Policy decisions on endocrine disruptors should be based on science across disciplines

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 Supplemental Table 1 published on The Endocrine Society's Journals Online website at 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.^2-5 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.^4-7 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 lifecycle. 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 non-genotoxic 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^11-15 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 (eg, refs. 16–20). 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 US 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.

Abbreviations:
EDC	=	endocrine disrupting chemical
UNEP	=	United Nations Environment Programme
WHO	=	World Health Organization

Acknowledgments

The following is the list of signatories. The complete list of their affiliations and disclosure information is provided in Supplemental Table 1.

Signatories

Journal Editors-in-Chief

1. Prof. 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. Professor 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, DrSci, Frontiers in Neuroendocrine Science; also Senior Editor, Journal of Neuroendocrinology; Associate Editor, Hormone and Metabolic Research; Associate Editor, General and Comparative Endocrinology; 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, FRCPath

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