Concordance of Rat- and Human-Based Risk Estimates for Particle-Related Lung Cancer

Abstract

In this study we use existing data in both rats and humans exposed to respirable, poorly soluble particles to compare the dose–response relationships for lung cancer. Exposure–response data for lung cancer were available in both species for crystalline silica and in rats for coal dust and titanium dioxide. Tumorigenic doses (TDs) associated with specified levels of excess risk (e.g. 1%) were computed, using multistage models in rats and relative rate models in humans. The rat-based and human-based TDs for crystalline silica are reasonably concordant (i.e. TD ratios near 1.0) for several dose metrics, including average internal dose in the lungs. The rat-based TDs associated with a 1% excess risk of lung cancer (TD 1 ) (extrapolated to humans, assuming a 45 yr working lifetime exposure) are point estimates from 0.007 to 0.24, 2 to 91 and 1.7 to 444 mg/m3, respectively, for crystalline silica, coal and titanium. The rat-based TD 1 values for silica, coal and titanium dioxide are consistent with the relative toxicity of these airborne particulates and with results from epidemiological studies. These findings provide some support for the continued use of risk assessment models based on rat bioassay data for particulates when human data are not available.