Universität zu Köln

Cote, Jonathan, Bonvalot, Yvette, Carrier, Gaetan, Lapointe, Caroline, Fuhr, Uwe, Tomalik-Scharte, Dorota, Wachall, Bertil and Bouchard, Michele (2014). A Novel Toxicokinetic Modeling of Cypermethrin and Permethrin and Their Metabolites in Humans for Dose Reconstruction from Biomarker Data. PLoS One, 9 (2). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

To assess exposure to pyrethroids in the general population, one of most widely used method nowadays consists of measuring urinary metabolites. Unfortunately, interpretation of data is limited by the unspecified relation between dose and levels in biological tissues and excreta. The objective of this study was to develop a common multi-compartment toxicokinetic model to predict the time courses of two mainly used pyrethroid pesticides, permethrin and cypermethrin, and their metabolites (cis-DCCA, trans-DCCA and 3-PBA) in the human body and in accessible biological matrices following different exposure scenarios. Toxicokinetics was described mathematically by systems of differential equations to yield the time courses of these pyrethroids and their metabolites in the different compartments. Unknown transfer rate values between compartments were determined from best fits to available human data on the urinary excretion time courses of metabolites following an oral and dermal exposure to cypermethrin in volunteers. Since values for these coefficients have not yet been determined, a mathematical routine was programmed in MathCad to establish the possible range of values on the basis of physiological and mathematical considerations. The best combination of parameter values was then selected using a statistic measure (reliability factor) along with a statistically acceptable range of values for each parameter. With this approach, simulations provided a close approximation to published time course data. This model allows to predict urinary time courses of trans-DCCA, cis-DCCA and 3-PBA, whatever the exposure route. It can also serve to reconstruct absorbed doses of permethrin or cypermethrin in the population using measured biomarker data.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cote, Jonathan UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonvalot, Yvette UNSPECIFIED UNSPECIFIED UNSPECIFIED Carrier, Gaetan UNSPECIFIED UNSPECIFIED UNSPECIFIED Lapointe, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Tomalik-Scharte, Dorota UNSPECIFIED UNSPECIFIED UNSPECIFIED Wachall, Bertil UNSPECIFIED UNSPECIFIED UNSPECIFIED Bouchard, Michele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-445680
DOI:	10.1371/journal.pone.0088517
Journal or Publication Title:	PLoS One
Volume:	9
Number:	2
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HORTICULTURAL GREENHOUSE WORKERS; PYRETHROID PESTICIDES; IN-VITRO; CLINICAL-MANIFESTATIONS; ANTIANDROGENIC ACTIVITY; PHARMACOKINETIC MODEL; GAS-CHROMATOGRAPHY; TRANS-PERMETHRIN; DNA-DAMAGE; EXPOSURE Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44568