Richard Denison, Ph.D., is a Senior Scientist.
In an opinion piece titled "Chemical regulators have overreached" in the August 27, 2009 issue of Nature, two prominent animal welfare advocates claim that vastly larger numbers of chemicals will have to be tested under the European Union's REACH regulation than previously estimated, and hence that 20 times more laboratory animals will be sacrificed. They call for a moratorium on some animal tests. Well, a closer look reveals that it's the opiners themselves that have greatly overreached.
[Update 8/28: The European Chemicals Agency (ECHA) has just issued this press release also disputing the findings of this new study.]
The authors of the Nature opinion piece are Thomas Hartung and Costanza Rovida. Hartung is the director of the Center for Alternatives to Animal Testing (CAAT), while Rovida is identified as a private consultant, but was formerly affiliated with the European Centre for the Validation of Alternative Methods (ECVAM), as was Hartung.
The Nature piece cites a longer, 22-page report by the same authors released by the Trans-Atlantic Think Tank for Toxicology (t4). t4 is a creation of CAAT.
The report is laid out to look like a peer-reviewed journal article but is self-published (more later on what the authors claim to be the expert review conducted of the report). [Note added 8/27: The report is to be published in a journal called ALTEX. According to its website, ALTEX is "the official journal of CAAT ... and t4, the transatlantic think tank of toxicology." According to an article appearing in today's BNA Daily Environment Report (p. A-4): "The study was prepared with funding from the Transatlantic Think Tank for Toxicology, which works with [CAAT]." Hence my characterization of the report as "self-published" is quite appropriate.]
This study has used numerous demonstrably false or highly questionable assumptions, one piled on another, to grossly inflate the number of chemicals requiring testing under REACH, and the number of animals involved.
Both the opinion piece and the accompanying report reflect a fundamental misunderstanding of the basics of REACH and an apparent willingness to inflate every number in long chains of calculations to yield the largest possible estimates for the number of animals to be sacrificed under REACH.
In this post, I will address in detail some of the more egregious claims. They include:
- Vastly overstating the number of chemicals in commerce, to be registered and required to tested under REACH.
- Vastly overstating the number of high-production-volume chemicals in the EU.
- Overstating the number of animals required for at least certain tests.
- Claiming expert review of its report, when 7 of the 8 reviewers are either close colleagues of the authors or representatives of the chemical industry. Not a single representative of the European Commission or the European Chemicals Agency reviewed the report.
Prepare for a fairly deep dive, with lots of numbers, because that's what the authors have based their claims on.
But first, some context. During the nearly decade-long debate over the final text of REACH, animal welfare advocates extracted major concessions from the EU. In addition to peppering REACH with statements to the effect that animal testing would be done only as a "last resort," the changes forced by animal welfare advocates included elimination of all animal testing for existing chemicals produced below 10 tons per year per manufacturer, and a requirement that only testing proposals, not test data, be submitted at the time of registration for any tests involving laboratory animals.
Most notably, an entire Title of REACH is devoted to "Data Sharing and Avoidance of Unnecessary Testing," setting in motion the mandatory formation of so-called Substance Information Exchange Forums (SIEFs) among makers and users of a chemical that have become the latest poster child for the chemical industry's ongoing gripes about REACH.
Let me be clear: I personally, and EDF organizationally, strongly support taking all possible measures consistent with good science and sound chemicals safety policy to reduce unnecessary animal testing. That includes unearthing and utilizing all available data, allowing and facilitating the appropriate use of alternatives to animal testing, including in vitro methods, read-across within chemical categories, and estimation models based on structure-activity relationships (SARs). It also means aggressively developing more alternatives, including high-throughput screening methods and computational toxicology – approaches that form the core of the long-term vision embodied in the National Academy of Sciences' seminal report Toxicity Testing in the 21st Century.
But we also need to address the fact that tens of thousands of chemicals are in active use today that have never been sufficiently tested or assessed for safety, due to policies put in place decades ago that simply presumed them to be safe. That is a very deep hole to dig ourselves out of.
But it's not nearly as deep as Hartung and Rovida would have us believe. Let's examine some of their claims:
Claim #1: "More than 100,000 synthetic chemicals are used in consumer products."
That's the very first sentence in the Nature opinion piece, and it's flat wrong. This number is derived from the number of chemicals listed in the EU's inventory of all chemicals that were in commerce in the EU at the time the inventory was developed in 1981. It is not an accurate count of chemicals currently in commerce.
