The 21st Century movement within the area of skin sensitization assessment: From the animal context towards current human-relevant in vitro solutions

Application of the adverse outcome pathway framework for investigating skin sensitization potential of nanomaterials using new approach methods

“…However, the ability of nanomaterials to overcome the skin barrier and reach deep layers of skin remains controversial. Most studies reported that skin layers preclude the penetration of nanomaterials into the deeper epidermis and dermis 6,8,12,13 . While dermal permeation of small amounts of nanomaterials was detected by Gulson and colleagues, 10,11,14 authors indicated that nanomaterial composition and size, repeated applications, methods for analysing the samples, and integrity of skin are regarded as critical factors that may influence nanoparticle penetration.…”

“…These approaches allow a broad evaluation of exposure, skin penetration, metabolism, and KEs by applying the skin sensitization AOP framework 25 . In addition, they have recently acquired regulatory acceptance and/or applicability in the weight of evidence for the next‐generation risk evaluation for skin sensitization 13 . This study determined the skin sensitization potential of SWNTs, TiO 2 , and C 60 covering the first and third KEs of skin sensitization AOP.…”

“…The characterization of a skin sensitization AOP allowed the development of nonanimal‐based innovative methods with higher predictive capacity for allergenicity assessment of chemicals, when compared with the traditional animal‐based methods, 13 for example, the local lymph node assay 14 . To this end, this study investigated the potential mechanisms of immunotoxicity of widely used nanomaterials such as single‐wall carbon nanotubes (SWNTs), titanium dioxide (TiO 2 ), and fullerene (C 60 ) using the framework of skin sensitization AOP.…”

Translatability and transferability of in silico models: Context of use switching to predict the effects of environmental chemicals on the immune system

“…However, in recent decades considerable progress has been made, and several in vitro methods have been validated to assess inappropriate immunostimulation. While the main achevements in using in vitro models to assess immunotoxicity have focused on chemical sensitization, and in particular, on skin sensitization [8] , [9] , important progress has also been made in the identification of immunosuppressive compounds [10] , [11] , [12] . Considering the complexity of the immune system, it is likely that several in vitro assays will be needed to identify immunotoxicants, and a tiered approach is believed to be the most appropriate means to assess immunotoxicity in vitro [13] .…”

Comparison of the predictive nature of the Genomic Allergen Rapid Detection (GARD) assay with mammalian assays in determining the skin sensitisation potential of agrochemical active ingredients

“…Consequently, agrochemicals are routinely tested for skin sensitisation using in vivo tests such as the guinea pig tests and the local lymph node assay (LLNA) (Basketter et al, 2012, Gwaltney-Brant, 2014. Recently attempts have been made to identify non animal-based methods with good predictive power for chemical hazard identification in a bid to reduce laboratory animal use (Alloul-Ramdhani et al, 2014, Doe and Botham, 2019, Reisinger et al, 2015, Ivan de Ávila et al, 2019. In accordance with Article 62 of the European Regulation (EC) No.…”