{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:49:48Z","timestamp":1780710588662,"version":"3.54.1"},"reference-count":25,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Counci","award":["MOST-110-2221-E-400-004-MY3"],"award-info":[{"award-number":["MOST-110-2221-E-400-004-MY3"]}]},{"name":"National Science and Technology Counci","award":["MOST-110-2313-B-002-051-"],"award-info":[{"award-number":["MOST-110-2313-B-002-051-"]}]},{"name":"National Science and Technology Counci","award":["109AS-24.1.2-PI-P3"],"award-info":[{"award-number":["109AS-24.1.2-PI-P3"]}]},{"name":"National Science and Technology Counci","award":["110AS-16.1.1-PI-P2"],"award-info":[{"award-number":["110AS-16.1.1-PI-P2"]}]},{"name":"National Science and Technology Counci","award":["111AS-13.1.1-PI-P2"],"award-info":[{"award-number":["111AS-13.1.1-PI-P2"]}]},{"name":"Taiwan Agricultural Chemicals and Toxic Substances Research Institute","award":["MOST-110-2221-E-400-004-MY3"],"award-info":[{"award-number":["MOST-110-2221-E-400-004-MY3"]}]},{"name":"Taiwan Agricultural Chemicals and Toxic Substances Research Institute","award":["MOST-110-2313-B-002-051-"],"award-info":[{"award-number":["MOST-110-2313-B-002-051-"]}]},{"name":"Taiwan Agricultural Chemicals and Toxic Substances Research Institute","award":["109AS-24.1.2-PI-P3"],"award-info":[{"award-number":["109AS-24.1.2-PI-P3"]}]},{"name":"Taiwan Agricultural Chemicals and Toxic Substances Research Institute","award":["110AS-16.1.1-PI-P2"],"award-info":[{"award-number":["110AS-16.1.1-PI-P2"]}]},{"name":"Taiwan Agricultural Chemicals and Toxic Substances Research Institute","award":["111AS-13.1.1-PI-P2"],"award-info":[{"award-number":["111AS-13.1.1-PI-P2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Skin sensitization is an important regulatory endpoint associated with allergic contact dermatitis. Recently, several adverse outcome pathway (AOP)-based alternative methods were developed to replace animal testing for evaluating skin sensitizers. The AOP-based assays were further integrated as a two-out-of-three method with good predictivity. However, the acquisition of experimental data is resource-intensive. In contrast, an integrated testing strategy (ITS) capable of maximizing the usage of laboratory data from AOP-based and in silico methods was developed as defined approaches (DAs) to both hazard and potency assessment. There are currently two in silico models, namely Derek Nexus and OECD QSAR Toolbox, evaluated in the OECD Testing Guideline No. 497. Since more advanced machine learning algorithms have been proposed for skin sensitization prediction, it is therefore desirable to evaluate their performance under the ITS framework. This study evaluated the performance of a new ITS DA (ITS-SkinSensPred) adopting a transfer learning-based SkinSensPred model. Results showed that the ITS-SkinSensPred has similar or slightly better performance compared to the other ITS models. SkinSensPred-based ITS is expected to be a promising method for assessing skin sensitization.<\/jats:p>","DOI":"10.3390\/ijerph191912856","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"12856","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["SkinSensPred as a Promising in Silico Tool for Integrated Testing Strategy on Skin Sensitization"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6163-120X","authenticated-orcid":false,"given":"Shan-Shan","family":"Wang","sequence":"first","affiliation":[{"name":"Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1272-1513","authenticated-orcid":false,"given":"Chia-Chi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3011-8440","authenticated-orcid":false,"given":"Chun-Wei","family":"Tung","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.yrtph.2018.03.003","article-title":"International Regulatory Requirements for Skin Sensitization Testing","volume":"95","author":"Daniel","year":"2018","journal-title":"Regul. Toxicol. Pharmacol. RTP"},{"key":"ref_2","unstructured":"OECD (2021). Test No. 406: Skin Sensitisation: OECD Guidelines for the Testing of Chemicals, OECD Publishing."},{"key":"ref_3","unstructured":"OECD (2010). Test No. 429: Skin Sensitisation: Local Lymph Node Assay, OECD Publishing."},{"key":"ref_4","unstructured":"OECD (2021). Test No. 442C: In Chemico Skin Sensitisation Assays Addressing the Adverse Outcome Pathway Key Event on Covalent Binding to Proteins, OECD Publishing."},{"key":"ref_5","unstructured":"OECD (2018). Test No. 442D: In Vitro Skin Sensitisation ARE-Nrf2 Luciferase Test Method, OECD Publishing."},{"key":"ref_6","unstructured":"OECD (2022). 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 Publishing."