Evaluation of PBK models using the OECD assessment framework
taking PFAS as case study

J 2025

Evaluation of PBK models using the OECD assessment framework taking PFAS as case study

DEEPIKA, Deepika; Kanchan BHARTI; Shubh SHARMA; Saurav KUMAR; Trine HUSOY et al.

Základní údaje

Originální název

Evaluation of PBK models using the OECD assessment framework taking PFAS as case study

Autoři

Vydání

Computational Toxicology, AMSTERDAM, Elsevier, 2025, 2468-1113

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30108 Toxicology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.900 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

PBK; OECD PBK guidance; PFAS; FAIR PBK; Rshiny application

Štítky

143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 19. 11. 2025 09:40, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

Physiologically based kinetic (PBK) models are becoming increasingly important in chemical risk assessment, helping in linking external and internal exposure concentrations, thereby supporting the development of regulatory health-based limits for chemicals with exposure from environmental, occupational, and consumer sources. To increase confidence in PBK models for regulatory purposes, the OECD published a guidance document in 2021 outlining the characterization, validation and reporting of PBK models. However, its use remains limited in chemical toxicology as reflected by the few publications that have applied it during model development. The aim of this study was to evaluate several published PBK models for Per- and polyfluoroalkyl substances (PFASs) as proof of concept to assess their validity and credibility for regulatory purposes, based on the OECD guidance. Out of 28 published PFASs human PBK models considered, 11 were selected for evaluation. The assessment used the OECD guidance document, encompassing two main areas: i) documentation (context/implementation, documentation, software implementation, verification, and peer engagement) and ii) assessment of model validity (biological basis, theoretical basis of model equations, input parameter's reliability, uncertainty and sensitivity analysis, goodness-of-fit and predictivity). To standardize this process, an online evaluation system based on the OECD guidance was developed and used for this model evaluation exercise. The collected data were analysed to assess the overall quality of published models and identify limitations in the current PFAS model landscape. Our analysis revealed opportunities for improvement in the biological representation within current PFAS models, particularly regarding the inclusion of diverse population groups. Currently, PFAS models primarily focus on only four compounds, highlighting an opportunity to extend coverage to other PFASs using read-across approaches for data-poor chemicals. Furthermore, our findings show that a harmonized approach for PBK model reporting is needed. To facilitate broader adoption of the OECD guidance, we developed and hosted an R Shiny template on our group's web server (https://app.shiny.insilicohub.org/Evaluation_PBPK/). This template can act as valuable tool for researchers evaluating PBK models according to the OECD guidance. GitHub: PBPK-OECD-EVALUATION.

Návaznosti

101057014, interní kód MU

Název: Partnership for the Assessment of Risks from Chemicals (Akronym: PARC)

Investor: Evropská unie, Partnership for the Assessment of Risks from Chemicals, Klastr 1 - Zdraví

Přiložené soubory

2533942.pdf

Citovat

DEEPIKA, Deepika; Kanchan BHARTI; Shubh SHARMA; Saurav KUMAR; Trine HUSOY; Marcin W. WOJEWODZIC; Klára KOMPRDOVÁ; Aude RATIER; Joost WESTERHOUT; Thomas GASTELLU; Meg-Anne MORICEAU; Sanah MAJID; Renske HOONDERT; Johannes KRUISSELBRINK; Jasper ENGEL; Annelies NOORLANDER; Carolina VOGS a Vikas KUMAR. Evaluation of PBK models using the OECD assessment framework taking PFAS as case study. Computational Toxicology. AMSTERDAM: Elsevier, 2025, roč. 36, December 2025, s. 1-10. ISSN 2468-1113. Dostupné z: https://doi.org/10.1016/j.comtox.2025.100381.

