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

Michele A La Merrill; Laura N Vandenberg; Martyn T Smith; William Goodson; Patience Browne; Heather B Patisaul; Kathryn Z Guyton; Andreas Kortenkamp; Vincent J Cogliano; Tracey J Woodruff; Linda Rieswijk; Hideko Sone; Kenneth S Korach; Andrea C Gore; Lauren Zeise; R Thomas Zoeller

doi:10.1038/s41574-019-0273-8

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

Michele A La Merrill^*, Laura N Vandenberg, Martyn T Smith, William Goodson, Patience Browne, Heather B Patisaul, Kathryn Z Guyton, Andreas Kortenkamp, Vincent J Cogliano, Tracey J Woodruff, Linda Rieswijk, Hideko Sone, Kenneth S Korach, Andrea C Gore, Lauren Zeise, R Thomas Zoeller

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	45-57
Number of pages	13
Journal	Nature Reviews Endocrinology
Volume	16
Issue number	1
Early online date	12 Nov 2019
DOIs	https://doi.org/10.1038/s41574-019-0273-8
Publication status	Published - Jan 2020

Keywords

BISPHENOL-A EXPOSURE
DEVELOPMENTAL EXPOSURE
DIETHYLSTILBESTROL DES
ENVIRONMENTAL ESTROGENS
ESTROGEN-RECEPTOR-ALPHA
GENE-EXPRESSION
HORMONE SYNTHESIS
IN-UTERO
PRENATAL EXPOSURE
SEXUAL-DIFFERENTIATION

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Cite this

La Merrill, M. A., Vandenberg, L. N., Smith, M. T., Goodson, W., Browne, P., Patisaul, H. B., Guyton, K. Z., Kortenkamp, A., Cogliano, V. J., Woodruff, T. J., Rieswijk, L., Sone, H., Korach, K. S., Gore, A. C., Zeise, L., & Zoeller, R. T. (2020). Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nature Reviews Endocrinology, 16(1), 45-57. https://doi.org/10.1038/s41574-019-0273-8

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

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.",

keywords = "BISPHENOL-A EXPOSURE, DEVELOPMENTAL EXPOSURE, DIETHYLSTILBESTROL DES, ENVIRONMENTAL ESTROGENS, ESTROGEN-RECEPTOR-ALPHA, GENE-EXPRESSION, HORMONE SYNTHESIS, IN-UTERO, PRENATAL EXPOSURE, SEXUAL-DIFFERENTIATION",

author = "{La Merrill}, {Michele A} and Vandenberg, {Laura N} and Smith, {Martyn T} and William Goodson and Patience Browne and Patisaul, {Heather B} and Guyton, {Kathryn Z} and Andreas Kortenkamp and Cogliano, {Vincent J} and Woodruff, {Tracey J} and Linda Rieswijk and Hideko Sone and Korach, {Kenneth S} and Gore, {Andrea C} and Lauren Zeise and Zoeller, {R Thomas}",

note = "Funding Information: Similar challenges were previously encountered in the evaluation of mechanistic data for cancer hazard identification. Therefore, the key characteristics (KCs) of human carcinogens were developed, providing a uniform basis for searching, organizing and evaluating mechanistic evidence to support the identification of carcinogens27. This KC-based approach is becoming widely applied by authoritative bodies, including the International Agency for Research on Cancer (IARC) and the National Toxicology Program, as according to the National Academies it “avoids a narrow focus on specific pathways and hypotheses and provides for a broad, holistic consideration of the mechanistic evidence”28. Funding Information: This project was supported by contract 17-E0023 from the California EPA and by the Research Translation Core of the NIEHS Superfund Research Center at Berkeley under NIH grant P42ES004705. The authors acknowledge funding from the National Institutes of Health (R01ES023254 and R56ES020662 to A.C.G.; 1ZIAES070065 to K.S.K.; R01ES028110 to H.B.P.; P42ES004705 to M.T.S.; P01ES022841 and R01ES027051 to T.J.W.), USEPA (RD-83543301 to T.J.W.), Department of Defense (AR160055 to H.B.P.), Office of Environmental Health Hazard Assessment (17-E0024 to M.A.L.M.; 17-E0023 to M.T.S.) and Japan Society for the Promotion of Science (KAKENHI-PROJECT-15H01749 to H.S.). We thank all other members of the 2018 Working Group who attended the workshop in Berkeley, California, for important discussion, including the following: X. Arzuaga, US EPA; B. Eskenazi, UC Berkeley; C. Gibbons, US EPA; R. Hauser, Harvard; U. Luderer, UC Irvine; C. McHale, UC Berkeley; G. Prins, University of Illinois at Chicago; M. Sandy, OEHHA; T. Schug, NIEHS; N. Skakkebaek, University of Copenhagen; G. Solomon, UC San Francisco; O. Udagawa, NIES, Japan; and L. Zhang, UC Berkeley. The views expressed in this article are those of the authors and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency, the California Environmental Protection Agency, the National Institute of Environmental Health Sciences, the Organization of Economic Cooperation and Development or the International Agency for Research on Cancer. Publisher Copyright: {\textcopyright} 2019, Springer Nature Limited.",

