A review and critique of U.S. EPA's risk assessments for asbestos

Our plain-English summary of A review and critique of U.S. EPA's risk assessments for asbestos, by S.H. Moolgavkar, E.L. Anderson, E.T. Chang, et al (Critical Reviews in Toxicology, 2014).

The study

• Authors: S.H. Moolgavkar, E.L. Anderson, E.T. Chang, E.C. Lau, P. Turnham, D.G. Hoel
• Journal: Critical Reviews in Toxicology
• Published: 2014;44(6):499-522
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

U.S. Environmental Protection Agency (EPA) recently conducted a risk assessment for exposure to Libby amphibole asbestos that is precedent-setting for two reasons. First, the Agency has not previously conducted a risk assessment for a specific type of asbestos fiber. Second, the risk assessment includes not only an inhalation unit risk (IUR) for the cancer endpoints, but also a reference concentration (RfC) for nonmalignant disease. In this paper, we review the procedures used by the Agency for both cancer and nonmalignant disease and discuss the strengths and limitations of these procedures. The estimate of the RfC uses the benchmark dose method applied to pleural plaques in a small subcohort of vermiculite workers in Marysville, Ohio. We show that these data are too sparse to inform the exposure-response relationship in the low-exposure region critical for estimation of an RfC, and that different models with very different exposure-response shapes fit the data equally well. Furthermore, pleural plaques do not represent a disease condition and do not appear to meet the EPA's definition of an adverse condition. The estimation of the IUR for cancer is based on a subcohort of Libby miners, discarding the vast majority of lung cancers and mesotheliomas in the entire cohort and ignoring important time-related factors in exposure and risk, including effect modification by age. We propose that an IUR based on an endpoint that combines lung cancer, mesothelioma, and nonmalignant respiratory disease (NMRD) in this cohort would protect against both malignant and nonmalignant disease. However, the IUR should be based on the entire cohort of Libby miners, and the analysis should properly account for temporal factors. We illustrate our discussion with our own independent analyses of the data used by the Agency.

In plain English

This was a review and critique of the U.S. Environmental Protection Agency's (EPA) 2011 draft risk assessment for Libby amphibole asbestos, a mixture of tremolite, winchite and richterite, with the authors' own reanalyses of EPA's data. EPA based its non-cancer reference concentration (RfC) on pleural plaques in 118 Marysville, Ohio, vermiculite workers with 12 plaque cases, drawn from 280 workers with 68 cases. EPA's own models, which fit these data about equally well, gave benchmark cumulative exposure estimates from 0.1544 to 1.5245 f/cc-years. One alternative model gave an RfC of 0.0004, 20 times EPA's 0.00002 f/cc. Among all 280 workers, age, not smoking or body mass index, was an important confounder. EPA's cancer estimate used a Libby miners subcohort holding 32 of 111 lung cancer deaths and 7 of 19 mesotheliomas. The authors' Libby analysis found the lung cancer relative risk clearly changed with age. The authors concluded pleural plaques do not appear to meet EPA's definition of an adverse condition. They proposed one estimate combining lung cancer, mesothelioma and nonmalignant respiratory disease in the whole Libby cohort. W. R. Grace & Company funded the work.

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 critique of EPA's draft risk assessment for Libby amphibole asbestos, including the authors' own independent reanalyses of the data EPA used
• Who was studied: Data sets used by EPA. For pleural plaques: the Rohs cohort of Marysville, Ohio, vermiculite workers (280 subjects, 68 with pleural plaques) and EPA's restricted subset (118 individuals, 12 with pleural plaques). For cancer: the Libby miners cohort (1,871 individuals, 111 lung cancer deaths), of which EPA used a subcohort of 880.
• Exposure: Libby amphibole asbestos (LAA), described as a mixture of tremolite, winchite and richterite, measured as cumulative exposure (f/cc-y) or as concentration
• Main results:
  • In EPA's restricted Rohs subcohort, only two pleural plaques occurred in the lower five deciles of cumulative exposure.
  • In the restricted Rohs subcohort, 4 of the 12 pleural plaques occurred in the highest decile of exposure.
  • The models EPA fitted to the restricted Rohs subcohort fit the data about equally well, in the authors' assessment.
  • These EPA models gave benchmark cumulative exposures (BMCEs) ranging from 0.1544 to 1.5245 f/cc-years. The article prints no unit beside this range; the unit is taken from the article's statement of EPA's chosen BMCE in f/cc-y. This range comes from EPA's model fits as reported and critiqued by the authors, not from the authors' own reanalyses.
  • EPA's chosen model gave a BMCE of 0.2642 f/cc-y and a lower confidence bound (BMCEL) of 0.1177 f/cc-y.
  • EPA proposed an RfC of 0.00002 f/cc.
  • In the authors' reanalysis, a logistic regression model using average concentration (BMC 0.06 f/cc, BMCL 0.04 f/cc) led to an RfC of 0.0004, 20 times EPA's RfC.
  • Using linear extrapolation from EPA's chosen model, the authors calculated an added pleural plaque risk of 5 in 10,000 from lifetime exposure at the proposed RfC.
  • In the full Rohs cohort of 280, neither cigarette smoking nor body mass index was an important confounder.
  • In the full Rohs cohort, age was an important confounder of the association between LAA and pleural plaques.
  • When age was included in the full Rohs cohort analysis, the cumulative exposure coefficient was attenuated by about a third.
  • In the full Rohs cohort, the authors found no evidence of an association between LAA and pleural plaques for exposure durations shorter than about 25 years.
  • EPA's Libby subcohort reduced the cohort from 1,871 to 880 individuals and reduced lung cancer deaths from 111 to 32.
  • Mesothelioma deaths numbered 19 in the full Libby cohort and 7 in EPA's subcohort.
  • In the authors' analysis of the Sullivan Libby cohort (95 lung cancers, follow-up through 2002), the lung cancer relative risk showed clear effect modification by age.
  • Declaration of interest: the work was financially supported by W. R. Grace & Company, and some authors are consultants to the company.
• The authors' conclusion: The authors concluded that pleural plaques do not appear to meet EPA's definition of an adverse condition and that the restricted Rohs subcohort is far too small for reliable estimation of an RfC. They proposed an inhalation unit risk based on lung cancer, mesothelioma and nonmalignant respiratory disease in the entire Libby cohort.
• Limitations the authors state:
  • Only yes/no smoking information was available in the Rohs data sets.
  • The full Rohs cohort is still a small data set.
  • The lack of association at exposure durations under 25 years may reflect a lack of statistical power.
  • The authors did not have access to the full Libby data set analyzed by Larson et al. (2010a).

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Libby vermiculite mine, Montana

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Talc and vermiculite.

Medical terms in this study, explained in our Lexicon: Libby amphiboles, Pleural Plaques, vermiculite, Lung Cancer, Mesothelioma.

Related studies

• Risk assessment using exposure intensity: an application to vermiculite mining — P.M. Vacek, J.C. McDonald (1991)
• An air quality data analysis system for interrelating effects, standards, and needed source reductions: Part 13--Applying the EPA Proposed Guidelines for Carcinogen Risk Assessment to a set of asbestos lung cancer mortality data — R.I. Larsen (2003)
• Electricians' chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer — J.E. Goodman, M.K. Peterson, et al. (2014)
• Comparing epidemiologic studies of ingested asbestos for use in risk assessment — L.S. Erdreich (1983)
• Potency factors for risk assessment at Libby, Montana — S.H. Moolgavkar, J. Turim, et al. (2010)
• Low levels of exposure to libby amphibole asbestos and localized pleural thickening — K.Y. Christensen, T.F. Bateson, et al. (2013)

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