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In Vitro Assessment of Dermal Absorption
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
Skin absorption is a complex phenomenon. It can be viewed as the translocation of surface-applied substances through the various layers of the epidermis and dermis to a location where they can enter the systemic circulation via the dermal microvasculature and lymphatics, or remain in the deeper layers of the skin. This transport of substances through the skin involves complex diffusional and metabolic processes and is influenced by the interactions of a variety of physiochemical, biophysical, and biochemical factors. Dermal absorption is the net result of the penetration outward margin, cutaneous metabolism, binding and permeation of a topically applied chemical into and through the different strata of the skin (Figure 1). The fundamental concepts in percutaneous absorption have been extensively reviewed in the literature, and noteworthy reviews found in the recent literature include the in-depth treatises of Schaefer et al.1 and Barry.2
Chemical injuries
Published in Jan de Boer, Marcel Dubouloz, Handbook of Disaster Medicine, 2020
Systemic toxicants produce a variety of systemic effects and can be divided into three groups according to their primary effects: chemical asphyxiants, volatile hydrocarbons and miscellaneous systemic poisons, including organophosphorus compounds (insecticides and nerve gases) and metal fumes13,23,25. Systemic effects may be due to skin absorption of chemicals, respiratory exposure and vapours produced on the skin or clothing. The systemic toxins may penetrate wounds and burns more easily than intact skin. Some systemic toxicants (hydrogen sulphide) can cause upper airway or alveolar injury27. It is important to identify as soon as possible the specific compound involved, since some of these toxins have specific antidotes.
In Vitro Methods: Alternatives to Animal Testing
Published in Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters, Cosmetic Formulation, 2019
Dayane Pifer Luco, Vânia Rodrigues Leite-Silva, Heather A.E. Benson, Patricia Santos Lopes
Skin absorption describes the passage of material from topical application on the stratum corneum surface into the skin, whilst skin penetration involves passage through the skin to the systemic circulation (Russell and Guy, 2009). The procedures and parameters for the in vitro testing of percutaneous absorption/penetration are well documented and described in the COLIPA Guidelines for Percutaneous Absorption/Penetration, and OECD TG 428. These guidelines describe a general process for measuring the absorption/penetration of test substances through excised fresh or previously frozen mammalian skin (human, pig and rat).
Modeling percutaneous absorption for successful drug discovery and development
Published in Expert Opinion on Drug Discovery, 2020
Hanumanth Srikanth Cheruvu, Xin Liu, Jeffrey E. Grice, Michael S. Roberts
This review has examined the potential of skin as a route of delivery based on current market demands. The key determinants for the success of any new dermal product or drug are the effectiveness of the skin barrier and its physicochemical properties. We first reviewed the target site of drugs delivered through skin, physiology of normal and damaged skin and the skin transport processes with parameters describing percutaneous absorption. We then went on to discuss the modeling strategies for prediction of percutaneous absorption with strengths and limitations of these models. Ideal solute properties to cross skin barriers, various methods of enhancement required for specific chemicals and safety-related properties were discussed as well. A basic understanding of all these principles is essential to the development of physiological models that describe and predict the processes of skin absorption of drugs from topical and transdermal products.
Utility of hairless rats as a model for predicting transdermal pharmacokinetics in humans
Published in Xenobiotica, 2020
Syunsuke Yamamoto, Noriyasu Sano, Chiharu Fukushi, Yuta Arai, Masatoshi Karashima, Hideki Hirabayashi, Nobuyuki Amano
Physiological factors and drug metabolism in the skin can affect in vivo skin absorption. Therefore, animal models should be carefully selected for the evaluation of transdermal drug absorption in human (Bartek et al., 1972). While Göttingen minipigs have been used worldwide as an animal model for investigating transdermal drug administration, the use of in vivo skin absorption profiles of Göttingen minipigs leads to an approximately three-fold underestimation of skin absorption in humans (Yamamoto et al., 2017b). Discrepancies between the in vitro and in vivo skin permeabilities of Göttingen minipigs are dependent on the thickness of the dermis. Compared to humans, Göttingen minipigs have a two-fold thicker dermis and a lower density of cutaneous vasculature, but a comparable epidermal thickness (Qvist et al., 2000). However, in vitro studies often employ dermis-split skin. It is possible that the difference between in vivo (from the skin surface to capillary vessels) and in vitro (from the skin surface to the site of adsorption) skin thicknesses accounts for the three-fold difference in the skin absorption of tested drugs. Thus, an animal model with a stratum corneum, epidermis and dermis of comparable thickness to that of humans might be more appropriate for mimicking the absorption profile of human skin.
Decontamination efficacy of soapy water and water washing following exposure of toxic chemicals on human skin
Published in Cutaneous and Ocular Toxicology, 2020
Emma Forsberg, Linda Öberg, Elisabet Artursson, Elisabeth Wigenstam, Anders Bucht, Lina Thors
The need for skin decontamination to mitigate systemic effects is related to the ability for dermal penetration of the chemical. For assessment of skin decontamination procedures in terms of life-saving measures, it is also mandatory to consider toxicity of the compound. Examples of hazardous compounds with well-known skin penetration properties are organophosphorus pesticides, chemical warfare nerve agents and certain toxic industrial chemicals. Dermal penetration is dependent on many different factors such as physicochemical properties of the chemical, substance concentration, involvement of a vehicle or carrier, possible occlusion, exposure pattern, environment factors and skin condition1,2. The epidermal membrane on top of human skin, including the corneal outer layer stratum corneum, serves as a protective barrier against foreign materials3. Skin absorption through the epidermal barrier occurs via diffusion and the stratum corneum protects the lower layers of the skin by limiting the dermal absorption rate4. Due to the hydrophobic nature of the stratum corneum, lipophilic molecules generally penetrate skin more readily than hydrophilic compounds5. Another major determinant for chemical penetration is the size of the molecule; the molecular weight should be below 500 Dalton to allow for skin absorption6. Volatility of chemicals is an additional parameter influencing dermal absorption and subsequently the need for decontamination7–9. As opposed to volatile compounds, non-volatile chemicals will remain on the surface for longer periods of time and consequently are more likely to penetrate the skin.