In 1991, Theo Colborn convened a group of international scientists to discuss concerns about the trans-generational effects of persistent chemicals on predator species in the Great Lakes.  Their report, and a subsequent book authored by Colborn and her colleagues entitled Our Stolen Future, Are We Threatening Our Fertility, Intelligence and Survival?,  proposed that many chemicals which display an ability to interact or interfere with the human endocrine system have the ability to elicit adverse health effects at doses far lower than the toxicities caused through other modes of action and required special regulation.  The hypothesis proved irresistible to the mass media who soon published a flurry of articles about “gender bending” chemicals and threats to human existence.

Legacy of Scientific Research and Debate

During the following 25 years, Colborn’s and her colleagues’ work inspired hundreds if not thousands of research studies into modes of action and potential health effects of so called endocrine disrupting chemicals (EDCs). And yet, nearly three decades later, scientists are still trying to provide concrete answers to some of the very same basic questions about exposures to low doses of chemicals –  Do they meet the definition of an EDC or not? Are there safe levels of exposure to EDCs?  Should certain chemicals be banned, or can they be managed safely?

Next week, the National Institute of Environmental Health Sciences (NIEHS), one of 27 institutes and centers that comprise the National Institutes of Health, will host a two-day conference to "celebrate the people and the science" investigating links between chemicals and the human endocrine system. Some of the conference organizers will undoubtedly highlight the dangers of chemicals with some self-congratulatory remarks, but the big questions still remain: how far has the science truly advanced, and where do we go from here? 

EPA’s Step-by-Step Science and Risk-Based Processes to Identify and Manage EDCs

Intense public discussion of potential EDC's at the time that Congress was debating amendments to the Safe Drinking Water Act and was drafting the Food Quality Protection Act led them to include language requiring the EPA to develop a program to screen for chemicals that have the potential to be EDCs.  To their credit, EPA  convened a multi-stakeholder process to help them design what became a two tiered screening program. EPA then led an effort to scientifically validate the eleven individual assays which now constitute Tier I of EPA's Endocrine Disruptor Screening Program (EDSP).  The assays were designed to detect interaction with endocrine systems of humans and wildlife and were chosen to be especially sensitive so as to minimize the chances that a true EDC would be missed at the risk of falsely identifying some chemicals as EDCs which are truly not.

Chemicals that screen positive in EDSP Tier I are then subjected to a weight of evidence (WOE) evaluation to determine whether additional testing is required in Tier II to develop evidence of any adverse health effects caused by an endocrine mode of action.  Screening and WOE evaluations were completed for 52 pesticide active and inert chemicals in 2015. EPA recently announced a pivot in the EDSP to introduce high throughput in vitro methods to replace several of the in vivo assays which will greatly accelerate the pace of the program and reduce numbers of animals used.  

Through the efforts of EPA, academia and others, considerable progress has been made to develop methods, tests and data that are answering questions about endocrine active and endocrine disrupting chemicals. Although the development and implementation of EDSP arguably represents the most significant accomplishment in terms of preventing future harm from EDC's, it is not as if EPA was doing nothing before to protect the public.  

For many years, EPA officials have required for pesticide approval a battery of animal tests designed to detect a chemical's ability to cause a range of adverse health effects, including cancer and reproductive and developmental disorders, and they and other regulatory agencies establish safe levels of exposure based on the most sensitive endpoint detected. 

The EDSP adds another layer of protection by exploring the ability of a chemical to act via an endocrine mode of action; however, regulators have never let a lack of knowledge of a chemical's mode of action be a barrier to taking steps to reduce risks.  EPA has also contributed their expertise and experience to an international effort, under the auspices of the Organisation for Economic Co-operation and Development (OECD), to develop recommendations for how to screen chemicals to detect EDCs.

Another significant accomplishment has been the development of a globally agreed upon definition of an EDC. This arose as part of a seminal "state of the science" report issued by the World Health Organization's International Programme on Chemical Safety in 2002. That definition requires that a chemical both "alter the function(s) of the endocrine system and consequently cause adverse effects in an intact organism, or its progeny, or (sub) populations.”  

Although there is widespread agreement on this definition, some stakeholders while acknowledging it, are also trying to subvert it. They want to conflate mere transitory endocrine activity, which is a property common to many everyday products human's ingest (e.g., coffee) with endocrine disruption, without demonstrating a consequent adverse health effect.  This is problematic for many reasons, not the least of which it would falsely identify many chemicals as EDC’s and confuse the public and marketplace.

Disagreements on the Science Persist

Beyond the development of EDSP and the definition of an EDC, agreement on progress in other areas is harder to find, and strong disagreements persist on important topics.  

Paramount among them is the degree of confidence in the existing scientific base to establish causal links between low level chemical exposures in the general population and a range of health conditions purported to be associated with perturbations in the functioning of the endocrine system. Included are neurobehavioral disorders and diseases (including autism and lowered IQ), male and female reproductive disorders, certain types of cancers, obesity and diabetes.  

Exposure Levels and Potency Matter

Disagreements also exist on whether safe levels of exposure to EDCs can be established, whether potency matters, and the appropriate weight that should be accorded data derived from un-replicated, new novel testing approaches versus those from internationally agreed upon animal testing protocols using Good Laboratory Practices when evaluating the evidence on a particular chemical.  

Unfortunately, just as is the case in the current US presidential campaign, serious debate on these topics is lacking and instead the discussion has been sidetracked by a tendency for proponents of the issue to engage in the politics of identity, branding anyone with a different perspective to be in industry's pockets. Such ad hominem attacks are a serious impediment to progress and must stop.

Looking to the future, it is difficult to be optimistic that many of these differences can be resolved anytime soon. However, at a minimum, the upcoming conference does present the leadership of NIEHS with an opportunity to foster a more objective and inclusive atmosphere for serious discussion of topics that many scientists still regard as unresolved. Setting an appropriate tone will be critical.

Clarity Needed in the Scientific Approach

It would also be helpful if NIEHS would publicly endorse EPA's EDSP program and the WHO/IPCS definition of an EDC and emphasize the importance of having a program that not only detects chemicals that are truly EDC's, but also determines with confidence chemicals that are not EDC's.  

Unfortunately, despite 25 years of NIEHS research there still exists much confusion about endocrine disruption among the public.  Stakeholders, particularly consumers whose health we are all trying to protect, but also industry who is trying to meet society's growing unmet needs, are best served by a system that is science and risk-based, transparent, predictable and fair and that delivers a positive safety evaluation and determination on chemicals before they come to market.  Fortunately,  through the recently adopted Lautenberg Chemical Safety Act, EPA  officials appear committed to deliver such a system, but they are not immune to political pressure or sharp competition for funding, and so we must all remain vigilant.