No abstract

This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.

In response to various legislative mandates, the US Environmental Protection Agency (USEPA) formed its Endocrine Disruptor Screening Program (EDSP), which in turn, formed the basis of a tiered testing strategy to determine the potential of pesticides, commercial chemicals, and environmental contaminants to disrupt the endocrine system. The first tier of tests is intended to detect the potential for endocrine disruption mediated through estrogen, androgen, or thyroid pathways, whereas the second tier is intended to further characterize the effects on these pathways and to establish a dose-response relationship for adverse effects. One of these tier 2 tests, the Medaka Extended One Generation Reproduction Test (MEOGRT), was developed by the USEPA for the EDSP and, in collaboration with the Japanese Ministry of the Environment, for the Guidelines for the Testing of Chemicals of the Organisation for Economic Co-operation and Development (OECD). The MEOGRT protocol was iteratively modified based on knowledge gained after the successful completion of 9 tests with variations in test protocols. The present study describes both the final MEOGRT protocol that has been published by the USEPA and the OECD, and the iterations that provided valuable insights into nuances of the protocol. The various tests include exposure to 17β-estradiol, 4-t-octylphenol, o,p'- dichlorodiphenyltrichloroethane, 4-chloro-3-methylphenol, tamoxifen, 17β-trenbolone, vinclozolin, and prochloraz. Environ Toxicol Chem 2017;36:3387-3403. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Metamorphosis of the amphibian tadpole is a thyroid hormone (TH)-dependent developmental process. For this reason, the tadpole is considered to be an ideal bioassay system to identify disruption of thyroid function by environmental contaminants. Here we provide an in-depth review of the amphibian thyroid system with particular focus on the role that TH plays in metamorphosis. The amphibian thyroid system is similar to that of mammals and other tetrapods. We review the amphibian hypothalamic-pituitary-thyroid (HPT) axis, focusing on thyroid hormone synthesis, transport, and metabolism. We also discuss the molecular mechanisms of TH action, including the role of TH receptors, the actions of TH on organogenesis, and the mechanisms that underlie the pleiotropic actions of THs. Finally, we discuss methods for evaluating thyroid disruption in frogs, including potential sites of action, relevant endpoints, candidate protocols for measuring thyroid axis disruption, and current gaps in our knowledge. The utility of amphibian metamorphosis as a model for evaluating thyroid axis disruption has recently led to the development of a bioassay using Xenopus laevis.