In vitro human skin penetration of geraniol and citronellol.
BACKGROUND
Geraniol and citronellol are commonly used fragrance components in consumer products. Both are listed as alleged fragrance allergens that should be declared in the European Union when used in cosmetics and consumer products. Such allergenic potential is determined largely by effects on the skin once these materials penetrate and elicit an immune response. Few data demonstrate their penetration abilities or their effects on percutaneous absorption. We wanted to determine the effects of these materials on skin absorption. Skin penetration characterization via flow-through diffusion study serves as a reasonable model for determining dermal dosing for fragrance materials. Such characterization can be used for more accurate safety exposure calculations and regulatory determinations. Extensive comparisons to in vivo data in humans or closely related animals will be required before accepting flow-through diffusion methods as in vivo alternatives by industry and regulatory bodies.


OBJECTIVE
To evaluate the penetration abilities of geraniol and citronellol when they are used in a typical vehicle in consumer products.


METHODS
In vitro skin penetration of radiolabeled geraniol and citronellol was studied under occlusion in human cadaver skin, using flow-through diffusion cells for scintillation counting to determine the percentage of dose absorbed. For comparison, two doses of each material were used: 2% and 5% in 3:1 diethyl phthalate/ethanol.


RESULTS
After 24 hours, geraniol and citronellol had relatively low skin absorption rates; 3.8% +/- 2.1% of 2% citronellol, 4.7% +/- 1.9% of 5% citronellol, 3.5% +/- 1.9% of 2% geraniol, and 7.3% +/- 1.1% of 5% geraniol were recovered from skin and receptor fluid compartments. These materials showed good mass-balance recovery. The majority of the dose was recovered in the skin washes (a minimum of 64.7% +/- 4.6% recovered for 2% citronellol and a maximum of 79.3% +/- 3.9% recovered for 5% geraniol). Receptor fluid collection points over time showed a linear increase in the amounts of citronellol and geraniol that penetrated the skin, although overall absorption values were quite small.


CONCLUSIONS
In vitro results indicate that geraniol and citronellol have low potentials for skin penetration, which has implications for their ability to induce allergenicity and for more predictive toxicologic profiling of these materials. In vivo studies should be done to correlate the in vitro results.
University of Minnesota, Minneapolis, MN, USA. sgilpin@aveda.com
Sarah
S
Gilpin
Xiaoying
X
Hui
Howard
H
Maibach
D000080462:Acyclic Monoterpenes; D000368:Aged; D000485:Allergens / Q000493:pharmacokinetics*; D002102:Cadaver; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D039821:Monoterpenes / Q000493:pharmacokinetics*; D010476:Perfume; D012869:Skin Absorption; D013729:Terpenes / Q000493:pharmacokinetics*
D000080462:Acyclic Monoterpenes; D000485:Allergens; D039821:Monoterpenes; D010476:Perfume; D013729:Terpenes; C007836:geraniol; C007078:citronellol