{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:37:22Z","timestamp":1777894642467,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:p>The carcinogenic potential of chlorpromazine hydrochloride, a psychotropic agent, was assessed in the p53 heterozygou s mouse assay. In a 4-week dose range fi nding study in p53 wild-type mice, doses of 20, 40, 60, and 80 mg\/kg were poorly tolerated becaus e of mortality secondary to the severe sedative and hypotensive effects of chlorpromazine. Based on 40% mortality at a dose of 20 mg\/kg in the dose-range fi nding study, a high dose of 10 mg\/kg was chosen for the 26-week carcinogenicity study in p53 heterozygous mice. Doses of 2.5, 5, and 10 mg\/kg chlorpromazin e hydrochloride were well tolerated in the 26-week study. The administration of chlorpromazine hydrochloride at dose levels up to and including 10 mg\/kg to p53 heterozygous and wild-type mice did not result in a dose-related increase in tumor incidence or in the type of tumors seen in comparison to controls. Findings related to the administration of chlorpromazine in the 26-week study were limited to minimal uterine and ovarian atrophy in p53 wild-type mice dosed with 10 mg\/kg chlorpromazine hydrochloride. However, p53 heterozygous mice administered 400 mg\/kg p-cresidine, a genotoxic carcinogen commonly used as a positive control for this model, developed urinary bladder tumors. Administration of p-cresidine also resulted in a regenerative anemia, splenic and hepatic hemosiderosis, renal findings, and ovarian and uterine atrophy. This study demonstrated that chlorpromazine hydrochloride, at the doses tolerated, was not carcinogenic in the p53 heterozygou s mouse assay.<\/jats:p>","DOI":"10.1080\/01926230290166788","type":"journal-article","created":{"date-parts":[[2003,1,6]],"date-time":"2003-01-06T23:28:16Z","timestamp":1041895696000},"page":"696-704","source":"Crossref","is-referenced-by-count":9,"title":["Toxicity and Carcinogenicity Studies of Chlorpromazine Hydrochloride and p-Cresidine in the p53 Heterozygous Mouse Model"],"prefix":"10.1177","volume":"30","author":[{"given":"Janet M.","family":"Petruska","sequence":"first","affiliation":[{"name":"Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, New Jersey 07848"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doyle W.","family":"Frank","sequence":"additional","affiliation":[{"name":"Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, New Jersey 07848"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary B.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Formerly of Battelle, Columbus, Ohio, currently at Pfi zer Global Research and Development, Groton, Connecticut 06340"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen W.","family":"Evans","sequence":"additional","affiliation":[{"name":"Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, New Jersey 07848"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James S.","family":"Macdonald","sequence":"additional","affiliation":[{"name":"Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, New Jersey 07848"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2002,10,1]]},"reference":[{"key":"atypb1","first-page":"165","volume":"238","author":"Bhargava HN","year":"1979","journal-title":"Arch Int Pharmacodyn"},{"key":"atypb2","unstructured":"Bithell TC (1993). 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