Endocrine disruptors: Why is hazard-based regulation of chemicals such a concern to industry?

May 23, 2016 at 3:50 pm | Posted in Feature Articles | Leave a comment

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Two new studies (here and here) have recently attracted attention because they found that rats exposed pre- or perinatally to low doses of BPA, below those used to set regulatory exposure limits, show a number of endocrine-mediated adverse health outcomes. These include abnormal mammary gland development, lower sperm count, masculinisation of female brains, and increased female body weight in later life.

Arguably the most significant finding, however, was the lack of a consistent pattern of responses across the range of doses of BPA which were administered to the rats, with the low doses producing different effects to the high doses. The authors conclude that the studies present robust evidence that BPA toxicity is non-monotonic, i.e. that lowering the dose of a toxin does not guarantee a less harmful effect on health.

Non-monotonic dose/response curves are of regulatory concern because they potentially make it extremely difficult, if not practically impossible, to predict health risks for certain chemicals. This is because traditional toxicological testing starts at high doses, reduces the dose until no effect is observed in the test group, and extrapolates from that dose a safe exposure limit. If the health effects vary down the dose range then this extrapolation from a no-effect dose cannot be done, because there is no guarantee that effects which disappear at one dose would not start showing again at another, lower one.

The expectation is that non-monotonic responses are the result of chemicals acting on the hormone system. Hence “endocrine disrupting chemicals” (EDCs) are being proposed as a class of chemical requiring special regulatory status to ensure the risks they pose to health are properly managed. Other classes of chemicals with special status include carcinogens, mutagens and reprotoxins (CMRs) and chemicals which are persistent, bioaccumulative and toxic (PBTs).

What is common to each of these classes is the belief that the chemicals in them pose risks to health which cannot be adequately anticipated and therefore controlled. As a hazard-based approach to regulation, there is not much opportunity for a manufacturer or user of a chemical to demonstrate that their particular proposed application poses small enough risk that use of the chemical can be permitted.

Most chemicals do not have this sort of special status and are regulated via a risk-based approach, whereby the use and environmental release of a chemical is modelled and (sometimes) measured to anticipate likely exposure in humans and wildlife, compared to the allowable dose determined by extrapolation from the no-effect dose determined in “traditional” toxicology studies, and then regulated to ensure that safe exposure is not exceeded. In this equation, it is exposure which is fundamental: so long as a chemical never reaches its target in sufficient quantities to cause harm, then it can always in principle be used.

One can therefore understand how the possibility of chemicals having special regulatory status as EDCs presents a challenge to the chemicals industry: existing chemicals classified as EDCs could be forced off the market, while the number of new compounds which could potentially be brought to market is restricted – regardless of how those chemicals might be used. It could certainly put a kink in the innovation pipeline, and (almost) unconditionally prevents the use of a chemical regardless of the real-world risk anyone might argue it actually represents.

One response is for companies simply to accept this and take current and potential product loss on the chin; however, if one is in the chemicals business, opting out of selling a potentially large and lucrative library of compounds (either in production or lined up for potential development) may not be entirely consistent with the business plan. In that context, lobbying against potentially restrictive hazard-based regulatory approaches in favour of exposure-driven risk-based approaches is largely to be expected.

And there is the rub: on the one hand, there is the commercial inconvenience of giving EDCs special regulatory treatment; on the other, there is concern that EDCs have fundamental properties which make it either impractical or impossible to predict the risks they pose to health. Finding a regulatory compromise between a commercial imperative which seems to demand a risk-based approach and an environmental imperative which seems to demand a hazard-based approach, with such an apparent gulf between the two positions, is going to be a challenge – to say the least.

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