Carcinogens dose-response characteristics

Overall, cancer risk assessment involves the four steps of hazard identification, dose-response, exposure assessment, and risk characterization. The dose-response curve established for cancer potency derivation for a chemical is based on evaluation of data on the carcinogenicity and dose-response characteristics of the chemical. The pharmacokinetics and mechanistic data evaluation (e.g., genotoxic or nongenotoxic) and a dose-response review of all adequate bioassays are conducted to determine, if target dose estimates or a dose-response model different from the default may be suggested. 

A crucial question for risk assessment is whether or not the dose-response characteristics for nongenotoxic carcinogens are different from those observed for genotoxic carcinogens, as has been inferred frequently (Ashby and Purchase 1992). Using tumor data from chronic feeding studies with more than 1500 mice at six... 

Krewski and Van Ryzin (40) examined the extrapolation characteristics of six of the more cbmmonly used dose-response models. They applied these models to 20 sets of toxic response data that were taken from the Report of the Scientific Committee of the Food Safety Council (15,16). The toxic responses were both carcinogenic and noncarcTnogenic in nature. Of the 19 data sets having... 

Several important characteristics of chemicals which induce the proliferation of peroxisomes in animals is that they display clear thresholds and species-dependency in the induction of proliferation (see review by Stott (73) and references contained therein). In rodent bioassays, no tumorigenic response is observed at nonproliferating dose levels and higher mammalian species are quite refractory to the proliferative effects of these chemicals. Indeed primates, including humans, appear to be so refractory to the chemically-induced proliferation of peroxisomes that this response, and any carcinogenic hazard associated with it, is generally considered to represent a rodent specific phenomenon. 

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