Automated In Vitro Dermal (AIVDA): A New In Vitro Method for Investigating Transdermal Flux

Richard P. Moody

Automated In Vitro Dermal Absorption (AIVDA), employed small autosampler vial inserts (Moody cells) to hold human skin (0.07cm2) in a standard autosampler carousel. HPLC was used to monitor the permeation rate of test compounds. Analysis was fully automated and remotely monitored and controlled via a modem. A modified Hank’s balanced salt solution was used to minimise HPLC background interference. Permeation assays conducted with Deep Woods®, a commercial N,N-diethyl-m-toluamide (DEET)-based mosquito repellent, showed no significant difference in DEET absorption between fresh and frozen human abdominal skin (Student’s t test [p ≤ 0.05] 56 ± 9.1% [n = 4] and 48 ± 6.3% [n = 4], respectively). No significant difference was obtained for DEET absorption in human skin pretreated with barrier cream. Preliminary tests conducted to validate AIVDA versus the standard Bronaugh procedure demonstrated excellent agreement for DEET permeation in rat skin (62 ± 12.8% [n = 4] Moody cells; 59 ± 8.1% [n = 3] Bronaugh cells). AIVDA has many advantages over other in vitro permeation tests, including automation, higher analytical sensitivity, rapid sample processing and the ability to use small (5mm outside diameter) skin specimens.
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A Proposed Study on the Transplacental Transport of Parabens in the Human Placental Perfusion Model

Line Mathiesen, Giuseppina Zuri, Maria H. Andersen and Lisbeth E. Knudsen

Human exposure to parabens as a preservative used in personal care products is of increasing concern, as there is evidence from in vivo and in vitro studies of hormone disruption in association with exposure to parabens. Transport across the placenta could be critical for risk assessment, but the available data are sparse. The aim is to develop a method for estimating fetal exposure, via the placenta, to the most  commonly-used parabens, by using a human placental perfusion model. The use of human tissue is vital for determining human fetal exposure, because animal studies are of little relevance, since the placenta exhibits significant interspecies variation. An HPLC model is currently being established to simultaneously quantify four different parabens, namely, methylparaben, ethylparaben, propylparaben and butylparaben, and their main metabolite, p-hydroxybenzoic acid. With this model, we aim to determine the transport kinetics of these parabens across the human placenta, and to investigate placental metabolism, including differences in transport due to molecular characteristics. This will facilitate assessment of the risks associated with the use of paraben-containing products during pregnancy.
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