Endocrine Timeline: Nearly 100 Years of Enhancing Scientific Understanding
Research into chemicals that can interact with the human endocrine system can be traced as far back as the 1920s. Since that time, hypotheses have been advanced by scientists about whether some of these substances can cause adverse health effects.
Many of these hypotheses have been examined in scientific studies on the part of academia, governments and industry, often working together to advance modern scientific understanding about how some chemicals can interact with the endocrine system, and whether interaction could have health effects.
What the science tells us today
Scientists know that some chemicals (natural and manmade) are endocrine active – they can interact with the endocrine system. But, interacting with the endocrine system does not necessarily result in adverse health effects. If there are no adverse health effects, there’s endocrine interaction but not endocrine disruption, and the substances are not endocrine disrupting chemicals, a label frequently misused by the media and others.
Some endocrine active substances have no health effect at all. The vast majority of endocrine active substances produce effects that are either neutral or beneficial in nature. Vitamins are often pointed to as an example of a beneficial health effect. There are lots of endocrine active substances, but the number of substances that also produce adverse effects – “endocrine disruptors” – is much smaller.
Public understanding and public policy are much better informed when we all work together to use clear and consistent descriptions of the difference between endocrine activity and endocrine disruption.
Current regulatory framework
EPA has used standardized test methods since the early 1970s to detect potential adverse effects of chemicals, including endocrine disruptive effects. The launch of the Endocrine Disruptor Screening Program (EDSP) in the late 1990s marked a new direction for how EPA would review certain chemicals for endocrine activity and effects.
The EDSP program uses high quality, validated screening assays and test methods to determine which substances have the potential to interact with the endocrine system. Substances with such potential may then be further evaluated by EPA to determine whether adverse effects can occur and what exposures might trigger such responses.
Chemicals that can cause adverse effects will undergo a comprehensive risk assessment, so researchers can understand the potential for exposure to the chemical and possible effects in real-life scenarios.
This science-based risk assessment helps scientists determine the difference between the magnitude and duration of exposure that can produce adverse effects, and the typical exposures experienced by humans and wildlife. EPA would then determine if real-world exposures would not be expected to result in adverse health effects, considering groups that might be particularly sensitive. This review provides a solid scientific and risk-based foundation for prudent regulation, if needed.
Timeline of Key Events
1923
The first estrogen bioassay, (a bioassay is a measurement of the potency of a substance by its effect on living cells or tissues), is developed for use in pharmaceutical research.
1962
General public book Silent Spring is published, which suggests a connection between reproductive health problems in wildlife and chemical exposure, particularly the insecticide dichlorodiphenyltrichloroethane, or DDT. The emotional public reaction to Silent Spring helps to inspire the modern environmental movement.
1971
Diethylstilbestrol (DES), a synthetic, non-steroidal estrogen, was prescribed for at-risk women to help prevent miscarriage. The U.S. Food and Drug Administration (FDA) later withdraws DES approval after it is connected to vaginal cancer in young-adult daughters who were exposed to it in the womb.
1970s-1980s
Researchers suggest a link between high exposures to polychlorinated biphenyls (PCBs), dioxins and furans with reproductive and/or developmental disorders and immune system effects. Some activists begin to refer to these substances as “endocrine disrupting chemicals” (EDCs) on the assumption that they cause those adverse effects by altering the functioning of the endocrine system.
Early 1990s
Studies are first published claiming that, in the laboratory, certain chemicals used to make plastics demonstrate potential estrogenic effects. Activists seize on these reports, marking the beginning of a multi-decade effort to exploit the issue with exaggerated and unproven claims.
Mid-1990s
Activist campaigns drive public concern in Japan and other Asian countries about the safety of polystyrene instant noodle cups.
1996
Theo Colburn’s Our Stolen Future helps to popularize the controversial endocrine disruptor hypothesis – that manmade chemicals could be disrupting normal hormonal processes and causing adverse health consequences. The hypothesis is based largely on anecdotal data and conjecture rather than scientific evidence, which leads many scientists to question the validity of the book’s claims.
