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 online supplementary table 1, www. karger.com/doi/10.1159/000355668.)
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. [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 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.
Acknowledgements
The following is the list of signatories. The complete list of their affiliations and disclosure information is provided in online supplementary 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 Paediatrics
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 & 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 Paediatrics
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