On February 9, the International Association of Mutual Benefit Societies (AIM) released a declaration on Endocrine Disrupting Chemicals (EDCs) in which the association implores the EU Commission to take a very conservative approach to identifying and regulating chemicals. If adopted, this approach would increase costs and reduce consumer choice while providing no commensurate benefits to public health. To support its case for taking action based on the "precautionary principle", AIM makes a number of claims of health effects attributable to EDCs that are highly speculative – i.e., the evidence is hardly as convincing as AIM would have its readers believe. The Declaration goes on to market AIM’s agenda by either exaggerating or misrepresenting the state of the science on EDCs.  

 

This document further explores those claims and presents the actual facts, citing independent, third parties as sources.

 

Before discussing the specific claims it is important to point out three general problems with the approach AIM has taken:

 

• The authors of the Declaration frequently confuse correlation with causation. This is a common misunderstanding – that if X follows or coincides with Y, that X must somehow be causing Y. Rarely is this proven to be true. 
• The authors make several claims without citing scientific evidence to support them. When they do cite evidence, it is often taken from animal studies in which very high doses of a chemical were administered, or from epidemiology studies of subgroups of humans who have had unusually high exposures -- much higher than the general population..  Yet, AIM ignores the differences in exposure levels and assumes low-level, background exposures pose the same magnitude of risks. Most of the scientists who have studied this issue consider this unlikely.
• The authors lump all chemicals they suspect of being EDCs into a single category and imply that they act via a common mechanism and with equal potency to cause the same diseases and disorders. This is a faulty worldview which assumes that, if one member of the category is linked to a specific health effect, no matter how weakly, then all chemicals in that category can be expected to cause that same effect.  According to the science vast differences can exist in both the types of effects and the potency with which chemicals act to produce adverse effects.

 

Fact-checking AIM

 

Claim #1: "Endocrine disruptors are thought to cause two diseases responsible for 70% of infertility cases."

 

The Facts: “Thought to cause”…? The authors neither provide a scientific reference to substantiate this claim, nor do they make it clear which two diseases they reference, or which chemicals they allege are EDCs and are acting as causal factors. Responding to this claim requires one to make certain assumptions about what AIM actually means by it.

 

Infertility affects approximately 10 percent of heterosexual couples who wish to conceive, and the causes are complex. Several recent literature reviews of the evidence linking exposure to EDCs and male and female reproductive disorders have been published. None has concluded that there is sufficient evidence of a causal link, and they have instead highlighted significant research data gaps.

 

The majority of scientists today consider blocked fallopian tubes as likely responsible for about 25 percent of infertility cases. The most common underlying causes for the blockage are:

 

-Pelvic Inflammatory Disease, often caused by Sexually Transmitted Diseases

-Endometriosis

-Uterine fibroids

-Ectopic pregnancy

 

Poor egg health is also a major cause of infertility in women and risk factors include:

 

-Poor lifestyle choices; smoking, drinking alcohol, poor diet, stress, environmental pollution and sedentary lifestyle (poor circulation).

-Hormonal balance

-Genetic predisposition

-Damage to the reproductive organs

-Illness, for example cancer treated with chemotherapy

-Auto-immune disorder

-Advancing age

 

We presume that at least a portion of AIM's allegation – that there is a role for EDCs in infertility– is based on speculation about their possible role in causing endometriosis and fibroids in women.

 

A recent review by Smarr and colleagues of the evidence linking EDC and endometriosis made the following conclusions:

 

"Although evidence supports a possible relation between many classes of EDCs and an endometriosis diagnosis, we are unaware of any evidence supporting a risk for bisphenol A or PBDEs. This observation may reflect the lack of attention to these compounds relative to other classes of chemicals. The remaining classes of EDCs addressed in this article have some evidence linking exposure to endometriosis, although often the findings are equivocal across studies. We believe this point underscores the need for future research responsive to important methodologic considerations if we are to answer this important question."

 

Hardly a strong endorsement for a causal link!

 

Katz et al recently reviewed the human epidemiology and animal toxicology evidence linking EDCs to fibroids. The authors reported evidence from the former to be inconsistent and inconclusive.  They regarded the animal toxicology evidence to be more compelling, but did not address how the high doses used in toxicology studies relate to the much lower environmental exposure levels humans typically receive.

 

We also presume that a portion of AIM's claim that EDCs are causing human infertility is due to their alleged effects on male reproductive health.

 

Infertility in men is most often caused by:

 

• A problem called varicocele. This happens when the veins on a man's testicle(s) are too large. This heats the testicles. The heat can affect the number or shape of the sperm.
• Other factors that cause a man to make too few sperm or none at all.
• Movement of the sperm. This may be caused by the shape of the sperm. Sometimes injuries or other damage to the reproductive system block the sperm.
• Sometimes a man is born with the problems that affect his sperm. Other times problems start later in life due to illness or injury. For example, cystic fibrosis often causes infertility in men.

 

A recent, state-of-the-art, systematic review of the published epidemiology literature on EDCs and male reproductive diseases and disorders -- including cryptorchidism, hypospadias, lowered sperm count and testicular cancer -- "...found no strong support for a global effect as a whole or on any specific outcome."  

 

Thus, once again, AIM has misrepresented the available scientific evidence.

 

Claim #2: Endocrine disrupting chemicals (EDCs) are everywhere nowadays. They are probably linked to many diseases whose incidence is rising. That trend can no longer be ignored – it involves reduced fertility, adverse pregnancy outcomes, obesity and type 2 diabetes, and childhood leukemia.

