title: EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals.
abstract: The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: A C
authors.initials: AC
authors.lastname: Gore
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: V A
authors.initials: VA
authors.lastname: Chappell
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: S E
authors.initials: SE
authors.lastname: Fenton
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: J A
authors.initials: JA
authors.lastname: Flaws
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: A
authors.initials: A
authors.lastname: Nadal
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: G S
authors.initials: GS
authors.lastname: Prins
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: J
authors.initials: J
authors.lastname: Toppari
authors.affiliation: Pharmacology and Toxicology (A.C.G.), College of Pharmacy, The University of Texas at Austin, Austin, Texas 78734; Division of the National Toxicology Program (V.A.C., S.E.F.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; Department of Comparative Biosciences (J.A.F.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Institute of Bioengineering and CIBERDEM (A.N.), Miguel Hernandez University of Elche, 03202 Elche, Alicante, Spain; Departments of Urology, Pathology, and Physiology & Biophysics (G.S.P.), College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, 20520 Turku, Finland; and Biology Department (R.T.Z.), University of Massachusetts at Amherst, Amherst, Massachusetts 01003.
authors.forename: R T
authors.initials: RT
authors.lastname: Zoeller
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000453:epidemiology; D052244:Endocrine Disruptors / Q000633:toxicity*; D004704:Endocrinology; D004781:Environmental Exposure; D005260:Female; D006540:Herbicides; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000453:epidemiology; D065886:Neurodevelopmental Disorders / Q000139:chemically induced / Q000453:epidemiology; D009490:Neurosecretory Systems / Q000187:drug effects; D009765:Obesity / Q000139:chemically induced / Q000453:epidemiology; D010575:Pesticides; D010636:Phenols; D010795:Phthalic Acids / Q000633:toxicity; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D012098:Reproduction / Q000187:drug effects; D012955:Societies, Medical; D013961:Thyroid Gland / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D006540:Herbicides; D010575:Pesticides; D010636:Phenols; D010795:Phthalic Acids; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds