Lack of concordance of the Salmonella/microsome assay with the mouse dermal carcinogenesis bioassay for complex petroleum hydrocarbon mixtures

• Published in: Fundamental and applied toxicology 1985-01, Vol.5 (2), p.382-390
• Main Authors: Cragg, Steven T., Conaway, C.Clifford, MacGregor, Judith A.
• Format: Article
• Language: English
• Subjects: Animals; Dimethyl Sulfoxide - toxicity; Hydrocarbons - toxicity; Mice; Mice, Inbred C3H; Microsomes - metabolism; Mutagenicity Tests; Mutagens; Petroleum - toxicity; Rats; Salmonella typhimurium; Salmonella typhimurium - genetics; Skin Neoplasms - chemically induced
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1016/0272-0590(85)90086-7

Typical petroleum hydrocarbon mixtures were tested directly, without extraction, in the Salmonella/microsome mutagenesis assay in order to determine if the assay would be useful to predict their carcinogenic activity. The carcinogenic activity of each sample had been previously characterized in the in vivo mouse dermal carcinogenesis bioassay. The series of samples evaluated offered several advantages. They spanned a wide boiling point range, were well characterized chemically, had been tested for carcinogenic activity in a single laboratory, and varied in potency in vivo from inactive to highly active. Mutagenicity testing was performed in several well-established contract laboratories that routinely perform the assay. These laboratories were the main contracting laboratories for these assays at the time and had previously tested petroleum samples for clients. Initially, the first laboratory tested 13 samples in five strains of Salmonella typhimurium with and without rat liver S-9 (Arochlor 1254 induced), utilizing both plate and suspension techniques. None of the 13 samples exhibited a mutagenic response, even though 9 of the 13 were slightly to highly dermally carcinogenic in mice. Because of the unexpected results, it was decided to repeat the mutagenicity assays in two other laboratories. Six of the thirteen samples were selected, ranging in carcinogenic potency from negative to highly active. Again, none were mutagenic in the second contract laboratory. In a third facility, only one sample of the six exhibited a definite mutagenic response. However, the response was observed with a sample having only weak carcinogenic activity and, unusual for petroleum hydrocarbons, occurred without activation. When this sample was recoded and retested in the same laboratory, negative results were obtained. The results from this multiple laboratory study clearly indicate that the methods employed routinely to perform the Salmonella/microsome assay are not useful to predict the dermal carcinogenic activity of typical complex petroleum mixtures. Various explanations for these results and some further experimental approaches are discussed.