Tags: chemicals, endocrine disrupter, environment, science, world health organisation
Some points in favour of the Endocrine Society’s definition of “endocrine disruptor”. Last month, Yannick Vicaire, Chemicals Policy Officer at Réseau Environnement Santé described the gulf between the identification and actual regulation of endocrine disrupting chemicals (EDCs). To follow up, this month we examine how the definition of EDC ultimately adopted by the EU may result in greater or fewer potential EDCs facing regulatory scrutiny.
One of the longest lists of potential endocrine disrupting chemicals (EDCs) so far produced is 870 compounds in length. Assembled by the Endocrine Disruption Exchange (TEDX), a chemical makes the list if a published, verified citation from the primary scientific literature demonstrates it has an effect either on the endocrine system or on the signalling cascades governing any of the body’s systems (TEDX 2011).
We can use this list as the basis for a conceptual, qualitative stress-test for elements of the various proposed regulatory definitions of “endocrine disrupting chemical”. Since each proposal will induce a tendency in any subsequent regulatory framework towards recognising more or less of the TEDX chemicals as EDCs, then proposals which recognise for regulatory purposes more of the TEDX compounds as potential EDCs can be considered more precautionary; those which recognise fewer compounds as potential EDCs would be less precautionary. How good or bad the proposals are depends on how precautionary one thinks the regulation ought to be.
The classic and widely (though not universally) accepted definition of endocrine disruptor, from which almost all subsequent definitions have been derived, was presented in 2002 by the World Health Organisation: “An endocrine disrupter is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations.” (WHO/IPCS 2002)
The most recent opinion on the criteria for identifying a substance as an EDC has come from the EU Joint Research Centre. Softer than the WHO/IPCS definition, it recommends: “the elements for identification of an endocrine disrupter [are] demonstration of an adverse effect for which there [is] convincing evidence of a biologically plausible causal link to an endocrine disrupting mode of action” (JRC 2013).
If either was adopted as the regulatory definition of EDC for the EU, the JRC definition would likely capture more potential EDCs than the WHO definition because of its emphasis on “convincing evidence” rather than “causal proof” of harm mediated via an endocrine-disruption mechanism. Neither scheme, however, would capture very many of the TEDX chemicals because at this early stage of research most evidence of ED effects come from preliminary in vitro test-tube data. Since this usually only shows interference with a hormonal or signalling pathway, rather than an adverse effect on health, it hardly amounts to “convincing evidence” of harm, let alone causal proof of it. These definitions require substantial proof of harm before a compound can even be considered for regulatory purposes as an EDC.
In contrast to the JRC and WHO/IPCS is the Endocrine Society’s definition of endocrine disruptor: “An ED is an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.” Since this can be demonstrated with simple in vitro tests, this would be almost maximally inclusive, bringing all the TEDX chemicals under the purview of EDC regulation. This definition is much more precautionary than the WHO/IPCS or JRC definitions, as it would force regulators to classify a compound for which there is some evidence of endocrine disruption potential as an endocrine hazard.
It is understandable that suddenly classifying a large number of chemicals as EDCs would be onerous for their users and manufacturers, which is why organisations such as CEFIC have expressed a preference for “tak[ing] into account what the real harm is versus the hazard of a substance” and “a high level of information before you call judgement” on whether something is an EDC (CW 4 April 2013). Industry obviously does not want the chemicals it produces to be classified as an endocrine hazard until there is proof of risk to health; classifying a chemical as an EDC just in case it turns out to be an EDC could pick up many chemicals which are in fact harmless.
If that is the case, why would we want a low level of proof for endocrine disruption?
Firstly, there is a simple logical argument for not requiring a strong level of proof in the regulatory definition of EDC: there is simply no correlation between strength of ED effect and strength of proof of ED effect. We have very little idea which of the chemicals out there are major endocrine disruptors because, as yet, we have very little information about them. Excluding chemicals from classification as EDCs on the basis of quantity of proof that they are EDCs will only capture the chemicals we know about, not the ones we do not. But it is what we do not know which is widely acknowledged to be our biggest problem.
Secondly, this creates a Catch-22: if chemicals are not classified as EDCs, there is no obligation to generate data which will settle whether they are EDCs or not; but it is that data which is needed in order to bring them under EDC regulation. The result will be orphaned chemicals for which there is some evidence of ED potential, but not enough to get the chemical regulated as an EDC. The identification of many EDCs will then occur on the whim of a manufacturer or producer, or according to the curiosity of independent researchers, rather than a systematic, regulation-backed effort to exert control over the manufacture and use of EDCs.
If we already knew a lot about endocrine disrupting chemicals, to the point where we could reliably distinguish between chemicals which cause harm via interference in the normal functioning of the hormone system and those which do not, then the WHO/IPCS or JRC definitions could be satisfactory. The problem is, we know very little about which chemicals are EDCs and which not, and have few established test methods for their identification, so excluding chemicals from classification as an EDC hazard simply because harm is not proven seems premature.
The case for a definition of EDC as that proposed by JRC or WHO/IPCS is weakened further if one considers that there is no reason why chemicals classified as EDCs should have to be treated as equally problematic. For example, a category system such as that being considered by the European Commission’s Directorate-General for the Environment (CW March 2013), which could function similarly to the International Agency on Cancer (IARC) categories of carcinogens (category 1a would be “known” endocrine disruptors; 1b would be “presumed”; category 2 “suspected”; and 3 “potential” EDCs), would present a mechanism by which all potential EDCs could be recognised as such within a regulatory framework but could nonetheless be subjected to different regulatory controls for each category. The WHO/IPCS and JRC definitions cut off this option by making categories 2 and 3 effectively redundant.
