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In vitro skin permeation studies are commonly used in the risk assessment of toxic compound skin exposure. The present study examined the utility of transepidermal water loss (TEWL) and electrical conductance as barrier integrity tests before skin permeation studies in vitro using a large number of skin samples and fentanyl. TEWL and conductance of the skin samples were measured before the permeation experiments in Franz diffusion cells in vitro with a vapometer and low voltage application, respectively. The data were analyzed based on the in vitro permeation results and in vivo skin absorption information from the transdermal fentanyl product labels. The results showed poor correlations between TEWL and electrical conductance for the skin samples. Weak correlations between fentanyl delivery rate (flux x area) and TEWL and skin conductance were observed. For comparison, TEWL and conductance were also examined after skin perturbation with a syringe needle, and both TEWL and conductance values of the skin samples increased after the perturbation. The data suggest that either TEWL of 10 g/m/h or skin conductance of 0.07 mS/cm can be used as exclusion criteria in skin integrity testing to remove skin samples with high permeabilities under the in vitro conditions examined.
This article was published in the following journal.
Name: Toxicology in vitro : an international journal published in association with BIBRA
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Loss of water by diffusion through the skin and by evaporation from the respiratory tract.
The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.
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