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 B6C3F1 mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and reproductive parameters. Groups of 10 rats 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 terminal body weight at 30 mg/kg/day, an increase in hematopoietic cell proliferation in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% decrease 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 hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the forestomach was increased at 3 mg/kg/day and higher doses in males and at 30 mg/kg/day in females. In the mouse studies, an increase in liver and spleen weight was observed up to approximately 25% in both males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and higher doses in both males and females. In males, a 30% decrease 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 hypertrophy of hepatocytes and an increase in hematopoietic cell proliferation 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 properties. Comparison of the effects of TCAB in the present study and in the literature to those with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) indicates that TCAB is from two to six orders of magnitude less potent than TCDD depending on the end point.
van Birgelen
A P
AP
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. VANBIRGE@NIEHS.NIH.GOV
Hébert
C D
CD
Wenk
M L
ML
Grimes
L K
LK
Chapin
R E
RE
Mahler
J
J
Travlos
G S
GS
Bucher
J R
JR
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D002722:Chlorobenzenes / Q000633:toxicity*; D004971:Estrus / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure; D013963:Thyroid Hormones / Q000097:blood
D001391:Azo Compounds; D002722:Chlorobenzenes; D013963:Thyroid Hormones; C013279:3,4,3',4'-tetrachloroazobenzene