An evaluation of reported no-effect chrysotile asbestos exposures for lung cancer and mesothelioma

Our plain-English summary of An evaluation of reported no-effect chrysotile asbestos exposures for lung cancer and mesothelioma, by J.S. Pierce, M.A. McKinley, D.J. Paustenbach, et al (Critical Reviews in Toxicology, 2008).

The study

• Authors: J.S. Pierce, M.A. McKinley, D.J. Paustenbach, B.L. Finley
• Journal: Critical Reviews in Toxicology
• Published: 2008;38(3):191-214
• Type of article: Review
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Numerous investigators have suggested that there is likely to be a cumulative chrysotile exposure below which there is negligible risk of asbestos-related diseases. However, to date, little research has been conducted to identify an actual "no-effect" exposure level for chrysotile-related lung cancer and mesothelioma. The purpose of this analysis is to summarize and present all of the cumulative exposure-response data reported for predominantly chrysotile-exposed cohorts in the published literature. Criteria for consideration in this analysis included stratification of relative risk or mortality ratio estimates by cumulative chrysotile exposure. Over 350 studies were initially evaluated and subsequently excluded from the analysis due primarily to lack of cumulative exposure information, lack of information on fiber type, and/or evidence of significant exposures to amphiboles. Fourteen studies meeting the inclusion criteria were found where lung cancer risk was stratified by cumulative chrysotile exposure; four such studies were found for mesothelioma. All of the studies involved cohorts exposed to high levels of chrysotile in mining or manufacturing settings. The preponderance of the cumulative "no-effects" exposure levels for lung cancer and mesothelioma fall in a range of approximately 25-1,000 fibers per cubic centimeter per year (f/cc-yr) and 15-500 f/cc-yr, respectively, and a majority of the studies did not report an increased risk at the highest estimated exposure. Sources of uncertainty in these values include errors in the cumulative exposure estimates, conversion of dust counts to fiber data, and use of national age-adjusted mortality rates. Numerous potential biases also exist. For example, smoking was rarely controlled for and amphibole exposure did in fact occur in a majority of the studies, which would bias many of the reported "no-effect" exposure levels towards lower values. However, many of the studies likely lack sufficient power (e.g., due to small cohort size) to assess whether there could have been a significant increase in risk at the reported no-observed-adverse-effects level (NOAEL); additional statistical analyses are required to address this source of bias and the attendant influence on these values. The chrysotile NOAELs appear to be consistent with exposure-response information for certain cohorts with well-established industrial hygiene and epidemiology data. Specifically, the range of chrysotile NOAELs were found to be consistently higher than upper-bound cumulative chrysotile exposure estimates that have been published for pre-1980s automobile mechanics (e.g., 95th percentile of 2.0 f/ cc-yr), an occupation that historically worked with chrysotile-containing friction products yet has been shown to have no increased risk of asbestos-related diseases. While the debate regarding chrysotile as a risk factor for mesothelioma will likely continue for some time, future research into nonlinear, threshold cancer risk models for chrysotile-related respiratory diseases appears to be warranted.

