Author, as appears in the article.: Deepika, Deepika; Sharma, Raju Prasad; Schuhmacher, Marta; Kumar, Vikas
Department: Enginyeria Química
URV's Author/s: Kumar, Vikas / Schuhmacher Ansuategui, Marta
Keywords: (tdcipp) 3-dichloro-2-propyl phosphate 3-dichloro-2-propyl) phosphate Absorption Binding Disposition Enterohepatic recirculation (ehr) Exposure Human Human health risk assessmen Human health risk assessment Metabolism Neurotoxicity Organophosphate flame retardants Pbk model Pbk-ivive Pbpk models Pbpk-ivive Phosphate Protein Toxicity Tris (1-chloro-2-propyl) phosphate (tcipp) Tris (2-chloroethyl) phosphate (tcep) Tris (2-chloroethyl), phosphate (tcep) Tris 1 Tris(1 Tris(1,3-dichloro-2-propyl), phosphate (tdcipp) Tris(13-dichloro-2-propyl)
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/FlameRetardant-PBPK-Model: It contains organophosphate flame retardant (OPFRs) PBK for TDCIPP, TCIPP and TCEP (github.com).
Thematic Areas: Astronomia / física Biodiversidade Biotecnología Ciência de alimentos Ciências ambientais Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Educação física Engenharias i Engenharias ii Engenharias iii Engenharias iv Farmacia General medicine Geociências Historia Interdisciplinar Materiais Medicina i Medicina ii Medicina veterinaria Medicine (miscellaneous) Nutrição Odontología Psicología Química Saúde coletiva Toxicology Zootecnia / recursos pesqueiros
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: marta.schuhmacher@urv.cat vikas.kumar@urv.cat
Author identifier: 0000-0003-4381-2490 0000-0002-9795-5967
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Papper original source: Toxicology Letters. 383 128-140
APA: Deepika, Deepika; Sharma, Raju Prasad; Schuhmacher, Marta; Kumar, Vikas (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
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Entity: Universitat Rovira i Virgili
Journal publication year: 2023
Publication Type: Journal Publications
Repositori URV