Permeability of Commercial Solvents Through Living Human Skin

Abstract

A procedure has been developed for measuring the steady state rate of permeation of commercial solvents through living human skin. To get the most consistent results, it was necessary with some solvents to normalize the solvent permeation rate of a given skin sample with its [3H]water permeation rate. For other solvents this was not necessary, so the un-normalized data were used. High [3H]water permeation rate also was used as a criterion for "defective" skin samples that gave erroneous permeability rates, especially for solvents having slow permeability. The linearity of the steady state data was characterized by calculation of the "percent error of the slope." The following permeability rates (g/m2h) of single solvents were measured: dimethyl sulfoxide (DMSO), 176; N-methyl-2-pyrrolidone, 171; dimethyl acetamide, 107; methyl ethyl ketone, 53; methylene chloride, 24; [3H]water, 14.8; ethanol, 11.3; butyl acetate, 1.6; gamma-butyrolactone, 1.1; toluene, 0.8; propylene carbonate, 0.7; and sulfolane, 0.2. The effect of [3H]water saturation on the shape of the presteady state portion of the permeation curve was determined and found to be very dependent on the solvent. The permeability of mixtures of DMSO and octyl acetate were measured. No octyl acetate was detected and the permeability of DMSO was proportional to its mole fraction in the mixture. The effect of two hours of solvent exposure on the viability of skin (based on DNA synthesis) was measured and found to be very dependent on the solvent.

Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker

“…A metabolic pathway in humans, where NMP is first hydroxylized to 5-HNMP and then further oxidized to N-methylsuccinimide (MSI), which in turn is hydrolyzed to 2-hydroxy-N-methylsuccinimide (2-HMSI), has been suggested (4). It has been shown that NMP possesses a high permeability through both human (5) and rat (6,7) skin. In rat, about 70% of the radioactivity of skin-administered radiolabeled NMP is excreted in urine (7).…”

Assessment of Reproductive Toxicity and Gonadotoxic Potential of N-Methyl-2-Pyrrolidone in Male Rats

“…This conjecture is confi rmed by experiments intended to test NMP's ability to permeate the skin of humans and experimental animals [2,3]. NMP is also easily absorbed in the respiratory and alimentary tracts of experimental animals.…”

Dimethyl sulfoxide (DMSO) [MAK Value Documentation, 2011]

“…The experimental design of this study (for example, unusually long storage of the excised skin in a liquid medium and stretching of the skin during exposure) deviates considerably from the OECD (2004) recommendations for conducting skin penetration studies by means of diffusion cells. However, when the fluxes determined for toluene, N-methyl-2-pyrrolidone and N,N-dimethylformamide in the study of Ursin et al (1995) were compared with those given in the literature (Ahaghotu et al 2005;Bader et al 2005;Kezic et al 2001;Larese et al 1994) the level of agreement of the values was acceptable. Dermal application of an 80% DMSO gel in a dose of 1000 mg/kg body weight and day induced central nervous symptoms in humans, transient eosinophilia and in some cases severe local skin reactions caused by the release of histamine (Brobyn 1975).…”

“…On the basis of the flux from the study of Ursin et al (1995), it was calculated that 35.2 g DMSO (about 500 mg/kg body weight assuming the body weight to be 70 kg) would be dermally absorbed each hour through an area of 2000 cm 2 of skin. This amount corresponds to about half the LOAEL (lowest observed adverse effect level) established in the study of Brobyn (1975).…”

“…In a diffusion cell study with excised human skin, a dermal penetration rate of 176 ± 42 g/m 2 and hour was calculated for DMSO; this corresponds to 17.6 mg/cm 2 and hour (Ursin et al 1995). The experimental design of this study (for example, unusually long storage of the excised skin in a liquid medium and stretching of the skin during exposure) deviates considerably from the OECD (2004) recommendations for conducting skin penetration studies by means of diffusion cells.…”