Application of partition coefficient methods to predict tissue:plasma affinities in common farm animals: Influence of ionisation state DOI Creative Commons
L.S. Lautz, J.L.C.M. Dorne, Ans Punt

et al.

Toxicology Letters, Journal Year: 2024, Volume and Issue: 398, P. 140 - 149

Published: June 24, 2024

Tissue affinities are conventionally determined from in vivo steady-state tissue and plasma or plasma-water chemical concentration data. In silico approaches were initially developed for preclinical species but standardly applied tested human physiologically-based kinetic (PBK) models. Recently, generic PBK models farm animals have been made available require partition coefficients as input parameters. the current investigation, data species-specific compositions collected, prediction of distribution various tissues livestock cattle, chicken, sheep swine performed. Overall, composition was very similar across four animal species. However, small differences observed moisture, fat protein content organs within each Such could be attributed to factors such variations age, breed, weight general conditions itself. With regards predictions tissue:plasma coefficients, 80 %, 71 77 % model a factor 10 using methods Berezhkovskiy (2004), Rodgers Rowland (2006) Schmitt (2008). The method (2004) often providing most reliable except swine, where (2008) performed best. addition, investigation impact classes on performance, all had reliability. Notwithstanding, no clear pattern regarding specific chemicals detected values predicted outside 10-fold change certain tissues. This manuscript concludes with need future research, particularly focusing lipophilicity binding.

Language: Английский

A Simple Physiologically Based Toxicokinetic Model for Multi-Route In Vitro–In Vivo Extrapolation DOI
John F. Wambaugh, Celia Schacht, Caroline Ring

et al.

Environmental Science & Technology Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Many chemicals found in the environment and commerce have been characterized for potential hazards by using vitro screens. Translating concentrations that cause bioactivity into real-world exposures, other words, vitro–in vivo extrapolation (IVIVE), requires chemical-specific parameters mathematical models. An administered (for example, oral) equivalent dose rate (milligrams per kilogram day) causes steady-state human plasma (micromolar) to bioactive can be derived a simple IVIVE equation. Herein, we explain how this equation approximates physiologically based toxicokinetic (PBTK) model. Through derivation of solution PBTK model, show relevant flows tissues. We then extend modifying oral exposure model include gas inhalation exhalation. Gas exhalation increases clearance, potentially allowing more accurate prediction semivolatile organic chemicals. The revised equations also allow doses, parts million concentration would concentrations. comparison an new developed, describing exhaled doses.

Language: Английский

Citations

0
User Guide for TKPlate 1.0: An open access platform for implementing new approach methodologies in chemical risk assessment through toxicokinetic and toxicodynamic modelling DOI Open Access
Han Bossier,

J. Cortinas-Abrahantes,

Keyvin Darney

et al.

EFSA Supporting Publications, Journal Year: 2023, Volume and Issue: 20(11)

Published: Nov. 1, 2023

This technical report provides a user guide for the TKPlate 1.0 platform which allows to implement New Approach Methodologies in chemical risk assessment process by means of toxicokinetic and toxicodynamic modelling chemicals humans, laboratory animals, farm animals species ecological relevance. is available as an open access web-based tool or downloadable application. The built workflow 7 modules: 1. Input module can select species, kinetic physiologically-based model, be modelled, exposure scenarios simulation times, 2. Forward dosimetry allowing simulate parameters, body fluid organ concentrations, 3. Reverse reconstruction distributions using internal dose such biomonitoring data, 4. Benchmark model averaging on basis, 5. Dynamic energy budget modelling, 6. Mixture characterisation methods from EFSA's Scientific committee guidance document, 7. Automated where input output data report, graphs datasets. For each module, structure applications are described with examples. development external scientific associated EFSA editorial two reports namely case studies illustrating 1.0. Finally, all models files also published Zenodo (https://zenodo.org/record/7494936).

Language: Английский

Citations

5
Application of partition coefficient methods to predict tissue:plasma affinities in common farm animals: Influence of ionisation state DOI Creative Commons
L.S. Lautz, J.L.C.M. Dorne, Ans Punt

et al.

Toxicology Letters, Journal Year: 2024, Volume and Issue: 398, P. 140 - 149

Published: June 24, 2024

Tissue affinities are conventionally determined from in vivo steady-state tissue and plasma or plasma-water chemical concentration data. In silico approaches were initially developed for preclinical species but standardly applied tested human physiologically-based kinetic (PBK) models. Recently, generic PBK models farm animals have been made available require partition coefficients as input parameters. the current investigation, data species-specific compositions collected, prediction of distribution various tissues livestock cattle, chicken, sheep swine performed. Overall, composition was very similar across four animal species. However, small differences observed moisture, fat protein content organs within each Such could be attributed to factors such variations age, breed, weight general conditions itself. With regards predictions tissue:plasma coefficients, 80 %, 71 77 % model a factor 10 using methods Berezhkovskiy (2004), Rodgers Rowland (2006) Schmitt (2008). The method (2004) often providing most reliable except swine, where (2008) performed best. addition, investigation impact classes on performance, all had reliability. Notwithstanding, no clear pattern regarding specific chemicals detected values predicted outside 10-fold change certain tissues. This manuscript concludes with need future research, particularly focusing lipophilicity binding.

Language: Английский

Citations

1