1938: Diethylstilbestrol (DES) - first synthetic estrogen – created

DES was prescribed to millions of pregnant women, primarily from 1938 – 1971 in the mistaken belief that the drug prevented miscarriage and ensured a healthy baby. DES didn’t work, and instead harmed the mothers who were prescribed it, the children born of those pregnancies, and possibly their grandchildren and beyond. The toxic effects of DES were later shown to involve the estrogen receptor. For More Information: DES Daughters

1940: Wildlife studies reveal abnormal reproductive patterns

Beginning in the 1940’s, ecologists noticed health effects related to reproduction in wildlife that were causing serious impacts on the populations of several species. Many of the health effects were subsequently linked to exposures to environmental chemicals, later known as endocrine-disrupting chemicals, challenging the assumption that environmental chemicals were predominantly of concern due to carcinogenicity. For example, polychlorinated biphenyls (PCBs) were linked to reproductive failure in mink and hexachlorobenzene was killing herring gull embryos within eggs. For More Information: D.M. Fry “Reproductive effects in birds exposed to pesticides and industrial chemicals” Aulerich, RJ, and Ringer, RK. “Current status of PCB toxicity to mink, and effect on their reproduction

1962: Silent Spring published

In 1962, the book Silent Spring by American biologist Rachel Carson was published. It cataloged the environmental impacts of indiscriminate DDT spraying in the United States and questioned the logic of releasing large amounts of potentially dangerous chemicals into the environment without a sufficient understanding of their effects on ecology or human health. The book claimed that DDT and other pesticides had been shown to cause cancer and that their agricultural use was a threat to wildlife, particularly birds. Its publication was a seminal event for the environmental movement and resulted in a large public outcry that eventually led, in 1972, to a ban on the agricultural use of DDT in the United States. A worldwide ban on its agricultural use was later formalized under the Stockholm Convention, but its limited use in disease vector control continues to this day and remains controversial, because of its effectiveness in reducing deaths due to malaria, which is countered by environmental and health concerns. For more information: NYT’s article - How ‘Silent Spring’ Ignited the Environmental Movement Silent Spring Environmental & Society Portal

1966: Division of Environmental Health Sciences established at NIH

The National Institute for Environmental Health Sciences (NIEHS) was originally established as the Division of Environmental Health within NIH in 1966. In 1969, the Division became a full institute with the mission to “reduce the burden of human illness and disability by understanding how the environment influences the development and progression of human disease.” NIEHS researchers conduct groundbreaking research on the scientific knowledge about EDCs and their health effects. For example, NIEHS researchers led the studies that showed how DES toxicity involved the estrogen receptor, establishing it as an endocrine disruptor. For more information: About NIEHS Endocrine Disruptors – NIEHS Webpage

1971: DES identified as transplacental carcinogen

Children born to mothers prescribed DES were found to have increased risk of a rare reproductive tract cancer in their early 20’s. This case showed that exposure to an estrogenic chemical in pregnant women can produce adverse effects in the offspring without necessarily harming the mother, and that the effect may be delayed by some decades. Currently, the effect of DES exposure on the third generation (children of affected children) is being assessed. Pregnant women today are exposed to a number of important estrogenic chemicals, but as the case of DES shows, it will be difficult and perhaps impossible to characterize these exposures and link exposure to adverse outcome in 20-30 years. For more information: Herbst AL, et al. "Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women" Diethylstilbestrol – National Toxicology Program Report on Carciongens, Thirteenth Edition

1972: DDT ban takes effect

On December 31, 1972, in response to evidence of environmental and toxicological effects, including the publication of Silent Spring, the EPA announced that the general use of the pesticide dichloro-diphenyl-trichloroethane (DDT) would no longer be legal in the United States. This officially ended the widespread use of the endocrine disruptor DDT in the United States, although exposures to DDT continue due to its long persistence in the environment and use in foreign countries. For more information: EPA Press Release National Pesticide Information Center Fact Sheet on DDT

1979: First conference on “Estrogens in the Environment”

In September, 1979, the NIEHS sponsored a symposium to determine “what an estrogen is and how it works, and what effect estrogenic substances might have on human health.” The symposium gathered researchers in a variety of fields and resulted in published proceedings in 1980. For more information: Estrogens in the Environment(.pdf)

1989: Basel convention on the "Transboundary Movements of Hazardous Wastes and their Disposal"

As developed countries improved legislation and regulation of toxic materials, hazardous wastes were increasingly disposed of in developing countries without an appropriate regulatory infrastructure to protect their citizens from harms to toxic chemicals. The Basel Convention aimed to reduce the generation of hazardous waste, promote sound management of waste, restrict transboundary movements except when in accordance with principles of sound waste management, and develop a regulatory system to apply to permissible cases of transboundary waste movement. For more information: Protocol on Liability and Compensation for Damage Resulting from Transboundary Movement of Hazardous Wastes and their Disposal.

