Safety Assays in Skin Pharmacology
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I.P.1 I.P.2 I.P.3 I.P.4 I.P.4.1 I.P.4.2 I.P.4.3 I.P.5 I.P.6 I.P.6.1 I.P.6.1.1 I.P.6.1.2 I.P.7 I.P.7.1 I.P.7.2 I.P.7.3
In Vivo Percutaneous Absorption Assays . . . . . . . . . . . . . In Vitro Percutaneous Absorption Assays . . . . . . . . . . . . . Guinea Pig Sensitization Tests . . Sensitization Tests In Mice . . . . . Local Lymph Node Assay (LLNA) . . . . . . . . . . . . . . . . . . . . . . . . . Mouse Ear Swelling Test (MEST). . . . . . . . . . . . . . . . . . . . . . . . . The Vitamin A Enhancement Test (VAET) . . . . . . . . . . . . . . . . . . . . . . . . . Human Sensitization Assays . . . . In Vitro Assays for Allergic Contact Dermatitis . . . . . . . . . . . . . Irritation Tests in Animals . . . . . . . Draize-Type Tests . . . . . . . . . . . . . . . Non-Draize Animal Studies . . . . . . Human Irritation Tests . . . . . . . . . Single-Application Irritation Patch Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . Repeat Application Irritation Patch Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . Exaggerated Exposure Irritation Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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chemical, and the metabolic capabilities of the species should be considered when selecting an animal model and designing the experiment.
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PROCEDURE
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I.P.1 In Vivo Percutaneous Absorption Assays PURPOSE AND RATIONALE
In vivo studies have been conducted in man and in several species to compare absorption fates of numerous compounds. Percutaneous absorption rates in the rat and rabbit were generally higher than in human while the skin permeability of monkeys and swine more closely resembles humans. Although these differences are not predicted by any single factor, such as epidermal thickness, they are not unexpected in light of differences in skin characteristics. There are interspecies differences in routes of excretion of some chemicals as well. This may be due in part to metabolism of the
Percutaneous absorption can be determined by applying a known amount of chemical to a specified surface area and then measuring the level of the chemical in the urine and/or feces. To correct for incomplete excretion of the material in urine/feces levels are measured following parenteral administration of the chemical. Radioactive-labeled chemicals, usually carbon 14 or tritium, are widely used for analytic convenience. Ingestion of the test material by the animal must be prevented, and this may require restraint of the animal or design of specialized protective apparatus for the site of application. Because urine and feces are collected for analysis, specialized cages are also required. EVALUATION
Although studies with radiolabeled compounds accurately reflect absorption, they may not provide accurate estimates of bioavailability. For example, comparison of bioavailability from nitroglycerin (unmetabolized drug) and level of radioactive tracer indicates that use of the tracer overestimates available drug by as much as 20 %. This corresponds t
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