The quantitative relationship between exposure to crystalline silica and development of silicosis is uncertain despite a number of studies. The uncertainty is due to the following reasons: (a) exposure reconstructions are typically based on sparse data with significant uncertainty; (b) dose reconstructions that obtain the cumulative lung burden of the worker, do not account for simultaneous exposures to less toxic dusts, categorized as particles not otherwise classified (PNOC). The purpose of this study is to obtain the quantitative dose-response relationship between crystalline silica and silicosis in a manner that addresses the above three issues. The North Carolina Dusty Trades program, provides a large data set of human exposures to silica and PNOC and silicosis cases from 1935-1980 for this purpose. A novel Bayesian methodology that synthesizes expert judgment, exposure models, and historical measurements will be used for exposure reconstruction. Pharmacokinetic modeling will be used to estimate the cumulative lung does of silica and PNOC, and PNOC, and the time to macrophage overload in this mixed exposure scenario. A case-control study will be conducted to compare silicotics and disease free referents and test the following hypotheses: (1) A cumulative exposure metric, which includes both silica and PNOC, is more related to the development of silicosis than cumulative silica exposure alone, (2) The time to macrophage overload is shorter among cases than non-cases employed in the dusty trades, (3) The time to macrophage overload, due to exposures to mixtures of silica and PNOC, is related to the time from first exposure to disease among silicosis cases.
