38th Scientific
Meeting (GV - SOLAS)
Society for Laboratory Animal Science
(Essen, 2000)
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38th Scientific
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(Essen, 2000) |
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Skin Abstract 1 The ´with blood perfused pig ear´; a model for studying interactions between chemicals and the skin Graham R. Elliott Dept. Pharmacology, TNO Prins Maurits Laboratorium, Postbus 45, 2280 AA, Rijswijk, NL For almost a century now, it has been established that the skin is not an impermeable organ. In the work place the skin can be an important route of systemic contamination and exposure levels can be 1000 higher than those experienced via the respiratory route. Pharmaceutical companies also use the skin as a route of drug administration and are more frequently formulating drugs for dermal administration. A great deal of research has been carried out to validate systems for measuring rates of percutaneous permeation of chemicals in order to set safety limits for the work place and develop drug formulations. In vivo animal models and in vitro systems, such as the diffusion cell, have been used for this purpose. However, despite much research there is no generally accepted method for predicting rates of dermal permeation of chemicals in humans.  Recently, we introduced a new model for in vitro percutaneous permeation studies: the with blood perfused pig ear (de Lange et al., 1990). The model has several advantages over other (alternative) systems. Firstly, we use waste material from a slaughter house, not experimental animals. Secondly, we use intact skin perfused with blood. In contrast to diffusion cell systems, we do not have to decide whether to use full skin, split skin or epidermal sheets. We do not have to decide whether to add an alcohol or detergent to the receptor fluid if the test chemical is not very soluble in water. Thirdly, chemicals are removed from the exposure area by the blood, i.e. chemicals remain in contact with the skin for a biologically relevant time. This is not the case for static diffusion cells. In order to validate the model we have compared the rates of percutaneous penetration of some chemicals using the pig ear model, rat and humans skin and epidermal sheets in a diffusion cell and human volunteers. The data obtained for steady state rates of percutaneous penetration using the pig ear model varied by a maximum of 2.5 x from the human data. We have also shown that the model can be used to investigate decontamination methods, the efficacy of barrier creams, repair of the skins barrier function following exposure to irritant chemicals and physiological factors influencing the dermal penetration of chemicals. In summary. The perfused pig ear is a simple and flexible model with which to investigate interactions between chemicals and the skin.  top Abstract 2 The use of the reflexion spectroscopy to study the distribution of carotinoids into the skin of the isolated perfused bovine udder F. Niedorf (1), H. Jungmann (2), W. Pittermann (3), M. Kietzmann (1) (1) Institute for Pharmacology, Pharmacy and Toxicology, Veterinary School Hannover, D-30559 Hannover (2) MBR Meßtechnik GmbH, D-58313 Herdecke, (3) Henkel KGaA, D40191 Duesseldorf The purpose of this study was to confirm the reflection spectroscopy as a non invasive analytic method for the determination of drug concentrations in the skin of the isolated perfused udder. As test compound ß-carotene was used. The udder was perfused with solutions of different ß-carotene concentrations. A dose dependent increase of the dermal ß-carotene level could be demonstrated in the range of 0.2 to 20 µg/ml ß-carotene. No increase of the dermal ß-carotene concentration could be detected in non vital organs. top Abstract 3 Opportunities of the BUS-model during development and characterisation of transdermal systems using estradiol-17ß Wolff M. (1), Kluge K .(2) , Arth C. (1), Bonn R. (1) and M. Kietzmann (3) (1) Schwarz Pharma AG, Alfred-Nobel-Straße 10, D-40789 Monheim (2) Institute for Pharmacology, Pharmacy and Toxicology, Veterinary Faculty Leipzig, University Leipzig, D-04103 Leipzig (3) Institute for Pharmacology, Pharmacy and Toxicology, Veterinary School Hannover, D-30559 Hannover The isolated perfused bovine udder is an in vitro model which maintains bovine udder skin with an isolated vasculature in a viable state. It is possible to compare the dermal penetration of substances after topical administration of different formulations. The presented data indicate that the system yields data which can be extrapolated to man. The presented data confirm differences between TTS-A and TTS-B which were found in a bioavailability study in human volunteers. The rate of transdermal absorption of estradiol-17ß after topical administration of TTS-A exceeded that of TTS-B. Therefore, the isolated perfused bovine udder is a useful in vitro model with predictive value for studies of dermal penetration and absorption of drug formulations. top Abstract 4 In-vitro assay for the local compatibility in skin and mucous membranes: Testing of market products, ingredients, household- and process chemicals Pittermann W., Förster T., B. Blume and M. Kietzmann Henkel KGaA, D40191 Duesseldorf There are complex interactions which may occur during the movement of molecules from the natural barrier of the outer surface of the skin into the systemic circulation [1]. The barrier properties and metabolic reactions remain comparable to living skin in this natural in vitro skin model [2]. Informations concerning irritation capability can be obtained by whole skin biopsies [3, 4, 5]. The BUS-model irritation assay allows to differentiate between the direct cytotoxicity (MTT-assay) and the reversible irritancy e.g. preinflammatory mediator concentration of PGE2 The cellular positions for both assays are located in the cell membrane (irritancy) and in the intracellulary located mitochondria (cytotoxicity). During the last years the acute skin and mucous membrane compatibility of market products, ingredients, household- and process chemicals were tested in various study designs. Figure 1 shows the number and main exposure periods of the historical data out of this test system. The oral presentation covers the principles and results of the tests using market products, ingredients, household- and process chemicals. Figure 1
*Main exposure periods (biopsies were also taken at other periods too) [[1] D. Howes et al.; Methods for Assessing Percutaneous Absorption - The Report and Recommendations of ECVAM Workshop XIII; ATLA 24 81-106 (1996) [2] M. Kietzmann et al.; Perfused Bovine Udder as an in Vitro Model of Percutaneous Drug Absorption. Skin Viability and Percutaneous Absorption of Dexamethasone, Benzoyl Peroxide and Etofenamate; J. Pharm.Toxicol. Meth. 30 75-84 (1993) [3] W. Pittermann et al.; The Isolated Perfused Bovine Udder Skin Model: A New in-Vitro Model for the Assessment of Skin Penetration and Irritation; In Vitro Toxicology 10 17-21 (1997) [4] W. Bäumer and M. Kietzmann; Effects of steroidal and nonsteroidal drugs on eicosanoid synthesis in the skin of the isolated perfused bovine udder, in Proceedings of a Workshop on Isolated Perfused Organs-Hamburg 1998 (eds.: W. Pittermann / M. Kietzmann / Ch. Grosse-Siestrup) publ. 1/2000, Lab. Animal Ldt. (London), ISBN 0-901334-12-X [5] H. Tesmann, J. Kahre und W. Pittermann; Alkylpolyglycoside: Prüfstrategie zur Wirkungsweise an der Haut in: Nutzen und Risiko von Kosmetika; O. Braun-Falco, M. Gloor und H.C. Korting, eds.; Springer Verlag Berlin Heidelberg (2000), Seite 137-145 for review: http://www.gd-online.de/english/originals_e/Pittermann2000.htm |
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| August 6, 2000 | Copyright
© 2000 (UNI - Klinikum |
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