Utilizing Biologically Based Models to Estimate Carcinogenic Risk

  • Christopher J. Portier


The limitations associated with using biologically-based mathematical models for the estimation of carcinogenic risks from long-term chemical exposures at low dose levels represents a statistical and mathematical challenge with special relevance to environmental research. Determining an adequate model for estimating the relationship between dose and response is critical to reducing potential bias in the risk estimation process. This talk discusses the various assumptions and models used in carcinogenic risk assessment. The emphasis will be on the accuracy with which the magnitude of the carcinogenic risk, the shape of the dose-response relationship and the overall variability of the risk estimates can be determined from the available data.


Equivalent Dose Tumor Incidence Intermediate Cell Cancer Risk Assessment Mixed Function Oxidase 
These keywords were added by machine and not by the authors.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andersen, M., Clewell, H., Gargas, F., Smith, F., and Reitz, R. (1987). Physiologically based pharmacokinetics and the risk assessment process for methylene chloride. Toxicology and Applied Pharmacology 87: 185–202.CrossRefGoogle Scholar
  2. Anderson, E. and the Carcinogen Assessment Group (1983). Quantitative approaches in use to assess cancer risk. Risk Analysis 3: 277–295.CrossRefGoogle Scholar
  3. Anderson, M. (1987). Issues in biochemical applications to risk assessment: How do we evaluate individual components of multistage models? Environmental Health Perspectives 76, 175–180.CrossRefGoogle Scholar
  4. Armitage, P. and Doll, R. (1954). The age distribution of cancer and a multistage theory of cancer. British Journal of Cancer 8: 1–12.CrossRefGoogle Scholar
  5. Barrett, J. C. and Wiseman, R. (1987). Cellular and molecular mechanisms of multistep carcinogenesis: Relevance to carcinogen risk assessment. Environmental Health Perspectives 76, 65–70.CrossRefGoogle Scholar
  6. Barrett, J. C. and Wiseman, R. W. (1989). Relevance of Cellulart and Molecular Mechanisms of Multistep Carcinogenesis to Risk Assessment, (unpublished manuscript).Google Scholar
  7. Bogen, K. (1989). Cell proliferation kinetics and multistage cancer risk models. Journal of the National Cancer Institute 81, 267–277CrossRefGoogle Scholar
  8. EPA (1986). Guidelines for carcinogen risk assessment. 51 Federal Register 33992, 1–17.Google Scholar
  9. Farber, E. (1984). Cellular biochemistry of the stepwise development of cancer with chemicals. Cancer Research 44: 5463–5474.Google Scholar
  10. Hoel, D., Kaplan, N. and Anderson, M. (1983). Implication of nonlinear kinetics on risk estimation in carcinogenesis. Science 219: 1032–1037.CrossRefGoogle Scholar
  11. Hoel, D. (1980). Incorporation of background in dose-response models. Federation Proceedings 39: 73–75.Google Scholar
  12. Kopp, A. and Portier, C. (1989). A note on approximating the cumulative distribution function of the time to tumor onset in multistage models, (unpublished manuscript).Google Scholar
  13. Lewis, J. and Adams, D. (1987). Inflammation, oxidative DNA damage and carcinogenesis. Environmental Health Perspectives 76, 19–28.CrossRefGoogle Scholar
  14. Moolgavkar, S. (1983). Model for human carcinogenesis: Action of environmental agents. Environmental Health Perspectives 50: 285–291.CrossRefGoogle Scholar
  15. Moolgavkar, S., Dewanji, A., and Venzon, D. (1988). A stochastic two-stage model for cancer risk assessment. I. The hazard function and the probability of tumor. Risk Analysis 8 (3), 383–392.CrossRefGoogle Scholar
  16. Moolgavkar, S. and Dewanji, A. (1988). Biologically based models for cancer risk assessment: A cautionary note. Risk Analysis 8(1), 5–6.CrossRefGoogle Scholar
  17. Pitot, H., Barsness, L. and Kitagawa, T. (1978). Stages in the process of hepatocarcinogenesis in rat liver. Carcinogenesis 2: 433–442.Google Scholar
  18. Portier, C. (1987). Statistical properties of a two-stage model of carcinogenesis. Environmental Health Perspectives 76: 125–131.CrossRefGoogle Scholar
  19. Portier, C. and Kaplan, N. (1989). The variability of safe dose estimates when using complicated models of the carcinogenic process. A case study: Methylene chloride. Fundamental and Applied Toxicology 13, 533–544.CrossRefGoogle Scholar
  20. Portier, C. (1989). Quantitative risk assessment. In Ragsdale, N. and Menzer, R. (eds.): Carcinogenicity and Pesticides. American Chemical Society Symposium Series Number 414; (to appear).Google Scholar
  21. Portier, C., Hoel, D., Kaplan, N. and Kopp, A. (1990) Biologically based models for risk assessment. In H. Vannio, M. Sorsa and A. J. McMichael (eds) Complex Mixtures and Cancer Risk. IARC Scientific Publications Number 104, International Agency for Research on Cancer, Lyon (to appear).Google Scholar
  22. Portier, C. and Edler, L. (1989) Two-stage models of carcinogenesis, classification of agents and design of experiments, (submitted)Google Scholar
  23. Prehn, R. (1964). A clonal selection theory of chemical carcinogenesis. Journal of the National Cancer Institute 32 (1): 1–17.Google Scholar
  24. Reynolds, S., Stowers, S., Patterson, R., Maronpot, R., Aaronson, S. and Anderson, M. (1987). Activated oncogenes in B6C3F1 mouse liver tumors: Implications for risk assessment. Science 237, 1309–1316.CrossRefGoogle Scholar
  25. Sakata, T., Masui, T., St. John, M. and Cohen, S. (1988). Uracil-induced calculi and proliferative lesions of the mouse urinary bladder. Carcinogenesis 9 (7), 1271–1276.CrossRefGoogle Scholar
  26. Schwartz, M., Pearson, D., Port, R. and Kunz, W. (1984). Promoting effect of 4-dimethylaminoazobenzene on enzyme altered foci in rat liver by N-nitrosodiethanolamine. Carcinogenesis 5: 725–730.CrossRefGoogle Scholar
  27. Swenberg, J., Richardson, F., Boucheron, J. and Dryoff, M. (1985). Relationships between DNA adduct formation and carcinogenesis. Environmental Health Perspectives 62: 177–183.CrossRefGoogle Scholar
  28. Swenberg, J., Richardson, F., Boucheron, J., Deal, F., Belinsky, S., Charbonneau, M. and Short, B. (1987). High to low dose extrapolation: Critical determinants involved in the dose response of carcinogenic substances. Environmental Health Perspectives 76, 57–63.CrossRefGoogle Scholar
  29. Thorslund, T., Brown, C. and Charnley, G. (1987). Biologically motivated cancer risk models. Risk Analysis 7: 109–119.CrossRefGoogle Scholar
  30. Travis, C. and White, R. (1988). Interspecies scaling of toxicity data. Risk Analysis 8, 119–125.CrossRefGoogle Scholar
  31. Whittemore, A. and Keller, J. (1978). Quantitative theories of carcinogenesis. SIAM Review 20, 1–30.CrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1990

Authors and Affiliations

  • Christopher J. Portier

There are no affiliations available

Personalised recommendations