Health & Environment

Why regulatory definitions of chemical hazards are important

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.