Policy decisions on endocrine disruptors should be based on science across disciplines: a response to Dietrich et al.

in European Journal of Endocrinology
View More View Less
  • 1 Division of Pharmacology and Toxicology, GIGA Neurosciences, VA Medical Center, Institute for Health and the Environment, Section of Integrative Biology, Professor Emeritus of Pediatrics, Medical School, Department of Biological Sciences, Department of Anatomy, Icahn School of Medicine at Mount Sinai, Harvard Medical School, Masonic Cancer Center, Cancer Institute and Magee Women's Research Institute, Wisconsin National Primate Research Center, UCT/MRC Receptor Biology Unit, Department of Neuroscience, School of Medicine, Uniformed Services University of the Health Sciences, Department of Biosciences, Department of Physiology and Biophysics, Department of Medicine, Department of Biochemistry and Molecular Genetics, Division of Medicine, Laboratory of Neuronal Structure and Function, Queensland Children's Medical Institute, Karolinska Institutet, Department of Obstetrics, Department of Cell Biology and Physiology, Institut National de la Santé et de la Recherche Médicale U982, Department of Psychology, Department of Psychology and Neuroscience, Department of Medicine, Department of Biochemistry and Molecular Biology, The University of Texas, Austin, Texas 78712, USA

We are writing as scientists and editors of leading peer-reviewed journals that have published important contributions in the study of endocrine disrupting chemicals (EDCs). By signing this editorial, we affirm that regulatory decisions on EDCs should be made based on the best available science and expertise that involves, among others, reproductive biology, endocrinology, medicine, genetics, behavior, developmental biology, and toxicology (1). For a complete list of Signatories and their Disclosures, see Supplementary Table 1, see section on supplementary data given at the end of this article published on The Endocrine Society's Journals Online web site (http://end.endojournals.org).

Thousands of published studies have revealed the health effects of EDCs on wildlife and laboratory animals and, moreover, have shown associations of EDCs with effects in humans. Many of these studies have been reviewed recently by The Endocrine Society, the United Nations Environment Programme (UNEP) and World Health Organization (WHO), and other independent scientists (2, 3, 4, 5). The conclusions presented in each of these documents are extraordinarily consistent: like hormones, EDCs are active at very low doses and can induce a range of adverse health outcomes, many of which are not examined in traditional toxicology assays (1). In sum, these reports point to the conclusion that EDCs pose a global health threat.

A recent editorial signed by a number of editors of toxicology journals argues for the status quo in the regulation of EDCs (6), despite the large volume of evidence indicating that current regulations are ineffective in protecting human populations from these chemicals (4, 5, 6, 7). As the UNEP/WHO report notes, the incidence of chronic disease is now greater than that of communicable disease; many of these diseases have an endocrine basis. Both experimental animal and epidemiology studies provide plausible causal links between EDCs and many of these diseases; for some, the data are sufficiently robust (8).

The dismissive approach to endocrine disruption science put forth by Dietrich et al. (6) is unfounded, as it is neither based on the fundamental principles of how the endocrine system works and how chemicals can interfere with its normal function, nor does it consider the consequences of that interference. Their letter also ignores a growing and rigorous body of literature on both endogenous hormonal and exogenous EDC effects.

Basic scientists, clinical investigators, and physicians understand that the endocrine system's functions and responses change remarkably across the life cycle. Of particular concern is incontrovertible evidence, published more than a half century ago (9, 10), that there are critical life stages, especially during early development, when hormones dictate the differentiation and development of tissues. Any perturbation of the delicate hormonal balance, whether due to the absence of natural hormones or the presence of exogenous hormones, can have irreversible effects on endocrine-sensitive organs. EDCs are known to upset this delicate balance.

