Non-animal test methods for predicting skin sensitization potentials

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 cytoprotective and the dark side of Nrf2

“…Further influential articles published in the Archives of Toxicology in recent years focus on nanotoxicity (Kim et al 2012;Landsiedel et al 2012;Nunes et al 2012;Trpkovic et al 2012;Gebel 2012;Oesch and Landsiedel 2012), the use of stem cells in toxicology (Wobus and Löser 2011;Krug et al 2013;Seiler et al 2011), carcinogenesis (Bernstein et al 2011Golka et al 2011;Burns and Korach 2012;Pavanello and Lotti 2012;Brambilla et al 2011), metal toxicology (Chasapis et al 2012, neurotoxicity (Soderlund 2012;Carvalho et al 2012;Mariussen 2012), in silico and in vitro methods (Karp and Caspi 2011;Godoy et al 2013;Mehling et al 2012;Geenen et al 2012) and oxidative stress (Matés et al 2012). The editors hope that this choice meets the current needs of our readers, and encourage them to suggest further In 1988, Paul Talalay and colleagues described a protein with highly reactive cysteine residues that protects against chemical carcinogenesis (Talalay et al 1988) This led to the discovery of an elaborate network of highly inducible, cytoprotective proteins that are controlled by the Keap1-Nrf2 pathway (Itoh et al 1999;Dinkova-Kostova et al 2002;Kobayashi et al 2004;Wakabayashi et al 2004;Motohashi and Yamamoto 2004;Zhang and Hannink 2003;Balogun et al 2003;McMahon et al 2003;Zhang et al 2004;Kwak et al 2003).…”

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 .…”

“…The VOI is calculated for a set of individual non-animal testing methods, including in vitro, in silico and in chemico methods, seven battery combinations, 62 two-test and 174 three test sequential combinations of these non-animal testing methods (Urbisch et al, 2015a). Their VOIs are compared to the VOI of the local lymph node assay (LLNA) as the animal test (Mehling et al, 2012;Basketter et al, 2014;Urbisch et al, 2015a).…”