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In vitro and short-term in vivo test systems for identifying chemicals with carcinogenic potential are described. Unlike other toxicity endpoints typically measured, cancer is the cumulative effect of a series of molecular, cellular, and tissue changes proceeding sequentially. Therefore, no single endpoint test system would be expected to accurately identify carcinogens and discriminate them from noncarcinogens, so that the only definitive test for carcinogenesis is a chronic animal test. The in vitro test systems currently used do not measure the induction of cancer, but mutation or genetic damage which is an initial step in the development of a cancer. However, a significant proportion of chemical carcinogens are not mutagenic and therefore not detected by the current genetic toxicity tests. For this reason, genetic toxicity tests are considered to be predictive for the effect because they do not measure cancer, per se, or all the events leading to the tumor. These genetic toxicity tests are not predictive of noncarcinogenicity because of the high proportion of carcinogens that are negative. Because of the central role carcinogenicity testing plays in the regulation of chemicals, efforts are underway to develop tests, or test combinations, that will be more predictive of both carcinogenicity and noncarcinogenicity.

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