Two-generation chronic toxicity study with hexachlorobenzene in the rat

Abstract

The toxicological effects of analytical grade hexachlorobenzene (HCB) were examined in a two-generation feeding study in which 40 male and 40 female weanling Sprague-Dawley rats, except where noted, were fed diets containing 0.0 (64 males, 64 females), 0.32, 1.6, 8.0 or 40.0 (66 males, 66 females) ppm HCB. After 3 months on test, the F0 rats were bred and 50 pups (F1) of each sex were randomly selected from every group. At weaning the F0 animals were killed, and the F1 animals were fed their parents' diet for the remainder of their lifetimes (130 weeks). There were no treatment-related effects on growth, feed consumption, haematological parameters or survival in either generation. Increased heart and liver weights were found in the F0 generation males fed 8.0 and 40 ppm HCB. HCB had no effect on fertility, but did significantly reduce pup viability in the 40.0-ppm group. Histopathological changes in the F1 generation included significant linear trends for the incidence of parathyroid adenomas and phaeochromocytomas in both sexes, neoplastic liver nodules in females, centrolobular basophilic chromogenesis of the liver in both sexes, peliosis of the liver in females, peribiliary lymphocytosis of the liver in males and chronic nephrosis of the kidney in males.