title: 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 microg/cm(2), 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 microg/cm(2) and 1.6 at 4 microg/cm(2), 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 microg/cm(2) to various body sites.
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, Ohio 45267-0004, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Miller
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
mesh_terms: D002250:Carbon Radioisotopes; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008954:Models, Biological; D010278:Parathion / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D011849:Radioactive Tracers; D012869:Skin Absorption; D012879:Skin Physiological Phenomena; D013696:Temperature
chemical_list: D002250:Carbon Radioisotopes; D007306:Insecticides; D011849:Radioactive Tracers; D010278:Parathion