The skin sensitization adverse outcome pathway: exploring the role of mechanistic understanding for higher tier risk assessment

References

• Ade N, Leon F, Pallardy M, Peiffer JL, Kerdine-Romer S, Tissier MH, Bonnet PA, Fabre I, Ourlin JC. 2009. HMOX1 and NQO1 genes are upregulated in response to contact sensitizers in dendritic cells and THP-1 cell line: role of the Keap1/Nrf2 pathway. Toxicol Sci. 107(2):451–460. doi: 10.1093/toxsci/kfn243.
   PubMed Web of Science ®Google Scholar
• Aiba S, Terunuma A, Manome H, Tagami H. 1997. Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co-stimulatory molecules. Eur J Immunol. 27(11):3031–3038. doi: 10.1002/eji.1830271141.
   PubMed Web of Science ®Google Scholar
• Ainscough JS, Frank Gerberick G, Dearman RJ, Kimber I. 2013. Danger, intracellular signaling, and the orchestration of dendritic cell function in skin sensitization. J Immunotoxicol. 10(3):223–234. doi: 10.3109/1547691X.2012.711782.
   PubMed Web of Science ®Google Scholar
• Albrekt A-S, Johansson H, Börje A, Borrebaeck C, Lindstedt M. 2014. Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency. BMC Pharmacol Toxicol. 15(1):5. doi: 10.1186/2050-6511-15-5.
   PubMedGoogle Scholar
• Aleksic M, Thain E, Roger D, Saib O, Davies M, Li J, Aptula A, Zazzeroni R. 2009. Reactivity profiling: covalent modification of single nucleophile peptides for skin sensitization risk assessment. Toxicol Sci. 108(2):401–411. doi: 10.1093/toxsci/kfp030.
   PubMed Web of Science ®Google Scholar
• Alépée N, Tourneix F, Singh A, Ade N, Grégoire S. 2023. Off to a good start? Review of the predictivity of reactivity methods modelling the molecular initiating event of skin sensitization. ALTEX. 40(4):606–618. doi: 10.14573/altex.2212201.
   PubMedGoogle Scholar
• Alinaghi F, Bennike NH, Egeberg A, Thyssen JP, Johansen JD. 2019. Prevalence of contact allergy in the general population: a systematic review and meta-analysis. Contact Dermatitis. 80(2):77–85. doi: 10.1111/cod.13119.
   PubMed Web of Science ®Google Scholar
• Alvarez-Sánchez R, Basketter D, Pease C, Lepoittevin JP. 2004a. Covalent binding of the 13C-labeled skin sensitizers 5-chloro-2-methylisothiazol-3-one (MCI) and 2-methylisothiazol-3-one (MI) to a model peptide and glutathione. Bioorg Med Chem Lett. 14(2):365–368. doi: 10.1016/j.bmcl.2003.11.002.
   PubMed Web of Science ®Google Scholar
• Alvarez-Sánchez R, Divkovic M, Basketter D, Pease C, Panico M, Dell A, Morris H, Lepoittevin J-P. 2004b. Effect of glutathione on the covalent binding of the (13)C-labeled skin sensitizer 5-chloro-2-methylisothiazol-3-one to human serum albumin: identification of adducts by nuclear magnetic resonance, matrix-assisted laser desorption/ionization mass spectrometry, and nanoelectrospray tandem mass spectrometry. Chem Res Toxicol. 17(9):1280–1288. doi: 10.1021/tx049935+.
   PubMed Web of Science ®Google Scholar
• Anders MW. 2008. Chemical toxicology of reactive intermediates formed by the glutathione-dependent bioactivation of halogen-containing compounds. Chem Res Toxicol. 21(1):145–159. doi: 10.1021/tx700202w.
   PubMed Web of Science ®Google Scholar
• Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, et al. 2010. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 29(3):730–741. doi: 10.1002/etc.34.
   PubMed Web of Science ®Google Scholar
• Ashikaga T, Yoshida Y, Hirota M, Yoneyama K, Itagaki H, Sakaguchi H, Miyazawa M, Ito Y, Suzuki H, Toyoda H. 2006. Development of an in vitro skin sensitization test using human cell lines: the human cell line activation test (h-CLAT). I. Optimization of the h-CLAT protocol. Toxicol In Vitro. 20(5):767–773. doi: 10.1016/j.tiv.2005.10.012.
   PubMed Web of Science ®Google Scholar
• Ayala A, Muñoz MF, Argüelles S. 2014. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014:360438. doi: 10.1155/2014/360438.
   PubMed Web of Science ®Google Scholar
• Bailey A, Nicholas B, Darley R, Parkinson E, Teo Y, Aleksic M, Maxwell G, Elliott T, Ardern-Jones M, Skipp P. 2021. Characterization of the Class I MHC peptidome resulting from DNCB exposure of HaCaT cells. Toxicol Sci. 180(1):136–147. doi: 10.1093/toxsci/kfaa184.
   PubMed Web of Science ®Google Scholar
• Baillie TA, Kassahun K. 1994. Reversibility in glutathione-conjugate formation. In: Anders MW, Dekant W, editors. Advances in pharmacology. Cambridge (MA): Academic Press; p. 163–181.
   Google Scholar
• Bang C, Thum T. 2012. Exosomes: new players in cell–cell communication. Int J Biochem Cell Biol. 44(11):2060–2064. doi: 10.1016/j.biocel.2012.08.007.
   PubMed Web of Science ®Google Scholar
• Barker JN, Mitra RS, Griffiths CE, Dixit VM, Nickoloff BJ. 1991. Keratinocytes as initiators of inflammation. Lancet. 337(8735):211–214. doi: 10.1016/0140-6736(91)92168-2.
   PubMed Web of Science ®Google Scholar
• Basketter DA, Alépée N, Ashikaga T, Barroso J, Gilmour N, Goebel C, Hibatallah J, Hoffmann S, Kern P, Martinozzi-Teissier S, et al. 2014. Categorization of chemicals according to their relative human skin sensitizing potency. Dermatitis. 25(1):11–21. doi: 10.1097/DER.0000000000000003.
   PubMed Web of Science ®Google Scholar
• Bauer B, Andersson SI, Stenfeldt AL, Simonsson C, Bergstroom J, Ericson MB, Jonsson CA, Broo KS. 2011. Modification and expulsion of keratins by human epidermal keratinocytes upon hapten exposure in vitro. Chem Res Toxicol. 24(5):737–743. doi: 10.1021/tx200030y.
   PubMed Web of Science ®Google Scholar
• Becker D, Mohamadzadeh M, Reske K, Knop J. 1992. Increased level of intracellular MHC class II molecules in murine Langerhans cells following in vivo and in vitro administration of contact allergens. J Invest Dermatol. 99(5):545–549. doi: 10.1111/1523-1747.ep12667308.
   PubMed Web of Science ®Google Scholar
• Bessems JG, Vermeulen NP. 2001. Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Crit Rev Toxicol. 31(1):55–138. doi: 10.1080/20014091111677.
   PubMed Web of Science ®Google Scholar
• Betts RJ, Perkovic A, Mahapatra S, Del Bufalo A, Camara K, Howell AR, Martinozzi Teissier S, De Libero G, Mori L. 2017. Contact sensitizers trigger human CD1-autoreactive T-cell responses. Eur J Immunol. 47(7):1171–1180. doi: 10.1002/eji.201746939.
   PubMed Web of Science ®Google Scholar
• Billman JH, Diesing AC. 1957. Reduction of Schiff bases with sodium borohydride. J Org Chem. 22(9):1068–1070. doi: 10.1021/jo01360a019.
   Web of Science ®Google Scholar
• Blauvelt A, Katz SI, Udey MC. 1995. Human langerhans cells express E-cadherin. J Invest Dermatol. 104(2):293–296. doi: 10.1111/1523-1747.ep12612830.
   PubMed Web of Science ®Google Scholar
• Blömeke B, Brans R, Coenraads PJ, Dickel H, Bruckner T, Hein DW, Heesen M, Merk HF, Kawakubo Y. 2009. Para-phenylenediamine and allergic sensitization: risk modification by N-acetyltransferase 1 and 2 genotypes. Br J Dermatol. 161(5):1130–1135. doi: 10.1111/j.1365-2133.2009.09352.x.
   PubMed Web of Science ®Google Scholar
• Bowes JH, Cater CW. 1968. The interaction of aldehydes with collagen. Biochim Biophys Acta. 168(2):341–352. doi: 10.1016/0005-2795(68)90156-6.
   PubMedGoogle Scholar
• Brand A, Diener N, Zahner SP, Tripp C, Backer RA, Karram K, Jiang A, Mellman I, Stoitzner P, Clausen BE. 2020. E-Cadherin is dispensable to maintain langerhans cells in the epidermis. J Invest Dermatol. 140(1):132–142.e133. doi: 10.1016/j.jid.2019.06.132.
   PubMed Web of Science ®Google Scholar
• Bruchhausen S, Zahn S, Valk E, Knop J, Becker D. 2003. Thiol antioxidants block the activation of antigen-presenting cells by contact sensitizers. J Invest Dermatol. 121(5):1039–1044. doi: 10.1046/j.1523-1747.2003.12510.x.
   PubMed Web of Science ®Google Scholar
• Bryniarski K, Ptak W, Jayakumar A, Püllmann K, Caplan MJ, Chairoungdua A, Lu J, Adams BD, Sikora E, Nazimek K, et al. 2013. Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity. J Allergy Clin Immunol. 132(1):170–181. doi: 10.1016/j.jaci.2013.04.048.
