Modelling dermal pharmacokinetics using in vitro data. Part II. Fluazifop-butyl in man.
In a previous paper it was demonstrated that dermal absorption of the herbicide fluazifop-butyl in the rat could be modelled by combining a knowledge of the pharmacokinetics following intravenous and oral dosing with in vitro measurements of dermal absorption. This paper demonstrates the validation of a similar model for the dermal absorption of fluazifop-butyl in man. Pharmacokinetic parameters derived from an oral dosing study are combined in a mathematical model with in vitro measurements of dermal absorption of fluazifop-butyl. Model predictions of the rate and extent of dermal absorption of fluazifop-butyl are compared with the results of dermal absorption studies in human volunteers. Good agreement is found between the model predictions and the experimental measurements. These results have implications for improved risk assessment. The model provides a tool for risk assessment based on both internal dose (e.g. peak plasma concentration, plasma area under the curve) as well as total absorbed dose. However, further work is required to evaluate whether the same techniques are applicable to a wider range of compounds.
Auton
T R
TR
ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Ramsey
J D
JD
Woollen
B H
BH
D000279:Administration, Cutaneous; D000284:Administration, Oral; D006540:Herbicides / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008954:Models, Biological; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012869:Skin Absorption / Q000187:drug effects*
D006540:Herbicides; D011725:Pyridines; C050585:fluazifop-butyl