Potential of the octanol-water partition coefficient (logP) 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 (logP) 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 logP. Compared with the neat applications, positive logP were associated with larger fluxes for eight of the diluted compounds, and negative logP 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 logP (i.e., positive or negative). This approach may be suitable as a first approximation in risk assessments of dermal exposure.

Percutaneous absorption and metabolism of 2-butoxyethanol in human volunteers: a microdialysis study.

We determined percutaneous absorption kinetics of 2-butoxyethanol (BE) in volunteers using microdialysis. Four male volunteers were dermally exposed twice to 90% and 50% aqueous solutions (v/v) of BE for 4.5h. To determine percutaneous absorption kinetics the concentration of BE was measured in the dialysate samples collected at 30 min-intervals throughout exposure. The systemic absorption, which is needed to determine recovery of the BE in the dialysate, was estimated from the concentration of the main metabolite of BE, free butoxyacetic acid (BAA) in urine. A pseudo steady-state percutaneous absorption was reached approximately at 2h of exposure for both BE concentrations. The maximum dermal flux of 50% BE was higher than that of 90% BE (2.8+/-0.4, 1.9+/-0.6 mg cm(-2)h(-1), respectively). The more diluted BE solution showed shorter lag time: 25 min versus 39 min. The amount of BAA was determined in the pooled dialysate samples collected at 4 and 4.5h. The dermal metabolism seems to be low, the BAA amount ranged from 0.03% to 1.9% of the BE in the same dialysate. Our study demonstrates applicability of microdialysis technique for assessment of percutaneous absorption kinetics and dermal metabolism without interference from the systemic compartment.

Penetration of beta-naphthylamine and o-toluidine through human skin in vitro.

Several aromatic amines (AAs) are known to be carcinogens for humans. AAs are considered to be substantially absorbed through the skin. However, the database for dermal absorption of AAs in general is limited and no specific studies on dermal absorption of beta-naphthylamine (BNA) and o-toluidine (OT) have been published. In the present study using diffusion cells, we investigated dermal penetration of BNA and OT through human skin. We have demonstrated that both AAs penetrate through human skin fast (lag time: approximately 1.2 vs. 0.8 h) and in high percentages (54 vs. 50%, respectively, of the applied dose within 24 h). A skin notation is therefore justified for these substances.