Physiological Modeling and Cancer Risk Assessment

  • Kannan Krishnan
  • Melvin E. Andersen
Part of the NATO ASI Series book series (NSSA, volume 221)


Quantitative risk assessment for carcinogens is frequently performed based on evidence of their tumorigenicity in animals. In animal bioassay studies, the test chemicals are administered at high doses and by routes often different from anticipated human exposures. A. particularly challenging aspect in cancer risk assessment is the extrapolation of tumor responses in animals to humans exposed at concentrations much below those tested under the range of the animal bioassay conditions. Since high doses of chemicals are usually administered during these studies, a metabolic saturation may lead to nonlinearities of target tissue dose and exposure concentrations. Tumor response in such cases may not be directly proportional to the external or exposure concentration of the chemical, but rather will reflect the complex nonlinear pharmacokinetic processes occurring in the organism at high concentrations. Therefore, a quantitative understanding of the critical biological determinants of pharmacokinetics and cancer response is necessary to confidently predict the carcinogenic risks associated with human exposure to chemicals. This chapter presents a review of the conventional cancer risk assessment methodology, and discusses the utility of biologically-based tissue dosimetry and cancer response modeling approaches in reducing some of the uncertainties associated with it.


Exposure Concentration PBPK Model Physiological Modeling Cancer Risk Assessment Threshold Limit Value 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Kannan Krishnan
    • 1
  • Melvin E. Andersen
    • 1
  1. 1.Chemical Industry Institute of ToxicologyResearch Triangle ParkUSA

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