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A physiologically based pharmacokinetic model of parathion dermal absorption.

Authors
van der Merwe-D; Brooks-JD; Gehring-R; Baynes-RE; Monteiro-Riviere-NA; Riviere-JE
Source
Toxicologist 2006 Mar; 90(1):165
NIOSHTIC No.
20029852
Abstract
The rate and extent of dermal absorption are important in the risk analysis from dermal exposure to toxic chemicals. Dermal absorption in in vitro flow-through diffusion cells is relevant to the initial processes of dermal absorption. This study describes a physiologically based pharmacokinetic (PBPK) model of parathion absorption through porcine skin using flow-through cells. It includes an effective tortuosity calculator for estimating the diffusional path length through the stratum corneum barrier. Parameters related to the structure of the stratum corneum and solvent evaporation rates were independently estimated. Solvent evaporation rate, diffusivity and a mass transfer factor were optimized based on experimental dermal absorption data. The model was validated across different dose ranges (22.5-106.9 ug/cm2, different solvent volumes (20-40 ul ethanol) and different temperatures (25 degrees C-37 degrees C). The effects of corneocyte removal by tape stripping were simulated and compared to experimental data. These studies demonstrated the explanatory and predictive value of this type of model and its use for in silico hypotheses generation and testing. It is relevant to topical organophosphate pesticide risk assessments.
Keywords
Models; Toxic-effects; Toxins; Risk-analysis; Physiological-testing; Physiological-effects; Solvents; Exposure-assessment; Temperature-effects
Publication Date
20060301
Document Type
Abstract
Funding Amount
746428
Funding Type
Grant
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007555
Issue of Publication
1
ISSN
1096-6080
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California
State
NC
Performing Organization
North Carolina State University, Raleigh, North Carolina
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