   PubMed Web of Science ®Google Scholar
• Bryniarski K, Ptak W, Martin E, Nazimek K, Szczepanik M, Sanak M, Askenase PW. 2015. Free extracellular miRNA functionally targets cells by transfecting exosomes from their companion cells. PLoS One. 10(4):e0122991. doi: 10.1371/journal.pone.0122991.
   PubMed Web of Science ®Google Scholar
• Buratti FM, Darney K, Vichi S, Turco L, Di Consiglio E, Lautz LS, Béchaux C, Dorne J-L, Testai E. 2021. Human variability in glutathione-S-transferase activities, tissue distribution and major polymorphic variants: meta-analysis and implication for chemical risk assessment. Toxicol Lett. 337:78–90. doi: 10.1016/j.toxlet.2020.11.007.
   PubMed Web of Science ®Google Scholar
• Cai XW, Zhu R, Ran L, Li YQ, Huang K, Peng J, He W, Zhou CL, Wang RP. 2017. A novel non‑contact communication between human keratinocytes and T cells: exosomes derived from keratinocytes support superantigen‑induced proliferation of resting T cells. Mol Med Rep. 16(5):7032–7038. doi: 10.3892/mmr.2017.7492.
   PubMed Web of Science ®Google Scholar
• Castro JP, Jung T, Grune T, Siems W. 2017. 4-Hydroxynonenal (HNE) modified proteins in metabolic diseases. Free Radic Biol Med. 111:309–315. doi: 10.1016/j.freeradbiomed.2016.10.497.
   PubMed Web of Science ®Google Scholar
• Chipinda I, Ajibola RO, Morakinyo MK, Ruwona TB, Simoyi RH, Siegel PD. 2010. Rapid and simple kinetics screening assay for electrophilic dermal sensitizers using nitrobenzenethiol. Chem Res Toxicol. 23(5):918–925. doi: 10.1021/tx100003w.
   PubMed Web of Science ®Google Scholar
• Chipinda I, Mbiya W, Adigun RA, Morakinyo MK, Law BF, Simoyi RH, Siegel PD. 2014. Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening electrophilic dermal sensitizers. Toxicology. 315:102–109. doi: 10.1016/j.tox.2013.11.009.
   PubMed Web of Science ®Google Scholar
• Cochrane SA, Arts JH, Ehnes C, Hindle S, Hollnagel HM, Poole A, Suto H, Kimber I. 2015. Thresholds in chemical respiratory sensitisation. Toxicology. 333:179–194. doi: 10.1016/j.tox.2015.04.010.
   PubMed Web of Science ®Google Scholar
• Cooper AJL, Hanigan MH. 2018. 10.17 - Metabolism of glutathione S-conjugates: multiple pathways. In: McQueen CA, editor. Comprehensive toxicology. 3rd ed. Oxford: Elsevier; p. 363–406.
   Google Scholar
• Cooper G. 2000. Lysosomes. The cell: a molecular approach. 2nd ed. Sunderland, MA: Sinauer Associates.
   Google Scholar
• Cottrez F, Boitel E, Auriault C, Aeby P, Groux H. 2015. Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin model. Development of the SENS-IS assay. Toxicol In Vitro. 29(4):787–802. doi: 10.1016/j.tiv.2015.02.012.
   PubMed Web of Science ®Google Scholar
• Cottrez F, Boitel E, Ourlin J-C, Peiffer J-L, Fabre I, Henaoui I-S, Mari B, Vallauri A, Paquet A, Barbry P, et al. 2016. SENS-IS, a 3D reconstituted epidermis based model for quantifying chemical sensitization potency: reproducibility and predictivity results from an inter-laboratory study. Toxicol In Vitro. 32:248–260. doi: 10.1016/j.tiv.2016.01.007.
   PubMed Web of Science ®Google Scholar
• Cyran AM, Zhitkovich A. 2022. HIF1, HSF1, and NRF2: oxidant-responsive trio raising cellular defenses and engaging immune system. Chem Res Toxicol. 35(10):1690–1700. doi: 10.1021/acs.chemrestox.2c00131.
   PubMed Web of Science ®Google Scholar
• D’Arcy C, Kiel C. 2021. Cell adhesion molecules in normal skin and melanoma. Biomolecules. 11(8):1213. doi: 10.3390/biom11081213.
   PubMed Web of Science ®Google Scholar
• de Ávila RI, Aleksic M, Zhu B, Li J, Pendlington R, Campos Valadares M. 2023a. Non-animal approaches for photoallergenicity safety assessment: needs and perspectives for the toxicology for the 21st century. Regul Toxicol Pharmacol 145:105499. doi: 10.1016/j.yrtph.2023.105499.
   PubMed Web of Science ®Google Scholar
• de Ávila RI, Carreira Santos S, Siino V, Levander F, Lindstedt M, Zeller KS. 2022. Adjuvants in fungicide formulations can be skin sensitizers and cause different types of cell stress responses. Toxicol Rep. 9:2030–2041. doi: 10.1016/j.toxrep.2022.11.004.
   PubMedGoogle Scholar
• de Ávila RI, Carreira Santos S, Siino V, Levander F, Lindstedt M, Zeller KS. 2023b. A proteomics dataset capturing myeloid cell responses upon cellular exposure to fungicides, adjuvants and fungicide formulations. Data Brief. 46:108878. doi: 10.1016/j.dib.2022.108878.
   PubMed Web of Science ®Google Scholar
• Debeuckelaere C, Berl V, Elbayed K, Moussallieh FM, Namer IJ, Lepoittevin JP. 2015. Matrix effect of human reconstructed epidermis on the chemoselectivity of a skin sensitizing alpha-methylene-gamma-butyrolactone: consequences for the development of in chemico alternative methods. Chem Res Toxicol. 28(11):2192–2198. doi: 10.1021/acs.chemrestox.5b00363.
   PubMed Web of Science ®Google Scholar
• Debeuckelaere C, Moussallieh F-M, Elbayed K, Namer I-J, Berl V, Giménez-Arnau E, Lepoittevin J-P. 2016. In situ chemical behaviour of methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI) in reconstructed human epidermis: a new approach to the cross-reactivity issue. Contact Dermatitis. 74(3):159–167. doi: 10.1111/cod.12524.
   PubMed Web of Science ®Google Scholar
• Domingues RM, Domingues P, Melo T, Pérez-Sala D, Reis A, Spickett CM. 2013. Lipoxidation adducts with peptides and proteins: deleterious modifications or signaling mechanisms? J Proteomics. 92:110–131. doi: 10.1016/j.jprot.2013.06.004.
   PubMed Web of Science ®Google Scholar
• Dupont M, Souriant S, Lugo-Villarino G, Maridonneau-Parini I, Vérollet C. 2018. Tunneling nanotubes: intimate communication between myeloid cells. Front Immunol. 9:43. doi: 10.3389/fimmu.2018.00043.
   PubMed Web of Science ®Google Scholar
• Eggink M, Wijtmans M, Ekkebus R, Lingeman H, de Esch IJ, Kool J, Niessen WM, Irth H. 2008. Development of a selective ESI-MS derivatization reagent: synthesis and optimization for the analysis of aldehydes in biological mixtures. Anal Chem. 80(23):9042–9051. doi: 10.1021/ac801429w.
   PubMed Web of Science ®Google Scholar
• Elbayed K, Berl V, Debeuckelaere C, Moussallieh FM, Piotto M, Namer IJ, Lepoittevin JP. 2013. HR-MAS NMR spectroscopy of reconstructed human epidermis: potential for the in situ investigation of the chemical interactions between skin allergens and nucleophilic amino acids. Chem Res Toxicol. 26(1):136–145. doi: 10.1021/tx300428u.
   PubMed Web of Science ®Google Scholar
• Emter R, Ellis G, Natsch A. 2010. Performance of a novel keratinocyte-based reporter cell line to screen skin sensitizers in vitro. Toxicol Appl Pharmacol. 245(3):281–290. doi: 10.1016/j.taap.2010.03.009.
   PubMed Web of Science ®Google Scholar
• Engeroff P, Fellmann M, Yerly D, Bachmann MF, Vogel M. 2018. A novel recycling mechanism of native IgE-antigen complexes in human B cells facilitates transfer of antigen to dendritic cells for antigen presentation. J Allergy Clin Immunol. 142(2):557–568.e556. doi: 10.1016/j.jaci.2017.09.024.
   PubMed Web of Science ®Google Scholar
• EU. 2009. Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. Off J Eur Union. 52(L342):59–209.
   Google Scholar
• Evans DC, Watt AP, Nicoll-Griffith DA, Baillie TA. 2004. Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem Res Toxicol. 17(1):3–16. doi: 10.1021/tx034170b.
   PubMed Web of Science ®Google Scholar
• Ezendam J, Braakhuis HM, Vandebriel RJ. 2016. State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies. Arch Toxicol. 90(12):2861–2883. doi: 10.1007/s00204-016-1842-4.
   PubMed Web of Science ®Google Scholar
• Ferreira I, Silva A, Martins JD, Neves BM, Cruz MT. 2018. Nature and kinetics of redox imbalance triggered by respiratory and skin chemical sensitizers on the human monocytic cell line THP-1. Redox Biol. 16:75–86. doi: 10.1016/j.redox.2018.02.002.
