Toward a better understanding of pesticide dermal absorption: diffusion model analysis of parathion absorption in vitro and in vivo.
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.
Miller
Matthew A
MA
James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, Ohio 45267-0004, USA.
Kasting
Gerald B
GB
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
D002250:Carbon Radioisotopes; D007306:Insecticides; D011849:Radioactive Tracers; D010278:Parathion