Chronic Study of Triprolidine for Oncogenicity in Mice

Triprolidine hydrochloride was fed to groups of 60 B6C3F1 miceper sex at dietary levels of 0, 500, 2000, or 4000 ppm (as thefree base) for up to 2 years. Up to 12 mice of each sex anddose group were terminated after 65 weeks for hematology andclinical chemistry. The control and high-dose groups were examinedhistologically. A complete histopathological examination wasperformed on the remaining 48 mice from each dose group whenremoved from study due to moribund condition, early death, orterminal euthanization at 105 weeks. Triprolidine did not significantlyalter the survival of either sex. High-dose male and mid- andhigh-dose female body weights were significantly less than controlsat the end of the study. Significant trends toward lower frequencywith increasing dose were noted in females for fatty changein the liver and lymphomas (combination of lymphocytic, mixed,and histiocytic lymphomas). Similar negative trends in maleswere for lymphocytic cellular infiltration in multiple organsand lung alveolar/bronchiolar adenomas or the combination ofalveolar/bronchiolar adenomas or carcinomas. Significant trendstoward increased frequency with increasing dose were found infemale mice for lymphocytic infiltration in multiple organsand cytoplasmic alterations of the acinar cells of the parotidgland. Similar positive trends were found in males for cytoplasmicalterations of the parotid gland and various he-patocellularchanges (e.g., hypertrophy and altered foci). While there wasa positive dose-response trend for hepatocellular adenomas inmales the combination of these and hepatocellular carcinomaseliminated the significant trend, and it was concluded thatthere was no evidence of a carcinogenic response to triprolidinein B6C3F1 mice. No effects considered to be adverse were observedin either sex at 500 ppm. Body weight depression was noted infemales and liver toxicity was indicated in males at 2000 and4000 ppm.