Update: On 19 February 2009, HSI Europe celebrated a major milestone in this campaign following a move by the European Commission and Member States to accept 21st century cell-based methods as full and complete replacements for cruel and outdated skin irritation tests using rabbits and other animals.

Humane Society International (HSI) Europe is leading the call for an immediate end to skin irritation testing on animals now that EU validation authorities have confirmed the validity of several high-tech human skin models as complete non-animal replacements.

For more than 60 years, rabbits have suffered and died to test and label cosmetics, consumer products, agricultural pesticides, biocides and other chemicals for their potential to irritate the skin. But this may soon be a thing of the past thanks to EPISKIN, EpiDerm and SkinEthic models—three-dimensional reconstructions of human skin using cells grown in culture, which have been shown to readily distinguish between skin irritants and non-irritants at a fraction of the time and cost of animal testing.

How human skin models work

Several dilutions of a test substance are applied to a reconstructed skin model for periods of three minutes, one hour and four hours. Irritants are identified by their ability to reduce the viability of cells in culture below 50 percent and/or trigger the release of an inflammation-inducing chemical from damaged cells.

EU authorities confirm validity

The accuracy and reliability of two of the skin models were formally evaluated against dozens of chemicals of many different classes in an international validation study [PDF] organised by the European Centre for the Validation of Alternative Methods (ECVAM). This study, together with subsequent ‘catch-up’ validation work [PDF], confirmed that all three skin models are able to identify irritant substances with a high degree of sensitivity and reproducibility, and can act as full replacements for skin irritation tests on animals.

Limitations of animal skin tests

Despite more than six decades of regulatory use, animal skin irritation tests have never been properly validated according to modern standards (OECD, 2005). Documented limitations include excessively inter-laboratory variability in test results (up to 117 percent; Weil & Scala, 1971) [1], as well as dubious accuracy in predicting real-world human skin reactions. For example, Robinson and colleagues (2001) [2] compared skin irritancy classifications based on the results of rabbit tests against the results of skin-patch tests in human volunteers for 65 consumer products and found that classifications based on animal data incorrectly predicted human responses in 45 percent of cases. Similar reports have appeared in the peer reviewed scientific literature for decades. For example:

• Nixon et al. (1975) [3] documented “greatly different reactions” in rabbits, guinea pigs and humans to 24 household products.
  
  
  
• Davies et al. (1972) [4] concluded, on the basis of replicate skin irritation tests in 7 different species that no single animal species is a suitable model for predicting irritancy potential to human skin.
  
  
  
• Phillips et al. (1972) [5] found that animal tests were unable to distinguish between mild and moderate irritant effects in humans for 12 substances examined.
  
  
  
• Carter & Griffith (1965) [6] reported poor agreement between rabbit and human patch test results.
  
• Complete replacement for animal testing
  
  
  
• Made from tissue from the relevant species (humans)
  
  
  
• High sensitivity in detecting skin irritants
  
  
  
• Low variability in test results within and between laboratories
  
  
  
• Half the cost of animal testing ($850 vs. $1,800/test)
  
  
  
• More rapid than animal testing (2 days vs. 14 days)

Campaign goals

HSI-Europe is committed to seeing animal skin irritation tests relegated to the history books, both in Europe and internationally. Critical steps toward this goal include the following:

• Creation of a new test guideline for human skin models for irritation
  
  
  
• Inclusion of this new test guideline in the EU Test Methods Regulation and deletion of the existing animal test (Method B.4 [PDF])
  
• EU-wide ban on animal testing for skin irritation (per Directive 86/609/EEC), including updating of applicable data requirements and guidance for agricultural pesticides, biocides, chemicals, cosmetics and pharmaceuticals (the UK has already committed to “replace the test used to assess the potential of chemical substances to cause irritation to human skin with the non-animal EPISKIN-SIT test—or any other suitable and validated non-animal model—where scientifically justified and amend existing licences, as necessary, once the agreed protocols for regulatory testing are agreed and published”)
  
  
  
• Reciprocal endorsement of human skin models for irritation as full replacements by validation authorities in the US, Japan and elsewhere
  
  
  
• Adoption as a new OECD Test Guideline, and deletion of the existing animal test (OECD TG 404)
  
  
  
• Revision of applicable data requirements, test guidelines and guidance documents in the United States and other developed countries to prevent future animal testing.

¹ Weil CS & Scala RA. Study of intra- and interlaboratory variability in the results of rabbit eye and skin irritation tests. Toxicology and Applied Pharmacology 19, 276-360 (1971).

² Robinson MK, McFadden JP & Basketter DA. Validity and ethics of the human 4-h patch test as an alternative method to assess acute skin irritation potential. Contact Dermatitis 45, 1-12 (2001).

³ Nixon GA, Tyson CA & Wertz WC. Interspecies comparisons of skin irritancy. Toxicology and Applied Pharmacology 31, 481-90 (1975).

⁴ Davies RE, Harper KH & Kyonch SR. Inter-species variation in dermal reactivity. Journal of the Society of Cosmetic Chemists 23, 371-83 (1972).

⁵ Phillips L, Steinberg M, Maibach HI & Akers WA. A comparison of rabbit and human skin response to certain irritants. Toxicology and Applied Pharmacology 21, 369-82 (1972).

⁶ Carter RO & Griffith JF. Experimental bases for the realistic assessment of safety of topical agents. Toxicology and Applied Pharmacology 7(Suppl 2), 60-73 (1965).

Other Literature Cited:

Derelanko MJ & Hollinger MA (Eds.). Handbook of Toxicology, Second Ed. Washington, DC: CRC Press (2002).

Draize JH, Woodard G & Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. Journal of Pharmacology and Experimental Therapeutics 82, 377-90 (1944).

ECVAM. Statement on the Validity of In Vitro Tests for Skin Irritation. Ispra, Italy: European Commission Joint Research Centre. 27 April 2007. Website.

Institute for In Vitro Sciences. IIVS Price List. Gaithersburg, MD: IIVS (2007).

Organisation for Economic Co-operation and Development. OECD Guideline for the Testing of Chemicals 404 – Acute Dermal Irritation/Corrosion. Paris: OECD (2002).

OECD. Guidance Document Number 34 on the Validation and International Acceptance of New or Updated Test Methods for Hazard Assessment. 18 August 2005. Website http://appli1.oecd.org/olis/2005doc.nsf/linkto/env-jm-mono(2005)14.

 Spielmann H, Hoffmann S, Liebsch M, et al., The ECVAM international validation study on in vitro tests for acute skin irritation: Report on the validity of EPISKIN and EpiDerm assays and on the Skin Integrity Function Test. Alternatives to Laboratory Animals 35, 559-601 (2007).