{"authors":[{"id":null,"fullName":"Evangelos Tsoukas","name":null,"surname":null,"rank":1,"pid":{"id":{"scheme":"orcid_pending","value":"0009-0008-0504-691x"},"provenance":null}},{"id":null,"fullName":"Michail Papadourakis","name":null,"surname":null,"rank":2,"pid":null},{"id":null,"fullName":"Eleni Chontzopoulou","name":null,"surname":null,"rank":3,"pid":null},{"id":null,"fullName":"Spyridon Vythoulkas","name":null,"surname":null,"rank":4,"pid":null},{"id":"orcid_______::180b6c38d0ebb4e15f0dc4c2f48a0364","fullName":"Christos Didachos","name":null,"surname":null,"rank":5,"pid":{"id":{"scheme":"orcid","value":"0000-0002-4100-1697"},"provenance":null}},{"id":null,"fullName":"Dionisis Cavouras","name":null,"surname":null,"rank":6,"pid":null},{"id":"orcid_______::1cd0d0b10ee3b2ca639a58dc5a00c707","fullName":"Panagiotis Zoumpoulakis","name":null,"surname":null,"rank":7,"pid":{"id":{"scheme":"orcid","value":"0000-0001-9348-6078"},"provenance":null}},{"id":"orcid_______::f2fce6e3ddbc4ac07148f3c80e8c3e78","fullName":"Minos-Timotheos Matsoukas","name":null,"surname":null,"rank":8,"pid":{"id":{"scheme":"orcid","value":"0000-0002-4642-8163"},"provenance":null}}],"openAccessColor":"hybrid","publiclyFunded":false,"eoscIfGuidelines":null,"type":"publication","language":{"code":"eng","label":"English"},"countries":null,"subjects":[{"subject":{"scheme":"keyword","value":"bioaccumulation"},"provenance":null},{"subject":{"scheme":"keyword","value":"ecotoxicity"},"provenance":null},{"subject":{"scheme":"keyword","value":"machine learning models"},"provenance":null},{"subject":{"scheme":"keyword","value":"Article"},"provenance":null}],"mainTitle":"G.AI.A: An Integrated Machine-Learning Platform for Predicting Bioaccumulation and Ecotoxicity of Pharmaceuticals","subTitle":null,"descriptions":["Pharmaceutical pollution in aquatic environments poses a significant ecological threat due to the accumulation of bioactive compounds from human and veterinary sources. In support of the EU Green Deal's Chemicals Strategy for Sustainability, this study presents a computational framework for predicting two key environmental risk indicators in fish: bioconcentration and ecotoxicity. Bioconcentration, quantified by the bioconcentration factor (BCF), reflects a chemical's tendency to accumulate in organisms, while ecotoxicity is assessed via the median lethal concentration (LC50) over defined exposure periods. We developed two high-performing machine learning (ML) models, achieving ROC AUC scores of 94.60% for bioconcentration and 96.06% for ecotoxicity, validated across both internal and external data sets. To expand the scope of risk evaluation, we incorporated metabolite prediction using the SyGMa tool, selected after benchmarking multiple alternatives. This enables the assessment of both parent compounds and their potentially toxic metabolites. Model interpretability was enhanced through molecular fingerprint analysis, which identified structural features associated with toxicity and accumulation, informing the early stages of drug design. To support practical implementation, we introduced G.AI.A (https://gaiatox.eu/), an intuitive web platform that allows users to input Simplified Molecular Input Line Entry System (SMILES) strings for rapid prediction of environmental risk end points. The application domain of G.AI.A lies in predictive toxicology, enabling researchers and regulatory bodies to assess the toxicological profiles of small organic compounds, excluding those containing heavy metals, by analyzing their chemical structures. The platform supports batch processing and offers interactive visualizations, facilitating compound screening and early stage environmental risk assessment. By integrating predictive modeling with interpretability and usability, our framework advances green-by-design pharmaceutical development and contributes to sustainable chemical management."],"publicationDate":"2026-01-16","publisher":"American Chemical Society (ACS)","embargoEndDate":null,"sources":["Crossref","J Chem Inf Model","Journal of Chemical Information and