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Endocrine Society Chemical Screening Recommendations

David Joffe, BSPharm, CDE, Editor-in-chief, Diabetes In Control

The Endocrine Society has published a new set of recommendations on the definition of endocrine-disrupting chemicals (EDC) and screening programs for such chemicals.

The recommendations, appearing as a Statement of Principles, will appear in the September print issue of Endocrinology.

The publication of the new recommendations follows an earlier Scientific Statement, published three years ago, that gave detailed reasons for concern about EDC exposure.

R. Thomas Zoeller, PhD, from the Biology Department and Molecular and Cellular Biology Program, University of Massachusetts, Amherst, and coauthors, write, “The Endocrine Society is in a unique position to help inform the ongoing debate about the health effects of endocrine disruptors (ED), and the purpose of this article is to outline (from an endocrine perspective) key issues related to identifying EDC and protecting humans and wildlife from their adverse effects.”

They first emphasize the importance of using an accurate definition for endocrine disruptors. “The definition of an ED is critical, because it will dictate the evidence required to identify a chemical as an EDC and will inform the subsequent steps of assessing the risk of EDC exposures,” they write.

After reviewing various definitions put forth by other health agencies worldwide, the authors settled on the following: “An ED is an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.”

The authors emphasize that their definition purposely omits reference to adverse effects, as there is no agreement on what that constitutes. “Risk will depend on the exposure and the potency of the chemical,” they write. However, they say, any chemical in the environment that interferes with any aspect of hormone action should be presumed to produce adverse effects.

After reviewing several salient principles of endocrinology that are relevant to EDC, including how hormone effects are mediated as well as the endpoints of hormone action, the authors propose a number of principles aimed at beefing up current EDC screening programs and improving new generations of assays. Included in those principles are the following:

  • An ED is an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.
  • Environmental chemicals that interfere with any aspect of hormone action should be presumed to produce adverse effects.
  • An EDC can interfere with hormone action on the receptor by affecting any number of steps in the biochemical pathway. This includes affecting the amount of hormones produced and interfering with the ability of a hormone to reach the right receptor at the right time and right location.
  • Hormone-receptor systems are “tuned” such that very low doses of hormones effectively alter development and adult physiology. Accordingly, chemicals can interfere with hormone action in very low doses, producing irreversible effects on development and critical physiological systems.
  • Some hormones exert their actions through more than one receptor. Therefore, different elements of the spectrum of effects produced by those hormones are attributable to the different individual receptors.
  • Likewise, chemicals that interact with only a subset of the endogenous hormone’s receptors will produce a mosaic of effects that does not reproduce an endocrine disease but may be detrimental nonetheless.
  • EDC exposures 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 EDC at the same time, and these mixtures can have a greater effect on the hormone system than any single EDC alone.
  • The weight-of-evidence guidance developed by the United States Environmental Protection Agency (EPA) must be strengthened by adhering to principles of endocrinology outlined here, including low-dose effects and nonlinear or nonmonotonic dose-response curves. 

Based on those principles, the authors make several recommendations, including:

  • Endocrine principles, such as those outlined in this document, should be incorporated into programs by the EPA and other agencies charged with evaluating chemicals for endocrine-disrupting potential.
  • 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.
  • The design and interpretation of tests must incorporate the biological principle that EDCs act through multiple mechanisms in physiological systems.
  • 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 Statement of Principles also emphasizes that a wide array of specialists from different fields need to be involved in the review process.

“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 EDC,” the authors write, adding, “Endocrinologists and specialists in other relevant disciplines should be involved in these processes as applicable.”

This work was supported in part by grants from the National Institute of Environmental Health Sciences, the National Institute of Child Health and Human Development, the New York Community Trust, the Forsythia Foundation, and the Passport Foundation. The authors have disclosed no relevant financial relationships.

Endocrinology. Published online June 25, 2012.