AN AUTOMATED INVITRO DERMAL ABSORPTION PROCEDURE .3. INVIVO AND INVITRO COMPARISON WITH THE INSECT REPELLENT N,N-DIETHYL-M-TOLUAMIDE IN MOUSE, RAT, GUINEA-PIG, PIG, HUMAN AND TISSUE-CULTURED SKIN

Cross-species in vitro dermal absorption tests were conducted with the C-14-ring-labelled insect repellent, DEET (N,N-diethyl-m-toluamide), dissolved in acetone and applied to skin sections (0.5 mm) from a dermatome at a dose rate of about 30 mug/cm2. Skin permeation was determined using an automated in vitro dermal. absorption procedure, and was calculated from the percentage recovery of C-14-activity in the receiver solution. Listed in decreasing order, the total percentage of in vitro dermal absorption obtained by 48 hr post-exposure for the six skin types (n = 4) was: 36 +/- 27.5% (rhino mouse), 28 +/- 4.2% (human), 21 +/- 2.2% (rat), 15 +/- 0.8% (pig), 13 +/- 9.6% (tissue cultured Testskin) and 11 +/- 1.4% (hairless guinea pig). Lag times for DEET in vitro dermal absorption in the six skin types ranged from 0.6 hr (human) to 1.9 hr (rat). The C-14-activity recovered in soapy water rinses of the skin specimens at 24 hr post-exposure ranged from 4% (rat) to 18% (mouse). The percentage recovery in methanol skin washes, skin digests, and of C-14-volatiles collected in air traps at 48 hr post-exposure are reported. The total mass balance recovery ranged from 70% (Testskin) to 93% (human). Comparative in vivo studies demonstrated 38 +/- 10.3% (n = 4) and 26 +/- 5.4% (n = 4) urinary recovery in rats and guinea pigs, respectively, by 14 days post-exposure. Total faecal percentage recovery 14 days post-exposure was 1 +/- 0.5% for rats and 3 +/- 0.8% for guinea pigs. A tissue autopsy conducted at 14 days post-exposure demonstrated a total tissue recovery of 2 +/- 0.4% C-14-DEET in rats and 1 +/- 0.3% in guinea pigs. Total percentage recovery in skin removed from the dose site at 14 days post-exposure was 0.2 +/- 0.11% and 0.1 +/- 0.06% in rats and guinea pigs, respectively. Soapy water skin washes conducted at 24 hr post-exposure had 8 +/- 0.5% recovery for rats and 5 +/- 2.8% recovery for guinea pigs. Total mass balance recovery was 84 +/- 9.2% and 108 +/- 2.9% for rats and guinea pigs, respectively. In summary, the in vitro data underestimated the dermal absorption observed in vivo and tentative explanations for this lack of agreement are discussed.