INTERPRETATION OF BIOASSAY RESULTS

SPECIES, SEX, AND TUMOR-SITE SPECIFIC CARCINOGENIC EFFECTS IN LONG-TERM STUDIES IN RATS AND MICE

Abstract

Correlation among species, sex, and tumor-site of neoplastic responses in 25 chemicals tested for carcinogenicity at the An-Pyo Center in 1981-1993 were evaluated. Of the 25 chemicals tested in rats and mice, 44 percent (11 of 25) were positive in at least one species and 56 percent (14 of 25) were negativein both rats and mice. Rats and mice exhibited a similar sensitivity to carcinogens as evidenced by 8 positive studies in rats and 9 positive studies in mice for a total of 17 positive studies. Three of the 25 chemicals evaluated were genotoxic and all tested positive in the carcinogenic bioassays in all groups and in both species and sexes. In addition, target tissues were similar between males and females. However, species specific or sex-related responses were evident at different dose levels with the non-genotoxic compounds tested.
Compilation ofhistorical tumor development data has revealed biological mechanisms whereby three classes of compounds produce characteristic positive results in rodent bioassays. Criteria for defining genotoxic, non-genotoxic and promotor/pseudo-carcinogens are presented and discussed.
Results of current bioassays together with mechanistic and refined, short-term studies may be evaluated collectively to aidin interpretation of results and in the mechanistic identification of these three classes of compounds.