@article{2533942,
   author = {Deepika, Deepika and Bharti, Kanchan and Sharma, Shubh and Kumar, Saurav and HusOy, Trine and Wojewodzic, Marcin W. and Komprdová, Klára and Ratier, Aude and Westerhout, Joost and Gastellu, Thomas and Moriceau, MegandAnne and Majid, Sanah and Hoondert, Renske and Kruisselbrink, Johannes and Engel, Jasper and Noorlander, Annelies and Vogs, Carolina and Kumar, Vikas},
   article_location = {AMSTERDAM},
   article_number = {December 2025},
   doi = {https://doi.org/10.1016/j.comtox.2025.100381},
   keywords = {PBK; OECD PBK guidance; PFAS; FAIR PBK; Rshiny application},
   language = {eng},
   issn = {2468-1113},
   journal = {Computational Toxicology},
   title = {Evaluation of PBK models using the OECD assessment framework taking PFAS as case study},
   url = {https://www.sciencedirect.com/science/article/pii/S2468111325000416?via%3Dihub},
   volume = {36},
   year = {2025}
}

TY  - JOUR
ID  - 2533942
AU  - Deepika, Deepika - Bharti, Kanchan - Sharma, Shubh - Kumar, Saurav - HusOy, Trine - Wojewodzic, Marcin W. - Komprdová, Klára - Ratier, Aude - Westerhout, Joost - Gastellu, Thomas - Moriceau, Meg-Anne - Majid, Sanah - Hoondert, Renske - Kruisselbrink, Johannes - Engel, Jasper - Noorlander, Annelies - Vogs, Carolina - Kumar, Vikas
PY  - 2025
TI  - Evaluation of PBK models using the OECD assessment framework taking PFAS as case study
JF  - Computational Toxicology
VL  - 36
IS  - December 2025
SP  - 1-10
EP  - 1-10
PB  - Elsevier
SN  - 24681113
KW  - PBK
KW  - OECD PBK guidance
KW  - PFAS
KW  - FAIR PBK
KW  - Rshiny application
UR  - https://www.sciencedirect.com/science/article/pii/S2468111325000416?via%3Dihub
N2  - Physiologically based kinetic (PBK) models are becoming increasingly important in chemical risk assessment, helping in linking external and internal exposure concentrations, thereby supporting the development of regulatory health-based limits for chemicals with exposure from environmental, occupational, and consumer sources. To increase confidence in PBK models for regulatory purposes, the OECD published a guidance document in 2021 outlining the characterization, validation and reporting of PBK models. However, its use remains limited in chemical toxicology as reflected by the few publications that have applied it during model development. The aim of this study was to evaluate several published PBK models for Per- and polyfluoroalkyl substances (PFASs) as proof of concept to assess their validity and credibility for regulatory purposes, based on the OECD guidance. Out of 28 published PFASs human PBK models considered, 11 were selected for evaluation. The assessment used the OECD guidance document, encompassing two main areas: i) documentation (context/implementation, documentation, software implementation, verification, and peer engagement) and ii) assessment of model validity (biological basis, theoretical basis of model equations, input parameter's reliability, uncertainty and sensitivity analysis, goodness-of-fit and predictivity). To standardize this process, an online evaluation system based on the OECD guidance was developed and used for this model evaluation exercise. The collected data were analysed to assess the overall quality of published models and identify limitations in the current PFAS model landscape. Our analysis revealed opportunities for improvement in the biological representation within current PFAS models, particularly regarding the inclusion of diverse population groups. Currently, PFAS models primarily focus on only four compounds, highlighting an opportunity to extend coverage to other PFASs using read-across approaches for data-poor chemicals. Furthermore, our findings show that a harmonized approach for PBK model reporting is needed. To facilitate broader adoption of the OECD guidance, we developed and hosted an R Shiny template on our group's web server (https://app.shiny.insilicohub.org/Evaluation_PBPK/). This template can act as valuable tool for researchers evaluating PBK models according to the OECD guidance. GitHub: PBPK-OECD-EVALUATION.
ER  -

DEEPIKA, Deepika; Kanchan BHARTI; Shubh SHARMA; Saurav KUMAR; Trine HUSOY; Marcin W. WOJEWODZIC; Klára KOMPRDOVÁ; Aude RATIER; Joost WESTERHOUT; Thomas GASTELLU; Meg-Anne MORICEAU; Sanah MAJID; Renske HOONDERT; Johannes KRUISSELBRINK; Jasper ENGEL; Annelies NOORLANDER; Carolina VOGS a Vikas KUMAR. Evaluation of PBK models using the OECD assessment framework taking PFAS as case study. \textit{Computational Toxicology}. AMSTERDAM: Elsevier, 2025, roč.~36, December 2025, s.~1-10. ISSN~2468-1113. Dostupné z: https://doi.org/10.1016/j.comtox.2025.100381.

Přehled o publikaci