Tulane University publishes a paper alleging endocrine effects of combined exposures to low levels of pesticides. Tulane later retracts the paper after four groups of independent scientists are unable to replicate the findings. Following an investigation, the U.S. Office of Research Integrity (ORI) rules that at least one of the Tulane researchers “committed scientific misconduct by intentionally falsifying the research results published in the journal Science and by providing falsified and fabricated materials to investigating officials.”
The U.S. Food Quality Protection Act and amendments to the Safe Drinking Water Act are passed, mandating that the U.S. Environmental Protection Agency (EPA) develop a new chemical screening program to help identify endocrine disruptors. After a multi-year dialogue with stakeholders, EPA would go on to develop the Endocrine Disruptor Screening Program (EDSP), a science- and risk-based endocrine screening and testing program focused on protecting public health and the environment.
1997
Frederick vom Saal publishes a study alleging endocrine effects of BPA at very low doses, giving rise to the still-unproven hypothesis known as the “low-dose hypothesis.”
1998
The Japanese government publishes Basic Policy on Environmental Endocrine Disruptors – Strategic Programs on Environmental Endocrine Disruptors: SPEED’98. The policy framework is designed to encourage the advancement of studies of alleged chemical effects on the endocrine system, new environmental surveys and chemical monitoring, and test development and implementation.
1998-Present
The Organisation for Economic Co-operation and Development (OECD), including Japanese and U.S. government agencies, work together to develop, validate, publish and adopt various screening and testing methods to identify EDCs.
2002
The joint International Programme on Chemical Safety (IPCS) of the World Health Organisation (WHO), the United Nations Environment Programme (UNEP), and the International Labour Organisation (ILO) publish the first State of the Science Report on Endocrine Disrupting Chemicals. The well-received report offers a widely accepted definition of EDCs and is lauded for using a weight-of-the-evidence approach to considering scientific studies. While the report claims to find evidence of endocrine disruption by some chemicals in wildlife, its authors conclude there is insufficient evidence to establish that endocrine disrupting chemicals have produced effects in humans.
2006
The EU chemical regulatory program known as REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) becomes law. Industrial chemicals that meet a statutory definition of EDCs are treated as “Substances of Very High Concern” (SVHC) under REACH.
2009
The U.S. EPA’s Endocrine Disruptor Screening Program takes a step forward, issuing test orders to manufacturers of EDSP List 1 chemicals (67 pesticides or high volume pesticide inserts), thus commencing Tier 1 screening (11 assays).
2012
The OECD updates its Conceptual Framework for the Testing and Assessment of Endocrine Disruptors, which includes guidelines for conducting various screens and tests.
The EU Biocidal Products Regulation is adopted. In the EU, all biocidal products require an authorization before they can be placed on the market, and the active substances contained in the products must be previously approved. Biocidal products that contain EDCs cannot be authorized unless it can be shown that their use results in negligible exposures.
2013
Bergman et al author a report published by WHO and UNEP which purported to challenge the 2002 WHO-UNEP State of the Science report on EDCs, claiming numerous human health effects attributed to EDC exposure. However, a critical review by Lamb et al notes serious shortcomings in the 2013 report’s methodology.
The U.S. EPA proposes a series of EDSP List 2 chemicals (109 total, including more pesticides and chemicals frequently found in potential drinking water sources) to be screened with EDSP Tier 1 assays.
2014
The EU Commission publishes a draft roadmap, Defining criteria for identifying Endocrine Disruptors in the context of implementation of the Plant Protection Product Regulation and Biocidal Products Regulation. European stakeholders differ significantly as to which criteria should be used to identify endocrine disruptors and whether decisions to regulate should be based on risk or merely on hazard only.
2015
EPA continues to make progress with its EDSP, publishing weight-of-the-evidence assessments of results of Tier 1 screening tests conducted for 52 List 1 chemicals.
Adopting 21st-century scientific advancements, the EPA announces a new approach that will use High Throughput Assays using EPA’s Toxicity Forecaster (ToxCast) for three Tier 1 screening assays. This is intended to accelerate the pace of chemicals screening and reduce the numbers of laboratory animals used.
Trasande et al publish a series of four papers alleging that exposures to EDCs cost the EU billions of dollars a year. While the report initially receives significant attention, its flawed underlying assumptions and methodology ultimately receive substantial expert criticism.