Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

The objective of the present work was to review the availability and predictive value of non-animal toxicokinetic approaches and to evaluate their current use in European risk evaluations of food contaminants, additives and food contact materials, as well as pesticides and medicines. Results revealed little use of quantitative animal or human kinetic data in risk evaluations of food chemicals, compared with pesticides and medicines. Risk evaluations of medicines provided sufficient in vivo kinetic data from different species to evaluate the predictive value of animal kinetic data for humans. These data showed a relatively poor correlation between the in vivo bioavailability in rats and dogs versus that in humans. In contrast, in vitro (human) kinetic data have been demonstrated to provide adequate predictions of the fate of compounds in humans, using appropriate in vitro-in vivo scalers and by integration of in vitro kinetic data with in silico kinetic modelling. Even though in vitro kinetic data were found to be occasionally included within risk evaluations of food chemicals, particularly results from Caco-2 absorption experiments and in vitro data on gut-microbial conversions, only minor use of in vitro methods for metabolism and quantitative in vitro-in vivo extrapolation methods was identified. Yet, such quantitative predictions are essential in the development of alternatives to animal testing as well as to increase human relevance of toxicological risk evaluations. Future research should aim at further improving and validating quantitative alternative methods for kinetics, thereby increasing regulatory acceptance of non-animal kinetic data.

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Main Authors: Punt, Ans, Peijnenburg, Ad A.C.M., Hoogenboom, Ron L.A.P., Bouwmeester, Hans
Format: Article/Letter to editor biblioteca
Language:English
Subjects:Alternatives to animal testing, In vitro kinetics, PBPK, Regulatory acceptance,
Online Access:https://research.wur.nl/en/publications/non-animal-approaches-for-toxicokinetics-in-risk-evaluations-of-f
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spelling dig-wur-nl-wurpubs-5305592024-08-14 Punt, Ans Peijnenburg, Ad A.C.M. Hoogenboom, Ron L.A.P. Bouwmeester, Hans Article/Letter to editor Altex 34 (2017) 4 ISSN: 1868-596X Non-animal approaches for toxicokinetics in risk evaluations of food chemicals 2017 The objective of the present work was to review the availability and predictive value of non-animal toxicokinetic approaches and to evaluate their current use in European risk evaluations of food contaminants, additives and food contact materials, as well as pesticides and medicines. Results revealed little use of quantitative animal or human kinetic data in risk evaluations of food chemicals, compared with pesticides and medicines. Risk evaluations of medicines provided sufficient in vivo kinetic data from different species to evaluate the predictive value of animal kinetic data for humans. These data showed a relatively poor correlation between the in vivo bioavailability in rats and dogs versus that in humans. In contrast, in vitro (human) kinetic data have been demonstrated to provide adequate predictions of the fate of compounds in humans, using appropriate in vitro-in vivo scalers and by integration of in vitro kinetic data with in silico kinetic modelling. Even though in vitro kinetic data were found to be occasionally included within risk evaluations of food chemicals, particularly results from Caco-2 absorption experiments and in vitro data on gut-microbial conversions, only minor use of in vitro methods for metabolism and quantitative in vitro-in vivo extrapolation methods was identified. Yet, such quantitative predictions are essential in the development of alternatives to animal testing as well as to increase human relevance of toxicological risk evaluations. Future research should aim at further improving and validating quantitative alternative methods for kinetics, thereby increasing regulatory acceptance of non-animal kinetic data. en application/pdf https://research.wur.nl/en/publications/non-animal-approaches-for-toxicokinetics-in-risk-evaluations-of-f 10.14573/altex.1702211 https://edepot.wur.nl/429077 Alternatives to animal testing In vitro kinetics PBPK Regulatory acceptance https://creativecommons.org/licenses/by/4.0/ Wageningen University & Research
institution WUR NL
collection DSpace
country Países bajos
countrycode NL
component Bibliográfico
access En linea
databasecode dig-wur-nl
tag biblioteca
region Europa del Oeste
libraryname WUR Library Netherlands
language English
topic Alternatives to animal testing
In vitro kinetics
PBPK
Regulatory acceptance
Alternatives to animal testing
In vitro kinetics
PBPK
Regulatory acceptance
spellingShingle Alternatives to animal testing
In vitro kinetics
PBPK
Regulatory acceptance
Alternatives to animal testing
In vitro kinetics
PBPK
Regulatory acceptance
Punt, Ans
Peijnenburg, Ad A.C.M.
Hoogenboom, Ron L.A.P.
Bouwmeester, Hans
Non-animal approaches for toxicokinetics in risk evaluations of food chemicals
description The objective of the present work was to review the availability and predictive value of non-animal toxicokinetic approaches and to evaluate their current use in European risk evaluations of food contaminants, additives and food contact materials, as well as pesticides and medicines. Results revealed little use of quantitative animal or human kinetic data in risk evaluations of food chemicals, compared with pesticides and medicines. Risk evaluations of medicines provided sufficient in vivo kinetic data from different species to evaluate the predictive value of animal kinetic data for humans. These data showed a relatively poor correlation between the in vivo bioavailability in rats and dogs versus that in humans. In contrast, in vitro (human) kinetic data have been demonstrated to provide adequate predictions of the fate of compounds in humans, using appropriate in vitro-in vivo scalers and by integration of in vitro kinetic data with in silico kinetic modelling. Even though in vitro kinetic data were found to be occasionally included within risk evaluations of food chemicals, particularly results from Caco-2 absorption experiments and in vitro data on gut-microbial conversions, only minor use of in vitro methods for metabolism and quantitative in vitro-in vivo extrapolation methods was identified. Yet, such quantitative predictions are essential in the development of alternatives to animal testing as well as to increase human relevance of toxicological risk evaluations. Future research should aim at further improving and validating quantitative alternative methods for kinetics, thereby increasing regulatory acceptance of non-animal kinetic data.
format Article/Letter to editor
topic_facet Alternatives to animal testing
In vitro kinetics
PBPK
Regulatory acceptance
author Punt, Ans
Peijnenburg, Ad A.C.M.
Hoogenboom, Ron L.A.P.
Bouwmeester, Hans
author_facet Punt, Ans
Peijnenburg, Ad A.C.M.
Hoogenboom, Ron L.A.P.
Bouwmeester, Hans
author_sort Punt, Ans
title Non-animal approaches for toxicokinetics in risk evaluations of food chemicals
title_short Non-animal approaches for toxicokinetics in risk evaluations of food chemicals
title_full Non-animal approaches for toxicokinetics in risk evaluations of food chemicals
title_fullStr Non-animal approaches for toxicokinetics in risk evaluations of food chemicals
title_full_unstemmed Non-animal approaches for toxicokinetics in risk evaluations of food chemicals
title_sort non-animal approaches for toxicokinetics in risk evaluations of food chemicals
url https://research.wur.nl/en/publications/non-animal-approaches-for-toxicokinetics-in-risk-evaluations-of-f
work_keys_str_mv AT puntans nonanimalapproachesfortoxicokineticsinriskevaluationsoffoodchemicals
AT peijnenburgadacm nonanimalapproachesfortoxicokineticsinriskevaluationsoffoodchemicals
AT hoogenboomronlap nonanimalapproachesfortoxicokineticsinriskevaluationsoffoodchemicals
AT bouwmeesterhans nonanimalapproachesfortoxicokineticsinriskevaluationsoffoodchemicals
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