Journal of Occupational Health

Our medical research library holds 31 studies published in Journal of Occupational Health (2003–2025). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 27 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it. For 1 study PubMed has no abstract for, we give the abstract printed in the article or, where there is none, a summary we wrote from it, each labeled as such.

About the journal

• Publisher: Oxford University Press
• Published: 1996 to the present, Australia
• Language: English
• ISSN: 1341-9145 (print), 1348-9585 (electronic)
• Its record in the NLM Catalog

2020s

• Carcinogenicity assessment: "modern toxicology" considerations from experience in the evaluation of a carbon nanotube. J. Kanno. 2025;67(1). PubMed · Publisher · Free full text

  Abstract

  The novel properties and functions of nanomaterials have naturally alerted toxicologists to the fact that such materials may also have novel effects on the human body and other living organisms. In particular, materials with high stability or biopersistency have been shown to have a tendency to accumulate in the body, leading to chronic toxicity including carcinogenicity. However, in the early stages of toxicity research, the information is often limited to the effects of short-term exposure studies, and findings on chronic effects are very much delayed. In this context, it was exceptional that studies on multi-walled carbon nanotubes (MWCNTs) have started with the verification of their potential to induce mesothelioma. This toxicological endpoint was expected on the basis of existing knowledge of asbestos and asbestos-like fiber particles. This movement has led to the achievement of the original mission of "modern toxicology," which is "to achieve a win-win situation where both industrial promotion and safety assurance are ensured by communicating and sharing toxicity information to developers and consumers at a stage before mass production and consumption begins, that is, before massive exposure of the general public begins." Inaccurate toxicity assessments of asbestos in the 1980s and 1990s allowed its spread to our living environment, which is difficult to decontaminate, and the damage continues to this day. However, the case described here could be an example of realizing the proposition that "nanomaterials, the flagship of high technology, must not repeat the same mistakes."

  © The Author(s) [2025]. Published by Oxford University Press on behalf of the Japan Society for Occupational Health.

• Decoding the molecular enigma behind asbestos and fibrous nanomaterial-induced carcinogenesis. S. Toyokuni, Y. Kong. 2025;67(1). Review PubMed · Publisher · Free full text

  Abstract

  Objectives: The natural fibrous mineral, asbestos, has been useful in industry for many centuries. In the 1960s, epidemiology recognized the association between asbestos exposure and mesothelioma, and in 1987 the International Agency for Research on Cancer designated all kinds of asbestos as Group 1 carcinogens. However, various scientific enigmas remained regarding the molecular mechanisms of asbestos-induced mesothelial carcinogenesis. This review article was undertaken to reveal and summarize recent discoveries to resolve those enigmas.

  Methods: We collected recent important findings from our own laboratory and others to explain why mesothelial cells are the target for asbestos-induced carcinogenesis and what are the key molecular mechanisms.

  Results: The long incubation period of 30-40 years for mesothelial carcinogenesis after asbestos exposure allows the asbestos fibers to go through the pulmonary parenchyma from the central to peripheral portions and ultimately reach the parietal mesothelium by piercing visceral pleura. Asbestos fibers have affinity for hemoglobin and histones, thus accumulating iron on the surface while traveling through the lung. Mesothelial cells are phagocytic cells, engulfing iron-coated asbestos fibers. Accordingly, homozygous deletion of the p16INK4a tumor suppressor gene, a signature of excess iron-induced carcinogenesis, is acquired through oxidative DNA damage. Recently, exosome-dependent iron transfer from asbestos-fed macrophages to mesothelial cells was reported. Similar molecular mechanisms are observed with multiwalled carbon nanotubes of ~50-nm diameter.

  Conclusions: Physical dimensions, biopersistence, and affinity to iron/histones are essential for fibrous material to be carcinogenic to mesothelial cells. Therefore, local iron reduction may be a strategy to prevent mesothelial carcinogenesis.

  © The Author(s) [2025]. Published by Oxford University Press on behalf of the Japan Society for Occupational Health.

• Oxidative and nitrative DNA damage induced by industrial chemicals in relation to carcinogenesis. Y. Hiraku. 2025;67(1). PubMed · Publisher · Free full text

  Abstract

  Objectives: Many chemicals have been used for industrial purposes, and some of them are carcinogenic to humans. However, the molecular mechanisms of their carcinogenetic effects have not been well understood. Reactive oxygen species are generated from industrial chemicals and contribute to carcinogenesis. Particles and fibers are accumulated in respiratory systems by inhalation exposure and cause chronic inflammation. Under inflammatory conditions, reactive nitrogen species are generated from inflammatory and epithelial cells. These species cause oxidative and nitrative DNA damage, leading to carcinogenesis. We carried out experiments on DNA damage induced by various industrial chemicals and investigated their molecular mechanisms.

  Methods: We examined oxidative DNA damage induced by industrial chemicals using DNA fragments derived from human cancer-relevant genes by polyacrylamide gel electrophoresis. Using immunohistochemistry and immunocytochemistry we also examined the formation of 8-nitroguanine (8-nitroG), a DNA lesion formed under inflammatory conditions, in lung tissues and cultured cells exposed to industrial chemicals.

  Results: Benzene and o-toluidine metabolites caused oxidative damage to DNA fragments in the presence of Cu(II). H2O2 and Cu(I) were generated during oxidation of these chemicals and involved in DNA damage. 8-NitroG formation was observed in lung tissues of asbestos-exposed mice and humans. Carbon nanomaterials and indium compounds induced 8-nitroG formation in human lung epithelial cells via the release of damage-associated molecular patterns from exposed cells.

  Conclusions: Various industrial chemicals are considered to induce carcinogenesis by causing oxidative and nitrative DNA damage. These findings provide an insight into risk assessment of industrial chemicals and prevention of carcinogenesis in workplaces.

