Effects of a polybrominated biphenyl mixture in the rat and mouse. I. Six-month exposure.

A 1973 environmental accident in Michigan resulted in exposure of humans via the food chain to polybrominated biphenyl (PBB). To better characterize the toxicity of the halogenated polycyclic aromatic hydrocarbon class of chemicals, rodents were dosed with PBB and their target organs examined for morphological, histological, biochemical, and selected endocrine changes. Male and female rats and mice were given 125 po doses of PBB over a 6-month period at 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg of body weight/day (5 days/week). There was a dose-related decrease in body weight gain in both male and female rats and male mice. Thymus weights were significantly decreased in all rats exposed to 0.3 mg/kg or more of PBB. Dose-related hepatotoxic effects were observed in both rats and mice characterized by marked increase in liver weight with accentuation of hepatic lobular markings. Microscopically, there were moderate to marked swelling, disorganization, and single cell necrosis of hepatocytes, fatty infiltration, bile duct proliferation, and presence of atypical hyperplastic foci. Hepatic porphyrin levels were markedly increased in both rats and mice primarily in females. There was a significant decrease in serum thyroxine (T4) and triiodothyronine (T3) suggesting that PBB may interfere with thyroid hormone secretion. There was a significant dose-related increase in serum cholesterol and gamma-glutamyl transpeptidase, and a decrease in serum glucose.