in the untreated control cultures. The absolute toxicity of a dust was found to depend principally on the method of exposing the cells to the dust. However, differences in the relative toxicities of the dusts depended on the source of the cells. The implications of these results for experiments in which Chinese hamster V79-4 cells are used in in vitro test systems to assess the potential pathogenicity of mineral dusts are discussed.
Cytotoxic effect of asbestos on macrophages in different activation states. A. Wright, K. Donaldson, J.M. Davis. 1983;51:147-52. PubMed · Publisher · Free full text

Abstract

The in vitro effects due to phagocytosis of asbestos by mouse peritoneal macrophages in various stages of activation have been compared. The amphiboles proved relatively inert; chrysotile, however, expressed a greater degree of cytotoxicity toward those populations of macrophages induced in vivo with asbestos, than toward any of the other populations of cells. These results are compared with data concerning the enzyme release from the different populations of macrophages following phagocytosis of asbestos. The results indicate that those macrophages that have been exposed to a prior stimulation of either amphibole or serpentine asbestos in vivo are particularly sensitive to exposure to a second dose of a toxic fiber.
Effect of asbestos on the metabolism of vasoactive substances in isolated perfused guinea pig lungs. A. Cadieux, S. Massé, P. Sirois. 1983;51:287-91. PubMed · Publisher · Free full text

Abstract

The measurement of pulmonary metabolism of three vasoactive substances and quantitative assessment of changes in lung morphology were performed in a long-term study of asbestos-exposed guinea pigs. Animals received intratracheal injections of a single dose of a sterile suspension of Canadian chrysotile B (5 mg), while control animals received only saline. Six months after the treatment, the guinea pigs were sacrificed, the lungs removed, perfused via the pulmonary artery and the metabolism of vasoactive substances was assessed (in vitro) in a cascade superfusion system. At the end of the experiments, the lungs were fixed in a glutaraldehyde solution for microscopic examination. The tissue response consisted of both inflammatory reaction of terminal and respiratory bronchioles and diffuse alveolar septal infiltration with interstitial fibrosis. The reaction was characterized at six months by a progressive bronchiolitis obliterans with fibroblastic proliferation and collagen formation. The development of the disease did not cause significant changes in the metabolism of acetylcholine and bradykinin. However, the metabolism of prostaglandin E2 decreased with the appearance of the bronchiolitis obliterans. Our results showed that asbestos exposure may produce early biochemical changes resulting in altered lung metabolism of vasoactive substances; these modifications could contribute to the pathogenesis of asbestosis.
Effect of asbestos on the P388D1 macrophagelike cell line: preliminary ultrastructural observations. N.F. Johnson, R. Davies. 1983;51:109-17. PubMed · Publisher · Free full text

Abstract

The ultrastructural effects of mineral dusts on a macrophagelike cell line (P388D1) were studied by transmission electron microscopy. The cells were found to contain virus particles which probably did not exert a cytopathic effect toward the cells. During mitosis the asbestos fibers appeared to be pushed to the periphery of the cell. The distribution of the asbestos in the P388D1 cells was similar to that seen previously in cultured peritoneal macrophages, and it was concluded that the cytotoxic effect of asbestos towards the cells was due to mechanical effects, e.g., by penetrating structures such as the nucleus or phagosomes, by preventing the ordered movement of organelles with the cell or by disrupting the cytoskeletal framework of the cell.
Effect of chrysotile asbestos and silica on the microsomal metabolism of benzo(a)pyrene. C. Kandaswami, P.J. O'Brien. 1983;51:311-4. PubMed · Publisher · Free full text

Abstract

The effects of chrysotile, water-leached chrysotile, and silica on microsomal metabolism of benzo(a)pyrene in vitro were studied. Examination of benzo(a)pyrene metabolites generated by 3-methylcholanthrene-pretreated rat liver microsomes, in the presence of chrysotile fibers, revealed a reduction in the overall metabolism of the hydrocarbon. Thus, chrysotile appeared to modify the activities of aryl hydrocarbon hydroxylase and epoxide hydrolase. Leaching chrysotile in deionized water for 24 hr elicited a similar response. Silica, in contrast to chrysotile, did not decrease the microsomal metabolism of benzo(a)pyrene. Chrysotile, as well as water-leached chrysotile, considerably diminished the microsomal production of water-soluble benzo(a)pyrene metabolites. Precoating the fibers with heparin or bovine serum albumin partially abolished this inhibition. The liver microsomal metabolism of benzo(a)pyrene in rats subjected to intraperitoneal administration of chrysotile was 58% of that in untreated rats.
Effect of intrabronchially instilled amosite on lavagable lung and pleural cells. G. Oberdoerster, J. Ferin, N.L. Marcello, et al. 1983;51:41-7. PubMed · Publisher · Free full text

Abstract

Rats were instilled intrabronchially with 1 mg UICC amosite suspended in 0.2 mL of filtered saline; control animals received the saline instillation only. Five animals from each group were killed on various days after instillation, up to day 128/129. Total retrieved cell counts and differential cell analysis were performed from lung and pleural lavages. In particular, the appearance of peroxidase-positive macrophages (PPM) as indicators of newly arrived macrophages was investigated. Polymorphonuclear cells (PMN) and PPMs in lung lavages increased in number 24 hr after amosite instillation and remained at increased levels until day 62. Alveolar macrophage numbers were significantly decreased after amosite instillation. There was only a very transient increase of PPMs and PMNs in the saline group. The number of PPMs in pleural lavage fluid was already increased 24 hr after amosite instillation. The pleural PPM increase was sustained throughout the study. No pleural reaction was seen in the saline instilled group. The inflammatory reactions indicated by the composition of the lavaged cells of the lung represent the in vivo toxicity of intrabronchially instilled amosite. The stimulus for recruitment of PMNs and PPMs is different, since no PMN response was detected in the pleural space. It is suggested that the response of the pleural PPMs is caused by the early arrival of fibers at the pleural sites, which results in the recruitment of PPMs to this space by an unknown mechanism.
Effect of mineral dusts on metabolic cooperation between Chinese hamster V79 cells in vitro. M. Chamberlain. 1983;51:5-9. PubMed · Publisher · Free full text

Abstract

The mode of action of inorganic fibers as carcinogens is unknown. There is conflicting evidence whether they act by inducing lesions in DNA, such as initiating carcinogens, or alternatively act as promoters of carcinogenesis. Recent evidence has suggested that promoters inhibit the process of cell-to-cell chemical communication known as metabolic cooperation. Chinese hamster V79-4 cells in culture exhibit metabolic cooperation which can be blocked by the promoter tetraphorbol-13-acetate (TPA). Three kinds of mineral dust were tested to determine whether or not they could interfere with the intercellular communication. The three dusts studied were: amosite, a fibrous asbestos from the Union Internationale Contre le Cancer (UICC) standard reference series, which is a typical carcinogenic fibrous dust inducing pleural tumors following intrapleural injection into rats; ball-milled amosite, a nonfibrous dust derived from UICC amosite by ball-milling, which has the physical properties characteristic of a noncarcinogenic dust; and Min-U-Sil silica, a widely available sample of fibrogenic quartz which does not induce pleural tumors following intrapleural injection into rats. The results demonstrated that metabolic cooperation between V79-4 cells cannot be reduced by carcinogenic asbestos fibers or by relatively large numbers of nontoxic dust particles. It is concluded that if inorganic fibers promote carcinogenesis, then they do not operate by blocking metabolic cooperation.
Effect of population density on the results of the study of water supplies in five California counties. P.M. Conforti. 1983;53:69-78. PubMed · Publisher · Free full text

Abstract

Two previous studies (1969-1971 and 1969-1974) examined the association between cancer incidence and chrysotile asbestos ingested through drinking water in the San Francisco-Oakland Standard Metropolitan Statistical Area (SMSA). Population density, an important covariable in the association between cancer and environmental agents, was not included in the analyses of these studies. The present work determines the effect of this covariable on the results of the second San Francisco-Oakland SMSA study. The original and reanalyzed results are compared to reassess the association between cancer and asbestos. The only change in the regression procedures of the original studies was the addition of population density as an independent variable in the reanalysis. The results of the reanalysis showed that population density had little effect on the results of the second study. Slightly more significance was found for asbestos regression coefficients in the reanalysis, including population density, than in the original analysis. These regression coefficients for asbestos indicated a positive association between ingested chrysotile asbestos and some cancer body sites. The conclusion of the reanalysis was that population density was distributed across the San Francisco-Oakland SMSA in such a way that it had little effect on the observation of an association between ingested asbestos and cancer.
Effects of chrysotile co-exposure on BaP binding in normal human fibroblasts. M.J. Chang, N.P. Singh, R.W. Hart. 1983;51:241-4. PubMed · Publisher · Free full text

Abstract

The effects of chrysotile and benzo(a)pyrene (BaP) co-exposure on uptake, metabolism and BaP binding to nucleic acids were investigated in normal human fibroblasts. A significant enhancement in these parameters was found when co-exposure was carried out under serum-free conditions. In the presence of serum, only a slight enhancement of BaP uptake was detected, while metabolism and binding to nucleic acids were not affected over the 8-hr incubation period studied.
Effects of chrysotile on a lysosomal enzyme preparation and on the hydrolytic enzyme activity of cultured alveolar macrophages. R. Desai, R.J. Richards. 1983;51:125-30. PubMed · Publisher · Free full text

Abstract

The interaction between chrysotile and three lysosomal enzymes (acid phosphatase, acid RNase and acid protease) in isolated lysosomal enzyme-rich preparations (LEP), from sheep alveolar macrophages maintained in the presence and absence of serum components or pulmonary surfactant at pH 5.0 and pH 7.0 for up to 22 days, is investigated. It is concluded that chrysotile does not inhibit or enhance lysosomal enzyme activity at either pH but may preferentially absorb specific enzymes and that the binding reaction between any given enzyme and mineral can be dependent on the presence of other organic compounds. The release of three hydrolytic enzymes (beta-galactosidase, acid RNase and protease) from cultured rabbit alveolar macrophages, in the presence of different concentrations of bovine serum (5-20%) and in the presence and absence of chrysotile for 72 hr, was also studied. Chrysotile enhances early differential release of each hydrolytic enzyme, but after 72 hr both control and chrysotile-treated cultures (maintained in 10-20% serum) have very similar intra- and extracellular levels of hydrolytic activity. The apparent differential release of lysosomal enzymes by untreated macrophages, which is dependent on serum concentration and time in vitro, is discussed.
Effects of crocidolite and chrysotile asbestos on cellular uptake and metabolism of benzo(a)pyrene in hamster tracheal epithelial cells. B.T. Mossman, A. Eastman, J.M. Landesman, et al. 1983;51:331-5. PubMed · Publisher · Free full text

Abstract

The incidence of bronchogenic carcinoma is increased substantially in asbestos workers who smoke. We used several approaches to determine possible mechanisms of synergism at the cellular level between asbestos and the polycyclic aromatic hydrocarbon (PAH), benzo(a)pyrene (BaP), a chemical carcinogen in cigarette smoke. Specifically, we hypothesized that cellular uptake and metabolism of BaP might be facilitated when the hydrocarbon was coated on asbestos. In addition, we were interested in whether asbestos, alone or in combination with BaP, caused single strand breakage of DNA in epithelial cells of the airway. UICC reference samples of crocidolite and chrysotile were coated with 3H-BaP before their addition to monolayers of hamster tracheal epithelial cells. In comparative studies, 3H-BaP at identical amounts was added to cells in culture medium. At intervals thereafter, uptake of BaP by cells was documented by scintillation spectrometry and by autoradiography. In addition, cells and media were assayed by use of high pressure liquid chromatography (HPLC) to demonstrate the water-soluble metabolites of BaP. The integrity of DNA was monitored by alkaline elution at intervals after exposure of tracheal cells to various concentrations of asbestos, BaP and BaP-coated asbestos. A rapid transfer of BaP to cells occurred after addition of BaP-coated asbestos to cultures. When BaP was adsorbed to both types of fibers before their addition to cultures, 70% of the total BaP introduced entered the cell within 1 hr; 50% remained intracellular after 8 hr. In contrast, if identical amounts of BaP were added directly to medium, an initial influx of 20% was observed and cells retained only 5% of the initial amount at 8 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of nonfibrous minerals in the V79-4 cytotoxicity test. G.H. Pigott, P.J. Pinto. 1983;51:173-9. PubMed · Publisher · Free full text

