chapter  2
Experimental approaches to evaluate mechanisms of developmental toxicity
ByElaine M. Faustman, Julia M. Gohlke, Rafael A. Ponce, Tom A. Lewandowski, Marguerite R. Seeley, Stephen G. Whittaker, William C. Griffith
Pages 35

Definitions In order to develop this paper, a few common definitions must be discussed. Mechanisms of toxic action will be used to refer to the detailed molecular understanding of how chemicals can impair normal physiological processes and hence, produce developmental toxicity. Mechanistic information can include biochemical, genetic, molecular, cellular, and/or organ systems information (6). Mode of action for developmental toxicants is frequently used to refer to the identification of critical steps that can explain how an agent can produce developmental toxicity and usually refers to a less-detailed but more comprehensive description of the overall process of developmental toxicity. This chapter will include a discussion of approaches used for understanding mechanisms for all four endpoints of developmental toxicity: lethality, growth retardation, morphological defects (teratogenicity), and functional impacts. Throughout this chapter, we will refer to developmental dynamics and will use this general term to describe the genetic, biochemical, molecular, cellular, organ, and organism-level processes that change throughout development and define and characterize the developing organism at each life stage (11). We will use the term, kinetics, to refer to the absorption, distribution, metabolism, and distribution of chemicals, as many of our discussions of developmental dynamics directly relate to the amount and form of the environmental or pharmacological agent that reaches the developing organism.