The predictive accuracy of in vitro measurements for the dermal absorption of a lipophilic penetrant (fluazifop-butyl) through rat and human skin.
The predictive accuracy of in vitro measurements in estimating dermal absorption has been evaluated in rat and human skin using fluazifop-butyl (FB), a lipophilic model compound, at dosage rates of 2.5, 25, and 250 micrograms/cm2. In vitro studies used rat and human epidermal membranes mounted in static diffusion cells with radiolabeled FB and receptor fluids of 50% aqueous ethanol (Aq Et), 6% polyethylene glycol 20 oleyl ether in saline (PEG), or tissue culture medium (TCM). In vivo rat studies with radiolabeled FB were carried out to parallel previously published human volunteer studies. For rat skin, in vitro measurements with all types of receptor fluid provide an adequate prediction (generally within a factor of 3) of in vivo absorption. Absorption data for human epidermal membranes with a receptor fluid of Aq Et were adequately predictive of the in vivo absorption. In contrast, membranes with PEG or TCM significantly underestimated the in vivo absorption. The results support the conclusion that in vitro studies are useful to predict in vivo dermal absorption in rat and man, when appropriate receptor fluids are used.
Ramsey
J D
JD
ZENECA Central Toxicology Laboratory, Cheshire, United Kingdom.
Woollen
B H
BH
Auton
T R
TR
Scott
R C
RC
D000818:Animals; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D011237:Predictive Value of Tests; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D013045:Species Specificity
D006540:Herbicides; D011725:Pyridines; C050585:fluazifop-butyl