Dietrich et al. (6) also misrepresent the state of science on thresholds, stating that the evidence ‘clearly demonstrates the presence of a threshold for nongenotoxic compounds including EDCs’. Dietrich et al. assert that their position constitutes ‘common sense’ and that the European Commission's approach departs from common sense. They do not, however, provide scientific support for this position. Instead, they list several references (11, 12, 13, 14, 15) that, upon examination, do not contain data supporting their assumption but rather simply assert that the assumption is true. They also fail to address the considerable literature that speaks against that assumption (e.g. references (16, 17, 18, 19, 20)). Finally, they argue that structuring regulation upon the assumption of no threshold ‘will set an unforeseen precedence (sic)’. This is simply and demonstrably not true. The assumption of no threshold has been widely used, for many years, in the regulation of genotoxic carcinogens, often based on in vitro data. We believe extending this precedent to EDCs is supported by the science (19).

Furthermore, we hold that common sense dictates that policies, particularly those in which public health is at stake, should be based on scientific evidence obtained from the world's leading researchers and should derive from a more evolved, modern understanding of the science, rather than on older, outdated concepts and data taught in classrooms 20 or more years ago. The European Commission policy, by that standard, does represent ‘common sense’.

Further, the USA National Academy of Sciences has concluded that because of the range of susceptibility to environmental chemicals across the population, such as that from age, preexisting conditions, and genetic variation, and because there are documented exposures to multiple chemicals, including EDCs, in the population, it is more appropriate to consider lack of thresholds at a population level (16).

Many toxicologists have developed rigorous research programs on EDCs that incorporate endocrinological principles, including two former presidents of the Society of Toxicology, Cheryl Walker and Linda Birnbaum. They and many other toxicologists do work in this area and report results that have contributed to the breadth and depth of concern about EDCs as a global public health threat. The ad hominem attacks in Dietrich et al. (6) do nothing to advance science or opportunities to protect public health; we refer readers to two additional responses to their editorial that support this point of view (21, 22). We need the fields of toxicology, endocrinology and other stakeholders to work together to address these issues, not engage in recriminations.

Policymakers in Europe and elsewhere should base their decisions on science, not on assumptions based on principles that arose out of research on chemicals that are not EDCs. The letter by Dietrich et al. does the European Commission, science, including the field of toxicology, and most importantly, public health, a profound disservice.


Journal Editors-in-Chief

  1. Jacques Balthazart, PhD, Frontiers in Neuroendocrinology.
  2. David O Carpenter, MD, Reviews on Environmental Health.
  3. Paul Czernichow, MD, Hormone Research in Pediatrics.
  4. Donald B DeFranco, PhD, Molecular Endocrinology.
  5. Robert M Dores, PhD, General and Comparative Endocrinology.
  6. Andrea C Gore, PhD, Endocrinology.
  7. David Grattan, PhD, Journal of Neuroendocrinology.
  8. Stephen R Hammes, MD, PhD, Editor-in-Chief elect, Molecular Endocrinology.
  9. Patrick R Hof, MD, Journal of Comparative Neurology.
  10. Carol Lange, PhD, Hormones and Cancer.
  11. Jon E Levine, PhD, Frontiers in Neuroendocrinology.
  12. Deborah M Power, PhD, General and Comparative Endocrinology.
  13. Robert P Millar, PhD, FRSE, Neuroendocrinology.
  14. E Chester Ridgway, MD, MACP, Endocrine Reviews.
  15. Johannes A Romijn, MD, PhD, European Journal of Endocrinology.
  16. Peter D Sly, MBBS, FRACP, MD, DSc, Reviews on Environmental Health.
  17. Hubert Vaudry, PhD, Dr Sci, Frontiers in Neuroendocrine Science; also Senior Editor, Journal of Neuroendocrinology; Associate Editor, Hormone and Metabolic Research; Associate Editor, General and Comparative Endocrinology; and Associate Editor, Peptides.
  18. Kim Wallen, PhD, Hormones and Behavior.
  19. Leonard Wartofsky, MD, MACP, Journal of Clinical Endocrinology and Metabolism.
  20. Cheryl S Watson, PhD, Endocrine Disruptors.

