Rat- and human-based risk estimates of lung cancer from occupational exposure to poorly-soluble particles: A quantitative evaluation

Abstract

In risk assessment there is a need for quantitative evaluation of the capability of animal models to predict disease risks in humans. In this paper, we compare the rat- and human-based excess risk estimates for lung cancer from working lifetime exposures to inhaled poorly-soluble particles. The particles evaluated include those for which long-term dose-response data are available in both species, i.e., coal dust, carbon black, titanium dioxide, silica, and diesel exhaust particulate. The excess risk estimates derived from the rat data were generally lower than those derived from the human studies, and none of the rat- and human-based risk estimates were significantly different (all p-values>0.05). Residual uncertainty in whether the rat-based risk estimates would over- or under-predict the true excess risks of lung cancer from inhaled poorly-soluble particles in humans is due in part to the low power of the available human studies, limited particle size exposure data for humans, and ambiguity about the best animal models and extrapolation methods. © 2009 IOP Publishing Ltd.