{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:25:02Z","timestamp":1788999902161,"version":"build-2803163510"},"reference-count":155,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Skin sensitization is a complex biological process induced by a wide range of chemicals, from single molecules to complex mixtures and finished products. While single chemical entities were used to design and validate sophisticated safety assessment assays, complex chemistries have proven challenging to test in practice using these methods. These assays range from in silico and in chemico methods to cell-based and reconstructed tissues-based approaches and target the key events now grouped within the Adverse Outcome Pathway. We focused our analysis on the use of New Approach Methodologies for skin sensitization assessments of complex mixtures, botanicals, medical and wearable devices, agrochemicals, and pollutants. We present the defined approaches that integrate these technologies, aligning with the principles of the replacement, reduction, and refinement of animal testing. We also detail the known challenges posed by these product classes in terms of testing and data interpretation. Our analysis indicates that validated and non-validated NAMs have shown some success in predicting skin sensitization potential across the product categories reviewed.<\/jats:p>","DOI":"10.3390\/toxics13080693","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T15:53:37Z","timestamp":1755705217000},"page":"693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["New Horizons in Skin Sensitization Assessment of Complex Mixtures: The Use of New Approach Methodologies Beyond Regulatory Approaches"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3611-2314","authenticated-orcid":false,"given":"Argel","family":"Islas-Robles","sequence":"first","affiliation":[{"name":"Department of Skin Sensitization, Institute for In Vitro Sciences, Inc. (IIVS), Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-8572","authenticated-orcid":false,"given":"Meera","family":"Ramani","sequence":"additional","affiliation":[{"name":"Department of Skin Sensitization, Institute for In Vitro Sciences, Inc. (IIVS), Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1614-3204","authenticated-orcid":false,"given":"Jakeb","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Skin Sensitization, Institute for In Vitro Sciences, Inc. (IIVS), Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-0334","authenticated-orcid":false,"given":"Gertrude-Emilia","family":"Costin","sequence":"additional","affiliation":[{"name":"Department of Skin Sensitization, Institute for In Vitro Sciences, Inc. (IIVS), Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s40521-015-0066-9","article-title":"Cosmeceutical Contact Dermatitis\u2014Cautions To Herbals","volume":"2","author":"Oliver","year":"2015","journal-title":"Curr. Treat. Options Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/cod.13119","article-title":"Prevalence of Contact Allergy in the General Population: A Systematic Review and Meta-analysis","volume":"80","author":"Alinaghi","year":"2019","journal-title":"Contact Dermat."},{"key":"ref_3","unstructured":"Scientific Committee on Consumer Safety SCCS (2012). 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