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Extrapolation of Carcinogenicity Between Species: Qualitative and Quantitative Factors

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  • Lois Swirsky Gold
  • Neela B. Manley
  • Bruce N. Ames

Abstract

Prediction of human cancer risk from the results of rodent bioassays requires two types of extrapolation: a qualitative extrapolation from short‐lived rodent species to long‐lived humans, and a quantitative extrapolation from near‐toxic doses in the bioassay to low‐level human exposures. Experimental evidence on the accuracy of prediction between closely related species tested under similar experimental conditions (rats, mice, and hamsters)indicates that: (1)if a chemical is positive in one species, it will be positive in the second species about 75% of the time; however, since about 50% of test chemicals are positive in each species, by chance alone one would expect a predictive value between species of about 50%. (2)If a chemical induces tumors in a particular target organ in one species, it will induce tumors in the same organ in the second species about 50% of the time. Similar predictive values are obtained in an analysis of prediction from humans to rats or from humans to mice for known human carcinogens. Limitations of bioassay data for use in quantitative extrapolation are discussed, including constraints on both estimates of carcinogenic potency and of the dose‐response in experiments with only two doses and a control. Quantitative extrapolation should be based on an understanding of mechanisms of carcinogenesis, particularly mitogenic effects that are present at high and not low doses.

Suggested Citation

  • Lois Swirsky Gold & Neela B. Manley & Bruce N. Ames, 1992. "Extrapolation of Carcinogenicity Between Species: Qualitative and Quantitative Factors," Risk Analysis, John Wiley & Sons, vol. 12(4), pages 579-588, December.
  • Handle: RePEc:wly:riskan:v:12:y:1992:i:4:p:579-588
    DOI: 10.1111/j.1539-6924.1992.tb00714.x
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    References listed on IDEAS

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    1. Lois Swirsky Gold & Leslie Bernstein & Bruce N. Ames, 1990. "The Importance of Ranking Possible Carcinogenic Hazards Using HERP," Risk Analysis, John Wiley & Sons, vol. 10(4), pages 625-628, December.
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    Cited by:

    1. Reuben Thomas & Russell S Thomas & Scott S Auerbach & Christopher J Portier, 2013. "Biological Networks for Predicting Chemical Hepatocarcinogenicity Using Gene Expression Data from Treated Mice and Relevance across Human and Rat Species," PLOS ONE, Public Library of Science, vol. 8(5), pages 1-10, May.
    2. Emmanuel Somers, 1995. "Perspectives on Risk Management," Risk Analysis, John Wiley & Sons, vol. 15(6), pages 677-684, December.
    3. David A. Freedman & Lois Swirsky Gold & Thomas H. Slone, 1993. "How Tautological Are Interspecies Correlations of Carcinogenic Potencies?," Risk Analysis, John Wiley & Sons, vol. 13(3), pages 265-272, June.
    4. Lois Swirsky Gold, 1993. "The Importance of Data on Mechanism of Carcinogenesis in Efforts to Predict Low‐Dose Human Risk," Risk Analysis, John Wiley & Sons, vol. 13(4), pages 399-401, August.

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    1. D. Krewski & D .W. Gaylor & A. P. Soms & M. Szyszkowicz, 1993. "An Overview of the Report: Correlation Between Carcinogenic Potency and the Maximum Tolerated Dose: Implications for Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 13(4), pages 383-398, August.

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