CHRONIC STUDY OF TRIPROLIDINE FOR ONCOGENICITY IN MICE

Triprolidine hydrochloride was fed to groups of 60 B6C3F1 mice per sex at dietary levels of 0, 500, 2000, or 4000 ppm (as the free base) for up to 2 years. Up to 12 mice of each sex and dose group were terminat ed after 65 weeks for hematology and clinical chemistry. The control a nd high-dose groups were examined histologically. A complete histopath ological examination was performed on the remaining 48 mice from each dose group when removed from study due to moribund condition, early de ath, or terminal euthanization at 105 weeks. Triprolidine did not sign ificantly alter the survival of either sex. High-dose male and mid- an d high-dose female body weights were significantly less than controls at the end of the study. Significant trends toward lower frequency wit h increasing dose were noted in females for fatty change in the liver and lymphomas (combination of lymphocytic, mixed, and histiocytic lymp homas). Similar negative trends in males were for lymphocytic cellular infiltration in multiple organs and lung alveolar/bronchiolar adenoma s or the combination of alveolar/bronchiolar adenomas or carcinomas. S ignificant trends toward increased frequency with increasing dose were found in female mice for lymphocytic infiltration in multiple organs and cytoplasmic alterations of the acinar cells of the parotid gland. Similar positive trends were found in males for cytoplasmic alteration s of the parotid gland and various hepatocellular changes (e.g., hyper trophy and altered foci). While there was a positive dose-response tre nd for hepatocellular adenomas in males the combination of these and h epatocellular carcinomas eliminated the significant trend, and it was concluded that there was no evidence of a carcinogenic response to tri prolidine in B6C3F1 mice. No effects considered to be adverse were obs erved in either sex at 500 ppm. Body weight depression was noted in fe males and liver toxicity was indicated in males at 2000 and 4000 ppm.