Prenatal and Postnatal Bisphenol A Exposure and Body Mass Index in Childhood in the CHAMACOS Cohort. The first prospective study to estimate effects of prenatal and early-life exposure to bisphenol A (BPA) on children’s body mass has found that girls who were exposed to the highest concentrations in utero had lower weight for their height and were less likely to be obese at age 9 than girls with the lowest exposures. However, the same was not true of boys, and a cross-sectional analysis of both sexes at age 9 showed a positive association between current BPA urinary concentrations and obesity.
Urinary Bisphenol A and Obesity in US Children. Examination of an association between urinary BPA and obesity in children aged 6-18 years from NHANES. It finds a positive association between increasing levels of urinary BPA and obesity, independent of age, sex, race/ethnicity, education, physical activity, serum cotinine, and urinary creatinine.
Association of Osteoarthritis with Perfluorooctanoate and Perfluorooctane Sulfonate in NHANES 2003–2008. Higher concentrations of serum PFOA were associated with osteoarthritis in women, but not men. PFOS was also associated with osteoarthritis in women only, though effect estimates for women were not significant. More research is needed to clarify potential differences in susceptibility between women and men with regard to possible effects of these and other endocrine-disrupting chemicals.
Associations of in Utero Exposure to Perfluorinated Alkyl Acids with Human Semen Quality and Reproductive Hormones in Adult Men. This investigation of whether in utero exposure to PFOA and PFOS affects semen quality, testicular volume, and reproductive hormone levels, suggests that in utero exposure to PFOA is associated with lower adjusted sperm concentration and total sperm count, and with higher adjusted levels of luteinizing hormone and follicle-stimulating hormone. PFOS did not appear to be associated with any of the outcomes assessed.
Serum Polyfluoroalkyl Concentrations, Asthma Outcomes, and Immunological Markers in a Case–Control Study of Taiwanese Children. This study suggests an association between PFC exposure and juvenile asthma. Because of widespread exposure to these chemicals, these findings may be of potential public health concern.
Circulating levels of persistent organic pollutants (POPs) are associated with left ventricular systolic and diastolic dysfunction in the elderly. Circulating levels of POPs were related to impairments in both left ventricular systolic and diastolic function independently of major congestive heart failure risk factors, suggesting a possible role of POPs in heart failure.
Two votes in the European Parliament in favour of reducing exposure to EDCs. The European Parliament voted to adopt a report by Swedish MEP Asa Westlund calling for the EU to reduce exposure to endocrine disrupting chemicals (EDCs); while the European Parliament’s environment committee’s vote on a new environment action programme for Europe said the EU should focus on reducing exposure to harmful chemical substances, including endocrine disrupting chemicals, between now and 2018.
Pesticide industry and NGO clash over EFSA definition of endocrine disruptors. The Pesticide Action Network Europe (PAN Europe) has sent an open letter to the Commissioner for Health and Consumer Policy Tonio Borg complaining about an Opinion by the European Food Safety Authority on endocrine disruptors, in particular the distinction EFSA has drawn on the difference between “endocrine active substances” and “endocrine disruptors”. Industry, however, backs EFSA’s views.
Chemical in food packaging can harm unborn babies, say French officials. ”In certain situations the exposure of a pregnant woman to BPA presents a risk for the mammary gland of the unborn child,” wrote ANSES, the French equivalent of the UK Food Standards Agency. The agency said its latest report reconfirms its previous opinion regarding health risks associated with exposure to BPA for pregnant women in terms of potential risk to the unborn child, although it described the confidence levels in the assessment as “moderate”. (A PDF of ANSES’ English summary of their findings is here.)
Think Those Chemicals Have Been Tested? The NYT is strongly critical of US chemical regulation, saying many Americans assume that the chemicals in their shampoos, detergents and other consumer products have been thoroughly tested and proved to be safe – but that assumption is wrong. They also describe the US Toxic Substances Control Act as “A Toothless Law on Toxic Chemicals“, stating it would be “hard to design a law more stacked against the regulators”.
Flame retardants in consumer products are linked to health and cognitive problems. NYT four-page feature: Synthetic chemicals added to consumer products to meet US federal and state flammability standards are showing up in waterways, wildlife and even human breast milk. In other news, early reports suggest ultrathin film made from a biopolymer and a sulfur-based acid could be an effective replacement for chlorine- and bromine-based commercial flame retardants.
The Impact of Endocrine Disruption: A Consensus Statement on the State of the Science. 20 scientists, a number of whom contributed to the WHO/UNEP State of the Science report on EDCs, present their consensus position on the impact of endocrine disruption on human and environmental health.
Phthalate Concentrations and Dietary Exposure from Food Purchased in New York State. Phthalates are widely present in U.S. foods. While estimated intakes for individual phthalates in this study were more than an order of magnitude lower than U.S. Environmental Protection Agency reference doses, it still concludes that cumulative exposure to phthalates is of concern and says a more representative survey of U.S. foods is needed.
Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children. A benchmark dose study of PFC exposure which suggests current acceptable limits on PFC levels in drinking water appear to be several hundred-fold too high.
What is in our environment that effects puberty? This review article summarizes the current understanding of the major environmental influences on pubertal timing, focusing on factors for which the most scientific evidence exists, including intrinsic factors unique to each individual, naturally occurring endocrine disruptors and chemical endocrine disruptors.
Exposure to indoor pesticides and the risk of childhood brain tumors. The results of this Australian study suggest that preconception domestic pesticide exposure, and possibly exposure during pregnancy, is associated with an increased CBT risk, concluding that it may be advisable for both parents to avoid pesticide exposure during this time.