After decades of campaigning by animal welfare groups, the 7th amendment to the EU Cosmetics Directive was hailed as a strategic achievement and a major milestone towards the replacement of animals in cosmetic tests. On the face of it, the 7th amendment paved the way for a testing ban on finished cosmetic products effective 11 September 2004, followed by a testing ban on ingredients or combination of ingredients from 11 March 2009. Finally, a far wider-reaching marketing ban is due to take effect in 2013, whereby cosmetics tested on animals outside the EU will not be allowed to be sold within the EU.
The public perception of this hard-won legislation was that the testing ban would replace all toxicity tests using animals by March 2009, with the exception of three categories (repeat-dose toxicity, toxicokinetics and reproductive toxicity). Indeed, based on official statements of the European Commission (EC), “The ban on the testing of finished cosmetic products has been in force since 11 September 2004, whereas the ban on testing ingredients or combination of ingredients will be implemented gradually as alternative methods are validated and adopted; however there will be a maximum cut-off date of six years after the entry into force of the Directive, i.e. 11 March 2009, irrespective of the availability of alternative non-animal tests.”
“The marketing ban will apply step by step as soon as alternative methods are validated and adopted in EU legislation, with due regard to the OECD validation process. This marketing ban will be introduced at the latest six years after entry into force of the Directive, i.e. by 11 March 2009, for all human health effects with the exception of repeated-dose toxicity, reproductive toxicity and toxicokinetics. For these specific health effects, a deadline of 10 years after entry into force of the Directive is laid down, i.e. 11 March 2013, regardless of the availability of alternative non-animal tests.” (1)
To get an idea of the scope of toxicity tests traditionally performed on animals, the following toxicity tests are required by law for cosmetic products (2):
- Acute toxicity
- Skin irritation/corrosion
- Eye irritation
- Skin sensitisation
- Skin absorption/penetration
- Subacute and subchronic toxicity
- Genotoxicity and mutagenicity
- UV-induced toxic effects
- Toxicokinetics and metabolism
- Reproductive and developmental toxicity
The number of animals used in cosmetics testing in the EU in 2005 was 5,571 (3).
The definitive campaign to stop the use of animals in cosmetics testing was launched in 1980 by Henry Spira when he placed a full-page advert in The New York Times entitled “How many rabbits does Revlon blind for beauty’s sake?“ Revlon responded to the advert with a pledge of three quarters of a million dollars towards funding alternatives to animal testing. Revlon was soon joined by Avon, Bristol Meyers, EstÃ©e Lauder, Max Factor, Chanel, et Mary Kay. These funds culminated in the establishment of the Centre for Alternatives to Animal Testing (CAAT) in Baltimore, USA, which was established in 1981 (4).
Obstacles to progress
While the US was now in pole position to develop alternatives to animal tests thanks to the public awareness brought about by Henry Spira and the full-page advert in The New York Times, the US nonetheless lagged behind the EU in terms of legislation that would enforce the use of alternatives. Thus, even though the CAAT has been in existence since 1981 one cannot help asking the question: “What have they achieved in 30 years?”
Ironically, although the EU has the legal mechanism in place to enforce the use of alternatives, it has achieved little more than the US in terms of replacement of animals in cosmetic tests. According to article 7.2 of directive 86/609/EC, “An experiment shall not be performed if another scientifically satisfactory method of obtaining the result sought, not entailing the use of an animal, is reasonably and practicably available.”
The EC’s response to article 7.2 was to establish the European Centre for the Validation of Alternative Methods (ECVAM) in 1992. Since its inception, ECVAM has been dogged by chronic under-funding and is also understaffed (5).
The main purpose of ECVAM is “to coordinate the validation of alternative test methods at the European Union level” (6). To date, ECVAM has validated around 30 alternative tests, most of which still rely on live animals (e.g. the mouse local lymph node assay) or animal products (e.g. isolated chicken eye test method). Some validated methods use human cells but still rely on animal products to keep the cells alive (e.g. the monocyte activation test to replace live rabbits uses human white blood cells but still relies on fetal calf serum to maintain the cells, whereas serum-free media could be used instead of calf serum).
