In vitro testing for carcinogens and mutagens.

A large number of in vitro assays for chemical carcinogenicity and mutagenicity have been developed. They have been validated to various extents with the use of known carcinogens and noncarcinogens. When applied to chemicals of unknown carcinogenicity, they must be used in a battery or a tiered testing protocol. This is necessary since false negatives may occur with any one assay. The size of the battery should depend upon the potential risk to humans. A chemical with high human exposure (e.g., food additives) should be tested with a larger number of assays than one with more limited human exposure. The tests should complement one another and detect different events. Thus bacterial or mammalian mutation, cell transformation, DNA repair and chromosome assays should all be included in a test battery. Results form in vitro assay can be utilized to determine whether the chemical should also be tested in an animal bioassay. While negative results in all tests may indicate low risk, a chemical with widespread human exposure may still be worth evaluating in a long-term animal bioassay. It is impossible to prove a chemical safe and without risk. Short-term assays do, however, provide a means for quickly obtaining reasonable information about the genotoxic potential of large numbers of chemicals.