  © The Author(s) [2025]. Published by Oxford University Press on behalf of the Japan Society for Occupational Health.

• Development of rapid and highly accurate method to measure concentration of fibers in atmosphere using artificial intelligence and scanning electron microscopy. Y. Iida, K. Watanabe, Y. Ominami, et al. 2021;63(1):e12238. PubMed · Publisher · Free full text

  Abstract

  Aim: We aimed to develop a measurement method that can count fibers rapidly by scanning electron microscopy equipped with an artificial intelligence image recognition system (AI-SEM), detecting thin fibers which cannot be observed by a conventional phase contrast microscopy (PCM) method.

  Methods: We created a simulation sampling filter of airborne fibers using water-filtered chrysotile (white asbestos). A total of 108 images was taken of the samples at a 5 kV accelerating voltage with 10 000X magnification scanning electron microscopy (SEM). Each of three expert analysts counted 108 images and created a model answer for fibers. We trained the artificial intelligence (AI) using 25 of the 108 images. After the training, the AI counted fibers in 108 images again.

  Results: There was a 12.1% difference between the AI counting results and the model answer. At 10 000X magnification, AI-SEM can detect 87.9% of fibers with a diameter of 0.06-3 μm, which is similar to a skilled analyst. Fibers with a diameter of 0.2 μm or less cannot be confirmed by phase-contrast microscopy (PCM). When observing the same area in 300 images with 1500X magnification SEM-as listed in the Asbestos Monitoring Manual (Ministry of the Environment)-with 10 000X SEM, the expected analysis time required for the trained AI is 5 h, whereas the expected time required for observation by an analyst is 251 h.

  Conclusion: The AI-SEM can count thin fibers with higher accuracy and more quickly than conventional methods by PCM and SEM.

  © 2021 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.

• MicroRNA expression in lung tissues of asbestos-exposed mice: Upregulation of miR-21 and downregulation of tumor suppressor genes Pdcd4 and Reck. Y. Hiraku, J. Watanabe, A. Kaneko, et al. 2021;63(1):e12282. PubMed · Publisher · Free full text

  Abstract

  Objectives: Asbestos causes lung cancer and malignant mesothelioma in humans, but the precise mechanism has not been well understood. MicroRNA (miRNA) is a short non-coding RNA that suppresses gene expression and participates in human diseases including cancer. In this study, we examined the expression levels of miRNA and potential target genes in lung tissues of asbestos-exposed mice by microarray analysis.

  Methods: We intratracheally administered asbestos (chrysotile and crocidolite, 0.05 or 0.2 mg/instillation) to 6-week-old ICR male mice four times weekly. We extracted total RNA from lung tissues and performed microarray analysis for miRNA and gene expression. We also carried out real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemistry to confirm the results of microarray analysis.

  Results: Microarray analysis revealed that the expression levels of 14 miRNAs were significantly changed by chrysotile and/or crocidolite (>2-fold, P < .05). Especially, miR-21, an oncogenic miRNA, was significantly upregulated by both chrysotile and crocidolite. In database analysis, miR-21 was predicted to target tumor suppressor genes programmed cell death 4 (Pdcd4) and reversion-inducing-cysteine-rich protein with kazal motifs (Reck). Although real-time PCR showed that Pdcd4 was not significantly downregulated by asbestos exposure, Western blotting and immunohistochemistry revealed that PDCD4 expression was reduced especially by chrysotile. Reck was significantly downregulated by chrysotile in real-time PCR and immunohistochemistry.

  Conclusions: This is the first study demonstrating that miR-21 was upregulated and corresponding tumor suppressor genes were downregulated in lung tissues of asbestos-exposed animals. These molecular events are considered to be an early response to asbestos exposure and may contribute to pulmonary toxicity and carcinogenesis.

  © 2021 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.

• Pleural mesothelioma in a circus worker. C. Mensi, C. Zellino, M. Polonioli, et al. 2021;63(1):e12250. Case report PubMed · Publisher · Free full text

  Abstract

  Objectives: To describe an unusual occupational asbestos exposure in a patient with mesothelioma.

  Methods: Since 2000, the Lombardy Mesothelioma Registry (LMR) collects cases of malignant mesothelioma (MM) occurring among people residing in the Lombardy Region, North-West Italy, with a population of 10 million inhabitants. For each case, clinical records and asbestos exposure are collected. Each case is then classified in agreement with the guidelines of the National Mesothelioma Registry.

  Results: We identified a male (86 years old), former smoker, who had been working for 53 years as a circus truck driver and tamer of lions and tigers. The first circumstance of exposure was the use of an asbestos tape that wrapped around the hoop in the feline jumping show with a flaming hoop. The second one was the presence of insulating panels protecting the engine placed inside the trucks.

  Conclusion: A new MM case with an occupational etiology has been found in the public entertainment, an occupational sector not usually considered at risk for the presence of asbestos.

  © 2021 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.

• Radiographic diagnosis of Pneumoconioses by AIR Pneumo-trained physicians: Comparison with low-dose thin-slice computed tomography. S. Nogami, N.A. J-P, M. Nogami, et al. 2020;62(1):e12141. PubMed · Publisher · Free full text

  Abstract

  Objectives: The Asian Intensive Reader of Pneumoconiosis (AIR Pneumo) is a training program designed to improve diagnostic skills for chest radiographies (CXRs) in accordance with the ILO/ICRP 2000. The purpose was to determine the prevalence of occupational environmental pulmonary disease findings in construction workers on thin-slice computed tomography (thin-slice CT), and to compare the diagnostic performance with CXR evaluated by AIR Pneumo-trained physicians.

