Physiologically based kinetic models for farm animals: Critical review of published models and future perspectives for their use in chemical risk assessment

L. S. Lautz*, R. Oldenkamp, J. L. Dorne, A. M. J. Ragas

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Physiologically based kinetic (PBK) models in the 10 most common species of farm animals were identified through an extensive literature search. This resulted In 39 PBK models, mostly for pharmaceuticals. The models were critically assessed using the WHO criteria for model evaluation, i.e. 1) purpose, 2) structure and mathematical representation, 3) computer implementation, 4) parameterisation, 5) performance, and 6) documentation. Overall, most models were calibrated and validated with published data (92% and 67% respectively) but only a fraction of model codes were published along with the manuscript (28 and local sensitivity analysis was performed without considering global sensitivity analysis. Hence, the reliability of these PBK models is hard to assess and their potential for use in chemical risk assessment is limited. In a risk assessment context, future PBK models for farm animals should include a more generic and flexible model structure, use input parameters independent on calibration and include assessment tools to assess model performance. Development and application of PBK models for farm animal species would furthermore benefit from the setup of structured databases providing data on physiological and chemical-specific parameters as well as enzyme expression and activities to support the development of species-specific QIVIVE models.
Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalToxicology in Vitro
Volume60
DOIs
Publication statusPublished - Oct 2019

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Domestic Animals
Risk assessment
Farms
Animals
Kinetics
Manuscripts
Documentation
Calibration
Sensitivity analysis
Databases
Enzymes
Pharmaceutical Preparations
Model structures
Parameterization

Cite this

@article{fe66676db8ff47d39512853abdf1331c,
title = "Physiologically based kinetic models for farm animals: Critical review of published models and future perspectives for their use in chemical risk assessment",
abstract = "Physiologically based kinetic (PBK) models in the 10 most common species of farm animals were identified through an extensive literature search. This resulted In 39 PBK models, mostly for pharmaceuticals. The models were critically assessed using the WHO criteria for model evaluation, i.e. 1) purpose, 2) structure and mathematical representation, 3) computer implementation, 4) parameterisation, 5) performance, and 6) documentation. Overall, most models were calibrated and validated with published data (92{\%} and 67{\%} respectively) but only a fraction of model codes were published along with the manuscript (28 and local sensitivity analysis was performed without considering global sensitivity analysis. Hence, the reliability of these PBK models is hard to assess and their potential for use in chemical risk assessment is limited. In a risk assessment context, future PBK models for farm animals should include a more generic and flexible model structure, use input parameters independent on calibration and include assessment tools to assess model performance. Development and application of PBK models for farm animal species would furthermore benefit from the setup of structured databases providing data on physiological and chemical-specific parameters as well as enzyme expression and activities to support the development of species-specific QIVIVE models.",
author = "Lautz, {L. S.} and R. Oldenkamp and Dorne, {J. L.} and Ragas, {A. M. J.}",
year = "2019",
month = "10",
doi = "10.1016/j.tiv.2019.05.002",
language = "English",
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journal = "Toxicology in Vitro",
issn = "0887-2333",
publisher = "Elsevier Ltd",

}

Physiologically based kinetic models for farm animals : Critical review of published models and future perspectives for their use in chemical risk assessment. / Lautz, L. S.; Oldenkamp, R.; Dorne, J. L.; Ragas, A. M. J.

In: Toxicology in Vitro, Vol. 60, 10.2019, p. 61-70.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Physiologically based kinetic models for farm animals

T2 - Critical review of published models and future perspectives for their use in chemical risk assessment

AU - Lautz, L. S.

AU - Oldenkamp, R.

AU - Dorne, J. L.

AU - Ragas, A. M. J.

PY - 2019/10

Y1 - 2019/10

N2 - Physiologically based kinetic (PBK) models in the 10 most common species of farm animals were identified through an extensive literature search. This resulted In 39 PBK models, mostly for pharmaceuticals. The models were critically assessed using the WHO criteria for model evaluation, i.e. 1) purpose, 2) structure and mathematical representation, 3) computer implementation, 4) parameterisation, 5) performance, and 6) documentation. Overall, most models were calibrated and validated with published data (92% and 67% respectively) but only a fraction of model codes were published along with the manuscript (28 and local sensitivity analysis was performed without considering global sensitivity analysis. Hence, the reliability of these PBK models is hard to assess and their potential for use in chemical risk assessment is limited. In a risk assessment context, future PBK models for farm animals should include a more generic and flexible model structure, use input parameters independent on calibration and include assessment tools to assess model performance. Development and application of PBK models for farm animal species would furthermore benefit from the setup of structured databases providing data on physiological and chemical-specific parameters as well as enzyme expression and activities to support the development of species-specific QIVIVE models.

AB - Physiologically based kinetic (PBK) models in the 10 most common species of farm animals were identified through an extensive literature search. This resulted In 39 PBK models, mostly for pharmaceuticals. The models were critically assessed using the WHO criteria for model evaluation, i.e. 1) purpose, 2) structure and mathematical representation, 3) computer implementation, 4) parameterisation, 5) performance, and 6) documentation. Overall, most models were calibrated and validated with published data (92% and 67% respectively) but only a fraction of model codes were published along with the manuscript (28 and local sensitivity analysis was performed without considering global sensitivity analysis. Hence, the reliability of these PBK models is hard to assess and their potential for use in chemical risk assessment is limited. In a risk assessment context, future PBK models for farm animals should include a more generic and flexible model structure, use input parameters independent on calibration and include assessment tools to assess model performance. Development and application of PBK models for farm animal species would furthermore benefit from the setup of structured databases providing data on physiological and chemical-specific parameters as well as enzyme expression and activities to support the development of species-specific QIVIVE models.

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DO - 10.1016/j.tiv.2019.05.002

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VL - 60

SP - 61

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JO - Toxicology in Vitro

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SN - 0887-2333

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