It should be obvious by now that the legislative requirement to validate every single alternative method is a mission impossible because the system simply cannot cope. In addition there are some fundamental issues that must be addressed. First, ECVAM’s terms of reference for the validation of a new test method is historical animal data, not human data. Second, the animal tests themselves have never undergone official validation. This preposterous state of affairs was even pointed out by a former head ofECVAM but the call went unheeded by the EC (7). Third, the public have been led to believe that the term “alternatives“ implies “non-animal methods“ which clearly it does not. Although the term “alternatives“ refers to the 3Rs (reduction, refinement, replacement), in reality, the category of “replacement“ is almost non-existent, as has been demonstrated above.
Removing the obstacles
PRIORITISATION OF FUNDS
On 19th July 2010, Commissioner Maire Geoghegan-Quinn announced nearly 6.4 billion euros of European Commission investment in research and innovation (8). There is clearly no shortage of funds in the EU for promoting research and innovation. Surely the replacement of outdated animal tests with modern testing methods should be a priority? The use of modern testing methods to replace animal tests would be a huge boost to pharmaceutical drug testing, industrial chemicals (REACH) and the cosmetics industry. This is particularly relevant with respect to the potential financial savings in human health costs with respect to REACH chemicals.
According to the EC’s Extended Impact Assessment, the benefits of REACH to public health will amount to around â‚¬50 billion over 30 years (9).
REMOVE THE VALIDATION BOTTLENECK
Animal testing does not stand up to scientific scrutiny. There is more than enough evidence to show that animal testing is not reliably predictive for human beings (10-24). While the concept of validation is sound, it is slow and cumbersome and relies largely on historical animal data. The way forward is to replace validation with a weight-of-evidence approach as outlined in REACH (article 1.2 Annex XI) and other scientific documents (25, 26).
APPLY A TIERED TESTING STRATEGY
On one hand, testing on animals is ineffective and on the other, no single test is going to be predictive for all humans. What is required therefore is a tiered testing strategy, as has been proposed by the NRC in its document “Toxicity testing in the 21st century: a vision and a strategy”, which incorporates human biology and high throughput screening (27). One of the key components of such a strategy is the use of toxicogenomics in conjunction with primary cells of human origin or human cell lines.
ALWAYS CHOOSE HUMAN DATA OVER ANIMAL DATA
We are faced with a choice between choosing incomplete human data (= relevant to humans) or choosing complete animal data (= largely irrelevant to humans). Based on the above, it should be clear that we should always choose human data over animal data. A tiered testing approach that relies on human material will always be more predictive for humans than animal data. It is essential not to equate, or confuse, the concept of prediction in science with retrospective analysis. The field of regulatory toxicology has arguably fallen prey far too often to this confusion (28).
There can be no excuse for delaying the implementation of modern testing methods to replace the use of animals in toxicity testing. The use of a tiered testing strategy using human material and human data will always surpass the results of historical and outdated animal tests. A weight-of-evidence approach can be used as a means of accelerating the validation of human-based testing methods. The funding of such a strategy is a political imperative. The science is already well established. We must therefore reject and actively resist any attempt by the EC to postpone the deadline for the ban on cosmetics testing (29). If anything, the animal tests should be banned before, not after, the deadline set by the EC.
The same non-animal tests that can replace the use of animals for cosmetic products can also be applied to industrial chemicals (the EU REACH programme to test 30 000 chemicals).
Please write to Mr Barroso to make it clear that, as EU citizens, we reject any attempt to postpone the March 2013 deadline on a ban on cosmetics testing and importation of animal-tested cosmetic products.
