title: Effect of serum-parathion interactions on cutaneous penetration of parathion in vitro.
abstract: The effect of serum and serum fractions on the cutaneous penetration of [35S]parathion from surface deposits or adsorbed formulations was determined. The total quantity of [35S]parathion which penetrated pig skin was significantly greater when the receptor fluid was whole swine serum or the 500 or 10,000 MW retentate from ultrafiltration of the serum than when phosphate-buffered saline (PBSA), the 500 MW filtrate or distilled water, respectively, was used. The enhanced penetration was observed without any associated evidence of metabolic change and with both dosing methods. This result is consistent with the hypothesis that serum-parathion interactions are the cause of the enhanced penetration. The apparent solubility of parathion was 16 times greater in whole serum than in PBSA. Gel-filtration chromatography of the serum-parathion mixture revealed that approximately 11% of the 35S activity was associated with two protein fractions which had consistently different elution volumes. Most of the radioactivity, however, was not tightly bound and the equilibrium between bound and free parathion was rapidly reversible. The result of interaction between parathion and serum proteins was an increased apparent solubility, relative to PBSA, and increased cutaneous penetration. The significance of these findings is clear: when designing in vitro systems to model in vivo percutaneous absorption, investigators should consider that the affinity of the fluid interfacing with the dermis in vivo may influence the kinetics of penetration when subcutaneous blood flow is low.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008970:Molecular Weight; D010278:Parathion / Q000097:blood / Q000378:metabolism*; D012867:Skin / Q000098:blood supply; D012869:Skin Absorption; D012995:Solubility; D013552:Swine
chemical_list: D010278:Parathion