In-vitro human skin penetration of the fragrance material geranyl nitrile

In-vitro human skin permeation and distribution of geranyl nitrile (GN) was determined using epidermal membranes following application (5 microl/cm(2)) in 70% ethanol, under non-occlusive conditions, at maximum in-use concentration (1%). Permeation was measured (12 time-points over 24 h) using 6% (w/v) Oleth-20 in pH 7.4 phosphate buffered saline as receptor. Permeation of reference benzoic acid was assessed using the same skin donors. Overall recovery of GN at 24 h was low (14.1+/-0.4%) due to evaporation. Evaporative loss of GN from polytetrafluoroethylene (PTFE) sheet, under the same conditions was rapid (93% over 24h) although this overestimated loss during permeation where evaporation competed with uptake. At 24 h, 1.89+/-0.15 microg/cm(2) GN, (3.74+/-0.30% of applied dose) (mean+/-standard error, SE, n=12), had permeated. Following rapid initial permeation, the absorption plateaued due to depletion. Levels of GN in the epidermis (plus any remaining stratum corneum after tape stripping), filter paper membrane support and receptor fluid were combined (as per SCCNFP guidelines) to produce a total absorbed dose value of 4.72+/-0.32%. Systemic exposure resulting from the use of GN as a fragrance ingredient, under unoccluded conditions, would be low based on the currently reported use levels.