Modeling"],"formats":null,"contributors":null,"coverages":null,"bestAccessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/"},"container":{"name":"Journal of Chemical Information and Modeling","issnPrinted":"1549-9596","issnOnline":"1549-960X","issnLinking":null,"ep":"1428","iss":null,"sp":"1414","vol":"66","edition":null,"conferencePlace":null,"conferenceDate":null},"documentationUrls":null,"codeRepositoryUrl":null,"programmingLanguage":null,"contactPeople":null,"contactGroups":null,"tools":null,"size":null,"version":null,"geoLocations":null,"id":"doi_dedup___::00d33efd87c2bf2569b4a1fd63b5e832","originalIds":["10.1021/acs.jcim.5c02286","50|doiboost____|00d33efd87c2bf2569b4a1fd63b5e832","41544240","oai:pubmedcentral.nih.gov:12892312","50|od_______267::919a87067fb9811377456a21e17e376d","50|dblp________::ef6f855c51d5393a5b9aaef96e79dd3a","oai:zenodo.org:18299017","50|od______2659::00d33efd87c2bf2569b4a1fd63b5e832","50|r3c4b2081b22::8fbb24c8445069731dc783096a5ab053","10.1021/ACS.JCIM.5C02286","50|sygma_______::00d33efd87c2bf2569b4a1fd63b5e832"],"pids":[{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"},{"scheme":"pmid","value":"41544240"}],"dateOfCollection":null,"lastUpdateTimeStamp":null,"indicators":{"citationImpact":{"citationCount":1.0,"influence":2.3841142E-9,"popularity":3.4417793E-9,"impulse":1.0,"citationClass":"C5","influenceClass":"C5","impulseClass":"C5","popularityClass":"C4"}},"projects":[{"id":"corda_____he::0168e1444c473bf8e51c9fe5940f70ae","code":"101057844","acronym":"ENVIROMED","title":"Next generation toolbox for greener pharmaceuticals design & manufacturing towards reduced environmental impact","funder":"European Commission","pids":[{"scheme":"doi","value":"10.3030/101057844"}]}],"organizations":[{"legalName":"University of West Attica","acronym":"TEI","id":"openorgs____::5f84d6d42d81e3250df4fd47c78c9fc9","pids":[{"scheme":"fundref","value":"501100021718"},{"scheme":"mag_id","value":"122380217"},{"scheme":"ISNI","value":"0000000472229074"},{"scheme":"PIC","value":"997755193"},{"scheme":"mag_id","value":"40479246"},{"scheme":"GRID","value":"grid.419877.4"},{"scheme":"OrgReg","value":"GR0065"},{"scheme":"OrgRef","value":"32433149"},{"scheme":"PIC","value":"905978255"},{"scheme":"OrgRef","value":"31162139"},{"scheme":"wikidata","value":"Q7692475"},{"scheme":"wikidata","value":"Q7692468"},{"scheme":"wikidata","value":"Q50359480"},{"scheme":"OrgReg","value":"GR0040"},{"scheme":"ROR","value":"https://ror.org/00ks0ea23"},{"scheme":"Wikidata","value":"Q7692468"},{"scheme":"FundRef","value":"501100021718"},{"scheme":"ISNI","value":"0000000093166632"},{"scheme":"Wikidata","value":"Q7692475"},{"scheme":"GRID","value":"grid.426224.4"},{"scheme":"GRID","value":"grid.499377.7"},{"scheme":"Wikidata","value":"Q50359480"},{"scheme":"ROR","value":"https://ror.org/044m46d61"},{"scheme":"ROR","value":"https://ror.org/00r2r5k05"},{"scheme":"OrgReg","value":"GR0038"}]}],"communities":[{"code":"eosc","label":"EOSC","provenance":null}],"collectedFrom":[{"key":"openaire____::a8db6f6b2ce4fe72e8b2314a9a93e7d9","value":"Sygma"},{"key":"opendoar____::358aee4cc897452c00244351e4d91f69","value":"ZENODO"},{"key":"openaire____::081b82f96300b6a6e3d282bad31cb6e2","value":"Crossref"},{"key":"openaire____::d8b68cc0a53121f6f896883a7d60c1db","value":"DBLP"},{"key":"opendoar____::8b6dd7db9af49e67306feb59a8bdc52c","value":"Europe PubMed Central"},{"key":"opendoar____::eda80a3d5b344bc40f3bc04f65b7a357","value":"PubMed Central"},{"key":"re3data_____::c4b2081b224be6b3e79d0e5e5556f631","value":"European Union Open Data Portal"}],"instances":[{"pids":[{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"}],"license":"CC BY NC ND","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":"hybrid"},"type":"Article","urls":["https://doi.org/10.1021/acs.jcim.5c02286"],"publicationDate":"2026-01-16","refereed":"peerReviewed","hostedBy":{"key":"issn___print::0c66c03ff206d62dbde8b84c35ac1ffa","value":"Journal of Chemical Information and