Mutagenicity ofN‐nitroso derivatives of carbofuran and its toxic metabolites

Abstract
Carbofuran (CF), an insecticide and nematocide, is metabolically oxidized to two less toxic forms, 3‐hydroxycarbofuran and 3‐ketocarbofuran. The N‐nitroso derivatives of carbofuran and its metabolites were synthesized by reaction with nitrite under acidic conditions. Products of the reaction were obtained by extraction, identified by thin‐layer chromatography, and purified by silica gel column chromatography. All three nitroso derivatives reacted positively with Gries reagent and gave characteristic triplet absorption spectra (387, 402, and 422 nm). Structural confirmation was by nuclear magnetic resonance and mass spectroscopy. Mutagenicity was determined by the Ames assay method with Salmonella typhimurium strains TA98 and TA100. The nitroso derivatives of all three compounds responded similarly, giving a mutation ratio of 45 at 5 μg per plate on TA100. In addition, all three produced chromosome aberrations in Chinese hamster ovary (CHO) cells. Only two of the three (nitroso‐carbofuran and 3‐hydroxynitrosocarbofuran) were also capable of inducing large numbers of sister chromatid exchanges in the same cells. Observed variations in maximum mutagenicity in the Ames test and the ability to induce sister chromatid exchanges in CHO cells arc consistent with the stability of the compounds in aqueous solution.

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