EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

Abstract

The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

Effects of Bisphenol A on ion channels: Experimental evidence and molecular mechanisms

“…The second reason is the strong translational evidence already accumulated for BPA exposure as a risk factor for obesity and diabetes [2,13,19]. in this channel type in coronary smooth cells [27] and in transfected cells [28], revealing a direct channel activation by BPA via α and β1 subunits, similar to that of estradiol [18,29].…”

“…This action of BPA could account for the effects on reproductive function observed in epidemiological studies [2]. However, in human embryonic kidney 293 (HEK) cells expressing T-type Ca 2+ channels, acute application of BPA at different doses (0.1 nM-100 µM) inhibited the Ca 2+ current through this channel.…”

“…These currently widespread substances are defined by the Endocrine Society as: "an exogenous chemical, or mixture of chemicals, that interfere with any aspect of hormone action" [1]. These compounds can persist in the environment and, once they gain access to the human body, they can alter the hormonal milieu and affect many target tissues and physiological functions, being the translational evidence strongest for obesity and diabetes, female and male reproduction, hormone-sensitive cancers in females, prostate, thyroid and neurodevelopment and neuroendocrine systems [2]. Given that general population is exposed to a complex mixture of environmental chemicals, many of which are known EDCs, the potential human health risk is substantial and far beyond the relatively modest effect that each of these chemicals may have individually.…”

Ablation of Ggnbp2 impairs meiotic DNA double‐strand break repair during spermatogenesis in mice

“…A recent comprehensive analysis revealed that sperm counts continually and significantly declined over a 38‐year period in men from Western countries 42. Numerous reports have provided evidence that a decline in sperm count links to chronic exposure to environmental endocrine disrupting chemicals (EDCs) 43, 44. Dioxins are a group of highly persistent and omnipresent EDCs 45.…”

Exposure to Thyroid-Disrupting Chemicals: A Transatlantic Call for Action

“…The fact that nearly 40% of the world's population still has inadequate nutritional iodine intake renders these individuals and risk groups even more vulnerable toward the adverse effects of TDCs, some of which might act as cogoitrogenic compounds interfering with the feedback regulation of the hypothalamus-pituitary-thyroid axis. In addition, interactions between the complex effects of TDC exposure and thyroid autoimmunity should be explored by taking into consideration various factors such as major sex differences in thyroid hormone-related diseases, the age of exposure, latency from exposure, synergistic effect of different EDC mixtures, nontraditional dose-response dynamics, and transgenerational effects (1).…”