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.