  Methods: Ninety-seven male construction workers underwent low-dose thin-slice CT and CXR on the same day. NIOSH B reader and a board-certified radiologist each interpreted the thin-slice CTs independently. The concordant findings on thin-slice CT were established as the reference standard and were statistically compared with CXRs. Four physicians interpreted CXRs independently according to the ILO/ICRP 2000.

  Results: Of the 97 cases, nine showed irregular or linear opacities, and 44 had pleural plaques on thin-slice CT. Five, four, three, and two of nine cases with irregular opacity were detected by the four readers on CXRs, respectively. Sixteen, 14, 9, and 5 of the 44 cases with pleural plaques were detected by the four readers, respectively. Specificities for irregular opacities ranged from 94% to 100%, and those for pleural plaques were from 86% to 96%.

  Conclusions: Thin-slice CT-detected irregular opacity was found in 9.3%, whereas pleural plaque was found in 45.4% among the construction workers. Chest radiography showed acceptable performance in classifying pneumoconiotic opacities according to ILO/ICRP 2000 by the AIR Pneumo and/or NIOSH-certified physicians.

  © 2020 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.

• Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist. T. Kishimoto, N. Fujimoto, K. Mizuhashi, et al. 2020;62(1):e12182. PubMed · Publisher · Free full text

  Abstract

  Objectives: In Japan, benign asbestos pleural effusion (BAPE) has been eligible for industrial accident compensation since 2003 as an asbestos-related disease despite the lack of good criteria. We compiled a criteria into a checklist of essential items and for excluding other diseases inducing pleural effusion as a diagnosis process.

  Method: Thoracentesis was performed in order to confirm the presence of pleural effusion at the initial diagnosis, and 105 suspected BAPE patients were retrospectively examined. We complied a checklist comprising the following diagnostic items: (a) occupational asbestos exposure; (b) confirmation of exudate of pleural effusion; (c) exclusion of pleural effusion with malignant tumors based on negative results of CEA and hyaluronic acid, and cytology of pleural effusion; (d) exclusion of rheumatic, bacterial, and tuberculous pleuritis; (d) radiological findings for exclusion of malignancies; and (e) histopathological findings based on thoracoscopy that exclude malignancies (when thoracoscopy was not performed, there was confirmation that no malignancies were present during 3-month follow-up observation). Cases that satisfied all items were defined as BAPE.

  Results: Among the 105 suspected cases, there were five cases that had no occupational asbestos exposure; six cases in which transudate of on pleural effusion; one case each of rheumatoid pleuritis and tuberculous pleuritis; and five cases of pleural mesothelioma based on chest radiography and histopathological findings within 3 months after initial diagnosis. Therefore, we excluded 18 cases from the 105 candidates and determined 87 cases of BAPE.

  Conclusion: We consider that six items described above are suitable for diagnosing BAPE.

  © 2020 Japan Organization of Occupational Health and Safety. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.

2010s

• Beyond Stanton and Pott hypothesis; carbon nanotubes-induced malignant mesothelioma as a disease of gene loss. G.J. Yoshida. 2019;61(2):203-205. Letter PubMed · Publisher · Free full text

• Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment. S. Fukushima, T. Kasai, Y. Umeda, et al. 2018;60(1):10-30. PubMed · Publisher · Free full text

  Abstract

  Objectives: This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT.

  Methods: MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation.

  Results: Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure.

  Conclusions: Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.

• Potential asbestos exposure among patients with primary lung cancer in Japan. A. Tamura, M. Funakoshi, N.A. J-P, et al. 2018;60(3):236-245. PubMed · Publisher · Free full text

  Abstract

  Objective: To investigate the extent of asbestos exposure among patients with primary lung cancer in Japan.

  Methods: A retrospective estimation of potential asbestos-exposed individuals, as determined by the presence of pleural plaques identified on chest computed tomography (CT), was conducted on 885 pathologically confirmed primary lung cancer patients (mean age 71.3 years, 641 males). All patients were diagnosed at 29 hospitals across Japan between 2006 and 2007. Since these hospitals belong to the Japan Federation of Democratic Medical Institutions (MIN-IREN), an organization of medical institutions for workers, the study subjects may contain a higher proportion of workers than the general population.

  Results: Pleural plaques were identified in 12.8% of subjects (15.8% in males and 4.9% in females), consisting exclusively of cases older than 50 years. They were found most frequently on the chest wall pleura (96.5%), followed by the diaphragm (23.9%) and mediastinum (9.7%). Calcifications were seen in 47 cases (41.6%). The highest prevalence of pleural plaques was seen among workers from construction-related fields (37.7%). No distinct lung cancer histology was observed in patients with pleural plaques. Coexistence of pleural plaques and small irregular opacities was observed in 2.5% of subjects.

  Conclusion: In a Japanese population representing more workers than general Japanese, 12.8% of patients with primary lung cancer may have experienced asbestos exposure at some time in the past. Special medical attention should be paid to individuals with a history of employment in construction-related occupations, as workers in this sector showed the highest prevalence of pleural plaques.

• Comments on the 2014 helsinki consensus report on asbestos. C. Ramazzini. 2016;58(2):224-7. PubMed · Publisher · Free full text

• Comments on the causation of malignant mesothelioma: rebutting the false concept that recent exposures to asbestos do not contribute to causation of mesothelioma. C. Ramazzini. 2016;58(2):228-9. PubMed · Publisher · Free full text

• In vitro chromosomal aberrations induced by various shapes of multi-walled carbon nanotubes (MWCNTs). T. Sasaki, M. Asakura, C. Ishioka, et al. 2016;58(6):622-631. PubMed · Publisher · Free full text

  Abstract

  Objectives: IARC has classified one type of multi-walled carbon nanotubes (MWCNTs), MWNT-7, as possibly carcinogenic to humans (Group 2B); however, other types of MWCNT were categorized as not classifiable as to their carcinogenicity to humans (Group 3). In vitro chromosomal aberration assays of MWNT-7 showed polyploid formation but not structural abnormalities. This study investigated the influence of the shape and size of MWCNT on in vitro induction of chromosomal aberrations.

