Human biomonitoring and toxicokinetics as key building blocks for next generation risk assessment
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| Titel: | Human biomonitoring and toxicokinetics as key building blocks for next generation risk assessment |
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| Autoren: | Reale, Elena, Jeddi, Maryam Zare, Paini, Alicia, Connolly, Alison, Duca, Radu, Cubadda, Francesco, Benfenati, Emilio, Bessems, Jos, Galea, Karen S., Dirven, Hubert, Santonen, Tiina, Koch, Holger M., Jones, Kate, Sams, Craig, Viegas, Susana, Kyriaki, Machera, Campisi, Luca, David, Arthur, Antignac, Jean-Philippe, Hopf, Nancy B. |
| Quelle: | ISSN:0160-4120 ; ISSN:1873-6750 ; Environment International, vol. 184, Art.No. ARTN 108474. |
| Verlagsinformationen: | Elsevier |
| Publikationsjahr: | 2024 |
| Schlagwörter: | Science & Technology, Life Sciences & Biomedicine, Environmental Sciences, Environmental Sciences & Ecology, PBPK, Adverse outcome pathway, Chemical risk assessment, Biomarkers of exposure and effect, IN-VITRO, URINE SAMPLES, TOXICITY DATA, EXPOSURE, EQUIVALENTS, BIOMARKERS, CHEMICALS, PHTHALATE, METABOLITES, GLYPHOSATE, Animals, Humans, Toxicokinetics, Models, Biological, Biological Monitoring, Risk Assessment, Adverse Outcome Pathways |
| Beschreibung: | Human health risk assessment is historically built upon animal testing, often following Organisation for Economic Co-operation and Development (OECD) test guidelines and exposure assessments. Using combinations of human relevant in vitro models, chemical analysis and computational (in silico) approaches bring advantages compared to animal studies. These include a greater focus on the human species and on molecular mechanisms and kinetics, identification of Adverse Outcome Pathways and downstream Key Events as well as the possibility of addressing susceptible populations and additional endpoints. Much of the advancement and progress made in the Next Generation Risk Assessment (NGRA) have been primarily focused on new approach methodologies (NAMs) and physiologically based kinetic (PBK) modelling without incorporating human biomonitoring (HBM). The integration of toxicokinetics (TK) and PBK modelling is an essential component of NGRA. PBK models are essential for describing in quantitative terms the TK processes with a focus on the effective dose at the expected target site. Furthermore, the need for PBK models is amplified by the increasing scientific and regulatory interest in aggregate and cumulative exposure as well as interactions of chemicals in mixtures. Since incorporating HBM data strengthens approaches and reduces uncertainties in risk assessment, here we elaborate on the integrated use of TK, PBK modelling and HBM in chemical risk assessment highlighting opportunities as well as challenges and limitations. Examples are provided where HBM and TK/PBK modelling can be used in both exposure assessment and hazard characterization shifting from external exposure and animal dose/response assays to animal-free, internal exposure-based NGRA. ; status: Published |
| Publikationsart: | article in journal/newspaper |
| Dateibeschreibung: | application/pdf |
| Sprache: | English |
| Relation: | https://lirias.kuleuven.be/handle/20.500.12942/749606; https://doi.org/10.1016/j.envint.2024.108474; https://pubmed.ncbi.nlm.nih.gov/38350256 |
| DOI: | 10.1016/j.envint.2024.108474 |
| Verfügbarkeit: | https://lirias.kuleuven.be/handle/20.500.12942/749606 https://hdl.handle.net/20.500.12942/749606 https://lirias.kuleuven.be/retrieve/9d23f25a-3fdd-41de-afc4-ec34316c0a63 https://doi.org/10.1016/j.envint.2024.108474 https://pubmed.ncbi.nlm.nih.gov/38350256 |
| Rights: | info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by/4.0/ |
| Dokumentencode: | edsbas.7A07DAE9 |
| Datenbank: | BASE |
Nájsť tento článok vo Web of Science | Abstract: | Human health risk assessment is historically built upon animal testing, often following Organisation for Economic Co-operation and Development (OECD) test guidelines and exposure assessments. Using combinations of human relevant in vitro models, chemical analysis and computational (in silico) approaches bring advantages compared to animal studies. These include a greater focus on the human species and on molecular mechanisms and kinetics, identification of Adverse Outcome Pathways and downstream Key Events as well as the possibility of addressing susceptible populations and additional endpoints. Much of the advancement and progress made in the Next Generation Risk Assessment (NGRA) have been primarily focused on new approach methodologies (NAMs) and physiologically based kinetic (PBK) modelling without incorporating human biomonitoring (HBM). The integration of toxicokinetics (TK) and PBK modelling is an essential component of NGRA. PBK models are essential for describing in quantitative terms the TK processes with a focus on the effective dose at the expected target site. Furthermore, the need for PBK models is amplified by the increasing scientific and regulatory interest in aggregate and cumulative exposure as well as interactions of chemicals in mixtures. Since incorporating HBM data strengthens approaches and reduces uncertainties in risk assessment, here we elaborate on the integrated use of TK, PBK modelling and HBM in chemical risk assessment highlighting opportunities as well as challenges and limitations. Examples are provided where HBM and TK/PBK modelling can be used in both exposure assessment and hazard characterization shifting from external exposure and animal dose/response assays to animal-free, internal exposure-based NGRA. ; status: Published |
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| DOI: | 10.1016/j.envint.2024.108474 |