title: In vitro dermal absorption of pesticides: IV. In vivo and in vitro comparison with the organophosphorus insecticide diazinon in rat, guinea pig, pig, human and tissue-cultured skin.
abstract: In vitro skin absorption tests are currently being developed as an alternative to in vivo animal tests for predicting the degree of occupational exposure to pesticides. In the study reported here, in vitro percutaneous absorption tests were conducted with the (14)C-ring-labelled pesticide, diazinon, dissolved in acetone and applied to the dermatomed skin (0.5 mm) of a number of species at a dose rate of 9.5-16.7 mug/cm(2). Skin permeation was determined for 48 hr after exposure using an in vitro flow-through system. Skin permeation was calculated from the sum of the percentage recovery of (14)C activity in the receiver solution and the percentage recovery obtained in methanol washes of the skin at 48 hr and in skin digests. Listed in decreasing order, the total percentage in vitro dermal absorptions (mean +/- SD) obtained by 48 hr after exposure for the five skin types were: 47 +/- 3.4% (rat), 36 +/- 0.9% (tissue cultured Testskin), 33 +/- 2.8% (hairless guinea pig), 20 +/- 3.1% (human) and 15 +/- 13.1% (pig). The percentage recoveries in soapy water skin washes at 24 hr, in methanol washes and skin digests at 48 hr and of (14)C-labelled volatiles collected in air traps at 48 hr after exposure are reported. Comparative in vivo studies demonstrated 37 +/- 0.8 and 24 +/- 5.7% recovery of (14)C in the urine of rats (dose rate, 6 mug/cm(2)) and hairless guinea pigs (dose rate, 5 mug/cm(2)), respectively, by 14 days after exposure. Total faecal recovery 14 days after exposure was 18 +/- 0.4 and 4 +/- 0.9% for rats and guinea pigs, respectively. Analysis of tissue taken at autopsy 14 days after exposure demonstrated a total tissue recovery of 0.6 +/- 0.1% [(14)C]diazinon in rats and 1 +/- 0.2% in hairless guinea pigs. The total recovery in skin removed from the dose site at 14 days after exposure was 0.2 +/- 0.02% and 0.1 +/- 0.05% in rats and hairless guinea pigs, respectively. Recovery of radioactivity from soapy water skin washes conducted at 24 hr after exposure was 21 +/- 3.8% for rats and 2 +/- 0.1% for hairless guinea pigs. Recovery in skin patches was 23 +/- 5.4% and 73 +/- 2.9% in rats and hairless guinea pigs, respectively. The in vitro data for dermal absorption of [(14)C]diazinon for rats (47 +/- 3.4%) and hairless guinea pigs (33 +/- 2.8%) were in good agreement with the data observed for rats (56 +/- 1.03%) and hairless guinea pigs (28 +/- 6.0%) in vivo. This study supported the use of in vitro skin absorption tests as an alternative to in vivo animal testing.
authors.affiliation: Health Canada, Environmental Health Centre, Tunney's Pasture, Ottawa, Ontario K1A 0L2, Canada.
authors.forename: R P
authors.initials: RP
authors.lastname: Moody
authors.forename: B
authors.initials: B
authors.lastname: Nadeau