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Dermal Absorption of Camphor, Menthol, and Methyl Salicylate in Humans

From the Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona (Ms. Martin, Dr. Mayersohn); Scottsdale Police Department, Laboratory Division, Scottsdale, Arizona (Ms. Valdez); and Radiant Research, Inc., Tucson, Arizona (Dr. Boren).

Camphor, menthol, and methyl salicylate occur in numerous over-the-counter products. Although extensively used, there have been no estimates of human exposure following administration via dermal application. Furthermore, there is little information about the pharmacokinetics of those compounds. The authors report the plasma concentrations of the intact compounds as a function of dose following dermal patch application. Three groups of 8 subjects (4 male, 4 female) applied a different number of commercial patches (2, 4, or 8) to the skin for 8 hours. Plasma samples were assayed using sensitive and selective gas-chromatographic methods. For the 8-patch group, the average maximum plasma concentrations (C_max ± SD) were 41.0 ± 5.8 ng/mL, 31.9 ± 8.8 ng/mL, and 29.5 ± 10.5 ng/mL for camphor, menthol, and methyl salicylate, respectively. The corresponding values for the 4-patch group were 26.8 ± 7.2 ng/mL, 19.0 ± 5.4 ng/mL, and 16.8 ± 6.8 ng/mL. The harmonic mean terminal half-lives were 5.6 ± 1.3 hours, 4.7 ± 1.6 hours, and 3.0 ± 1.2 hours for camphor, menthol, and methyl salicylate, respectively. The 2-patch group had measurable but low plasma concentrations of each compound. Low-dose dermal application for an extended time results in low plasma concentrations of all 3 compounds. Four and 8 patches, when applied for 8 hours, gave measurable and nearly proportional plasma concentrations. Although unable to determine the absolute dermal bioavailability of these compounds, there appears to be relatively low systemic exposure to these potentially toxic compounds, even when an unrealistically large number of patches are applied for an unusually long time.

Key Words: Camphor • menthol • methyl salicylate • absorption • toxicity • dermal patches

Address for reprints: Michael Mayersohn, College of Pharmacy, University of Arizona, Tucson, AZ 85721.

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