Comparative toxicity of 1,2,3,4‐, 1,2,4,5‐, and 1,2,3,5‐tetrachlorobenzene in the rat: Results of acute and subacute studies

Abstract

Groups of 10 male and 10 female rats were dosed orally with 1,2,3,4-, 1,2,4,5- or 1,2,3,5-tetrachlorobenzene (TCB) 200-400 mg/kg, and were observed clinically for 14 days. LD50 values for 1,2,3,4-, 1,2,4,5- and 1,2,3,5-TCB were 1470, 3105 and 2297 mg/kg, respectively. Clinical signs of toxicity included depression, flaccid muscle tone, prostration, piloerection, loose stool, hypothermia, dacryorrhea, coma and death. In a subacute study, groups of 10 males and 10 females were fed diets containing 0, 0.5, 5.0, 50 or 500 ppm 1,2,3,4-, 1,2,4,5- or 1,2,3,5-TCB for 28 days. No deaths or clinical signs of toxicity were observed, and growth rate or food consumption was not affected. At 500 ppm, 1,2,4,5- but not 1,2,3,4- or 1,2,3,5-TCB caused a significant increase in the liver weight and serum cholesterol of male and female rats. Hepatic microsomal aniline hydroxylase and ethoxyresorufin deethylase were induced by 500 ppm 1,2,4,5-TCB. Hepatic microsomal aminopyrine demethylase activity was increased by the administration of this compound at .gtoreq. 50 ppm in males and at 500 ppm in the females. Rats fed 1,2,3,4- and 1,2,3,5-TCB at 500 ppm also showed a significant increase in aminopyrine demethylase activity. Moderate to severe histological changes were found in the liver, thyroid, kidney and lungs of rats fed 500 ppm 1,2,4,5-TCB. Histological changes in the tissues produced by the administration of the 1,2,3,4- and 1,2,3,5-isomer were mild even at the highest dose levels. Tissue residue data showed that 1,2,4,5-TCB accumulated at higher levels than the other 2 isomers. The position of Cl substitution affected the tissue accumulation and toxicity of chlorinated benzenes in rats.