© 1992 Oxford University Press
research-article |
In Vivo and in Vitro Percutaneous Absorption and Skin Evaporation of Isofenphos in Man
*Department of Dermatology, University of California San Francisco, California
Occidental Chemical Corporation Niagara Falls, New York 14302
Department of Food and Agriculture State of California, Sacramento, California
Received September 19, 1991; accepted May 21, 1992
Studies were done to determine the percutaneous absorption of isofenphos in human volunteers from whom informed consent had been 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-hr exposure. Skin wash recovery data show that isofenphos evaporates from in vivo skin during the absorption process; the surface dose is minimal (<1%) by 24 hr. Skin stripping showed no residual isofenphos in stratum corneum. This explains the similar absorption for 24 and 72-hr dose prewash exposures. Skin surface recovery in vivo with soap and water was 61.4±10.4 for the first dosing time (15 mm). Time-recovery response declined with time to 0.5±0.2% at 24 hr. In vitro absorption utilizing flow-through diffusion methodology with human cadaver skin and human 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 surface wash at 24 hr recovered 79.7±2.2% and skin content was 6.5±2.4% (total dose accountability of 88.7±4.6%). Thus, isofenphos was available for absorption during the whole dosing period. Neither in vitro absorption nor in vitro evaporation studies predicted the potential skin evaporation of isofenphos. Published dermal studies in the rat had predicted isofenphos absorption at 47% of applied dose (12-fold greater than actual in man). Subsequent toxicokinetic modeling predicted possible concern with the use of isofenphos. This is an example where the choice of the rat produced a nonrelevant absorption prediction. In vivo studies in human volunteers seem more relevant for predicting percutaneous absorption in man.