  Methods: Microscopic analysis and viable cell counting were used to assay for chromosomal aberrations and cytotoxicity induced in a Chinese hamster lung cell line (CHL/IU) exposed to different MWCNTs.

  Results: Using scanning electron microscopy, seven MWCNTs were classified into three types: straight fibrous, curved fibrous, and tangled. The straight fibrous MWCNTs were the strongest inducers of polyploidy and the most cytotoxic among the three types of MWCNTs. The curved fibrous MWCNTs induced more polyploidy than the tangled MWCNTs, and the cytotoxicity of both types seemed to be a reflection of their induction of polyploidy. None of the seven MWCNTs induced structural chromosomal aberrations.

  Conclusion: The non-clastogenicity of the MWCNTs indicates that the MWCNTs may not interact directly with DNA. Since the straight fibrous MWCNTs, which exhibit a structure similar to asbestos, were the strongest inducers of polyploidy, MWCNT shape may be an important factor in induction of polyploidy. We hypothesize that CHL/IU cells endocytosed MWCNTs and formed endosomes with shapes corresponding to those of the endocytosed MWCNTs, and that the long axis diameter of the endosome is important in the capability of MWCNTs to induce polyploidy.

• The global health dimensions of asbestos and asbestos-related diseases. C. Ramazzini. 2016;58(2):220-3. PubMed · Publisher · Free full text

  Abstract

  The Collegium Ramazzini (CR) reaffirms its long-standing position that responsible public health action is to ban all extraction and use of asbestos, including chrysotile. This current statement updates earlier statements by the CR with a focus on global health dimensions of asbestos and asbestos-related diseases (ARDs). The ARD epidemic will likely not peak for at least a decade in most industrialized countries and for several decades in industrializing countries. Asbestos and ARDs will continue to present challenges in the arena of occupational medicine and public health as well as in clinical research and practice, and have thus emerged as a global health issue. Industrialized countries that have already gone through the transition to an asbestos ban have learned lessons and acquired know-how and capacity that could be of great value if deployed in industrializing countries embarking on the transition. The accumulated wealth of experience and technologies in industrialized countries should thus be shared internationally through global campaigns to eliminate ARDs.

  PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

• Formation of the nitrative DNA lesion 8-nitroguanine is associated with asbestos contents in human lung tissues: a pilot study. Y. Hiraku, K. Sakai, E. Shibata, et al. 2014;56(3):186-96. PubMed · Publisher

  Abstract

  Objectives: Asbestos causes lung cancer and malignant mesothelioma, and chronic inflammation is considered to participate in carcinogenesis. However, biomarkers to evaluate its carcinogenic risk have not been established. Reactive oxygen/nitrogen species are generated in biological systems under inflammatory conditions and may contribute to carcinogenesis by causing DNA damage. In this study, we examined the relationship between the formation of 8-nitroguanine (8-nitroG), a mutagenic DNA lesion formed during inflammation, and asbestos contents in human lung tissues.

  Methods: We obtained non-tumor lung tissues from patients with (n=15) and without mesothelioma (n=21). The expression of 8-nitroG and related molecules was examined by immunohistochemistry, and their staining intensities were semiquantitatively evaluated. Asbestos contents in lung tissues were analyzed by analytical transmission electron microscopy.

  Results: In subjects without mesothelioma, staining intensities of 8-nitroG and apurinic/apyrimidinic endonuclease 1 (APE1) were significantly correlated with total asbestos and amphibole contents (p<0.05), but not with chrysotile content. In mesothelioma patients, their staining intensities were not correlated with asbestos contents. The double immunofluorescence technique revealed that APE1 was expressed in 8-nitroG-positive cells, suggesting that abasic sites were formed possibly due to the removal of 8-nitroG. The staining intensities of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative DNA lesion, and its repair enzyme 8-oxoguanine DNA-glycosylase were correlated with age (p<0.05), but not with asbestos contents in subjects without mesothelioma.

  Conclusions: This is the first study to demonstrate that 8-nitroG formation is associated with asbestos contents in human lung tissues. This finding raises a possibility that 8-nitroG serves as a biomarker that can be used to evaluate asbestos exposure and carcinogenic risk.

• Past occupational dust exposure, depressive symptoms and anxiety in retired Chinese factory workers: the Guangzhou Biobank Cohort Study. Q.H. Lin, C.Q. Jiang, T.H. Lam, et al. 2014;56(6):444-52. PubMed · Publisher

  Abstract

  Objective: Few studies have systematically investigated the impact of past occupational dust exposure on mental health. We examined whether retired factory workers exposed to any of the 4 dusts of silica, cement, coal and asbestos had more depressive symptoms and anxiety in southern China, which has experienced rapid economic development.

  Methods: We used data from the Guangzhou Biobank Cohort Study phase 3. Exposures, lifestyle, symptoms and medical history of the participants were assessed with a structured interview. Self-reported intensity and duration of past occupational dust exposure were used to derive cumulative exposure. Outcome measures were assessed by the 15-item Chinese version of the Geriatric Depression Scale (score ≥5) and the single-item on anxiety.

  Results: The results revealed that 359 workers were exposed to at least one of the 4 dusts and that 1,253 were unexposed (controls). After adjustment of multiple confounders, greater risks of depressive symptoms were associated with high exposure to silica (odds ratio (OR) of 3.12, 95% CI of 1.17-8.31) and asbestos (OR of 6.90; CI of 1.29-36.75). Risks of anxiety were higher in those with low or high exposures to dust (OR of 2.01 and CI of 1.04-3.87 and OR of 2.29 and CI of 1.30-4.03, respectively) and cement (OR of 3.20 and CI of 1.27-8.07 and OR of 2.30 and CI of 1.09-4.87, respectively), and those with high exposure to silica (OR of 5.29, CI of 1.76-15.92).