1990s: Alligator population imbalances due to endocrine disruption identified

Professor Lou Guillette, studying alligators in Lake Apopka, shows that alligators exposed to pesticides (including DDT) and pesticide breakdown products had elevated estrogen levels, stunted sexual organs, and genetic abnormalities. Exposures to these EDCs contributed to reproductive failure of alligators in in Florida and subsequent population reductions. For more information: Guillette LJ, Jr., et al., “Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida.” Guillette LJ, Jr., et al., “Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment

1990: David Barker proposes causal relationship between fetal development and adult disease

In 1990, David Barker proposed the concept, originally called the "Barker Hypothesis" that in utero environmental conditions, such as undernutrition, can permanently alter metabolism and other functions in ways that dramatically affect health later in life and cause e.g., heart disease. This concept has been expanded in recent years to include chemical exposures such as EDCs and is now called the Developmental Origins of Adult Health and Disease (DOHaD). For more information: Barker DJ and Osmond C. “Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.” Barker DJ, et al., “Weight in infancy and death from ischaemic heart disease.

1991: The term “Endocrine Disrupter” is first used at the Wingspread Conference

Theodora Colborn's 1988 research on the state of the environment of the Great Lakes revealed that top predator female birds, fish, mammals, and reptiles transferred persistent, man-made chemicals to their offspring, which undermined the development and programming of their youngsters’ organs before they were born or hatched. In 1991, in light of this evidence, Colburn convened 21 international scientists from 15 different disciplines to share their research relevant to transgenerational health impacts. During that meeting, the term “endocrine disruption” was coined. In 1992 a book followed entitled Chemically Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection, which is a collection of technical manuscripts by those who attended the session. The information from this volume and numerous subsequent scientific publications on the result of low-dose and/or ambient exposure effects of endocrine disruptors was popularized in Colborn’s 1996 book, Our Stolen Future, co-authored with Dianne Dumanoski and John Peterson Myers and published in 18 languages. Colborn’s work has prompted the enactment of new laws around the world and redirected the research of independent scientists, governments, and the private sector. For more information: Wingspread Consensus Statement 8pp excerpt from, Chemically induced alterations in sexual and functional development: The wildlife/Human connection. Editors Theo Colburn and C. Clement. 1992, Princeton Scientific Publishing.

1992: Study shows dramatic increase in testicular cancer following chemical exposure

Emerging evidence by a research team in Denmark showed a striking decline in mean sperm density and seminal volume from 1938 to 1991 in Danish men. This and other work further suggested that increases in testicular cancer, cryptorchidism and hypospadias could be due to environmental factors such as EDCs, and that these abnormalities could contribute to reduced fertility. For more information: Carlsen, E. et al., “Evidence for decreasing quality of semen during past 50 years.” Skakkebaek, NE. “Endocrine Disrupters and Testicular Dysgenesis Syndrome

1992: PCBs shown to affect cognitive function in children

Polychlorinated biphenyls (PCBs) are a type of EDC used in a variety of materials through the 1970s before they were banned. However, low levels of contamination in fish and wildlife continued to serve as sources of human exposure. Jacobson et. al., linked PCB exposure to impairment in cognitive functioning and showed that impairments were predominantly due to developmental, intrauterine exposure, rather than postnatal effects. For more information: Jacobson JL, et al., “Effects of prenatal PCB exposure on cognitive processing efficiency and sustained attention.

1995: Government agencies advance research on endocrine disruptors

In 1995, the Environmental Protection Agency (EPA) convened two workshops in response to the identification of EDCs as a high-priority research topic. These workshops then resulted in a research plan on EDCs with a series of key scientific questions, including questions related to multiple exposures, and whether testing guidelines adequately evaluate potential health effects. At the same time, the National Institute of Environmental Health Sciences (NIEHS) identified research “on the health effects of chemicals and other exposures that are suspected to disrupt the normal activity of the endocrine system” as a high-priority for both NIEHS and the Office of Research on Women’s Health (ORWH). To promote research in this area, the NIEHS and ORWH issued a Request for Applications (RFA) on October 27, 1995 to solicit applications from researchers intending to study EDCs and women’s health outcomes. For more information: EPA Research Plan for Endocrine Disruptors Endocrine Disrupting Chemicals and Women’s Health Outcomes

1996: Safe Drinking Water Act amended: Launch of the Endocrine Disruptor Screening Program EDSTAC