Abstract

The use of the V79-4 system as a primary screen for fiber carcinogenicity is dependent on the observed correlation between cytotoxicity of the test material in the system and mesothelioma following intrapleural injection in animals. This correlation has been established for relatively pure samples of fibrous minerals. The wider application of the system as a screen for industrial dusts may depend on the ability of the system to show an unequivocal response to small yet significant percentages of fibrous dust in the presence of a large excess of nonfibrous material. Some materials tested, including platy minerals, show a response in the test which, while clearly less than that from UICC asbestos samples, could be construed as a positive result. Some, though not all, of these minerals show a nonlinear dose response in the test. This anomalous dose response may aid in the identification of some false positive results but the variety of responses to nonfibrous minerals places a limit on the predictive value of the test mixtures. Results obtained from mixtures of "standard" dust samples suggest this limit is reached at or above 10% fibrous content. Such levels would be significant in terms of human exposure. Extension of the concentration range tested does not improve the predictive value of the test.
Engineering and operating approaches for controlling asbestos fibers in drinking water. G.S. Logsdon. 1983;53:169-76. PubMed · Publisher · Free full text

Abstract

Techniques are available to minimize the concentration of asbestos fibers in drinking water. Filtration research conducted at locations on Lake Superior and in the Cascade Mountains in Washington has shown that amphibole and chrysotile fibers can be removed by granular media filtration. Removal percentages can exceed 99% when the raw water is coagulated properly and the filtered water turbidity is 0.10 ntu (nephelometric turbidity units) or lower. Filtered water fiber counts below detectable limits of 0.1 to 0.01 X 10(6) fibers/L can be attained. A study by the Metropolitan Water District of Southern California showed that when raw water chrysotile counts ranged from 200 X 10(6) fibers/L to 2000 X 10(6) fibers/L, filtered water fiber counts frequently exceeded 1 X 10(6) fibers/L. Even so, striving to attain a filtered water turbidity of 0.1 ntu resulted in improved fiber removal. Pilot scale and distribution system research projects have shown that asbestos cement (AC) pipes can be protected from dissolution and leaching effects that can result in release of asbestos fibers into drinking water. Suggested techniques include modifying low pH, low alkalinity waters so they are not aggressive; coating the pipe wall with a chemical precipitate; and applying a cement mortar lining to the pipe wall. Operation and maintenance practices related to the distribution system, when AC water mains are in service, can influence the fiber count in tapwater. Main flushing can stir up sediment that accumulates in low-flow and dead-end areas, raising the fiber count. If mains are tapped and the cuttings are not flushed away through the tapping machine, but are instead permitted to fall into the water main, the fiber count can be raised.
Epidemiologic basis for the asbestos standard. P.E. Enterline. 1983;52:93-7. PubMed · Publisher · Free full text

Abstract

The current standard for occupational exposure to asbestos is 2 fibers/cm3 averaged over an 8-hr day. A NIOSH/OSHA committee has recently concluded that the 2 fiber/cm3 standard is grossly inadequate to protect workers from asbestos-related disease, and that all levels of asbestos exposure studied thus far have demonstrated asbestos-related disease. The committee recommends that a 0.1 fiber/cm3 limit replace the current 2 fiber/cm3 standard on the grounds that this is the lowest level detectable with currently available analytical techniques. Thus a 0.1 fiber/cm3 limit is not based on epidemiological data but on the presumption that any level of exposure is disease producing. This paper addresses the question of whether it would be possible to detect health effects of exposure below the current 2 fiber/cm3 standard. Five studies are reviewed which provide evidence on the strength of the relationship between asbestos fiber exposure and lung cancer. Calculation of sample sizes needed to be 95% certain of detecting the kind of excess probably associated with exposure to 2 fibers/cm3 suggests that epidemiology is not likely to be useful in detecting lung cancer below the current standard. Some outcome measures other than lung cancer or clinical asbestosis will be needed if observations on humans are to be used as evidence for a lowering of the present standard.
Epidemiology study of the use of asbestos-cement pipe for the distribution of drinking water in Escambia County, Florida. J.R. Millette, G.F. Craun, J.A. Stober, et al. 1983;53:91-8. PubMed · Publisher · Free full text

Abstract

Cancer mortality for the population census tracts of Escambia County, FL, which use asbestos-cement (AC) pipe for public potable water distribution, was compared with cancer mortality data collected from census tracts in the same county where other types of piping materials are used. An analysis of covariance was run to test for differences in standard mortality ratios for seven cancer sites among three potential asbestos exposure groups based on AC pipe usage. Twelve variables representing nonexposure-related influences on disease rates were combined in four independent factors and used as covariates in these analyses. No evidence for an association between the use of AC pipe for carrying drinking water and deaths due to gastrointestinal and related cancers was found. The limitations on the sensitivity of the analysis are discussed.
Factors involved in the cytotoxicity of UICC amosite towards macrophages. R. Davies, D.M. Griffiths, A.W. Preece. 1983;51:245-8. PubMed · Publisher · Free full text

Abstract

The cytotoxicity of various ball-milled UICC amosite samples toward mouse peritoneal macrophages in vitro was examined. On increased ball milling, the cytotoxicity of the amosite samples fell. This decreased biological activity seemed to correlate best with number of fibers longer than 4 micron/micrograms dust, rather than total number of fibers or the electrophoretic mobility of the amosite samples.
How are the physical and chemical properties of chrysotile asbestos altered by a 10-year residence in water and up to 5 days in simulated stomach acid?. K. Seshan. 1983;53:143-8. PubMed · Publisher · Free full text

Abstract

Although there have been a number of studies on the ingestion of asbestos, few studies exist on how the chrysotile asbestos itself is altered by the exposure to the acid stomach environment. This study has found that there are changes in the physical, chemical and surface properties of chrysotile asbestos as a result of exposure to water, strong acids, and simulated gastric juices. It was observed that the charge on the surface (the zeta potential) is changed from positive to negative; the surface becomes silicalike; and the magnesium is lost from the fibers of asbestos upon exposure to water and acid. It was also noted that the smaller the fiber diameter, the faster the loss of the magnesium. Notable among the changes in physical properties is a change in the refractive index. This means that asbestos exposed to acids or water may not be detectable using the dispersion staining techniques that identify asbestos based on the refractive index. Other physical property changes include the destruction of the gross crystallinity of the fibers. The x-ray diffraction signal disappears when fibers are exposed to acid. However, this study shows that the fibers may still be detected by electron diffraction. It appears that upon acid exposure, the magnesium ions are leached out, leaving a magnesium-free silica network. A positive ion, possibly the proton (H+) or the hydronium ion (H3O+), replaces the lost magnesium ion.
Human cancer risk from ingested asbestos: a problem of uncertainty. W.J. Nicholson. 1983;53:111-3. PubMed · Publisher · Free full text

Summary

This commentary considered whether population studies could show a cancer risk from asbestos in drinking water. The author modeled a hypothetical 10-year study of deaths in a city of 1 million people whose water contained 100 million fibers per liter, which he called a gross overestimate of any real situation. He used the lifetime risk from the U.S. EPA asbestos criteria document (3.3 x 10^-3 per person over 70 years), an average residence time of 14 years, and a 7-year latency. Of about 100,000 deaths, about 40 excess cancers were expected (17 gastrointestinal tumors and 23 peritoneal mesotheliomas). A cruder calculation gave 94. No more than about six mesotheliomas would be expected to appear on death certificates. Against about 4,100 expected gastrointestinal cancers (standard deviation 64), the study would reach statistical significance only if the risk were 7.5 times greater or the population 50 times larger. The author noted that shipyard employment could confound such studies, since areas with high waterborne asbestos were also shipbuilding areas. He argued that animal studies may miss an effect if asbestos acts as a promoter. He concluded that ingestion risk cannot be verified by population studies. He recommended flocculation and sedimentation, which can reduce fiber concentrations by about 90%, in areas with very high concentrations, and treatment or coating to limit erosion of asbestos-cement pipes. He estimated 4.7 deaths per year in a population of 100,000 exposed to 100 million fibers per liter.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.
Identification of chlorite and serpentine in cosmetic or pharmaceutical talc. A.M. Blount, A.H. Vassiliou. 1983;51:379-85. PubMed · Publisher · Free full text

Abstract

Chlorite is the most common accessory mineral group found in high purity talc ore used in cosmetic or pharmaceutical consumer talcum products. X-ray diffraction and wet chemical analytical data obtained on geologic samples representing commercial talc ore deposits of high purity and on processed samples representing talc found in consumer talcum products indicate that clinochlore and penninite are the two chlorite minerals most commonly found in all talc samples irrespective of origin or source, but sheridanite is also found in some samples representing talc deposits that are associated with serpentinite rocks. The chlorite minerals exhibit certain well-defined X-ray diffraction characteristics which differentiate them from each other as well as from those of serpentine minerals, including the hazardous chrysotile asbestos.
In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts. B.T. Mossman. 1983;53:155-61. Review PubMed · Publisher · Free full text

Abstract

Organ and cell cultures of gastrointestinal and tracheobronchial epithelium have been used to document both the interaction of asbestos with mucosal cells and the sequence of cellular events occurring after exposure of cells to fibers. The biological activity of various types of asbestos in vitro is related to surface charge, crystallization, and dimensional characteristics. These factors also influence adsorption of natural secretions and serum components to fibers, a process that ameliorates cytotoxicity. Although mechanistic studies at the cellular level are lacking using epithelial cells of the digestive tract, asbestos appears to elicit a constellation of morphologic and biochemical changes in tracheal epithelium that resemble effects of classical tumor promoters on target cells.
In vitro assessment of asbestos genotoxicity. F.B. Daniel. 1983;53:163-7. Review PubMed · Publisher · Free full text

Abstract

Asbestos fibers are highly cytotoxic to cultured mammalian cells and produce chromosomal aberrations in several rodent cell types. There is some uncertainty in the literature as to whether these fibers are clastogenic to cultured human cells. Asbestos fibers do not produce either DNA damage or back mutations in prokaryotic assay systems, and they do not appear to cause DNA strand breaks in either rodent or human cells. The evidence that these fibers can produce either forward mutation or neoplastic transformation of mammalian cells is weak. Asbestos fibers are clearly oncogenic to humans and animals, but, except for clastogenic effects in rodent cells, there is little evidence for genotoxicity of fibers. It is reasonable to expect, therefore, that these materials may be oncogenic by virtue of mechanisms rather than as tumor initiators.
In vitro effects of mineral fibers. L.D. Palekar, P.M. Cook, D.L. Coffin. 1983;51:11-6. PubMed · Publisher · Free full text

Abstract

In vivo tests available to determine the toxicity of mineral fibers are too expensive and time-consuming to be regularly employed in the evaluation of the potential health hazard posed by natural and man-made fibers. In vitro procedures, while economical, convenient and capable of ranking "relative toxicity," are uncertain predictors of specific lesions. Thus, it is of interest to compare the results of various standard in vitro tests with the results of in vivo tests. Data are available for intratracheal and intrapleural exposures of animals to amphibole mineral fibers from UICC amosite and a fibrous form of ferroactinolite. This paper presents data from parallel in vitro studies employing these minerals. The methods used were mammalian erythrocyte lysis, Chinese hamster ovary cell clonal cytotoxicity assay, and rabbit alveolar macrophage cytotoxicity assay. The experiments were conducted in triplicate to determine dose effect by mass and by number of fibers with aspect ratios greater than 3. A comparison of relative toxicity was made between the ferroactinolite and amosite. In the erythrocyte system, there was a greater lytic effect per unit of fibers for ferroactinolite than for the UICC amosite.
Influence of well-defined mineral fibers on proliferating cells. F. Tilkes, E.G. Beck. 1983;51:275-9. PubMed · Publisher · Free full text

