[en] Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Trasande, L.; Department of Pediatrics, New York University School of Medicine, New York, NY, United States, Department of Environmental Medicine and Population Health, New York University School of Medicine, New York, NY, United States, Department of Population Health, New York University School of Medicine, New York, NY, United States, NYU Wagner School of Public Service, New York, NY, United States, Department of Nutrition, Food and Public Health, NYU Steinhardt School of Culture, Education and Human Development, New York, NY, United States, NYU Global Institute of Public Health, New York, NY, United States
Vandenberg, L. N.; Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts-Amherst, Amherst, MA, United States
Bourguignon, Jean-Pierre ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Myers, J. P.; Environmental Health Sciences, Charlottesville, VA, United States
Slama, R.; Inserm, CNRS and Univ. Grenoble Alpes joint research center (IAB), Team of Environmental Epidemiology, Grenoble, France
vom Saal, F.; Division of Biological Sciences, University of Missouri-Columbia, Columbia, MO, United States
Zoeller, R. T.; Department of Biology, University of Massachusetts, Amherst, MA, United States
Language :
English
Title :
Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals
Publication date :
2016
Journal title :
Journal of Epidemiology and Community Health
ISSN :
0143-005X
eISSN :
1470-2738
Publisher :
BMJ Publishing Group
Volume :
70
Issue :
11
Pages :
1051-1056
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
NIEHS - National Institute of Environmental Health Sciences [US-NC] [US-NC] NIH - National Institutes of Health [US-MD] [US-MD] Wallace Genetic Foundation - WGF Broad Reach Fund Fund for the Carolinas Marisla Foundation
Zoeller RT, Brown TR, Doan LL, et al. Endocrine-disrupting chemicals and public health protection: a statement of principles from the Endocrine Society. Endocrinology 2012;153:4097-110.
Kavlock RJ, Daston GP, DeRosa C, et al. Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the US EPA-sponsored workshop. Environ Health Perspect 1996;104(Suppl 4):715-40.
USEPA. Prioritizing the Universe of Endocrine Disruptor Screening Program (EDSP) Chemicals using Computational Toxicology Tools. http://www.regulations.gov/#! docketDetail;D=EPA-HQ-OPP-2012-0818 (accessed 24 Nov 2015).
TEDX (The Endocrine Disruptor Exchange). TEDX list of endocrine disruptors. 2015. http://endocrinedisruption.org/endocrine-disruption/tedx-list-of-potential-endocrinedisruptors/chemicalsearch?sname=&x=65&y=19&action=search&sall= 1&searchfor=any&scas=&use1=1&searchcats=all (accessed 24 Nov 2015).
Ding D, Xu L, Fang H, et al. The EDKB: an established knowledge base for endocrine disrupting chemicals. BMC Bioinformatics 2010;11(Suppl 6):S5.
Damstra T, Barlow S, Bergman A, et al., eds. Global assessment of the state-of-the-science of endocrine disruptors. Geneva (Switzerland): World Health Organization, 2002.
Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, et al. Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocr Rev 2009;30:293-342.
Gore AC, Chappell VA, Fenton SE, et al. EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals. Endocr Rev 2015;36: E1-150.
Bergman Å, Heindel JJ, Jobling S, et al. eds. Global assessment of state-of-the-science for endocrine disruptors. 2012. http://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/(accessed 6 Oct 2014).
Di Renzo GC, Conry JA, Blake J, et al. International Federation of Gynecology and Obstetrics opinion on reproductive health impacts of exposure to toxic environmental chemicals. Int J Gynaecol Obstet 2015;131:219-25.
Bellanger M, Demeneix B, Grandjean P, et al. Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 2015;100:1256-66.
Legler J, Fletcher T, Govarts E, et al. Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 2015;100:1278-88.
Lamb JC, Boffetta P, Foster WG, et al. Critical comments on the WHO-UNEP State of the science of endocrine disrupting chemicals-2012. Regul Toxicol Pharmacol 2014;69:22-40.
Dietrich D, von Aulock S, Marquardt HW, et al. Open letter to the European commission: scientifically unfounded precaution drives European commission's recommendations on EDC regulation, while defying common sense, well-established science, and risk assessment principles. Arch Toxicol 2013;87:1739-41.
Beronius A, Vandenberg LN. Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals. Rev Endocr Metab Disord 2015;16:273-87.
Hill A. The environment and disease: association or causation?Proc R Soc Med 1965;58:295-300.
Bergman Å, Becher G, Blumberg B, et al. Manufacturing doubt about endocrine disrupter science-a rebuttal of industry-sponsored critical comments on the UNEP/WHO report"State of the Science of Endocrine Disrupting Chemicals 2012". Regul Toxicol Pharmacol 2015;73:1007-17.
Bergman A, Andersson AM, Becher G, et al. Science and policy on endocrine disrupters must not be mixed: a reply to a"common sense"intervention by toxicology journal editors. Environ Health 2013;12:69.
