Journal Articles Environment International Year : 2024

Human biomonitoring and toxicokinetics as key building blocks for next generation risk assessment

1 UNIL - Université de Lausanne = University of Lausanne
2 RIVM - National Institute for Public Health and the Environment [Bilthoven]
3 esqLABS
4 UCD - University College Dublin [Dublin]
5 NUI Galway - National University of Ireland [Galway]
6 LNS - Laboratoire National de Santé [Luxembourg]
7 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
8 ISS - Istituto Superiore di Sanità = Italian National Institute of Health [Roma, Italia]
9 IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" = Mario Negri Institute for Pharmacological Research
10 VITO - Flemish Institute for Technological Research
11 Institute of Occupational Medicine (IOM)
12 NIPH - Norwegian Institute of Public Health [Oslo]
13 FIOH - Finnish Institute of Occupational Health of Helsinki
14 IPA - Institute for Prevention and Occupational Medicine of the German Social Accident Insurance
15 HSE - Health and Safety Executive Science and Research Centre
16 National School of Public Health
17 BPI - Benaki Phytopathological Institute
18 UniPi - University of Pisa [Italy] = Università di Pisa [Italia] = Université de Pise [Italie]
19 UR - Université de Rennes
20 Irset - Institut de recherche en santé, environnement et travail
21 LERES - Laboratoire d'étude et de recherche en environnement et santé
22 EHESP - École des Hautes Études en Santé Publique
23 DEESSE - Département des sciences en santé environnementale
24 LABERCA - Laboratoire d'étude des Résidus et Contaminants dans les Aliments
25 Oniris VetAgroBio - École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique
Alicia Paini
  • Function : Author

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.

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hal-04484068 , version 1 (24-05-2024)

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Elena Reale, Maryam Zare Jeddi, Alicia Paini, Alison Connolly, Radu Duca, et al.. Human biomonitoring and toxicokinetics as key building blocks for next generation risk assessment. Environment International, 2024, 184, pp.108474. ⟨10.1016/j.envint.2024.108474⟩. ⟨hal-04484068⟩
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