Short-term toxicity and reproduction studies in rats with hexachloro-(1,3)-butadiene

Abstract

In rats given daily doses of 0. 0.4, 1.0, 2.5, 6.3, and 15.6 mg of hexachloro-(1,3)-buta-diene (HCBD)/kg by gavage for 13 weeks, no effect levels of 1.0 and 2.5 mg/kg were established for females and males, respectively. Inhibition of growth occurred in both sexes at the two highest doses and degeneration of proximal renal tubules occurred at doses of 2.5 and 6.3 mg/kg or more in females and males, respectively. Urine-concentrating ability was significantly reduced in females at doses of 2.5 mg/kg or more and in males at 15 mg/kg. Relative kidney weights were increased at the two highest doses in both sexes. Increased cytoplasmic basophilia of hepatocytes occurred in males at the two highest doses, associated with an increase in liver weight. In females, liver weights were increased only at the 15.6 mg/kg dose. In other studies, nephrotoxicity was noted after 2 weeks of administration of 150 and 450 ppm in the diet, characterized by epithelial hyperplasia of the proximal renal tubules. Ataxia associated with demyelination and fragmentation of femoral nerve fibers also occurred at a dietary level of 1500 ppm. Except for decreased body weights at birth and weaning, no effects on fertility or progeny were found. No porphyrinogenic effects were noted.