1. The elimination of alpha-1,2,3,4,5,6-hexachlorocyclohexane (alpha-HCH) by rats, as assessed by g.l.c. determination of the chemical's disappearance from depot fat, exhibited a sex difference (males:females = 4:1) and a sizeable deuterium isotope effect (6.3 in males). 2. Lindane (gamma-HCH), by contrast, disappeared from depot fat, skeletal muscle, brain and blood at nearly the same rates in both sexes. Perdeuteration, though effective in reducing hepatic removal, did not significantly retard the overall elimination of this isomer (isotope effect in males less than 2). Partial explanation of this finding is that lindane and lindane-d6 are equally subject to dechlorination in the gut. 3. alpha-HCH distributed into cerebral white matter in preference to grey matter to a much higher degree than did lindane and the beta-isomer of HCH, and elimination from that tissue was slow. The finding is considered to indicate a stereoselective affinity of alpha-HCH to some component(s) of myelin.
1. Free 2,4,5- and 2,4,6-trichlorophenol (TCP) have been identified by co-crystallization with authentic carrier as constituents of the urine of rats given 3-H-labelled alpha-hexachlorocyclohexane (alpha-HCH). The two TCP's constituted 7% and 63%, respectively, of the free phenol fraction which was found to account for less than 5% of all urinary metabolites. 2. 75% of the label contained in the urine of rats collected for four weeks after an i.p. dose of 14-C-alpha-HCH could be extracted into an organic solvent after alkaline and acid hydrolysis. The radioactive material thus extracted was examined by TLC and GLC. It is shown to consist mainly of chlorophenols and chlorothiophenols. 3. The extracts' major constituent was 2,4,6-TCP. Its amount was determined by GLC and was found to account for, on average, 45% of the total urinary metabolites. In conjunction with other evidence, this is considered to establish 2,4,6-TCP as the major product of alpha-HCH-biodegradation in the rat. 4. Chromatographic evidence is presented for 2,3,4,5-tetrachlorophenol and 2,4,5-TCP being other components of the chlorophenol fraction isolated from hydrolysed urine. 5. The amount of label associated with the chlorothiophenol fraction suggests a pathway involving endogenous thiol to be of significance in alpha-HCH-biodegradation in rats. Pretreatment with the drug itself increased the proportion of label associated with the fraction.
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