AN AUTOMATED INVITRO DERMAL ABSORPTION PROCEDURE .2. COMPARATIVE INVIVO AND INVITRO DERMAL ABSORPTION OF THE HERBICIDE FENOXAPROP-ETHYL (HOE-33171) IN RATS

Dermal absorption of the C-14-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 C-14 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-mu-g/cm2 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-mu-g/cm2; when doses of 10 and 100-mu-g/cm2 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-mu-g/cm2 and Excel 1.8, 10 and 100-mu-g/cm2 treatments, respectively. Significantly less residual C-14 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-mu-g/cm2 dose rates, respectively). Comparative studies conducted at a dose rate of 1.4-mu-g/cm2 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-mu-g/cm2. 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.