Abstract
The selection process for chemicals tested in the rodent carcinogenicity bioassay has been biased toward chemicals suspected of potential carcinogenicity. Results from carcinogenicity bioassays of 400 chemicals tested by the National Cancer Institute/National Toxicology Program (NCI/NTP) were analyzed to determine the dependence of positive results on chemical selection criteria: those suspected of being carcinogenic and those selected based on large volumes produced and widespread exposures. Of these chemicals, 210 (52%) induced carcinogenicity in at least one organ of one sex of one species of the four sex/species groups typically used by NCI/NTP. Only 92 of the 400 chemicals (23%) were positive in two species and thus by international criteria are considered likely to pose a carcinogenic hazard to humans. A total of 267 chemicals (67%) were selected as suspect carcinogens, and 187 (68%) of these were carcinogenic. Suspect chemicals account for 86% of chemicals with at least one positive result and account for 90% of chemicals considered positive in two species. The International Agency for Research on Cancer (IARC) lists only 5 of the 400 chemicals as carcinogenic to humans (group 1) and 10 as probably carcinogenic to humans (group 2A). The majority (80%) of the 133 chemicals selected only on production/exposure considerations were not carcinogenic in animals, even when tested at the maximum tolerated (or minimally toxic) dose. Only 9 (6.8%) were positive in two species, and none is listed in IARC groups 1 or 2A. Thus, on the basis of our analyses we predict that less than 5-10% of the 75,000 chemicals in commercial use might be reasonably anticipated to be carcinogenic to humans.
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- Ames B. N., Gold L. S. Too many rodent carcinogens: mitogenesis increases mutagenesis. Science. 1990 Aug 31;249(4972):970–971. doi: 10.1126/science.2136249. [DOI] [PubMed] [Google Scholar]
- Barrett J. C. Mechanisms of multistep carcinogenesis and carcinogen risk assessment. Environ Health Perspect. 1993 Apr;100:9–20. doi: 10.1289/ehp.931009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bertram J. S., Kolonel L. N., Meyskens F. L., Jr Rationale and strategies for chemoprevention of cancer in humans. Cancer Res. 1987 Jun 1;47(11):3012–3031. [PubMed] [Google Scholar]
- Boyd J. A., Barrett J. C. Genetic and cellular basis of multistep carcinogenesis. Pharmacol Ther. 1990;46(3):469–486. doi: 10.1016/0163-7258(90)90028-z. [DOI] [PubMed] [Google Scholar]
- Chhabra R. S., Huff J. E., Schwetz B. S., Selkirk J. An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program. Environ Health Perspect. 1990 Jun;86:313–321. doi: 10.1289/ehp.9086313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chu K. C., Cueto C., Jr, Ward J. M. Factors in the evaluation of 200 National Cancer Institute carcinogen bioassays. J Toxicol Environ Health. 1981 Jul-Aug;8(1-2):251–280. doi: 10.1080/15287398109530068. [DOI] [PubMed] [Google Scholar]
- Fung V. A., Huff J., Weisburger E. K., Hoel D. G. Predictive strategies for selecting 379 NCI/NTP chemicals evaluated for carcinogenic potential: scientific and public health impact. Fundam Appl Toxicol. 1993 May;20(4):413–436. doi: 10.1006/faat.1993.1053. [DOI] [PubMed] [Google Scholar]
- Huff J. E., McConnell E. E., Haseman J. K., Boorman G. A., Eustis S. L., Schwetz B. A., Rao G. N., Jameson C. W., Hart L. G., Rall D. P. Carcinogenesis studies: results of 398 experiments on 104 chemicals from the U.S. National Toxicology Program. Ann N Y Acad Sci. 1988;534:1–30. doi: 10.1111/j.1749-6632.1988.tb30085.x. [DOI] [PubMed] [Google Scholar]
- Huff J. Absence of morphologic correlation between chemical toxicity and chemical carcinogenesis. Environ Health Perspect. 1993 Dec;101 (Suppl 5):45–53. doi: 10.1289/ehp.93101s545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huff J. Chemicals and cancer in humans: first evidence in experimental animals. Environ Health Perspect. 1993 Apr;100:201–210. doi: 10.1289/ehp.93100201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huff J. Design strategies, results and evaluations of long-term chemical carcinogenesis studies. Scand J Work Environ Health. 1992;18 (Suppl 1):31–37. [PubMed] [Google Scholar]
