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Regulators adopt mechanistically-based non-animal test methods to assess the potential of chemicals to cause skin allergy

News details
Apr 26, 2016

EURL ECVAM validated methods adopted by the OECD paved the way for the revision of regulatory requirements for skin sensitisation under REACH

On 20 April, the REACH Committee, comprising representatives of the EU Member States, adopted a revision to Annex VII of the REACH regulation which means that validated and accepted non-animal tests will become the default information requirement for assessing whether chemicals have the potential to cause skin sensitisation i.e. to induce an allergic response following skin contact. This will affect registrants who need to meet the 2018 REACH registration deadline for chemicals produced or imported in the range of 1-100 tonnes per year.

Marking a significant departure from the use of animal tests (typically the Local Lymph Node Assay; LLNA), mechanistic information on three key events of the skin sensitisation adverse outcome pathway, generated by using alternative test methods, will become the default information requirement for this adverse health effect. These key events are related to the reactivity of chemicals towards proteins in the skin, and to their ability to activate responses in keratinocytes and dendritic cells. The amendment also explicitly foresees the possibility of adaptation (i.e. waiving of one or two alternative tests) in cases where adequate weight of evidence is provided.

The standard animal test, the LLNA, becomes the second choice approach in cases where the alternative tests are not applicable to the substance in question, or do not provide adequate data. The use of animal tests other than the LLNA is not excluded in this second step, but needs to be justified. In case existing animal data are already adequate for classification, no in vitro testing is required.

The revised legal text also introduces a requirement to "assess whether a substance can be presumed to have the potential to produce significant sensitisation in humans" irrespective of whether the information is generated by alternative tests or traditional animal methods.

Following the adoption by the OECD of two methods validated and/or peer reviewed by EURL ECVAM, The Direct Peptide Reactivity Assay (DPRA) (OECD TG 442C) and the KeratinoSensTM (OECD TG 442D), this week a third EURL ECVAM validated method, the human Cell Line Activation Test (h-CLAT), which addresses responses in dendritic cells, has been approved by the OECD Working Group of the National Coordinators of the Test Guidelines Programme (WNT) during its 28th meeting

The OECD adoption of the three EURL ECVAM validated methods will contribute to reducing the number of animals used to generate information on the skin sensitisation potential of about 25,000-50,000 substances that need to be registered under the 2018 REACH deadline. They are the first three in a series of in vitro methods that will gradually replace in vivo animal Test Guidelines on skin sensitisation.

The OECD Test Guidelines are a collection of internationally agreed test methods used by government, industry and independent laboratories. They are used to determine the safety of chemicals and chemical preparations, including pesticides and industrial chemicals.