year = "2020",

month = jan,

doi = "10.1038/s41574-019-0273-8",

language = "English",

volume = "16",

pages = "45--57",

journal = "Nature Reviews Endocrinology",

issn = "1759-5029",

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La Merrill, MA, Vandenberg, LN, Smith, MT, Goodson, W, Browne, P, Patisaul, HB, Guyton, KZ, Kortenkamp, A, Cogliano, VJ, Woodruff, TJ, Rieswijk, L, Sone, H, Korach, KS, Gore, AC, Zeise, L & Zoeller, RT 2020, 'Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification', Nature Reviews Endocrinology, vol. 16, no. 1, pp. 45-57. https://doi.org/10.1038/s41574-019-0273-8

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T1 - Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification

AU - La Merrill, Michele A

AU - Vandenberg, Laura N

AU - Smith, Martyn T

AU - Goodson, William

AU - Browne, Patience

AU - Patisaul, Heather B

AU - Guyton, Kathryn Z

AU - Kortenkamp, Andreas

AU - Cogliano, Vincent J

AU - Woodruff, Tracey J

AU - Rieswijk, Linda

AU - Sone, Hideko

AU - Korach, Kenneth S

AU - Gore, Andrea C

AU - Zeise, Lauren

AU - Zoeller, R Thomas

N1 - Funding Information: Similar challenges were previously encountered in the evaluation of mechanistic data for cancer hazard identification. Therefore, the key characteristics (KCs) of human carcinogens were developed, providing a uniform basis for searching, organizing and evaluating mechanistic evidence to support the identification of carcinogens27. This KC-based approach is becoming widely applied by authoritative bodies, including the International Agency for Research on Cancer (IARC) and the National Toxicology Program, as according to the National Academies it “avoids a narrow focus on specific pathways and hypotheses and provides for a broad, holistic consideration of the mechanistic evidence”28. Funding Information: This project was supported by contract 17-E0023 from the California EPA and by the Research Translation Core of the NIEHS Superfund Research Center at Berkeley under NIH grant P42ES004705. The authors acknowledge funding from the National Institutes of Health (R01ES023254 and R56ES020662 to A.C.G.; 1ZIAES070065 to K.S.K.; R01ES028110 to H.B.P.; P42ES004705 to M.T.S.; P01ES022841 and R01ES027051 to T.J.W.), USEPA (RD-83543301 to T.J.W.), Department of Defense (AR160055 to H.B.P.), Office of Environmental Health Hazard Assessment (17-E0024 to M.A.L.M.; 17-E0023 to M.T.S.) and Japan Society for the Promotion of Science (KAKENHI-PROJECT-15H01749 to H.S.). We thank all other members of the 2018 Working Group who attended the workshop in Berkeley, California, for important discussion, including the following: X. Arzuaga, US EPA; B. Eskenazi, UC Berkeley; C. Gibbons, US EPA; R. Hauser, Harvard; U. Luderer, UC Irvine; C. McHale, UC Berkeley; G. Prins, University of Illinois at Chicago; M. Sandy, OEHHA; T. Schug, NIEHS; N. Skakkebaek, University of Copenhagen; G. Solomon, UC San Francisco; O. Udagawa, NIES, Japan; and L. Zhang, UC Berkeley. The views expressed in this article are those of the authors and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency, the California Environmental Protection Agency, the National Institute of Environmental Health Sciences, the Organization of Economic Cooperation and Development or the International Agency for Research on Cancer. Publisher Copyright: © 2019, Springer Nature Limited.

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

KW - BISPHENOL-A EXPOSURE

KW - DEVELOPMENTAL EXPOSURE

KW - DIETHYLSTILBESTROL DES

KW - ENVIRONMENTAL ESTROGENS

KW - ESTROGEN-RECEPTOR-ALPHA

KW - GENE-EXPRESSION

KW - HORMONE SYNTHESIS

KW - IN-UTERO

KW - PRENATAL EXPOSURE

KW - SEXUAL-DIFFERENTIATION

U2 - 10.1038/s41574-019-0273-8

DO - 10.1038/s41574-019-0273-8

M3 - Article

C2 - 31719706

SN - 1759-5029

VL - 16

SP - 45

EP - 57

JO - Nature Reviews Endocrinology

JF - Nature Reviews Endocrinology

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ER -