- Huff J., Haseman J., Rall D. Scientific concepts, value, and significance of chemical carcinogenesis studies. Annu Rev Pharmacol Toxicol. 1991;31:621–652. doi: 10.1146/annurev.pa.31.040191.003201. [DOI] [PubMed] [Google Scholar]
- Huff J., Hoel D. Perspective and overview of the concepts and value of hazard identification as the initial phase of risk assessment for cancer and human health. Scand J Work Environ Health. 1992;18 (Suppl 1):83–89. [PubMed] [Google Scholar]
- Huff J. Issues and controversies surrounding qualitative strategies for identifying and forecasting cancer causing agents in the human environment. Pharmacol Toxicol. 1993;72 (Suppl 1):12–27. doi: 10.1111/j.1600-0773.1993.tb01664.x. [DOI] [PubMed] [Google Scholar]
- Huff J. Mechanisms, chemical carcinogenesis, and risk assessment: cell proliferation and cancer. Am J Ind Med. 1995 Feb;27(2):293–300. doi: 10.1002/ajim.4700270213. [DOI] [PubMed] [Google Scholar]
- Lijinsky W. Species differences in carcinogenesis. In Vivo. 1993 Jan-Feb;7(1):65–72. [PubMed] [Google Scholar]
- Melnick R. L., Huff J., Barrett J. C., Maronpot R. R., Lucier G., Portier C. J. Cell proliferation and chemical carcinogenesis: a symposium overview. Mol Carcinog. 1993;7(3):135–138. doi: 10.1002/mc.2940070302. [DOI] [PubMed] [Google Scholar]
- Melnick R. L., Huff J., Barrett J. C., Maronpot R. R., Lucier G., Portier C. J. Cell proliferation and chemical carcinogenesis: symposium overview. Environ Health Perspect. 1993 Dec;101 (Suppl 5):3–7. doi: 10.1289/ehp.93101s53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melnick R. L., Huff J. Liver carcinogenesis is not a predicted outcome of chemically induced hepatocyte proliferation. Toxicol Ind Health. 1993 May-Jun;9(3):415–438. doi: 10.1177/074823379300900303. [DOI] [PubMed] [Google Scholar]
- Preston-Martin S., Pike M. C., Ross R. K., Jones P. A., Henderson B. E. Increased cell division as a cause of human cancer. Cancer Res. 1990 Dec 1;50(23):7415–7421. [PubMed] [Google Scholar]
- Tennant R. W., Spalding J., Stasiewicz S., Ashby J. Prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 44 chemicals by the National Toxicology Program. Mutagenesis. 1990 Jan;5(1):3–14. doi: 10.1093/mutage/5.1.3. [DOI] [PubMed] [Google Scholar]
- Tennant R. W. Stratification of rodent carcinogenicity bioassay results to reflect relative human hazard. Mutat Res. 1993 Mar;286(1):111–118. doi: 10.1016/0027-5107(93)90006-2. [DOI] [PubMed] [Google Scholar]
- Tomatis L., Aitio A., Wilbourn J., Shuker L. Human carcinogens so far identified. Jpn J Cancer Res. 1989 Sep;80(9):795–807. doi: 10.1111/j.1349-7006.1989.tb01717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomatis L. The predictive value of rodent carcinogenicity tests in the evaluation of human risks. Annu Rev Pharmacol Toxicol. 1979;19:511–530. doi: 10.1146/annurev.pa.19.040179.002455. [DOI] [PubMed] [Google Scholar]
- Wachsman J. T., Bristol D. W., Spalding J., Shelby M., Tennant R. W. Predicting chemical carcinogenesis in rodents. Environ Health Perspect. 1993 Oct;101(5):444–445. doi: 10.1289/ehp.93101444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinstein I. B. Mitogenesis is only one factor in carcinogenesis. Science. 1991 Jan 25;251(4992):387–388. doi: 10.1126/science.1989073. [DOI] [PubMed] [Google Scholar]
- Weisburger E. K. History of the Bioassay Program of the National Cancer Institute. Prog Exp Tumor Res. 1983;26:187–201. doi: 10.1159/000407260. [DOI] [PubMed] [Google Scholar]
- Wilbourn J., Haroun L., Heseltine E., Kaldor J., Partensky C., Vainio H. Response of experimental animals to human carcinogens: an analysis based upon the IARC Monographs programme. Carcinogenesis. 1986 Nov;7(11):1853–1863. doi: 10.1093/carcin/7.11.1853. [DOI] [PubMed] [Google Scholar]

