Cancer dose-response extrapolations
Journal Article
·
· Environ. Sci. Technol.; (United States)
Quantitative dose-response modeling is an important contributor to cancer risk assessment; hence, it is a major factor in cancer risk management and the regulatory process. The dose-response models now used in the regulatory process are overly simplistic, probabilistic representations of highly complex biological phenomena; these models are not biological models. Several of these simplistic models provide similar fits to the high-dose data generated in chronic animal bioassays but provide dissimilar projections of risk at the lower doses of interest to man. The possibilities for the low-dose behavior of a simplistic model can be so independent of the fit of that model to the experimental data that an upper confidence limit, or upper bound, on the risk at a low dose can be orders of magnitude larger than the fitted model. The potency measures, such as unit risks and relative risks, cited by the regulatory agencies are based on upper bounds and not on fitted model values. These measurements do not differentiate between carcinogens on the basis of available experimental data about the shapes of the dose-response relationship. In order to obtain more useful quantitative dose-response assessments, the plethora of simplistic models must be replaced by more biologically reflective dose-response models that utilize the available scientific information. New dose-response modeling techniques can incorporate representations of the exposure in terms of dose scales based on cell turnover rates, repair processes, immune system responses, and physiological and pharmacokinetic models of the absorption, delivery, metabolism, and elimination of chemicals.
- Research Organization:
- Sielken, Inc., Bryan, TX (USA)
- OSTI ID:
- 5101652
- Journal Information:
- Environ. Sci. Technol.; (United States), Journal Name: Environ. Sci. Technol.; (United States) Vol. 21:11; ISSN ESTHA
- Country of Publication:
- United States
- Language:
- English
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