The European Chemicals Agency is working on updated guidance for using in chemico/in vitro test methods to assess skin sensitization under the EU's REACH program, with new rules pending that are expected to greatly reduce firms' reliance on animal tests to comply with the law's data requirements.

In April, the Member State Committee, which advises ECHA in functions integral to the Registration, Evaluation, Authorization and Restriction of Chemicals law in Europe, voted in favor of REACH annex amendments that will authorize use of alternative methods for evaluating substances across targeted safety endpoints, including skin sensitization.

The changes also will clear the way for use of non-animal tests to assess skin corrosion/irritation, serious eye damage/eye irritation and acute toxicity, according to the European Commission's recent announcement.

"The amendments reflect the significant scientific progress made in recent years in the development of non-animal test methods. The amendments are timely and will significantly reduce the amount of animal tests needed in the run-up to meet the last REACH registration deadline in 2018," the EC says.

The May 31, 2018 REACH deadline pertains to companies that manufacture or import chemicals in the EU in volumes of 1 ton to 100 tons annually, and ECHA expects the tonnage band to account for the largest number of REACH registrations yet ([A#02160328003]).

According to the EC, the new testing rules will go into effect following their publication in the EU's Official Journal, which is expected in September 2016 for the sensitization testing rule, while the other was targeted for publication this month.

Under the sensitization rule, available in its draft form on the EC's website, companies will be free to consider alternative methods for assessing skin sensitization that have been validated by the European Union Reference Laboratory for Alternatives to Animal Testing and/or internationally agreed by the Organization for Economic Co-operation and Development.

ECHA will treat such techniques as viable replacements for standard animal tests in situations "where adequate information can be obtained through this approach and where the available test methods are applicable for the substance to be tested," according to the rule.

It indicates that in instances where non-animal methods are deemed insufficient, the murine local lymph node assay should be used.

The rule notes that currently available test strategies endorsed by the OECD are based on an adverse outcome pathway that describes biological events recognized as factoring in sensitization development.

An OECD document published in September 2014 – The Adverse Outcome Pathway for Skin Sensitization Initiated by Covalent Binding to Proteins – outlines key events thus:

"The first key event is the molecular interaction with skin proteins, the site of action. Specifically, the target chemical or a metabolite or abiotic transformation product of the target chemical covalently binds to cysteine and/or lysine residues";
"The second key event takes place in the keratinocyte. This includes inflammatory responses as well as gene expression associated with particular cell signaling pathways (e.g. antioxidant/electrophile response element-dependent pathways)";
"The third key event is activation of dendritic cells which is typically assessed by expression of specific cell surface markers, chemokines and cytokines."

Alternative methods exploring those key events should be used in combination by REACH registrants in their assessment of a chemical's sensitization potential, according to the rule.

The rule acknowledges that in certain circumstances it may be possible for a company to generate sufficient information without explicitly addressing all three key events via separate test methods, in which case the registrant should provide a scientific justification for omitting certain tests.

The regulation to amend REACH requirements for evaluating skin and eye irritation similarly seeks to replace standard animal studies with in vitro data.

The EC notes that "animal studies should only be needed in exceptional cases where in vitro tests are not suitable."

It adds: "In another change to the Annexes, there will be no longer a need to perform an additional dermal test for substances that did not show acute toxicity in oral tests."

Overarching REACH legislation includes provisions encouraging use of alternative methods and the revision of regulatory requirements to accept non-animal data when suitable tests become available.

The new rules likely will be received favorably by animal-welfare groups, which have questioned the extent to which European authorities have upheld the principles for replacing, reducing and refining animal tests under REACH to date Also see "ECHA May Be Stickler In 2018 For ‘Last Resort’ Animal Tests Only" - HBW Insight, 5 March, 2015..

New REACH Rules Will Reduce Animal Use For Assessing Sensitization, Other Endpoints

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