What do Trans-Atlantic trade talks and the endocrine system have in common? (A: The ability the impact your product!)

The prompt for this piece was seeing the recent Joint Research Center on alternative methods and how it adds to the ongoing complexity of trying to find a global approach to chemical regulation in certain areas.

The European Commission's Joint Research Center (JRC) was contracted by European Chemicals Agency (ECHA) to review the state of the science of available alternative tox and ecotox methods. This report ("Alternative methods for regulatory toxicology -- a state-of-the-art review") compiles current status of these methods for a range of human health and ecotoxicological endpoints, as well as provides discussion of mechanistic basis and regulatory acceptability.  "Alternative" in this case referring to in vitro, in silico, and other "non-standard" animal-based tests.  (Want to know more about alternatives to animal testing? Peruse the web site of my colleagues at the Center for Alternatives to Animal Testing at Johns Hopkins Bloomberg School of Public Health.)

The report covers a wide range of endpoints, to  include skin irritation, corrosion and sensitivity;  eye irritation; acute and chronic toxicity; genotoxicity and mutagenicity; carcinogenicity; reproductive and developmental toxicity; and "endocrine disruption relevant to human health" (back to this compelling topic in a moment).  While the report is more geared to meet the regulatory needs of the European industrial/commodity chemicals (i.e. REACH, CLP and the more recent Biocidal Products Regulation [BPR]), the information within is certainly useful for the application of alternative methods in other areas, such as cosmetics and pesticides (otherwise known as "plant protection products" in European policy speak).  More specifically, companies have opportunities to use alternative methods/data for hazard assessment under REACH, CLP and the BPR, all of which fall under the jurisdiction of ECHA, who requires "state of the science" detailed knowledge of those best practices likely to be included in future/existing dossiers.  Additionally, in Europe, the "3Rs" (replace, reduce and refine) are written in legislation for the use of animals used for scientific purposes, so the use of alternative methods is institutionally encouraged.

Now back the concept of "endocrine disruption relevant to human health."  Global regulation of substances in the environment that are considered "endocrine active" or "endocrine modulators" has been of an area of intense debate for several years now. (Sorry, I particularly dislike the term "endocrine disruptor," as it sounds like something that Marvin the Martian would used on his nemesis Bugs, so I won't use it.)  The focal point of the debate has really been Trans-Atlantic: the US Environmental Protection Agency has established its "Endocrine Disruptor Screening Program" based on a tiered system that considers both hazard and exposure in its relatively well-defined testing program while, in essence, the EC has a hazard-only based regulatory system that relies on (yet to be written) screening criteria that operates in a climate of heightened precaution.  

In fact, it is this exact desire to ground the European endocrine regulatory system in the precautionary principle that has many subject matter experts up in arms, with many intense exchanges in the editorial pages of journals, web sites, etc.  For a more detailed description of the back and forth between scientists, see here, here and here.  In addition to a leaked document from the EC (opining on precaution) last year, the main report the EC relies upon (WHO UNEP State of the Science of Endocrine Disrupting Chemicals) has likewise been intensely critiqued.  The former document, recommending substance be considered "known" or "suspected" to be endocrine active, prompted a joint letter from the editors of some two dozen science journals, while the latter report prompted publication of a joint critique by some really huge names in academia and scientific consulting.

Back to the JRC report (thought I had forgotten about that, didn't you?)... which takes an expectedly conservative stance in describing why the issue is of concern; however, takes an unexpected selective use of the literature in support of its position.  For example, the statement that endocrine-related effects "often result" in non-classical dose-response relationships (termed non-monotonic dose-response relationships, NMDR) seen with some hormones is still being debated in the scientific community.  EPA released its own white paper, which was then reviewed and critiqued by the National Academies of Science (which was not particularly favorable) and there have been pro articles -- like this one, written by many of the same people who wrote the WHO UNEP report and who work is selectively reference by JRC -- and con articles (like this one) published in the literature as well.  Why does it matter? If a regulatory body has to account for NMDRs, then the likely technical response will be to expand existing testing requirements to be able to capture a sufficient level of dose-response detail to allow for a NMDR analysis.

The bottom line regarding the ongoing endocrine regulatory drama (of which, dear reader, you have seen a small taste of at this point) is that there are still very large specific differences in the two regulatory systems that are rooted in very large broad differences in regulatory philosophy and mandate.  These differences are not imaginary and are accompanied by very real costs in the global chemical and consumer goods marketplace. (Don't believe me? See the industry-sponsored economic analysis here.)  While these differences and trade effects have been recognized in the ongoing US-EU trade talks (Trans-Atlantic Trade Investment Partnership), the timeline and resolution of the endocrine regulatory issue through a trade deal seem blurry at best right now.  

It is hoped that much progress on any potential EU-US joint "pilot program" in endocrine regulation will be made next month, when EPA Assistant Administrator for Toxics, Jim Jones, goes to visit the Commission.  While a Trans-Atlantic compromise is sought, companies should take a hard look at their chemical portfolio products, their formulants and other chemical inputs, and the markets they intend to sell into and develop a global approach to portfolio management and associated internal policy.