A physiologically based pharmacokinetic model of parathion dermal absorption.
van der Merwe-D; Brooks-JD; Gehring-R; Baynes-RE; Monteiro-Riviere-NA; Riviere-JE
Toxicologist 2006 Mar; 90(1):165
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.
Models; Toxic-effects; Toxins; Risk-analysis; Physiological-testing; Physiological-effects; Solvents; Exposure-assessment; Temperature-effects
Work Environment and Workforce: Mixed Exposures
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California
North Carolina State University, Raleigh, North Carolina