In vitro human skin absorption of ethyl salicylate, pentyl salicylate, and (Z)-3-hexenyl salicylate from topical formulations: Effects on permeation and distribution.

In vitro human skin permeation and distribution of the fragrance materials ethyl salicylate (CAS 118-61-6, ES), (Z)-3-hexenyl salicylate (CAS 65405-77-8, HS) and pentyl salicylate (CAS 2050-08-0, PS) from separate 0.5 % (w/w) cream formulations were determined under unoccluded and occluded conditions for 24 h. For PS only, a 0.5 % (w/v) solution in 70/30 (v/v) ethanol/water was also assessed. Consumer relevant finite formulation doses were applied (5 mg/cm2 or 5 μl/cm2) with salicylate application of ∼25 μg/cm2. Although specifically assessing metabolism was not an aim, the common hydrolysis product salicylic acid (SA) was also quantified and included in overall test compound absorption values. For ES, absorbed doses (mean ± standard error, SE) were 12.0 ± 1.0 and 24.7 ± 1.3 % applied dose under unoccluded and occluded conditions, respectively. For HS these values were 7.28 ± 0.52 and 11.1 ± 0.7 % applied dose. For the PS cream, corresponding values were 4.43 ± 0.48 and 7.52 ± 0.63 % applied dose. Whilst for the PS solution values were 8.26 ± 0.31 and 16.1 ± 0.7 % applied dose. The salicylate structure, application vehicle and level of occlusion impacted on the observed skin absorption. Considering salicylates are commonly used fragrance ingredients and have limited skin absorption data, the current research will be helpful in risk assessment to determine systemic exposure that is realistic and fill data gaps.