Lindane bioassay studies and human cancer risk assessment

Benzene hexachloride or hexachlorocyclohexane comes in eight isomeric forms which differ in the spatial positions of the chlorine atoms on the boat and chair forms. Only one, however, gamma-isomer (lindane) possesses relevant insecticidal activity. The majority of studies on the potential carcinogenicity of benzene hexachloride, however, did not discriminate between the various isomers because they assumed that carcinogenicity is independent of steric structure. Also, proper differentiation between morphologic endpoints was not duly carried out and considered. The present evaluation of lindane's biologic activity was restricted to the lifelong studies in which pure lindane (greater than 99.5%) was utilized and the morphology of the observed lesions, mainly in the liver, were classified according to their biologic behavior into hyperplastic, benign neoplastic, and malignant entities. None of the studies gave evidence that lindane was carcinogenic in mice and rats. An enhancement of benign liver tumors (tumorigenic effect) was observed only in CF1 male mice (17/56 at the only tested dose: 400 ppm vs. 3/89 observed in the nontreated controls). Dose-response function of this tumor response in conjunction with two other lifetime studies (80 and 160 ppm in B6C3F1 and 50, 25, and 12.5 ppm in NMRI mice) were best described by the Weibull model, giving a relatively high estimate of its shape parameter (m = 2.5). Assuming similar susceptibility of humans to lindane and considering maximal occupational exposure to this agent (professional applicators), the probability of lindane associated tumor development was estimated as 2.2 X 10(-10). Because this cancer risk is five orders of magnitude below the acceptable health risk, this evaluation concludes that environmental exposure to lindane does not pose a threat to human health.