Noncancer Risk Assessment: Principles and Practice in Environmental and Occupational Settings

Abstract

Abstract The scientific process of risk assessment aims to define hazards associated with human exposure to chemicals. This chapter focuses primarily on the first two steps of the risk assessment process for noncancer endpoints, or more broadly, for modes of action not involving interaction with DNA. Hazard characterization consists of a systematic evaluation of available data to identify toxicologically relevant adverse outcomes, the associated mode of action, and evaluation of human relevance of the effects. Data quality and the overall weight of evidence are also evaluated. We summarize available technologies for dose–response assessment to define the critical effect and to extrapolate effect levels to human exposure scenarios and exposure durations, and we discuss methods for addressing uncertainties. Methods for evaluating data–poor chemicals or conducting screening assessments are also reviewed. Finally, we discuss how to interpret the dose–response information in the context of specific exposure data. Although this chapter focuses on the methods for deriving risk values from in vivo studies, we also address the use of data from the rapidly evolving field of new approach methodologies (including in vitro methods such as high‐throughput transcriptomics and in silico approaches such as modeling of structure–activity relationships). Ultimately, these new methodologies will foster a better understanding of how chemical exposures may cause toxicity, allow for more rapid assessment of chemicals, and support a reduction in the need for future toxicity testing in animals.