Oncogenicity of hexachlorobenzene

Abstract

Subchronic and chronic toxicities of hexachlorobenzene (HCB) were studied in both sexes of Swiss mice, Syrian golden hamsters and Sprague-Dawley rats, at dietary dosages of 0, 100 and 200 ppm (mice), and 0, 200 and 400 ppm (hamsters and rats) for 90 days. At day 91, 25/50 animals in each of 18 groups were killed for histology studies. The rest were killed at 6-week intervals until the study was ended. Marked hepatosplenomegaly, enlarged thymuses and lymph nodes, or swollen and granular-looking renal cortices with depressions or nodulary areas were commonly observed. Dose- and sex-dependent progressive changes included toxic-degenerative hepatitis, chronic cirrhosis, hepatomas, bile-duct adenomas and a few hepatocarcinomas in older animals. A generalized lymphohaematopoietic response led to thymic, splenic and nodal lymphosarcomas, especially in female mice. Toxic-tubular nephritis with cortical infarcts developed into regenerative foci and renal adenomas in low incidences. Liver lesions were more prominent in females, while renal changes were most common in male rats. HCB was retested in both sexes of rats at oral doses of 0, 75 and 150 ppm for up to 2 years. At the start, each group contained 94 rats, and four randomly selected rats were killed at weeks 0, 1, 2, 3, 4, 8, 16, 32, 48 and 64 for microscopy. Progressive liver lesions started as hyperaemia and degenerations (4 weeks), and developed into toxic hepatitis, cirrhosis and formation of pre- and neoplastic foci (36 weeks), with hepatomas, bile-duct adenomas and hepatocellular carcinomas (64 weeks) in very high incidences in females and renal adenomas in male rats.