2,4,5,2',4',5'-Hexachlorobiphenyl: distribution, metabolism, and excretion in the dog and the monkey

The tissue distribution, metabolism, and excretion of 2,4,5,2′,4′,5′-hexachlorobiphenyl (2,4,5-HCB) were investigated in beagle dogs and cynomolgus monkeys (Macacca fascicularis). Following a single iv dose of ¹⁴C]2,4,5-HCB (0.6 mg/kg), excreta, blood, and tissues were collected at time intervals ranging from 30 min to 15 days for dogs and 2 hr to 90 days for monkeys. The concentration of 2,4,5-HCB and its metabolites was determined in all samples. Elimination of the parent PCB from the blood of both species was biphasic with a terminal phase elimination rate constant of 0.045 day^?1 for the dog and 0.015 day^?1 for the monkey. By 15 days the dog had excreted 66% of the dose, 63% in the feces, and 3% in the urine. The percentage dose remaining was found largely as parent compound in the adipose tissue (16%), skin (6%), and muscle (2%). By 90 days, the monkey had excreted only 18% of the dose (17% in feces, 1% in urine). Again, the major storage depots for nonexcreted dose were adipose tissue 945%) and skin (5%). In anesthetized dogs, 0.8% of the dose appeared in the bile within 2 hr, while only 0.2% of the dose appeared in the bile of anesthetized monkeys in 2 hr. The monkey excreted a greater percentage of dose as parent compound into the bile than the dog. The data provide evidence that the pharmacokinetic behavior of 2,4,5-HCB in the monkey is similar to that observed in other species. However, the dog is unique from other species in that it can readily eliminate 2,4,5-HCB.