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Review
. 2020 Jan;16(1):45-57.
doi: 10.1038/s41574-019-0273-8. Epub 2019 Nov 12.

Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification

Michele A La Merrill  1 , Laura N Vandenberg  2 , Martyn T Smith  3 , William Goodson  4 , Patience Browne  5 , Heather B Patisaul  6 , Kathryn Z Guyton  7 , Andreas Kortenkamp  8 , Vincent J Cogliano  9 , Tracey J Woodruff  10 , Linda Rieswijk  3   11 , Hideko Sone  12 , Kenneth S Korach  13 , Andrea C Gore  14 , Lauren Zeise  15 , R Thomas Zoeller  16
Affiliations
Review

Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification

Michele A La Merrill et al. Nat Rev Endocrinol. 2020 Jan.

Abstract

Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects. In this Expert Consensus Statement, we describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs. We reflect on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and we use diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.

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Conflict of interest statement

M.T.S. has served as a consultant and expert witness in US litigation involving chemical and pharmaceutical exposures and various disease outcomes, including neuropathies and cancer. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The key characteristics of endocrine-disrupting chemicals.
Arrows identify the ten specific key characteristics (KCs) of endocrine-disrupting chemicals (EDCs). The ± symbol indicates that an EDC can increase or decrease processes and effects. KC1 states that an EDC can interact with or activate hormone receptors. KC2 states that an EDC can antagonize hormone receptors. KC3 states that an EDC can alter hormone receptor expression. KC4 states that an EDC can alter signal transduction (including changes in protein or RNA expression, post-translational modifications and/or ion flux) in hormone-responsive cells. KC5 states that an EDC can induce epigenetic modifications in hormone-producing or hormone-responsive cells. KC6 states that an EDC can alter hormone synthesis. KC7 states that an EDC can alter hormone transport across cell membranes. KC8 states that an EDC can alter hormone distribution or circulating hormone levels. KC9 states that an EDC can alter hormone metabolism or clearance. KC10 states that an EDC can alter the fate of hormone-producing or hormone-responsive cells. Depicted EDC actions include amplification and attenuation of effects. Ac, acetyl group; Me, methyl group.
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