DETECTION OF MUTAGENIC IMPURITIES IN CARCINOGENS AND NON-CARCINOGENS BY HIGH-PRESSURE LIQUID-CHROMATOGRAPHY AND SALMONELLA-MICROSOME TEST

Abstract

High-pressure liquid chromatography and the Salmonella/rat liver microsome mutagenicity test were used to look for mutagenic impurities in 11 carcinogens and noncarcinogens. Because of the million-fold range in mutagenic potency observed in the Salmonella test, even trace amounts of potent mutagenic impurities in a nonmutagenic compound could be detected. The mutagenicity of 7-hydroxy-2-acetylaminofluorene, a noncarcinogen in the standard animal carcinogenicity tests, is due to a small amount of impurity, which is probably the potent carcinogen 2-acetylaminofluorene. This is discussed in relation to the statistical limitations of animal carcinogenicity tests. The role of mutagenic impurities in assessing the mutagenicity of environmental (and industrial) chemicals with high-sensitivity mutagenicity assays, such as the Salmonella/microsome test was discussed.