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Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure

Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunte...

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Autores principales: Sams, Craig, Jones, Kate, Galea, Karen S., MacCalman, Laura, Cocker, John, Teedon, Paul, Cherrie, John W., van Tongeren, Martie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606630/
https://www.ncbi.nlm.nih.gov/pubmed/29051415
http://dx.doi.org/10.3390/toxics4020010
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author Sams, Craig
Jones, Kate
Galea, Karen S.
MacCalman, Laura
Cocker, John
Teedon, Paul
Cherrie, John W.
van Tongeren, Martie
author_facet Sams, Craig
Jones, Kate
Galea, Karen S.
MacCalman, Laura
Cocker, John
Teedon, Paul
Cherrie, John W.
van Tongeren, Martie
author_sort Sams, Craig
collection PubMed
description Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54%) in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.
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spelling pubmed-56066302017-10-18 Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure Sams, Craig Jones, Kate Galea, Karen S. MacCalman, Laura Cocker, John Teedon, Paul Cherrie, John W. van Tongeren, Martie Toxics Article Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54%) in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended. MDPI 2016-05-13 /pmc/articles/PMC5606630/ /pubmed/29051415 http://dx.doi.org/10.3390/toxics4020010 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sams, Craig
Jones, Kate
Galea, Karen S.
MacCalman, Laura
Cocker, John
Teedon, Paul
Cherrie, John W.
van Tongeren, Martie
Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure
title Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure
title_full Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure
title_fullStr Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure
title_full_unstemmed Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure
title_short Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure
title_sort development of a biomarker for penconazole: a human oral dosing study and a survey of uk residents’ exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606630/
https://www.ncbi.nlm.nih.gov/pubmed/29051415
http://dx.doi.org/10.3390/toxics4020010
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