Vehicle effects on in vitro percutaneous absorption through rat and human skin.
We studied the effects of three vehicles (propylene glycol, octanol and ethyl decanoate) with differing polarity on the in vitro percutaneous absorption of three chemicals (fluazifop-butyl, dimethyl phthalate and fomesafen sodium salt) with a range of physico-chemical properties. Absorption rate measurements were made from high vehicle volume (200 microliters/cm2) and low vehicle volume (< 10 microliters/cm2) applications. For the lipophilic fluazifop-butyl absorption rate was highest from the more polar vehicle propylene glycol, but this effect was only significant under high-volume conditions. There was a variable vehicle effect on absorption of the intermediate chemical dimethyl phthalate. The largest vehicle effect was seen for the more hydrophilic fomesafen sodium salt where absorption was fastest from the least polar vehicle ethyl decanoate. These results support the hypothesis that the absorption process can in part be predicted from a knowledge of solute solubility. Vehicle effects were greater from high volume applications than from those more comparable to occupational exposure conditions.
Hilton
J
J
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, England.
Woollen
B H
BH
Scott
R C
RC
Auton
T R
TR
Trebilcock
K L
KL
Wilks
M F
MF
D000818:Animals; D003651:Decanoates / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D000442:Octanols / Q000737:chemistry / Q000494:pharmacology; D014677:Pharmaceutical Vehicles / Q000737:chemistry / Q000494:pharmacology*; D011409:Propylene Glycols / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013045:Species Specificity
D003651:Decanoates; D000442:Octanols; D014677:Pharmaceutical Vehicles; D011409:Propylene Glycols; C091960:ethyl decanoate