The comparative toxicity of chlorinated dibenzo-p-dioxins in mice and guinea pigs

Abstract

Mice and guinea pigs were given a single oral dose of various chlorinated dibenzo-p-dioxins (CDD) to establish and compare the LD50 and clinical and pathologic manifestations of toxicity. It was apparent that the 2,3,7, and 8 positions must be chlorinated to achieve the greatest degree of toxicity. Additional chlorine atoms at an ortho position reduced toxicity but not nearly to the degree caused by deletion of a chlorine atom at one of the lateral positions. A decrease in body weight gain was the most sensitive clinical parameter and animals severely intoxicated showed a marked weight loss, especially guinea pigs. The median time to death at a LD50 was 17 to 20 days in guinea pigs and 22 to 25 days in mice. Doses 10 times greater did not markedly shorten this period. At the toxic dose the spectrum and severity of lesions and organ weight effects were similar for all homologs and isomers within the same animal species; however, there were interspecies differences. The thymus was greatly reduced in size in both animal species due to a reduction in the number of cortical lymphocytes. Significant macroscopic and histopathologic hepatic effects including porphyria were observed only in the mouse and were found at does levels well below the LD50. Hyperplasia of the transitional epithelium in the urinary tract was found in guinea pigs. There was a reduction of total serum protein in the mouse due to lower levels of α-globulin. Other lesions were generally interpreted to be a secondary response to debilitation.