Chemicals skin penetration

Many drugs exhibit low skin penetration, which results in poor efficacy. As opposed to common chemical skin penetration enhancers, organic solvents, which are... 

Grandjean, P. (1990) Skin Penetration, Hazardous Chemicals at Work, Taylor and Francis, London. 

Matousek J. Protective properties of standard combat clothing against skin penetration of supertoxic lethal chemical warfare agents. In Sohns T., Voicu V. A. (Eds.) NBC Risks Current Capabilities and Future Perspectives for Protection. Kluwe Academic Publishers, Dordrecht - Boston - London, 1999, pp 303-310. 

No studies were located that specifically address the rate or amount of absorption of 1,4-dichlorobenzene by humans or animals after dermal exposure to 1,4-dichlorobenzene. Solid 1,4-dichlorobenzene produces a burning sensation when held closely to the skin for an excessive period of time, but it does not produce irritation or systemic effects (Hollingsworth et al. 1956). This observation indicates that some of the chemical must penetrate the skin to produce an effect on nerve endings in the skin. In a... 

The other major route of chemical hazards to plant workers is penetration through the skin, which has a surface area of about 1.8 m for a male adult, and is lined with a tough horny layer of densely packed cells without nuclei. So the skin is reasonably impervious to the penetration of chemical substances, and penetration depends on the lipid solubility of the compound, where the diffusion speed is inversely related to molecular weight. Skin penetration hazard becomes relatively more important than breathing for high boiling point liquids, which have lower vapor pressures. 

In the context of skin sensitization bioavailability can be seen as the capacity of the compound to reach the viable epidermis, where it interacts with keratinocytes and Langerhans cells. This capacity is dependent on its molecular weight and solubility in polar and apolar solvents [115]. Importantly, potency prediction solely on the basis of cell culture models (steps 3 and 4) does not account for skin penetration rate and may thus wrongly predict potency in vivo. Possible in vitro approaches to detect allergic capacity of chemicals/pharmaceuticals are presented in Table 18.5. 

Skin penetration rates and permeability constants ( p) for C-labelled diethanolamine (Table 7) were determined in vitro using full-thickness skin preparations from rats, mice, rabbits and humans (female mammoplasty patients). Human skin proved to be the best barrier against aqueous diethanolamine (37%, w/w) followed by rat, rabbit and mouse skin when the chemical was applied as an infinite dose (20 mg/cm to cm of skin for 6 h). The total absorbed dose from aqueous diethanolamine was greater (0.23-6.68%) than that from undiluted material (0.02-1.3%) (Sun et al, 1996). 

Marzulli, F.N., Anjo, D.M. Maibach, H.l. (1981) In vivo skin penetration studies of 2,4-toluenediamine, 2,4-diaminoanisole, 2-nitro-/>-phenylenediamine, />-dioxane and N-nitrosodiethanolamine in cosmetics. Food Cosmet Toxicol., 19, 743-747 Michejda, C.J., Koepke, S.R., Kroeger-Koepke, M.B. Hernandez, L. (1994) Activation of (1-hydroxyalkylnitrosamines. Evidence for involvement of a sulfotransferase. In Pignatelli, M., Loeppky, R.N. Michejda, C.J., eds, Nitrosamines and Related N-Nitroso Compounds. Chemistry and Biochemistry (ACS Symposium Series 553), Washington DC, American Chemical Society, pp. 195-210... 

Wang Q, Hikima T, Tojo K. Skin penetration enhancement by the synergistic effect of supersaturated dissolution and chemical enhancers. J Chem Eng Japan 2003 36 92-97. 

Combined Chemical and Electroporation Methods of Skin Penetration Enhancement... 

P. Grandjean, ed. Skin Penetration Hazardous Chemicals at Work. London Taylor and Francis, 1990. 

Chemical PEs have recently been studied for increasing transdermal delivery of ASOs or other polar macromolecules [35]. Chemically induced transdermal penetration results from a transient reduction in the barrier properties of the stratum corneum. The reduction may be attributed to a variety of factors such as the opening of intercellular junctions due to hydration [36], solubilization of the stratum corneum [37, 38], or increased lipid bilayer fluidization [39, 40]. Combining various surfactants and co-solvents can be used to achieve skin penetration, purportedly resulting in therapeutically relevant concentrations of ASO in the viable epidermis and dermis [41]. In summary, it appears feasible to deliver ASO to the skin using a number of different delivery techniques and formulations. 

Much of the methyl mercaptan and dimethyl sulfide can be oxidized to dimethylsulfoxide, a useful side product that is a common polar, aprotic solvent in the chemical industry. This is in fact the primary method of its manufacture, as a kraft by-product. Caution must be used when handling it because of its extremely high rate of skin penetration. 

This chapter is not an exhaustive list of all chemicals with skin-penetrating abilities. Consequently, any exclusion of a chemical from this list does not necessarily imply an inability for percutaneous absorption. When in doubt, the user should check the chemical label, material safety data sheet, manufacture date, and other details to achieve chemical safety (Table 16-1). 

Solid chemicals may be pulverized to a tine powder. The test chemical should be moistened sufficiently with water or other suitable vehicle to ensure good contact with the skin. When a vehicle is used, the influence of the vehicle on skin penetration should be considered. Liquid chemicals are generally used without dilution. 

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