ABSTRACT
This chapter focuses on the derivation and use of mechanistic information for the development of tissue dosimetry models and for evaluations of human health risks associated with exposure to toxic or carcinogenic agents. Health concerns exist for chemicals that are members of a class of compounds that induce toxic effects in humans or animal models. Pharmacodynamic modeling provides an approach to estimate rates of tissue responses in relation to the delivered dose. Pharmacodynamic models may also lead to mechanistic hypotheses, which if properly tested, may shed new insights on cellular processes that are altered by the agent under study. The development of a dosimetry model for the genotoxic carcinogen, 1,3-butadiene, and pharmacodynamic models for dioxin-induced receptor-mediated processes provide several examples illustrating how toxicity and mechanistic studies can help elucidate critical information for use in risk assessments. A biologically based dose–response model for peroxisome proliferator-induced cell proliferation and suppression of apoptosis is needed.