   PubMed Web of Science ®Google Scholar
• Fujita M, Yamamoto Y, Tahara H, Kasahara T, Jimbo Y, Hioki T. 2014. Development of a prediction method for skin sensitization using novel cysteine and lysine derivatives. J Pharmacol Toxicol Methods. 70(1):94–105. doi: 10.1016/j.vascn.2014.06.001.
   PubMed Web of Science ®Google Scholar
• Fujita M, Yamamoto Y, Watanabe S, Sugawara T, Wakabayashi K, Tahara Y, Horie N, Fujimoto K, Kusakari K, Kurokawa Y, et al. 2019. Cause of and countermeasures for oxidation of the cysteine-derived reagent used in the amino acid derivative reactivity assay. J Appl Toxicol. 39(2):191–208. doi: 10.1002/jat.3707.
   PubMed Web of Science ®Google Scholar
• Furio L, Briotet I, Journeaux A, Billard H, Péguet-Navarro J. 2010. Human langerhans cells are more efficient than CD14(-)CD1c(+) dermal dendritic cells at priming naive CD4(+) T cells. J Invest Dermatol. 130(5):1345–1354. doi: 10.1038/jid.2009.424.
   PubMed Web of Science ®Google Scholar
• Galbiati V, Bianchi S, Martínez V, Mitjans M, Corsini E. 2014. NCTC 2544 and IL-18 production: a tool for the in vitro identification of photoallergens. Toxicol in Vitro. 28(1):13–17. doi: 10.1016/j.tiv.2013.06.008.
   PubMed Web of Science ®Google Scholar
• García-Piñeres AJ, Castro V, Mora G, Schmidt TJ, Strunck E, Pahl HL, Merfort I. 2001. Cysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones. J Biol Chem. 276(43):39713–39720. doi: 10.1074/jbc.M101985200.
   PubMed Web of Science ®Google Scholar
• Gerberick F, Troutman JA, Foertsch LM, Vassallo JD, Quijano M, Dobson RLM, Goebel C, Lepoittevin JP. 2009. Ivestigation of peptide reactivity of pro-hapten skin sensitizers using a peroxidase-peroxide oxidation system. Toxicol Sci. 112(1):164–174. doi: 10.1093/toxsci/kfp192.
   PubMed Web of Science ®Google Scholar
• Gerberick GF, Ryan CA, Kern PS, Schlatter H, Dearman RJ, Kimber I, Patlewicz GY, Basketter DA. 2005. Compilation of historical local lymph node data for evaluation of skin sensitization alternative methods. Dermatitis. 16(4):157–202.
   PubMed Web of Science ®Google Scholar
• Gerberick GF, Vassallo JD, Bailey RE, Chaney JG, Morrall SW, Lepoittevin JP. 2004. Development of a peptide reactivity assay for screening contact allergens. Toxicol Sci. 81(2):332–343. doi: 10.1093/toxsci/kfh213.
   PubMed Web of Science ®Google Scholar
• Gerberick GF, Vassallo JD, Foertsch LM, Price BB, Chaney JG, Lepoittevin JP. 2007. Quantification of chemical peptide reactivity for screening contact allergens: a classification tree model approach. Toxicol Sci. 97(2):417–427. doi: 10.1093/toxsci/kfm064.
   PubMed Web of Science ®Google Scholar
• Gilmour N, Alépée N, Hoffmann S, Kern PS, Van Vliet E, Bury D, Miyazawa M, Nishida H, Cosmetics E. 2023. Applying a next generation risk assessment framework for skin sensitisation to inconsistent new approach methodology information. ALTEX. 40( 3):439–451. doi: 10.14573/altex.2211161.
   PubMedGoogle Scholar
• Gilmour N, Kern PS, Alépée N, Boislève F, Bury D, Clouet E, Hirota M, Hoffmann S, Kühnl J, Lalko JF, et al. 2020. Development of a next generation risk assessment framework for the evaluation of skin sensitisation of cosmetic ingredients. Regul Toxicol Pharmacol. 116:104721. doi: 10.1016/j.yrtph.2020.104721.
   PubMed Web of Science ®Google Scholar
• Gilmour N, Kimber I, Williams J, Maxwell G. 2019. Skin sensitization: uncertainties, challenges, and opportunities for improved risk assessment. Contact Dermatitis. 80(3):195–200. doi: 10.1111/cod.13167.
   PubMed Web of Science ®Google Scholar
• Gilmour N, Reynolds J, Przybylak K, Aleksic M, Aptula N, Baltazar MT, Cubberley R, Rajagopal R, Reynolds G, Spriggs S, et al. 2022. Next generation risk assessment for skin allergy: decision making using new approach methodologies. Regul Toxicol Pharmacol. 131:105159. doi: 10.1016/j.yrtph.2022.105159.
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Collin MP, Bogunovic M, Abel M, Leboeuf M, Helft J, Ochando J, Kissenpfennig A, Malissen B, Grisotto M, et al. 2007. Blood-derived dermal langerin + dendritic cells survey the skin in the steady state. J Exp Med. 204(13):3133–3146. doi: 10.1084/jem.20071733.
   PubMed Web of Science ®Google Scholar
• Girolomoni G, Cruz PD, Jr., Bergstresser PR. 1990. Internalization and acidification of surface HLA-DR molecules by epidermal Langerhans cells: a paradigm for antigen processing. J Invest Dermatol. 94(6):753–760. doi: 10.1111/1523-1747.ep12874611.
   PubMed Web of Science ®Google Scholar
• Gradin R, Forreryd A, Mattson U, Jerre A, Johansson H. 2021. Quantitative assessment of sensitizing potency using a dose–response adaptation of GARDskin. Sci Rep. 11(1):18904. doi: 10.1038/s41598-021-98247-7.
   PubMed Web of Science ®Google Scholar
• Griffiths CE, Nickoloff BJ. 1989. Keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression precedes dermal T lymphocytic infiltration in allergic contact dermatitis (Rhus dermatitis). Am J Pathol. 135(6):1045–1053.
   PubMed Web of Science ®Google Scholar
• Groves RW, Allen MH, Ross EL, Barker JN, MacDonald DM. 1995. Tumour necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression. Br J Dermatol. 132(3):345–352. doi: 10.1111/j.1365-2133.1995.tb08666.x.
   PubMed Web of Science ®Google Scholar
• Han B, Stevens JF, Maier CS. 2007. Design, synthesis, and application of a hydrazide-functionalized isotope-coded affinity tag for the quantification of oxylipid-protein conjugates. Anal Chem. 79(9):3342–3354. doi: 10.1021/ac062262a.
   PubMed Web of Science ®Google Scholar
• Helou DG, Martin SF, Pallardy M, Chollet-Martin S, Kerdine-Römer S. 2019. Nrf2 involvement in chemical-induced skin innate immunity. Front Immunol. 10:1004. doi: 10.3389/fimmu.2019.01004.
   PubMed Web of Science ®Google Scholar
• Hernandez-Jaimes OA, Cazares-Olvera DV, Line J, Moreno-Eutimio MA, Gómez-Castro CZ, Naisbitt DJ, Castrejón-Flores JL. 2022. Advances in our understanding of the interaction of drugs with t-cells: implications for the discovery of biomarkers in severe cutaneous drug reactions. Chem Res Toxicol. 35(7):1162–1183. doi: 10.1021/acs.chemrestox.1c00434.
   PubMed Web of Science ®Google Scholar
• Hooyberghs J, Schoeters E, Lambrechts N, Nelissen I, Witters H, Schoeters G, Van Den Heuvel R. 2008. A cell-based in vitro alternative to identify skin sensitizers by gene expression. Toxicol Appl Pharmacol. 231(1):103–111. doi: 10.1016/j.taap.2008.03.014.
   PubMed Web of Science ®Google Scholar
• Hough KP, Deshane JS. 2019. Exosomes in allergic airway diseases. Curr Allergy Asthma Rep. 19(5):26. doi: 10.1007/s11882-019-0857-3.
   PubMed Web of Science ®Google Scholar
• Hough KP, Trevor JL, Strenkowski JG, Wang Y, Chacko BK, Tousif S, Chanda D, Steele C, Antony VB, Dokland T, et al. 2018. Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells. Redox Biol. 18:54–64. doi: 10.1016/j.redox.2018.06.009.
   PubMed Web of Science ®Google Scholar
• Hulbert AJ, Kelly MA, Abbott SK. 2014. Polyunsaturated fats, membrane lipids and animal longevity. J Comp Physiol B. 184(2):149–166. doi: 10.1007/s00360-013-0786-8.
   PubMed Web of Science ®Google Scholar
• Jacquoilleot S, Sheffield D, Olayanju A, Sison-Young R, Kitteringham NR, Naisbitt DJ, Aleksic M. 2015. Glutathione metabolism in the HaCaT cell line as a model for the detoxification of the model sensitisers 2,4-dinitrohalobenzenes in human skin. Toxicol Lett. 237(1):11–20. doi: 10.1016/j.toxlet.2015.05.016.
   PubMed Web of Science ®Google Scholar
• Jakob T, Udey MC. 1998. Regulation of E-cadherin-mediated adhesion in Langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo. J Immunol. 160(8):4067–4073. doi: 10.4049/jimmunol.160.8.4067.
