Effect of dosing vehicle on the dermal absorption of fluazifop-butyl and fomesafen in rats in vivo.
One important factor which may influence the extent and rate of percutaneous absorption is the dosing vehicle. The purpose of the experiments described was to compare the effect of dosing vehicles of different polarities on the absorption of two herbicides across rat skin in vivo. Rats were dosed dermally with either fluazifop-butyl (logP(oct) 4.5) or fomesafen sodium salt (logP(oct) -1.2) in propylene glycol (PG), octanol (OCT), or ethyl decanoate (ED), and the amount of radioactivity excreted in urine was determined. Absorption rates were estimated from the urinary excretion data and from blood kinetic data derived from intravenously dosed rats. For fluazifop-butyl the average rate of absorption (x10(-2) micrograms/hr-1 +/- SE) was not greatly influenced by the dosing vehicle (OCT, 2.94 +/- 0.08; ED, 3.66 +/- 0.10; PG, 3.95 +/- 0.32) despite relatively large differences in solubility (PG, 38 mg/ml; OCT, and ED, > 600 mg/ml). These results were consistent with the finding that there was at most only a twofold difference in the epidermal membrane:vehicle partition coefficients (km). In contrast, the absorption rate of fomesafen from PG (1.98 +/- 0.04) was approximately half that of ED (3.98 +/- 0.06) and OCT (4.49 +/- 0.08) for the first 30 hr after application and was in keeping with solubility data (PG, 638 mg/ml; OCT, 12 mg/ml; ED, < 10 mg/ml). At later time points the absorption of fomesafen from PG increased; this is discussed in relation to the penetration-enhancing properties of PG.(ABSTRACT TRUNCATED AT 250 WORDS)
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, England.
J M
JM
Rawlings
J
J
Hilton
K L
KL
Trebilcock
B H
BH
Woollen
M F
MF
Wilks
D000279:Administration, Cutaneous; D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D005260:Female; D006540:Herbicides / Q000493:pharmacokinetics*; D008954:Models, Biological; D014677:Pharmaceutical Vehicles / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*
D001549:Benzamides; D006540:Herbicides; D014677:Pharmaceutical Vehicles; D011725:Pyridines; C050585:fluazifop-butyl; C088563:fomesafen