Abstract

The effects of well-defined asbestos and man-made mineral fibers, as well as glass and synthetic fluoroamphibole, on phagocytizing permanent rat tumor cells were tested. The following parameters were compared: cell proliferation as determined by cell count and 3H-thymidine incorporation, RNA synthesis by 3H-uridine uptake, protein synthesis by incorporation of 3H-labeled amino acids, protein content and plasma membrane permeability by release of lactic dehydrogenase. The dosage of most of the dusts was estimated gravimetrically, but for some dusts also numerically. Because of the wide range of different fibers lengths, diameters and specific weights, it was sometimes difficult to compare chemically and physically differing fiber fractions with the same fiber counts. In some cases, resulting weights are so different that a direct comparison of the conclusions is impossible. The results with fibers of diverse sources showed the same trends: the toxicity of fibers increases with increasing length and dose. In this test system we found an inhibition of DNA and RNA synthesis. Protein synthesis as measured by amino acid uptake per total cell culture decreased, but the protein content of the single cell increased as determined by the Lowry method. The increase of plasma membrane permeability as determined by lactic dehydrogenase was also dependent on fiber length and concentration. Generally the thinner the fiber, the greater the toxicity when gravimetrical dosage and the same length distributions are employed. Beyond that we can state that the toxicity of fibers from different sources with similar fiber dimensions is similar. One of the glass fiber fractions has a comparable geometry (length, diameter) to the UICC fraction of chrysotile and exhibits the same high toxicity.
Interaction of asbestos with metaplastic squamous epithelium developing in organ cultures of hamster trachea. C.D. Woodworth, B.T. Mossman, J.E. Craighead. 1983;51:27-33. PubMed · Publisher · Free full text

Abstract

The normal mucociliary epithelium of the respiratory tract in chronic cigarette smokers often is replaced focally by a metaplastic squamous epithelium. Because asbestos workers who smoke have a substantially greater risk of bronchogenic carcinoma than nonsmokers, we hypothesized that interaction of asbestos with squamous epithelium might be a contributing factor. To address this question, an in vitro model was developed to study the interaction of asbestos with both mucociliary and squamous epithelium. Explants of tracheas from hamsters were cultured in either a chemically defined minimal essential medium, which maintains a differentiated epithelium, or a nutritionally complex medium, which encourages the development of squamous metaplasia. Scanning electron microscopy (SEM) was used to measure quantitatively the development of a squamous epithelial surface on the explants. The interaction of chrysotile and crocidolite asbestos with cells of the mucociliary and squamous epithelium was studied using both SEM and transmission electron microscopy (TEM). Long fibers of asbestos were cleared, whereas shorter fibers were phagocytized by cells of the mucociliary epithelium. In contrast, asbestos was phagocytized by superficial squamous cells regardless of fiber length, and fibers penetrated between intercellular junctions in the metaplastic epithelium. The relevance of these interactions to the induction of bronchogenic carcinoma is discussed.
Interaction of erythrocyte membranes with particulates. A.C. Ottolenghi, L.B. Joseph, H.A. Newman, et al. 1983;51:253-6. PubMed · Publisher · Free full text

Abstract

Chrysotile fibers promoted the fusion of human erythrocyte membranes and the hemolysis and fusion of fowl erythrocytes. Amosite and glass fibers did not show the same effect. These findings provide a model for the internalization of the fibers by animal cells.
Interactions of asbestos-activated macrophages with an experimental fibrosarcoma. K. Donaldson, J.M. Davis, A. Ewing, et al. 1983;51:97-101. PubMed · Publisher · Free full text

Abstract

Supernatants from in vivo asbestos-activated macrophages failed to show any cytostatic activity against a syngeneic fibrosarcoma cell line in vitro. UICC chrysotile-induced peritoneal exudate cells also failed to demonstrate any growth inhibitory effect on the same cells in Winn assays of tumor growth. Mixing UICC crocidolite with inoculated tumor cells resulted in a dose-dependent inhibition of tumor growth; this could, however, be explained by a direct cytostatic effect on the tumor cells of high doses of crocidolite, which was observed in vitro.
Interactions of chrysotile and benzopyrene in a human cell culture systems. R.E. Stephens, L.B. Joseph, F.B. Daniel, et al. 1983;51:257-65. PubMed · Publisher · Free full text

Abstract

The risk of lung cancer related to asbestos exposure has been shown to increase disproportionately by cigarette smoking, suggesting a synergistic effect. Differing lengths of NIEHS chrysotile with benzopyrene [B(a)P, B(e)P] (organic by-products of combustion) were applied on normal human fibroblasts (cell line CI) to test for cytotoxicity (survival determined by colony-forming efficiency), binding of benzopyrene to DNA, and the production of benzopyrene metabolites. At concentrations of 100 micrograms/mL, NIEHS short chrysotile was more cytotoxic than NIEHS intermediate chrysotile (3% and 17% survival, respectively); B(a)P and B(e)P concentrations up to and including 10 microM were not cytotoxic. Simultaneous application of NIEHS short chrysotile with B(a)P or B(e)P did not decrease survival synergistically. On the contrary, application of B(a)P simultaneously with NIEHS intermediate chrysotile resulted in increased survival over that of intermediate chrysotile alone (25% and 17% survival, respectively). There were low levels of B(a)P bound to DNA in the presence of NIEHS short chrysotile or NIEHS intermediate chrysotile. Measurable levels of B(a)P-DNA adducts were formed both in the absence and in the presence of each size of NIEHS chrysotile. However, there was no strong indication of a perturbation of the level of DNA-B(a)P binding following simultaneous administration of increasing levels of asbestos in addition to 1 microM hydrocarbon. The asbestos had no demonstrable influence on the level of B(a)P metabolism during the 24-hr period following simultaneous exposure of asbestos and hyrdocarbons.(ABSTRACT TRUNCATED AT 250 WORDS)
Interactions of chrysotile asbestos with erythrocyte membranes. A.R. Brody, L.H. Hill. 1983;51:85-9. PubMed · Publisher · Free full text

Abstract

Chrysotile asbestos causes lysis of red blood cells. It has been proposed that the mechanism of hemolysis is mediated through interactions between asbestos and cell membrane glycoproteins. Our studies support this concept and the following results are reported. Electron microscopy shows that asbestos fibers distort red blood cells and bind to cell membranes which may become wrapped around the fibers. This reaction is prevented by pretreatment of the cells with neuraminidase. The distribution of lectins which bind to membrane glycoproteins is altered by treating the cells with asbestos. Cell distortion and membrane deformation consequent to asbestos treatment correlate with a clear increase in the ratio of intracellular Na+:K+ ions.
Keynote address: potential of in vitro tests in asbestos-related problems. I.J. Selikoff, A.L. Frank. 1983;51:1-4. PubMed · Publisher · Free full text
Macrophage functions after exposure to mineral fibers. F. Tilkes, E.G. Beck. 1983;51:67-72. PubMed · Publisher · Free full text

Abstract

UICC, other well-defined asbestos samples and different man-made mineral fibers (MMM) such as glass fiber and synthetic amphibole asbestos were studied in vitro by using rat and guinea pig lung macrophages. These samples had relatively narrow length and diameter spectra. Most of the fiber samples were added to the cultures on a gravimetric basis, although some were added on a numerical basis. Electrocorundum and DQ12 (Dorentruper Quartz) were used as controls at comparable gravimetrical concentrations. The assays used were the release of lactate dehydrogenase (to demonstrate plasma membrane permeability) and the release of beta-glucuronidase (to indicate lysosomal permeability). Carbohydrate metabolism was monitored by the measurement of lactic acid production and, as one of the tests for macrophage function, the production of lysozyme was determined. The phagocytic ability of the cells was measured, after the addition of opsonized zymosan, by bioluminescence following luminol enhancement. Only some results could be evaluated, however, due to technical difficulties. A length- and dose-dependent cytotoxicity of the fibers was found in this system which was similar to that previously described with permanent cell lines. No great differences were found between fibers having different physicochemical compositions if their geometric dimensions were similar. Long, very thin fibers of glass, chrysotile, crocidolite and synthetic fluoroamphiboles were all toxic in the test system.
Measurement and analysis of chemically changed mineral fibers after experiments in vitro and in vivo. K.R. Spurny. 1983;51:343-55. PubMed · Publisher · Free full text

Abstract

Asbestos, as well as other natural and man-made mineral fibers used for in vitro and in vivo experiments, must be described and defined physically and chemically as exactly as possible before any application. The interactions of fibers with the physical, chemical (air, water, etc.) and biological (cells, tissues, etc.) environments cause important changes in fiber chemistry and crystalline structure. Also, these should be detected as precisely as possible after each experiment. Our recent investigations dealt with the development of a complex analytical system for such measurements and with some applications of these analytical procedures for fibrous material sampled in the environment and from biological materials. Chemical and physical microanalyses of asbestos and glass fibers obtained by environmental sampling (air, water) and from human and animal tissue have shown chemical and crystalline changes in these particles. Scanning electron microscopy, electron microprobe analysis and mass spectrometry analysis were used in these investigations. A partial or total leakage of elements could be observed. The leakage of elements in fibers is of a statistical nature. Some fibers remained chemically unchanged; in some fibers some elements were partially leached; and in some fibers the majority of metallic elements were leached. The potential meaning of this effect is also discussed.
Morphological transformation in vitro of normal human fibroblasts by chrysotile. L.B. Joseph, R.E. Stephens, A.C. Ottolenghi, et al. 1983;51:17-22. PubMed · Publisher · Free full text

Abstract

Pathologic response of tissue to asbestos in vivo gives rise to fibromatoma, granuloma and mesothelioma. We are attempting to develop a model system in vitro using human cells in order to investigate the possible mechanisms responsible for these pathologies. Within the first 12 hr of exposure to chrysotile, the fibroblasts showed distinctive morphological changes. Cells appeared elongated with occasional vacuolated nuclei and granular cytoplasm. Cells showed no other obvious morphological changes by light microscopy and were serially passaged at confluence. The cells with vacuolated nuclei were successfully serially passaged. Binucleated cells were first observed 48 hr after passaging. As time in culture increased (3 days to 2 weeks) many cells lost their distinctive bipolar properties and developed "stress striations" and multiple vacuoles in the cytoplasm. Multinucleated giant cells (2-11 nuclei/cell) with lobate nucleoli became more numerous. With increasing passages, the confluent cell density decreased and cell size increased. Cells usually had condensed nucleoli and had lost all control of directional growth. Preliminary indications suggest that these in vitro morphological transformations are due--at least in part--to a lack of control over cytokinesis.
Observations of cancer incidence surveillance in Duluth, Minnesota. E.E. Sigurdson. 1983;53:61-7. PubMed · Publisher · Free full text

Abstract

In 1973, amphibole asbestos fibers were discovered in the municipal water supply of Duluth, Minnesota. The entire city population of approximately 100,000 was exposed from the late 1950s through 1976 at levels of 1-65 million fibers per liter of water. Because of previous epidemiologic studies that linked mesothelioma, lung and gastrointestinal cancers to occupational exposure to asbestos, surveillance of cancer incidence in residents of Duluth was initiated to determine the health effect from ingestion of asbestos. The methodology of the Third National Cancer Survey (TNCS) and SEER Program was used. Duluth 1969-1971 rates were compared with TNCS rates for the cities of Minneapolis and St. Paul during 1969-1971; Duluth rates during 1974-1976 are compared with Duluth 1969-1971; Duluth rates during 1979-1980 are compared with Duluth 1969-1971 and with Iowa SEER; and a table of the occurrence of malignant mesothelioma is presented. Statistically significant excesses are observed in several primary sites in Duluth residents. However, lung cancer in Duluth females is the only primary site considered also of biological significance. The mesothelioma incidence rate is no more than expected. This paper also describes the problems of long-term surveillance of exposed populations considered at risk of environment cancer, the need for improved study methodologies and the use of federal records for follow up of exposed individuals.
Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test. K. Szyba, A. Lange. 1983;51:337-41. PubMed · Publisher · Free full text

Abstract

The potential effect of asbestos fibers on mutagenicity of benzo(a)pyrene was investigated by using the Ames test. Asbestos fibers without a coating of benzo(a)pyrene or benzo(a)pyrene when not dissolved in DMSO lacked any mutagenic effect in the Salmonella/mammalian microsome mutagenicity test. However, when benzo(a)pyrene was adsorbed onto asbestos, significant numbers of mutated bacteria were observed. This shows that asbestos fibers can serve a carrier role presenting benzo(a)pyrene to the enzymatic microsomal system, thus enhancing mutagenicity of this compound.
Reaction of mineral dusts with primary lung fibroblast cultures. R.J. Richards, J. Hunt. 1983;51:61-5. PubMed · Publisher · Free full text

