An automated in vitro dermal absorption procedure: II. Comparative in vivo and in vitro dermal absorption of the herbicide fenoxaprop-ethyl (HOE 33171) in rats

Abstract

Dermal absorption of the 14C-ring-labelled herbicide fenoxaprop-ethyl (FPE; ethyl 2-[4-[(6-chloro-2-benzoxazolyl)oxy]phenoxy]propanoate) was examined after topical applications of the herbicide in either acetone or in field formulation (Excel) to the shaved backs of rats (n = 6) according to our standard in vivo procedure. The total percentage dermal absorption was determined from the mean percentage recoveries of 14C in the urine after correction for incomplete urinary excretion using the recovery figures obtained from intramuscular (im) dose studies (49 ± 17.7% recovery). The mean percentage dermal absorption of FPE applied in acetone at a dose of 1.8 μg/cm 2 was 32 ± 6.8% and was significantly greater than that obtained at the same dose of FPE applied in the Excel formulation (18 ± 4.5%). Increasing the applied dose of FPE had no effect on dermal absorption within the dose-range 1.8 to 100 μg/cm 2; when doses of 10 and 100 μg/cm 2 were applied in Excel, 20 ± 6.7% and 21 ± 4.5% was absorbed, respectively. Mass balance studies with the total percentage recovery in urine (im-corrected) added to recovery from foam patches covering the dose site, and from gauze swabs moistened with soapy water taken of dosed skin 24 hr after treatment, demonstrated only 56 ± 3.7%, 54 ± 3.8%, 56 ± 5.4% and 53 ± 3.9% total recovery for the acetone 1.8 μg/cm 2 and Excel 1.8, 10 and 100 μg/cm 2 treatments, respectively. Significantly less residual 14C activity was detected in the skin swabs taken for the acetone (8 ± 3.5%) than for the Excel treatments (21 ± 6.0%, 27 ± 4.0% and 25 ± 5.8% for the 1.8, 10 and 100 μg/cm 2 dose rates, respectively). Comparative studies conducted at a dose rate of 1.4 μg/cm 2 with our automated in vitro dermal absorption (AIDA) procedure demonstrated no significantly different total percentage dermal absorption in dermatomed skin taken from the same rats tested in vivo at a dose rate of 1.8 μg/cm 2. There was no significant difference between the total percentage dermal absorption obtained for AIDA analysis of fresh rat skin (27 ± 9.3%; n = 20) compared with that for rat skin frozen for 7 days in liquid nitrogen (25 ± 7.6%; n = 19) and the implications of this for tissue storage are discussed.