Biologically-Based Models to Predict Cancer Risk
Mathematical dose-response models are currently used to extrapolate cancer risk from the high dose levels used in laboratory bioassays to the low, environmental dose levels to which humans are generally exposed. These models are empirical in nature and lack a biological basis. It has long been recognized that the accuracy with which a mathematical model predicts cancer risks at low doses is dependent upon the validity of the underlying biological paradigm on which it is based. A model that is chosen because it provides a “best fit” to tumor data observed at high doses may greatly over- or underestimate risk at low doses. Historically, regulatory agencies have had to use the available models in the absence of more appropriate alternatives; however, this is no longer the case. Our under standing of the mechanisms of carcinogenesis has advanced to a point where use of a biologically-based cancer model is now feasible.
KeywordsPolycyclic Aromatic Hydrocarbon Mitotic Division Susceptible Cell Syrian Golden Hamster National Toxicology Program
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