Biological responses of the rat to polychlorinated biphenyls

Abstract

A commercial polychlorinated biphenyl mixture (PCBs), Aroclor 1242, was administered to rats po by intubation in order to determine toxic manifestations of acute and subacute ingestion. In addition, the effect of PCBs on hepatic microsomal enzyme systems in rats was evaluated. The oral, 14-day LD50 was determined to be approximately 4.25 g/kg. Major toxic signs observed upon administration of high doses of PCBs included diarrhea, chromodacryorrhea, loss of body weight, unusual stance and gait, lack of response to pain stimuli, and terminal ataxia. Progressive dehydration and CNS depression appeared to be contributing factors in each fatality. Histopathologic alterations were evident only in the liver and kidneys, manifest as foci of sudanophilic vacuolation. Rats maintained on an oral dosage regimen of 100 mg/kg every other day for 3 weeks exhibited similar histopathologic changes, but no overt signs of toxicity. Serum GOT activities were elevated over controls in both the acute and subacute groups. A single ip injection (100 mg/kg) increased liver weight, total hepatic microsomal enzyme activity (measured as hydroxylation of acetanilide and N-demethylation of aminopyrine), and hepatic cytochrome P450 and b5 levels. Hepatic microsomal enzyme activity remained elevated 10 days after a single dose of PCBs, suggesting that PCBs may play an important role in altering biologic responses of mammals subjected to environmental chemical stress.