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Title: | Development of an in chemico high-throughput screening method for the identification of skin sensitization potential | Authors: | Ferreira, Isabel Brites, Gonçalo Silva, Ana Caramelo, Francisco Oliveiros, Bárbara Neves, Bruno Miguel Cruz, Maria Teresa |
Keywords: | Skin sensitization; Direct peptide reactivity assay; In chemico method; Low-molecular-weight chemicals | Issue Date: | Sep-2023 | Publisher: | Springer Nature | Project: | This work was supported by the Cosmetic Europe in the scope of the project “Optimization of a defined approach for skin sensitizer potency integrating in silico, in chemico, and in vitro cell data for classifying chemicals accordingly to five categories (extreme, strong, moderate, weak and non-sensitizer)”. Isabel Ferreira and Gonçalo Brites were supported by a Doctoral Scholarship through FCT – Fundação para a Ciência e a Tecnologia under Grant Nos. SFRH/ BD/110717/2015 and PD/BDE/142926/2018, respectively. This work was also financed by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT, under projects UIDB/04539/2020, UIDP/04539/2020 and LA/P/0058/2020. Open access funding was provided by FCT|FCCN (b-on) | Serial title, monograph or event: | Archives of Toxicology | Volume: | 97 | Issue: | 9 | Abstract: | It is well established that chemical-peptide conjugation represents the molecular initiating event (MIE) in skin sensitization. This MIE has been successfully exploited in the development of in chemico peptide reactivity assays, with the Direct Peptide Reactivity Assay (DPRA) being validated as a screening tool for skin sensitization hazard as well as an OECD test guideline. This test relies on the use of a high-performance liquid chromatography/ultraviolet detection method to quantify chemical-peptide conjugation through measurement of the depletion of two synthetic peptides containing lysine or cysteine residues, which is labor-intensive and time-consuming. To improve assay throughput, sensitivity, and accuracy, we have developed a spectrophotometric assay for skin sensitization potential based on MIE measurement-the ProtReact assay. ProtReact is also a cheaper, faster, simpler, and more accessible alternative for the DPRA, giving comparable results. A set of 106 chemicals was tested with ProtReact and the peptide depletion values compared with those reported for the DPRA. The predictive capacity of both assays was evaluated with human reference data. ProtReact and DPRA assays show similar predictive capacities for hazard identification (75% and 74%, respectively), although ProtReact showed a higher specificity (86% versus 74%, respectively) and lower sensitivity (69% versus 73%). Overall, the results show that ProtReact assay described here represents an efficient, economic, and accurate assay for the prediction of skin sensitization potential of chemical haptens. | URI: | https://hdl.handle.net/10316/111948 | ISSN: | 0340-5761 1432-0738 |
DOI: | 10.1007/s00204-023-03550-z | Rights: | openAccess |
Appears in Collections: | I&D CIBB - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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