Are EDCs Blurring Issues of Gender?

Abstract

Although scientists have postulated a wide range of adverse human health effects of exposure to endocrine-disrupting chemicals (EDCs), the nexus of the debate is the concern that prenatal and childhood exposure to EDCs may be responsible for a variety of abnormalities in human sexuality, gender development and behaviors, reproductive capabilities, and sex ratios. Scientists today are asking hard questions about potential human effects: Do EDC exposures impair fertility in men or women? Can they cause sexual organ malformations, stunted reproductive development, or testicular or breast cancer? Do fetal exposures to EDCs alter sex phenotypes? Do they change later gender-related neurobiological characteristics and behaviors such as play activity and spatial ability? Could such exposures even be involved in the etiology of children born with ambiguous gender? EDCs include a spectrum of substances that can be loosely classified according to their known or suspected activity in relation to sex hormone receptors and pathways. The most-studied and best known are the environmental estrogens, which mimic estradiol and bind to estrogen receptors (ERs). ER agonists include the pesticide methoxychlor, certain polychlorinated biphenyls (PCBs), bisphenol A (BPA; a high production volume chemical used to make polycarbonate plastic), pharmaceutical estrogens such as diethylstilbestrol (DES) and ethinyl estradiol, and phytoestrogens, which occur naturally in many plants, most notably in soybeans in the form of genistein and related substances. There are a few known ER antagonists, or antiestrogens. Antiandrogens, or androgen receptor (AR) antagonists, include the fungicide vinclozolin, the DDT metabolite p,p′-DDE, certain phthalates (a group of chemicals used to soften polyvinyl chloride plastics), and certain other PCBs. And there are other types of EDCs that affect particular endocrine targets. The various EDCs differ greatly in their potencies relative to natural hormones, and in their affinity for target receptors. Some have been shown to act via non–receptor-mediated mechanisms, for example by interfering with hormone synthesis. In many well-documented cases of high-level fetal exposures to known EDCs such as DES, certain PCBs, and DDT, the answer to the question of whether exposure is associated with gender-related effects is clearly yes. But high-level exposures such as these are relatively rare and isolated. The debate today centers on low-dose exposures—generally defined as doses that approximate environmentally relevant levels—and the idea that low-dose intrauterine exposure to some EDCs during certain critical windows of development can have profound, permanent impacts on subsequent fetal development and adult outcomes. Critics of this idea maintain that thus far there is no credible evidence to suggest that low-dose exposures cause any adverse human health effects. But if low-dose exposures were confirmed to be the threat that proponents of the concept insist they are, public health would clearly be at risk, regulatory agencies’ risk assessment approach would need to be revised, and certain common chemicals—including some that are massively produced and economically important—would likely disappear from the marketplace. In a June 2000 EHP review article on human health problems associated with EDCs, Stephen Safe, director of the Center for Environmental and Genetic Medicine at Texas AM however, at present the evidence is not compelling.” Frederick vom Saal, a developmental biologist at the University of Missouri–Columbia, disagrees, particularly in light of the research that’s been presented in the years since that review. “The jury is not out on human effects,” he says. “In terms of the amount of information we have in animals and the amount of information we have in humans, clearly there is a huge difference, but that’s a lot different than saying the jury is out on whether EDCs influence humans.” One thing both scientists might agree on, though, is that right now there are still more questions than answers.