Abstract

The complex metabolism of rabbit lung fibroblast cultures maintained over 24 days in vitro and their interaction with the fibrogenic group of asbestos minerals is reviewed. The differential effects of nine dusts given as a single dose to 3-day-old fibroblast cultures which were then analyzed for DNA, protein and cell mat hydroxyproline after 3 weeks are discussed. A comparison is made of the ability of these minerals to promote reticulin deposition in vivo following instillation into rats with the ability of each mineral to alter cell mat hydroxyproline levels in fibroblast cultures. Because this comparison is poor for some of the minerals investigated, it is concluded that with the current methodology the fibroblast cultures do not provide an adequate in vitro test system for assessing the potential fibrogenicity of a mineral in vivo.
Relative source contributions of diet and air to ingested asbestos exposure. J.N. Rowe. 1983;53:115-20. PubMed · Publisher · Free full text

Abstract

Reliable assessments of the relative contributions of diet (food, beverages, and orally administered drugs) and air (inhaled fibers) to total ingested asbestos exposure are not feasible due to the paucity of quantitative data on the subject. Instead, scenarios for both modes of exposure were developed from the limited information available to give crude estimates of ingestion of asbestos from these routes. They suggest that such sources are potentially significant relative to the contribution of asbestos exposure derived from drinking water. Research recommendations are discussed.
Response of bovine alveolar macrophages in vitro to welding fume particles. L.R. White, A.B. Marthinsen, K. Jakobsen, et al. 1983;51:211-5. PubMed · Publisher · Free full text

Abstract

Alveolar macrophages (AM) from bovine lungs were exposed in culture to manual metal are (MMA) welding fume particles, chromium (Cr), UICC chrysotile A or anatase for 17-20 hr. All the welding particle samples were more cytotoxic to AM than to anatase. Particles from the welding of mild steel with a rutile-coated electrode were less cytotoxic than those produced with a basic-coated electrode. Particles from the welding of stainless steel were slightly more cytotoxic, and much of this activity was probably due to CrVI. Selective release of N-acetyl-beta-glucosaminidase (beta-NAG) was only detected after exposure of AM to chrysotile. Supplementation of the incubation medium with 10% serum increased the viability of all exposed AM cultures, an effect not produced by serum albumin alone. Incubation of particle samples with dipalmitoyl phosphatidylcholine (DPPC) prior to addition to AM reduced the cytotoxicity of the "rutile" welding particles and of chrysotile.
Review of published studies of orally administered asbestos. L.W. Condie. 1983;53:3-9. Review PubMed · Publisher · Free full text

Abstract

There has been great public concern about the adverse health effects resulting from the presence of asbestos fibers in municipal drinking water supplies. This article reviews and summarizes the experimental findings of 11 published papers that have evaluated the carcinogenic potential of asbestos following its ingestion. The long-term, high-level ingestion of various types of asbestos fibers in more than one animal species failed to produce any definite, reproducible, organ-specific carcinogenic effect.
Review of published studies on gut penetration by ingested asbestos fibers. P.M. Cook. 1983;53:121-30. PubMed · Publisher · Free full text

Abstract

During the 1970s, potential health risks associated with exposure to asbestos in drinking water became a national concern. One of the key questions that arose from debate over whether ingestion of mineral fibers could result in increased gastrointestinal cancer risk was whether fibers can penetrate the gastrointestinal mucosa and thus have some chance of residing in tissue. It is likely that such movement of a large number of fibers is a necessary precursor for carcinogenesis following ingestion of asbestos. Studies of the potential for fiber accumulation in tissues and body fluids following introduction of asbestos to the alimentary canal have provided seemingly contradictory observations. This review, which places particular emphasis on the impact of experimental and analytical limitations on the evidential strengths of each study, indicates the likelihood that a very small fraction of ingested microscopic asbestos fibers penetrates the gastrointestinal mucosa. A reliable estimate of the magnitude of long-term fiber retention in tissues as a consequence of chronic human ingestion of asbestos cannot be made at this time.
Some observations on the in vitro cytotoxicity of chrysotile prepared by the wet dispersion process. I.P. Gormley, R.E. Bolton, G.M. Brown, et al. 1983;51:35-9. PubMed · Publisher · Free full text

Abstract

Samples of the chrysotile taken during and after treatment by the wet dispersion process have been tested for their cytotoxic effect in vitro and the results compared with both a UICC chrysotile A sample and a dust prepared from a standard chrysotile textile yarn. Results were obtained from three different in vitro assay systems utilizing P388D1, V79-4 and A549 cells. A sample which still contained the wetting agent used in the wet dispersion process failed to show activity in any of these assays. The other samples, however, were all active with those dusts obtained by milling the final product and by sampling the air of the factory consistently proving significantly more cytotoxic than the standard chrysotile controls. Preliminary results from a parallel in vivo study suggest that these samples are also more active in producing mesotheliomas in rats.
Studies on in vitro chrysotile-pleural mesothelial cell interaction: morphological aspects and metabolism of benzo-3,4-pyrene. M.C. Jaurand, I. Bastie-Sigeac, L. Magne, et al. 1983;51:159-65. PubMed · Publisher · Free full text

Abstract

Cultures of rat pleural mesothelial cells (PMC) were exposed to nonlethal doses of UICC chrysotile A. The morphology was studied by optical and electron microscopy. The consequences of chrysotile ingestion on the rate of pinocytosis of horseradish peroxidase (HPR) metabolism and benzo-3-4-pyrene (BP) were studied. Nonlethal doses of chrysotile (5 micrograms/mL) induced a time-dependent vacuolation of PMC; a dose-dependent inhibition of the vacuolation was observed when PMC were pretreated with DMSO. The origin of the vacuoles is not clear, but some features of autophagy and lysosomal storage were observed. Chrysotile fibers did not modify the rate of pinocytosis of HRP. Similarly, the metabolism of BP was unchanged when BP and chrysotile were both added to the culture medium or when PMC were preincubated with the fibers 24 hr prior to the addition of BP.
Studies using lectins to determine mineral interactions with cellular membranes. B.T. Mossman, L. Jean, J.M. Landesman. 1983;51:23-5. PubMed · Publisher · Free full text

Abstract

Chrysotile asbestos interacts with mucin-secreting cells of tracheal organ cultures, causing an increase in secretion of mucin into the culture medium. This response occurs in the absence of obvious morphologic damage to tracheal epithelial cells. We speculated that asbestos-induced hypersecretion was regulated by the interaction of fibers with specific carbohydrate residues on the cell surface. To test this hypothesis, lectins, i.e., proteins with a high affinity for mono- and oligosaccharides on the plasma membrane, were added to tissues 30 min before addition of chrysotile. Secretion of mucin into the medium was then determined over a 2-hr period by using incorporation of 3H-glucosamine. Blocking of alpha-D-mannose and alpha-D-glucose residues inhibited chrysotile-induced hypersecretion (p less than 0.05), whereas lectins blocking residues of alpha-D-N-acetylgalactosamine, beta-D-N-acetylglucosamine, alpha-L-fucose and sialic acids were ineffective. Preincubation of cultures with carboxypeptidase A or phospholipase A2, but not with neuraminidase, diminished mucin secretion caused by chrysotile. To determine if the positive surface charge of chrysotile was important in interaction with mucin cells, we examined comparatively the effects of various polycations (cationic ferritin, polylysine, DEAE-dextran) and chrysotile after leaching of fibers to remove Mg2+. Although use of polycations enhanced secretion of mucin, effects were not as striking as those observed with chrysotile. In contrast, leached chrysotile failed to elicit a hypersecretory response. These results suggest the interaction of a positively charged component (presumably Mg2+) of chrysotile with glycolipids and glycoproteins containing terminal residues of alpha-D-mannose or alpha-D-glucose.
Study of the cell-transforming ability of amosite and crocidolite asbestos and the ability to induce changes in the metabolism and macromolecular binding of benzo(a)pyrene in C3H10T1/2 cells. A. Poole, R.C. Brown, G.T. Fleming. 1983;51:319-24. PubMed · Publisher · Free full text

Abstract

The cell transforming ability of asbestos dusts was investigated using C3H10T1/2 murine fibroblasts. In a series of experiments, crocidolite and amosite caused no increase in the number of transformed colonies over that seen in cultures from untreated cells. The dusts were, however, capable of augmenting the oncogenic effect of benzo(a)pyrene. This synergistic effect was evident when fibers and chemicals were added to cultures as simple mixtures and when benzo(a)pyrene was adsorbed to the surface of fibers. Asbestos dust did not, however, appear to exert its oncogenic enhancing effect by modifying the metabolism of benzo(a)pyrene in C3H10T1/2 cells.
Suppression of the neutral protease activity of macrophages treated with asbestos in vitro. J.A. Hamilton. 1983;51:103-8. PubMed · Publisher · Free full text

Abstract

Macrophages are often conspicuous in asbestos-induced inflammatory lesions. Chrysotile type B elicits macrophages into the peritoneal cavity of mice which produce high levels of the neutral protease, plasminogen activator; in vitro addition of these same fibers to mouse peritoneal macrophages stimulates enzyme production. It is reported here that, for endotoxin-elicited mouse peritoneal macrophages fed chrysotile type B in vitro, the increased plasminogen activator activity is suppressed by low concentrations of anti-inflammatory steroids. Other active drugs include colchicine and vinblastine. These studies are considered important, as they suggest an approach to controlling the levels of a potentially deleterious enzyme system (PA-plasmin) from macrophages treated with asbestos fibers.
The advantages and limitations of an in vivo test system for investigating the cytotoxicity and fibrogenicity of fibrous dusts. S.E. Sykes, A. Morgan, S.R. Moores, et al. 1983;51:267-73. PubMed · Publisher · Free full text

Abstract

The acute response of the rat lung to a range of fibrous materials has been investigated by bronchopulmonary lavage, at dose levels of 0.5 and 1.0 mg, 1 and 7 days after their administration by intratracheal instillation. The materials chosen for study included UICC chrysotile A, amosite, crocidolite and anthophyllite, and samples of S. African "long" amosite and glass fiber. In addition, the subacute response to 1, 2 and 3 mg of chrysotile and amosite has been studied at 50 and 100 days after instillation. In the acute phase at 1 day after instillation, the response to chrysotile was greater than that to any of the other materials, but by 7 days there was no gradation in the response to different dusts. In the subacute phase, cell recoveries were low, and it was not possible to assess the long-term cytotoxic or fibrogenic effects of amosite and chrysotile by analyses of lung washes, even though biochemical and histological methods indicated gross changes in lung pathology.
The San Francisco Bay epidemiology studies on asbestos in drinking water and cancer incidence: relationship to studies in other locations and pointers for further research. M.S. Kanarek. 1983;53:105-6. PubMed · Publisher · Free full text
Thermal modification of chrysotile asbestos: evidence for decreased cytotoxicity. R. Valentine, M.J. Chang, R.W. Hart, et al. 1983;51:357-68. PubMed · Publisher · Free full text

Abstract

Many asbestiform minerals exhibit temperature-dependent thermoluminescence. Since thermoluminescence involves electronic transitions within crystalline materials, the effect of temperature on asbestos cytotoxicity was evaluated. Heat pretreatment of Canadian chrysotile asbestos reduces its cytotoxicity towards cultured human fibroblasts and bovine alveolar macrophages. When monitored 44 hr after the addition of either 200 degrees C or 400 degrees C heat-pretreated asbestos, alveolar macrophage viability was approximately 40% higher than comparable amounts of unheated asbestos. Similarly, asbestos toxicity, expressed as fibroblast growth inhibition, was inversely related to the asbestos pretreatment temperature in the following manner, 70 degrees C greater than 200 degrees C greater than 400 degrees C = unexposed fibroblast controls. Pretreatment of chrysotile asbestos to 400 degrees C reduced its adsorptive capacity for bovine serum albumin by 25%. Furthermore, asbestos heated to 200 degrees C followed by irradiation with 4 MeV X-rays (4500 rads) resulted in reactivation of asbestos cytotoxicity. Scanning electron microscopy indicated that the ratios of free to fiber-associated alveolar macrophages and the fiber fragment size distributions were unaffected by either heat pretreatment or X-ray irradiation. These observations strongly suggest that the surface charge characteristics and electronic state of asbestos fibers may be responsible for its biological activity.
Transmigration of ingested asbestos. M.E. Meek. 1983;53:149-52. PubMed · Publisher · Free full text

