Detection of mutagenic impurities in carcinogens and noncarcinogens by high-pressure liquid chromatography and the Salmonella/microsome test.

Abstract

We have used high-pressure liquid chromatography and the Salmonella/microsome mutagenicity test 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 shown to be 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. We also discuss the role of mitogenic impurities in assessing the mutagenicity of environmental (and industrial) chemicals with high-sensitivity mutagenicity assays, such as the Salmonella/microsome test.