Case Study: Health Risks from Asbestos Exposures

Louis Anthony Cox
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Louis Anthony Cox: Cox Associates and University of Colorado

Chapter Chapter 5 in Quantitative Risk Analysis of Air Pollution Health Effects, 2021, pp 117-158 from Springer

Abstract: Abstract Can a single fiber of amphibole asbestos increase the risk of lung cancer or malignant mesothelioma (MM)? Traditional linear no-threshold (LNT) risk assessment assumptions imply that the answer is yes: there is no safe exposure level. This chapter draws on recent scientific progress in inflammation biology, especially elucidation of the activation thresholds for NLRP3 inflammasomes and resulting chronic inflammation as discussed in Chaps. 3 and 4 , to model dose-response relationships for malignant mesothelioma and lung cancer risks caused by asbestos exposures. Similar to the model for respirable crystalline silica in Chap. 4 , the modeling in this chapter integrates a physiologically based pharmacokinetics (PBPK) front end with inflammation-driven two-stage clonal expansion (I-TSCE) models of carcinogenesis to describe how exposure leads to chronic inflammation, which in turn promotes carcinogenesis. Together, the combined PBPK and I-TSCE modeling predict that there are practical thresholds for exposure concentration below which asbestos exposure does not cause chronic inflammation in less than a lifetime, and therefore does not increase chronic inflammation-dependent cancer risks. Quantitative examples using model parameter estimates drawn from the literature suggest that practical thresholds may be within about a factor of 2 of some past exposure levels for some workers. The I-TSCE modeling framework presented here explains some previous puzzling aspects of asbestos epidemiology, such as why age at first exposure is a better predictor of lifetime MM risk than exposure duration.

Date: 2021
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DOI: 10.1007/978-3-030-57358-4_5

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