Modeling"},"collectedFrom":{"key":"openaire____::081b82f96300b6a6e3d282bad31cb6e2","value":"Crossref"}},{"pids":[{"scheme":"pmid","value":"41544240"}],"alternateIdentifiers":[{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"}],"type":"Article","urls":["https://pubmed.ncbi.nlm.nih.gov/41544240"],"refereed":"nonPeerReviewed","hostedBy":{"key":"issn___print::0c66c03ff206d62dbde8b84c35ac1ffa","value":"Journal of Chemical Information and Modeling"},"collectedFrom":{"key":"opendoar____::8b6dd7db9af49e67306feb59a8bdc52c","value":"Europe PubMed Central"}},{"alternateIdentifiers":[{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"}],"license":"CC BY NC ND","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":null},"type":"Article","urls":["https://pubmed.ncbi.nlm.nih.gov/41544240/","https://doi.org/10.1021/acs.jcim.5c02286","https://pmc.ncbi.nlm.nih.gov/articles/PMC12892312/"],"publicationDate":"2026-01-16","refereed":"nonPeerReviewed","hostedBy":{"key":"opendoar____::eda80a3d5b344bc40f3bc04f65b7a357","value":"PubMed Central"},"collectedFrom":{"key":"opendoar____::eda80a3d5b344bc40f3bc04f65b7a357","value":"PubMed Central"}},{"alternateIdentifiers":[{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"}],"type":"Article","urls":["https://doi.org/10.1021/acs.jcim.5c02286"],"publicationDate":"2026-01-01","refereed":"nonPeerReviewed","hostedBy":{"key":"openaire____::d8b68cc0a53121f6f896883a7d60c1db","value":"DBLP"},"collectedFrom":{"key":"openaire____::d8b68cc0a53121f6f896883a7d60c1db","value":"DBLP"}},{"alternateIdentifiers":[{"scheme":"oai","value":"oai:zenodo.org:18299017"},{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"}],"license":"CC BY","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":null},"type":"Article","urls":["http://dx.doi.org/10.1021/acs.jcim.5c02286","https://zenodo.org/records/18299017"],"publicationDate":"2026-01-19","refereed":"nonPeerReviewed","hostedBy":{"key":"opendoar____::358aee4cc897452c00244351e4d91f69","value":"ZENODO"},"collectedFrom":{"key":"opendoar____::358aee4cc897452c00244351e4d91f69","value":"ZENODO"}},{"alternateIdentifiers":[{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"}],"type":"Article","urls":["http://dx.doi.org/10.1021/ACS.JCIM.5C02286"],"publicationDate":"2026-01-01","refereed":"peerReviewed","hostedBy":{"key":"issn___print::0c66c03ff206d62dbde8b84c35ac1ffa","value":"Journal of Chemical Information and Modeling"},"collectedFrom":{"key":"re3data_____::c4b2081b224be6b3e79d0e5e5556f631","value":"European Union Open Data Portal"}},{"alternateIdentifiers":[{"scheme":"doi","value":"10.1021/acs.jcim.5c02286"}],"license":"CC BY NC ND","accessRight":{"code":"c_abf2","label":"OPEN","scheme":"http://vocabularies.coar-repositories.org/documentation/access_rights/","openAccessRoute":null},"type":"Article","urls":["http://dx.doi.org/10.1021/acs.jcim.5c02286"],"refereed":"nonPeerReviewed","hostedBy":{"key":"issn___print::0c66c03ff206d62dbde8b84c35ac1ffa","value":"Journal of Chemical Information and Modeling"},"collectedFrom":{"key":"openaire____::a8db6f6b2ce4fe72e8b2314a9a93e7d9","value":"Sygma"}}],"links":[{"header":{"relationType":"resultProject","relationClass":"isProducedBy","relatedIdentifier":"corda_____he::0168e1444c473bf8e51c9fe5940f70ae","relatedRecordType":"project","relationProvenance":"sysimport:crosswalk:repository","trust":"0.9"},"collectedfrom":[{"dsId":"openaire____::3f264f93cf3b0cfc4ede188a6300455c","dsName":"CORDA - COmmon Research DAta Warehouse - Horizon Europe"}],"projectTitle":"Next generation toolbox for greener pharmaceuticals design & manufacturing towards reduced environmental impact","code":"101057844","funding":{"funder":{"id":"ec__________::EC","shortname":"EC","name":"European Commission","jurisdiction":{"code":"EU","label":"European Union"},"pid":null},"level0":{"id":"ec__________::EC::HE","description":"Horizon Europe Framework Programme","name":"HE"},"level1":{"id":"ec__________::EC::HE::HORIZON-RIA","description":"HORIZON  Research and Innovation Actions","name":"HORIZON-RIA"},"level2":{"id":null,"description":null,"name":null}},"startDate":"2022-06-01","endDate":"2025-11-30"}],"otherTitles":null,"inDiamondJournal":false,"green":true,"isGreen":true,"isInDiamondJournal":false}