Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lack of a first-pass effect for locally-applied substances is often not considered. This is especially true for such central nervous system agents as salicylic acid, hexachlorophene or caffeine which have a relatively low toxicity when applied orally. Manifestation of dermal irritation, such as a beginning rash or inflammation, are often tolerated because the beneficial effects of some topically applied substances outweight the damage (Dithranol, 5-Fluorouracil). This applies to some anti-phlogistics as well, which may also cause skin irritation. Some substances, such as benzoyl peroxide, vitamin-A acid and beta-estradiol have direct or indirect desiccative effects so that skin irritations may occur. Other substances, such as tar, for example, are applied locally although they may have a carcinogenic potential when misused, or when contraindications for its use are disregarded. Local risks can be recognized in clinical-experimental and clinical testing of dermatological products. One must, however, look carefully for an intensification of possible risks related to the method of application, the condition of the skin, the site of application, supporting therapeutic measures or changes in the composition of the vehicle. Lanolin, cetyl alcohol and myristyl alcohol, sorbitol, isopropyl-myristate as well as polyethylene glycols (PEG) penetrate the skin like active substances. Some have been connected with skin allergies. In addition, some preservatives have mutagenic properties. Many vehicles cause dehydration of the horny layer and thus result in chronic surface damage. This is true for hygroscopic substances such as PEG as well as for liquid paraffins, lipid solvents (alcohol, acetone), solvents such as propylene glycol and for some O/W emulsifiers.
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PMID:Adverse reactions of externally applied drugs and inert substances. 297 21

The effects of the application of skin irritants on the in vitro percutaneous absorption of three model compounds of diverse physico-chemical properties, caffeine, indomethacin, and hydrocortisone, were investigated. Norephedrine and imipramine, basic drugs with a known skin irritation potential, were employed to damage the skin. Treatment with norephedrine increased the permeation of caffeine and hydrocortisone by two- to fourfold, while absorption of indomethacin declined an order of magnitude. A similar result was obtained for the effect of treatment with imipramine on transport of caffeine. Pretreatment with imipramine promoted hydrocortisone absorption 10-fold but, unlike norephedrine, did not alter indomethacin permeation. While both treatments in vivo caused an increase (norephedrine > imipramine) in the pH on the surface of skin and after tape-stripping the skin, only norephedrine caused changes in transepidermal water loss in vivo in man. Since imipramine was the more severe irritant as judged by erythema, alterations by irritants of barrier function appeared rather complex.
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PMID:Influence of skin irritants on percutaneous absorption. 830 62

For screening of a potential irritant it is essential that an early marker for irritation should be chosen which could be detected before the physiological signs of irritation occur. Interleukin 1 alpha (IL-1alpha) is widely accepted as such a marker in both in vivo and in vitro test systems. In this study, we have determined the mRNA levels of IL-1alpha in the epidermis after topical application of sodium dodecyl sulphate (SLS) in both a commercially available epidermal kit (EpiDerm) and in excised skin. Furthermore, we have determined the effect of water, the vehicle for SLS, on IL-1alpha mRNA levels. Topical application of water to excised skin increases IL-1alpha mRNA levels sixfold in the epidermis whereas topical application of water to EpiDerm cultures did not alter IL-1alpha mRNA levels. This is explained by the finding that EpiDerm cultures have a sub-optimal barrier function when compared with excised skin - topical application of SLS was clearly toxic at much lower concentrations in EpiDerm cultures (0.2% SLS) than in excised skin (5% SLS). Also caffeine penetration was 10-fold higher through EpiDerm cultures than through the excised skin. Therefore, incubation of control EpiDerm cultures at 100% humidity effectively mimics topical exposure to water. An additional increase in IL-1alpha mRNA levels observed between topical application of water and SLS is similar (about threefold) in both experimental systems. In conclusion, in vitro reconstructed epidermis models, such as EpiDerm, can be used as a predictive model for irritancy screening. However, great care should be taken when interpreting the results due to the fact that EpiDerm cultures do not have a competent barrier function and therefore lower irritant concentrations are required than in in vivo or ex vivo studies in order to induce cytotoxic effects. Furthermore, the irritant effects of the vehicle should not be neglected. Our results show clearly that the topical application of water to excised skin results in increased levels of IL-1alpha mRNA in the epidermis. This is a cytokine that is widely used as an early marker for skin irritation.
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PMID:Effect of skin barrier competence on SLS and water-induced IL-1alpha expression. 1210 60

The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present study demonstrates that a limited damage to the skin significantly increases the permeability coefficient (K (p)) as well as total percutaneous penetration of chemicals, and most significantly for those compounds that due to their physicochemical characteristics (the most hydrophilic as well as the most lipophilic) have low penetration rates through intact skin. The present experiment not only confirms the proportionality between lipophilicity and potential for percutaneous penetration, but also illustrates that at a certain degree of lipophilicity of a model compound, the different skin compartments become more attractive for temporary deposition of model compounds. Moreover, a clear change from epidermal deposition towards a dominating dermis deposition of chemicals temporarily deposited within the skin is seen following damage to the skin barrier. Thus, the distribution of chemicals within the skin compartments is affected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This observation may have implications when evaluating the possibility of removing chemicals from the skin through different cleansing procedures following unintended dermal exposures.
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PMID:Defense against dermal exposures is only skin deep: significantly increased penetration through slightly damaged skin. 1788 42

This study focuses on the properties of topical vehicles based on alkylpolyglucoside natural surfactant-mixed emulsifier, cetearyl glucoside and cetearyl alcohol, in order to propose their use as "ready to use" pharmaceutical bases for a number of model drugs. We were interested to investigate how the alternative use of three lipophilic excipients (Ph. Eur. 6.0), differing in their polarity indexes (medium chain triglycerides (MG), decyl oleate (DO), and isopropyl myristate (IPM), respectively), affects the colloidal structure of the alkylpolyglucoside-based vehicles and in vitro permeation profiles of two model drugs: diclofenac sodium (DC) and caffeine (CF), both sparingly soluble in water. Finally, we aimed to evaluate the safety profile of such vehicles in vitro (acute skin irritation test using a cytotoxicity assay), comparing it with in vivo data obtained by the methods of skin bioengineering. The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. Varying of lipophilic excipient influenced noteworthy variations in the colloidal structure demonstrated as different rheological profiles accompanied to the certain degree by different water distribution modes, but notably provoked by drug nature (an amphiphilic electrolyte drug vs. nonelectrolyte). In vitro permeation data obtained using ASC membranes in an infinite dose-type of experiment stressed the importance of the vehicle/solute interactions in case of small variation in formulation composition, asserting the drug properties in the first hours of permeation and rheological profile of the vehicles in the later phase of experiment as decisive factors. In vitro skin irritation test demonstrated a mild nature of the emulsifying wax and the absence of negative effects of used oil phases on cell viability in formulation concentrations correspondent to the therapeutic need. This result alongside with data obtained from in vivo study, could additionally promote investigated topical vehicles as prospective "ready to use" pharmaceutical bases.
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PMID:Natural surfactant-based topical vehicles for two model drugs: Influence of different lipophilic excipients on in vitro/in vivo skin performance. 1961 85