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A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment

Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose. So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of...

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Autores principales: Bednarska, Agnieszka J., Edwards, Peter, Sibly, Richard, Thorbek, Pernille
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599210/
https://www.ncbi.nlm.nih.gov/pubmed/23430408
http://dx.doi.org/10.1007/s10646-013-1047-z
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author Bednarska, Agnieszka J.
Edwards, Peter
Sibly, Richard
Thorbek, Pernille
author_facet Bednarska, Agnieszka J.
Edwards, Peter
Sibly, Richard
Thorbek, Pernille
author_sort Bednarska, Agnieszka J.
collection PubMed
description Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose. So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of potential exposure in the field taking account of the timescale of exposure and individual patterns of feeding. Internal concentration is the net result of absorption, distribution, metabolism and excretion (ADME). We present a case study for thiamethoxam to show how data from ADME study on rats can be used to parameterize a body burden model which predicts body residue levels after exposures to LD(50) dose either as a bolus or eaten at different feeding rates. Kinetic parameters were determined in male and female rats after an intravenous and oral administration of (14)C labelled by fitting one-compartment models to measured pesticide concentrations in blood for each individual separately. The concentration of thiamethoxam in blood over time correlated closely with concentrations in other tissues and so was considered representative of pesticide concentration in the whole body. Body burden model simulations showed that maximum body weight-normalized doses of thiamethoxam were lower if the same external dose was ingested normally than if it was force fed in a single bolus dose. This indicates lower risk to rats through dietary exposure than would be estimated from the bolus LD(50). The importance of key questions that should be answered before using the body burden approach in risk assessment, data requirements and assumptions made in this study are discussed in detail.
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spelling pubmed-35992102013-03-19 A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment Bednarska, Agnieszka J. Edwards, Peter Sibly, Richard Thorbek, Pernille Ecotoxicology Article Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose. So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of potential exposure in the field taking account of the timescale of exposure and individual patterns of feeding. Internal concentration is the net result of absorption, distribution, metabolism and excretion (ADME). We present a case study for thiamethoxam to show how data from ADME study on rats can be used to parameterize a body burden model which predicts body residue levels after exposures to LD(50) dose either as a bolus or eaten at different feeding rates. Kinetic parameters were determined in male and female rats after an intravenous and oral administration of (14)C labelled by fitting one-compartment models to measured pesticide concentrations in blood for each individual separately. The concentration of thiamethoxam in blood over time correlated closely with concentrations in other tissues and so was considered representative of pesticide concentration in the whole body. Body burden model simulations showed that maximum body weight-normalized doses of thiamethoxam were lower if the same external dose was ingested normally than if it was force fed in a single bolus dose. This indicates lower risk to rats through dietary exposure than would be estimated from the bolus LD(50). The importance of key questions that should be answered before using the body burden approach in risk assessment, data requirements and assumptions made in this study are discussed in detail. Springer US 2013-02-22 2013 /pmc/articles/PMC3599210/ /pubmed/23430408 http://dx.doi.org/10.1007/s10646-013-1047-z Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Article
Bednarska, Agnieszka J.
Edwards, Peter
Sibly, Richard
Thorbek, Pernille
A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment
title A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment
title_full A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment
title_fullStr A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment
title_full_unstemmed A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment
title_short A toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment
title_sort toxicokinetic model for thiamethoxam in rats: implications for higher-tier risk assessment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599210/
https://www.ncbi.nlm.nih.gov/pubmed/23430408
http://dx.doi.org/10.1007/s10646-013-1047-z
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