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USE OF GAMMA-HEXACHLOROCYCLOHEXANE (LINDANE) TO DETERMINE THE ONTOGENY OF METABOLISM IN THE DEVELOPING RAT
Citation:
Copeland, M., R. Chadwick, N. Cooke, D. Whitehouse, AND D. Hill. USE OF GAMMA-HEXACHLOROCYCLOHEXANE (LINDANE) TO DETERMINE THE ONTOGENY OF METABOLISM IN THE DEVELOPING RAT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-86/179 (NTIS PB87116679).
Description:
The compound lindane has been used as a model substrate to study the ontogeny of metabolism in the developing Fischer 344 rat. The distribution and metabolic fate of the model substrate at 2, 9, 16, and 23 days of age was investigated following subcutaneous administration of 20 mg/kg of lindane containing 0.5 micro Ci (U14C)-lindane in peanut oil. Groups of ten pups (5 male and 5 female) were sacrificed at 4 hr intervals during the 24 hr period following dosing. Adrenals, blood, brain, heart, lung, liver, and kidneys were analyzed for radioactivity. Urine samples were analyzed for radioactivity and metabolites of lindane. There was a significant age dependent increase in the metabolism of lindane in the rat. High levels of radioactivity in the lung and increased reductive dechlorination suggest that the lung may play a greater role in metabolism of lindane by young rats. Oxidative phase I reactions increased significantly while anaerobic reductive dechlorination of lindane to 4-chlorophenylmercapturic acid decreased significantly with age.