In Vivo and in Vitro Percutaneous Absorption and Skin Evaporation of Isofenphos in Man

Studies were done to determine the percutaneous absorption ofisofenphos in human volunteers from whom informed consent hadbeen obtained. In vivo absorption in man was 3.6±3.6%of applied dose for 24-hr exposure and 3.6±0.5% for 72-hrexposure. Skin wash recovery data show that isofenphos evaporatesfrom in vivo skin during the absorption process; the surfacedose is minimal (<1%) by 24 hr. Skin stripping showed noresidual isofenphos in stratum corneum. This explains the similarabsorption for 24 and 72-hr dose prewash exposures. Skin surfacerecovery in vivo with soap and water was 61.4±10.4 forthe first dosing time (15 mm). Time-recovery response declinedwith time to 0.5±0.2% at 24 hr. In vitro absorption utilizingflow-through diffusion methodology with human cadaver skin andhuman plasma receptor fluid gave 2.5±2.0% dose absorbed,an amount similar to In vivo studies. An additional 6.5±24%was recovered in the skin samples (total of 9%). Skin surfacewash at 24 hr recovered 79.7±2.2% and skin content was6.5±2.4% (total dose accountability of 88.7±4.6%).Thus, isofenphos was available for absorption during the wholedosing period. Neither in vitro absorption nor in vitro evaporationstudies predicted the potential skin evaporation of isofenphos.Published dermal studies in the rat had predicted isofenphosabsorption at 47% of applied dose (12-fold greater than actualin man). Subsequent toxicokinetic modeling predicted possibleconcern with the use of isofenphos. This is an example wherethe choice of the rat produced a nonrelevant absorption prediction.In vivo studies in human volunteers seem more relevant for predictingpercutaneous absorption in man.