The Endocrine Society: Protocol for defining, identifying EDCs insufficient

HOUSTON — Today, The Endocrine Society has issued a Statement of Principles regarding the definition of endocrine-disrupting chemicals, and proposes recommendations to strengthen the ability of current screening programs to identify these chemicals. Experts also expressed concerns about exposure during developmental stages, citing these as the most detrimental.

“This new statement is motivated by the fact that we’re concerned that the current regulatory testing process is not up to the same standard that endocrinologists would use to study hormones in their own laboratories,” Andrea C. Gore, PhD, division of pharmacology and toxicology at the University of Texas at Austin, said during a press conference. “Testing needs to happen at a broader range of doses, low doses need to be incorporated and we need to use endocrine principles to interpret the results. The recommendation is that we have to incorporate our understanding of the endocrine system and engage endocrinologists with experts in these areas to contribute to designing and interpreting the tests that are used for regulatory processes; unfortunately that isn’t happening enough right now.”

Gore, who is a member of The Endocrine Society and co-author of the Statement of Principles, presented data from her study of pregnant Sprague–Dawley rats that were exposed to the industrial contaminants polychlorinated biphenyls, a class of endocrine-disrupting chemicals (EDCs).

She and colleagues found that offspring of exposed rats experienced developmental effects associated with prenatal exposure to EDC, which manifested as age-dependent alterations in gene expression. The effects were most profound among 15-day old (juvenile) males and 45-day old (young adult) females. They identified gene expression changes in two hypothalamic regions — the ARC and AVPV — that were age-, sex- and developmental stage-specific, suggesting EDCs could alter development of a network of genes in the hypothalamus.

“The bottom line is that, as the brain and body develop, effects of early life exposure are manifested in life stage, sex and tissue-specific manners,” she said of her findings.

New definition of EDCs

In 2009, The Endocrine Society published a Scientific Statement that provided a detailed summary of the scientific background that justifies concern for the effects of EDC exposure to both humans and wildlife.

Now, the society proposes that EDCs be defined as exogenous chemicals, or a mixture of chemicals, that interfere with any aspect of hormone action. Due to the lack of agreement in the scientific community on what constitutes adverse effects from EDCs, the statement deliberately does not include the word "adverse" in its definition. However, according to the statement, the ability of a chemical to interfere with hormone action is a clear predictor of adverse outcomes if exposure occurs during critical periods or developmental processes, according to a society press release.

The statement includes the following recommendations:

Basic scientists actively engaged in the development of new knowledge in relevant disciplines should be involved in evaluating the weight-of-evidence of EDC studies, as well as in the design and interpretation of studies that inform the regulation of EDCs;
State-of-the-art molecular and cellular techniques, and highly sensitive model systems, need to be built into current testing, in consultation with the appropriate system experts;
Testing needs to include models of developmental exposure during critical life periods when organisms may be most vulnerable to even very low-dose exposures;
The design and interpretation of tests must incorporate the biological principle that EDCs act through multiple mechanisms in physiological systems; and
Endocrine principles, such as those outlined in this document, should be incorporated into programs by the US Environmental Protection Agency (EPA) and other agencies charged with evaluating chemicals for endocrine-disrupting potential.

Additionally, the statement outlines principles intended to enhance the ability of current screening programs to identify EDCs:

Environmental chemicals that interfere with any aspect of hormone action should be presumed to produce adverse effects;
EDC exposure during development can have effects on hormone action that cannot be corrected, leaving permanent adverse impacts on cognitive function and other health parameters.
People are exposed to multiple EDCs at the same time, and these mixtures can have a greater effect on the hormone system than any single EDC alone; and
The weight-of-evidence guidance developed by the EPA must be strengthened by adhering to principles of endocrinology outlined here, including low-dose effects and nonlinear or nonmonotonic dose-response curves.

The statement will be published in the September 2012 issue of Endocrinology.

“We do need more research, and it’s important to incorporate the latest research in regulatory decisions, but it’s also important for us to be educated and cautious prior to getting definitive evidence that will lead to changes in regulation,” Hugh S. Taylor, MD, professor of obstetrics, gynecology and reproductive sciences amdreproductive endocrinology and infertility at Yale University School of Medicine, said during the press conference.

Hugh S. Taylor

He and colleagues exposed pregnant CD-1 mice to bisphenol-A (BPA) or vehicle and demonstrated that altered gene expression (365 genes) occurred in uteri among offspring exposed to BPA prenatally. The differences, however, occurred only after endogenous estrogen exposure at puberty or with E2.

“Early-life exposure to estrogens can program how the body responds to estrogens throughout life,” he said.

Taylor also recommended that pregnant women minimize BPA exposure. – by Stacey L. Fisher

For more information:

Gore AC. Abstract #SAT-567.

Jorgensen EM. Abstract #OR31-6. All presented at: the Endocrine Society’s 94th Annual Meeting and Expo; June 23-26, 2012; Houston.