Development of a Short-Term Testing Matrix for Estimating Relative Carcinogenic Risk

Abstract

A variety of problems in environmental carcinogenesis, especially those revolving around questions of human exposure to complex mixtures cannot be addressed properly in long-term animal studies. Yet the primary concerns involved with these complex mixtures are those relating to chronic exposure. Considerable progress has been made in describing some of the early events associated with chemical carcinogenesis. It is suggested in the present paper that a collection of shorter-term testing procedures that take advantage of benign lesions could be used to predict relative carcinogenic potency of individual chemicals or complex mixtures if properly developed and validated. Although benign, it is hypothesized that these lesions are sufficiently well related to the development of the malignant state so as to be predictive within the context of particular environmental problems. Because these test systems are potentially selective in their responses to chemical carcinogens it is suggested that a matrix involving two or more systems would be required to adequately estimate relative carcinogenic risk. The bioassays of the Carcinogenesis Testing Matrix are (I) mouse skin initiation/promotion, (2) Strain A mouse adenoma, (3) rat liver foci, (4) cell transformation, and (5) in vivo sister chromatid exchange.