   PubMed Web of Science ®Google Scholar
• Jaworska J, Dancik Y, Kern P, Gerberick F, Natsch A. 2013. Bayesian integrated testing strategy to assess skin sensitization potency: from theory to practice. J Appl Toxicol. 33(11):1353–1364. doi: 10.1002/jat.2869.
   PubMed Web of Science ®Google Scholar
• Jella KK, Nasti TH, Li Z, Malla SR, Buchwald ZS, Khan MK. 2018. Exosomes, their biogenesis and role in inter-cellular communication, tumor microenvironment and cancer immunotherapy. Vaccines (Basel). 6(4):69. doi: 10.3390/vaccines6040069.
   PubMed Web of Science ®Google Scholar
• Ji C, Kozak KR, Marnett LJ. 2001. IkappaB kinase, a molecular target for inhibition by 4-hydroxy-2-nonenal. J Biol Chem. 276(21):18223–18228. doi: 10.1074/jbc.M101266200.
   PubMed Web of Science ®Google Scholar
• Jiang D, Liang J, Noble PW. 2011. Hyaluronan as an immune regulator in human diseases. Physiol Rev. 91(1):221–264. doi: 10.1152/physrev.00052.2009.
   PubMed Web of Science ®Google Scholar
• Johansson H, Albrekt AS, Borrebaeck CA, Lindstedt M. 2013. The GARD assay for assessment of chemical skin sensitizers. Toxicol In Vitro. 27(3):1163–1169. doi: 10.1016/j.tiv.2012.05.019.
   PubMed Web of Science ®Google Scholar
• Johansson H, Gradin R, Johansson A, Adriaens E, Edwards A, Zuckerstätter V, Jerre A, Burleson F, Gehrke H, Roggen EL. 2019. Validation of the GARD™skin assay for assessment of chemical skin sensitizers: ring trial results of predictive performance and reproducibility. Toxicol Sci. 170(2):374–381. doi: 10.1093/toxsci/kfz108.
   PubMed Web of Science ®Google Scholar
• Johansson H, Lindstedt M, Albrekt A-S, Borrebaeck CAK. 2011. A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests. BMC Genomics. 12(1):399. doi: 10.1186/1471-2164-12-399.
   PubMedGoogle Scholar
• JRC EC. 2021. ESAC opinion on the scientific validity of the GARDskin and GARDpotency test methods. Luxembourg: Publications Office.
   Google Scholar
• Kaplan DH, Kissenpfennig A, Clausen BE. 2008. Insights into Langerhans cell function from Langerhans cell ablation models. Eur J Immunol. 38(9):2369–2376. doi: 10.1002/eji.200838397.
   PubMed Web of Science ®Google Scholar
• Karlsson I, Samuelsson K, Ponting DJ, Törnqvist M, Ilag LL, Nilsson U. 2016. Peptide reactivity of isothiocyanates – implications for skin allergy. Sci Rep. 6(1):21203. doi: 10.1038/srep21203.
   PubMedGoogle Scholar
• Karlsson I, Samuelsson K, Simonsson C, Stenfeldt A-L, Nilsson U, Ilag LL, Jonsson C, Karlberg A-T. 2018. The fate of a hapten - from the skin to modification of macrophage migration inhibitory factor (MIF) in lymph nodes. Sci Rep. 8(1):2895. doi: 10.1038/s41598-018-21327-8.
   PubMedGoogle Scholar
• Kavasi RM, Berdiaki A, Spyridaki I, Papoutsidakis A, Corsini E, Tsatsakis A, Tzanakakis GN, Nikitovic D. 2019. Contact allergen (PPD and DNCB)-induced keratinocyte sensitization is partly mediated through a low molecular weight hyaluronan (LMWHA)/TLR4/NF-κB signaling axis. Toxicol Appl Pharmacol. 377:114632. doi: 10.1016/j.taap.2019.114632.
   PubMed Web of Science ®Google Scholar
• Kawai Y, Takeda S, Terao J. 2007. Lipidomic analysis for lipid peroxidation-derived aldehydes using gas chromatography-mass spectrometry. Chem Res Toxicol. 20(1):99–107. doi: 10.1021/tx060199e.
   PubMed Web of Science ®Google Scholar
• Kawakami T, Isama K, Ikarashi Y, Jinno H. 2020. Evaluation of the sensitization potential of volatile and semi-volatile organic compounds using the direct peptide reactivity assay. J Toxicol Sci. 45(11):725–735. doi: 10.2131/jts.45.725.
   PubMed Web of Science ®Google Scholar
• Kazem S, Linssen EC, Gibbs S. 2019. Skin metabolism phase I and phase II enzymes in native and reconstructed human skin: a short review. Drug Discov Today. 24(9):1899–1910. doi: 10.1016/j.drudis.2019.06.002.
   PubMed Web of Science ®Google Scholar
• Kim S-M, Studnitzer B, Esser-Kahn A. 2022. Heat shock protein 90’s mechanistic role in contact hypersensitivity. J Immunol. 208(12):2622–2631. doi: 10.4049/jimmunol.2101023.
   PubMed Web of Science ®Google Scholar
• Kimber I, Basketter DA, Gerberick GF, Dearman RJ. 2002. Allergic contact dermatitis. Int Immunopharmacol. 2(2–3):201–211. doi: 10.1016/s1567-5769(01)00173-4.
   PubMed Web of Science ®Google Scholar
• Kimber I, Basketter DA, Gerberick GF, Ryan CA, Dearman RJ. 2011. Chemical allergy: translating biology into hazard characterization. Toxicol Sci. 120(Supplement 1):S238–S268. doi: 10.1093/toxsci/kfq346.
   PubMedGoogle Scholar
• Kimber I, Maxwell G, Gilmour N, Dearman RJ, Friedmann PS, Martin SF. 2012. Allergic contact dermatitis: a commentary on the relationship between T lymphocytes and skin sensitising potency. Toxicology. 291(1–3):18–24. doi: 10.1016/j.tox.2011.11.007.
   PubMed Web of Science ®Google Scholar
• Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P, Romani N, Tripp CH, Douillard P, Leserman L, Kaiserlian D, et al. 2005. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity. 22(5):643–654. doi: 10.1016/j.immuni.2005.04.004.
   PubMed Web of Science ®Google Scholar
• Klechevsky E, Morita R, Liu M, Cao Y, Coquery S, Thompson-Snipes L, Briere F, Chaussabel D, Zurawski G, Palucka AK, et al. 2008. Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells. Immunity. 29(3):497–510. doi: 10.1016/j.immuni.2008.07.013.
   PubMed Web of Science ®Google Scholar
• Kleinstreuer NC, Hoffmann S, Alépée N, Allen D, Ashikaga T, Casey W, Clouet E, Cluzel M, Desprez B, Gellatly N, et al. 2018. Non-animal methods to predict skin sensitization (II): an assessment of defined approaches (*). Crit Rev Toxicol. 48(5):359–374. doi: 10.1080/10408444.2018.1429386.
   PubMed Web of Science ®Google Scholar
• Knox S, O’Boyle NM. 2021. Skin lipids in health and disease: a review. Chem Phys Lipids. 236:105055. doi: 10.1016/j.chemphyslip.2021.105055.
   PubMed Web of Science ®Google Scholar
• Kotzerke K, Mempel M, Aung T, Wulf GG, Urlaub H, Wenzel D, Schön MP, Braun A. 2013. Immunostimulatory activity of murine keratinocyte-derived exosomes. Exp Dermatol. 22(10):650–655. doi: 10.1111/exd.12230.
   PubMed Web of Science ®Google Scholar
• Krishnan S, Miller RM, Tian B, Mullins RD, Jacobson MP, Taunton J. 2014. Design of reversible, cysteine-targeted Michael acceptors guided by kinetic and computational analysis. J Am Chem Soc. 136(36):12624–12630.
   PubMed Web of Science ®Google Scholar
• Kühn U, Brand P, Willemsen J, Jonuleit H, Enk AH, van Brandwijk-Petershans R, Saloga J, Knop J, Becker D. 1998. Induction of tyrosine phosphorylation in human MHC class II-positive antigen-presenting cells by stimulation with contact sensitizers. J Immunol (Baltimore, Md: 1950). 160(2):667–673. doi: 10.4049/jimmunol.160.2.667.
   PubMed Web of Science ®Google Scholar
• Kwok BH, Koh B, Ndubuisi MI, Elofsson M, Crews CM. 2001. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 8(8):759–766. doi: 10.1016/s1074-5521(01)00049-7.
   PubMedGoogle Scholar
• Lambrechts N, Vanheel H, Nelissen I, Witters H, Van Den Heuvel R, Van Tendeloo V, Schoeters G, Hooyberghs J. 2010. Assessment of chemical skin-sensitizing potency by an in vitro assay based on human dendritic cells. Toxicol Sci. 116(1):122–129. doi: 10.1093/toxsci/kfq108.
   PubMed Web of Science ®Google Scholar
• Landsteiner K, Jacobs J. 1935. Studies on the sensitization of animals with simple chemical compounds. J Exp Med. 61(5):643–656. doi: 10.1084/jem.61.5.643.
   PubMedGoogle Scholar
• Lee C-U, Grossmann TN. 2012. Reversible covalent inhibition of a protein target. Angew. Chem. Int. Ed. 51(35):8699–8700.
   PubMed Web of Science ®Google Scholar
• Lindberg T, de Ávila RI, Zeller KS, Levander F, Eriksson D, Chawade A, Lindstedt M. 2020. An integrated transcriptomic- and proteomic-based approach to evaluate the human skin sensitization potential of glyphosate and its commercial agrochemical formulations. J Proteomics. 217:103647. doi: 10.1016/j.jprot.2020.103647.
