Toxicity of 3,3 ',4,4 '-tetrachloroazoxybenzene in rats and mice

The toxicity of 3,3'4,4'-tetrachloroazoxybenzene (TCAOB),vas evaluated in 1 3-meek gavage studies in male and female F44/N rats and B6C3F(1) mice. In a ddition to histopathology, evaluations included clinical chemistry, hematol ogy, thyroid hormone analyses, and effects on sperm morphology and estrous cycle length. Groups of 10 rats and 10 mice of each sex were exposed to TCA OB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg 5 days a week for 13 wee ks. In the rat studies, the major effects included death in the 30 mg TCAOB /kg dose group; at lower exposure levels, a decrease in body weight gain, a decrease in thymus weight, an increase in liver weight, an increase in hem atopoietic cell proliferation in the spleen and liver, a responsive anemia, a decrease in platelet counts, a chronic active inflammation of the vascul ature in the lung, an increase in cardiomyopathy, hyperplasia of the forest omach, and a marked decrease in circulating thyroxine concentrations were o bserved. In male rats a decrease in sperm motility in the epididymides was observed. In addition, in female rats an increase in lung, spleen, kidney, and heart weights and nephropathy was observed. Furthermore, the estrous cy cle length was increased. In the mouse studies, the major effects for males ; and females included a decrease in thymus weights, an increase in liver a nd kidney weights, centrilobular hypertrophy in the liver, hematopoietic ce ll proliferation, hyperplasia of the forestomach, and dilatation of hair fo llicles. The spectrum of effects in both rats and mice after exposure to TC AOB indicates that dioxin-like effects occur in addition to effects that ha ve not been observed with dixon-like compounds. No no-observed-adverse-effe ct level was reached in male or female rats or mice. (C) 1999 Academic Pres s.