Measuring the penetration of a skin sensitizer and its delivery vehicles simultaneously with confocal Raman spectroscopy.

Among the factors determining the propensity of a chemical to induce skin allergy are the penetration into skin and the kinetics of ingress. Confocal Raman spectroscopy can provide such information as it enables direct, spatially resolved measurement of the skin and of any chemical uptake. Several chemicals can be monitored at once, and the method is non-destructive (light in, light out) so that the skin can be kept intact for repeated and continuous measurement. Raman spectroscopy was used to follow the penetration of 2.5 weight percent trans-cinnamaldehyde and its delivery vehicle into skin in vitro, up to 24 h after topical application. A custom-made Bronaugh-type diffusion cell that was suitable for the Raman experiment was used. Four different vehicles were tested: absolute ethanol, 50% aqueous ethanol, propylene glycol and acetone:olive oil (4:1); these gave different time scales for cinnamaldehyde penetration. The acetone:olive oil vehicle phase-separated on the skin surface and the cinnamaldehyde penetrated at different rates in the different phases, which may be of significance since this is the preferred solvent for the local lymph node assay (an in vivo animal test used to generate hazard information on skin sensitization). In conclusion, the Raman method gives valuable detailed information on chemical ingress, clearly differentiates between different delivery rates and allows solvent monitoring alongside the chemical of interest.