   PubMed Web of Science ®Google Scholar
• Lindberg T, Forreryd A, Bergendorff O, Lindstedt M, Zeller KS. 2019. In vitro assessment of mechanistic events induced by structurally related chemical rubber sensitizers. Toxicol In Vitro. 60:144–153. doi: 10.1016/j.tiv.2019.05.006.
   PubMed Web of Science ®Google Scholar
• Lu K, Hsiao Y-C, Liu C-W, Schoeny R, Gentry R, Starr TB. 2022. A review of stable isotope labeling and mass spectrometry methods to distinguish exogenous from endogenous DNA adducts and improve dose–response assessments. Chem Res Toxicol. 35(1):7–29. doi: 10.1021/acs.chemrestox.1c00212.
   PubMed Web of Science ®Google Scholar
• Łuczaj W, Gęgotek A, Skrzydlewska E. 2017. Antioxidants and HNE in redox homeostasis. Free Radic Biol Med. 111:87–101. doi: 10.1016/j.freeradbiomed.2016.11.033.
   PubMed Web of Science ®Google Scholar
• Luís A, Martins JD, Silva A, Ferreira I, Cruz MT, Neves BM. 2014. Oxidative stress-dependent activation of the eIF2α–ATF4 unfolded protein response branch by skin sensitizer 1-fluoro-2,4-dinitrobenzene modulates dendritic-like cell maturation and inflammatory status in a biphasic manner. Free Radic Biol Med. 77:217–229. doi: 10.1016/j.freeradbiomed.2014.09.008.
   PubMed Web of Science ®Google Scholar
• Lyss G, Knorre A, Schmidt TJ, Pahl HL, Merfort I. 1998. The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65. J Biol Chem. 273(50):33508–33516. doi: 10.1074/jbc.273.50.33508.
   PubMed Web of Science ®Google Scholar
• Manevski N, Swart P, Balavenkatraman KK, Bertschi B, Camenisch G, Kretz O, Schiller H, Walles M, Ling B, Wettstein R, et al. 2015. Phase II metabolism in human skin: skin explants show full coverage for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. Drug Metab Dispos. 43(1):126–139. doi: 10.1124/dmd.114.060350.
   PubMed Web of Science ®Google Scholar
• Marnett LJ, Riggins JN, West JD. 2003. Endogenous generation of reactive oxidants and electrophiles and their reactions with DNA and protein. J Clin Invest. 111(5):583–593. doi: 10.1172/JCI200318022.
   PubMed Web of Science ®Google Scholar
• Martin SF. 2017. The role of the innate immune system in allergic contact dermatitis. Allergol Select. 1(1):39–43. doi: 10.5414/ALX01274E.
   PubMedGoogle Scholar
• Martin SF, Esser PR, Weber FC, Jakob T, Freudenberg MA, Schmidt M, Goebeler M. 2011. Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergy. 66(9):1152–1163. doi: 10.1111/j.1398-9995.2011.02652.x.
   PubMed Web of Science ®Google Scholar
• Matos TJ, Jaleco SP, Gonçalo M, Duarte CB, Lopes MC. 2005. Release of IL-1beta via IL-1beta-converting enzyme in a skin dendritic cell line exposed to 2,4-dinitrofluorobenzene. Mediators Inflamm. 2005(3):131–138. doi: 10.1155/MI.2005.131.
   PubMedGoogle Scholar
• Mattii M, Ayala F, Balato N, Filotico R, Lembo S, Schiattarella M, Patruno C, Marone G, Balato A. 2013. The balance between pro- and anti-inflammatory cytokines is crucial in human allergic contact dermatitis pathogenesis: the role of IL-1 family members. Exp Dermatol. 22(12):813–819. doi: 10.1111/exd.12272.
   PubMed Web of Science ®Google Scholar
• Mayumi N, Watanabe E, Norose Y, Watari E, Kawana S, Geijtenbeek TBH, Takahashi H. 2013. E-cadherin interactions are required for Langerhans cell differentiation. Eur J Immunol. 43(1):270–280. doi: 10.1002/eji.201242654.
   PubMed Web of Science ®Google Scholar
• McKim JM, Jr., Keller DJ, 3rd, Gorski JR. 2012. An in vitro method for detecting chemical sensitization using human reconstructed skin models and its applicability to cosmetic, pharmaceutical, and medical device safety testing. Cutan Ocul Toxicol. 31(4):292–305. doi: 10.3109/15569527.2012.667031.
   PubMed Web of Science ®Google Scholar
• Mee JB, Alam Y, Groves RW. 2000. Human keratinocytes constitutively produce but do not process interleukin-18. Br J Dermatol. 143(2):330–336. doi: 10.1046/j.1365-2133.2000.03759.x.
   PubMed Web of Science ®Google Scholar
• Mehrotra P, Mishra KP, Raman G, Banerjee G. 2005. Differential regulation of free radicals (reactive oxygen and nitrogen species) by contact allergens and irritants in human keratinocyte cell line. Toxicol Mech Methods. 15(5):343–350. doi: 10.1080/15376520500191490.
   PubMed Web of Science ®Google Scholar
• Merad M, Ginhoux F, Collin M. 2008. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol. 8(12):935–947. doi: 10.1038/nri2455.
   PubMed Web of Science ®Google Scholar
• Metz B, Kersten GF, Baart GJ, de Jong A, Meiring H, ten Hove J, van Steenbergen MJ, Hennink WE, Crommelin DJ, Jiskoot W. 2006. Identification of formaldehyde-induced modifications in proteins: reactions with insulin. Bioconjug Chem. 17(3):815–822. doi: 10.1021/bc050340f.
   PubMed Web of Science ®Google Scholar
• Metz B, Kersten GFA, Hoogerhout P, Brugghe HF, Timmermans HAM, de Jong A, Meiring H, ten Hove J, Hennink WE, Crommelin DJA, et al. 2004. Identification of formaldehyde-induced modifications in proteins: reactions with model peptides. J Biol Chem. 279(8):6235–6243. doi: 10.1074/jbc.M310752200.
   PubMed Web of Science ®Google Scholar
• Michiels TJM, Schöneich C, Hamzink MRJ, Meiring HD, Kersten GFA, Jiskoot W, Metz B. 2020. Novel formaldehyde-induced modifications of lysine residue pairs in peptides and proteins: identification and relevance to vaccine development. Mol Pharm. 17(11):4375–4385. doi: 10.1021/acs.molpharmaceut.0c00851.
   PubMedGoogle Scholar
• Migneault I, Dartiguenave C, Bertrand MJ, Waldron KC. 2004. Glutaraldehyde: behavior in aqueous solution, reaction with proteins, and application to enzyme crosslinking. Biotechniques. 37(5):790–802. doi: 10.2144/04375RV01.
   PubMed Web of Science ®Google Scholar
• Mizuashi M, Ohtani T, Nakagawa S, Aiba S. 2005. Redox imbalance induced by contact sensitizers triggers the maturation of dendritic cells. J Invest Dermatol. 124(3):579–586. doi: 10.1111/j.0022-202X.2005.23624.x.
   PubMed Web of Science ®Google Scholar
• Mizumoto N, Mummert ME, Shalhevet D, Takashima A. 2003. Keratinocyte ATP release assay for testing skin-irritating potentials of structurally diverse chemicals. J Invest Dermatol. 121(5):1066–1072. doi: 10.1046/j.1523-1747.2003.12558.x.
   PubMed Web of Science ®Google Scholar
• Mol M, Regazzoni L, Altomare A, Degani G, Carini M, Vistoli G, Aldini G. 2017. Enzymatic and non-enzymatic detoxification of 4-hydroxynonenal: methodological aspects and biological consequences. Free Radic Biol Med. 111:328–344. doi: 10.1016/j.freeradbiomed.2017.01.036.
   PubMed Web of Science ®Google Scholar
• Moll R, Divo M, Langbein L. 2008. The human keratins: biology and pathology. Histochem Cell Biol. 129(6):705–733. doi: 10.1007/s00418-008-0435-6.
   PubMed Web of Science ®Google Scholar
• Moussallieh FM, Moss E, Elbayed K, Lereaux G, Tourneix F, Lepoittevin JP. 2020. Modifications induced by chemical skin allergens on the metabolome of reconstructed human epidermis: a pilot high-resolution magic angle spinning nuclear magnetic resonance study. Contact Dermatitis. 82(3):137–146. doi: 10.1111/cod.13415.
   PubMed Web of Science ®Google Scholar
• Naik SM, Cannon G, Burbach GJ, Singh SR, Swerlick RA, Wilcox JN, Ansel JC, Caughman SW. 1999. Human keratinocytes constitutively express interleukin-18 and secrete biologically active interleukin-18 after treatment with pro-inflammatory mediators and dinitrochlorobenzene. J Invest Dermatol. 113(5):766–772. doi: 10.1046/j.1523-1747.1999.00750.x.
   PubMed Web of Science ®Google Scholar
• Nakahara T, Moroi Y, Uchi H, Furue M. 2006. Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement. J Dermatol Sci. 42(1):1–11. doi: 10.1016/j.jdermsci.2005.11.004.
   PubMed Web of Science ®Google Scholar
• Natsch A. 2023. Integrated skin sensitization assessment based on OECD methods (III): adding human data to the assessment. ALTEX. 40(4):571–583. doi: 10.14573/altex.2302081.