Zoeller RT, Bergman A, Becher G, et al. A path forward in the debate over health impacts of endocrine disrupting chemicals. Environ Health 2014;13:118.
Grandjean P, Ozonoff D. Transparency and translation of science in a modern world. Environ Health 2013;12:70.
Strategic Alliance for International Chemicals Management. Endocrine disrupting chemicals. 2015. http://www.saicm.org/index.php?option=com_content&view= article&id=452&Itemid=685.
Beausoleil C, Ormsby JN, Gies A, et al. Low dose effects and non-monotonic dose responses for endocrine active chemicals: science to practice workshop: workshop summary. Chemosphere 2013;93:847-56.
Federal Institute for Risk Assessment. The BfR publishes workshop report based on the expert meeting on endocrine disruptors. BfR communication No. 11/2016, 4 May 2016. http://www.bfr.bund.de/cm/349/the-BfR-publishes-workshop-reportbased-on-the-expert-meeting-on-endocrine-disruptors.pdf (accessed 5 Jul 2016).
Slama R, Bourguignon JP, Demeneix B, et al. Scientific Issues Relevant to Setting Regulatory Criteria to Identify Endocrine Disrupting Substances in the European Union. Environ Health Perspect2016. http://dx.doi.org/10.1289/EHP217
Oreskes N, Carlat D, Mann ME, et al. Viewpoint: why disclosure matters. Environ Sci Technol 2015;49:7527-8.
American Chemistry Council. Principles for identifying endocrine-active and endocrine-disrupting chemicals. 2016. http://www.americanchemistry.com/Policy/Chemical-Safety/Endocrine-Disruption/Endocrine-Testing-Program-Principles.pdf (accessed 29 Jan 2016).
Michaels D. Doubt is their product: how industry's assault on science threatens your health. New York (NY): Oxford University Press, 2008.
Agrawal DK, Arevalo M, Bhalla S, et al. Handbook: good laboratory practice (GLP): quality practices for regulated non-chemical research and development. 2nd edn. In: Kioy D, Long D, Bhalla S, et al., eds. World Health Organization library, cataloguing-in-publication data. Switzerland: UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, 2009.
vom Saal FS, Hughes C. An extensive new literature concerning low-dose effects of bisphenol a shows the need for a new risk assessment. Environ Health Perspect 2005;113:926-33.
Hayes TB. Atrazine has been used safely for 50 years? In: Elliott JE, Bishop CA, Morrissey CA, eds. Wildlife ecotoxicology: forensic approaches. New York (NY): Spring Science+Business Media, LLC, 2011:301-24.
Myers JP, vom Saal FS, Akingbemi BT, et al. Why public health agencies cannot depend upon good laboratory practices as a criterion for selecting data: the case of bisphenol A. Environ Health Perspect 2009;117:309-15.
vom Saal FS, Akingbemi BT, Belcher SM, et al. Flawed experimental design reveals the need for guidelines requiring appropriate positive controls in endocrine disruption research. Toxicol Sci 2010;115:612-13.
vom Saal FS, Myers JP. Good laboratory practices are not synonymous with good scientific practices, accurate reporting, or valid data. Environ Health Perspect 2010;118:A60.
Vandenberg LN, Colborn T, Hayes TB, et al. Regulatory decisions on endocrine disrupting chemicals should be based on the principles of endocrinology. Reprod Toxicol 2013;38:1-15.
Myers JP, Zoeller RT, vom Saal FS. A clash of old and new scientific concepts in toxicity, with important implications for public health. Environ Health Perspect 2009;117:1652-5.
Vandenberg LN. Low-dose effects of hormones and endocrine disruptors. Vitam Horm 2014;94:129-65.
OECD. Good Laboratory Practice (GLP). 2015. http://www.oecd.org/chemicalsafety/testing/goodlaboratorypracticeglp.htm (accessed 2 Dec 2015).
Franssen D, Ioannou YS, Alvarez-real A, et al. Pubertal timing after neonatal diethylstilbestrol exposure in female rats: neuroendocrine vs peripheral effects and additive role of prenatal food restriction. Reprod Toxicol 2014;44:63-72.
Newbold RR. Lessons learned from perinatal exposure to diethylstilbestrol. Toxicol Appl Pharmacol 2004;199:142-50.
McLachlan JA, Newbold RR, Burow ME, et al. From malformations to molecular mechanisms in the male: three decades of research on endocrine disrupters.APMIS 2001;109:263-72.
Soto AM, Vandenberg LN, Maffini MV, et al. Does breast cancer start in the womb? Basic Clin Pharmacol Toxicol 2008;102:125-33.
Bourguignon JP, Juul A, Franssen D, et al. Contribution of the endocrine perspective in the evaluation of endocrine disrupting chemical effects: the case study of pubertal timing. Horm Res Paediatr 2016; doi:10.1159/000442748
Franssen D, Gérard A, Hennuy B, et al. Delayed neuroendocrine sexual maturation in female rats after a very low dose of bisphenol a through altered GABAergic neurotransmission and opposing effects of a high dose. Endocrinology 2016;157:1740-50.
