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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Heredia-Ortiz, Roberto Berthet, Aurélie Bouchard, Michèle
Description	Country affiliation: Canada Author Affiliation: Heredia-Ortiz R ( Département de santé environnementale et santé au travail, Chaire d'analyse et de gestion des risques toxicologiques and Institut de recherche en santé publique de l'Université de Montréal, Faculté de Médecine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec, Canada.)
Abstract	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.
File Format	HTM / HTML
ISSN	0260437X
Issue Number	7
Volume Number	33
e-ISSN	10991263
Journal	Journal of Applied Toxicology
Language	English
Publisher	Wiley
Publisher Date	2013-07-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Biological Markers Analysis Fungicides, Industrial Pharmacokinetics Toxicity Phthalimides Administration, Oral Administration, Topical Algorithms Area Under Curve Biotransformation Half-life Humans Inhalation Exposure Models, Biological Models, Statistical Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Toxicology

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