The Usual Suspects—Influence of Physicochemical Properties on Lag Time, Skin Deposition, and Percutaneous Penetration of Nine Model Compounds

Abstract

The influence of physicochemical properties of nine model compounds on lag time, skin deposition, and percutaneous penetration was evaluated. Static diffusion cells mounted with human skin were used as the experimental model, and experiments were carried out in accordance with Organization for Economic Cooperation and Development (OECD) guidelines. The model compounds were chosen to cover a wide spectrum of solubilities and molecular weights. The pesticides included were glyphosate, dimethoate, pirimicarb, malathion, paclobutrazol, methiocarb, prochloraz, and benzoic acid, with the ninth model compound being caffeine. The fastest dermal penetration was observed for compounds with log Pow values between 1.5 and 4. Malathion did not fit into this generalization. No clear relationship was observed between molecular weight and Kp values. The shortest lag time was observed for the most hydrophilic model compounds. With increasing molecular weight, the lag time rose. Thus, the lag time for the smallest model compound was close to 1.5 h, while the lag time exceeded 20 h for a model compound with a molecular weight of 377 g. A difference in lag time of this magnitude inevitably produces differences in the amounts of a chemical able to penetrate the skin within a limited period of time. The relative deposition in the skin was highest for the lipophilic model compounds. For log Pow values between -1 and 2, a linear relationship was observed between log Pow and log Kp. Comparisons between theoretical Kp values based on the Potts–Guy equation and experimental Kp values demonstrated good agreement. Experimental Kp values based on experiments using full-thickness human skin generally underestimated the calculated Kp values by 25%. The observations are relevant to industrial hygienists and regulatory agencies using experimental data for assessing systemic toxicity following dermal exposures as for development of structure activity relationships for dermal absorption of chemicals.

The study was funded by the Danish Environmental Protection Agency, programme on pesticides. The authors are grateful to F. Lind for technical assistance with the experimental work.