Potential of the octanol–water partition coefficient (log P) to predict the dermal penetration behaviour of amphiphilic compounds in aqueous solutions

Aqueous amphiphilic compounds may exhibit enhanced skin penetration compared with neat compounds. Conventional models do not predict this percutaneous penetration behaviour. We investigated the potential of the octanol–water partition coefficient (log P) to predict dermal fluxes for eight compounds applied neat and as 50% aqueous solutions in diffusion cell experiments using human skin. Data for seven other compounds were accessed from literature. In total, seven glycol ethers, three alcohols, two glycols, and three other chemicals were considered. Of these 15 compounds, 10 penetrated faster through the skin as aqueous solutions than as neat compounds. The other five compounds exhibited larger fluxes as neat applications. For 13 of the 15 compounds, a consistent relationship was identified between the percutaneous penetration behaviour and the log P. Compared with the neat applications, positive log P were associated with larger fluxes for eight of the diluted compounds, and negative log P were associated with smaller fluxes for five of the diluted compounds. Our study demonstrates that decreases or enhancements in dermal penetration upon aqueous dilution can be predicted for many compounds from the sign of log P (i.e., positive or negative). This approach may be suitable as a first approximation in risk assessments of dermal exposure.

► Percutaneous penetration behaviours of aqueous solvents can be predicted from the sign of log P values (i.e., positive or negative).
► Positive log P are associated with penetration enhancement of aqueous chemicals.
► Negative log P are associated with flux decrease of chemicals from aqueous solutions.
► This approach can be suitable for a first approximation in risk assessments of dermal exposure.