Toxicity of 1,2,3,4-, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene in the rat: results of a 90-day feeding study.

Tetrachlorobenzenes (TCB) are industrial chemicals which have been used as intermediates for chemical synthesis and for electrical insulation. Recently TCB residues have been found in Great Lakes fish. The present study was designed to determine the subchronic toxicity of these compounds. Groups of 15 male and 15 female rats were fed diets containing 0, 0.5, 5.0, 50 or 500 ppm of each of 1,2,3,4-, 1,2,3,5- and 1,2,4,5-TCB for 13 weeks. Rats fed 500 ppm 1,2,4,5-TCB exhibited significant increases in liver and kidney weight. 1,2,4,5-TCB at the highest dose level caused a significant increase in serum cholesterol levels. Hepatic microsomal aminopyrine demethylase and aniline hydroxylase activities were induced by this compound at 50 and 500 ppm in the males, and 500 ppm in the females. Moderate to severe histological changes occurred in the liver and kidney of rats fed the three TCB isomers but the 1,2,4,5-isomer caused the most severe lesions. 1,2,4,5-TCB accumulated in fat and liver in a dose-dependent manner. Results indicate that 1,2,4,5-TCB is the most toxic isomer of the three and accumulates in liver and fat in a dose-dependent manner.