Paul Whaley is Editor of Health & Environment and Communications Manager for the Cancer Prevention and Education Society. He contributed this commentary piece in exclusivity for EurActiv.
“Industry and regulators have a data problem: although EU chemicals regulation will ultimately require almost all substances to be risk assessed before they can be used, the toxicological data needed for this hardly exist.
Gathering sufficient data on these 30-70,000 existing chemicals which appear as pesticide residues on food, contaminants in the food chain, or leach from packaging, is going to be time-consuming and expensive enough as it is.
However, these thousands of substances break down into thousands more. Gathering data on these accidental contaminants, metabolites and breakdown products is almost unimaginably burdensome.
There is much discussion, therefore, of how to assess and manage potential health risks from chemicals when detailed toxicological data is unavailable.
In this context, the European Food Safety Authority has been examining the use of thresholds of toxicological concern (TTCs), which would reduce the research burden by waiving toxicological data requirements in risk assessment when exposure levels for a substance are very low (read more about how they work here).
Waiving data requirements on the basis of exposure is something of a crystal-ball exercise: you look at the low-dose toxicity data you have now and you decide there is no need to generate any more of it, in the belief that no new research will change what you think you already know.
In the case of TTCs, you would want to be doubly confident that your cut-off really is safe, because by deciding that nobody needs to generate toxicity data below that level, you take away your means of finding out if you have made a mistake – unless you have the time, money and inclination to do all that testing yourself.
Judging from EFSA’s draft opinion on TTCs, in which it endorsed their use, EFSA is clearly confident that, for the purposes of risk assessment, we already know everything we need about low-dose toxicity of chemicals, and that future low-dose research will never turn up any data which is relevant to risk assessment.
EFSA must have a better crystal ball then I do, because when I peer into mine, all I see for the future is low dose effects being the subject of increasingly intensive research and controversy. Right now, findings are barely even beginning to be established, let alone concluded one way or the other, and it is hard to see how research efforts might slow down rather than speed up.
Toxicologists on EFSA’s TTC expert advisory panel have pointed out that studies based on globally-harmonised test protocols have failed to reproduce low-dose effects. However, this hardly entails there are no effects are to be found; the failure could equally count as evidence that the standardised tests are inadequate for determining chemical toxicity at low-doses.
Indeed, the recently-published final version of the EU-commissioned state-of-the-art report on endocrine disruptors (EDCs), classic subjects of low-dose testing, concluded that globally-harmonised studies are unlikely to be as clearly definitive as EFSA would have us believe (see page 7 of the report here), precisely because they capture only a 'limited range' of potential EDC effects.
On top of this a review of 845 studies, published last month in the journal Endocrine Reviews, concludes that 'low-dose effects are remarkably common' (you can read the review here). Some of these results are observed at levels far lower than those which EFSA considers relevant for risk assessment.
I don’t personally know how many low-dose findings are needed to refute the databases from which the TTCs are derived, but you might at least expect the databases to reflect the most up-to-date findings. However, they do not: many of the studies date from the 1960s. And the only data to which EFSA refers in validating its proposed TTCs are generated by the globally-harmonised research protocols which are increasingly seen as limited.
EFSA must have quite some crystal ball if it can look at a study carried out with a 1960s knowledge of toxicology and use it to set a threshold of toxicological concern, as it is tantamount to predicting that in the thousands of studies carried out over the next 50 years, there would be no new science which could supersede the no-effect level found in that study.
I’m not going to second-guess EFSA’s powers of foresight. But even if EFSA were to be correct and little of the low-dose data turns out to be sound, I would still wonder how appropriate it is for them to legislate against the relevance of new toxicological research to the risk assessment of a substance.
Ordinarily one would give the science the chance to speak for itself; even if data is not expected to alter the risk assessment, it would look rather unscientific to exclude the data from the assessment before examining it.
Given that the implication of adopting TTCs is to declare low-dose findings irrelevant in perpetuity to the risk assessment process, then a decision on TTCs must surely be too important for EFSA to take on its own. If so, then perhaps it is no wonder EFSA felt obliged to delayed publishing its opinion on TTCs; I would not have had the confidence to publish it myself.”