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

The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13- week gavage studies in male and female F344/N rats and B6C3F(1) mice. In ad dition to histopathology, evaluations included clinical chemistry, hematolo gy, thyroid hormone analyses, and reproductive parameters. Groups of 10 rat s and 10 mice of each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for 5 days a week for 13 weeks. In the rat studies, the major effects for both males and females included a 10% decrease in termin al body weight at 30 mg/kg/day, an increase in hematopoietic cell prolifera tion in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 an d 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% dec rease in thymus weights was observed at 10 and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males and at 30 mg /kg/day in females. A marked decrease in circulating total thyroxine (TT4) was found in both males and females at all dose levels tested. TT4 could ha rdly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of t he forestomach was increased at 3 mg/kg/day and higher doses in males and a t 30 mg/kg/day in females. In the mouse studies, an increase in liver and s pleen weight was observed up to approximately 25% in bath males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 m g/kg/day and higher doses in both males and females. In males, a 30% decrea se in thymus weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and 30 mg/kg/day was observed. Also in males, centrilobular h ypertrophy of hepatocytes and an increase in hematopoietic cell proliferati on in the spleen was observed at 3 mg/kg/day and higher doses. Based on the current study and information in the literature, TCAB has dioxin-like prop erties. Comparison of the effects of TCAB in the present study and in the l iterature to those with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) indicate s that TCAB is from two to six orders of magnitude less potent than TCDD de pending on the end point. (C) 1999 Academic Press.