Two-generation chronic toxicity study with hexachlorobenzene in the rat.

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.

Long-term toxicity of hexachlorobenzene in the rat and the effect of dietary vitamin A.

The toxicological effects of analytical-grade hexachlorobenzene (HCB) were examined in two chronic studies. Study I was an in utero exposure carcinogenicity feeding experiment in which Sprague-Dawley rats, in groups of 40 males and 40 females except where noted, were fed from weaning on diets containing 0.0 (64 M/64 F), 0.32, 1.6, 8.0 or 40.0 (66 M/66 F) 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. From weaning, when the F0 animals were killed, the F1 animals were fed their parents' diet for the rest of their life (130 wk). 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 8.0 and 40 ppm F0 males. HCB had no effect on fertility but pup viability was significantly reduced in the 40 ppm group. Histopathological changes in the F1 generation included significant linear trends in the incidence of parathyroid adenomas and phaeochromocytomas in both sexes, neoplastic liver nodules in females, centrilobular 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. In Study II, the toxicological effects of HCB were examined as a consequence of varying the dietary levels of vitamin A. In this single generation lifetime (119 wk) feeding study, groups of 50 weanling Sprague-Dawley male rats were randomly assigned to each of the following dietary groups: control, control + 40 ppm HCB, 1/10 the vitamin A content of the control diet, 1/10 vitamin A + 40 ppm HCB, 10 times the vitamin A content of the control diet and 10 times vitamin A + 40 ppm HCB. After 25 and 49 wk on test, five animals from each group were killed and subjected to haematological and histological examinations. All other aspects of evaluation were similar to those for the F1 generation in Study I. No consistent differences were observed in the haematological parameters and there were no significant differences in the incidence of pathological lesions between the test groups. The animals in the 1/10 vitamin A groups, with or without HCB, had significantly lower body weights and poorer survival than did their corresponding control (normal vitamin A) groups.

Reversibility of ethylenethiourea-induced thyroid lesions.

Groups of 50 male and 50 female Sprague-Dawley rats were fed diets containing 0, 75, 100, or 150 ppm ethylenethiourea (ETU) for 7 weeks, at which time subgroups of 10 animals from each group were killed. Subsequent subgroups of 10, 10, and 20 animals were killed after an additional 2, 3, and 4 weeks, respectively, on the control diet in order to examine whether the toxicological effects induced by ETU were reversible. In both sexes, the mean body weight and feed consumption were significantly decreased in all treated groups, while the mean thyroid weight (absolute as well as relative to both body and brain weight) appeared to increase linearly with dose. Mean T4 blood levels in animals fed 150 ppm ETU were significantly below those in controls. The magnitude of the changes in body weight, thyroid weight, and T4 blood levels observed during the first 7 weeks of the study decreased after ETU was removed from the diet. The statistical procedures developed and applied here may be useful in other experiments designed to assess the reversibility of other toxicological endpoints.