Moving away from animal testing

Toxicologists in the EU Member States need accurate testing methods and processes to apply alternatives to animal testing. Employing alternative approaches, to comply with regulation, always involves complex scientific discussions.

Moving away from animal testing

Addressing this issue, the European Partnership for Alternative Approaches to Animal Testing (EPAA) held its annual conference called: ‘Knowledge sharing to facilitate regulatory decision-making’ on 19 of October 2014 in Brussels.  The ‘3 Rs’ approach to animal testing: Replacement, Reduction and Refinement, is followed by EPAA - a unique voluntary cooperation between seven industry sectors and five European Commission services

At the EU level, an animal testing ban is in force for cosmetic products and ingredients. For chemicals, the REACH Regulation – Registration, Evaluation, Authorisation and Restriction of Chemicals – promotes alternative methods for the assessment of hazards in chemicals. Progress can also be observed in the field of pharmaceuticals: over the past several years, there has been a tendency towards regulatory acceptance of in-vitro (mainly cell- based) methods replacing animal testing.

The workshop gathered 50 participants from the European Commission, national and EU authorities, the animal health, chemicals, cosmetics, crop protection, fragrances and soaps/detergents industry sectors and animal protection organisations.

As a thought starter, four case studies were presented from the industry and the regulatory authority perspectives:

(1) The waiving of two-year rodent carcinogenicity studies in the pharmaceutical sector. Retrospective analyses revealed that these studies lead to high rates of incorrect results because the studies often indicate a condition that does not exist in reality (false positives). However, lack of carcinogenicity can often be predicted based upon negative data from genotoxicity tests and chronic rat studies combined with lack of hormonal perturbation signals. A prospective evaluation of this proposed hypothesis is ongoing by the pharmaceutical industry and responsible European and North American authorities are aiming to substantiate these findings to support the waiving of the two-year carcinogenicity test.

(2) The application of alternative methods for skin sensitisation in the chemicals sector. To date, the murine Local Lymph Node Assay is recognised as the reduction/refinement alternative method of choice under the EU chemicals regulation REACH. Integrated Testing Strategies (ITS) reflecting key elements of the adverse-outcome-pathway of skin sensitisation have been developed and validated in-house, of which one was presented. EURL ECVAM validation of individual in-vitro assays have been finalised and regulatory acceptance is underway. Nevertheless, the absence of a commonly accepted ITS and the complex interplay between acceptance on the EU level and international adoption of the corresponding OECD Test Guidelines, endanger timely adoption of the testing and assessment strategy for the REACH registration deadline of 2018.

(3) The replacement of animal testing in the cosmetics sector exemplified by genotoxicity assessment.In accordance with the recast Cosmetic Products Regulation, cosmetic ingredients and products may no longer be tested using animal experiments. This represented a challenge with regard togenotoxicity testing, as the classical in-vitro test battery (consisting of three tests) provides a high rate of false positives. By optimising the in-vitromicronucleus test (MNvit), the rate of false positives could be decreased while the prediction of true genotoxins remained high. In spring 2014, the Scientific Committee for Consumer Safety (SCCS) accepted a more predictive battery of two in-vitro tests (the Ames test and the MNvit). Furthermore the SCCS considered reconstructed human skin-based genotoxicity assays as a valuable part of follow up Tier 2 testing of dermally exposed substances to add to the final weight-of-evidence of all available data. The cosmetics industry is currently validating these improved test methods.

(4) The use of Thresholds of Toxicological Concern (TTC) for non-animal safety assessment of fragrances. The TTC concept implies that exposure thresholds exist below which substances no longer cause toxicological concern. Since some fragrances have very low odour thresholds, they may typically be applied at very low dosages. In some regulatory contexts, the TTC is being accepted for fragrance safety assessment if a) reliable exposure information is available or b) occupational and consumer exposures are controlled.

The subsequent breakout groups and final plenary discussion at the workshop put forward several recommendations to facilitate the regulatory acceptance of alternative approaches.

These identified opportunities to apply 3Rs alternative methods, ways to support their application in the regulatory context and the requirements for an alternative method to be used for regulatory purposes.

The recommendations will be evaluated further by EPAA and all stakeholders as the dialogue continues. Clearly the discussions have shown that dialogue and collaboration between all actors involved – industry, scientific community, NGOs, regulators at national and international level as well as politicians – is essential. EPAA provides an ideal forum for such a dialogue and allows all stakeholders to work together hand-in-hand in a scientifically-based, constructive and co-operative way to achieve the common objective.