Chapter 7 - Nonmonotonic Responses in Endocrine Disruption

Abstract

There are a number of features of endocrine-disrupting chemicals (EDCs) that distinguish them from traditional toxicants. One such attribute is the ability of EDCs to induce nonmonotonic dose response curves (NMDRCs), where low and high doses can produce opposite effects. NMDRCs are often described as U- or inverted U-shaped, and they are a common feature in a number of scientific fields, including endocrinology, nutrition, and pharmacology. This chapter describes the mechanisms by which NMDRCs can manifest and some specific examples from the EDC literature. It also describes the recent debate over whether NMDRCs are “real,” and whether they are common enough to influence chemical safety assessments for EDCs. Finally, this chapter concludes with a discussion about a related but distinct phenomenon known as low-dose effects. Together, these two features of EDCs suggest that the methods used to determine safe doses for human exposures are flawed.