Nonlinear Dose-Time-Response Risk Models for Protecting Worker Health

Why have occupational safety regulations in the United States not been more successful in protecting worker health from mesothelioma risks, while apparently succeeding relatively well in reducing silicosis risks? This chapter seeks to apply insights from the simulation models developed in Chaps. 4 and 5 to address this important practical question and to suggest possible directions for revising regulations of occupational exposures to make them more causally effective in protecting worker health. It is less technical than Chaps. 4 and 5 , however. The main goal of this chapter is not to develop, but to apply, the pharmacokinetic (PBPK) models from Chaps. 4 and 5 to perform computational experiments illuminating how different time courses of exposure with the same time-weighted average (TWA) concentration affect internal doses in target tissues (lung for RCS and mesothelium for asbestos). Key conclusions are that (1) For RCS, but not asbestos, limiting average (TWA) exposure concentrations also tightly constrains internal doses and ability to trigger chronic inflammation and resulting increases in disease risks; (2) For asbestos, excursions (i.e., spikes in concentrations) and especially the times between them are crucial drivers of internal doses and time until chronic inflammation; and hence (3) These dynamic aspects of exposure, which are not addressed by current occupational safety regulations, should be constrained to better protect worker health. Adjusting permissible average exposure concentration limits (PELs) and daily excursion limits (ELs) is predicted to have little impact on reducing mesothelioma risks, but increasing the number of days between successive excursions is predicted to be relatively effective in reducing worker risks, even if it has little or no impact on TWA average concentrations.