Summary report on the evaluation of short-term tests for carcinogens: collaborative study on in vitro tests

Abstract

Summarizes the methodology and findings of a large international collaborative study designed to establish the most useful short-term in vivo tests for confirming the mammalian genotoxicity and carcinogenic potential of chemicals. The study, which involved the collaboration of ninety-seven investigators from sixteen countries, evaluated some fifty different in vivo techniques. The objective was to generate a comprehensive data profile from a broad range of short-term test procedures as a means of understanding how various genetic endpoints in key target tissues respond to chemicals defined as genotoxic in vitro. The study also aimed to dispel some of the controversy and confusion regarding precisely which tests and test batteries are needed to produce a reliable and sensitive assessment of the carcinogenic potential of chemicals in mammals, including humans. The design of the study, which involved numerous tests replicated in a number of different laboratories, allows unique insight into the utility, reproducibility, and reliability as well as the accuracy of each test included in the study. The report also constructs a profile, in qualitative terms, of the genotoxic activity of the test chemicals in the whole animal, followed by a second profile of quantitative differences in response according to sex, species, route of exposure, and technical variations. The report concludes with a detailed assessment of the most effective in vivo assays in relation to their performance. The concluding section also identifies assays that are not appropriate for routine testing of chemicals, as well as tests that performed well but are not widely used or available, or that cannot be regarded as practical because of their technical complexity or the length of time required to produce results