 

The Facts: No definition is provided for EDCs in this context. A precise definition is importantbecause the majority of the substances that may interact with the endocrine system result in activity that is benign, or in some cases, even essential to our well-being. Terms becoming popular in media reports mislabel many chemicals as “endocrine disrupting chemicals” or “EDCs,” when, in fact, scientific study is still underway or does not support such labels. From a regulatory policy and scientific perspective, it is important to distinguish and focus on those substances that have a real potential to cause harm to people or the environment, versus those that merely interact with the endocrine system in a benign or beneficial way. “Everywhere nowadays” is hardly a factual statement.

 

AIM says EDCs are "probably linked to many diseases whose incidence is rising". Such a casual statement is highly speculative and is not supported by a robust review of the available scientific evidence. So, how might AIM have arrived at this claim?

 

Firstly, AIM concludes that because the increase in disease trends has occurred primarily over the last few decades, these trends cannot be entirely attributable to genetic causes. It is implied that if these trends are not the result of genetic heritability, then the only other explanation is environmental exposure to chemicals. However, environmental factors go well beyond chemicals, and cover a multitude of characteristics in human populations including: diet, exercise, lifestyle factors, infectious agents, and even drug use - factors which can be completely unrelated to environmental chemical exposures. 

 

There are many factors that can influence the appearance of an increasing trend (either temporally or geographically) in disease incidence or prevalence. For human health considerations, these include changes in diagnostic criteria, screening, medical interventions, and treatment. Life style trends are also very important for example, delayed childbearing can greatly impact fertility and the incidence of birth defects.

 

No reference is provided to support the alleged link between EDCs and childhood leukemia.  Such an allegation not is unsupported by the weight of scientific evidence and was given only the briefest of mention by the authors of the controversial UNEP/WHO 2012 report on EDCs which was criticized for not using state of the art review methods.  The authors of the UNEP/WHO report concluded the few epidemiological studies available "...lacked any detailed exposure information, only studied small numbers, and are limited by a recall bias of the parents."

 

Claim#3: "Worse still, global rates of endocrine-related cancers have dramatically increased over the past decades."

 

The Facts: Let’s first tackle the allegation that trends for endocrine cancers are increasing, and focus on cancers of the breast, testes, prostate and ovary, which are the types of cancer most often described as "endocrine-related." First of all, reliable cancer trend data for Europe as a whole is difficult to find as there are significant variations in incidence and mortality rates across the individual countries. These reflect differences in the national health system policies (e.g. organized screening); the completeness of recording cancer incidence and death; the varying prevalence of risk factors between countries and regions; and disparities in human development and the effective delivery of cancer control measures.

 

With the exception of lung cancer among women and pancreatic cancer among both sexes, overall cancer mortality has been steadily declining in Europe since its peak in 1988, translating to an overall 26% fall in men and 21% in women, and the avoidance of over 325 000 deaths in 2015 compared with the peak rate.  Since 2009, breast cancer rates in women fell 10.2% and prostate cancer rates among men fell 12.2%.

 

In the U.S., during the last decade, breast cancer incidence has been level, prostate cancer has been falling on average 5.1% each year, and ovarian cancer has been declining 1.9% each year.  Although testicular cancer incidence has been rising 0.8% per year, this appears completely attributable to earlier detection as mortality rates have been stable and five year survival rates have been increasing.  

 

Thus, contrary to the assertion in the AIM declaration, rates for endocrine related cancers are not increasing.  Nor is there scientific consensus that EDCs play a causal role in the etiology of cancers of the breast, testis, prostate and ovary.

 

Claim #4:  "Of the over 1300 chemicals known or suspected to be capable of interfering with endocrine systems, only a small fraction has been properly investigated and the great majority of the chemicals which are currently commercially used have not been tested at all for endocrine disruption effects."

 

The Facts: the figure of 1300 chemicals alleged by AIM as known or suspected to be capable of interfering with endocrine systems derives from work done by the NGO TEDX, whose main purpose is to advocate for changes in the way chemicals are regulated.

 

The TEDX list of alleged EDCs has been roundly criticized for having the following weaknesses:

 

• It does not employ the widely accepted WHO/IPCS definition of an EDC, but instead conflates mere endocrine activity with endocrine disruption (see earlier discussion).
• There is no consideration of the quality of the underlying research evidence.
• It does not use state of the art systematic review and/or weight of the evidence evaluation of a body of literature on a chemical.
• The reviewers tasked with evaluating the literature lack sufficient scientific qualifications to undertake a robust evaluation of the evidence.
• It employs a very low threshold for listing a chemical resulting in too many chemicals that truly are not EDCs being listed as potential EDCs (a single, un-replicated study is deemed sufficient to identify a substance as an EDC).
• Once a chemical is listed, no amount of new contradictory evidence is sufficient to de-list it, even if that new evidence is of superior quality and reliability to the original evidence.
• It lacks a multi-stakeholder process for nominating chemicals or appealing listed chemicals, i.e., there is no peer review of the TEDX classification of chemicals.
• It does not take into account endocrine potency or real world exposures, and thus ignores the real potential for health risks.

 

 

Given the importance of open and transparent scientific debate, I would welcome the authors of the AIM declaration on EDCs to respond to the concerns I have shared here, or acknowledging the errors I have cited, significantly revise their declaration to reflect the actual state of the science on EDCs.