Toward a Better Understanding of Pesticide Dermal Absorption: Diffusion Model Analysis of Parathion Absorption in Vitro and in Vivo

Abstract

Human skin absorption of radiolabeled parathion was studied in vitro at specific doses (mass loadings) of 0.4, 4.0, 41, or 117 μg/cm², with and without occlusion. The compound was applied in small volumes of acetone solution to split-thickness skin. Permeation of radiolabel into the receptor solutions was monitored for 76 h, after which the tissue was dissected and analyzed for residual radioactivity. For the 3 lower doses, cumulative permeation after 76 h was approximately dose-proportional, ranging from 28.5–30.5% of applied dose (unoccluded) to 45.5–55.7% (occluded). Total absorption, calculated as receptor fluid plus dermis content, followed a similar pattern. Both permeation rate and total absorption continued to increase up to the highest dose tested, consistent with results from other laboratories. These results are compared with predictions from a previously developed skin diffusion model (Kasting et al., 2008a). The model predicted total absorption to within a factor of 1.4 at 0.4 μg/cm² and 1.6 at 4 μg/cm², but substantially underpredicted absorption at the 2 higher doses. The analysis showed that parathion partitioned more favorably into the stratum corneum than the diffusion model prediction. Nevertheless, comparison of the model predictions to a previously reported human study showed that the skin absorption model, when corrected for surface losses occurring in vivo, satisfactorily described in vivo dermal absorption of parathion applied at 4 μg/cm² to various body sites.

Acknowledgments

We acknowledge a helpful conversation with Dr. John Kissel. Financial support for this study was provided by NIOSH/CDC grant R01 OH007529. The conclusions reached represent the opinions of the authors and have not been endorsed by NIOSH.