Publicação
Using effect biomarker thresholds in regulatory risk assessment
| Resumo: | The international initiative titled: “Using Adverse Outcome Pathways (AOP) to address combined exposures to chemicals with relevant effect-biomarkers”, was coordinated by the OECD’s Working Parties on Exposure Assessment (WPEA) and Hazard Assessment (WPHA). It brought together over 90 experts from 25 countries to advance the regulatory and scientific use of effect biomarkers for assessing exposures to chemical mixtures and their associated biological and health-relevant effects. Effect biomarkers provide biologically integrated information that can complement traditional single-substance approaches by supporting the interpretation of combined chemical exposures and associated biological responses. While the official OECD Guidance targets primarily regulatory audiences, this article communicates the project’s rationale and methodology to academic, industrial, and regulatory communities. Assessing chemical mixture exposures through effect biomarkers overcomes the limitations of traditional single-substance approaches that have guided regulatory frameworks for decades. Effect biomarkers, anchored in AOPs, offer biologically integrated assessments resulting from both known and unknown exposures integrating all exposure routes. Effect biomarkers are powerful in identifying biologically relevant responses, enabling targeted health assessments of vulnerable populations within human biomonitoring programs. This OECD project has produced a harmonised framework for deriving effect-based mixture threshold levels, applicable to both Occupational Biomonitoring Effect Levels (OBELs) for human health and Effect-Based Trigger values (EBTs) for environmental assessments. The framework establishes biologically anchored trigger values that help identify risks from exposures to complex chemical mixtures and can guide appropriate risk management measures. The derivation was guided by four core selection criteria and additional quality principles, ensuring biological relevance to regulatory-defined adversity, quantifiability, robustness, sensitivity, and interpretability for risk assessment. A four-tiered system (Tiers 0–3) reflects increasing toxicological and methodological certainty and relevance, with thresholds informing risk management decisions based on observed changes in biomarkers. Seven case studies demonstrate the framework’s applicability across key hazard classes (genotoxicity/carcinogenicity, endocrine disruption, neurotoxicity, and reproductive toxicity), thus supporting harmonised group- and individual-level assessments and broader integration of effect biomarkers into occupational and environmental health assessments. |
|---|---|
| Autores principais: | Hernández, Antonio F. |
| Outros Autores: | Jeddi, Maryam Zare; Wilks, Martin F.; FitzGerald, Rex; Duca, Radu Corneliu; Villeneuve, Dan; Viegas, Susana; Hotta, Asako; Baucher, Marie Ange; Browne, Patience; Scholten, Bernice; Simon, Eszter; Poddalgoda, Devika; Bal-Price, Anna; Mustieles, Vicente; van Thriel, Christoph; Bonassi, Stefano; Fenech, Michael; Ndaw, Sophie; Pieper, Christina; Rissler, Jörg; Paini, Alicia; Farcal, Lucian; Schmid, Kaspar; Pasanen-Kase, Robert; Hopf, Nancy B. |
| Assunto: | Adverse Outcome Pathways (AOPs) Chemical mixtures Effect biomarkers Environmental biomonitoring Mixture threshold derivation Occupational biomonitoring General Environmental Science SDG 3 - Good Health and Well-being |
| Ano: | 2026 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1866752610169520128 |
|---|---|
| author | Hernández, Antonio F. |
| author2 | Jeddi, Maryam Zare Wilks, Martin F. FitzGerald, Rex Duca, Radu Corneliu Villeneuve, Dan Viegas, Susana Hotta, Asako Baucher, Marie Ange Browne, Patience Scholten, Bernice Simon, Eszter Poddalgoda, Devika Bal-Price, Anna Mustieles, Vicente van Thriel, Christoph Bonassi, Stefano Fenech, Michael Ndaw, Sophie Pieper, Christina Rissler, Jörg Paini, Alicia Farcal, Lucian Schmid, Kaspar Pasanen-Kase, Robert Hopf, Nancy B. |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Hernández, Antonio F. Jeddi, Maryam Zare Wilks, Martin F. FitzGerald, Rex Duca, Radu Corneliu Villeneuve, Dan Viegas, Susana Hotta, Asako Baucher, Marie Ange Browne, Patience Scholten, Bernice Simon, Eszter Poddalgoda, Devika Bal-Price, Anna Mustieles, Vicente van Thriel, Christoph Bonassi, Stefano Fenech, Michael Ndaw, Sophie Pieper, Christina Rissler, Jörg Paini, Alicia Farcal, Lucian Schmid, Kaspar Pasanen-Kase, Robert Hopf, Nancy B. |
| author_role | author |
| contributor_name_str_mv | Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo ENSP) Comprehensive Health Research Centre (CHRC) - Pólo ENSP Escola Nacional de Saúde Pública (ENSP) Centro de Investigação em Saúde Pública (CISP/PHRC) Elsevier RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Hernández, Antonio F.\"},{\"Person.name\":\"Jeddi, Maryam Zare\"},{\"Person.name\":\"Wilks, Martin F.\"},{\"Person.name\":\"FitzGerald, Rex\"},{\"Person.name\":\"Duca, Radu Corneliu\"},{\"Person.name\":\"Villeneuve, Dan\"},{\"Person.name\":\"Viegas, Susana\"},{\"Person.name\":\"Hotta, Asako\"},{\"Person.name\":\"Baucher, Marie Ange\"},{\"Person.name\":\"Browne, Patience\"},{\"Person.name\":\"Scholten, Bernice\"},{\"Person.name\":\"Simon, Eszter\"},{\"Person.name\":\"Poddalgoda, Devika\"},{\"Person.name\":\"Bal-Price, Anna\"},{\"Person.name\":\"Mustieles, Vicente\"},{\"Person.name\":\"van Thriel, Christoph\"},{\"Person.name\":\"Bonassi, Stefano\"},{\"Person.name\":\"Fenech, Michael\"},{\"Person.name\":\"Ndaw, Sophie\"},{\"Person.name\":\"Pieper, Christina\"},{\"Person.name\":\"Rissler, Jörg\"},{\"Person.name\":\"Paini, Alicia\"},{\"Person.name\":\"Farcal, Lucian\"},{\"Person.name\":\"Schmid, Kaspar\"},{\"Person.name\":\"Pasanen-Kase, Robert\"},{\"Person.name\":\"Hopf, Nancy B.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo ENSP) Comprehensive Health Research Centre (CHRC) - Pólo ENSP Escola Nacional de Saúde Pública (ENSP) Centro de Investigação em Saúde Pública (CISP/PHRC) Elsevier RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Hernández, Antonio F. Jeddi, Maryam Zare Wilks, Martin F. FitzGerald, Rex Duca, Radu Corneliu Villeneuve, Dan Viegas, Susana Hotta, Asako Baucher, Marie Ange Browne, Patience Scholten, Bernice Simon, Eszter Poddalgoda, Devika Bal-Price, Anna Mustieles, Vicente van Thriel, Christoph Bonassi, Stefano Fenech, Michael Ndaw, Sophie Pieper, Christina Rissler, Jörg Paini, Alicia Farcal, Lucian Schmid, Kaspar Pasanen-Kase, Robert Hopf, Nancy B. |
| datacite.date.Accepted.fl_str_mv | 2026-05-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2026-05-22T14:06:01Z |
| datacite.date.embargoed.fl_str_mv | 2026-05-22T14:06:01Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Adverse Outcome Pathways (AOPs) Chemical mixtures Effect biomarkers Environmental biomonitoring Mixture threshold derivation Occupational biomonitoring General Environmental Science SDG 3 - Good Health and Well-being |
| datacite.titles.title.fl_str_mv | Using effect biomarker thresholds in regulatory risk assessment an OECD-based framework for assessing cumulative exposures to chemical mixtures |
| dc.contributor.none.fl_str_mv | Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo ENSP) Comprehensive Health Research Centre (CHRC) - Pólo ENSP Escola Nacional de Saúde Pública (ENSP) Centro de Investigação em Saúde Pública (CISP/PHRC) Elsevier RUN |
| dc.creator.none.fl_str_mv | Hernández, Antonio F. Jeddi, Maryam Zare Wilks, Martin F. FitzGerald, Rex Duca, Radu Corneliu Villeneuve, Dan Viegas, Susana Hotta, Asako Baucher, Marie Ange Browne, Patience Scholten, Bernice Simon, Eszter Poddalgoda, Devika Bal-Price, Anna Mustieles, Vicente van Thriel, Christoph Bonassi, Stefano Fenech, Michael Ndaw, Sophie Pieper, Christina Rissler, Jörg Paini, Alicia Farcal, Lucian Schmid, Kaspar Pasanen-Kase, Robert Hopf, Nancy B. |
| dc.date.Accepted.fl_str_mv | 2026-05-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2026-05-22T14:06:01Z |
| dc.date.embargoed.fl_str_mv | 2026-05-22T14:06:01Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/203321 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Adverse Outcome Pathways (AOPs) Chemical mixtures Effect biomarkers Environmental biomonitoring Mixture threshold derivation Occupational biomonitoring General Environmental Science SDG 3 - Good Health and Well-being |
