ASSESSMENT OF GENOTOXIC EFFECTS BY LINDANE

The well known and previously widespread insecticide lindane has been re-assessed for DNA-damaging activity. A first group of investigations using standard in vitro and in vivo mutagenicity assays did not indic ate any genotoxic effects of lindane at all. The assay systems used we re for the induction of HPRT mutations and sister chromatid exchanges in CHO cells cultured in vitro, and for micronuclei induction in vivo in bone marrow cells of rats, hamsters and mice. Also, lindane was ass essed for its potential to induce sister chromatid exchanges in vivo i n the bone marrow of Chinese hamsters. These specific assay systems ha d not been used previously for elucidating the genotoxic effects of th is compound, but they are basically similar to other standard mutageni city assays in which lindane has been shown to be devoid of genotoxic activity. The second part of the investigations was directed at re-eva luating a previously reported positive effect of the compound in prima ry rat hepatocytes in vitro. We performed in vitro and in vivo studies with hepatocytes from the rat liver and used alkaline elution to dete ct DNA damage. However, we could not demonstrate that lindane induced genotoxicity, unless considerable concomitant cytotoxicity was apparen t as well. Finally, since lindane can be ingested and inhaled by human s, we also measured the induction of DNA damage in local target organs of absorption using single cell microgelelectrophoresis (the comet as say). In these cases lindane was genotoxic in cells of the gastric and nasal mucosa in vitro and also in vivo following appropriate routes o f application (oral and inhalational exposure).