An automated in vitro dermal absorption procedure: III. In vivo and in vitro comparison with the insect repellent N, N-diethyl- m-toluamide in mouse, rat, guinea pig, pig, human and tissue-cultured skin

Abstract

Cross-species in vitro dermal absorption tests were conducted with the 14C-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 μg/cm 2. Skin permeation was determined using an automated in vitro dermal absorption procedure, and was calculated from the percentage recovery of 14C-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 14C-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 14C-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% 14C-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.