Nohynek GJ, Borgert CJ, Dietrich D, et al. Endocrine disruption: fact or urban legend? Toxicol Lett 2013;223:295-305.
Autrup H, Barile FA, Blaauboer BJ, et al. Principles of pharmacology and toxicology also govern effects of chemicals on the endocrine system. Toxicol Sci 2015;146:11-15.
Borgert CJ, Sargent EV, Casella G, et al. The human relevant potency threshold: reducing uncertainty by human calibration of cumulative risk assessments. Regul Toxicol Pharmacol 2012;62:313-28.
Soriano S, Alonso-Magdalena P, García-Arévalo M, et al. Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor beta. PLoS One 2012;7:e31109.
Kanno J, Onyon L, Peddada S, et al. The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies. Environ Health Perspect 2003;111:1530-49.
Markey CM, Michaelson CL, Veson EC, et al. The mouse uterotrophic assay: a reevaluation of its validity in assessing the estrogenicity of bisphenol A. Environ Health Perspect 2001;109:55-60.
Cao J, Rebuli ME, Rogers J, et al. Prenatal bisphenol a exposure alters sex-specific estrogen receptor expression in the neonatal rat hypothalamus and amygdala. Toxicol Sci 2013;133:157-73.
Rhomberg LR, Goodman JE. Low-dose effects and nonmonotonic dose-responses of endocrine disrupting chemicals: has the case been made?Regul Toxicol Pharmacol 2012;64:130-3
USEPA. Toxicological review of 2, 2 0, 4, 4 0-tetrabromodiphenyl ether (BDE-47). 2014. http://www.epa.gov/iris/toxreviews/1010tr.pdf (accessed 3 Oct 2014).
Braun JM, Kalkbrenner AE, Just AC, et al. Gestational exposure to endocrine-disrupting chemicals and reciprocal social, repetitive, and stereotypic behaviors in 4-and 5-year-old children: the HOME study. Environ Health Perspect 2014;122:513-20.
Rosenberg RE, Law JK, Yenokyan G, et al. Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Arch Pediatr Adolesc Med 2009;163:907-14.
New York Times. Flint weighs scope of harm to children caused by lead in water. 2016. http://www.nytimes.com/2016/01/30/us/flint-weighs-scope-of-harm-tochildren-caused-by-lead-in-water.html?_r=0 (accessed 29 Jan 2016).
Weiss B. Neurobehavioral toxicity as a basis for risk assessment. Trends Pharmacol Sci 1988;9:59-62.
Tsai PL, Hatfield TH. Global benefits of phasing out leaded fuel. J Environ Health 2011;74:8-15.
Vandenberg LN, Colborn T, Hayes TB, et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 2012;33:378-455.
Birnbaum LS. Environmental chemicals: evaluating low-dose effects. Environ Health Perspect 2012;120:A143-4.
Weiss B. Anogenital distance: defining"normal". Environ Health Perspect 2006;114:A399; author reply A.
Woodruff TJ, Zeise L, Axelrad DA, et al. Meeting report: moving upstreamevaluating adverse upstream end points for improved risk assessment and decision-making. EnvironHealthPerspect 2008;116:1568-75.
Pope CA III, Dockery DW. Health effects offine particulate air pollution: lines that connect. J Air Waste Manag Assoc 2006;56:709-42.
Pope CA III, Bates DV, Raizenne ME. Health effects of particulate air pollution: time for reassessment? Environ Health Perspect 1995;103:472-80.
Hauser R, Skakkebaek NE, Hass U, et al. Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 2015;100:1267-77.
Trasande L, Zoeller RT, Hass U, et al. Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 2015;100:1245-55.
Hunt PA, Sathyanarayana S, Fowler PA, et al. Female reproductive disorders, diseases, and costs of exposure to endocrine disrupting chemicals in the European Union. J Clin Endocrinol Metab 2016;101:1562-70.
Trasande L, Zoeller RT, Hass U, et al. Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis. Andrology2016.
Trasande L, Liu Y. Reducing the staggering costs of environmental disease in children, estimated at $76.6 Billion in 2008. Health Affairs 2011;30: 863-70.
European Commission. REACH. 2010. http://ec.europa.eu/environment/chemicals/reach/reach_intro.htm (accessed 8 Dec 2010).
USEPA. Prioritizing the Universe of Endocrine Disruptor Screening Program (EDSP) chemicals using computational toxicology tools. 2015. http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2012-0818 (accessed 24 Nov 2015).
EPA. Endocrine Disruptor Screening Program Tier 1 assessments. 2015. http://www2.epa.gov/ingredients-used-pesticide-products/endocrine-disruptor-screeningprogram-tier-1-assessments (accessed 24 Nov 2015).
European Commission. Endocrine disruptors. 2015. http://ec.europa.eu/environment/chemicals/endocrine/documents/index_en.htm#SubThemes5 (accessed 24 Nov 2015).
