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Use of Mechanistic Models to Estimate Low‐Dose Cancer Risks
Author(s) -
Crump Kenny S.
Publication year - 1994
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/j.1539-6924.1994.tb00073.x
Subject(s) - risk analysis (engineering) , environmental science , environmental health , forensic engineering , computer science , engineering , medicine
The utility of mechanistic models of cancer for predicting cancer risks at low doses is examined. Based upon a general approximation to the dose‐response that is valid at low doses, it is shown that at low doses the dose‐response predicted by a mechanistic model is a linear combination of the dose‐responses for each of the physiological parameters in the model that are affected by exposure. This demonstrates that, unless the mechanistic model provides a theoretical basis for determining the dose‐responses for these parameters, the extrapolation of risks to low doses using a mechanistic model is basically “curve fitting,” just as is the case when extrapolating using statistical models. This suggests that experiments to generate data for use in mechanistic models should emphasize measuring the dose‐response for dose‐related parameters as accurately as possible and at the lowest feasible doses.