The Predictive Accuracy of in Vitro Measurements for the Dermal Absorption of a Lipophilic Penetrant (Fluazifop-Butyl) through Rat and Human Skin |
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Authors: | RAMSEY J D; WOOLLEN B H; AUTON T R; SCOTT R C |
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Institution: | ZENECA Central Toxicology Laboratory Alderley Park, Nr Macclesfield, Cheshire, SK10 4TJ, United Kingdom
Received May 26, 1993;
accepted February 21, 1994 |
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Abstract: | The predictive accuracy of in vitro measurements in estimatingdermal absorption has been evaluated in rat and human skin usingfluazifop-butyl (FB), a lipophilic model compound, at dosagerates of 2.5, 25, and 250 µg/cm2 In vitro studies usedrat and human epidermal membranes mounted in static diffusioncells with radiolabeled FB and receptor fluids of 50% aqueousethanol (Aq Et), 6% polyethylene glycol 20 oleyl ether in saline(PEG), or tissue culture medium (TCM). In vivo rat studies withradiolabeled FB were carried out to parallel previously publishedhuman volunteer studies. For rat skin, in vitro measurementswith all types of receptor fluid provide an adequate prediction(generally within a factor of 3) of in vivo absorption. Absorptiondata for human epidermal membranes with a receptor fluid ofAq Et were adequately predictive of the in vivo absorption.In contrast, membranes with PEG or TCM significantly underestimatedthe in vivo absorption. The results support the conclusion thatin vitro studies are useful to predict in vivo dermal absorptionin rat and man, when appropriate receptor fluids are used. |
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