Toxicity testing and endocrine disrupting chemicals

Abstract

Regulatory agencies around the world depend on standardized testing approaches to evaluate environmental chemicals for endocrine disrupting properties. The US Environmental Protection Agency (EPA) has developed a two-tiered testing approach within its Endocrine Disruptor Screening Program (EDSP). The eleven Tier 1 and three Tier 2 EDSP assays can be used to identify chemicals that act as agonists or antagonists of estrogen receptor, androgen receptor, or thyroid hormone receptor, or chemicals that interfere with steroidogenesis. Additional assays have been developed in the context of Tox21, and others have been validated by the OECD. In spite of the availability of validated toxicity tests, problems have been identified with the approaches and methods used to identify endocrine disrupting chemicals (EDCs). This chapter will provide an overview of several of these issues including: (1) The way an EDC is defined by an agency impacts whether a specific test can be used to determine if a chemical is an EDC. This is especially important when considering which assays examine outcomes that are considered "adverse effects." (2) Some assumptions about the validated studies used to identify EDCs may not be true (e.g., their reproducibility has been questioned). (3) Many of the validated assays are less sensitive than other methods that have not yet been validated. Ultimately, these and other problems contribute to the current landscape, where testing approaches have failed to protect the public from known EDCs. The chapter concludes with a review of approaches that have been taken to improve current guideline studies.

Keywords: Ethinyl estradiol; Invertebrate; Metamorphosis; OECD; Reproducible; Test guideline; Tox21; Uterotrophic.