Dimethyl sulfoxide , penetration

Strong acids and strong alkaUes can severely bum the skin, chromium compounds can produce skin rashes, and repeated exposure to solvents causes removal of natural oils from the skin. Infection is always a concern for damaged skin. Absorption through the skin is possible for materials that are appreciably soluble iu both water and oil, eg, nitrobenzene, aniline, and tetraethyllead. Other materials can be absorbed if first dissolved iu extremely good solvents, eg, dimethyl sulfoxide. Subcutaneous iujection can occur accidentally by direct exposure of the circulatory system to a chemical by means of a cut or scratch or iuadvertent penetration of the skin with a hypodermic needle. 

Dimethyl sulfoxide occurs widely at levels of <3 ppm. It has been isolated from spearmint oil, com, barley, malt, alfalfa, beets, cabbage, cucumbers, oats, onion, Swiss chard, tomatoes, raspberries, beer, coffee, milk, and tea (5). It is a common constituent of natural waters, and it occurs in seawater in the 2one of light penetration where it may represent a product of algal metaboHsm (6). Its occurrence in rainwater may result from oxidation of atmospheric dimethyl sulfide, which occurs as part of the natural transfer of sulfur of biological origin (7,8). 

Dimethyl sulfoxide (DMSO) is a particularly well-known sulfoxide that is often used as a polar aprotic solvent. It must be handled with care, however, because it has a remarkable ability to penetrate the skin, carrying along whatever is dissolved in it. 

Solvents have been added to nerve agents to facilitate handling, to stabilize the agents, or to increase the ease of percutaneous penetration by the agents. Percutaneous enhancement solvents include dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylpalmitamide, N,N-dimethyldecanamide, and saponin. Color and other properties of these solutions may vary from the pure agent. Odors will vary depending on the characteristics of the solvent(s) used and concentration of nerve agent in the solution. 

McDermot, H.L., Murray, G.W., Heggie, R.M. 1965. Penetration of guinea pig and rabbit skin by dimethyl sulfoxide solutions of a quaternary oxime. Canad. J. Physiol. Pharmacol. 43 845-848. 

The main obstacle to percntaneous penetration of water and xenobiotics is the onter-most membrane of the epidermis. This is called the stratum comeum. All entry of substances through the stratum comeum occurs by passive diffusion across several cell layers. The locus of entry varies, depending on the chemical properties of xenobiotics. Polar substances are believed to penetrate cell membranes through the protein filaments nonpolar ones enter through the hpid matrix. Hydration of the stratnm comenm increases its permeability for polar substances. Electrolytes enter mainly in a nonionized form, and thus the pH of the solution applied to the skin affects permeabUity. Many hpophdic substances, such as carbon tetrachloride and organophosphate insecticides, readily penetrate the stratum comeum. Pretreatment of the skin with solvents, snch as dimethyl sulfoxide, methanol, ethanol, hexane, acetone, and, in particular, a mixture of chloroform and methanol, increases permeability of the skin (Loomis, 1978). 

Dimethyl sulfoxide is a relatively stable solvent of low toxiaty. However, DMSO can penetrate the skin and may carry with it certain chemicals with which it is combined under certain conditions. Dimethyl sulfoxide has received considerable attention as a useful agent m medicine. In veterinary medicine, DMSO is used for horses and dogs as a topical application to reduce swelling resulting from injury or trauma. 

Fig. 6.14. Label-free chemical imaging of the penetration pathways for the topically applied drug diffusion enhancer dimethyl sulfoxide (DMSO) into mouse skin tissue Dual-frequency SRS imaging tuned into the characteristic vibration of DMSO at 670 cm-1 (bright gray regions) and the CH2 vibration of lipid-rich adipocytes at 2845 cm-1 (dark gray regions) at a depth of 65pm into the tissue. DMSO is hydrophilic and hence avoids lipid structures such as adipocytes (Image courtesy of Brian Saar, Chris Freudiger, and Wei Min [12])...

Caspers, P.J., et al. 2002. Monitoring the penetration enhancer dimethyl sulfoxide in human stratum corneum in vivo by confocal Raman spectroscopy. Pharm Res 19 1577. 

A. Dimethyl sulfoxide is a non-polar compound that rapidly penetrates the skin. 

Repeated Dose Dermal Tests. Twenty-one to 28-day dermal tests are particularly important when the expected route of human exposure is by contact with the skin, as is the case with many industrial chemicals or pesticides. Compounds to be tested are usually applied daily to clipped areas on the back of the animal, either undiluted or in a suitable vehicle. In the latter case, if a vehicle is used, it is also applied to the controls. Selection of a suitable solvent is difficult because many affect the skin, causing either drying or irritation, whereas others may markedly affect the rate of penetration of the test chemical. Com oil, methanol, or carboxymethyl cellulose are preferred to dimethyl sulfoxide (DMSO) or acetone. It should also be considered that some of the test chemical may be ingested as a result of grooming by the animal, although this can be controlled to some extent by use of restraining collars and/or wrapping. 

Apart from this classic approach, it would be possible to improve the properties of known CWs, e.g. microencapsulation so that less stable or highly volatile substances can be used. Nanotechnology offers new possibilities, as described recently by Price and Peterson (2008). The other option is to improve penetration using known enhancers like dimethyl sulfoxide (DMSO). While the percutaneous toxicity (expressed as LD50 in rats) of one of the toxic organophosphates - O-isopropyl 5-2-diisopropylaminoethyl methyl phosphnothiolate - is 59.1 P-g/kg, in mixture with DMSO this value is decreased to 10.1 pg/kg (Bajgar, 1989). 

Anigbogu, A. N. C. et al. Fourier-transform Raman spectroscopy of interactions between the penetration enhancer dimethyl-sulfoxide and human stratum comeum. International Journal of Pharmaceutics 725(2) 265-282, 1996. 

In paint formulations of idoxuridine, dimethyl sulfoxide acts both as a solvent to increase drug solubility and a means of enabling penetration of the antiviral agent to the deeper levels of the epidermis. See Table I. 

Dimethyl sulfoxide enhances the skin penetration of several drugs, which may result in producing the adverse effects associated with those drugs. 

Dimethyl sulfoxide (DMSO) has excellent solvent properties and acts as a skin penetration enhancer for drugs and other substances by increasing the permeability of the barrier layer of the skin. It is used in the topical administration of drugs, the production of synthetic fibers, the application of pesticides, as an antifreeze, hydraulic fluid, and in the manufacturing of industrial cleaners and paint strippers. Its antiinflammatory and analgesic effects, and the ability to quench free radicals have been by physicians and others for various therapeutic uses. 

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