Bioassay of 4,4'-Oxydianiline for Possible Carcinogenicity (CAS No. 101-80-4).

4,4'-Oxydianiline is used in the manufacture of high temperature resistant metal adhesives, molding and machine parts, and insulators. A bioassay of this chemical for possible carcinogenicity was conducted by feeding diets containing 200, 400, or 500 ppm of the test chemical to groups of 50 male or female F344 rats and 150, 300, or 800 ppm to groups of 50 male or female B6C3F1 mice for 104 weeks. Matched controls consisted of 50 untreated rats and 50 untreated mice of each sex. All surviving animals were killed at 104 to 105 weeks. A dose-related decrement in mean body weight gain was observed for all groups of dosed rats and mice. Survival was significantly shortened in the high-dose female rats and in the low- and mid-dose female mice. In male and female rats, hepatocellular carcinomas or neoplastic nodules occurred at incidences that were dose-related, and the incidences in all dosed groups (except low-dose females) were higher than those in the controls. The occurrence of follicular-cell adenomas or carcinomas of the thyroid was dose-related. Among groups of male and female rats, the incidences in the mid- and high-dose groups of either sex were significantly higher than those of the corresponding controls. In male and female mice, adenomas in the harderian glands occurred in all dosed groups at incidences that were significantly higher than the incidence in the matched controls. In low-dose male mice and in high-dose female mice, hepatocellular adenomas or carcinomas occurred at incidences significantly higher than those in the matched controls. In female mice, follicular-cell adenomas in the thyroid occurred with a positive linear trend, and in a direct comparison the incidence in the high-dose group was also significantly higher than that in the controls. Tumors occurring among male mice at increased incidences which could not be statistically related to the chemical were adenomas in the pituitary and hemangiomas of the circulatory system. Under the conditions of this bioassay, 4,4'-oxydianiline was carcinogenic for male and female F344 rats, inducing hepatocellular carcinomas or neoplastic nodules and follicular-cell adenomas or carcinomas of the thyroid. 4,4'-Oxydianiline was also carcinogenic for male and female B6C3F1 mice, including adenomas in the harderian glands, hepatocellular adenomas or carcinomas in both sexes, and follicular-cell adenomas in the thyroid of females. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive