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Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Towards a systematic use of effect biomarkers in population and occupational biomonitoring
https://orcid.org/0000-0002-7518-2465
https://orcid.org/0000-0001-5718-0733
https://orcid.org/0000-0003-3454-7947
https://orcid.org/0000-0001-8189-1826
https://orcid.org/0000-0001-9744-7332
Highlights Reliable effect biomarkers are available for most of the relevant MoAs. Increasing AOP knowledge fosters the use of effect biomarkers in regulatory context. PBK/D models allow interpretation and simulation of biomarkers of effect. An inter-regulatory setting of effect-based trigger values is demanded. Effect-biomarkers have in many cases reached a level of maturity ensuring use in mixture assessments.
Abstract Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as ‘omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.
Towards a systematic use of effect biomarkers in population and occupational biomonitoring
https://orcid.org/0000-0002-7518-2465
https://orcid.org/0000-0001-5718-0733
https://orcid.org/0000-0003-3454-7947
https://orcid.org/0000-0001-8189-1826
https://orcid.org/0000-0001-9744-7332
Highlights Reliable effect biomarkers are available for most of the relevant MoAs. Increasing AOP knowledge fosters the use of effect biomarkers in regulatory context. PBK/D models allow interpretation and simulation of biomarkers of effect. An inter-regulatory setting of effect-based trigger values is demanded. Effect-biomarkers have in many cases reached a level of maturity ensuring use in mixture assessments.
Abstract Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as ‘omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.
Towards a systematic use of effect biomarkers in population and occupational biomonitoring
https://orcid.org/0000-0002-7518-2465
https://orcid.org/0000-0001-5718-0733
https://orcid.org/0000-0003-3454-7947
https://orcid.org/0000-0001-8189-1826
https://orcid.org/0000-0001-9744-7332
Highlights Reliable effect biomarkers are available for most of the relevant MoAs. Increasing AOP knowledge fosters the use of effect biomarkers in regulatory context. PBK/D models allow interpretation and simulation of biomarkers of effect. An inter-regulatory setting of effect-based trigger values is demanded. Effect-biomarkers have in many cases reached a level of maturity ensuring use in mixture assessments.
Abstract Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as ‘omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.
Towards a systematic use of effect biomarkers in population and occupational biomonitoring
Zare Jeddi, Maryam (Autor:in) / Hopf, Nancy B. (Autor:in) / Viegas, Susana (Autor:in) / Price, Anna Bal (Autor:in) / Paini, Alicia (Autor:in) / van Thriel, Christoph (Autor:in) / Benfenati, Emilio (Autor:in) / Ndaw, Sophie (Autor:in) / Bessems, Jos (Autor:in) / Behnisch, Peter A. (Autor:in)
30.10.2020
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
Exposure science , Mixture assessment , Adverse outcome pathways (AOP) , Physiologically based pharmacokinetic (PBPK) , Biomonitoring , Risk assessment , ACGIH , American Conference of Governmental Industrial Hygienists , ADME , Adsorption, Distribution, Metabolism, Excretion , AOP , Adverse Outcome Pathways , AO , adverse outcome , AOP-KB , Adverse Outcome Pathway Knowledge Base , B-Pb , Blood Lead , BBLV , Binding Biological Limit Value , Biological , limit value , BOELV , Binding Occupational Exposure Limit Value , CAD , Chemical Agents Directive , CMD , Carcinogenic and Mutagenic Directive , DNEL , Derived No-Effect Level , DNT , Developmental Neurotoxicity , EC , European Commission , ECHA , European Chemicals Agency , EFSA , European Food Safety Authority , Effect , Biomarker Effect biomarkers are measurable biochemical, physiological, and behavioral effects or other alterations within an organism that depending upon the magnitude, can be recognized as associated with an established or possible health impairment or disease , EQ , Equivalent concentration, integrative response of an effect biomarker translated in an effect concentration of a reference compound , EGMAST , Extended Advisory Group on Molecular Screening and Toxicogenomics , HBM , Human Biomonitoring , HBM4EU , European Human Biomonitoring Initiative , IOELV , Indicative Occupational Exposure Limit Value , ISES , International Society for Exposure Science , ISO , International Organization for Standardization , IUCLID , International Uniform Chemical Information Database , MIE , Molecular Initiating Event , KE , Key Event , KER , Key Event Relationship , MDA , malondialdehyde , MoA , Mode of Action , OECD , Organization for Economic Co-operation and Development , OBL , Occupational Biomonitoring Level , OBEL , Occupational Biomonitoring Effect Level , OEL , Occupational Exposure Limit , OSH , Occupational Safety and Health , PBK modelling , Physiologically Based Kinetic modelling , PBD modelling , Physiologically Based Dynamic modelling , PoD , Points of Departure , PPE , Personal Protective Equipment , RAC , Risk Assessment Committee, European Chemicals Agency , REACH , Registration, Evaluation, Authorization and Restriction of Chemicals , RMM , Risk Management Measure , SCOEL , Scientific Committee on Occupational Exposure Limits , SEGs , Similar Exposure Groups , WHO , World Health Organization , WPEA , Working Party on Exposure Assessment , WPHA , Working Party on Hazard Assessment
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