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A novel toxicokinetic modeling of cypermethrin and permethrin and their metabolites in humans for dose reconstruction from biomarker data.

Côté J, Bonvalot Y, Carrier G, Lapointe C, Fuhr U, Tomalik-Scharte D, Wachall B, Bouchard M - PLoS ONE (2014)

Bottom Line: 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.It can also serve to reconstruct absorbed doses of permethrin or cypermethrin in the population using measured biomarker data.

View Article: PubMed Central - PubMed

Affiliation: 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 (IRSPUM), Université de Montréal, Montreal, Quebec, Canada.

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.

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Related in: MedlinePlus

Comparison of model simulations with experimental data for DCCA (volunteers dermally exposed).Comparison of model simulations (lines) with experimental data of Tomalik-Scharte et al. (2005) (symbols) on the average time courses of DCCA excretion rate (A) and cumulative excretion (B) (% of applied dose) in healthy volunteers following a dermal application of 215 mg of a permethrin solution on the scalp. Diamond symbols represent average experimental values and vertical bars the experimental standard deviation (n = 6).
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pone-0088517-g009: Comparison of model simulations with experimental data for DCCA (volunteers dermally exposed).Comparison of model simulations (lines) with experimental data of Tomalik-Scharte et al. (2005) (symbols) on the average time courses of DCCA excretion rate (A) and cumulative excretion (B) (% of applied dose) in healthy volunteers following a dermal application of 215 mg of a permethrin solution on the scalp. Diamond symbols represent average experimental values and vertical bars the experimental standard deviation (n = 6).

Mentions: Using parameter values based on the kinetics of cypermethrin and its metabolites (Table 1), the model also provided a very good fit to independent sets of data by Tomalik-Scharte et al. [16] on the urinary excretion time courses of the sum of trans- and cis-DCCA in individuals dermally exposed to permethrin (Figures 7–9). The model developed from excretion time course data in cypermethrin-exposed volunteers thus appears suitable to simulate the kinetics of common metabolites in permethrin-exposed individuals. Even the dermal absorption rate and fraction of permethrin were kept as determined for cypermethrin.


A novel toxicokinetic modeling of cypermethrin and permethrin and their metabolites in humans for dose reconstruction from biomarker data.

Côté J, Bonvalot Y, Carrier G, Lapointe C, Fuhr U, Tomalik-Scharte D, Wachall B, Bouchard M - PLoS ONE (2014)

Comparison of model simulations with experimental data for DCCA (volunteers dermally exposed).Comparison of model simulations (lines) with experimental data of Tomalik-Scharte et al. (2005) (symbols) on the average time courses of DCCA excretion rate (A) and cumulative excretion (B) (% of applied dose) in healthy volunteers following a dermal application of 215 mg of a permethrin solution on the scalp. Diamond symbols represent average experimental values and vertical bars the experimental standard deviation (n = 6).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935837&req=5

pone-0088517-g009: Comparison of model simulations with experimental data for DCCA (volunteers dermally exposed).Comparison of model simulations (lines) with experimental data of Tomalik-Scharte et al. (2005) (symbols) on the average time courses of DCCA excretion rate (A) and cumulative excretion (B) (% of applied dose) in healthy volunteers following a dermal application of 215 mg of a permethrin solution on the scalp. Diamond symbols represent average experimental values and vertical bars the experimental standard deviation (n = 6).
Mentions: Using parameter values based on the kinetics of cypermethrin and its metabolites (Table 1), the model also provided a very good fit to independent sets of data by Tomalik-Scharte et al. [16] on the urinary excretion time courses of the sum of trans- and cis-DCCA in individuals dermally exposed to permethrin (Figures 7–9). The model developed from excretion time course data in cypermethrin-exposed volunteers thus appears suitable to simulate the kinetics of common metabolites in permethrin-exposed individuals. Even the dermal absorption rate and fraction of permethrin were kept as determined for cypermethrin.

Bottom Line: 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.It can also serve to reconstruct absorbed doses of permethrin or cypermethrin in the population using measured biomarker data.

View Article: PubMed Central - PubMed

Affiliation: 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 (IRSPUM), Université de Montréal, Montreal, Quebec, Canada.

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.

Show MeSH
Related in: MedlinePlus