Dose–Effect and Dose–Response Assessment

Abstract Dose–effect and dose–response assessments are important to the overall risk assessment process by providing a quantitative estimation of the relationship between dose/exposure and the occurrence of adverse effects from human exposure to metallic species. This chapter defines the concepts of dose–effect and dose–response relationships, discusses the importance of identifying the critical effect and estimates the critical concentration for toxicity in the critical organ. It further describes how to use these concepts in quantitation of the overall relationship between external exposure, internal exposure/dose, and the likelihood of occurrence of adverse effects in groups or populations. This chapter gives definitions of the no-observed-adverse-effect level, benchmark dose, and its lower confidence limit, which are important concepts in risk assessment. It further describes various approaches to estimate a low (acceptable) risk to humans, based on experimental and epidemiological data. The chapter gives special emphasis on quantitative estimation of dose–response relationships based on the mechanism of action and toxicokinetic and toxicodynamic modeling and describes results of such modeling in terms of dose–response curves. It includes discussions of the use of adverse outcome pathways.