Percutaneous penetration

Sartorelli P, Aprea C, Bussani R, et al. 1997. In vitro percutaneous penetration of methyl-parathion from a commercial formulation through the human skin. Occup Environ Med 54 524-525. 

Typically, there is a latent period with no visible effects between the time of exposure and the sudden onset of symptoms. This latency can range from 1 minutes to 18 hours and is affected by such factors as the amount of agent involved, the amount of skin surface in contact with the agent, and the area of the body exposed (see Liquids). Moist, sweaty areas of the body are more susceptible to percutaneous penetration by solid nerve agents. 

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. 

Individuals who have had previous exposure to materials that chap or dry the skin, such as alcohols, gasoline, or paint thinners, may be more susceptible to percutaneous penetration of liquid agents. In these situations, the rate of percutaneous penetration of the agent is greatly increased resulting in a decrease in the survival time that would otherwise be expected. 

Another key factor is the part of the body that is exposed to the agent. It takes more time for the agent to penetrate areas of the body that are covered by thicker and tougher skin. The regions of the body that allow the fastest percutaneous penetration are the groin, head, and neck. The least susceptible body regions are the hands, feet, front of the knee, and outside of the elbow. 

F.-X. Mathy, C. Lombry, R. Verbeeck, and V. Preat. Study of percutaneous penetration of flubiprofen by cutaneous and subcutaneous microdialysis after iontophoretic delivery in rat. J. Pharm. Sci. 94 144—152 (2005). 

Bando H, Mohri S, Yamashita F, Takakura Y, Hashida M (1997) Effects of skin metabolism on percutaneous penetration of lipophilic drugs. J Pharm Sci 86 759-761. 

Susten AS et al Percutaneous penetration of benzene in hairless mice An estimate of dermal absorption during tire building operations. 7/wii 7 323-335, 1985... 

Frankild S, Andersen KE, Nielsen GD. 1995. Effect of sodium lauryl sulfate (SLS) on in vitro percutaneous penetration of water, hydrocortisone and nickel. Contact Dermatitis 32 338-345. 

Rougier et al. reported that the percutaneous penetration of benzoic acid in human skin depended on the anatomical location of the skin. The rank order in skin permeability of benzoic acid appears to be arm < abdomen < postauricular < forehead [49]. 

Percutaneous penetration of 7V-nitrosodiethanolamine was measured using cryo-preserved human trunk skin and three vehicle formulations (isopropyl myristate, sunscreen cream or a 10% shampoo) containing 7V-nitroso[ C]diethanolamine. The absorption rate of a low dermal dose (10 ixg/cm ) of 7V-nitrosodiethanolamine was a linear function of the concentration (0.06, 0.2 or 0.6 Xg/ xL) applied to the skin. The peak rates for the isopropyl m uistate and shampoo vehicles were seen within five hours and for the sunscreen somewhat later. Total 48-h absorption ranged from 35 to 65% of the dose and was formulation-dependent (isopropyl m uistate > shampoo > sunscreen). A total absorption of 4-6 x JcaE was estimated to equate to an applied N-nitrosodiethanolamine dose of 10 x%lcaE. When applied as a large infinite dose (0.5 mg/cm ), total 7V-nitrosodiethanolamine absorption (4-35% of the applied dose) followed a different rank order (shampoo > isopropyl m uistate > sunscreen), probably due to the barrier-damaging properties of the vehicles. The permeability coefficient for isopropyl myristate was 3.5 X 10 cm/h (Franz etal., 1993). 

Bronaugh R, Maibach HI Percutaneous Penetration Principles and Practices, 4th ed. Taylor Francis, 2005. 

Smith WW, Maibach HI. Percutaneous penetration enhancers the fundamentals. In Smith EW, Maibach HI, eds. Percutaneous Penetration Enhancers. Boca Raton, Florida CRC Press, 1995b 1-4. 

Walker R, Smith E. The role of percutaneous penetration enhancers. Adv Drug Delivery Rev 1996 18 295-301. 

Bucks, D.A.W., Guy, R.H. Maibach, H.I. (1990) Percutaneous penetration and mass balance accountability technique and implications for dermatology. J. Toxicol, cutan. ocul. Toxicol., 9, 439-451... 

Microscopically, the skin is a multilayered organ composed of many histological layers. It is generally subdivided into three layers the epidermis, the dermis, and the hypodermis [1]. The uppermost nonviable layer of the epidermis, the stratum corneum, has been demonstrated to constitute the principal barrier to percutaneous penetration [2,3]. The excellent barrier properties of the stratum corneum can be ascribed to its unique structure and composition. The viable epidermis is situated beneath the stratum corneum and responsible for the generation of the stratum corneum. The dermis is directly adjacent to the epidermis and composed of a matrix of connective tissue, which renders the skin its elasticity and resistance to deformation. The blood vessels that are present in the dermis provide the skin with nutrients and oxygen [1]. The hypodermis or subcutaneous fat tissue is the lowermost layer of the skin. It supports the dermis and epidermis and provides thermal isolation and mechanical protection of the body. 

Bodde, H.E., et al. 1991. Visualization of in vitro percutaneous penetration of mercuric chloride transport through intercellular space versus cellular uptake through desmosomes. J Control Release 15 227. 

Delgado-Charro, M.B., and R.H. Guy. 1998. Percutaneous penetration and transdermal drug delivery. Prog Dermatol 32 1. 

From the finding that the 14C-butylparaben flux decreased at increasing lipid content, it was concluded that only 14C-butylparaben dissolved in the water phase contributed to the percutaneous penetration. However, another mechanism may also play a role. An increase in lipid content reduces the thermodynamic activity of butylparaben in the bilayers, which might lead to a decrease in the driving force from the lipid phase to either the water phase or the SC. This may also contribute to a reduced penetration through the skin. 

C. Michel, T. Purmann, E. Mentrup, E. Seiller, and J. Kreuter. Effect of liposomes on percutaneous penetration of lipophilic materials. Int. J. Pharm. 84 93-105 (1992). 

H. Kumatsu, K. Higazi, H. Okamoto, K. Miyakwa, M. Hashida, and H. Sezaki, Preservative activity and in vivo percutaneous penetration of butylparaben entrapped in liposomes, Chem. Pharm. Bull. 34 3415-3422 (1986). 

H. Tanojo, H. E. Junginger, and H. E. Bodde, Effects of oleic acid on human trans-epidermal water loss using ethanol or propylene glycol as vehicles, Prediction of Percutaneous Penetration, Vol. 3 (K. R. Brain, V. J. James, K. A. Walters, eds.), STS Publishing, Cardiff, UK, 1993, pp. 319-324. 

---