The Tritiated Water Skin Barrier Integrity Test: Considerations for Acceptance Criteria with and Without14C-Octanol.
A study was designed to assess barrier integrity simultaneously using separate compounds (probes) for polar and non-polar pathways through the skin,3H2O and14C-octanol, respectively; and to determine whether the two probe approach could better define barrier integrity.



A 5-min dose of water containing3H2O and14C -octanol was applied to ex vivo human skin mounted in Franz diffusion cells. The receptor solution was sampled at 30 min, analyzed for3H and14C content, and the correlation between water and octanol absorption was determined by statistical tests suitable for non-normally distributed data. This study was conducted on skin from 37 donors with from 3 to 30 replicate skin sections per donor (a total of 426 sections).



The correlation between3H2O and14C-octanol absorption was low (Pearson correlation coefficient = 0.3485). The3H2O absorption cutoff used in this study to select for a normal skin barrier rejected some sections in which14C-octanol absorption was within normal limits and accepted others in which14C-octanol absorption was abnormally high. The converse was true for3H2O absorption when the14C-octanol-based cutoff was used.



The results of the3H2O test or of similar tests that primarily assess the permeability of polar pathways through the skin may not necessarily provide information relevant to the absorption of highly lipophilic compounds. Octanol, or another molecule that more closely matches the physicochemical attributes of the test compound, may characterize properties of the skin barrier that are more relevant to compounds of low water solubility.
Dermal & Transdermal Research Services, QPS Holdings LLC, 3 Innovation Way, Suite 240, Newark, Delaware, 19711, USA.
Paul A
PA
Lehman
Translational Medicine, Upsher-Smith Laboratories Inc, 6701 Evenstad Drive N, Minneapolis, Minnesota, 55369, USA.
Kacie
K
Beatch
Office of Generic Drugs, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Sam G
SG
Raney
, 10716 SE Forest View LN, Happy Valley, Oregon, 97086, USA. franzcell@frontier.com.
Thomas J
TJ
Franz
D002250:Carbon Radioisotopes / Q000378:metabolism*; D004058:Diffusion; D006801:Humans; D000442:Octanols / Q000378:metabolism*; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology; D012995:Solubility; D014316:Tritium / Q000378:metabolism; D014867:Water / Q000378:metabolism*
D002250:Carbon Radioisotopes; D000442:Octanols; D014867:Water; D014316:Tritium
IVPT; skin barrier; skin permeation; stratum corneum; tritiated water