Author, as appears in the article.: Laroche C, Aggarwal M, Bender H, Benndorf P, Birk B, Crozier J, Dal Negro G, De Gaetano F, Desaintes C, Gardner I, Hubesch B, Irizar A, John D, Kumar V, Lostia A, Manou I, Monshouwer M, Müller BP, Paini A, Reid K, Rowan T, Sachana M, Schutte K, Stirling C, Taalman R, van Aerts L, Weissenhorn R, Sauer UG

Department: Enginyeria Química

URV's Author/s: Kumar, Vikas

Keywords: Weight-of-evidence (woe) threshold of toxicological concern (ttc) physiologically-based kinetic (pbk) modelling metabolism integrated approach for testing and assessment (iata) in vitro to in vivo extrapolation (ivive) hazard and risk assessment excretion (adme) distribution and elimination absorption

Abstract: The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. Currently, lacking toxicokinetic data often prevent the application of read-across. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance. In certain sectors, PBK modelling is being used for risk assessment, but less so in others. Specific activities were identified to facilitate the use of in vitro and in silico toxicokinetic data to support read-across: The collation of available tools indicating the parameters and applicability domains covered; endpoint-specific guidance on toxicokinetics parameters required for read-across; case studies exemplifying how toxicokinetic data help support read-across. Activities to enhance the scientific robustness of read-across include the further user-friendly combination of read-across tools and formal guidance by the authorities specifying the minimum information requirements to justify read-across for a given toxicity endpoint. The EPAA was invited to continue dissemination activities and to explore possibilities to collate a contemporaneous list of open toxicokinetics tools that assist risk assessment.

Thematic Areas: Toxicology Saúde coletiva Química Pharmacology & pharmacy Odontología Medicine, legal Medicine (miscellaneous) Medicina ii Medicina i Interdisciplinar Farmacia Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciência de alimentos Biotecnología Biodiversidade

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 02732300

Author's mail: vikas.kumar@urv.cat

Author identifier: 0000-0002-9795-5967

Last page: 21

Record's date: 2023-02-18

Journal volume: 99

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.sciencedirect.com/science/article/pii/S0273230018302186

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Regulatory Toxicology And Pharmacology. 99 5-21

APA: Laroche C, Aggarwal M, Bender H, Benndorf P, Birk B, Crozier J, Dal Negro G, De Gaetano F, Desaintes C, Gardner I, Hubesch B, Irizar A, John D, Kumar (2018). Finding synergies for 3Rs - Toxicokinetics and read-across: Report from an EPAA partners' Forum. Regulatory Toxicology And Pharmacology, 99(), 5-21. DOI: 10.1016/j.yrtph.2018.08.006

Article's DOI: 10.1016/j.yrtph.2018.08.006

Entity: Universitat Rovira i Virgili

Journal publication year: 2018

First page: 5

Publication Type: Journal Publications