  Conclusions: Past occupational exposures to silica, cement, coal and asbestos dusts were associated with adverse mental health outcomes in retired factory workers. The mechanism underlying the relationship between occupational exposures and psychological symptoms in later life needs to be further studied.

• Occupational exposure and thoracic malignancies, is there a relationship?. S. Baser, O. Duzce, F. Evyapan, et al. 2013;55(4):301-6. PubMed · Publisher

  Abstract

  Objectives: The aim of this study was to evaluate the effect of occupational exposure in the occurrence of lung cancer.

  Method: Three-hundred lung cancer cases diagnosed between September 1, 1999, and September 31, 2007, and 300 healthy controls were enrolled in this case-control study. Life-long occupational history, gender, age, exposure to asbestos, comorbidities, and smoking status were collected.

  Results: The mean age of the 300 lung cancer cases was 60.3 ± 9.9 year (91.7% male and 8.3% female), and the mean age of healthy control group was 60.4 ± 10.5 year (95.0% male and 5.0% female). The most frequent histological types were squamous (172, 57.3%), adeno (69, 23.1%), and small cell (37, 12.3%). There was an increased risk of lung cancer occurrence among agriculture workers (OR=1.89, 95% Cl=1.17-2.98) (p=0.009). Inorganic dust exposure (OR=1.81, 95% Cl=1.0-3.25) (p=0.049) and organic dust exposure (OR=1.89, 95% Cl=1.0-3.59) (p=0.05) were found to be related with high frequency of having lung cancer.

  Conclusion: Workers who had occupational exposure to organic and inorganic dust, especially in the agricultural field, had higher risk of lung cancer occurrence when compared with office workers.

• Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers. Y. Obata, Y. Morimoto, M. Hirohashi, et al. 2011;53(4):267-73. PubMed · Publisher

  Abstract

  Objectives: Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to potassium octatitanate whiskers (PT1), which is one of the asbestos substitutes.

  Methods: Male Wistar rats were administered 1 mg or 2 mg PT1 suspended in saline by a single intratracheal instillation and were sacrificed after recovery for 3 days, 1 wk, 1 mo, 3 mo or 6 mo. Gene expression of HO-1 protein and mRNA and immunostaining were investigated in rat lungs.

  Results: HO-1 protein expression was increased from 3 days to 1 mo and at 6 mo in the 1 or 2 mg PT1-exposed groups, and the gene expression of HO-1 mRNA was also increased at 3 days and from 1 mo to 6 mo. HO-1-positive cells were mainly found in the alveolar macrophages and the bronchial epithelial cells in immunostaining.

  Conclusions: These findings suggest that HO-1 is involved in lung damage caused by PT1.

• Non-response bias in a surveillance program for asbestos-related lung cancer. L. Knoll, M.K. Felten, D. Ackermann, et al. 2011;53(1):16-22. PubMed · Publisher

  Abstract

  Objectives: In a cohort study non-response might lead to a biased selection of cohort members and may affect the validity and reliability of the study outcome. To detect the possible effects of a non-response bias on study results, we evaluated the reasons for non-participation and the differences of respondents and non-respondents in a health surveillance program for power industry workers, formerly exposed to asbestos.

  Methods: A cohort of former power plant workers was formed to participate in an early detection program for lung cancer. We evaluated the results of 1,019 individuals (mean age 66 yr), of which 839 took part in at least one examination, 180 refused to participate or did not respond. To obtain the reasons for non-response, we interviewed the cohort members by telephone or we requested them by mail to complete and return a brief questionnaire. Further sources of information were the communal registration offices and local health offices.

  Results: The main reasons for non-participation were refusal (35%), illness (23.3%), death (16.7%) and difficulties with traveling (13.3%). It was impossible to make contact with or obtain an explanation from 11.7%. In a logistic regression model we demonstrated that advanced age and a long travel distance from the study center negatively affected the participation rate (p<0.001). There was no difference between respondents and non-respondents regarding prevalence (p=0.559) and incidence of lung cancer (p=0.882).

  Conclusion: We concluded that in our cohort non-participation did not cause a selection bias in terms of lung cancer rates.

• Cytotoxicity study of high temperature wool (HT wool) by cell magnetometric evaluation. Y. Kudo, M. Kotani, Y. Aizawa. 2010;52(2):106-14. PubMed · Publisher

  Abstract

  Objectives: We performed a cytotoxicity study by cell magnetometry, measured lactate dehydrogenase (LDH) activity by enzyme assay, detected DNA ladder formation, and performed morphological examination by electron microscopy in order to evaluate the safety of high temperature wool (HT wool), an asbestos substitute, using long and short chrysotile fibers (CF) as positive controls and phosphate buffered saline (PBS) as a negative control.

  Methods: Alveolar macrophages were isolated from male Fisher rats. Following the addition of iron oxide particles (Fe(3)O(4)) to macrophages, HT wool, long or short CF was added. Then, the remanence strength was measured for 20 min after magnetization by an external field. Percent LDH release was calculated after determining LDH activity. DNA was detected using an apoptosis detection kit. Morphological observation was performed by taking electron micrographs of macrophages in the groups treated with HT wool and long- and short-CF.

  Results: Rapid relaxation, an indicator of decay of cytotoxicity, was observed by cell magnetometry immediately after magnetization was ended in the groups treated with HT wool and PBS, showing that HT wool causes no harmful effect on the cytoskeleton. The CF-treated groups had higher LDH activity than the PBS- and HT wool-treated groups. No fragmentation of DNA was observed in any group. In morphological observation, cytotoxicity in macrophages was lower in the HT wool-treated groups than in the CF-treated groups.

