Permeability of the skin

Exercise also increases skin circulation and perspiration, which both enhance dermal penetration of compounds into the body. Furthermore, skin lesions, such as wounds and dermatitis, can increase the permeability of the skin to chemicals. Also, exposure of the skin to solvents and removal of skin fat increase dermal penetration of a number of compounds. Compounds penetrate the skin more readily in places where the skin is thin, like the face, hands and scrotum. Increased dermal blood flow due to exercise facilitates the penetration of the skin by chemicals. 

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). 

The permeability of the skin to a toxic substance is a function of both the substance and the skin. The permeability of the skin varies with both the location and the species that penetrates it. In order to penetrate the skin significantly, a substance must be a liquid or gas or significantly soluble in water or organic solvents. In general, nonpolar, lipid-soluble substances traverse skin more readily than do ionic species. Substances that penetrate skin easily include lipid-soluble endogenous substances (hormones, vitamins D and K) and a number of xenobiotic compounds. Common examples of these are phenol, nicotine, and strychnine. Some military poisons, such as the nerve gas sarin (see Section 18.8), permeate the skin very readily, which greatly adds to then-hazards. In addition to the rate of transport through the skin, an additional factor that influences toxicity via the percutaneous route is the blood flow at the site of exposure. 

In order to increase the number of drugs which can be administered transdermally, the barrier function of the skin must be reduced. The kinetic model can be used to assess the role of a penetration enhancer as a function of the physicochemical properties of the drug. In its simplest form a penetration enhancer may be considered to act in one of two ways. Firstly it may increase the permeability of the skin and, secondly, it may additionally modify the partitioning characteristics at the stratum corneum-viable tissue interface. For illustration, two enhancers have been arbitrarily chosen, the first PE1 increases the permeability by a factor of 10, i.e. k- is increased ten fold. The second, PE2, increases k- by a factor of 10 and decreases kg by a similar amount. Thus PE2 additionally reduces the partition coefficient by a factor of 10. The relative effects can be seen by considering two model drug... 

In the assessment of the uptake of a chemical after dermal exposure, for instance, the dermal permeability of the skin is often estimated using the Potts-Guy quantitative structure-activity relationship (Guy Potts, 1992), which was derived from an experimental data set of in vitro measured steady-state skin permeations (Wilschut et al., 1995). Uncertainty in the use of a value for the skin permeation obtained this way comes from questions of how well a regression model based on Kow and molecular weight predicts the skin permeability of a chemical that was not in the original data set, and how representative the steady-state permeability measured in vitro is for a (possibly) non-steady-state permeability in vivo (see also IPCS, 2006b). 

Essential oils enter the body through the skin by the ducts of the sweat glands and the hair follicles. The permeability of the skin at various locations in the body can be linked to the number of available ducts acting as entry points. Sites such as the palms of the hands, soles of the feet, armpits, genitals, forehead and scalp are quite permeable to absorption of essential oils, while the limbs, buttocks, abdomen and trunk are relatively impermeable. 

For dermal toxicity testing the drug substance is applied by innunction of a certain volume onto a depilated (mechanically or by depilatories) skin areas. However, these methods can alter the permeability of the skin. In order to avoid licking off from the treated skin areas, Elizabethan collars can be fixed around the neck of the animals. 

Therapeutic ultrasound has been found to first expand and then collapse air huhhles in the stratum corneum (the process of cavitation). Cavitation tends to liquefy the solid fats and allows molecules such as insulin to pass through the skin at levels which in diabetic rats causes blood sugar lowering. The permeability of the skin was found to increase as the frequency of ultrasound decreased and no long-term damage was caused. 

More direct approaches for monitoring skin absorption have been proposed - for example, measuring the rate of disappearance of the chemical at the application site. However, the generally low permeability of the skin means that the rate of disappearance is often very slow, and the accuracy of the measurement will depend on analytical techniques that are capable of accurately quantifying minute differences. Reliable results can only be obtained with chemicals that are rapidly absorbed and/or easily quantitated analytically. The main use of this technique is monitoring the loss of radioactivity from the skin surface, but it should be appreciated that... 

Dilute bleach is a skin irritant, potentially increasing the permeability of the skin to the chemical agent... 

Sodium chloride Frog Reduced mortality 100% by replacing Cl lost by higher permeability of the skin 246... 

Third application (third day) contact time 30-35 minutes. The third application must be carried out with extreme caution if the resorcinol membrane that is forming has modified the permeability of the skin, epidermolysis is present and the skin has been badly injured rough handling (or paste that is too compact) could pull away the skin and sharply increase the risk of post-peel complications in the form of erythema and pigmentary changes. 

Pressure waves (PW), which can be generated by intense laser radiation, without incurring direct ablative effects on the skin have also been recently found to increase the permeability of the skin [66-68]. It is thought that PW form a continuous or hydrophilic pathway across the skin due to expansion of the lacunae domains in the SC. Important parameters affecting delivery such as peak pressure. 

Evidently, a large variation is observed in the data of the levels of VX in blood. Presumably, this spread is caused by the variation in thickness and permeability of the skin in the various animals. The curve through the data points has been drawn by the eye. The AUC was estimated at 43 8ng min mL and was calculated as the mean of the individual curves. The bioavailability can be calculated as the ratio of the AUC after percutaneous application and the extrapolated AUC that would have been derived after i.v. injection of the same dose. The bioavailability after percutaneous (p.c.) application appeared to be only 2.5%. In view of... 

As mention previously, dermal absorption of contaminants in water can be significant. The permeability of the skin to a chemical is influenced by an agent s molecular weight, electrostatic charge, hydrophobicity, and solubility in aqueous and lipid media. Chemicals that can penetrate the skin easily, are generally nonio-nized, lipid soluble, low molecular weight substances. Chemical-specific permeability coefficients should be used to estimate dermal absorption of a chemical from water. 

Iodine readily crosses the placenta (Wolff, 1969), and significant amounts of iodine are concentrated by the mammary gland and secreted into the breast milk (Spencer et aly 1986 Koga et aly 1995 Roti and degli Uberti, 2001). The high permeability of the skin of neonates can lead to iodine overload when iodine-containing antiseptics are applied (Mitchell et al, 1991 Pyati et al, 1977). Additionally, the renal clearance of iodine is poor in newborn infants (Aliefendioglu et al, 2006). 

Scheuplein, R.J., 1977, Permeability of the skin, in D. Lee (ed.). Handbook of Physiology Reactions to Environmental Agents, Bethesda, MD American Physiological Society, pp. 299-322. 

Because of the low permeability of the skin to many drugs, trans-dermal delivery has limited applications. The low permeability is attributed primarily to the stratum comeum, the outermost skin layer which consists of flat, dead cells filled with keratin fibers surrounded by lipid bilayers. One common method of increasing the passive transdermal diffusional drug flux involves pretreating the skin with a skin permeation enhancer. 

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