Chapter 7 - The Role of Pathology in Evaluation of Reproductive, Developmental, and Juvenile Toxicity

Abstract

Drug and chemical product labels are expected to specifically address risks to special populations such as pregnant women and children and are expected to highlight potential effects on male and female fertility. Therefore, developmental and reproductive toxicity (DART) studies are a key component of toxicology programs to assess both drugs and environmental chemicals. Pathology is a critical endpoint for many of these studies, especially those that assess fertility or offspring. In assessing potential effects on pregnancy and developmental toxicity, pathology is not routinely included but can aid study interpretation when added for cause. Importantly, these specialized studies often include assessments that are not part of any other study in the toxicology program. Therefore, an integrated assessment of endpoints and studies including pathology is often necessary for appropriate interpretation and to guide human risk assessment. In this chapter, we will review experimental strategies and the objectives of these assessments, including pathology, where appropriate. Next, we will discuss features of postnatal development across species that can help inform interpretation of pathology from offspring or juveniles. Finally, the current regulatory context is discussed, and selected references are provided for more in-depth study of specific topics introduced. Importantly, the DART and juvenile testing approach should be flexible, and focus on the scientific objectives for risk assessment rather than simply a “check box” approach.