  Conclusions: The results suggest that HT wool has no cytotoxicity, as evaluated by cell magnetometry, enzyme assay, DNA ladder detection and morphological examination.

• Effect of a two-hour training on physicians' skill in interpreting Pneumoconiotic chest radiographs. N.R. Ngatu, S. Suzuki, Y. Kusaka, et al. 2010;52(5):294-301. PubMed · Publisher

  Abstract

  Objective: Occupational lung diseases have specific radiographic manifestations not always well known by physicians. In Japan, asbestos-related diseases became a public health concern after the "Kubota Shock", when a number of workers and residents living nearby a manufacturer of asbestos-made ducts developed mesothelioma caused by asbestos exposure. This preliminary intervention trial evaluated the effect of two-hour training on inexperienced physicians' skill in interpreting pneumoconiotic chest radiographs.

  Methods: One hundred-two Japanese physicians participated in two reading-tests, using 12 radiographs, before and after the two-hour training with ILO/ICRP and Japan Pneumoconioses Study Group (JPSG) reading materials. Physicians had to check for the presence or absence of small opacity and pleural plaque consistent with pneumoconiosis. Sensitivity and specificity equal or greater than 70% were considered good, 50 to 69% acceptable and less than 50%, poor.

  Results: Post-training improvements in physicians' skills were seen. For small opacity, there was an increase in the proportion of physicians with good specificity, from 42% to 60%. For pleural plaque, the proportion of physicians with good specificity and good sensitivity increased, from 60% to 67% and from 18% to 25%, respectively. Also, significant improvements were observed in overall sensitivity for pleural plaque, from 46% to 60% (p<0.0001), and specificity for small opacity, from 65% to 73% (p<0.0001).

  Conclusions: This study showed that two-hour participatory training may enhance physicians' skill in interpreting pneumoconiotic chest radiographs. There are countries without any pneumoconiosis screening program despite the WHO/ILO call for worldwide cooperation in eliminating it. Although the two-hour course cannot replace the five-day ILO workshop, such a program would be useful in areas with environmental or occupational exposure to dust.

• Genotoxicity and cytotoxicity of multi-wall carbon nanotubes in cultured Chinese hamster lung cells in comparison with chrysotile A fibers. M. Asakura, T. Sasaki, T. Sugiyama, et al. 2010;52(3):155-66. PubMed · Publisher

  Abstract

  Objectives: The potential applications and industrial production of multi-wall carbon nanotubes (MWCNT) have raised serious concerns about their safety for human health and the environment. The present study was designed to examine the in vitro cytotoxicity and genotoxicity of MWCNT and UICC chrysotile A (chrysotile).

  Methods: Cytotoxicity using both colony formation and lactate dehydrogenase (LDH) assays and genotoxicity including chromosome aberration, micronucleus induction and hgprt mutagenicity were examined by exposing cultured Chinese hamster lung (CHL/IU) cells to MWCNT or chrysotile at different concentrations.

  Results: The in vitro cytotoxicity of MWCNT depended on the solvent used for suspension of MWCNT and ultrasonication duration of the MWCNT suspension. A combination of DMSO/culture medium and 3-minute ultrasonication resulted in a well-dispersed medium with dispersion and isolation of agglomerated MWCNT by ultrasonication which manifested the highest cytotoxicity. The cytotoxicity was more potent for chrysotile than MWCNT. The genotoxicity of MWCNT was characterized by the formation of polyploidy without structural chromosome aberration, and an increased number of bi- and multi-nucleated cells without micronucleus induction, as well as negative hgprt mutagenicity. Chrysotile exhibited essentially the same genotoxicity as MWCNT, except for marginal but significant induction of micronuclei. MWCNT and chrysotile were incompletely internalized in the cells and localized in the cytoplasm.

  Conclusions: MWCNT and chrysotile were cytotoxic and genotoxic in Chinese hamster lung cells, but might interact indirectly with DNA. The results suggest that both test substances interfere physically with biological processes during cytokinesis.

• Longitudinal changes in pulmonary function of asbestos workers. X. Wang, M. Wang, H. Qiu, et al. 2010;52(5):272-7. PubMed · Publisher

  Abstract

  Objective: To observe the longitudinal changes in pulmonary function associated with exposure to asbestos in a group of highly exposed workers.

  Methods: Pulmonary diffusing capacity (DLco) and spirometry of 243 Chinese asbestos workers were measured and remeasured after 5 and 10 yr. Their annual changes in relation to cumulative asbestos exposure and asbestosis were determined using multivariate analysis.

  Results: The greatest annual decline was observed in DLco, particularly in workers with asbestosis, followed by FVC and FEV(1). A greater decline in DLco accorded with a higher level of cumulative asbestos exposure. A similar trend was also seen in FVC, in which the highest exposure level was associated with 223 ml loss over each 5 yr period or 45 ml/yr.

  Conclusions: There were substantial declines in DLco and FVC over time in the asbestos workers, and a dose-response trend between asbestos exposure and accelerating functional loss.

