The goitrogenic effect of 4,4'-oxydianiline in rats and mice

Fischer 344 rats and B6C3F1 mice were fed diets that contained 0.03, 0.06, 0.1 and 0.2% 4,4'-oxydianiline for 13 weeks. The 0.1 to 0.2% diet caused 40 to 70% mortality in female rats. Although mice ate about 3.5 times more chemical than rats, no mice died. Alopecia, dyspnea and cyanosis in rats, and lethargy in both species occurred in the 0.1 to 0.2% groups. Goiter was found in rats that died as early as the 4th to 5th week of study in the groups given the 0.06 to 0.1% diet. At the end of the study, diffuse parenchymatous goiter was seen in all rats given the 0.06% and higher concentration diets and in most mice given the 0.2% diet. In rats, the thyroids also were heavily encapsulated and had interstitial fibrosis and vascular degeneration. There was concomitant hyperplasia of pituitary basophils in both species, but an increase of cells that secrete thyrotropin was seen in rats only.