Biotransformation and toxicity of lindane and its metabolite hexachlorobenzene in mammals

Lindane (gamma-hexachlorocyclohexane) is an important organochlorine pesticide used extensively for agricultural and public health purposes in India and in other developing countries. Because of its relative chemical stability and lipid solubility, it is known to enter food chains. This study was carried out in order to identify the metabolic capacity of rat-liver enzymes to transform lindane. It has been observed that lindane is made aromatic in this animal, yielding hexachlorobenzene (HCB) both in vivo and in vitro. Following the incubation of liver slices with U-14C-lindane, a significant amount of radioactivity was found to be incorporated into HCB. Although it has been reported earlier that detoxification of the pesticide occurs through dehydrochlorination reactions in mammalian species, the direct aromatization of lindane to HCB is a novel pathway and may have implications for the safety of this pesticide, since several studies have reported that HCB is carcinogenic in experimental animals. In view of the reported correlation between carcinogenicity and mutagenicity, both lindane and HCB have been tested for possible mutagenicity using the Salmonella typhimurium test system. The mutagenic response was found to be variable in different experiments.