Lung Tumor Risk Estimates from Rat Studies with Not Specifically Toxic Granular Dusts

摘要

Since 1985 several carcinogenicity studies have been published about lung tumors in rats after exposure to respirable granular biodurable particles without known significant specific toxicity (abbreviation of this complex definition by the three letters GBP to substitute the former term inert dusts). During this time, the relevance of the carcinogenicity of GBP in rats was questioned, for example, because no lung tumors from GBP were found in hamsters and carcinogenicity in mice was questionable. However, the carcinogenesis and the tumor risk from quartz appear similar in men and rats, and the effects of GBP in rats appear not to differ, on principle, from that of quartz, but at a much higher dose level. We calculated the excess risk (ER) of GBP in rats from the final results of an instillation study with 16 GBP types in connection with results of inhalation experiments with carbon black, titanium dioxide, and diesel particles. Retained particle volume together with some indicator of particle size was identified as the best suitable dose metric and the dose-response relationships were analyzed on the basis of the multistage model. By relating the results to the available dose–response slopes after inhalation, ER for workplace-like exposure were calculated for three particle size classes and an exposure to 0.3 mg/m3 (density 2– 2.5 g/mL); mean diameter 1.8-4 μm (GBP-fine-large): ER 0.1%; 0.09– 0.2 (GBP-fine-small): ER 0.2%; 0.01-0.03 (GBP-ultra-fine): ER 0.5%.