Author, as appears in the article.: Deepika D; Sharma RP; Schuhmacher M; Kumar V
Department: Enginyeria Química
URV's Author/s: Kumar, Vikas / Schuhmacher Ansuategui, Marta
Keywords: Tris(1,3-dichloro-2-propyl), phosphate (tdcipp) Tris (2-chloroethyl), phosphate (tcep) Tris (1-chloro-2-propyl) phosphate (tcipp) Pbpk-ivive Pbpk models Pbk-ivive Pbk model Organophosphate flame retardants Neurotoxicity Human health risk assessment Enterohepatic recirculation (ehr)
Abstract: Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), Tris (1-chloro-2-propyl) phosphate (TCIPP) and tris (2-chloroethyl) phosphate (TCEP) are three widely used organophosphate flame retardants (OPFRs) being frequently detected in human body fluids. Although OPFRs are being detected in human beings, the toxicological effects of their exposure are not clearly understood due to limited data. For this, a physiologically based kinetic model (PBK) was developed in MCSIM integrated with R studio and validated in rats to understand the toxicokinetics of OPFRs for the first time. The model required the enterohepatic recirculation (EHR) mechanism which was included to explain the non-linear data. Model parameters were optimized using the Bayesian framework (Markov Chain Monte Carlo) along with a visual fitting to explain toxicokinetic data. Goodness-of-fit was calculated to evaluate model predictability power in Rstudio. The model can appropriately predict the concentration of OPFRs in several organs like plasma, urine, kidney, etc. within 1-2-fold of experimental data. Slow elimination of OPFRs was observed from adipose tissue and brain at late time points, showing their potential to accumulate upon daily exposure. The use of PBK was demonstrated by reconstructing the oral exposure equivalent to the in-vitro toxic dose to support neurotoxic risk assessment. This version of PBK can be extrapolated to human for toxicological risk assessment. Nonetheless, further investigation is required to understand whether these chemicals follow similar kinetics in humans, which could lead to a greater risk to human health. CODE AVAILABILITY: The model will be available to access through Rshiny using GIThub soon, InSilicoVida/Flame-Retardant-PBPK-Model: It contains organophosphate flame retardant (OPFRs) PBK for TDCIPP, TCIPP and TCEP (github.com).Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Thematic Areas: Zootecnia / recursos pesqueiros Toxicology Saúde coletiva Química Psicología Odontología Nutrição Medicine (miscellaneous) Medicina veterinaria Medicina ii Medicina i Materiais Interdisciplinar Historia Geociências General medicine Farmacia Engenharias iv Engenharias iii Engenharias ii Engenharias i Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciência de alimentos Biotecnología Biodiversidade Astronomia / física
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: vikas.kumar@urv.cat marta.schuhmacher@urv.cat
Author identifier: 0000-0002-9795-5967 0000-0003-4381-2490
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.sciencedirect.com/science/article/pii/S0378427423002060
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Toxicology Letters. 383 128-140
APA: Deepika D; Sharma RP; Schuhmacher M; Kumar V (2023). Development of a Rat Physiologically Based Kinetic Model (PBK) for three Organophosphate Flame Retardants (TDCIPP, TCIPP, TCEP). Toxicology Letters, 383(), 128-140. DOI: 10.1016/j.toxlet.2023.06.006
Article's DOI: 10.1016/j.toxlet.2023.06.006
Entity: Universitat Rovira i Virgili
Journal publication year: 2023
Publication Type: Journal Publications
Repositori URV