The in vitro hydrolysis of diisopropyl fluorophosphate during penetration through human full-thickness skin and isolated epidermis.
Skin may play an important role in the detoxification of certain substances during their passage into the body. The degree of hydrolysis of diisopropyl fluorophosphate, DFP, in skin suspensions and during penetration through isolated epidermis and full-thickness skin from humans was investigated in vitro. When isolated sheets of epidermis were used, 11% of the penetrated amount of DFP was hydrolyzed whereas 46% was hydrolyzed during penetration through full-thickness skin. A comparison is made between the degree of hydrolysis during penetration as obtained from direct measurements and that calculated from kinetic data of the enzyme (Kappm and Vappmax), the half-life of DFP, the skin concentration, and the lag time. The concentration of DFP in the skin was not measured, but the concentration of DFP equivalents (DFP and metabolites formed during penetration) was determined at different times. At steady state, the amount of DFP equivalents in the skin corresponded to the amount that had penetrated into the skin during the lag time. This indicates that the penetration rate corresponded to the uptake via the skin and that no diffusion barrier existed between the skin and the receptor medium. It was also found that the concentration in the skin was proportional to the penetration rate, thus indicating that the enzymatic degree of hydrolysis depends upon the penetration rate.
D000328:Adult; D004817:Epidermis / Q000201:enzymology; D004950:Esterases; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D006868:Hydrolysis; D007531:Isoflurophate / Q000378:metabolism*; D007700:Kinetics; D044345:Phosphoric Triester Hydrolases; D012867:Skin / Q000201:enzymology / Q000378:metabolism*
D007531:Isoflurophate; D006867:Hydrolases; D004950:Esterases; D044345:Phosphoric Triester Hydrolases; C020061:diisopropyl-fluorophosphatase