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Editor-in-chief:
Johanna Salomaa-Valkamo

Editor:
Päivi Jokiniemi

Article related to: REACH

Skin sensitisation – new methods to replace animal testing

Skin sensitisation - new methods to replace animal testing.

All substances registered under REACH need to contain information on their skin sensitisation potential. Silvia Casati, Senior scientific officer from the European Union Reference Laboratory for alternatives to animal testing (EURL-ECVAM) at the European Commission's Joint Research Centre (JRC) tells ECHA Newsletter about some new methods that can be used to replace animal testing in many REACH registrations.

In the last 10 years, there has been great progress in developing non-animal test methods. These methods include for example in vitro tests using cells or tissues and in silico methods using computer-based models. "I see two factors behind this development: a better understanding of the biology behind the adverse effects of substances and the changes in the European regulatory framework," Ms Casati explains.

She mentions two pieces of European legislation that have promoted the development of alternatives to testing on animals: the Cosmetics Regulation with its ban on animal testing, and REACH in promoting the use of alternative methods and having animal testing only as a last resort. For ECVAM, REACH has been the primary driver for validating new alternative test methods in recent years.

"A recent example of REACH encouraging the use of alternative test methods is related to skin corrosion/irritation and to serious eye damage/eye irritation. The availability of scientifically valid alternative methods that have been accepted by the regulators has resulted in a much greater use of in vitro data by registrants," she points out.

Silvia Casati.
Image: ECHA.

Alternative methods to be used in combination

Ms Casati highlights that we now have a variety of alternative methods, addressing the biological and chemical mechanisms of skin sensitisation. However, none of these methods can currently be used in isolation.

"They don't predict the final effect, but provide information on specific mechanisms, underlining the adverse effect. The challenge is to understand how to use these alternative methods in combination, so that the information is accurate enough to be used for regulatory purposes," she says.

New methods on the way

To help registrants identify the relevant alternative test methods, ECHA and the EURL-ECVAM have been working together on new test guidelines for skin sensitisation which were recently adopted by the OECD.

"These in vitro and in chemico methods address key mechanisms of the skin sensitisation pathway. Advice on how to use the methods is already available for REACH registrants. Additionally, we at EURL-ECVAM have validated a third new in vitro method called the human cell line activation test (h-CLAT). The draft test guideline is currently being discussed in the OECD," Ms Casati says.

EURL-ECVAM is also evaluating a variety of other methods from research laboratories and industry.

Anyone interested in these upcoming alternative test methods can follow their progress with the Tracking System for Alternative test methods towards Regulatory Acceptance (TSAR) provided by the JRC. "TSAR shows how an alternative method progresses from a proposal for validation through to its final adoption into the regulatory framework at the OECD and EU level," she adds.

TSAR is currently being updated to give more comprehensive tracking information through a user-friendly web interface. The updated system will also track test methods that are under evaluation by other international validation centres. Its public release is planned for autumn 2015.

Reducing animal tests for the REACH 2018 deadline

Ms Casati clarifies that a complete replacement of all animal tests for assessing skin sensitisation will be hard to achieve. "There will still be cases where the alternative methods might not give all the relevant information. For example, the potency of the sensitiser still remains a problem. It is key for risk and safety assessment, but we still need time to understand how in vitro methods could predict potency," she says.

For many chemicals, however, non-animal test methods are very relevant for the 2018 registration deadline. With the new guidelines, an increase in the use of in vitro data for dossiers, even before 2018, can be expected. "Most of the alternative test methods are designed for hazard identification, which is relevant for a large number of REACH registrants. In terms of scientific progress in hazard identification, we are almost there," she highlights.

Ms Casati is also confident that new methods, currently under development, might overcome some of the existing limitations in the near future. The information that the new alternative methods provide needs to be used well and interpreted in a rational way. "With the existing methods available, it is now up to the registrant to build a well-thought case, based on the guidance and advice provided. Then it is also up to the regulators to decide whether the registrants' arguments are convincing," she concludes.

Definitions

In vitro: Studies using cells, tissues or organs in glass or plastic vessels in the laboratory.

In vivo: Test conducted on a living organism.

In chemico: The use of abiotic (non-animal or in vitro) measurements of the reactivity or other physicochemical properties of compounds.

In silico: Test which is done or produced by using computer software or simulation, for example, QSARs.

New OECD test guidelines available

ECHA has published advice on using the new OECD test guidelines on skin sensitisation. The new non-animal test guidelines each address a specific key event in the adverse outcome pathway for skin sensitisation, describing the main biological steps. They are relevant for many registrants preparing for the 2018 REACH registration deadline and, if used correctly, can replace the need to use animal test methods.

The adopted OECD test guidelines are:

442C: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA), and
442D: In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method (KeratinosensTM).

The draft OECD test guideline is:

In Vitro human cell line activation test (h-CLAT).

OECD and EU test guidelines

Further information:

Did you know?

The European Union Reference Laboratory for alternatives to animal testing (EURL-ECVAM) was established in 2011.

Research laboratories can submit alternative methods that they have developed to EURL-ECVAM for scientific validation. EURL-ECVAM also promotes the development and dissemination of alternative methods and approaches, their application in industry and their acceptance by regulators.

European Union Reference Laboratory for alternatives to animal testing

Interview by Tiiu Bräutigam

Top image: Fotolia