| dc.title.fl_str_mv | Using effect biomarker thresholds in regulatory risk assessment an OECD-based framework for assessing cumulative exposures to chemical mixtures |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | The international initiative titled: “Using Adverse Outcome Pathways (AOP) to address combined exposures to chemicals with relevant effect-biomarkers”, was coordinated by the OECD’s Working Parties on Exposure Assessment (WPEA) and Hazard Assessment (WPHA). It brought together over 90 experts from 25 countries to advance the regulatory and scientific use of effect biomarkers for assessing exposures to chemical mixtures and their associated biological and health-relevant effects. Effect biomarkers provide biologically integrated information that can complement traditional single-substance approaches by supporting the interpretation of combined chemical exposures and associated biological responses. While the official OECD Guidance targets primarily regulatory audiences, this article communicates the project’s rationale and methodology to academic, industrial, and regulatory communities. Assessing chemical mixture exposures through effect biomarkers overcomes the limitations of traditional single-substance approaches that have guided regulatory frameworks for decades. Effect biomarkers, anchored in AOPs, offer biologically integrated assessments resulting from both known and unknown exposures integrating all exposure routes. Effect biomarkers are powerful in identifying biologically relevant responses, enabling targeted health assessments of vulnerable populations within human biomonitoring programs. This OECD project has produced a harmonised framework for deriving effect-based mixture threshold levels, applicable to both Occupational Biomonitoring Effect Levels (OBELs) for human health and Effect-Based Trigger values (EBTs) for environmental assessments. The framework establishes biologically anchored trigger values that help identify risks from exposures to complex chemical mixtures and can guide appropriate risk management measures. The derivation was guided by four core selection criteria and additional quality principles, ensuring biological relevance to regulatory-defined adversity, quantifiability, robustness, sensitivity, and interpretability for risk assessment. A four-tiered system (Tiers 0–3) reflects increasing toxicological and methodological certainty and relevance, with thresholds informing risk management decisions based on observed changes in biomarkers. Seven case studies demonstrate the framework’s applicability across key hazard classes (genotoxicity/carcinogenicity, endocrine disruption, neurotoxicity, and reproductive toxicity), thus supporting harmonised group- and individual-level assessments and broader integration of effect biomarkers into occupational and environmental health assessments. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/2247ff25-20dc-4d6e-93c1-11fac702c72d/download |
| id | run_a3cb6d5ca8fc68b99c543a8a135c185c |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/203321 |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/203321 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Hernández, Antonio F. Jeddi, Maryam Zare Wilks, Martin F. FitzGerald, Rex Duca, Radu Corneliu Villeneuve, Dan Viegas, Susana Hotta, Asako Baucher, Marie Ange Browne, Patience Scholten, Bernice Simon, Eszter Poddalgoda, Devika Bal-Price, Anna Mustieles, Vicente van Thriel, Christoph Bonassi, Stefano Fenech, Michael Ndaw, Sophie Pieper, Christina Rissler, Jörg Paini, Alicia Farcal, Lucian Schmid, Kaspar Pasanen-Kase, Robert Hopf, Nancy B. |
| publishDate | 2026 |
| reponame_str | Repositório Institucional da UNL |
| repository_id_str | urn:repositoryAcronym:run |
| service_str_mv | urn:repositoryAcronym:run |
| spelling | engenThe international initiative titled: “Using Adverse Outcome Pathways (AOP) to address combined exposures to chemicals with relevant effect-biomarkers”, was coordinated by the OECD’s Working Parties on Exposure Assessment (WPEA) and Hazard Assessment (WPHA). It brought together over 90 experts from 25 countries to advance the regulatory and scientific use of effect biomarkers for assessing exposures to chemical mixtures and their associated biological and health-relevant effects. Effect biomarkers provide biologically integrated information that can complement traditional single-substance approaches by supporting the interpretation of combined chemical exposures and associated biological responses. While the official OECD Guidance targets primarily regulatory audiences, this article communicates the project’s rationale and methodology to academic, industrial, and regulatory communities. Assessing chemical mixture exposures through effect biomarkers overcomes the limitations of traditional single-substance approaches that have guided regulatory frameworks for decades. Effect biomarkers, anchored in AOPs, offer biologically integrated assessments resulting from both known and unknown exposures integrating all exposure routes. Effect biomarkers are powerful