{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:54:37Z","timestamp":1785322477707,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"am","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon Europe Research and Innovation Programme","award":["101057014"],"award-info":[{"award-number":["101057014"]}]},{"name":"Swiss Federal Office for the Environment"},{"name":"RECETOX Research Infrastructure","award":["LM2023069"],"award-info":[{"award-number":["LM2023069"]}]},{"DOI":"10.13039\/501100001823","name":"the Ministry of Education, Youth and Sports","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The hazard identification of chemicals is a key step of the \u201cSafe and Sustainable by Design\u201d (SSbD) framework introduced by the European Commission, aiming to eliminate hazardous substances early in innovation. In this context, in silico methods such as (Quantitative) Structure\u2013Activity Relationship ((Q)SAR) models offer rapid, cost-effective, and animal-free alternatives for early-stage hazard screening. The Partnership for the Assessment of Risks from Chemicals (PARC) is developing a toolbox to facilitate SSbD assessments containing numerous (Q)SAR models. Challenges, however, exist in using and combining multiple in silico tools. Here, we developed a workflow to assess chemical hazards using multiple in silico tools within the PARC toolbox. The workflow consists of three phases: (1) the preparation stage, (2) running the models, and (3) the evaluation stage. To demonstrate the approach, we applied it to a case study comparing bisphenol A, isosorbide, and bisphenol AP. Tools from the PARC toolbox were screened for relevance, transparency, and open access availability. Only models aligned with SSbD-required endpoints and adequately documented via (Q)SAR Model Reporting Formats were retained. The properties assessed in this study cover carcinogenicity, germ cell mutagenicity, reproductive toxicity, endocrine disruption, persistence, bioaccumulation, and aquatic toxicity. Predictions were filtered using applicability domain criteria and reliability scores. Next, three strategies were applied for integrating different model outputs. Model agreement varied across endpoints and integration methods. This emphasizes the possibility of different SSbD assessment outcomes and thus the need for transparent documentation of the chosen strategy and explicit handling of uncertainty. Our study demonstrates how multiple models can systematically and transparently be integrated via the developed workflow. Key areas for improvement are to refine integration strategies, harmonize the definition and communication of applicability domains across tools, expand in silico coverage for currently underrepresented endpoints, and develop approaches to consider data gaps in SSbD assessments.<\/jats:p>","DOI":"10.1093\/inteam\/vjag067","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:05:41Z","timestamp":1777439141000},"source":"Crossref","is-referenced-by-count":1,"title":["A framework for chemical hazard assessments under \u201cSafe and Sustainable by Design\u201d using multiple in silico tools"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-8636","authenticated-orcid":false,"given":"Joanke","family":"van Dijk","sequence":"first","affiliation":[{"name":"Technology and Societa Laboratory, Empa\u2014Swiss Federal Laboratories for Material Science and Technology , St. Gallen,","place":["Switzerland"]},{"name":"TEMAS Solutions GmbH , Hausen,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Agalliadou","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Environmental Engineering Laboratory, Aristotle University of Thessaloniki , Thessaloniki,","place":["Greece"]},{"name":"Center for Interdisciplinary Research and Innovation, HERACLES Research Center on the Exposome and Health , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Laura","family":"Battistelli","sequence":"additional","affiliation":[{"name":"Environment and Health Department, Istituto Superiore di Sanit\u00e0 , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Benfenati","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Bossa","sequence":"additional","affiliation":[{"name":"Environment and Health Department, Istituto Superiore di Sanit\u00e0 , Rome,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Halling","sequence":"additional","affiliation":[{"name":"IVL, Swedish Environmental Research Institute , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros","family":"Karakitsios","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Environmental Engineering Laboratory, Aristotle University of Thessaloniki , Thessaloniki,","place":["Greece"]},{"name":"Center for Interdisciplinary Research and Innovation, HERACLES Research Center on the Exposome and Health , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0703-4318","authenticated-orcid":false,"given":"Achilleas","family":"Karakoltzidis","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Environmental Engineering Laboratory, Aristotle University of Thessaloniki , Thessaloniki,","place":["Greece"]},{"name":"Center for Interdisciplinary Research and Innovation, HERACLES Research Center on the Exposome and Health , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9264-0431","authenticated-orcid":false,"given":"Fotini","family":"Nikiforou","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Environmental Engineering Laboratory, Aristotle University of Thessaloniki , Thessaloniki,","place":["Greece"]},{"name":"Center for Interdisciplinary Research and Innovation, HERACLES Research Center on the Exposome and Health , Thessaloniki,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimosthenis A","family":"Sarigiannis","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Environmental Engineering Laboratory, Aristotle University of Thessaloniki , Thessaloniki,","place":["Greece"]},{"name":"Center for Interdisciplinary Research and Innovation, HERACLES Research Center on the Exposome and Health , Thessaloniki,","place":["Greece"]},{"name":"National Hellenic Research Foundation , Athens,","place":["Greece"]},{"name":"School for Advanced Study (IUSS), Science, Technology and Society Department, Environmental Health Engineering , Pavia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Selvestrel","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ane\u017eka","family":"Sharma","sequence":"additional","affiliation":[{"name":"Recetox, Faculty of Science, Masaryk University , Brno,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsi M","family":"Siivola","sequence":"additional","affiliation":[{"name":"Finnish Institute of Occupational Health , Helsinki,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziye","family":"Zheng","sequence":"additional","affiliation":[{"name":"IVL, Swedish Environmental Research Institute , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"2026060409320220700_vjag067-B1","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.oneear.2022.09.012","article-title":"Understanding and addressing the planetary crisis of chemicals and plastics","volume":"5","author":"Almroth","year":"2022","journal-title":"One Earth"},{"key":"2026060409320220700_vjag067-B2","doi-asserted-by":"publisher","author":"Benfenati","year":"2019","DOI":"10.1016\/j.envint.2019.105060"},{"key":"2026060409320220700_vjag067-B3","first-page":"21","article-title":"VEGA-QSAR: AI inside a platform for predictive toxicology","volume":"1107","author":"Benfenati","year":"2013","journal-title":"CEUR Workshop Proceedings"},{"key":"2026060409320220700_vjag067-B4","unstructured":"Benfenati E., Selvestrel G., Colombo E., Vigan\u00f2 E. L., Raitano G., Lombardo A. (2025). In silico models: Assessment of the results of the VEGA models within an exercise of the PARC project. Zenodo. 10.5281\/zenodo.15131130"},{"key":"2026060409320220700_vjag067-B5","volume-title":"Safe and sustainable by design chemicals and materials\u2014Framework for the definition of criteria and evaluation procedure for chemicals and materials. EUR 31100 EN","author":"Caldeira","year":"2022"},{"key":"2026060409320220700_vjag067-B6","doi-asserted-by":"publisher","author":"Caldeira","year":"2023","DOI":"10.2760\/769211%2520(print)"},{"key":"2026060409320220700_vjag067-B7","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.3109\/17435390.2012.741725","article-title":"Can the Ames test provide an insight into nano-object mutagenicity? 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