Mr Jose Manuel Barroso
President, European Commission
200 rue de la Loi
2. http://ec.europa.eu/consumers/sectors/cosmetics/files/doc/antest/(2 )_executive_summary_en.pdf
10. Horn, J., de Haan, R.J., Vermeulen, M., & Limburg, M. (2001). Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review. Stroke 32, 2433-38.
11. Hunter, W. J., Lingk, W., & Recht, P. (1979). Intercomparison study on the determination of single administration toxicity in rats. Association of Official Analytical Chemists 62(4), 864-73.
12. Bailey, J. (2009). An examination of chimpanzee use in human cancer research. Alternatives to Laboratory Animals 37(4), 399-416
13. Balcombe, J.P., Barnard, N.D., & Sandusky, C. (2004). Laboratory routines cause animal stress. Contemporary Topics in Laboratory Animal Science 43(6), 42-51.
14. Bugelski, P.J., & Treacy, G. (2004). Predictive power of preclinical studies in animals for the immunogenicity of recombinant therapeutic proteins in humans. Current Opinion in Molecular Therapeutics 6, 10-16.
15. Chalmers, I. (2005). From a presentation for the Scottish Wellcome Trust Clinical Research Facility, Edinburgh cited on the Sabre Research UK website. Retrieved on 16 February, 2010, from http://www.sabre.org.uk/#/background/4524921993
16. Flynn, S., Satkoski, J., Lerche, N., Kanthaswamy, S. & Smith, D. 2009. Genetic variation at the TNF-alpha promoter and malaria susceptibility in rhesus (Macaca mulatta) and long-tailed (Macaca fascicularis) macaques. Infect Genet Evol 9(5):769-77.
17. Greek, C. R., & Greek, J. S. (2000). Sacred Cows and Golden Geese: The Human Cost of Experiments on Animals. New York & London: The Continuum International Publishing Group Inc.
18. Home Office response to Parliamentary Question by Michael Hancock MP. (2004). Retrieved on 16 February, 2010, fromhttp://www.publications.parliament.uk/pa/cm200304/cmhansrd/vo040331/text/40331w06.htm
19. Knight, A. (2008). Systematic reviews of animal experiments demonstrate poor contributions toward human healthcare. Reviews of Recent Clinical Trials 3(2), 89-96.
20. Knight, A., Bailey, J., & Balcombe, J. (2006). Animal carcinogenicity studies: implications for the REACH system. Alternatives to Laboratory Animals 34 Suppl 1, 139-47.
21. Lindl, T., Voelkel, M. & Kolar, R. (2005). Animal experiments in biomedical research. An evaluation of the clinical relevance of approved animal experimental projects. Alternatives to Animal Experiments 22(3), 143-51.
22. Perel, P., Roberts, I., Sena, E., Wheble, P., Briscoe, C., Sandercock, P. et al. (2006). Comparison of treatment effects between animal experiments and clinical trials: systematic review. British Medical Journal 334, 197.
23. Pound, P., Ebrahim, S., Sandercock, P., Bracken, M.B. & Roberts, I. (2004). Where is the evidence that animal research benefits humans? British Medical Journal 328(7438), 514-7.
24. Shanks, N. & Greek, R. (2009). Animal Models in Light of Evolution. Florida: BrownWalker Press.
29. http://www.buav.org/a/2010/08/06/377After decades of campaigning by animal welfare groups, the 7th amendment to the EU Cosmetics Directive was hailed as a strategic achievement and a major milestone towards the replacement of animals in cosmetic tests. On the face of it, the 7th amendment paved the way for a testing ban on finished cosmetic products effective 11 September 2004, followed by a testing ban on ingredients or combination of ingredients from 11 March 2009. Finally, a far wider-reaching marketing ban is due to take effect in 2013, whereby cosmetics tested on animals outside the EU will not be allowed to be sold within the EU.
The public perception of this hard-won legislation was that the testing ban would replace all toxicity tests using animals by March 2009, with the exception of three categories (repeat-dose toxicity, toxicokinetics and reproductive toxicity). Indeed, based on official statements of the European Commission (EC),