Abstract

There has been speculation that the ingestion of asbestos in food and drinking water may play some role in the etiology of cancer of the gastrointestinal (GI) tract. An important question in the evaluation of the possible human cancer risk associated with asbestos ingestion is whether fibers can penetrate into and through the GI tract in sufficient numbers to cause adverse systemic or local effects. Factors that complicate interpretation of the available data on the transmigration of ingested asbestos are discussed, and the preliminary results of our ongoing investigation of the penetration of amosite fibers into the normal and abnormal intestinal mucosa of the Wistar rat are reported.
Use of quantitative analysis of urine to assess exposure to asbestos fibers in drinking water in the Puget Sound region. E.S. Boatman, T. Merrill, A. O'Neill, et al. 1983;53:131-41. PubMed · Publisher · Free full text

Abstract

An earlier epidemiologic and electron microscopy study of drinking water in the Everett area of Washington State indicated large numbers of naturally occurring chrysotile asbestos fibers in the water. The purpose of the present study was to determine whether significant numbers of asbestos fiber could be demonstrated in the urine of donors residing in that area for less than 3 yr and over 20 yr where the tapwater contained about 200 X 10(6) fibers/L. A control group was obtained from Seattle where the tapwater asbestos fiber content was 100 times less. Urine samples, filtered control water, tapwater samples, and additional controls were processed for transmission electron microscopy by the use of the Nuclepore membrane filter-Jaffe wick procedure. Interference by mucus in the urine was reduced by treatment with hydrogen peroxide. Samples were taken over a period of 21 months. At no time during this period did the asbestos content of the urine samples consistently exceed that of the control waters. There was a significant difference (p less than 0.05) in the asbestos content of urine samples from subjects with less than 3 yr residence times versus greater than 20 yr. Asbestos concentration in urine samples from Everett residents as a whole did not differ significantly from that in samples from Seattle residents. Variable degrees of chrysotile contamination of control water samples and of Nuclepore membrane filters presented a problem. At present, the data are inconclusive but would suggest no relationship between high concentrations of fibers in drinking water and the numbers estimated for voided urine.
Extrapolation from occupational studies: a substitute for environmental epidemiology. P.E. Enterline. 1981;42:39-44. PubMed · Publisher · Free full text

Abstract

Extrapolation from occupational data to general environmental exposures gives some interesting results, and these results might be useful in our decision-making process. These results could never be observed by environmental epidemiology and this method probably represents the only way of quantifying the health effects of low-exposure levels. Three linear models for extrapolating to low levels are presented--one from Canadian data, one from American data and one from British data. One or more of these is applied to two recently publicized asbestos exposures; exposures resulting from asbestos heat shields in hair dryers and exposures in public school buildings. Predictions are derived as to the effects of asbestos exposures on cancer mortality. A comparison is made between predictions made on the basis of a linear and nonlinear model.
Metal interactions in carcinogenesis: enhancement, inhibition. G.F. Nordberg, O. Andersen. 1981;40:65-81. Review PubMed · Publisher · Free full text

Abstract

Metals constitute a fundamentally important part of the total human environment. Since human exposure often involves complex mixtures of metal compounds and, possibly, organic compounds which may be carcinogenic per se, interactions between these compounds may add significantly to human cancer risk. Our present knowledge about these kinds of interactions is very limited. The best investigated area is benzo(a)pyrene (BP)-metal oxide particle interactions in respiratory carcinogenesis in the hamster. Metal oxide particles were also shown to modify the carcinogenic effect of nitrosamines. Several reports describe experiments in which selenium compounds exerted a generally anticarcinogenic and antimutagenic activity. Inorganic arsenic compounds, which are accepted to be carcinogenic in man, have so far been negative in animal experiments except for one recent suggested report. Several authors have, however, suggested that these compounds may act as cocarcinogens due to their inhibition of DNA repair, although animal experiments to demonstrate a cocarcinogenic effect of arsenic compounds have been negative so far, except for one preliminary report. The concentration of zinc in the diet seemed to influence both transplanted tumor growth and the carcinogenicity of several organic compounds, and the possibility of a correlation between dietary zinc and certain cancer forms in man has been suggested. Protection against development of Leydigiomas usually induced by cadmium injection was afforded by simultaneous injection of zinc salts. Nickel carcinogenesis has been reported to be antagonized by manganese, and synergism between Ni and organic carcinogens, e.g. BP, has been demonstrated. There is no firm evidence that lead may be a cocarcinogen, although some limited experimental evidence is available. Oxidizing agents have been demonstrated to increase, and reducing agents to antagonize, the mutagenic effect of chromium compounds in vitro. The content of carcinogenic and other metals in asbestos has been suggested to modify the carcinogenic properties of asbestos. Since much of the information available at present is suggestive, further research on these interactions as well as other possible interactions in metal carcinogenesis is needed. Studies should be made both in well defined in vitro systems and in relevant animal models.
Cellular effects of asbestos and other fibers: correlations with in vivo induction of pleural sarcoma. L.E. Lipkin. 1980;34:91-102. PubMed · Publisher · Free full text

Abstract

The phenomenon of fiber-induced cytotoxicity to P388D1 macrophagelike cells has been demonstrated to parallel (thus far without exception) the probability that the fiber will induce a pleural sarcoma (mesothelioma) in rats. This startling parallel in both cases seems to be essentially independent of the chemical nature of the fiber and correlates best with the presence of fibers greater than 8 micrometers in length and fibers with diameters in the range 0.5 to 1.0 micrometer (Stanton Hypothesis). In both systems evidence has been produced which cast strong doubts on any role played by absorbed (or adherent) impurities. The existence of multiple physical forms of the same chemical moiety (aluminum oxide, dihydroxy-sodium aluminum carbonate, borosilicate glass, etc.,) provides additional test material for the chemical independence corollary. The similar, cytotoxic or sarcomatogenous behavior of chemically different materials (e.g. amosite, chrysotile, aluminum oxide) exhibits the necessary converse argument. As long as the fiber size-shape dependency effect was limited to whole animal phenomena, such as tumor induction, one could make implicitly what were essentially statistical or probabilistic inferences involving transport and/or distribution of fibers to account for the physical effect. The demonstration of strict parallelism at the cellular level in vitro suggests the possibility that in the case of durable fiber toxicology we are dealing with a form of cell-solid interaction in which physical properties for which we have as yet no known receptors play a prominent role.
Clinical observations following asbestos exposure. A.L. Frank. 1980;34:27-30. PubMed · Publisher · Free full text

Abstract

There is a spectrum of clinical entities following occupational exposure to asbestos. Methods of evaluation for these problems are reviewed. Nonmalignant clinical conditions include asbestos warts, asbestos bodies, parenchymal fibrosis (asbestosis), pleural fibrosis and calcification, and benign asbestotic pleural effusion. Asbestosis, though a benign process, is a significant cause of death. Malignant conditions associated with asbestos exposure include lung cancer, accounting for about 20% of all deaths among insulation workers and significantly related to cigarette smoking. The lung cancers tend to occur more frequently in the lower lobes and are more peripheral. Pleural and peritoneal mesothelioma and some excesses in gastrointestinal cancers are found with asbestos exposure, although these are not related to cigarette smoking. Increased rates of malignancy first become significant after 20 years from onset of exposure and are also related to duration of exposure. Difficulties with the use of death certificate data are reviewed.
Comparative studies on the cytotoxicity of amphibole and serpentine asbestos. J.E. Craighead, B.T. Mossman, B.J. Bradley. 1980;34:37-46. Review PubMed · Publisher · Free full text

Abstract

The chemical and physical properties of serpentine and amphibole asbestos are considered in the context of their interaction with tissue of the tracheobronchial tree and lungs. In vitro studies in cultures of several types are evaluated and work with the erythrocyte hemolysis system is reviewed. Although fibers of the two major mineral types differ substantially, it is likely they are modified by secretions and membranes of cells after inhalation to the respiratory tract. Investigations using virgin asbestos might not provide an accurate picture of events in vitro.
Concentration and size of asbestos in water supplies. J.R. Millette, P.J. Clark, M.F. Pansing, et al. 1980;34:13-25. PubMed · Publisher · Free full text

Abstract

A review of the results of over 1500 asbestos analyses from U.S. water supplies suggests that the majority of water consumers are not exposed to asbestos concentrations in their drinking water over 1 x 10(6) fibers per liter. There are, however, some populations that are exposed to waterborne asbestos concentrations over 10 x 10(6) fibers per liter caused by natural erosion, mine processing wastes, waste pile erosion, corrosion of asbestos cement pipe, or disintegration of asbestos tile roofs running into cisterns. The distribution of fiber sizes in the water is dependent on the source of the fibers. The average length of chrysotile fibers found in an asbestos cement distribution system was 4 micrometers, while the average fiber length of chrysotile fibers contributed to a water supply by natural erosion was 1 micrometer.
Elemental modifications and polycyclic aromatic hydrocarbon metabolism in human fibroblasts. R.W. Hart, F.B. Daniel, O.R. Kindig, et al. 1980;34:59-68. PubMed · Publisher · Free full text

Abstract

Mineral fibers and particulates represent one of the best documented, economically important, and ubiquitously occurring categories of human carcinogens. Yet, while a wealth of information exists concerning the mechanism of action of physical, chemical, and viral carcinogens, virtually nothing is known relative to the mechanism of action of this economically important class of carcinogenic compounds known as mineral fibers and particulates. While the length and diameter of various forms of asbestos have been associated with both cellular toxicity in vitro and tumor occurrence in vivo, nothing is known about whether or not these same physical properties are responsible for the purported synergistic interaction between cigarette smoking and asbestos exposure relative to the induction of bronchogenic carcinoma. Thus, while the risk of bronchogenic carcinoma for nonsmokers exposed to asbestos appears to be only slightly greater than that for unexposed nonsmoking populations, the risk of occurrence of this same tumor in asbestos workers who also smoke is approximately 100-fold greater than in nonsmoking asbestos workers. The risk of bronchogenic carcinoma is increased approximately 8-fold in asbestos workers who smoke over non-exposed smokers. Since it is clear that cigarette smoke contains over 150 polycyclic aromatic hydrocarbons, some of which are known animal carcinogens, and since other laboratories have reported that metals associated with asbestos redirect the metabolism of these agents, it was of interest to us to investigate the effects of mineral fibers on the metabolism and biochemistry of polycyclic aromatic hydrocarbons.
Epidemiology of asbestos-related diseases. R.A. Lemen, J.M. Dement, J.K. Wagoner. 1980;34:1-11. Review PubMed · Publisher · Free full text

Abstract

This paper is intended to give the reader an overview of the epidemiology of asbestos-related diseases and is restricted to primarily occupational exposure studies. However, some mention of nonoccupational exposures are made because of their direct relationship to a worker or to a secondary occupational source. Over 100 epidemiological studies are reviewed, dating back to the first case of asbestos-associated disease reported by Montague Murray in 1906. The studies are divided by specific fiber type and by specific disease outcomes and the interaction of asbestos and cigarette smoking is discussed in great detail.
Experimental approaches for exposure to sized glass fibers. D.M. Bernstein, R.T. Drew, M. Kuschner. 1980;34:47-57. PubMed · Publisher · Free full text

Abstract

A number of studies have shown that glass fibers induce both malignant mesothelioma and fibrosis in rats and that these reactions may be primarily a function of the physical properties of the fiber. However, these studies were carried out with fibers having broad size distributions and used methods of administration which bear little resemblance to the way man is exposed. To better characterize the health effects of glass fibers, techniques have been developed to expose rats to glass fibers of defined sizes by intratracheal instillation of aqueous suspensions and by "nose only" inhalation exposure, and to determine the deposition, translocation, and ultimate fate of these fibers in the rat. The fibers have known size distributions with geometric mean diameters of 1.5 micrometers (sigma g = 1.1) and lengths of either 5 micrometers (sigma g = 1.49) or 60 micrometers (sigma g = 3.76). The fibers have been activated with neutron irradiation. Of the several resulting radionuclides, 65Zn appeared to be the most suitable for long-term clearance studies by use of in vivo whole body radioassay techniques. A fluidized bed aerosol generator has been developed to expose rats by "nose only" inhalation to approximately 500 fibers/cm3. The generator and exposure system permits reuse of fibers which pass through the exposure chamber and produces no significant alteration of the fiber size distribution. Rats were exposed by intratracheal instillations to 20 mg of the longer fibers and to equal numbers (2 mg) and equal mass (20 mg) of the shorter fibers. Through approximately 19 weeks little difference was observed in the whole rat clearance rate of long versus short fibers in the initial exposure group. Histopathology, however, showed differences at this time with the short fibers apparently successfully phagocytized by alveolar macrophages and cleared to the lymph nodes, while the long fibers were not.
Macrophage stimulation and the inflammatory response to asbestos. J.A. Hamilton. 1980;34:69-74. PubMed · Publisher · Free full text

