Steric factors in the pharmacokinetics of lindane and alpha-hexachlorocyclohexane in rats.

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.