The Safe Drinking Water Act (SDWA) was first enacted in 1974 to establish standards and regulations to ensure that the public is protected from harmful contaminants in drinking water. In 1996, the act was significantly amended in the Food Quality Protection Act (FQPA), which amended the Federal Food, Drug, and Cosmetic Act (FFDCA), and the Safe Drinking Water Act (SDWA) to require that EPA screen pesticide chemicals for their potential to produce effects similar to those produced by the female hormones (estrogen) in humans. It also gives EPA the authority to examine certain other chemicals for non-estrogen endocrine effects. To provide recommendations and enable EPA to carry out these directives, EPA established the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC). For more information: History of the EDSP

1996: "Our Stolen Future" published

In 1996, international representatives from regulatory agencies, national authorities, and international agencies gathered for a workshop on “the Impact of Endocrine Disruptors on Human Health and Wildlife” in Weybridge, UK. Workshop participants discussed current research and knowledge gaps on EDCs, and identified future priorities for the European Commission and Member States. For more information: Conclusions and Recommendations of Weybridge Conference

1996: First Weybridge conference on EDCs

In 1996, international representatives from regulatory agencies, national authorities, and international agencies gathered for a workshop on “the Impact of Endocrine Disruptors on Human Health and Wildlife” in Weybridge, UK. Workshop participants discussed current research and knowledge gaps on EDCs, and identified future priorities for the European Commission and Member States. For more information: Conclusions and Recommendations of Weybridge Conference

1998: First Gordon Research Conference on EDCs

The Gordon Research Conferences are a unique series of meetings that provide researchers opportunities to share new and unpublished results with an international group of scientists and experts. The first meeting on Environmental Endocrine Disruptors was held at Plymouth State College and chaired by Harriette L. Phelps. Subsequent meetings were held every 2 years.

1998: Rotterdam convention on the prior informed consent procedure for certain hazardous chemicals and pesticides in international trade

In 1998, over 150 countries ratified an international treaty to promote information exchange and shared responsibility among countries to protecting human health and the environment from hazardous chemicals and pesticides. The chemicals listed in the Rotterdam Convention include known EDCs, such as polychlorinated biphenyls (PCBs). For more information: Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade

1999: European Commission adopts community strategy for endocrine disruptors

Building on a 1998 Resolution calling on the Commission to “take action on the issue of endocrine disruptors” the Commission published a Community Strategy for Endocrine Disruptors. This document sought to identify the causes and consequences of endocrine disruption, and propose policy actions to protect the public in alignment with the precautionary principle. The strategy included short, medium, and long term actions, and called for further research, international coordination and cooperation, communication with the public, and policy actions. Implementation reports on the Community Strategy have been published periodically through 2011. For more information: European Commission Website on Endocrine Disruptors

2001: Conference of Plenipotentiaries adopts Stockholm Convention on Persistent Organic Pollutants

Recognizing that Persistent Organic Pollutants (POPs) can cause serious health effects, the Stockholm Convention on POPs is a global treaty establishing expectations that parties should eliminate, restrict, or take measures to reduce the unintentional release of certain chemicals to protect human and environmental health. Many of the regulated chemicals include EDCs such as PCBs, hexachlorobenzene, and DDT. For more information: Overview of the Stockholm Convention on POPs

2002: WHO Issues First Global Assessment of the State of the Science of Endocrine Disruptors

Through the International Programme on Chemical Safety (IPCS), the World Health Organization (WHO) sought to address concerns related to EDCs by conducting a comprehensive evaluation of the state of the science for the effects of EDCs on animal and human health. The document examined human health impacts on reproduction, neurobehavior, cancer, the immune system, and other endocrine systems potentially vulnerable to EDCs. The WHO also sought to create a proposed framework for assessing endocrine disruptors. For more information: WHO/IPCS 2002 State of the Science of EDCs

2006: SAICM Adopted by International Conference on Chemicals Management

The Strategic Approach to International Chemicals Management (SAICM) is a “policy framework to foster the sound management of chemicals. SAICM incorporates the perspectives of a variety of stakeholders, including regulatory agencies, governments, industry, and environmental groups. Working together, stakeholders in SAICM contribute to achieving the goal of sound management of chemicals and waste by implementing actions at the national, regional, and global levels. SAICM subsequently recognized EDCs as an emerging policy issue and adopted resolutions specific to EDCs. For more information: Overview of SAICM EDCs as an Emerging Policy Issue

2006: First use of the term “obesogen”

In 2006, researchers at the University of California, Irvine, highlighted the role of environmental chemicals in the emerging obesity epidemic and coined the term “obesogen”. Many of the chemicals, termed “obesogens” are also EDCs acting on endocrine pathways. For more information: Felix Grün, and Bruce Blumberg “Environmental Obesogens: Organotins and Endocrine Disruption via Nuclear Receptor Signaling