Abstract

Chrysotile fibers injected into the peritoneal cavity of mice elicit a cellular exudate. Macrophages appearing in this exudate produce high levels of the neutral protease, plasminogen activator, when compared with the resident peritoneal macrophage population. In contrast, the levels of lysozyme and two lysosomal enzymes are the same for the two macrophage types. The asbestos-induced macrophages producing the plasminogen activator appear to have descended from recently divided precursors. Low concentrations of anti-inflammatory glucocorticoids inhibit macrophage plasminogen activator synthesis. Preliminary experiments indicate that different asbestos types induce hyperemia in skin, and also shorten the partial thromboplastin time of plasma and generate the release of kinins. These observations could be interrelated and are suggested as representing some aspects of the inflammatory response of the host to asbestos exposure.
Mesothelioma in man and experimental animals. M. Kannerstein, J. Churg. 1980;34:31-6. Review PubMed · Publisher · Free full text

Abstract

Asbestos has been established as the cause of most cases of diffuse malignant mesothelioma occurring in the industrialized world. The morphology of mesothelioma may be complex, and the employment of chemical, histochemical and ultrastructural studies are often helpful in identification. Diagnostic difficulties may to some degree blur the extent of its prevalence and reliance on exposure history may not reveal its association with asbestos. Reference panels can be useful in assessing the former and analysis of lung tissue asbestos content may help to clarify the latter, especially in the low dose range. Electron microscopy may prove to be of assistance in this respect, possibly with particular attention to the peripheral areas of the lung. Animal experimentation has supported epidemiologic conclusions and revealed the phenomenon of fiber carcinogenesis. The morphology of mesothelioma in experimental animals is very similar to that in humans, including ultrastructural and biochemical features.
Protein abnormalities in macrophages bearing asbestos. P. Lemkin, L. Lipkin, C. Merril, et al. 1980;34:75-89. PubMed · Publisher · Free full text

Abstract

Computerized techniques for the evaluation of O'Farrell two-dimensional electrophoretic gels have been applied to proteins derived from asbestos bearing macrophages. Preliminary results indicate definite changes in the protein content of cells depending on fiber phagocytosis.
Putative inhibitory effects of chrysotile, crocidolite, and amosite mineral fibers on the more complex surface membrane glycolipids and glycoproteins. H.A. Newman, Y.A. Saat, R.W. Hart. 1980;34:103-11. PubMed · Publisher · Free full text

Abstract

Syrian hamster embryo cells were treated with galactose oxidase, followed by reduction with tritiated sodium borohydride at pH 7.4. The labeling patterns of galactosyl and N-acetyl galactosaminyl residues on the cell surface were altered in comparing scraped vs. unscraped and buffer vs. media-soaked cells treated with galactose oxidase. From these preliminary studies, the procedure to be used in most of the asbestos treatment studies was to treat cells in situ, in buffer with galactose oxidase, and then to label treated scraped cells with NaB(3)H(4). After 20 hr interaction between chrysotile asbestos and Syrian hamster cell cultures, an alteration in surface labeling of glycolipids and glycoproteins was observed. Tritiated disialogangliosides (G(Dla)) and the higher molecular weight labeled glycoproteins were significantly reduced by asbestos treatment. Similar chrysotile asbestos-treated cultures were grown in monolayers in MEM (Eagles) with 10% fetal bovine serum for 2, 24, 48, and 72 hr and then surface-labeled with galactose oxidase-. NaB(3)H(4) in phosphate buffer. Little or no difference was observed between surface-labeled lipid or protein distribution in untreated cells and those treated with asbestos for 2 hr. Asbestos-induced polar and neutral glycolipid pattern changes were observed at 24, 48, and 72 hr. Disialo- and trisialogangliosides (the more complex gangliosides) were decreased 85%, whereas globoside GL-4 was decreased by 60% at 72 hr. An overall decrease of labeled glycoproteins was observed at 24-48 hr. By 72 hr there was a complete loss of labeled protein bands with 80,000 dalton molecular mass. Since the changes in glycoproteins and glycolipids occur only after extended exposure of the cells to asbestos, the present studies support the concept that a metabolic rather than immediate masking effect is involved. Comparisons of treatment of Syrian hamster embryo cells with various asbestos fibers for 48 hr in the order of decreasing reduction in complex gangliosides were crocidolite>chrysotile (intermediate)>amosite. Effects of the above fibers on high molecular weight glycoproteins labeling followed the same order. The labeling pattern is reminiscent of the increased simplification of glycolipids and glycoproteins found in transformed cells. In the case of asbestos which appears to have no independent mutagenic capability, it is more likely that the membrane changes induced by asbestos serve to allow other mutagens to pass into the cell so as to act on the nuclear structure.

1970s

The use of Soluene and KOH as tissue digestants for the determination of asbestos in tissue. G.R. Grieger, I.M. Stewart. 1976;18:222-3. Letter PubMed · Publisher · Free full text
Additives in plastics. R.D. Deanin. 1975;11:35-9. PubMed · Publisher · Free full text

Abstract

The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products.
A health view of asbestos: an annotated literature collection--1960-1974. J.E. Huff, C.Y. Dinger, B.W. Kline, et al. 1974;9:341-417. PubMed · Publisher · Free full text
Analysis for asbestos in environmental samples. G. Everett. 1974;9:181-2. PubMed · Publisher · Free full text
Analysis of amphibole asbestiform fibers in municipal water supplies. W.J. Nicholson. 1974;9:165-72. PubMed · Publisher · Free full text

Abstract

Details are given of the techniques used in the analysis of asbestiform fibers in the water systems of Duluth, Minnesota and other cities. Photographic electron diffraction and electron microprobe analyses indicated that the concentration of verified amphibole mineral fibers ranged from 20 x 10(6) to 75 x 10(6) fibers/l. Approximately 50-60% of the fibers were in the cummingtonite-grunerite series and 20% were in the actinolite-tremolite series. About 5% were chemically identical with amosite. A wide variety of analytical techniques must be employed for unique identification of the mineral species present in water systems.
Approaches and constraints to identification and quantitation of asbestos fibers. A.M. Langer. 1974;9:133-6. PubMed · Publisher · Free full text

Abstract

Asbestos fibers, members of complex crystal-chemical systems, possess some range in characteristic properties. Identification of fibers requires morphological, structural, and chemical data. Most current work centers on identification of single, sublight-microscopic fibers present as contaminants in a range of media. Constraints encountered in the analysis of such materials are: sample preparation of the differing media; level of fiber exposure (contamination); presence (kind and amount) of other particles; tissue types and their different preparation techniques; homogeneity of samples and their preparations; use of proper instrumental technique; time required for analysis, and quantitation.
Asbestos bodies and fibers in lung tissues. A. Fondimare, J. Desbordes. 1974;9:147-8. PubMed · Publisher · Free full text

Abstract

It is suggested that the ratio of asbestos bodies observable by light microscopy to asbestos fibers counted by electron microscopy be examined in a series of cases of asbestosis of varying severity. If the ratio is reasonably constant an estimate of fiber content could be made from the more easily conducted count of asbestos bodies by light microscopy.
Asbestos fibers in the colonic wall. G.E. Westlake. 1974;9:227. PubMed · Publisher · Free full text
Asbestos in talc. A.N. Rohl. 1974;9:129-32. PubMed · Publisher · Free full text

Abstract

Talc deposits include asbestos minerals such as chrysotile and amphiboles that may be carried over into consumer products. Optical microscopy and x-ray diffraction analyses may not reveal their presence. Examples are given of electron microscopy procedures that permit detection and measurement.
Asbestos in the workplace and the community. W.J. Smither. 1974;9:327-9. PubMed · Publisher · Free full text

Abstract

Information developed by Newhouse in a survey of an asbestos factory in London suggests that the risk of mesothelial tumors is strongly related to both the degree and the length of exposure to asbestos dust.
Biological effects of ingested asbestos: report and commentary. D.H. Lee. 1974;9:113-22. Review PubMed · Publisher · Free full text
Chrysotile in water. S. Speil. 1974;9:161-3. PubMed · Publisher · Free full text

Abstract

The problems of quantitating chrysotile in water by fiber count techniques are reviewed briefly and the use of mass quantitation is suggested as a preferable measure. Chrysotile fiber has been found in almost every sample of natural water examined, but generally transmission electron miscroscopy (TEM) is required because of the small diameters involved. The extreme extrapolation required in mathematically converting a few fibers or fiber fragments under the TEM to the fiber content of a liquid sample casts considerable doubt on the validity of numbers used to compare chrysotile contents of different liquids.
Correlation between the tissue response and asbestos fiber content. A.G. Heppleston. 1974;9:295-6. PubMed · Publisher · Free full text

Abstract

Asbestos fiber concentration increases in proportion to the degree of pulmonary fibrosis as far as the moderate grade. No such correlation occurs with severe asbestosis, nor with the morphological form which the fibrosis assumes, and here secondary factors may be concerned. Electron microscopy suggests that optically visible fibers constitute a reasonably constant proportion of the total irrespective of the pathological reaction. Light microscopy may thus afford a guide to the total asbestos concentration. Finally, the development of mesothelioma, whether of the pleura or the peritoneum, appears to be unrelated to the concentration of coated or uncoated asbestos fibers residing in the lung.
Cytotoxicity of heated chrysotile. H. Hayashi. 1974;9:267-70. PubMed · Publisher · Free full text

Abstract

Cytotoxicity and hemolysis were studied in chrysotile and quartz. The biological activity of the surface seemed to be different between chrysotile and quartz. Quartz lost its cytotoxicity on heating over about 500 degrees C. However chrysotile showed remarkable toxicity and induced hemolysis on heating between 650 and 800 degrees C, compared with the original unheated specimens. The mice injected intraperitoneally with minerals heated in this temperature range generally died within 48 hr after injection, while those injected with untreated chrysotile or chrysotile heated in the other heat ranges did not. The products in this range were highly disorded materials. It was assumed that the change of biological effects resulting from heat treatment may be related to the disordered state of chrysotile in the process of transformation into forsterite. The relationship between chemical character and cytotoxicity of the heated chrysotile specimens was also studied.
Deep sea sedimentation. P.E. Biscaye. 1974;9:177-8. PubMed · Publisher · Free full text

Abstract

An important problem in the study of microparticles in the marine environment, suspended in the water column or deposited as sediment on the ocean bottom, is the determination of provenance of the microparticles-where did they come from and by what processes were they transported to the sampling location? Two techniques of possible interest to those concerned with tracing the origins and dispersion paths of asbestos particles are described. One utilizes variations in the naturally occurring rubidium-strontium isotope system and is used to characterize a bulk sample, i.e., a large number of particles. The other utilizes scanning electron microscopy to observe variations in surface texture of individual grains which, in the case of quartz particles in the natural environment, can be related to the transport processes to which they have been subjected.
Detection and identification of asbestos by microscopical dispersion staining. W.C. McCrone. 1974;9:57-62. PubMed · Publisher · Free full text

Abstract

Asbestos fibers as small as 1 mum in diameter can be uniquely identified by light microscopy by employing dispersion staining methods. The technique described herein involves suspension of fibers in liquids of known refractive indices and observation of color display by means of a dispersion staining objective. Wavelengths or indices of refraction may be determined at right angles to and parallel to fiber axes. This method is rapid and sensitive for identification purposes.
Digestive system cancer among persons subjected to occupational inhalation of asbestos particles: a literature review with emphasis on dose response. M.A. Schneiderman. 1974;9:307-11. PubMed · Publisher · Free full text

Abstract

Human data show a dose-response relationship between industrial exposure to asbestos and later development of cancer of the bronchus and lung and of cancer of the digestive tract. The data do not provide much evidence for a threshold or for the existence of a clearly "safe" level of exposure. Good dose-response data, with quantitative estimates of dose are uncommon; however, in all the literature reviewed only one paper did not support the conclusion that increased exposure to inhaled asbestos particles leads to increased digestive system cancer.
Effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract and liver of the rat. D.E. Amacher, A. Alarif, S.S. Epstein. 1974;9:319-24. PubMed · Publisher · Free full text

Abstract

The effects of chrysotile on DNA synthesis in the gastrointestinal tract of the rat were studied by measuring the uptake of tritium-labeled thymidine; whole stomach, small intestine, colon liver were removed, cleaned, and homogenized and the DNA was isolated and assayed for tritium label.A dose-response study indicated that 2 weeks after a 5 mg/kg dose of chrysotile, DNA synthesis was increased in the small intestine and colon and reduced in the liver; synthesis was reduced in the small intestine 2 weeks after a 500 mg/kg dose. Following a 100 mg/kg dose of chrysotile, a transient increase in DNA synthesis was noted in the stomach and small intestine at 1 and 7 days, respectively, besides increased synthesis in the colon from 28 to 63 days. These data suggest that asbestos penetrates the gastrointestinal mucosa and influences regulation of DNA synthesis in the gastrointestinal tract.
Electron microscopical investigation of asbestos fibers. A.M. Langer, A.D. Mackler, F.D. Pooley. 1974;9:63-80. PubMed · Publisher · Free full text

Abstract

Examination of asbestos fibers by electron microscopical techniques enables the observer to distinguish among the fiber types by morphological and structural characteristics. Chrysotile asbestos fibers are composed of bundles of fibrils. Fibers are often curvilinear with splayed ends. Individual fibrils consist of a central capillary defined by an electron dense crystalline wall. With increasing time of electron bombardment, the capillary wall decreases in thickness, deforms, and is encapsulated in an electron translucent material. The change in electron opacity is considered to be a product of structural disruption brought about by dehydroxylation due to electron radiation. A well recognized sequential deformation pattern may be used for identification purposes.Amphibole fibers tend to be straight, splintery, and electron-opaque, although curved fibers are occasionally observed. Diffraction contrast figures are visible as dark bands moving parallel and at right angles to the fiber axis. Crocidolite forms the shortest and thinnest fibers, followed in size by amosite and anthophyllite. Size distribution characteristics of the amphibole fiber types are different. The selected area electron diffraction pattern for chrysotile is unique. Reflections range in forms from streaked to arcuate. Reflection intensity and shape are related to the degree of openness of the fiber bundle and the extent of physical degradation of the fiber. The amphibole asbestos fibers possess diffraction patterns having similar characteristics prohibiting individual identification. Microchemical analysis is required for identification in such cases.A discussion of the industrial hygiene threshold limit values for ampliphibole asbestos fibers is presented. The discussion is based on their differing size distribution characteristics.
Elemental analysis of asbestos fibers by means of electron probe techniques. I.A. Rubin, C.J. Maggiore. 1974;9:81-94. PubMed · Publisher · Free full text

Abstract

The identification and characterization of microparticles has become an important field of study in recent years due to their presence in the environment and association with pathogenesis. Asbestos fibers have been intensively studied for these reasons. Since conventional microscopy has not provided unique identification of these materials, electron probe microanalysis, which yields chemical data, has been utilized in conjunction with other techniques to provide the necessary answers.The options now available to undertake electron probe analysis are discussed with relation to their utilization for microparticle analyses. Two types of electron sources are available, thermionic and field emission. The x-ray spectroscopy requires the use of either wavelength-dispersive focussing crystal spectrometers or an energy-dispersive Si(Li) x-ray detector. Data are presented to demonstrate the feasibility of asbestos identification by using modified raw data obtained with a scanning electron microscope and energy-dispersive x-ray spectrometer. Further, the extension of the technique to other microparticle identification problems is discussed.
Epidemiology of gastrointestinal cancer. I.J. Selikoff. 1974;9:299-305. PubMed · Publisher · Free full text

Abstract

Some 99,000 new cases of cancer of the colon are expected next year, an incidence rate higher than that for both cancer of the lung and cancer of the breast. Evidence from geographic pathology suggests that some environmental factors play a strong role in its etiology. Data obtained in the 1959 survey of one million people by the American Cancer Society and followed since, has failed to show correlation with any of the large number of factors listed. It is suggested that the etiology is one of multiple factors. The synergistic effect of exposure to asbestos and cigarette smoking in the production of bronchogenic carcinoma is demonstrated by data on cohorts of insulation workers. There was also a modest increase in the number of deaths from gastrointestinal cancer in asbestos workers, but smoking did not seem to act in synergistic fashion at that site, except perhaps in the esophagus. Deaths from cancer occurred almost entirely after a period of 20 years or more from initial exposure. The death rate from cancer tended to increase with duration of exposure, but a distinct rise over the expected was seen in those who had been exposed less than one year to amosite dust.
Fibrogenesis. J.S. Harington. 1974;9:271-9. Review PubMed · Publisher · Free full text

Abstract

A review of fibrogenesis by asbestos fibers is given. There is nothing to indicate that the fibrogenic effects of inhaled asbestos fibers should differ in any way from those of ingested asbestos. Recently, ingestion has assumed some importance concerning human exposure. Three sections dealing with the process of fibrogenesis are covered: the first deals with in vitro fibrogenesis, in particular the interrelation of macrophages damaged by dusts and the subsequent laying down of collagen by fibroblasts in culture; the second deals with in vivo fibrogenesis after the inoculation of extracts of silica-treated macrophages into various animals, and the third, with the fibrogenicity of a wide variety of mineral fibers in man and experimental animals. Recent studies described in the first section of the present review appear to offer a better understanding of the effects of macrophages on fibroblasts after tissue damage of various kinds has occurred.
Geology, asbestos, and health. M. Ross. 1974;9:123-4. PubMed · Publisher · Free full text

Abstract

A brief discussion of three types of geologic occurences of asbestos-like minerals is given. The problem of mining ore free of asbestos is considered.
Identification and quantitation of asbestos in talc. A.N. Rohl, A.M. Langer. 1974;9:95-109. PubMed · Publisher · Free full text

Abstract

The currently used analytical methods for identification, characterization and quantitation of asbestos fiber in consumer talcum products include polarized light microscopy, x-ray diffraction analysis, transmission electron microscopy with selected area electron diffraction and electron microprobe techniques. Light microscope methods have severe limitations imposed by the ultimate size resolution of the light-optical system. Small particles go unresolved; those marginally resolved may possess optical properties different from those properties cited in the literature; most optical properties, e.g., indices of refraction, are difficult to measure on small particles. In addition to these difficulties, talc fibers often possess optical properties different from those of talc plates, which further confound analysis. Light microscopy is recommended for use only as a preliminary tool on limited, large-sized, samples. Transmission electron microscopy is a good standard technique for visualization of contaminant asbestos fibers. Together with selected area electron diffraction, talc fibers may be easily differentiated from amphibole asbestos fibers on the basis of both morphological and structural characterization. Chrysotile fibers are easily distinguished on this basis as well. The amphibole asbestos minerals require chemical characterization to differentiate among the different fiber types. Probe analysis is mandatory for such fibers. The major drawbacks to electron beam instrumentation for the mineralogical characterization of talcum products are the time and effort required for data acquisition. These techniques do not lend themselves to routine study.X-ray diffraction analysis, utilizing the step-scan method, offers a relatively rapid, quantitative technique for gross fiber analysis. Based on comparison with standard specimens the fiber content of talcs may be quantitatively determined. It is essential to employ a specimen preparation technique which yields homogeneously dispersed particles. Tremolite may be determined at levels as low as 0.10% by weight, chrysotile 0.25%, and anthophyllite at 2.0% by weight occurrence in talc. The variance of these values depends upon many factors, including the mass absorption coefficient of the fiber types as compared to talc and selected diagnostic reflections and their relative intensities. Each of the above techniques is described in detail. A method for routine analysis of consumer talcum products is suggested.
Identification and quantitation of microparticles in solid materials. D.R. Bowes. 1974;9:125-7. PubMed · Publisher · Free full text

Abstract

Variation in the precise conditions of geological formation may produce variations in the exact composition of asbestos minerals of a particular class, and thus in their biological interactions. Examples are given of differences in O(18)/O(16) ratios, TiO(2) content, lattice substitutions, substitution of Al (III) for Si (IV) and attachments to spare hydrostatic charges.
Immunological reflections on asbestos. R. Burrell. 1974;9:297-8. PubMed · Publisher · Free full text
Ingestion of asbestos. S.H. Zaidi. 1974;9:239-40. PubMed · Publisher · Free full text
Inorganic particle content of foods and drugs. W.V. Eisenberg. 1974;9:183-91. PubMed · Publisher · Free full text

Abstract

Inorganic particulate matter in foods and drugs is discussed from the standpoint of determination by optical microscopy, source, and regulatory significance. Some particulate matter may be generated as extraneous material and traced to specific operational practices during processing and production with excessive levels associated with deficiencies in good manufacturing practices. Other particles, such as talc and asbestos, may be incorporated as additives during their use in production. Data on particles in parenteral drugs are discussed generally. Specific data on glass particles in foods and sand and soil particles in spices are presented.
Inorganic particles in human tissues and their association with neoplastic disease. A.M. Langer. 1974;9:229-33. PubMed · Publisher · Free full text

Abstract

An increased gastrointestinal cancer risk is associated with occupational exposure to asbestos fiber. Examination of tissues obtained from extrapulmonary organs of exposed workmen demonstrates the presence of asbestos fibers and bodies. The amount of fiber present in these tissues is many magnitudes less than encountered in the lung tissues from the same individuals. Ingestion of asbestos fiber in some environmental instances may approach in magnitude the amount resulting from occupational exposure. Disease factors are discussed.
Inorganic particles of agricultural origin. K. Kay. 1974;9:193-5. PubMed · Publisher · Free full text

Abstract

Substantial quantities of mineral silicates are used as carriers for agricultural pest control agents. Most of this material is applied by air dissemination, either dry or as a droplet spray. Therefore, pulmonary and gastric deposition of the mineral carriers (and active agents) will occur among pesticide application personnel and some proportion of the general population in the vicinity of pest control operations-to the extent that particle size of the disseminated material is below the critical 5mum respirable diameter. Furthermore, ingestion of particulates deposited on food crops may be expected as well as mineral finding its way into drinking water supplies. It has been found that the silicates widely used in America can contain three forms of asbestos, anthophyllite, tremolite, and chrysolite. Of these, anthophyllite and chrysotile have been found associated with a neoplastic outcome after many years of exposure. It is therefore proposed that comprehensive mineralogical investigation of pesticide carriers is warranted, including epidemiological and clinical study of formulation and application personnel as well as exposed nonoccupational populations.
Interaction of asbestos with alveolar cells. Y. Suzuki. 1974;9:241-52. PubMed · Publisher · Free full text

Abstract

A number of electron microphotographs are presented showing the various aspects of phagocytosis of fibers in lung tissue. The fibers were rapidly phagocytosed by alveolar macrophages, by polymorphonuclear leucocytes, and less frequently by alveolar epithelial cells. They were also found in the cytoplasm of the alveolar stromal macrophages. In the late stage of the disease, macrophages containing the minerals were recognized in the fibrous submesothelial connective tissues. In this stage, a cell intermediate in structure between the epithelial cell and the macrophage was observed in the alveolar lining. This cell showed strong phagocytic activity against the fibers. The process of phagocytosis of the fibers was quite similar to that of other microparticles such as Thorotrast and India ink. It had been suggested that phagosomes containing the fibers became transformed into secondary lysosomes. The fate of the phagocytosed fibers varied. Some were partly dissolved or digested with marked reduction in the thickness of the wall of the chrysotile fibril. Many became coated by hemosiderin which accumulated in the cytoplasm of the phagocytic cells. This coating transformed the fibers into asbestos bodies. Finally many fibers were released because of the death of the host cell. Uncoated fibers as well as various stages of phagocytosis were observed in all animals, including those 1 to 2 years after the instillation of asbestos. This strongly suggests that fibers may be repeatedly phagocytosed, released and rephagocytosed, inducing a continuous response of the alveolar cells and maintaining the disease.
Investigation and analysis of asbestos fibers and accompanying minerals in biological materials. L. Le Bouffant. 1974;9:149-53. PubMed · Publisher · Free full text

