NEOPLASTIC LESIONS OF QUESTIONABLE SIGNIFICANCE TO HUMANS

Many compounds giving a positive result in animal carcinogenicity stud ies through mechanisms involving secondary carcinogenesis pose little or no risk to humans. This article provides an overview of current und erstanding, with particular reference to renal tumors in male rats wit h alpha2mu-globulin nephropathy, urinary bladder neoplasia in rodents, mesovarian leiomyomas induced in rats by beta2-receptor stimulants, c arcinoid tumors in the rodent stomach induced by prolonged suppression of acid secretion, thyroid follicular cell tumors in rodents, canine mammary neoplasia due to administration of progestagens, rodent mammar y neoplasia induced by estrogens, uterine endometrial carcinomas of ra ts induced by dopamine agonists, Leydig cell tumors in the testis of r ats, and ovarian tubulostromal adenomas in mice. A positive result on a rodent carcinogenicity study should not automatically preclude furth er development of a compound; future progress in this field should inc rease the accuracy of the rodent carcinogenicity study as a tool in hu man safety assessment.