Summary
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<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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Back O, Larsen A (1982) Contact sensitivity in mice evaluated by means of ear swelling and radiometric test. J Invest Dermatol 78:309–312
Brooks SC, Baumann CA (1956) Skin sterols. X. Studies with certain hyperplasia-inducing hydrocarbon. Cancer Res 16:357–363
Brown VKH, Box VL (1970) Skin arginase activity as a measure of skin change under the influence of some alkanes and alkenes. Br J Dermatol 82:606–612
Bus JS (1985) Alkanes. In: Anders MW (ed) Bioactivation of foreign compounds. Academic Press, Orlando, pp 111–120
Cole C, Sambuco C, Forbes P, Davies R (1984) Response to ultraviolet radiation: ear swelling in hairless mice. Photodermatology 1:114–118
Elias PM (1981) Epidermal lipids, membranes, and keratinization. Int J Dermatol 20:1–19
Franz TJ (1978) The finite dose technique as a valid in vitro model for the study of percutaneous absorption in man. Curr Probl Dermatol 7:309–312
Gibson WT, Teall MR (1983) Interactions of C12 surfactants with the skin: studies on enzyme release and percutaneous absorption in vitro. Food Chem Toxicol 5: 581–586
Hassing JH, Nater JP, Bleumink E (1982) Irritancy of low concentrations of soaps and synthetic detergents as measured by skin water loss. Dermatologica 164:314–321
Hoekstra WG, Phillips PH (1963) Effects of topically applied mineral oil fractions on the skin of guinea-pigs. J Invest Dermatol 40:79–88
Kao J, Hall J, Holland JM (1983) Quantitation of cutaneous toxicity: an in vitro approach using skin organ culture. Toxicol App Pharmacol 68:206–217
Lampe MA, Williams ML, Elias PM (1983) Human epidermal lipids: characterization and modulation during differentiation. J Lipid Res 24:131–140
MacMillan FSK, Raft RR, Elvers WB (1975) A comparison of the skin irritation produced by cosmetic ingredients and formulations in the rabbit, guinea pig, and beagle dog to that observed in man. In: Maibach H (ed) Animal models in dermatology. Churchill Livingstone, London New York, pp 12–22
Mol MAE, van Genderen J, Wolthuis OL (1986) Cultured human epidermal cells as a tool in skin toxicology. Food Chem Toxicol 24:519–520
Moloney SJ, Fromson JM, Bridges JW (1982) Cytochrome P-450 dependent deethylase activity in rat and hairless mouse skin microsomes. Biochem Pharmacol 24: 4011–4018
Murahata RI, Crowe DM, Roheim JR (1986) The use of transepidermal water loss to measure and predict the irritation response to surfactants. Int J Cosmet Sci 8:225–231
Parish WE (1986) Evaluation of in vitro predictive tests for irritation and allergic sensitization. Food Chem Toxicol 24:481–494
Pittz EP, Smerbeck RV, Rieger MM (1985) An animal test procedure for the simultaneous assessment of irritancy and efficacy of skin care products. In: Maibach HI, Lowe NJ (eds) Models in dermatology 2. Karger, Basel, pp 209–224
Sambuco CP, Forbes PD (1984) Quantitative assessment of phototoxicity in the skin of hairless mice. Food Chem Toxicol 22:233–236
Tubaro A, Dri D, Melato M, Mulas G, Bianchi P, Del Negro P, Della Logia R (1986) In the croton oil ear test the effect of nonsteroidal antiinflammatory drugs (NSAIDs) are dependent on the dose of the irritant. Agents Actions 19:371–373
van der Valk PGM, Nater JP, Bleumink E (1984) Skin irritancy of surfactants as assessed by water vapor loss measurements. J Invest Dermatol 82:291–293
Williams ML, Elias PM (1982) N-Alkanes in normal and pathological human scale. Biochem Biophys Res Commun 107:322–328
Young JM, Spires DA, Bedford CJ, Wagner B, Bullaron SJ, De Young LM (1984) The mouse ear inflammatory repsonse to topical arachidonic acid. J Invest Dermatol 82:367–371
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Moloney, S.J., Teal, J.J. Alkane-induced edema formation and cutaneous barrier dysfunction. Arch Dermatol Res 280, 375–379 (1988). https://doi.org/10.1007/BF00426617
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00426617