Bioisomerization of lindane in rats

Abstract

The major environmental problem associated with the use of gamma-hexachlorocyclohexane (gamma-HCH, lindane) has been the appearance of the more oncogenic alpha- and beta- isomers as terminal residues in nature. To account for these residues it was suggested that gamma-hexachlorocyclohexane had been bioisomerized to the more stable alpha- and beta- isomers. In this study the effect of dose and duration of treatment on the proposed bioisomerization of gamma-hexachlorocyclohexane in the rat was investigated. Weanling female Sprague-Dawley rats were randomly assigned to one of four groups receiving Purina Lab Chow fortified with 0, 130, 215, or 350 ppm gamma-HCH. Six animals from each group were sacrificed after 1, 2, 4, 8, 16, and 24 weeks of treatment. Twenty-four hours prior to sacrifice all rats received a single oral dose of gamma-HCH in peanut oil. There were no significant differences in food consumption or body weights, and no deaths occurred throughout the study. The in vitro dechlorinase activity of the treated rats was significantly higher after 1, 4, and 24 weeks of treatment. Except at 4 weeks after treatment began, the liver/body weight ratios of the rats fed diets containing 350 ppm and 215 ppm lindane were significantly greater than the controls; while those receiving 130 ppm lindane were significantly greater than the controls after 1 and 2 weeks of treatment. No beta-HCH was detected in any of the samples analyzed throughout the study. The levels of alpha-HCH found in the adipose tissue after 24 weeks of treatment could be accounted for by trace contamination of the lindane used in this study. There was a negative correlation between the hepatic content of alpha-, gamma-, and sigma-HCH and duration of treatment. It was concluded that bioisomerization does not play a significant role in the metabolism of lindane by rats.