In the US, about 84,000 chemicals are listed on the cumulative TSCA Inventory, first set in 1979, but again not all of those are currently in commerce. EPA's latest count of those manufactured or imported above 25,000 pounds/year is less than 7,000 chemicals. While that is clearly an underestimate as there are many chemicals below this threshold, and the reporting system has a number of exemptions, nowhere near 84,000 chemicals are in active commerce in the U.S. Given the global nature of the chemicals market, it seems highly unlikely that the situation is radically different in the EU.
Claim #2. "Our report … is based on the pre-registration of chemicals [under REACH]."
The authors' primary analysis is based on the gross number of substances that were pre-registered under REACH last year. However, as the European Chemicals Agency (ECHA), which administers and oversees REACH, has made clear, pre-registration is not an accurate representation of the number of chemicals to be registered under REACH.
ECHA's press release from March of this year states:
- "ECHA does not expect all of these [preregistered] substances to be registered."
- "In ECHA’s opinion the list contains many preparations and substances that did not require registration."
ECHA has already found that the list of pre-registered substances contains many substances (as well as items such as articles) that are duplicates or are entirely exempt from or inapplicable under REACH and will not need to be registered at all. Pre-registrations were filed not only by chemical makers and importers, but by downstream users, as well as contract testing labs, consultants and others, mining for business opportunities.
Bizarrely, Hartung and Rovida acknowledge "a large abuse of preregistration" as well as significant duplicative entries. Yet they proceed unfazed to base much of their analysis on the inflated pre-registration numbers.
Claim #3. "The latest published list of REACH chemicals contains 143,835 substances that are supposed to be fully registered, each requiring a chemical safety report."
There are a total of "140,008 substances that may require extensive testing for registration."
These sentences contain several significant errors. First, they reflect the gross number of pre-registered substances. It is true that ECHA's pre-registration list contains more than 140,000 entries. But as noted above, that number is highly inflated and the number of substances to be registered under REACH is expected by ECHA to be far lower.
In a statement sent to Nature by ECHA in response to Hartung and Rovida's study (referred to in NatureNews here), ECHA reiterates that, based on its review of the pre-registration lists, it still believes its original estimates for the number of unique substances to be registered under REACH (about 30,000) is quite close to accurate.
Second, only those registered substances above 10 tonnes/year are required to have chemical safety reports (CSRs). The EU estimates that the large majority (about two-thirds) of all registered substances will fall under this threshold and not require CSRs. For these chemicals, no animal testing is to be required under REACH.
Claim #4. We estimate "68,000 chemicals falling under REACH, and this is the lower (optimistic) estimate in our study."
The authors characterize the estimate they derived from pre-registration lists as "worst-case," yet they use it as the primary basis for their analysis.
But even their "best case" number of 68,000 chemicals is also highly inflated. Its derivation is frankly, laughable:
- They start with the EU's own estimate that about 30,000 chemicals will be registered under REACH. That number was derived by data collected by the EU in the mid-1990s, compelling the authors to seek to "update" it.
- First they note that chemical production as measured by sales volume has increased substantially in the EU, nearly doubling between the mid-1990s and today. I have no reason to doubt this.
- Second, they point out that the EU itself has grown by accepting into its ranks a number of new countries. They put that growth at about 20%. Again, all fine.
- But then, astoundingly, they assume that the number of chemicals produced in the EU has increased in direct proportion to these growth factors. That leads them to multiply the 30,000 EU estimate by about 2 and then again by about 1.2, to yield the 68,000.
The notion that recent growth in the sales and volumes of chemicals in the EU was derived entirely by introduction of new chemicals, and not primarily by increases in production of existing chemicals, is contradicted by all empirical evidence – including the statistics cited by the authors themselves in the very first paragraph of the Nature opinion piece.
They point out that "existing 'old' chemicals represent about 97% of those in use today and 99% of the production volume." I'll let you do the math to conclude that there is simply no way that 38,000 new REACH-eligible chemicals have been introduced in the EU since the mid-1990s. OK, I'll do the math: That would mean, among other things, that the "old" chemicals would account for well under half of those in use today, not 97%!
Indeed, the actual number of new chemicals registered in the EU since 1981 (which is cited by the authors elsewhere but ignored here!) is about 4,400.
Claim #5. After going through more arcane calculations, the authors finally arrive at the following numbers of chemicals that they claim will require extensive animal testing:
- 47,858 chemicals marketed above 1000 tonnes/year, to which a 2010 registration deadline applies
- 53,040 chemicals marketed above 100 tonnes/year, to which a 2013 registration deadline applies
The former of these numbers represents what the EU calls high-production-volume (HPV) chemicals. The authors claim there are nearly 48,000 such HPV chemicals. The EU estimates there are only a few thousand. Who's right?
