Identification of mammary carcinogens in rodent bioassays

Results from chemical carcinogenesis studies in rodents are useful to identify substances in our environment that may contribute to cancer development. The National Toxicology Program (NTP) was established in 1978 to coordinate research and testing of potential human carcinogens and to publish the Report on Carcinogens, which lists human carcinogens. The results for over 500 chemicals tested in the NTP 2-year bioassays have been published in Technical Reports and include data for chemical, agent, or complex mixture exposures. The bioassays have identified 42 chemicals that induce tumors in the rodent mammary gland. The physical and chemical characteristics of the carcinogens vary, but epoxides (including chemicals metabolized to epoxides) and nitro-containing compounds are well represented. The 9th Report on Carcinogens, issued in 2000, lists 21 of the 42 chemicals as human carcinogens including benzene, ethylene oxide, 1,3-butadiene, isoprene, chloroprene, C.I. basic red 9, and C.I. acid red 114. Ethylene oxide was associated with increased breast cancer risk in an epidemiologic study, whereas other listed chemicals, for which human data are available, display different target organ specificity. Bioassays other than those conducted by the NTP also provide information about rodent mammary gland carcinogens. Several carcinogen exposures are associated with breast tumor induction in both humans and rodents including radiation, diethylstilbestrol, and estrogens. These studies demonstrate that route, timing and frequency of exposure, and genetic factors contribute to the overall susceptibility to breast cancer development. More information is needed on the effects of chemicals to which humans are exposed and the manner by which they influence breast cancer risks.