A toxicokinetic model to assess exposure to folpet fungicide from urinary biomarkers

Détails

ID Serval
serval:BIB_0B77B2578A3C
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
A toxicokinetic model to assess exposure to folpet fungicide from urinary biomarkers
Titre de la conférence
50th Annual Meeting Society of Toxicology, March 6-10, 2011, Washington, D.C.
Auteur⸱e⸱s
Heredia Ortiz Roberto, Berthet Aurélie, Bouchard Michèle
ISBN
1096-6080
Statut éditorial
Publié
Date de publication
2011
Volume
120
Série
The Toxicologist CD
Pages
265-266
Langue
anglais
Résumé
Folpet is one of the most widely employed fungicides in agriculture. It is typically used in the culture of vegetables, fruits and ornamental plants. Once absorbed in the human body, it has been found to be very reactive, especially in acid conditions. According to various in vitro and in vivo experiments in animals, Folpet is first fractioned at the N-S link when in contact with aqueous solutions and thiol groups. From this non-enzymatic process a phthalimide (PI) molecule is formed, which may be used as a biomarker of exposure, along with the short-lived thiophosgene. We have built a human toxicokinetic model to account for the biotransformation of Folpet into PI and its subsequent excretion while accounting for other non-monitored metabolites. The mathematical parameters of the model were determined accordingly from best-fits to the time courses of PI in blood and urine of five volunteers administered orally 1 mg/kg and dermally 10 mg/kg of Folpet. In both cases, the mean elimination half-life of PI from the body (either through faeces, urine or metabolism) was found to be 31.6 h. The average final fractions of administered dose recovered in urine as PI were 0.025% and 0.002%, for oral and dermal administration, respectively after 96 h. According to the model, when orally administered, PI rapidly hydrolyzes to phthalamic and phthalic acids such that only 0.04%
of the PI found in the gastrointestinal tract is absorbed into the blood stream. Likewise, after dermal application, model predicts that only 7.4% of the applied Folpet dose crosses the epidermis. In the model, the PI initial metabolite of Folpet is formed in the dermis and further metabolized prior to reaching systemic circulation, such that only 0.125% of PI formed at the site-of-entry reaches systemic blood. Our mathematical model is in accordance with both measures of blood (R2=0.57 for dermal and R2=0.66 for oral) and urine (R2
=0.98 for dermal and R2=0.99 for oral).
Mots-clé
Fungicides, Industrial , Occupational Exposure , Models, Biological , Markers, Biological ,
Création de la notice
02/09/2011 11:02
Dernière modification de la notice
20/08/2019 12:33
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