Mirex uptake and tissue disposition in intact and adrenalectomized rats

Abstract

The toxicity of mirex, an organochlorine insecticide, is increased significantly in adrenalectomized rats. To determine if this might be due to alterations in the tissue distribution of mirex, a disposition study was conducted in intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats. The peak plasma levels of [ 14C]mirex were shifted from 2 hr in intact and adrenalectomized corticosterone-supplemented rats to 4 hr in the adrenalectomized rats. The initial uptake and disposition of [ 14C]mirex in the brain of the intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats was essentially the same from 0.5 to 6 hr after dosing. By 48 hr after dosing, the [ 14C]mirex concentration in the brain of intact and adrenalectomized rats was significantly higher than that in adrenalectomized corticosterone-supplemented rats. Brain to plasma ratios reflected this difference. Corticosterone supplements to adrenalectomized rats decreased the absorption of [ 14C]mirex in the brain. The uptake of [ 14C]mirex during the initial 6 hr after dosing in all other tissues studied (liver, kidney, testes, and omental fat) was essentially the same for the three treatment groups. By 48 hr postdose, [ 14C]mirex concentration per liver was significantly higher in intact than in adrenalectomized and adrenalectomized corticosterone-supplemented rats. The difference in [ 14C]mirex disposition between the three treatment groups was not due to alterations in metabolism or elimination.