   PubMedGoogle Scholar
• Natsch A, Emter R. 2016. Nrf2 activation as a key event triggered by skin sensitisers: the development of the stable KeratinoSens reporter gene assay. Altern Lab Anim. 44(5):443–451. doi: 10.1177/026119291604400513.
   PubMed Web of Science ®Google Scholar
• Natsch A, Emter R. 2017. Reaction chemistry to characterize the molecular initiating event in skin sensitization: a journey to be continued. Chem Res Toxicol. 30(1):315–331. doi: 10.1021/acs.chemrestox.6b00365.
   PubMed Web of Science ®Google Scholar
• Natsch A, Emter R, Haupt T, Ellis G. 2018. Deriving a no expected sensitization induction level for fragrance ingredients without animal testing: an integrated approach applied to specific case studies. Toxicol Sci. 165(1):170–185. doi: 10.1093/toxsci/kfy135.
   PubMed Web of Science ®Google Scholar
• Natsch A, Gerberick GF. 2022a. Integrated skin sensitization assessment based on OECD methods (I): deriving a point of departure for risk assessment. ALTEX. 39(4):636–646. doi: 10.14573/altex.2201141s4.
   PubMedGoogle Scholar
• Natsch A, Gerberick GF. 2022b. Integrated skin sensitization assessment based on OECD methods (II): hazard and potency by combining kinetic peptide reactivity and the “2 out of 3” defined approach. ALTEX. 39(4):647–655. doi: 10.14573/altex.2201142s4.
   PubMedGoogle Scholar
• Natsch A, Gfeller H. 2008. LC-MS-based characterization of the peptide reactivity of chemicals to improve the in vitro prediction of the skin sensitization potential. Toxicol Sci. 106(2):464–478. doi: 10.1093/toxsci/kfn194.
   PubMed Web of Science ®Google Scholar
• Natsch A, Gfeller H, Rothaupt M, Ellis G. 2007. Utility and limitations of a peptide reactivity assay to predict fragrance allergens in vitro. Toxicol In Vitro. 21(7):1220–1226. doi: 10.1016/j.tiv.2007.03.016.
   PubMed Web of Science ®Google Scholar
• Natsch A, Haupt T, Laue H. 2011. Relating skin sensitizing potency to chemical reactivity: reactive Michael acceptors inhibit NF-κB signaling and are less sensitizing than S(N)Ar- and S(N)2- reactive chemicals. Chem Res Toxicol. 24(11):2018–2027. doi: 10.1021/tx2003678.
   PubMed Web of Science ®Google Scholar
• Natsch A, Haupt T, Wareing B, Landsiedel R, Kolle SN. 2020. Predictivity of the kinetic direct peptide reactivity assay (kDPRA) for sensitizer potency assessment and GHS subclassification. ALTEX. 37(4):652–664.
   PubMedGoogle Scholar
• Ndreu L, Erber LN, Törnqvist M, Tretyakova NY, Karlsson I. 2020. Characterizing adduct formation of electrophilic skin allergens with human serum albumin and hemoglobin. Chem Res Toxicol. 33(10):2623–2636. doi: 10.1021/acs.chemrestox.0c00271.
   PubMed Web of Science ®Google Scholar
• Ndreu L, Sasse S, Karlberg AT, Karlsson I. 2022. Haptenation of macrophage migration inhibitory factor: a potential biomarker for contact hypersensitivity. Front Toxicol. 4:856614. doi: 10.3389/ftox.2022.856614.
   PubMedGoogle Scholar
• Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R. 2008. Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. Br J Pharmacol. 153(1):6–20. doi: 10.1038/sj.bjp.0707395.
   PubMed Web of Science ®Google Scholar
• Nikitovic D, Berdiaki A, Galbiati V, Kavasi RM, Papale A, Tsatsakis A, Tzanakakis GN, Corsini E. 2015. Hyaluronan regulates chemical allergen-induced IL-18 production in human keratinocytes. Toxicol Lett. 232(1):89–97. doi: 10.1016/j.toxlet.2014.09.026.
   PubMed Web of Science ®Google Scholar
• Niklasson IB, Ponting DJ, Luthman K, Karlberg AT. 2014. Bioactivation of cinnamic alcohol forms several strong skin sensitizers. Chem Res Toxicol. 27(4):568–575. doi: 10.1021/tx400428f.
   PubMed Web of Science ®Google Scholar
• Nordberg J, Arnér ESJ. 2001. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radical Biol Med. 31(11):1287–1312. doi: 10.1016/S0891-5849(01)00724-9.
   PubMed Web of Science ®Google Scholar
• Nukada Y, Miyazawa M, Kosaka N, Ito Y, Sakaguchi H, Nishiyama N. 2008. Production of IL-8 in THP-1 cells following contact allergen stimulation via mitogen-activated protein kinase activation or tumor necrosis factor-alpha production. J Toxicol Sci. 33(2):175–185. doi: 10.2131/jts.33.175.
   PubMed Web of Science ®Google Scholar
• OECD. 2010a. Test No. 429: skin sensitisation: Local lymph node assay, OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing. doi: 10.1787/9789264071100-en.
   Google Scholar
• OECD. 2010b. Test No. 442A: skin sensitization: Local lymph node assay: DA, OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing. doi: 10.1787/9789264090972-en.
   Google Scholar
• OECD. 2014. The adverse outcome pathway for skin sensitisation initiated by covalent binding to proteins. OECD series on testing and assessment, No. 168. Paris: OECD Publishing. doi: 10.1787/9789264221444-en.
   Google Scholar
• OECD. 2018. Test No. 442B: skin sensitization: Local lymph node assay: BrdU-ELISA or –FCM, OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing. doi: 10.1787/9789264090996-en.
   Google Scholar
• OECD. 2022a. Test No. 442D: in vitro skin sensitisation: ARE-Nrf2 Luciferase test method, OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing. doi: 10.1787/9789264229822-en.
   Google Scholar
• OECD. 2022b. Test No. 406: skin sensitisation, OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing. doi: 10.1787/9789264070660-en.
   Google Scholar
• OECD. 2022c. Report on considerations from case studies on integrated approaches for testing and assessment (IATA). OECD Series on Testing and Assessment No 369. Paris: OECD Publishing.
   Google Scholar
• OECD. 2023a. Guideline No. 497: defined approaches on skin sensitisation, OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing. doi: 10.1787/b92879a4-en.
   Google Scholar
• OECD. 2023b. Test No. 442C: in chemico skin sensitisation: assays addressing the adverse outcome pathway key event on covalent binding to proteins, OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing. doi: 10.1787/9789264229709-en.
   Google Scholar
• OECD. 2023c. Test No. 442E: in vitro skin sensitisation: in vitro skin sensitisation assays addressing the key event on activation of dendritic cells on the adverse outcome pathway for skin sensitisation, OECD guidelines for the testing of chemicals, Section 4. Paris: OECD Publishing, Paris. doi: 10.1787/9789264264359-en
   Google Scholar
• Oesch F, Fabian E, Guth K, Landsiedel R. 2014. Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models. Arch Toxicol. 88(12):2135–2190. doi: 10.1007/s00204-014-1382-8.
   PubMed Web of Science ®Google Scholar
• Pamplona R. 2011. Advanced lipoxidation end-products. Chem Biol Interact. 192(1–2):14–20. doi: 10.1016/j.cbi.2011.01.007.
   PubMed Web of Science ®Google Scholar
• Papac-Milicevic N, Busch CJL, Binder CJ. 2016. Chapter one - Malondialdehyde epitopes as targets of immunity and the implications for atherosclerosis. In: Alt FW, editor. Advances in immunology. Cambridge (MA): Academic Press; p. 1–59.
   Google Scholar
• Parkinson E, Aleksic M, Arthur R, Regufe Da Mota S, Cubberley R, Skipp PJ. 2020a. Proteomic analysis of haptenation by skin sensitisers: diphencyprone and ethyl acrylate. Toxicol In Vitro. 62:104697. doi: 10.1016/j.tiv.2019.104697.
   PubMed Web of Science ®Google Scholar
• Parkinson E, Aleksic M, Cubberley R, Kaur-Atwal G, Vissers JPC, Skipp P. 2018. Determination of protein haptenation by chemical sensitisers within the complexity of the human skin proteome. Toxicol Sci. 162(2):429–438. doi: 10.1093/toxsci/kfx265.
   PubMed Web of Science ®Google Scholar
• Parkinson E, Aleksic M, Kukic P, Bailey A, Cubberley R, Skipp P. 2020b. Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 445:152603. doi: 10.1016/j.tox.2020.152603.
   PubMed Web of Science ®Google Scholar
• Parkinson E, Boyd P, Aleksic M, Cubberley R, O’Connor D, Skipp P. 2014. Stable isotope labeling method for the investigation of protein haptenation by electrophilic skin sensitizers. Toxicol Sci. 142(1):239–249. doi: 10.1093/toxsci/kfu168.
   PubMed Web of Science ®Google Scholar
• Patlewicz G, Casati S, Basketter DA, Asturiol D, Roberts DW, Lepoittevin J-P, Worth AP, Aschberger K. 2016. Can currently available non-animal methods detect pre and pro-haptens relevant for skin sensitization? Regul Toxicol Pharmacol. 82:147–155. doi: 10.1016/j.yrtph.2016.08.007.
