The 1994 U.S. Physicians' Desk Reference reports the results of rodent carcinogenicity tests on 241 pharmaceutical agents. Positive results were reported for 101 agents, with a class label implying a carcinogenic hazard also attached to 9 estrogenic, 4 androgenic, and 3 progestogenic agents. Of the positive agents tested in both rats and mice, 39 of 72 were positive in both species, 22 were positive in rats only, and 11 were positive in mice only. There were few (19) unequivocally genotoxic agents, and only one of these was not reported to be tumorigenic to rodents. The liver was a common target organ in rats and mice. In rats, the other most common target organs for tumors were (in decreasing order) the thyroid, testis, mammary, adrenal, and pituitary. In mice, the only other common target organ was the lung.
Alison RH, Capen CC, Prentice DE. (1994) Neoplastic lesions of questionable significance to humans. Toxicol Pathol22:179–86.
2.
Ashby J. (1991) Determination of the genotoxic status of a chemical. Mutat Res248:221–31.
3.
Ashby J, Tennant RW. (1991) Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat Res257:229–306.
4.
Butterworth BE. (1989) Non-genotoxic carcinogens in the regulatory environment. Regul Toxicol Pharmacol8:244–56.
5.
Gold LS, Bernstein L, Magaw R, Slone T. (1989) Interspecies extrapolation in carcinogenesis: prediction between rats and mice. Environ Health Perspect81:211–9.
6.
Goodman JI, Ward JM, Popp JA, Klaunig JE, Fox TR. (1991) Mouse liver carcinogenesis: mechanisms and relevance. Fundam Appl Toxicol17:651–65.
7.
Grasso P, Sharratt M, Cohen AJ. (1991) Role of persistent, non-genotoxic tissue damage in rodent cancer and relevance to humans. Annu Rev Pharmacol Toxicol31:253–87.
8.
Griffith RW. (1988) Carcinogenic potential of marketed drugs. J Clin Res Drug Devel2:141–4.
9.
Huff J, Haseman J, Rail D. (1991) Scientific concepts, value, and significance of chemical carcinogenesis studies. Annu Rev Pharmacol Toxicol31:621–52.
10.
MacDonald JS, Lankas GR, Morrissey RE. (1994) Toxicokinetic and mechanistic considerations in the interpretation of the rodent bioassay. Toxicol Pathol22:124–40.
11.
Malkinson AM. (1989) The genetic basis of susceptibility to lung tumors in mice. Toxicology54:241–71.
12.
Marselos M, Vainio H. (1991) Carcinogenic properties of pharmaceutical agents evaluated in the IARC Monographs programme. Carcinogenesis12:1751–6.
13.
McAuslane JAN, Lumley CE. (1993) Carcinogenicity studies for pharmaceuticals: classification and misclassification. Drug Info J27:509–14.
14.
McClain RM. (1994) Mechanistic considerations in the regulation and classification of chemical carcinogens. In: Kotsonis FN, Mackey M, Hjelle J, eds. Nutritional Toxicology.New York: Raven Press, 273–304.
15.
Monro A. (1993) How useful are chronic (life-span) toxicology studies in rodents in identifying pharmaceuticals that pose a carcinogenic risk to humans?Adverse Drug React Toxicol Rev12:5–34.
16.
Neumann F. (1991) Early indicators for carcinogenesis in sex-hormone-sensitive organs. Mutat Res248:341–56.
17.
NTP. (1992) Final report of the advisory review by the NTP board of scientific counselors. Fed Regist57:31721–30.
18.
PDR. (1994) Des Moines, Iowa: Medical Economics Data.
19.
Roe FJC. (1987) Liver tumors in rodents: extrapolation to man. Adv Veter Sci Comp Med31:45–68.
20.
Roe FJC. (1989) Non-genotoxic carcinogenesis: implications for testing and extrapolation to man. Mutagenesis4:407–11.
21.
Schach von Wittenau M, Estes PC. (1983) The redundancy of mouse carcinogenicity bioassays. Fundam Appl Toxicol3:631–9.
22.
Stevenson DE, McClain RM, Popp JA, Slaga TJ, Ward JM, Pitot HC. (1990) Mouse Liver Carcinogenesis; Mechanisms and Species Comparisons. New York: Wiley-Liss.
23.
Tennant RW. (1993) Stratification of rodent carcinogenicity bioassay results to reflect relative human hazard. Mutat Res286:111–8.
24.
Tomatis L, Aitio A, Wilbourn J, Shuker L. (1989) Human carcinogens identified so far. Jpn J Cancer Res80:795–807.