Abstract

A method is described for isolating asbestos fibers contained in biological tissues. It consists in incinerating the biological material in activated oxygen at 150 degrees C, and attacking the ash by 1N HC1 for 18 hr. The residue is then filtered on a membrane covered with a carbon film. Electron microscope examination of the deposit makes it possible to determine fiber concentrations when the weight or volume of primary material is known, and to make size analyses. By x-ray diffraction, the mineralogical nature of the asbestos is determined by comparison with an aluminum reference diagram. For x-ray diffraction, a micromethod is used, with an ash sample of about 10 mug. These techniques are used for identifying and counting asbestos fibers in small fragments of lungs or other organs. It was found that asbestos fibers generally go along with other minerals which may be abundant. Most fibers found in lung are less than 5 mum long. Counts on lungs of asbestos workers give concentrations often greater than 10(7) particles per gram of dry tissue. The evolution of inhaled chrysotile seems to be different from that of amphiboles. In the case of pleural mesothelioma, a comparison of fibers within the tumor with fibers in the adjacent parenchyma shows only slight differences in the particle sizes, but marked differences in their nature, with a chrysotile enrichment in the pleural zone. Pleural plaques were analyzed in the same way. After decalcification, many small sized asbestos fibers were found. The same technique is now being used for determining ingested particles. A great number of observations concerning fiber counts, their nature and sizes, and the presence of various clays minerals will be necessary to establish the role of the different factors in the formation of lesions caused by the inhalation or the ingestion of asbestos fibers.
Lymphohematogenous spread of asbestos. A. Brown. 1974;9:203-4. PubMed · Publisher · Free full text
Microfiltration method for quantitative study of fibrous particles in biological specimens. J. Bignon, P. Sebastien, M.C. Jaurand, et al. 1974;9:155-60. PubMed · Publisher · Free full text

Abstract

Counting coated and uncoated inorganic fibers in sputum has been used to investigate the level of environmental or occupational asbestos exposure and the concentration of fibrous dusts in human lung. Inorganic fibers in sputum were counted by light microscopy after chemical digestion and microfiltration processing. The same method was used for processing gastric juice and lung tissue. There were no ferruginous bodies (FB) in sputum from 49 patients without any asbestos exposure. The study of sputum from 125 patients with various asbestos exposure pointed out a high correlation between the number of FB in sputum and the level of asbestos exposure. These 125 patients were classified into three groups according to the type of their asbestos occupational hazard: group I, raw asbestos workers; group II, workers manufacturing asbestos products; group III, workers with mixed industrial dust exposure. For these three groups, the mean number of FB in sputum was 100, 10, and 1, respectively. The comparison of the FB content of sputum and lung parenchyma showed the absence of FB in sputum when the concentration of FB in lung parenchyma was under 1000/cm(3) of lung parenchyma; above this concentration the number of FB in sputum was in good correlation with fiber concentration in lung parenchyma. A preliminary study with the use of gastric juice showed that gastric juice is a less sensitive sample for evaluating fiber concentration in lung. The microfiltration method for the counting of uncoated fibers gave results as accurate as those in the centrifugation method.
Modification of biological surface activity of particles. R.J. Schnitzer. 1974;9:261-6. PubMed · Publisher · Free full text

Abstract

The hemolytic activity of fibrous asbestos varieties and of fibrous or granular silica dust can be markedly reduced by adsorption of polymers. Polyanions exert a specific action on asbestos, particularly chrysotile, whereas silica is inactivated by nonionic polymers. A high degree of reduction of the lytic action by comparatively small amounts of the antagonistic polymers can be demonstrated after short exposure to concentrations of 0.1-0.4 mg/ml of appropriate polymers. Inactivation is based on stable adsorption. Repeated washings of inactivated mineral sediments or exposure to elevated temperatures (80-120 degrees C) produced no essential loss of the reduction of lytic potency. In one example, inactivation of chrysotile by sodium alginate, depolymerization by ascorbic acid was also ineffective.
Multiple factors in carcinogenesis. S.S. Epstein. 1974;9:331-3. PubMed · Publisher · Free full text
Penetration of cells by asbestos fibers. J.M. Davis, R.E. Bolton, J. Garrett. 1974;9:255-60. PubMed · Publisher · Free full text

Abstract

Studies on the behavior of asbestos fibers within tissues have shown that the only cells that regularly contain asbestos are macrophages and their derivatives. However, these cells actively incorporate the asbestos fibers by the process of phagocytosis, and there is little evidence of direct penetration. Examination of the gut lining after prolonged asbestos ingestion has shown no evidence of dust penetration either through or between the epithelial cells. The structure and arrangement of these cells is discussed, and it is suggested that they are exceptionally well adapted to prevent penetration by any solid material.
Peritoneal mesothelioma. J. Churg. 1974;9:317-8. PubMed · Publisher · Free full text
Pharmacology of fibrosis and tissue injury. M. Chvapil. 1974;9:283-94. PubMed · Publisher · Free full text

Abstract

Methods controlling tissue fibrosis are classified into those specifically inhibiting various metabolic aspects of collagen selectively in the injured tissue (ascorbic acid deficiency, effect of agent chelating Fe(2+), proline analogs, lathyrogens). The most promising method seems to be the blocking of crosslinks formation among collagen molecules by beta-aminopropionitrile, a competitive inhibitor of a crosslinking enzyme, lysyl oxidase. The second group of methods is called nonspecific, as they affect any stage of inflammatory process preceding the activation of fibroblasts. The importance of activated macrophages in the stimulation of fibroblast is discussed. Finally, a new concept is proposed, indicating the function of zinc ions in the control of the integrity of biomembrances, tissue reactivity to noxious agents. It is suggested that zinc may control NADPH dependent lipid peroxidation at the membrane level by inhibiting NADPH oxidase activity. The implication of these ideas to lung fibrosis induced by silica or asbestos is discussed.
Research perspectives concerning asbestos minerals and their effects on biological systems. A.M. Langer. 1974;9:335-8. PubMed · Publisher · Free full text

Abstract

The interaction of asbestos minerals with biological materials is under intensive investigation throughout the world today. Physical scientists should be responsible for the selection of fibers, and their varietal types, for biological studies; they should characterize these experimental materials physically and chemically to the level of sophistication which currently exists in their fields; they should develop definitive assay methods to monitor changes in such characteristics after biological residence; they should actively participate in the formulation of theories or mechanisms of particle interaction in biological systems.Physical scientists should begin the characterization of minerals in the environment and the determination of ambient fiber levels in air and potable water supplies. Such characterization of the environment requires standardized instrumentation and preparation techniques. Acquisition of data in numbers large enough to achieve statistical significance requires the development of automated counting strategies. Instrumentation and software have yet to be developed. The training of physical scientists in environmental areas is lagging behind current national needs and must be accelerated.
Response of cell cultures to asbestos fibers. J. Bruch. 1974;9:253-4. PubMed · Publisher · Free full text

Abstract

The reaction of macrophages to asbestos and glass fibers was studied by light and by electron microscopy. Measurements were made of LDH release, staining with erythrosine B, and lactate production. Size and shape of asbestos fibers were found to have more effect than the physicochemical properties of the surface. Long fibers resulted in a protracted pathogenic but no acute cytotoxic effect.
Small animals in the study of pathological effects of asbestos. P.F. Holt. 1974;9:205-11. PubMed · Publisher · Free full text

Abstract

The main pathological effects attributed to asbestos are carcinogenesis and fibrogenesis. Statistical studies have shown that asbestos workers may expect a higher morbidity not only from cancer of the lung and mesothelioma but also from cancer at other sites. Carcinomas have been reported in animals following the injection of asbestos, but the production of carcinomas by inhaled asbestos is less easy to demonstrate; most examples of experimental carcinogenesis with asbestos have been produced in rats. Rats and man react differently to asbestos in that rats do not produce asbestos bodies. The fibrosis that follows inhalation of asbestos has been frequently described, but studies with specific pathogen free animals have shown that, like the fibrosis that may follow the inhalation of silica dust, gross fibrosis involving the production of abnormal amount of collagen probably requires the intervention of infection as well as asbestos. Because of the difficulties encountered in the direct investigation of carcinogenesis and fibrogenesis resulting from the inhalation of asbestos, attention has been directed to the mechanisms by which the lung is able to protect itself against these fibrous dusts. While non-fibrous dusts and short fibers can be ingested by macrophages and removed via the bronchus, the long fibers that may also reach the alveolar regions may not be removed by this mechanism. The probability that a fiber may reach the alveoli depends largely on the fiber diameter and only to a small extent on the fiber length, so that, for example, fibers 100 mum long may reach the alveoli of a guinea pig. These long fibers may become coated with a ferroprotein derived from hemoglobin to form an asbestos body and, after morphological changes, the asbestos body may be broken up, the fragments ingested by macrophages and dissolved. The lung is thus cleared of asbestos. In the guinea pig lung, consolidated areas from which the asbestos has disappeared shows signs of return to normal. THIS CLEARANCE MECHANISM IS INHIBITED BY OTHER FACTORS: quartz dust may almost completely inhibit asbestos body formation; tobacco smoke has a considerable effect, and even very heavy loads of carbon may act similarly. The normal lung appears able to efficiently eliminate small loads of both nonfibrous and fibrous dust, including the carcinogenic asbestos fibers. The capacity is not unlimited, however, and when the load is heavy there is a much greater probability that fibers will not be detoxicated. In addition, other factors such as silica dust and tobacco smoke may remove the protective mechanism in the lungs.
Structural information in diffuse diffraction patterns. J.H. Konnert. 1974;9:137-8. PubMed · Publisher · Free full text

Abstract

The radiation diffraction pattern for amorphous materials requires special analysis for information on atomic groupings. Powdered crystalline material may also give diffuse patterns requiring this type of analysis. Absence of a sharp diffraction pattern does not necessarily indicate absence of the material. Examples are given for chrysotile and powdered chrysotile.
Technique for the systematic examination of colon--rectum specimens. R.R. Rickert. 1974;9:237. PubMed · Publisher · Free full text
The ingestion of asbestos fibers. I. Webster. 1974;9:199-202. PubMed · Publisher · Free full text

Abstract

Feeding of baboons with crocidolite showed small numbers of asbestos needles 0.5-1 mum in ashed tissue of the gut wall, which probably came from iron-containing macrophages. It is suggested that pleural plaques and hyaline nodules in the peritoneum represent a hypersensitivity reaction to ferritin protein coating on asbestos fibers. In South Africa only a few peritoneal mesotheliomas come from the asbestos areas, and the incidence of gastrointestinal carcinomas is no greater than normal. Intrapleural and intraperitoneal injection produces unrealistic situations. Calcium salts are deposited on asbestos cement pipes from hard water and organic material from soft water. It is difficult to envisage asbestos contamination of the water so reticulated.
The subject of continuous vigilance. A.M. Langer. 1974;9:53-6. PubMed · Publisher · Free full text

Abstract

Asbestos disease in the occupational setting has been documented since the beginning of this century. Modern usage of asbestos fiber has brought with it concomitant and widespread contamination of the environment. The need to control asbestos is required in the forms of legislation and surveillance, to prevent the spread of asbestos disease into the general population.
Tumorigenic effect of fibrous dusts in experimental animals. F. Pott, F. Huth, K.H. Friedrichs. 1974;9:313-5. PubMed · Publisher · Free full text

Abstract

Fibrous dusts (chrysotile, glass fibers, nemalite, palygorscite, and gypsum) and granular dusts (actinolite, biotite, hematite, pectolite, sanidine, and talcum) were injected intraperitoneally into rats. The fibrous dusts (other than gypsum) resulted in a high incidence of mesothelioma (30 - 67%). Gypsum produced only 5% and granular dusts none at all. It is suggested that the fibrous shape leads to a high multiplication rate of cells and predisposes to tumor formation. Fibrosis, in the other hand, does not so predispose. Milled chrysotile with 99.8% fibers than 5 mum in length are carcinogenic in our experience. The carcinogenicity of glass fibers in our experiments may have significance for occupational situations.

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