Alkane-induced edema formation and cutaneous barrier dysfunction

Abstract

Certain mineral oils and hydrocarbons require repeated topical application to cause irritation. A structure activity relationship of pure n-alkanes was undertaken in a mouse ear edema model to investigate the mechanism of cumulative irritancy. Alkanes were applied twice daily over a 4-day period. Dodecane was found to be non-irritating, while tridecane elicited a response only at 96 h. Tetradecane was the strongest irritant with significant increases (p less than 0.05) in ear thickness observed at 48 h. Hexadecane, octadecane, and eicosane exhibited progressively decreasing activity. Permeability of the ears to hydrocortisone was monitored in vitro during tridecane- and tetradecane-induced irritation. Significant increases in permeability were observed 24 h before edema formation. A positive correlation was found between the extent of edema formation and enhancement of permeability. Loss of barrier function would result in increased cutaneous availability of the alkanes. Increased permeability prior to edema formation indicates that induction of barrier dysfunction may be a factor in the mechanism of alkane-induced irritation.

Exogenous Origin of n-Alkanes in Pathologic Scale

“…However, it is well rec¬ ognized that topically applied alkanes are not biologi¬ cally inert but alter arachidonic acid metabolism,34 in¬ duce hyperplasia,3537 produce edema,38 and perturb barrier function. 38 Thus, the possibility that these emollient lipids could further impair epidermal function in certain DOC must be considered.…”

TIMES-SS—A Mechanistic Evaluation of an External Validation Study Using Reaction Chemistry Principles

“…Other investigators have reported nonspecific lymph node proliferation in the LLNA with tetradecane that has been principally attributable to its skin irritancy potential rather than a skin-sensitizing effect (31). In addition, tetradecane has been reported to cause ear edema following topical application to the ears of mice at 50% concentration, which is also suggestive of potential skin irritation (32). No refinement to TIMES-SS was therefore considered necessary.…”

Development of an Amphiphilic Chitin Derivative with Lipid/Peptide-Type Side Chains Having Skin Protective Ability

“…Some hydrocarbons are known to cause skin irritation after repeated application. 39 The TEWL values on the dorsal skin of normal hairless mice were less than 10 g•m -2 •h -1 . After continued treatment with n-hexadecane for 1week, TEWL values on the dorsal skin of hairless mice came to exceed 20 g•m -2 •h -1 constantly due to cutaneous barrier disruption.…”