in identifying biologically relevant responses, enabling targeted health assessments of vulnerable populations within human biomonitoring programs. This OECD project has produced a harmonised framework for deriving effect-based mixture threshold levels, applicable to both Occupational Biomonitoring Effect Levels (OBELs) for human health and Effect-Based Trigger values (EBTs) for environmental assessments. The framework establishes biologically anchored trigger values that help identify risks from exposures to complex chemical mixtures and can guide appropriate risk management measures. The derivation was guided by four core selection criteria and additional quality principles, ensuring biological relevance to regulatory-defined adversity, quantifiability, robustness, sensitivity, and interpretability for risk assessment. A four-tiered system (Tiers 0–3) reflects increasing toxicological and methodological certainty and relevance, with thresholds informing risk management decisions based on observed changes in biomarkers. Seven case studies demonstrate the framework’s applicability across key hazard classes (genotoxicity/carcinogenicity, endocrine disruption, neurotoxicity, and reproductive toxicity), thus supporting harmonised group- and individual-level assessments and broader integration of effect biomarkers into occupational and environmental health assessments.application/pdfenUsing effect biomarker thresholds in regulatory risk assessmentSubtitleenan OECD-based framework for assessing cumulative exposures to chemical mixturesHernández, Antonio F.Jeddi, Maryam ZareWilks, Martin F.FitzGerald, RexDuca, Radu CorneliuVilleneuve, DanViegas, SusanaHotta, AsakoBaucher, Marie AngeBrowne, PatienceScholten, BerniceSimon, EszterPoddalgoda, DevikaBal-Price, AnnaMustieles, Vicentevan Thriel, ChristophBonassi, StefanoFenech, MichaelNdaw, SophiePieper, ChristinaRissler, JörgPaini, AliciaFarcal, LucianSchmid, KasparPasanen-Kase, RobertHopf, Nancy B.Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo ENSP)Comprehensive Health Research Centre (CHRC) - Pólo ENSPEscola Nacional de Saúde Pública (ENSP)Centro de Investigação em Saúde Pública (CISP/PHRC)ElsevierHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf0160-4120URNIsPartOfPURE: 163408614URNIsPartOfPURE UUID: 9bdbf2ed-4a98-44fa-a8e1-cb7db31fe021URNIsPartOfScopus: 105036589343URNIsPartOfPubMed: 42013552URNIsPartOfWOS: 001752207400001DOIIsPartOf10.1016/j.envint.2026.1102152026-05-22T14:06:01Z2026-052026-05-01T00:00:00ZHandlehttp://hdl.handle.net/10362/203321http://purl.org/coar/access_right/c_abf2open accessAdverse Outcome Pathways (AOPs)Chemical mixturesEffect biomarkersEnvironmental biomonitoringMixture threshold derivationOccupational biomonitoringGeneral Environmental ScienceSDG 3 - Good Health and Well-being4004322 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/2247ff25-20dc-4d6e-93c1-11fac702c72d/download |
| spellingShingle | Using effect biomarker thresholds in regulatory risk assessment Hernández, Antonio F. Adverse Outcome Pathways (AOPs) Chemical mixtures Effect biomarkers Environmental biomonitoring Mixture threshold derivation Occupational biomonitoring General Environmental Science SDG 3 - Good Health and Well-being |
| status | SINGLETON |
| subject.fl_str_mv | Adverse Outcome Pathways (AOPs) Chemical mixtures Effect biomarkers Environmental biomonitoring Mixture threshold derivation Occupational biomonitoring General Environmental Science SDG 3 - Good Health and Well-being |
| title | Using effect biomarker thresholds in regulatory risk assessment |
| title_full | Using effect biomarker thresholds in regulatory risk assessment |
| title_fullStr | Using effect biomarker thresholds in regulatory risk assessment |
| title_full_unstemmed | Using effect biomarker thresholds in regulatory risk assessment |
| title_short | Using effect biomarker thresholds in regulatory risk assessment |
| title_sort | Using effect biomarker thresholds in regulatory risk assessment |
| topic | Adverse Outcome Pathways (AOPs) Chemical mixtures Effect biomarkers Environmental biomonitoring Mixture threshold derivation Occupational biomonitoring General Environmental Science SDG 3 - Good Health and Well-being |
| topic_facet | Adverse Outcome Pathways (AOPs) Chemical mixtures Effect biomarkers Environmental biomonitoring Mixture threshold derivation Occupational biomonitoring General Environmental Science SDG 3 - Good Health and Well-being |
| url | http://hdl.handle.net/10362/203321 |
| visible | 1 |