Absorption percutaneous

In general, permeation of test chanicals throngh the RhE models exceeded that of human epidermis and pig skin, but the ranking of substance permeation through the three RhE models and pig skin accurately reflected the permeation through human epidermis. The EpiDerm RhE model provided the best correlation to human epidermal sheets (HES), as demonstrated by Papp values and a correlation coefiBcient of r =0.932. These studies demonstrate that RhE models are useful alternatives to human skin for the in vitro assessment of chemical permeation and penetration. Advantages of the RhE models compared to heat-separated human/animal epidermal sheets are their reproducibility, commercial availability, and xenobiotic metabolism capabilities, which have 

A second genotoxicity test, the comet assay, detects a broad spectrum of DNA damage. A comet assay protocol developed and evaluated using the EpiDerm model demonstrated good interlaboratory reproducibility and concordance with in vivo data (Reus et al., 2013). Additional in vitro RhE comet assay development and evaluation of intra- and interlaboratory reproducibihty with EpiDerm, Realskin, and the Phenion model are currently ongoing. 

Cutaneous reactions are among the most prevalent adverse effects of therapeutic drugs. Ranging from relatively minor skin rashes to more serious toxic consequences such as SJS and TEN, these cutaneous effects can impose major limitations on clinical therapeutic use. Mechanisms of adverse cutaneous drug reactions may be immune mediated, photochemical, directly related to therapeutic activity, or idiosyncratic toxidties for which the mechanisms are poorly understood. 

In vitro models that are relevant for assessing the potential for adverse cutaneous reactions include monolayer or suspension cultures of skin and immune cells, as well as 3D organotypic RhE models, some of which are commercially available and vahdated for specific regulatory applications. Deficiencies of currently available in vitro RhE models include a lack of fatty layer, skin appendages innervations. 

Aardema, M.J., Barnett, B.C., Khambatta, Z., Reisinger, K., Ouedraogo-Arras, G., Faquet, B., Ginestet, A.C., Mun, G.C., Dahl, E.L., Hewitt, N.J., Corvi, R., Curren, R.D. (2010) International prevalidation studies of the EpiDerm 3D human reconstructed skin micronucleus (RSMN) assay transferability and reproducibility. MutatRes, 701 (2), 123-131. 

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Skin. The skin may become contaminated accidentally or, in some cases, materials may be deHberately appHed. Skin is a principal route of exposure in the industrial environment. Local effects that are produced include acute or chronic inflammation, allergic reactions, and neoplasia. The skin may also act as a significant route for the absorption of systemicaHy toxic materials. Eactors influencing the amount of material absorbed include the site of contamination, integrity of the skin, temperature, formulation of the material, and physicochemical characteristics, including charge, molecular weight, and hydrophilic and lipophilic characteristics. Determinants of percutaneous absorption and toxicity have been reviewed (32—35,42,43,46—49). 

PERCUTANEOUS ABSORPTION Absoi ption via the skin, e.g. due to local contamination or a splash of chemical. 

Riihimaki, V. (1979), Percutaneous absorption of iB-xylene from a mixture of m-xyleiie and isobutyl alcohol in man. Scand. ]. Work Environ. Health 5, 14,3-150,... 

Alcohol and alcohol ether sulfates have also been studied to determine their toxicity by percutaneous absorption in rats and guinea pigs [354-356]. Alcohol ether sulfates penetrate in the order of 1 ng/cm2/day and alcohol sulfates are less penetrant by a factor of 10. The surfactant absorbed was metabolized. Since it is known that human skin is less permeable than animal skin, only very small amounts of alcohol or alcohol ether sulfates can be absorbed even in the case of complete body exposure. 

Taking into account the low oral toxicity and the low intestinal and percutaneous absorption of alcohol sulfates and alcohol ether sulfates, the possibility of systemic toxic effects in humans is extremely unlikely [344]. 

Takahara J, Takayama K, Isowa K, Nagai T. Multi-objective simultaneous optimization based on artificial neural network in a ketoprofen hydrogel formula containing o-ethylmenthol as a percutaneous absorption enhancer. Int J Pharm 1997 158 203-10. 

Wu P-C, Obata Y, Fijukawa M, Li CJ, Higashiyama K, Takayama K. Simultaneous optimization based on artificial neural networks in ketoprofen hydrogel formula containing o-ethyl-3-burylcyclohexanol as a percutaneous absorption enhancer. J Pharm Sci 2001 90 1004-14. 

TsurutaH. 1978. Percutaneous absorption of trichloroethylene in mice. Ind Health 16 145-148. 

Wester RC, Maibach HI. 1987. Percutaneous absorption of organic solvents. In Maibach HI, ed. Occupational and industrial dermatology, 2nd ed. Chicago, IL Year Book Medical Publishers, Inc., 213-226. 

The percutaneous absorption picture can be qualitatively clarified by considering Fig. 3, where the schematic skin cross section is placed side by side with a simple model for percutaneous absorption patterned after an electrical circuit. In the case of absorption across a membrane, the current or flux is in terms of matter or molecules rather than electrons, and the driving force is a concentration gradient (technically, a chemical potential gradient) rather than a voltage drop [38]. Each layer of a membrane acts as a diffusional resistor. The resistance of a layer is proportional to its thickness (h), inversely proportional to the diffusive mobility of a substance within it as reflected in a... 

W. M. Smith, An Inquiry into the Mechanism of Percutaneous Absorption of Hydrocortisone and its n-Alkyl Esters, thesis, University of Michigan, 1982. 

H. Schaefer and T. E. Redelmeier, Skin Barrier— Principles of Percutaneous Absorption, Karger, Basel, 1996, pp. 213-223. 

Laug EP, Draize JH. 1942. The percutaneous absorption of ammonium hydrogen sulfide and hydrogen sulfide. J Pharmacol Exp Ther 76 179-188. 

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