What do animal cancer tests tell us about human cancer risk?: Overview of analyses of the carcinogenic potency database.

Many important issues in carcinogenesis can be addressed using our Carcinogenic Potency Database, which analyzes and standardizes the literature of chronic carcinogenicity tests in laboratory animals. This review is an update and overview of our analyses during the past 15 years, using the current database that includes results of 5152 experiments on 1298 chemicals. We address the following: 1. More than half the 1298 chemicals tested in long-term experiments have been evaluated as carcinogens. We describe this positivity rate for several subsets of the data (including naturally occurring and synthetic chemicals), and we hypothesize and important role in the interpretation of results for increased cell division due to administration of high doses. 2. Methodological issues in the interpretation of animal cancer tests: constraints on the estimation of carcinogenic potency and validity problems associated with using the limited data from bioassays to estimate human risk, reproducibility of results in carcinogenesis bioassays, comparison of lifetable and summary methods of analysis, and summarizing carcinogenic potency when multiple experiments on a chemical are positive. 3. Positivity is compared in bioassays for two closely related species, rats and mice, tested under similar experimental conditions. We assess what information such a comparison can provide about interspecies extrapolation. 4. Rodent carcinogens induce tumors in 35 different target organs. We describe the frequency of chemicals that induce tumors in rats or mice at each target site, and we compare target sites of mutagenic and nonmutagenic rodent carcinogens. 5. A broad perspective on evaluation of possible cancer hazards from rodent carcinogens is given, by ranking 74 human exposures (natural and synthetic) on the HERP indes.