ES Series: Cancer Risk Assessment. 2. Physiological pharmacokinetic modeling.

Risk assessment often defines the approach and the degree of regulation, decisions in risk assessment often have major regulatory impacts. Chemicals that have economic value or that were byproducts of the chemical industry are common subjects of such decisions. Regrettably, decisions related to risk assessment, science, or regulatory matters will frequently be made with incomplete information and on the basis of intuitive reasoning. Statistical fits to experimental data have been used to estimate risks in humans from experimental data in animals. These treatments have not taken into account the obvious differences in physiology, biochemistry, and size between aniamals and humans. In this article the use of mathematical models based on continuous relationships, rather than quantal events, are discussed. The mathematical models can be used to adjust the dose in the quantal response model, but the emphasis will be on how these mathematical models are conceived and what implications their use holds for risk assessment. Experiments with humans that produce toxic effects cannot be done. Data for human toxicity will always be lacking.