Systematic evaluation of non-animal test methods for skin sensitisation safety assessment

Abstract

The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitization potency prediction. The results of the first phase – systematic evaluation of 16 test methods – are presented here. This evaluation involved generation of data on a common set of ten substances in all methods and systematic collation of information including the level of standardisation, existing test data,potential for throughput, transferability and accessibility in cooperation with the test method developers.A workshop was held with the test method developers to review the outcome of this evaluation and to discuss the results. The evaluation informed the prioritisation of test methods for the next phase of the non-animal testing strategy development framework. Ultimately, the testing strategy – combined with bioavailability and skin metabolism data and exposure consideration – is envisaged to allow establishment of a data integration approach for skin sensitisation safety assessment of cosmetic ingredients.

Integrated Testing Strategies for Skin Sensitization Hazard and Potency Assessment—State of the Art and Challenges

“…Similar legislation may be proposed in the United States in 2015 [2]. This resulted in acceleration of mechanistic understanding of skin sensitization [3,4] and many novel promising alternatives to animal testing tests [5]. The new data streams are heterogeneous in metrics, levels of biological organization and times scales of the biological events they address.…”

“…The AOP for skin sensitization triggered by chemicals that bind covalently to proteins [9] includes four key events (KE) that occur after a substance (parent chemical or abiotically transformed product) penetrates through the skin and is potentially transformed into active metabolites: KE1: covalent binding to skin proteins; KE2: activation of inflammatory cytokines and induction of cyto-protective genes in the keratinocyte; KE3: activation (induction of inflammatory cytokines and surface molecules) and mobilization of dendritic cells in the skin; KE4: activation and proliferation of antigen-specific T-cells. Reisinger et al 2015 [5] provides a very good overview of how different existing assays map onto the AOP.…”

An economic approach to non-animal toxicity testing for skin sensitisation

“…Given both the economic and the toxicological relevance of the skin sensitisation endpoint, several non-animal methods for assessing skin sensitisation potential have been developed in recent years (Mehling et al, 2012;Reisinger et al, 2015). The Direct Peptide…”

“…an ACD incident). Since non-animal testing methods are not considered suitable to provide sufficient information to draw conclusions upon the skin sensitisation potential of chemicals (Mehling et al, 2012;Reisinger et al, 2015), a solution suggested is to integrate information from different sources and testing methods by using hypothesis-based approaches such as Bayesian networks (Jaworska and Hoffmann, 2010;Jaworska et al, 2011;Hartung et al, 2013;Jaworska et al, 2013;Jaworska, 2016) or deterministic ITS approaches (Bauch et al, 2012;Urbisch et al, 2015a). For the development of integrated strategies assessing skin sensitisation potential and potency (Jaworska, 2016) different sets of criteria have been proposed including transparency, coherency, ambiguity, or cost effectiveness (Hartung et al, 2013;Rovida et al, 2015) which are applicable also for other toxicological endpoints .…”

“…Non-animal testing methods and toxicity testing strategies aim at a subsequent reduction of the number of animal tests used and, ultimately, a full replacement of animal testing (Ahlers et al, 2008;Hartung, 2010a;Adler et al, 2011;Reisinger et al, 2015). During the past decade, non-animal testing strategies have been developed for several toxicological endpoints.…”