2000s

• Railways and asbestos in Japan (1928-1987)--epidemiology of pleural plaques, malignancies and pneumoconioses-. Y. Hosoda, Y. Hiraga, S. Sasagawa. 2008;50(4):297-307. Review PubMed · Publisher

  Abstract

  Asbestos has been an indispensable insulating material for railway industries, especially steam locomotives (SLs). This review (1928-1987) consists of three parts. 1) Pleural plaques: Since the 1970s, pleural plaques have been regarded as evidence of past asbestos inhalation, and more recently recognized as a risk factor of asbestos-related malignancies. For diagnostic criteria on plain radiographs, the modified ILO 1980 International Classification of Radiographs of Pneumoconioses was used. Most cases had pleural plaques with normal lungs. Large plant workers showed a significantly higher rate of plaques than workers in smaller plants. Bilateral plaques were dominant followed by the left, then the right lung, and chest wall plaques were dominant over the diaphragm. The manifestation of pleural plaques was more correlated to years since the onset of the asbestos exposure than the sum of asbestos work years, although the result was not significant. The boilermen of railway ferry steamers had a significantly higher plaque rate than other seamen. CT studies on plaques started in 1978. 2) Asbestos-related malignancies: Five retrospective cohort studies 1960-1970 were made on primary lung cancer incidence and mortality among 350,000 active railway men with smoking information. The follow-up period was 20 yr at the longest. Almost all plant workers showed a tendency of higher incidence or mortality than the controls. Two cases of mesothelioma were reported in 1980. 3) Pneumoconioses: Most studies (1928-1975) had relatively low prevalence rates among SL-related workers.

• 24 years of pneumoconiosis mortality surveillance in Australia. D.R. Smith, P.A. Leggat. 2006;48(5):309-13. PubMed · Publisher

  Abstract

  Asbestosis, silicosis and Coal Worker's Pneumoconiosis (CWP) represent three of the most important occupationally-related dust diseases in Australia. To gain a clear picture of pneumoconiosis trends over time, a 24-yr retrospective analysis of national mortality data was performed for the period 1979 to 2002. Over 1,000 pneumoconiosis-related fatalities occurred during this time, 56% of which were caused by asbestosis, 38% by silicosis and 6% by CWP. Between 1979 and 1981, silicosis accounted for 60% of all pneumoconiosis-related fatalities in Australia, followed by asbestosis (31%). By 2002 however, asbestosis was causing 78% of all fatalities, while silicosis accounted for only 19%. Asbestos-related mortality increased three-fold between 1979 and 2002, with a clear excess risk demonstrated among males. On the other hand, mortality rates for silicosis and CWP declined significantly during the same time period. Overall, this study suggests that pneumoconiosis, particularly asbestosis, continues to be an important occupational disease in Australia. Although progress has been made in reducing deaths due to occupational silicosis and CWP, asbestosis rates continue to rise, reflecting the long latency between dust exposure and clinical disease. Countries which continue to use asbestos products in the workplace should note the tragic legacy of this material within contemporary Australia.

• Cancer incidence among Australian nuclear industry workers. R.R. Habib, S.M. Abdallah, M. Law, et al. 2006;48(5):358-65. PubMed · Publisher

  Abstract

  To assess whether workers at Lucas Heights Science and Technology Centre (LHSTC) had different levels of cancer incidence from the New South Wales (NSW) population in Australia. A retrospective cohort study was undertaken at LHSTC. Data on 7,076 workers employed between 1957-98 were abstracted from personnel, dosimetry, and medical files. An inception cohort was defined which included 4,523 workers in employment between 1972-96 to examine cancer incidence. Cancer registrations in the inception cohort were identified to 1996 through electronic linkage of records with the NSW and the Australian national registers of cancer incidence. All-cancer incidence in workers at LHSTC was 15% below the NSW rates [SIR=0.85; 95% CI=(0.75, 0.95)]. Of 37 specific cancers and groups of cancers examined, statistically significant excesses relative to NSW rates were observed only for pleural cancer incidence [SIR=17.71; 95%=(7.96, 39.43)], and for incidence of cancer of the small intestine [SIR=4.34; 95% CI=(1.40, 13.46)]. This study gives little evidence of an increased risk of cancers associated with radiation exposure in a cohort of nuclear workers in Australia. The observed increase in the risk of cancer of the pleura was probably due to unmeasured exposures, given the lack of an established association with radiation exposure, and the strong link to asbestos exposure. Findings for cancers of the small intestine were based on small numbers and were likely to be due to chance.

• The effect of lung burden on biopersistence and pulmonary effects in rats exposed to potassium octatitanate whiskers by intratracheal instillation. T. Oyabu, H. Yamato, A. Ogami, et al. 2006;48(1):44-8. PubMed · Publisher

  Abstract

  In our previous inhalation studies on health effects of the asbestos substitute, potassium octatitanate whiskers (POW), we showed that an excess amount of POW deposition in the rat lung increased biopersistence resulting in fibrotic changes. The critical deposition amount which induced the higher biopersistence was estimated to lie between 1.5 mg and 2.4 mg. In order to find the exact amount, the relationship between the lung POW burden and biopersistence was investigated by the intratracheal instillation method. The chemical formula of POW is K2Ti8O17 and the geometric mean fiber diameter (geometric standard deviation, GSD) and geometric mean fiber length (GSD) are 0.35 microm (1.6) and 4.4 microm (2.7), respectively. Rats were intratracheally instilled with 0.5 mg, 1.0 mg, 2.0 mg or 5.0 mg of POW and sacrificed at 1 day and 1, 3, 6 and 12 months after the instillation. The POW amount in each lung was chemically analyzed by ICP-AES after microwave digestion and the biological half time (BHT) of each POW dose was calculated. The BHTs of each group were 10, 15, 20 and 42 months for 0.5, 1.0, 2.0 and 5.0 mg of POW, respectively, and BHT showed a linear dose-dependent increase, but without a threshold within the range of 0.5 mg to 5.0 mg, which was recognized in our earlier inhalation studies. In the histopathological photograph just after the instillation, many macrophages, which had phagocytized many more fibers, existed around the bronchiole compared with the earlier inhalation study at almost the same deposited amount. The relationship between POW amount and biopersistence in this intratracheal instillation study was different from that of our previous inhalation studies, probably due to the unnatural method of the fiber introduction to the lung, which in turn led to a different fiber distribution. It is suggested that an intratracheal instillation study is not an appropriate method for estimating excess deposition amounts of POW and an inhalation study will be needed. However, this intratracheal instillation study clarified that the clearance of POW was delayed as compared with previous inhalation studies at similar deposition amounts and this result has importance for the hazard assessment of dusts in animal experiments.