Journal Associate Editors

  1. Åke Bergman, PhD, Archives of Environmental Contamination and Toxicology; Environmental Science and Pollution Research.
  2. Daniel Bikle, MD, PhD, Endocrinology.
  3. Barbara A Cohn, PhD, Endocrine Disruptors.
  4. David Crews, PhD, Endocrine Disruptors; Journal of Experimental Zoology; Ecological Genetics and Physiology; Sexual Development; Epigenetics.
  5. Peter L DeFur, PhD, Endocrine Disruptors.
  6. Evanthia Diamanti-Kandarakis, MD, PhD, European Journal of Endocrinology.
  7. Anthony N Hollenberg, MD, Endocrinology.
  8. Susan Jobling, PhD, Endocrine Disruptors.
  9. Jun Kanno, MD, PhD, Environmental Health Perspectives.
  10. Carolyn Klinge, PhD, Endocrine Disruptors.
  11. B Paige Lawrence, PhD, Endocrine Disruptors.
  12. Adrian V Lee, PhD, Endocrinology.
  13. J P Myers, PhD, Endocrine Disruptors.
  14. Randy J Nelson, PhD, Hormones and Behavior.
  15. Miquel Porta, MD, MPH, PhD, Journal of Epidemiology and Community Health; European Journal of Clinical Investigation; European Journal of Epidemiology.
  16. Merrily Poth, MD, Journal of Clinical Endocrinology and Metabolism.
  17. Gail S Prins PhD, Endocrinology; Andrology.
  18. Emilie F Rissman, PhD, Endocrinology.
  19. Paul E Sawchenko, PhD, Journal of Comparative Neurology.
  20. Olle Söder, MD, PhD, Hormone Research in Pediatrics.
  21. Ana M Soto, MD, Progress in Biophysics and Molecular Biology.
  22. Shanna Swan, PhD, Endocrine Disruptors.
  23. Hugh S Taylor, MD, Endocrinology.
  24. Manuel Tena-Sempere, MD, PhD, Endocrinology.
  25. Frederick vom Saal, PhD, Endocrine Disruptors.
  26. Zuoxin Wang, PhD, Hormones and Behavior.
  27. Wade V Welshons, PhD, Endocrine Disruptors.
  28. R Thomas Zoeller, PhD, Endocrine Disruptors.

Additional Signatories

  1. Benson T Akingbemi, PhD.
  2. Koji Arizono, PhD.
  3. Scott M Belcher, PhD.
  4. Fiorella Belpoggi, PhD.
  5. Carl-Gustaf Bornehag, PhD.
  6. Jean-Pierre Bourguignon, MD, PhD.
  7. Terry R Brown, PhD.
  8. Ernesto Burgio, MD.
  9. Terrence J Collins, PhD.
  10. D Andrew Crain, PhD.
  11. Barbara Demeneix, PhD.
  12. Rodney R Dietert, PhD.
  13. Loretta Doan, PhD.
  14. Thea M Edwards, PhD.
  15. Mariana F Fernandez, PhD.
  16. R William Field, PhD, MS.
  17. Linda C Giudice, MD, PhD.
  18. Louis J Guillette, PhD.
  19. Y Leon Guo, MD, PhD, MPH.
  20. Tyrone Hayes, PhD.
  21. Andrea Hinwood, PhD.
  22. C Vyvyan Howard, MB, ChB, PhD, FRC Path.
  23. Eric R Hugo, PhD.
  24. Patricia Hunt, PhD.
  25. Taisen Iguchi, PhD.
  26. Richard J Jackson, MD, MPH, AIA (Hon), ASLA (Hon).
  27. Patricia Joseph-Bravo, PhD.
  28. Hans Laufer, PhD.
  29. Duk-Hee Lee, MD, PhD.
  30. Rachel Morello-Frosch, PhD, MPH.
  31. Jane Muncke, PhD.
  32. Angel Nadal, PhD.
  33. David O Norris, PhD.
  34. Jörg Oehlmann, PhD.
  35. Nicolas Olea, MD, PhD.
  36. Edward F Orlando, PhD.
  37. Vasantha Padmanabhan, PhD.
  38. Paola Palanza, PhD.
  39. Stefano Parmigiani, PhD.
  40. Donald W Pfaff, PhD.
  41. Beverly S Rubin, PhD.
  42. Joan V Ruderman, PhD.
  43. Arnold Schecter, MD, MPH.
  44. Toshi Shioda, MD, PhD.
  45. Martin Scheringer, PhD.
  46. Niels E Skakkebaek, MD.
  47. Howard M Snyder III, MD.
  48. Carlos Sonnenschein, MD.
  49. Richard W Stahlhut, MD, MPH.
  50. Laura Vandenberg, PhD.
  51. Catherine VandeVoort, PhD.
  52. Martin Wagner, PhD.
  53. Hong-Sheng Wang, PhD.
  54. Bernard Weiss, PhD.
  55. Teresa Woodruff, PhD.
  56. Tracey Woodruff, PhD.