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1080\/10408444.2018.1528207","article-title":"Computational Approaches for Skin Sensitization Prediction","volume":"48","author":"Wilm","year":"2018","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_8","first-page":"33","article-title":"Evaluation of the Global Performance of Eight in Silico Skin Sensitization Models Using Human Data","volume":"38","author":"Golden","year":"2021","journal-title":"ALTEX"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"655771","DOI":"10.3389\/fphar.2021.655771","article-title":"In Silico Prediction of Skin Sensitization: Quo Vadis?","volume":"12","author":"Ta","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/jat.3479","article-title":"Non-Animal Assessment of Skin Sensitization Hazard: Is an Integrated Testing Strategy Needed, and If so What Should Be Integrated?","volume":"38","author":"Roberts","year":"2018","journal-title":"J. Appl. Toxicol. JAT"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1080\/10408444.2018.1429386","article-title":"Non-Animal Methods to Predict Skin Sensitization (II): An Assessment of Defined Approaches","volume":"48","author":"Kleinstreuer","year":"2018","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.yrtph.2018.11.001","article-title":"A Defined Approach for Predicting Skin Sensitisation Hazard and Potency Based on the Guided Integration of in Silico, in Chemico and in Vitro Data Using Exclusion Criteria","volume":"101","author":"Macmillan","year":"2019","journal-title":"Regul. Toxicol. Pharmacol. RTP"},{"key":"ref_13","unstructured":"OECD (2021). Supporting Document to the OECD Guideline 497 on Defined Approaches for Skin Sensitisation, OECD Publishing."},{"key":"ref_14","unstructured":"(2022, September 01). Lhasa Limited Derek Nexus v6.1.0 [WWW Document]. Available online: https:\/\/www.lhasalimited.org\/products\/derek-nexus.htm."},{"key":"ref_15","unstructured":"OECD (2022, September 01). The OECD QSAR Toolbox v4.5. Available online: https:\/\/qsartoolbox.org\/."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.comtox.2019.01.006","article-title":"Automated and Standardized Workflows in the OECD QSAR Toolbox","volume":"10","author":"Yordanova","year":"2019","journal-title":"Comput. Toxicol."},{"key":"ref_17","unstructured":"United Nations (UN) (2019). Globally Harmonized System of Classification and Labelling of Chemicals (GHS), United Nations Publications. [8th ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"852856","DOI":"10.3389\/ftox.2022.852856","article-title":"Application of Defined Approaches for Skin Sensitization to Agrochemical Products","volume":"4","author":"Strickland","year":"2022","journal-title":"Front. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.yrtph.2018.02.014","article-title":"Mechanism-Informed Read-across Assessment of Skin Sensitizers Based on SkinSensDB","volume":"94","author":"Tung","year":"2018","journal-title":"Regul. Toxicol. Pharmacol. RTP"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00204-019-02420-x","article-title":"Transfer Learning for Predicting Human Skin Sensitizers","volume":"93","author":"Tung","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1021\/acs.chemrestox.0c00186","article-title":"Pred-Skin: A Web Portal for Accurate Prediction of Human Skin Sensitizers","volume":"34","author":"Borba","year":"2021","journal-title":"Chem. Res. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13321-017-0194-2","article-title":"SkinSensDB: A Curated Database for Skin Sensitization Assays","volume":"9","author":"Wang","year":"2017","journal-title":"J. Cheminform."},{"key":"ref_23","unstructured":"Kuhn, M. (2022, September 01). Caret: Classification and Regression Training. Available online: https:\/\/CRAN.R-project.org\/package=caret."},{"key":"ref_24","unstructured":"Wickham, H., Fran\u00e7ois, R., Henry, L., and M\u00fcller, K. (2022, September 01). Dplyr: A Grammar of Data Manipulation. Available online: https:\/\/CRAN.R-project.org\/package=dplyr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1080\/1062936X.2018.1518261","article-title":"Evaluation and Improvement of QSAR Predictions of Skin Sensitization for Pesticides","volume":"29","author":"Braeuning","year":"2018","journal-title":"SAR QSAR Environ. Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/19\/12856\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:47:53Z","timestamp":1760143673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/19\/12856"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,7]]},"references-count":25,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijerph191912856"],"URL":"https:\/\/doi.org\/10.3390\/ijerph191912856","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,7]]}}}