Copeland M F, Chadwick R W, Cooke N, Whitehouse D A, Hill D M
J Toxicol Environ Health. 1986;18(4):527-42. doi: 10.1080/15287398609530892.
The compound lindane (gamma-hexachlorocyclohexane) has been used to study the ontogeny of metabolism in the developing Fischer 344 rat. The distribution and metabolic fate of lindane at 2, 9, 16, and 23 d of age was investigated following subcutaneous administration of lindane at 20 mg/kg containing 0.5 microCi [U-14C]lindane in peanut oil. Groups of 10 pups (5 male and 5 female) were sacrificed at 4-h intervals during the 24-h 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. Phase II sulfate and glutathione conjugations decreased significantly and glucuronide conjugation increased significantly with age. Metabolism and excretion of lindane appear to parallel development of the hepatic enzymes involved in phase I and phase II reactions.
化合物林丹（γ-六氯环己烷）已被用于研究发育中的Fischer 344大鼠的代谢个体发生。在20毫克/千克林丹（含0.5微居里[U-14C]林丹于花生油中）皮下给药后，研究了2、9、16和23日龄大鼠林丹的分布和代谢归宿。给药后24小时内，每隔4小时处死一组10只幼崽（5只雄性和5只雌性）。分析肾上腺、血液、脑、心脏、肺、肝脏和肾脏的放射性。分析尿液样本的放射性和林丹代谢物。大鼠林丹代谢存在显著的年龄依赖性增加。肺中高水平的放射性和还原脱氯增加表明，肺在幼鼠林丹代谢中可能发挥更大作用。随着年龄增长，氧化I相反应显著增加，而林丹厌氧还原脱氯生成4-氯苯基巯基尿酸则显著减少。随着年龄增长，II相硫酸盐和谷胱甘肽结合显著减少，葡糖醛酸结合显著增加。林丹的代谢和排泄似乎与参与I相和II相反应的肝酶发育平行。