Supplementary data

This is linked to the online version of the paper at http://dx.doi.org/10.1530/EJE-13-0763.


The following is the list of signatories. The complete list of their affiliations and disclosure information is provided in Supplemental Table 1) (see section on supplementary data given at the end of this article).


  • 1

    American Society of Human Genetics, American Society for Reproductive Medicine, Endocrine Society, Genetics Society of America, Society for Developmental Biology, Society for Pediatric Urology, Society for the Study of Reproduction, Society for Gynecologic Investigation Assessing chemical risk: societies offer expertise. Science 2011 331 1136. (doi:10.1126/science.331.6021.1136-a.

    • Search Google Scholar
    • Export Citation
  • 2

    Diamanti-Kandarakis E, Bourguignon JP, Guidice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocrine Reviews 2009 30 293342. (doi:10.1210/er.2009-0002).

    • Search Google Scholar
    • Export Citation
  • 3

    Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH, Shioda T, Soto AM, vom Saal FS, Welshons WV et al. . Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocrine Reviews 2012 33 378455. (doi:10.1210/er.2011-1050).

    • Search Google Scholar
    • Export Citation
  • 4

    Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, Woodruff TJ, vom Saal FS. Endocrine-disrupting chemicals and public health protection: a statement of principles from the Endocrine Society. Endocrinology 2012 153 40974110. (doi:10.1210/en.2012-1422).

    • Search Google Scholar
    • Export Citation
  • 5

    Eds Bergman A, Heindel JJ, Jobling S, Kidd KA & Zoeller RT. State of the Science of Endocrine Disrupting Chemicals – 2012. An Assessment of the State of the Science of Endocrine Disruptors Prepared by a Group of Experts for the United Nations Environment Programme and World Health Organization. Geneva, Switzerland: United Nations Environment Programme and the World Health Organization, 2013

  • 6

    Dietrich DR, Aulock SV, Marquardt H, Blaauboer B, Dekant W, Kehrer J, Hengstler J, Collier A, Gori GB, Pelkonen O et al. . Scientifically unfounded precaution drives European Commission's recommendations on EDC regulation, while defying common sense, well-established science and risk assessment principles. Chemico-Biological Interactions 2013 205 A1A5. (doi:10.1016/j.cbi.2013.07.001).

    • Search Google Scholar
    • Export Citation
  • 7

    Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, Myers JP, Shioda T, Soto AM, vom Saal FS et al. . Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology. Reproductive Toxicology 2013 38 115. (doi:10.1016/j.reprotox.2013.02.002).

    • Search Google Scholar
    • Export Citation
  • 8

    Birnbaum LS. Environmental chemicals: evaluating low-dose effects. Environmental Health Perspectives 2012 120 A143A144. (doi:10.1289/ehp.1205179).

    • Search Google Scholar
    • Export Citation
  • 9

    Phoenix CH, Goy RW, Gerall AA, Young WC. Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 1959 65 369382. (doi:10.1210/endo-65-3-369).