   PubMed Web of Science ®Google Scholar
• Patlewicz GY, Wright ZM, Basketter DA, Pease CK, Lepoittevin J-P, Arnau EG. 2002. Structure-activity relationships for selected fragrance allergens. Contact Dermatitis. 47(4):219–226. doi: 10.1034/j.1600-0536.2002.470406.x.
   PubMed Web of Science ®Google Scholar
• Piroird C, Ovigne JM, Rousset F, Martinozzi-Teissier S, Gomes C, Cotovio J, Alépée N. 2015. The myeloid U937 skin sensitization test (U-SENS) addresses the activation of dendritic cell event in the adverse outcome pathway for skin sensitization. Toxicol In Vitro. 29(5):901–916. doi: 10.1016/j.tiv.2015.03.009.
   PubMed Web of Science ®Google Scholar
• Pizzorno J. 2014. Glutathione! Integr Med (Encinitas). 13(1):8–12.
   Google Scholar
• Ponec M, Weerheim A, Kempenaar J, Mommaas AM, Nugteren DH. 1988. Lipid composition of cultured human keratinocytes in relation to their differentiation. J Lipid Res. 29(7):949–961. doi: 10.1016/S0022-2275(20)38476-5.
   PubMed Web of Science ®Google Scholar
• Rambukkana A, Pistoor FH, Bos JD, Kapsenberg ML, Das PK. 1996. Effects of contact allergens on human Langerhans cells in skin organ culture: migration, modulation of cell surface molecules, and early expression of interleukin-1 beta protein. Lab Invest. 74(2):422–436.
   PubMed Web of Science ®Google Scholar
• Ramirez T, Mehling A, Kolle SN, Wruck CJ, Teubner W, Eltze T, Aumann A, Urbisch D, van Ravenzwaay B, Landsiedel R. 2014. LuSens: a keratinocyte based ARE reporter gene assay for use in integrated testing strategies for skin sensitization hazard identification. Toxicol In Vitro. 28(8):1482–1497. doi: 10.1016/j.tiv.2014.08.002.
   PubMed Web of Science ®Google Scholar
• Read A, Schröder M. 2021. The unfolded protein response: an overview. Biology (Basel). 10(5):384. doi: 10.3390/biology10050384.
   PubMedGoogle Scholar
• Reynolds G, Reynolds J, Gilmour N, Cubberley R, Spriggs S, Aptula A, Przybylak K, Windebank S, Maxwell G, Baltazar MT. 2021. A hypothetical skin sensitisation next generation risk assessment for coumarin in cosmetic products. Regul Toxicol Pharmacol. 127:105075. doi: 10.1016/j.yrtph.2021.105075.
   PubMed Web of Science ®Google Scholar
• Reynolds J, Gilmour N, Baltazar MT, Reynolds G, Windebank S, Maxwell G. 2022. Decision making in next generation risk assessment for skin allergy: using historical clinical experience to benchmark risk. Regul Toxicol Pharmacol. 134:105219. doi: 10.1016/j.yrtph.2022.105219.
   PubMed Web of Science ®Google Scholar
• Reynolds J, Gilmour N, Reynolds G, Reinkeb EN, Strickland J, Germolec D, Allen DG, Maxwell G, Kleinstreuer NC. 2024. Deriving a point of departure for Quantitative Risk Assessment for Skin Sensitisation: defined approach application to isothiazolinones. Manuscript in preparation.
   Google Scholar
• Reynolds J, MacKay C, Gilmour N, Miguel-Vilumbrales D, Maxwell G. 2019. Probabilistic prediction of human skin sensitiser potency for use in next generation risk assessment. Comput Toxicol. 9:36–49. doi: 10.1016/j.comtox.2018.10.004.
   Google Scholar
• Roberts DW, Aptula AO, Patlewicz G. 2007. Electrophilic chemistry related to skin sensitization. Reaction mechanistic applicability domain classification for a published data set of 106 chemicals tested in the mouse local lymph node assay. Chem Res Toxicol. 20(1):44–60. doi: 10.1021/tx060121y.
   PubMed Web of Science ®Google Scholar
• Roberts DW, Natsch A. 2009. High throughput kinetic profiling approach for covalent binding to peptides: application to skin sensitization potency of Michael acceptor electrophiles. Chem Res Toxicol. 22(3):592–603. doi: 10.1021/tx800431x.
   PubMed Web of Science ®Google Scholar
• Roberts DW, Schultz TW, Api AM. 2017. Skin sensitization QMM for HRIPT NOEL data: aldehyde Schiff-Base domain. Chem Res Toxicol. 30(6):1309–1316. doi: 10.1021/acs.chemrestox.7b00050.
   PubMed Web of Science ®Google Scholar
• Rustom A, Saffrich R, Markovic I, Walther P, Gerdes H-H. 2004. Nanotubular highways for intercellular organelle transport. Science. 303(5660):1007–1010. doi: 10.1126/science.1093133.
   PubMed Web of Science ®Google Scholar
• Ryan CA, Troutman JA, Kern PS, Quijano M, Dobson RLM, Jian Dai H, Burt TM, Gerberick GF. 2020. Refinement of the peroxidase peptide reactivity assay and prediction model for assessing skin sensitization potential. Toxicol Sci. 178(1):88–103. doi: 10.1093/toxsci/kfaa137.
   PubMed Web of Science ®Google Scholar
• Saito K, Takenouchi O, Nukada Y, Miyazawa M, Sakaguchi H. 2017. An in vitro skin sensitization assay termed EpiSensA for broad sets of chemicals including lipophilic chemicals and pre/pro-haptens. Toxicol In Vitro. 40:11–25. doi: 10.1016/j.tiv.2016.12.005.
   PubMed Web of Science ®Google Scholar
• Sánchez-Gómez FJ, Díez-Dacal B, García-Martín E, Agúndez JA, Pajares MA, Pérez-Sala D. 2016. Detoxifying enzymes at the cross-roads of inflammation, oxidative stress, and drug hypersensitivity: role of glutathione transferase P1-1 and aldose reductase. Front Pharmacol. 7:237. doi: 10.3389/fphar.2016.00237.
   PubMed Web of Science ®Google Scholar
• Sand J, Haertel E, Biedermann T, Contassot E, Reichmann E, French LE, Werner S, Beer HD. 2018. Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes. Cell Death Dis. 9(2):24. doi: 10.1038/s41419-017-0009-4.
   PubMedGoogle Scholar
• Sanderson PN, Simpson W, Cubberley R, Aleksic M, Gutsell S, Russell PJ. 2016. Mechanistic understanding of molecular initiating events (MIEs) using NMR spectroscopy. Toxicol Res (Camb). 5(1):34–44. doi: 10.1039/c5tx00246j.
   PubMed Web of Science ®Google Scholar
• Schaefer L. 2014. Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem. 289(51):35237–35245. doi: 10.1074/jbc.R114.619304.
   PubMed Web of Science ®Google Scholar
• Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR. 2006. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol. 177(2):1272–1281. doi: 10.4049/jimmunol.177.2.1272.
   PubMed Web of Science ®Google Scholar
• Scheinman PL, Vocanson M, Thyssen JP, Johansen JD, Nixon RL, Dear K, Botto NC, Morot J, Goldminz AM. 2021. Contact dermatitis. Nat Rev Dis Primers. 7(1):38. doi: 10.1038/s41572-021-00271-4.
   PubMed Web of Science ®Google Scholar
• Schnurr M, Then F, Galambos P, Scholz C, Siegmund B, Endres S, Eigler A. 2000. Extracellular ATP and TNF-alpha synergize in the activation and maturation of human dendritic cells. J Immunol. 165(8):4704–4709. doi: 10.4049/jimmunol.165.8.4704.
   PubMed Web of Science ®Google Scholar
• Schultz TW, Yarbrough JW, Johnson EL. 2005. Structure–activity relationships for reactivity of carbonyl-containing compounds with glutathione. SAR QSAR Environ Res. 16(4):313–322. doi: 10.1080/10659360500204152.
   PubMed Web of Science ®Google Scholar
• Schürer N, Köhne A, Schliep V, Barlag K, Goerz G. 1993. Lipid composition and synthesis of HaCaT cells, an immortalized human keratinocyte line, in comparison with normal human adult keratinocytes. Exp Dermatol. 2(4):179–185. doi: 10.1111/j.1600-0625.1993.tb00030.x.
   PubMedGoogle Scholar
• Schwensen JF, White IR, Thyssen JP, Menné T, Johansen JD. 2015. Failures in risk assessment and risk management for cosmetic preservatives in Europe and the impact on public health. Contact Dermatitis. 73(3):133–141. doi: 10.1111/cod.12446.
   PubMed Web of Science ®Google Scholar
• Simonsson C, Andersson SI, Stenfeldt A-L, Bergström J, Bauer B, Jonsson CA, Ericson MB, Broo KS. 2011. Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis. J Invest Dermatol. 131(7):1486–1493. doi: 10.1038/jid.2010.422.
   PubMed Web of Science ®Google Scholar
• Singleton H, Popple A, Gellatly N, Maxwell G, Williams J, Friedmann PS, Kimber I, Dearman RJ. 2016. Anti-hapten antibodies in response to skin sensitization. Contact Dermatitis. 74(4):197–204. doi: 10.1111/cod.12486.
