Toxicokinetic modeling of folpet fungicide and its ring-biomarkers of exposure in humans.

Détails

Ressource 1Télécharger: 2013_Herredia_JAT_postprint.pdf (530.90 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_E81E7FFC6428
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Toxicokinetic modeling of folpet fungicide and its ring-biomarkers of exposure in humans.
Périodique
Journal of Applied Toxicology
Auteur⸱e⸱s
Heredia-Ortiz Roberto, Berthet Aurélie, Bouchard Michèle
ISSN
1099-1263 (Electronic)
ISSN-L
0260-437X
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
33
Numéro
7
Pages
607-617
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
A human in vivo toxicokinetic model was built to allow a better understanding of the toxicokinetics of folpet fungicide and its key ring biomarkers of exposure: phthalimide (PI), phthalamic acid (PAA) and phthalic acid (PA). Both PI and the sum of ring metabolites, expressed as PA equivalents (PAeq), may be used as biomarkers of exposure. The conceptual representation of the model was based on the analysis of the time course of these biomarkers in volunteers orally and dermally exposed to folpet. In the model, compartments were also used to represent the body burden of folpet and experimentally relevant PI, PAA and PA ring metabolites in blood and in key tissues as well as in excreta, hence urinary and feces. The time evolution of these biomarkers in each compartment of the model was then mathematically described by a system of coupled differential equations. The mathematical parameters of the model were then determined from best fits to the time courses of PI and PAeq in blood and urine of five volunteers administered orally 1 mg kg(-1) and dermally 10 mg kg(-1) of folpet. In the case of oral administration, the mean elimination half-life of PI from blood (through feces, urine or metabolism) was found to be 39.9 h as compared with 28.0 h for PAeq. In the case of a dermal application, mean elimination half-life of PI and PAeq was estimated to be 34.3 and 29.3 h, respectively. The average final fractions of administered dose recovered in urine as PI over the 0-96 h period were 0.030 and 0.002%, for oral and dermal exposure, respectively. Corresponding values for PAeq were 24.5 and 1.83%, respectively. Finally, the average clearance rate of PI from blood calculated from the oral and dermal data was 0.09 ± 0.03 and 0.13 ± 0.05 ml h(-1) while the volume of distribution was 4.30 ± 1.12 and 6.05 ± 2.22 l, respectively. It was not possible to obtain the corresponding values from PAeq data owing to the lack of blood time course data.
Mots-clé
Administration, Oral, Administration, Topical, Algorithms, Area Under Curve, Biological Markers/analysis, Biotransformation, Fungicides, Industrial/pharmacokinetics, Fungicides, Industrial/toxicity, Half-Life, Humans, Inhalation Exposure, Models, Biological, Models, Statistical, Pharmacokinetics, Phthalimides/pharmacokinetics, Phthalimides/toxicity
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/02/2012 10:25
Dernière modification de la notice
20/08/2019 16:10
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