    • Search Google Scholar
    • Export Citation
  • 10

    Wallen K. The Organizational Hypothesis: reflections on the 50th anniversary of the publication of Phoenix, Goy, Gerall, and Young (1959). Hormones and Behavior 2009 55 561565. (doi:10.1016/j.yhbeh.2009.03.009).

    • Search Google Scholar
    • Export Citation
  • 11

    Boobis AR, Daston GP, Preston RJ, Olin SS. Application of key events analysis to chemical carcinogens and noncarcinogens. Critical Reviews in Food Science and Nutrition 2009 49 690707. (doi:10.1080/10408390903098673).

    • Search Google Scholar
    • Export Citation
  • 12

    Borgert CJ, Sargent EV, Casella G, Dietrich DR, McCarty LS, Golden RJ. The human relevant potency threshold: reducing uncertainty by human calibration of cumulative risk assessments. Regulatory Toxicology and Pharmacology 2012 62 313328. (doi:10.1016/j.yrtph.2011.10.012).

    • Search Google Scholar
    • Export Citation
  • 13

    Piersma AH, Hernandez LG, van Benthen J, Muller JJ, van Leuven FX, Vermiere TG, van Raaij MT. Reproductive toxicants have a threshold of adversity. Critical Reviews in Toxicology 2011 41 545554. (doi:10.3109/10408444.2011.554794).

    • Search Google Scholar
    • Export Citation
  • 14

    Rhomberg LR, Goodman JE, Haber LH, Dourson M, Andersen ME, Klaunig JE, Meek B, Price PS, McClellan RO, Cohen SM. Linear low-dose extrapolation for noncancer health effects is the exception, not the rule. Critical Reviews in Toxicology 2011 41 119. (doi:10.3109/10408444.2010.536524).

    • Search Google Scholar
    • Export Citation
  • 15

    Rhomberg LR, Goodman JE. Low-dose effects and nonmonotonic dose–responses of endocrine disrupting chemicals: has the case been made? Regulatory Toxicology and Pharmacology 2012 64 130133. (doi:10.1016/j.yrtph.2012.06.015).

    • Search Google Scholar
    • Export Citation
  • 16

    vom Saal FS, Sheehan DM. Challenging risk assessment. Forum for Applied Research and Public Policy 1998 13 1118.

  • 17

    Sheehan DM, Willingham E, Gaylor D, Bergeron JM, Crews D. No threshold dose for estradiol-induced sex reversal of turtle embryos: how little is too much? Environmental Health Perspectives 1999 107 155159. (doi:10.1289/ehp.99107155).

    • Search Google Scholar
    • Export Citation
  • 18

    Sheehan DM, vom Saal FS. Low dose effects of hormones: a challenge for risk assessment. Risk Policy Report 1997 4 3139.

  • 19

    Sheehan DM. No-threshold dose–response curves for nongenotoxic chemicals: findings and application for risk assessment. Environmental Research 2006 100 9399. (doi:10.1016/j.envres.2005.09.002).

    • Search Google Scholar
    • Export Citation
  • 20

    Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, vom Saal FS. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environmental Health Perspectives 2003 111 9941006. (doi:10.1289/ehp.5494).

    • Search Google Scholar
    • Export Citation
  • 21

    Grandjean P, Ozonoff D. Transparency and translation of science in a modern world. Environmental Health 2013 12 70. (doi:10.1186/1476-069X-12-70).

    • Search Google Scholar
    • Export Citation
  • 22

    Bergman A, Andersson AM, Becher G, van den Berg M, Blumberg B, Bjerregaard P, Bornehag CG, Bornman R, Brandt I, Brian JV et al. . Science and policy on endocrine disrupters must not be mixed: a reply to a “common sense” intervention by toxicology journal editors. Environmental Health 2013 12 69. (doi:10.1186/1476-069X-12-69).

    • Search Google Scholar
    • Export Citation


     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 808 37 6
PDF Downloads 287 76 9