An association between mutagenicity of the Ara test of Salmonella typhimurium and carcinogenicity in rodents for 16 halogenated aliphatic hydrocarbons

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Abstract
Sixteen halogenated aliphatic hydrocarbons were assayed for genotoxicity using the Ara mutagenicity assay with Salmonella typhimurium. Seven substances (1,2-dibromo-3-chloro-propane, 1,2-dibromoethane, 1,2-dichloroethane, vinyl bromide, hexachloro-1, 3-butadiene, iodoform and vinilydene chloride) were mutagenic at non-lethal doses. Comparatively, nine compounds (chloroform, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2-trichloroethane, tetrachloro-ethylene, trichloroethylene, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrahloroethane and hexachloroethane) were non-mutagenic after being assayed both in the presence and absence of metabolic activation with a rat liver microsomal fraction (S9). All negative compounds (except hexachloro-ethane) gave a lethal response, which could be an indication that bacteria were adequately exposed. The concordance between mutagenicity in the Ara test and carcinogenicity in rodents for this group of halogenated hydrocarbons was (31%) significantly lower than the concordance (72%) previously found in the Ara test with respect to a wider range of chemical classes. This result is in agreement with data reported for other genotoxicity assays. The presence of non-genotoxic carcinogens versus genotoxic non-carcinogens is discussed as a possible explanation. Five positive compounds (1, 2-di-bromo-3-chloropropane, 1, 2-dibromoethane, 1, 2-dichloro-ethane, vinyl bromide and hexachloro-1, 3-butadiene) were analyzed for a quantitative relationship between carcinogenic potency in rats and the potency of response in the Ara mutagenicity test. This was possible because the Ara test, for volatile compounds (such as vinyl bromide), did not require the use of special vaporization techniques, which are difficult to evaluate quantitatively for mutagenic activity. A highly significant correlation was found between the mutagenic efficiencies of the five compounds in the Ara test and their carcinogenic potencies in rats. These results suggest that the Ara test might be capable of reflecting the relative potency of genotoxic animal carcinogens beyond the group of direct acting monofunctional alkylating compounds previously studied by our group.

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