IN-VITRO INVESTIGATION OF TOXAPHENE GENOTOXICITY IN SALMONELLA-TYPHIMURIUM AND CHINESE-HAMSTER V79 LUNG FIBROBLASTS

The polychlorinated pesticide toxaphene has been identified as a persi stent environmental contaminant and is of particular concern in the Gr eat Lakes and Arctic regions of Canada. Inconsistencies in published i n vitro genotoxicology studies have hindered risk assessments of toxap hene exposure. When toxaphene mutagenicity was re-evaluated in the Ame s Salmonella/microsome assay at 10-10,000 mu g/plate, a dose-dependent increase in His revertants occurred in all five strains of S. typhimu rium tested (TA97, TA98, TA100, TA102 and TA104) with higher mutation frequencies observed in the absence of S9 metabolic activation. Howeve r, the mutagenic potential of toxaphene was relatively low with concen trations greater than 500 mu g/plate required to induce mutation. Toxa phene genotoxicity was also examined in a mammalian system using Chine se hamster V79 lung fibroblasts with metabolic activation provided by human HepG2 hepatoma cells. Genotoxicity of 1-10 mu g/ml toxaphene was examined by measuring the frequency of sister chromatid exchange (SCE ) and mutation induction at the hypoxanthine guanine phosphoribosyl tr ansferase (HGPRT) gene locus. Although small increases in SCE were obs erved at toxic concentrations of toxaphene approaching the LD50 (10 mu g/ml), they were not found to be statistically significant relative t o control. Toxaphene was also unable to induce HGPRT mutagenesis at th e concentrations tested. These results show that while toxaphene is a weak, direct-acting mutagen in the Ames Salmonella Test, convincing ev idence of dose-dependent SCE induction and mutagenicity at the HGPRT g ene locus could not be demonstrated in V79 cells. (C) 1998 Elsevier Sc ience B.V.