In plain English

This article was a review of published studies of workers exposed mainly to chrysotile asbestos. For each study, the authors looked for the highest cumulative exposure at which no statistically significant increase in lung cancer or mesothelioma was reported, which they called a no-observed-adverse-effect level (NOAEL). Over 350 studies were evaluated and excluded. The authors took 14 lung cancer NOAELs from 12 studies and found four cohorts in which pleural mesothelioma risk was broken down by exposure. Lung cancer NOAELs ranged from 1.4 to 2.7 f/cc-yr among South Carolina textile workers to 1600 to 3200 f/cc-yr in a Belgian cement factory. Mesothelioma NOAELs ranged from under 15 f/cc-yr among Swedish cement workers to 800 to 1599 f/cc-yr. Most values fell near 25 to 1000 f/cc-yr for lung cancer and 15 to 500 f/cc-yr for mesothelioma. The authors compared these levels with earlier estimates for 1970s vehicle mechanics and concluded that low chrysotile exposures like mechanics' are unlikely to cause mesothelioma. They cautioned that the levels are not proven thresholds. Smoking was rarely adjusted for, some amphibole exposure likely occurred in every cohort, and many studies may have lacked statistical power.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review and summary of published cohort studies, extracting from each the highest cumulative exposure group with no statistically significant increase in risk (NOAEL)
• Who was studied: Published occupational cohorts of asbestos miners and millers and of workers making cement, friction and textile products (Belgium, United Kingdom, Pennsylvania, Connecticut, New Orleans, Sweden, Austria, Italy, Quebec, South Carolina). There were 14 lung cancer NOAELs from 12 studies and four cohorts with stratified pleural mesothelioma risk.
• Exposure: Cumulative exposure to predominantly chrysotile asbestos, in f/cc-yr. Included cohorts had less than 10% of potential asbestos exposure involving amphiboles.
• Main results:
  • Over 350 studies were evaluated and excluded from the analysis.
  • Most lung cancer studies found no increased risk even at their highest exposure. In those studies, NOAELs ranged from more than 25 f/cc-yr (Austrian cement workers) to 1600 to 3200 f/cc-yr (Belgian cement workers).
  • In lung cancer studies that did report increased risk at higher exposures, NOAELs ranged from 1.4 to 2.7 f/cc-yr (South Carolina textile workers) to 314 to 942 f/cc-yr (Quebec Thetford Mines workers).
  • The mesothelioma NOAELs were:
• more than 400 f/cc-yr (Italian miners)
• 112 f/cc-yr or more (Connecticut friction workers)
• 800 to 1599 f/cc-yr (Belgian cement workers)
• less than 15 f/cc-yr (Swedish cement workers)
  • In the Swedish cement worker study, pleural mesothelioma risk was significantly increased in the two highest exposure groups:
• 15 to 39 f/cc-yr: relative risk 21.2 (95% CI 2.5 to 178)
• 40 f/cc-yr or more: relative risk 22.8 (95% CI 2.4 to 212)
  • Most NOAELs fell at approximately 25 to 1000 f/cc-yr for lung cancer and 15 to 500 f/cc-yr for mesothelioma.
  • An earlier study (Finley et al. 2007) estimated 95th and 99th percentile cumulative exposures of 2.0 and 5.7 f/cc-yr for 1970s vehicle mechanics. All mesothelioma NOAELs were well above these figures. All lung cancer NOAELs except the South Carolina textile study's were far above them.
• The authors' conclusion: The authors concluded that the findings seem to indicate that low occupational chrysotile exposures, such as those historically experienced by vehicle mechanics, are unlikely to cause mesothelioma. They said the analysis cannot directly answer whether chrysotile is a risk factor for mesothelioma under any circumstances.
• Limitations the authors state:
  • The NOAELs cannot be treated as true thresholds without further statistical analysis.
  • Lack of statistical power could make reported NOAELs artificially high. For example, the South Carolina textile cohort had only 29.8% power to detect an SMR of 2.0 at its NOAEL.
  • Only 2 of the 11 lung cancer cohorts reported smoking-adjusted risk estimates.
  • Amphibole exposure (amosite and crocidolite) likely occurred to some degree in all cohorts.
  • The accuracy of the original studies' exposure estimates could not be evaluated.
  • No universal factor exists for converting older dust counts to fiber counts.
  • Many studies allowed insufficient latency (time since first exposure).
  • The mesothelioma cohorts had very few cases.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chrysotile, Asbestos Exposure, Lung Cancer, Mesothelioma, Cumulative Exposure, Relative Risk, Amphibole Group, Fibers per Cubic Centimeter (f/cc).

Related studies

• An updated evaluation of reported no-observed adverse effect levels for chrysotile asbestos for lung cancer and mesothelioma — J.S. Pierce, P.S. Ruestow, et al. (2016)
• Evaluation of tremolite asbestos exposures associated with the use of commercial products — B.L. Finley, J.S. Pierce, et al. (2012)
• Exposures from chrysotile-containing joint compound: evaluation of new model relating respirable dust to fiber concentrations — G.P. Brorby, P.J. Sheehan, et al. (2013)
• Malignant pleural mesothelioma in US automotive mechanics: reported vs expected number of cases from 1975 to 2007 — B.L. Finley, J.S. Pierce, et al. (2012)
• Evaluation of take-home exposure and risk associated with the handling of clothing contaminated with chrysotile asbestos — J. Sahmel, C.A. Barlow, et al. (2014)
• Comparative Risks of Cancer from Drywall Finishing Based on Stochastic Modeling of Cumulative Exposures to Respirable Dusts and Chrysotile Asbestos Fibers — F.W. Boelter, Y. Xia, et al. (2015)

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