• Emphysema findings associated with heavy asbestos-exposure in high resolution computed tomography of finnish construction workers. O. Huuskonen, L. Kivisaari, A. Zitting, et al. 2004;46(4):266-71. PubMed · Publisher

  Abstract

  Asbestos fibers are known to cause lung fibrosis, but their role in emphysema is unclear. We wanted to evaluate the relationship between asbestos exposure and emphysema by using high-resolution computed tomography (HRCT). Conventional and high resolution CT was performed on 600 smoking construction workers with an asbestos-related occupational disease. Emphysema subtypes (centrilobular, paraseptal, panlobular emphysema and bullae) were separately scored on a semiquantitative scale from 0 to 5, which scores were added up to yield the total emphysema score. Occupation, exposure duration, age, pack years and asbestosis diagnosis were analyzed in general linear models for possible associations with emphysema. The inter- (quadratic weighted kappa, kappa(qw)=0.46-0.72) and intraobserver (kappa(qw)=0.78-0.94) agreements for the subtype-scores and the reliability of the total score (Cronbach's alpha=0.87) were good. Insulators had a significantly higher paraseptal, panlobular and total score than the other occupational groups when adjusted for age and smoking. An asbestosis diagnosis was also a significant independent predictor of a higher total score. Emphysema was more common when workers had asbestosis or were heavily exposed to asbestos (insulators), but due to confounding factors the causative role of asbestos in emphysema needs further study.

• The effect of lung burden on biopersistence and pulmonary effects in rats exposed to potassium octatitanate whiskers by inhalation. T. Oyabu, H. Yamato, A. Ogami, et al. 2004;46(5):382-90. PubMed · Publisher

  Abstract

  The effect of lung burden on biopersistence and histopathological changes caused by potassium octatitanate whiskers (POW) which is one of the asbestos substitutes were investigated for 1-yr and 4-wk inhalation periods. In the 1-yr inhalation experiment, male Wistar rats were exposed to POW (TW) for 6 h/d, 5 d/wk under the same conditions as a previous study of POW (PT1, JFM fiber) which is made by different manufacturer. The exposure concentration was 1.9 +/- 0.7 mg/m(3) and the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) in the chamber were 1.6 microm and 2.9. Rats were sacrificed at 3 d and 1 yr after the inhalation experiment and TW deposits in the lungs were determined by ICP-AES. Lung burden at 3 d and 1 yr after the inhalation was 2.39 +/- 0.50 mg and 1.37 +/- 0.96 mg, respectively, the deposition fraction was 8.1% and biological half time (BHT) was 15 months. Aggregated dust cells and mild fibrotic changes around these dust cells were observed in the exposed rat lung. These results were almost the same as those obtained in the previous 1-yr PT1 study. In the 4-wk inhalation experiment, to investigate the effect of lung burden on biopersistence and histopathological change, male Wistar rats were exposed to PT1. The exposure concentration was 102 +/- 21 mg/m(3), MMAD (GSD), the geometiric mean length and diameter (GSD) of the PT1 in the chamber were 1.6 microm (3.0), 2.2 microm (1.8) and 0.33 microm (1.5), respectively. Rats were sacrificed at 3 d, 1 wk, and 1, 3, 6 and 12 months after the inhalation experiment. The lung burden of POW at 3 d after 4 wk inhalation was 1.49 +/- 0.19 mg, which was close to the estimated amount of overload. The BHT of the total mass (4.1 months) was not prolonged, but aggregated dust cells were observed in the subpleural region and around the bronchioles and mild fibrotic changes were observed only around the dust cells at one year after the 4-wk inhalation. It is considered that the excessive exposure which impairs the function of alveolar macrophage mediated clearance may cause the aggregation of dust cells and fibrotic changes.

• Gene expression of surfactant protein-A and thyroid transcription factor-1 in lungs of rats exposed to silicon-carbide whisker in vivo. Y. Morimoto, L. Ding, T. Oyabu, et al. 2003;45(5):307-12. PubMed · Publisher

  Abstract

  Intratracheal instillation studies have shown that exposure to silicon carbide whisker (SiCW), an asbestos substitute, produces pulmonary fibrotic changes, suggesting that SICW might have a fibrogenic potential. It is thought that surfactant protein is a good biomarker of lung injury and pulmonary fibrotic activity. In order to explore whether or not surfactant protein is associated with lung disorder through exposure to SiCW, we examined the expression of SP-A, SP-C and thyroid transcription factor-1 (TTF-1), a common transcription factor of SP-A and SP-C mRNA in lungs exposed to SiCW. Male Wistar rats were administered 2 mg or 10 mg of SiCW suspended in saline by a single intratracheal instillation, and were sacrificed at 3 d, 1 wk, 1 month, 3 months and 6 months after the intratracheal instillation. RNA was subsequently extracted from the lungs, and expression of SP-A, SP-C and TTF-1 mRNA from the lungs was observed by reverse transcription-polymerase chain reaction (RT-PCR). Exposure to 2 mg of SiCW showed a decrease in mRNA of SP-A and TTF-1 at 6 months, but exposure to 10 mg of SiCW showed decreased levels of SP-A and TTF-1 mRNA at 3 d and 6 months. On the other hand, 2 mg of SiCW increased the level of SP-C mRNA from 3 d to 3 months, and 10 mg of SiCW decreased the levels of SP-C mRNA in the rat lungs at 3 d, 1 month and 6 months. No clear tendency to the expression of SP-C was observed, but the patterns of expression of TTF-1 and SP-A were similar. These data suggest that SP-A and TTF-1 are associated with not only the acute phase but also the chronic phase in lungs exposed to SiCW.

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