Percutaneous penetration of diethanolamine through human skin in vitro: Application from cosmetic vehicles

Concern has been raised over the safety of diethanolamine (DEA) which may be present as a minor component of alkanolamide ingredients of cosmetic formulations. Skin penetration data were therefore generated for a range of typical formulations under in-use conditions. Seven rinse-off formulations (A–E, G and H), a leave-on emulsion (F), representing prototype cosmetic formulations and containing representative levels of DEA were prepared. Target levels of DEA were attained by inclusion of DEA as either 14C-DEA or a combination of 14C-DEA and unlabeled DEA. Skin permeation and distribution were evaluated using human skin in vitro, static diffusion cells and phosphate buffered saline (pH 7.4) as the receptor phase. At least 12 replicate epidermal membranes were prepared from a minimum of four donors for each test group. Receptor phase samples were taken at appropriate time intervals. At the end of the test period, radioactivity remaining on the skin surface and on the diffusion cell donor cap was determined before the skin samples were tape-stripped. The remaining tissue was solubilized and radioactivity determined. Permeation was very low from all vehicles applied under in-use conditions (range 1–48 ng/cm 2 over 24 h). Comparison was also made between permeation and distribution of DEA from an infinite dose of a simple aqueous solution and the leave-on formulation (F) through paired samples of fresh and frozen full thickness skin from the same donors. When applied as an infinite dose in aqueous solution DEA permeation at 24 h was greater through frozen than through fresh skin. From the leave-on formulation, permeation was similar and very low for both fresh and frozen skin. Recovery of DEA after application of the aqueous solution to fresh human skin and subsequent aqueous and organic extraction of the epidermal and dermal tissue indicated that the majority (>98%) of DEA was in the aqueous extract, suggesting that DEA was in the free state and not associated with the lipid fraction. These data provide a basis for the estimation of the potential systemic exposure and safety margins for DEA in representative cosmetic formulations.