Abstract for TR-222

A carcinogenesis bioassay of C.I. Disperse Yellow 3 (87.6% dye), a textile dye, was conducted by feeding diets containing 5,000 or 10,000 ppm of the test substance to groups of 50 F344 rats of either sex for 103 weeks. Similar groups of 50 B6C3F1 mice received diets containing 2,500 or 5,000 ppm of the test substance for 103 weeks. Groups of 50 untreated rats and mice of each sex served as controls.

Throughout the bioassay, mean body weights of dosed rats and mice of either sex were lower than those of the controls. Survival of dosed rats of either sex was significantly greater than that of the corresponding controls. No other compound-related clinical signs or effects on survival were observed.

A significant increase in neoplastic nodules of the liver occurred in dosed male rats as compared to controls (controls 1/49, 2%; low-dose 15/50, 30%; P<0.001; high-dose, 10/50, 20%; P<0.01). No increase was observed for female rats.

Stomach tumors, rare in F344 rats (10/2960, 0.3%), were found in the dosed male rats: one adenocarcinoma and a sarcoma in a high-dose male and in the low-dose group a squamous cell papilloma, fibrosarcoma, adenoma, and mucinous adenocarcinoma. The incidence of these tumors was not significantly greater than that in controls; thus, the association between the administration of C.I. Disperse Yellow 3 and the stomach tumors in male rats is not clearly established.

Negative trends in the incidences of certain primary tumors in dosed rats included: decreased lymphocytic leukemia in both sexes; decreased malignant mesothelioma and C-cell carcinoma of the thyroid in males; and decreased pituitary chromophobe adenoma and endometrial stromal polyps in females.

Hepatocellular adenomas occurred in dosed female mice at incidences significantly higher than that in the controls (control 0/50, 0%; low-dose 6/50, 12%, P<0.05; high-dose 12/50, 24%, P<0.001). The incidences of hepatocellular carcinomas were also higher in the dosed female mice than in the controls, but the increased incidences were not statistically significant (2/50, 4/50, 5/50). A significantly (P<0.05) lower incidence of hepatocellular adenomas was detected among low-dose (7/50, 1/49, 7/49) male mice.

Alveolar/bronchiolar adenomas occurred in high-dose male mice at an incidence significantly (P%lt;0.05) higher than that in the controls (control 2/50, 4%; low-dose 6/49, 12%; high-dose 9/49, 18%). However, the high-dose effect was not significant when adenomas and carcinomas were combined; the incidence among low-dose female mice was significantly reduced as compared with controls. Thus, the incidence of alveolar/bronchiolar adenomas among males is not considered to be related to treatment with C.I. Disperse Yellow 3.

Malignant lymphomas occurred in a dose-related (P<0.05) trend in female mice and at incidences greater (P<0.05) in the high-dose group than that in the controls (10/50; 16/50; 19/50). However, because of the range of variability in the historical incidence of this tumor and because of the lack of a similar effect in male mice or in male and female rats, this increase was not regarded as being unequivocally related to the administration of C.I. Disperse Yellow 3.

Under the conditions of this bioassay, C.I. Disperse Yellow 3 was considered to be carcinogenic for male F344 rats, causing an increased incidence of neoplastic nodules of the liver; this dye was not carcinogenic for female F344 rats. In addition, the stomach tumors found in the male rats may have been induced by the administration of the test chemical. C.I. Disperse Yellow 3 was carcinogenic for female B6C3F1 mice, as evidenced by the increased incidence of hepatocellular adenomas; C.I. Disperse Yellow 3 was not carcinogenic for male B6C3F1 mice. Also, the increased incidence of malignant lymphoma in female mice may have been associated with the administration of C.I. Disperse Yellow 3.