TRIPROLIDINE - 104-WEEK FEEDING STUDY IN RATS

The antihistamine, triprolidine hydrochloride, was fed at dietary conc entrations of 0, 250, 1000, or 2000 ppm (as the free base) to groups o f 60 Fischer 344 (F344) rats of each sex for up to 2 years to evaluate its potential carcinogenicity. Up to 12 per sex from each group were killed at 65 weeks, and hematology, clinical chemistry, and histopatho logy were evaluated. A complete histopathological evaluation was perfo rmed on all other animals; survivors were killed at 2 years. Survival was significantly extended in triprolidine-treated males and females, particularly at the high dose. At the close of the study high-dose mal es and females had gained significantly less body weight than controls . Among rats killed at 65 weeks females in the mid- and high-dose grou ps weighed significantly less than controls, but weights of control an d dosed males were not significantly different. The incidences of nume rous lesions tended to decrease with increasing triprolidine dose. In females, clitoral gland adenomas, thyroid c-cell hyperplasia and neopl asia, mammary gland hyperplasia and fibroadenomas, and uterine stromal polyps, and in males, anterior pituitary gland adenomas, preputial gl and neoplasia, thyroid c-cell hyperplasia, pancreatic islet neoplasia, mononuclear cell leukemia, and the combination of lymphocytic, histio cytic, and undifferentiated cell malignant lymphomas and mononuclear l eukemia, all exhibited negative dose trends. Cytoplasmic alterations o f the parotid gland and numerous liver lesions tended to be more frequ ent in treated than in control animals. Liver lesions that exhibited p ositive dose trends include chronic inflammation and centrilobular fat ty change in both sexes, mixed cell foci, and the combination of mixed cell foci and eosinophilic foci in females, and in males, basophilic foci and eosinophilic foci. Triprolidine was not carcinogenic in F344 rats. (C) 1995 Society of Toxicology