Subacute toxicity of hexachlorobenzene in the rat

Abstract

Male and female rats of the Charles River strain were fed a commercial diet supplemented with 5% corn oil. Hexachlorobenzene (HCB) was added to the corn oil to give 0, 0.5, 2, 8, or 32 mg of HCB/day/kg/body weight. Subgroups of four rats of each sex were killed at 3, 6, 9, 12, and 15 weeks of feeding. To measure the reversibility of changes noted and the decline of HCB residues, the rats remaining at 15 weeks were fed an HCB-free diet and subgroups were killed after 1, 2, 4, 7, 16, and 33 weeks. Tissue residues of HCB reached a plateau before 15 weeks and were dose related, with concentrations in adipose tissue ≧ liver ≧ brain ≧ serum. In both sexes at the two highest dose levels, relative liver weight was increased when compared to control rats for most of the treatment period. Histopathological changes were confined to the liver and spleen. In the liver, there was an increase in the size of centrilobular hepatocytes. Serum sorbitol dehydrogenase activity, an indicator of liver damage, was maximally increased at 6 weeks at the highest dose level in males. Histochemically, this was related to a depletion of this enzyme in the liver. A change in distribution of other enzymes in the liver also was noted. Females developed porphyria, with high porphyrin values persisting after the rats were placed on an HCB-free diet. Pathological examination of the other organs indicated no changes. Females were more sensitive than males to the toxic effects of HCB. The overall results indicated a sex difference in the response to HCB.