   PubMed Web of Science ®Google Scholar
• Sousa BC, Pitt AR, Spickett CM. 2017. Chemistry and analysis of HNE and other prominent carbonyl-containing lipid oxidation compounds. Free Radic Biol Med. 111:294–308. doi: 10.1016/j.freeradbiomed.2017.02.003.
   PubMed Web of Science ®Google Scholar
• Spickett CM, Wiswedel I, Siems W, Zarkovic K, Zarkovic N. 2010. Advances in methods for the determination of biologically relevant lipid peroxidation products. Free Radic Res. 44(10):1172–1202. doi: 10.3109/10715762.2010.498476.
   PubMed Web of Science ®Google Scholar
• Spinu N, Cronin MTD, Enoch SJ, Madden JC, Worth AP. 2020. Quantitative adverse outcome pathway (qAOP) models for toxicity prediction. Arch Toxicol. 94(5):1497–1510. doi: 10.1007/s00204-020-02774-7.
   PubMed Web of Science ®Google Scholar
• Spriggs S, Cubberley R, Loadman P, Sheffield D, Wierzbicki A. 2018. A study of inter-individual variability in the Phase II metabolism of xenobiotics in human skin. Toxicol Lett. 292:63–72. doi: 10.1016/j.toxlet.2018.04.011.
   PubMed Web of Science ®Google Scholar
• Spriggs S, Sheffield D, Olayanju A, Kitteringham NR, Naisbitt DJ, Aleksic M. 2016. Effect of repeated daily dosing with 2,4-dinitrochlorobenzene on glutathione biosynthesis and Nrf2 activation in reconstructed human epidermis. Toxicol Sci. 154(1):5–15. doi: 10.1093/toxsci/kfw140.
   PubMed Web of Science ®Google Scholar
• Su Q, Igyártó BZ. 2019. Keratinocytes share gene expression fingerprint with epidermal Langerhans cells via mRNA transfer. J Invest Dermatol. 139(11):2313–2323.e8. doi: 10.1016/j.jid.2019.05.006.
   PubMed Web of Science ®Google Scholar
• Sullivan KM, Enoch SJ, Ezendam J, Sewald K, Roggen EL, Cochrane S. 2017. An adverse outcome pathway for sensitization of the respiratory tract by low-molecular-weight chemicals: building evidence to support the utility of in vitro and in silico methods in a regulatory context. Appl In Vitro Toxicol. 3(3):213–226. doi: 10.1089/aivt.2017.0010.
   Google Scholar
• Takahashi T, Kimura Y, Saito R, Nakajima Y, Ohmiya Y, Yamasaki K, Aiba S. 2011. An in vitro test to screen skin sensitizers using a stable THP-1-derived IL-8 reporter cell line, THP-G8. Toxicol Sci. 124(2):359–369. doi: 10.1093/toxsci/kfr237.
   PubMed Web of Science ®Google Scholar
• Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC. 2002. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med. 195(1):99–111. doi: 10.1084/jem.20001858.
   PubMed Web of Science ®Google Scholar
• Trompezinski S, Migdal C, Tailhardat M, Le Varlet B, Courtellemont P, Haftek M, Serres M. 2008. Characterization of early events involved in human dendritic cell maturation induced by sensitizers: cross talk between MAPK signalling pathways. Toxicol Appl Pharmacol. 230(3):397–406. doi: 10.1016/j.taap.2008.03.012.
   PubMed Web of Science ®Google Scholar
• Troutman JA, Foertsch LM, Kern PS, Dai HJ, Quijano M, Dobson RLM, Lalko JF, Lepoittevin JP, Gerberick F. 2011. The incorporation of lysine into the peroxidase peptide reactivity assay for skin sensitization assessments. Toxicol Sci. 122(2):422–436. doi: 10.1093/toxsci/kfr101.
   PubMed Web of Science ®Google Scholar
• Tsujita-Inoue K, Atobe T, Hirota M, Ashikaga T, Kouzuki H. 2015. In silico risk assessment for skin sensitization using artificial neural network analysis. J Toxicol Sci. 40(2):193–209. doi: 10.2131/jts.40.193.
   PubMed Web of Science ®Google Scholar
• UN. 2021. Globally harmonised system of classification and labelling of chemicals (GHS). New York, Geneva: United Nations.
   Google Scholar
• Urbisch D, Becker M, Honarvar N, Kolle SN, Mehling A, Teubner W, Wareing B, Landsiedel R. 2016. Assessment of pre- and pro-haptens using non-animal test methods for skin sensitization. Chem Res Toxicol. 29(5):901–913. doi: 10.1021/acs.chemrestox.6b00055.
   PubMed Web of Science ®Google Scholar
• Uter W, Werfel T, Lepoittevin J-P, White IR. 2020. Contact allergy—emerging allergens and public health impact. Int J Environ Res Public Health. 17(7):2404. doi: 10.3390/ijerph17072404.
   PubMed Web of Science ®Google Scholar
• Vallion R, Kerdine-Römer S. 2022. Regulation of the immune response to contact sensitizers by Nrf2. Contact Dermatitis. 87(1):13–19. doi: 10.1111/cod.14073.
   PubMed Web of Science ®Google Scholar
• van der Veen JW, Hodemaekers H, Reus AA, Maas WJM, van Loveren H, Ezendam J. 2015. Human relevance of an in vitro gene signature in HaCaT for skin sensitization. Toxicol In Vitro. 29(1):81–84. doi: 10.1016/j.tiv.2014.08.010.
   PubMed Web of Science ®Google Scholar
• van der Veen JW, Paskel RF, Smits NA, Hodemaekers H, van Loveren H, Ezendam J. 2016. The involvement of the toll-like receptor signaling and Nrf2-Keap1 pathways in the in vitro regulation of IL-8 and HMOX1 for skin sensitization. J Immunotoxicol. 13(1):1–6. doi: 10.3109/1547691X.2014.975897.
   PubMed Web of Science ®Google Scholar
• van Vliet E, Kühnl J, Goebel C, Martinozzi-Teissier S, Alépée N, Ashikaga T, Blömeke B, Del Bufalo A, Cluzel M, Corsini E, et al. 2018. State-of-the-art and new options to assess T cell activation by skin sensitizers: cosmetics Europe workshop. ALTEX. 35(2):179–192. doi: 10.14573/altex.1709011.
   PubMedGoogle Scholar
• Wareing B, Urbisch D, Kolle SN, Honarvar N, Sauer UG, Mehling A, Landsiedel R. 2017. Prediction of skin sensitization potency sub-categories using peptide reactivity data. Toxicol In Vitro. 45(Pt 1):134–145. doi: 10.1016/j.tiv.2017.08.015.
   PubMedGoogle Scholar
• Watanabe H, Gaide O, Pétrilli V, Martinon F, Contassot E, Roques S, Kummer JA, Tschopp J, French LE. 2007. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol. 127(8):1956–1963. doi: 10.1038/sj.jid.5700819.
   PubMed Web of Science ®Google Scholar
• Yamamoto Y, Tahara H, Usami R, Kasahara T, Jimbo Y, Hioki T, Fujita M. 2015. A novel in chemico method to detect skin sensitizers in highly diluted reaction conditions. J Appl Toxicol. 35(11):1348–1360. doi: 10.1002/jat.3139.
   PubMed Web of Science ®Google Scholar
• Yang J, Tallman KA, Porter NA, Liebler DC. 2015. Quantitative chemoproteomics for site-specific analysis of protein alkylation by 4-hydroxy-2-nonenal in cells. Anal Chem. 87(5):2535–2541. doi: 10.1021/ac504685y.
   PubMed Web of Science ®Google Scholar
• Zeller KS, Forreryd A, Lindberg T, Gradin R, Chawade A, Lindstedt M. 2017. The GARD platform for potency assessment of skin sensitizing chemicals. ALTEX. 34(4):539–559. doi: 10.14573/altex.1701101.
   PubMedGoogle Scholar
• Zepter K, Häffner A, Soohoo LF, De Luca D, Tang HP, Fisher P, Chavinson J, Elmets CA. 1997. Induction of biologically active IL-1 beta-converting enzyme and mature IL-1 beta in human keratinocytes by inflammatory and immunologic stimuli. J Immunol (Baltimore, Md: 1950). 159(12):6203–6208. doi: 10.4049/jimmunol.159.12.6203.
   PubMed Web of Science ®Google Scholar
• Zgheib E, Gao W, Limonciel A, Aladjov H, Yang H, Tebby C, Gayraud G, Jennings P, Sachana M, Beltman JB, et al. 2019. Application of three approaches for quantitative AOP development to renal toxicity. Comput Toxicol. 11:1–13. doi: 10.1016/j.comtox.2019.02.001.
   Google Scholar
• Zhang H, Forman HJ. 2017. Signaling by 4-hydroxy-2-nonenal: exposure protocols, target selectivity and degradation. Arch Biochem Biophys. 617:145–154. doi: 10.1016/j.abb.2016.11.003.
   PubMed Web of Science ®Google Scholar
• Zhou S, Chan E, Duan W, Huang M, Chen YZ. 2005. Drug bioactivation, covalent binding to target proteins and toxicity relevance. Drug Metab Rev. 37(1):41–213. doi: 10.1081/dmr-200028812.
   PubMed Web of Science ®Google Scholar
• Zimniak P. 2011. Relationship of electrophilic stress to aging. Free Radic Biol Med. 51(6):1087–1105. doi: 10.1016/j.freeradbiomed.2011.05.039.
   PubMed Web of Science ®Google Scholar