Alterations in tissue distribution of chlordecone (kepone) in the rat following phenobarbital or SKF-525A administration.

Phenobarbital (PB) or SKF-525A were injected ip into adult male rats prior to administration of 1.6 microCi [14C] chlordecone (CD) by gavage. Effects of these liver function modulators on tissue distribution of CD was assessed. In all cases, animals were sacrificed at 24 h following [14C]CD gavage. The timing and number of injections of PB or of SKF-525A were varied. Doses of PB (65 mg/kg) or of SKF-525A (75 mg/kg) were used except as noted, and controls received saline. Specific radioactivities of major tissues were assayed by scintillation counting. Rats pre-treated with a single dose of SKF-525A at 6, 12, or 24 h prior to [14C]CD distribution. Similarly, PB administered at 6 h prior to [14C]CD gavage was without effect on distribution. Rats pretreated 12 or 14 h before [14C]CD with PB appeared to have increased liver specific activities and had reduced [14C]CD levels in several other tissues. These trends were more marked in a second study, in which multiple doses of PB (3 consecutive daily doses of 65 mg/kg, the final dose 24 h prior to [14C]CD or SKF-525A (1 dose of 75 mg/kg 90 min prior to [14C]CD, followed by a second dose of 38 mg/kg at 6.5 h after [14C]CD) were given. Tissue [14C]CD levels were assayed as before; urine and feces samples were also counted and reported as percent of [14C]CD administered. SKF-525A animals had significantly high [14C] levels in digestive system, while fecal and urinary levels were significantly low. No other significant alterations were observed in these animals, except that testes levels were reduced. Livers of rats receiving multiple doses of PB had significantly elevated [14C]CD levels, and all other tissues examined had levels significantly below controls. Fecal and urinary excretion of [14C]CD was significantly depressed. Studies indicate that an inducer of hepatic metabolism can dramatically alter the distribution and hence the relative toxicity of CD.