The Organization for Economic Cooperation and Development (OECD) maintains a list of HPV chemicals produced in its 33 member countries. OECD includes not only all of the EU, but also the U.S., Japan, Australia, Canada, Korea and all of the rest of the developed world.
How many HPV chemicals does the OECD list? About 5,000.
So yet again, Hartung and Rovida grossly overstate reality: They are off by at least an order of magnitude.
Claim #6. "The two-generation study for reproductive toxicity … consumes an average of 3,200 rats per chemical."
The authors zero in on this particular test as a primary culprit, calling for a moratorium on such testing under REACH. Let's look at the claim.
The authors claim this "average" number was calculated in a paper by Höfer et al (2004). That paper, however, merely asserts the number and provides no calculation. It does, however, characterize the number as a "maximum" number, and includes it in a table of "theoretical extrapolation of a maximum number of animals to be used."
The authors allude to a second paper by Cooper et al. (2006) that estimates only 2,600 rats per test, but doggedly stick with the higher number for all of their calculations. Even that number seems high to experts we have contacted. The Cooper et al. estimate assumed an average of 15 offspring per mated pair of rats; Hartung and Rovida themselves cited data that the average litter size for rats is only 8.2 offspring, while others put it at around 10. Yet the authors appear unaware of and certainly never flag this major discrepancy.
There are, of course, many reasons why understanding a chemical's effects on reproduction is critical, and there is a large number of chemicals for which we are already finding such effects. ECHA's statement summarizes the need for this test as follows:
"The two generation study is the only study where functional fertility (including mating, fertility, number of implantations and litter size) is investigated in parental animals exposed during vulnerable life stages from conception, in utero up to puberty. Such an exposure design may be of special importance, e.g., for endocrine disrupting chemicals. This is not covered by any other reproductive study, including one-generation study protocols, as long as mating of the F1 generation [offspring of the exposed parents] is not performed."
Claim #7. "The plausibility of our assumptions and calculations was checked by eight experts from industry, academia and regulatory authorities."
This paper has not been peer-reviewed in any normal sense of the term.
A footnote on the first page identifies two reviewers. One is the current Chair of the Board and former director of CAAT, the organization Hartung now directs. The other is a colleague of Hartung's at the University of Konstanz in Germany, where Hartung has a joint appointment.
Six other expert reviewers are cited in the Acknowledgement section of the paper. Five of the six work for the chemical industry or its trade associations: ECETOC (a trade association "financed by its membership, which comprises 50 of the leading companies with interests in the manufacture and use of chemicals"), Dupont, Shell, Exxon-Mobil and BASF. CAAT's advisory board is also well-stocked with industry representatives.
This is no accident: There is, shall we say, a strongly shared interest between the chemical industry and animal welfare advocates in undercutting chemical testing programs. This isn't the first instance of such close cooperation, and I very much doubt it will be the last.
A single reviewer was drawn from government (a German federal agency).
The paper received no review whatsoever from anyone from the European Commission or ECHA. Perhaps had that occurred, some of the huge errors might have been caught before publication.
As noted at the start, this study has used numerous demonstrably false or highly questionable assumptions, one piled on another, to grossly inflate the number of chemicals requiring testing under REACH, and the number of animals involved.
Why? One need only look at the last concluding sentence of the author's study for what I think is at least part of the answer:
"It is beyond dispute that the primary aim of REACH is protecting human health and the environment from unwanted consequences of exposure to chemicals. The challenge will be to do it sensibly within the context of REACH while using all the information and experience we have and recognizing that most chemicals have been produced and used safely for many years without extensive testing on animals. (emphasis added)
That naïve assumption – that what we haven't tested can't hurt us – is what got us into this mess in the first place. I cited many sources of information that demolish that argument in the Introduction to my 2007 report, Not That Innocent.
There is a near-total absence in either the Nature piece or the accompanying study of mention of concern for the need to protect human health from the effects of toxic chemicals. More striking, given the animal welfare orientation of the authors, is their utter failure to recognize or acknowledge that gaining a better understanding of chemical hazards is essential to protecting animals in the wild from toxic chemicals.
Our knowledge of the endocrine-disrupting effects of chemicals originated with studies of animals in the wild. DDT's devastating effects first came to light through witnessing the dramatic declines in reproductive success of ospreys and eagles in the wild. Growing evidence indicates that the widespread and increasing deformations and gender-bending effects seen in wild fish and amphibians are the result of chemical exposures. We now know that wildlife in the remotest parts of the Earth carry dangerous levels of persistent substances in their bodies.
All of these impacts of untested and under-assessed chemicals affect untold billions or trillions of animals in the wild.
Doesn't that matter?
[My EDF colleague and toxicologist, Dr. Cal Baier-Anderson, helped with some aspects of the content of this post.]