2009: Endocrine Society issues Scientific and Position Statements on EDCs

In 2005, the Society created a Task Force charged with summarizing current knowledge about EDCs, and with recommending actions the Society could take to promote EDC research. The Task Force’s work resulted in a comprehensive scientific document published in 2009 as the Society’s first Scientific Statement. The Statement presented a review of EDC literature, focused on the effects of low-dose exposure to EDCs on endocrine systems, and clearly elaborates a strong basis for concern about EDC health risks. That same year, the Endocrine Society issued a Position Statement on EDCs, establishing the Society’s core policy positions on EDCs. The Scientific Statement was a landmark document, and along with the Position Statement established the Endocrine Society as a thought leader on the subject of EDCs. For more information: Endocrine Society Scientific Statement on EDCs Endocrine Society Position Statement on EDCs

2012: Endocrine Society publishes “Endocrine-Disrupting Chemicals and Public Health Protection: A Statement of Principles from The Endocrine Society"

Recognizing that the regulatory approach is insufficient for the reduction of harms due to EDCs, a group of scientists with expertise in hormone biology and EDCs proposed that “principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations.” The statement emphasized the importance of critical windows of development, and that it cannot be assumed that there exists a safe dose for endocrine disrupting chemicals. For more information: Zoeller RT., et al., “Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society

2012: WHO Updates State-of-the-Science of EDCs

In 2012, the WHO/IPCS updated the State of the Science of EDCs, incorporating additional insights and knowledge from scientific literature in the decade after the original 2002 document. For more information: http://www.who.int/ceh/publications/endocrine/en/

2015: Endocrine Society issues Position Statement on EDCs in the EU

Public interest in health threats posed by EDCs lead to the development of policies, laws, and regulations designed to mitigate health risks due to EDCs. In the European Union, relevant policy activities included Europe’s Strategy on EDCs, and Regulation on Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH). In 2015, the Endocrine Society issued a statement with positions for policymakers in the European Union to consider in the development of criteria to define EDCs and establish science-based regulatory frameworks. For more information: Position Statement on Endocrine-Disrupting Chemicals in the European Union

2015: Endocrine Society releases Second Scientific Statement on EDCs

In the update to the landmark 2009 statement, a task force of experts led by Andrea C. Gore reviewed advances in scientific understanding of EDCs since the publication of the Society’s first Scientific Statement on EDCs. The statement notes new evidence that has emerged in the past five years showing an association between EDC exposure and increased risk of diseases and disorders such as diabetes and obesity. In addition, the statement authors wrote that the evidence that EDCs are associated with health risks is stronger than ever before. The results of epidemiological studies in humans, research in people who have been exposed to known endocrine disruptors in the workplace, mechanistic studies, and animal studies all support the conclusion that the scientific evidence for harms due to EDC exposures is stronger than ever. For more information: EDC-2 - The Endocrine Society's Second Scientific Statement on EDCs

2016: European Commission proposes criteria to identify EDCs.

Although European Union law contains provisions to protect consumers from EDCs in commerce, the relevant legislation lacked criteria on how to define what an EDC is. On June 15, following years of evaluation of potential criteria, the Commission proposed hazard-based criteria for identifying EDCs. However, the criteria set an extremely high bar for identifying a chemical as an EDC. The Endocrine Society will continue to work with legislators to ensure that identification of EDCs is based on science and will protect human and environmental health. For more information: European Commission Press Release

2016: NIEHS Workshop on 25 Years of Endocrine Disruption

As part of the NIEHS 50th Anniversary Celebration, the Institute will hold a special workshop on EDCs entitled “25 years of Endocrine Disruption: Past Lessons and Future Directions. The multi-day event will celebrate the science of EDCs and the people involved in driving the field forward. The event will also be forward-thinking, including discussions on how to translate science into action, design safer chemicals, and build a safer future. For more information Meeting Flyer Draft Agenda

2017: First SAICM Intersessional Process Meeting

During the 4th session of the International Conference on Chemicals Management (ICCM4) the conference initiated an intersessional process to consider how to advance the goal of sound management of chemicals and waste beyond 2020 as part of the Strategic Approach to International Chemicals Management (SAICM). The first meeting is scheduled to take place in February 2017, with future meetings of the SAICM Open-ended Working Group scheduled for 2018/2019, and ICCM5 to be held in 2020. The Endocrine Society will remain involved in the SAICM process to ensure that EDCs are managed by the international community in agreement with the latest scientific information and principles of endocrinology. For more information: The Strategic Approach and sound management of chemicals and waste beyond 2020.