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

Abstract

Abstract:The paper provides an overview of existing Integrated Testing Strategies (ITS) for assessing hazard and potency of skin sensitization. The ITS research is active, diverse and constantly evolving as new assays are being developed and new mechanistic insights are discovered. Despite the need to assess potency, the majority of the ITS approaches developed to date assess hazard only. Reasons for this situation are analyzed and include, for example, the dynamic range of existing alternative assays versus the range of in vivo responses, but also sporadic use of kinetic information and molar units. Depending on the application, regulatory or product development, standardized and nonstandard ITS approaches will be developed. Challenges to practical applications, with focus on regulatory are discussed.

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

“…Chapter 2 reviews existing non-animal testing strategies for the assessment of skin sensitisation potential and potency. This chapter also identifies the criteria suggested in the toxicological literature for developing non-animal testing strategies (Jaworska, 2016) and further evaluates them from the economic perspective. Chapter 2 introduces the standard economic approach by suggesting the conceptual and informational criteria necessary to establish resource-efficiency in the development of testing strategies.…”

“…At the same time there has been increasing support for a systematic reduction and replacement of animal testing (Kinsner-Ovaskainen et al, 2009;Daston et al, 2015). The need for adequate and sufficient information derived from fast and less costly non-animal testing methods has emerged the development of testing strategies, integrating information from individual non-animal testing methods (Jaworska and Hoffmann, 2010;Jaworska et al, 2011;Hartung et al, 2013;Rovida et al, 2015;Jaworska, 2016). From an economic perspective this requires to balance the informational gains from performing testing methods with costs such as testing costs and the costs of making errors.…”

“…For skin sensitisation potential and potency assessment criteria for developing nonanimal testing strategies have been suggested in the literature (Jaworska and Hoffmann, 2010;Jaworska et al, 2011;Hartung et al, 2013;Rovida et al, 2015;Jaworska, 2016).…”

“…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 . It has also been suggested that the combination of individual non-animal testing methods into batteries or sequential strategies should be guided by the skin sensitisation AOP (Vinken, 2013;Patlewicz et al, 2014).…”

“…During the past decade, a lot of attention has been dedicated to developing non-animal testing methods and testing strategies for the toxicological endpoint skin sensitisation (Jaworska and Hoffmann, 2010;Jaworska et al, 2011;Hartung et al, 2013;Rovida et al, 2015;Jaworska, 2016). Skin sensitisation is the toxicological endpoint assessing a substance's ability to cause allergic contact dermatitis (ACD) (UNECE, 2011).…”