In Vitro Human Skin Penetration of the Fragrance Material Linalool

The in vitro human skin penetration of linalool [CAS # 78-70-6] was assessed in three vehicles relevant to fragrance exposure [1:3 Ethanol:diethyl phthalate (1:3 EtOH:DEP), 1:3 Ethanol:dipropylene glycol (1:3 EtOH:DPG) and petrolatum]. The assays were conducted under both occlusive and non-occlusive conditions. Diffusion cells were prepared with epidermal membranes obtained from surgical donors. Permeation of linalool, from a 5 μl/cm2 target dose of a 4 % (w/v) solution, was measured at twelve time-points over 24 hours, using a phosphate buffered saline receptor phase. At 24 hours, the epidermal membranes were wiped, tape stripped 10 times and the linalool content of the wipes, strips and remaining epidermis determined. The fi lter paper skin supports were extracted and the diffusion cell donor chambers washed and wiped. Potential evaporative loss of linalool was estimated by measuring the loss from PTFE sheets under the same experimental conditions. Levels of linalool in the epidermis (plus any remaining stratum corneum after tape stripping), fi lter paper membrane support and receptor fl uid were combined to produce a total absorbed dose value. Under non-occlusive conditions 2.71 ± 0.2 % of the applied dose was absorbed at 24 hours in 1:3 EtOH:DEP, 2.01 ± 0.2 % in 1:3 EtOH:DPG and 3.54 ± 0.4 % in petrolatum. Under occlusive conditions 7.33 ± 0.58 % of the applied dose was absorbed at 24 hours in 1:3 EtOH:DEP, 12.1 ± 1.5 % in 1:3 EtOH:DPG and 10.5 ± 1.1% in petrolatum. Evaporative loss was signifi cant and accounted for the differences in absorption between occluded and non-occluded conditions. From these results, systemic exposure to linalool from use in fragrances would be expected to be low based on currently reported use levels. In addition to providing information to risk assessments, the variety of vehicles will provide comparative data to assist in the development of dermal absorption models for this material