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Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The availability of an in vitro test system to replace animal testing of potential irritants is becoming more and more urgent especially in Europe as a consequence of the European Community Cosmetics Directive. To evaluate the ability of Advanced Tissue Sciences' (ATS) ZK1301 skin model to predict the skin irritation potential of surfactants, we performed a pilot validation study utilizing four different laboratories. The in vitro protocol was designed as a quantitative pre-screen for the clinical patch studies. Sixteen substances, representing various surfactant categories and ranges of irritation potential, were tested. The 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to quantitate viability in vitro. We documented the viability of tissues exposed to unknown substances for specific periods. The in vitro results were calculated as percent distilled water controls (DWC). The time required to reduce the viability of each tissue to 50% of the distilled water controls (T50) was compared to mean erythema and edema scores from the clinical studies by Pearson's correlation. The individual laboratories demonstrated coefficients of 0.72. The results indicated that the 30 min percent untreated control values best predicted the 24 h clinical patch scores. No statistically significant interlab variability was found. Only one false negative was seen when non/mild and moderate/severe irritant categories were assigned according to the in vitro scores. These results demonstrate that the skin2 in vitro test system may serve as a good screening method prior to clinical patch studies.
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PMID:Skin2--an in vitro human skin model: the correlation between in vivo and in vitro testing of surfactants. 951 18

We have studied the effect of various detergents on keratinocyte gene expression in vitro, using an anionic detergent (sodium dodecyl sulfate), a cationic detergent cetyltrimethylammoniumbromide (CTAB), and two nonionic detergents, Nonidet P-40 and Tween-20. We measured the effect of these detergents on direct cellular toxicity (lactate dehydrogenase release), on the expression of markers for normal differentiation (cytokeratin 1 and involucrin expression), and on disturbed keratinocyte differentiation (SKALP) by northern blot analysis. As reported in other studies, large differences were noted in direct cellular toxicity. In a culture model that mimics normal epidermal differentiation we found that low concentrations of sodium dodecyl sulfate could induce the expression of SKALP, a proteinase inhibitor that is not normally expressed in human epidermis but is found in hyperproliferative skin. Sodium dodecyl sulfate caused upregulation of involucrin and downregulation of cytokeratin 1 expression, which is associated with the hyperproliferative/inflammatory epidermal phenotype found in psoriasis, wound healing, and skin irritation. These changes were not induced after treatment of cultures with CTAB, Triton X-100, and Nonidet-P40. This effect appeared to be specific for the class of anionic detergents because sodium dodecyl benzene sulfonate and sodium laurate also induced SKALP expression. These in vitro findings showed only a partial correlation with the potential of different detergents to induce clinical, biophysical, and cell biologic changes in vivo in human skin. Both sodium dodecyl sulfate and CTAB were found to cause induction and upregulation of SKALP and involucrin at low doses following a 24 h patch test, whereas high concentrations of Triton X-100 did not. Sodium dodecyl sulfate induced higher rates of transepidermal water loss, whereas CTAB treated skin showed more signs of cellular toxicity. We conclude that the action of anionic detergents on epidermal keratinocytes is qualitatively different from the other detergents tested, which might have implications for in vitro toxicology studies that use cell biologic parameters as a read-out. We would hypothesize that detergents cause skin injury by several mechanisms that include direct cellular toxicity, disruption of barrier function, and detergent specific effects on cellular differentiation, as demonstrated here for sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, and sodium laurate.
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PMID:Differential effects of detergents on keratinocyte gene expression. 954 Sep 75

No data are available on the irritant effect of nitroxide free radicals in human skin. Nitroxides are important biomedical skin probes used in Electron Paramagnetic Resonance spectroscopy and imaging. Our purpose was to study the skin irritation potential of different nitroxide free radical structures in skin of healthy human subjects. We investigated the following nitroxides: Tempo (2,2,6,6-tetramethyl-1-piperidinoxy), Doxo (2,2,5,5-tetramethyl-3-oxazolidinoxy), Proxo (2,2,5,5-tetramethyl- -dihydro-pyrrolinoxy), and Imidazo (2,2,3,4,5,5-hexamethyl-imidazoline-1-yloxyl). Cutaneous irritation was determined in human skin following a single application and after repetitive applications in comparison to the standardized irritant sodium lauryl sulfate (SLS). The response was evaluated clinically as well as by a bioengineering method analyzing transepidermal water loss (TEWL) and skin hydration (capacitance). The nitroxides were classified clinically from nonirritant (Imidazo, Proxo), to slightly irritant (Doxo, 100 mM), or moderately irritant (Tempo 100 mM) after a single application. The TEWL values were significantly increased by Doxo and Tempo, but capacitance values were not changed significantly. In the cumulative irritation test Tempo was scored as a slight irritant (10 mM). TOLH (2,2,6,6-tetramethyl-1-hydroxypiperidin), the hydroxylamine of Tempo, which is the major skin metabolite, did not cause skin irritation after a single or repetitive applications. This may indicate that a loss of cellular reducing equivalents may be involved in the inflammation process caused by Tempo. The order of nitroxide irritation potency (Tempo > Doxo >> Imidazo = Proxo) is inverse to the order of nitroxide biostability in human skin (Imidazo = Proxo >> Doxo > Tempo). In conclusion, nitroxide free radicals are classified as nonirritant to moderately irritant in human skin. Particularly, the pyrrolidine and imidazoline type nitroxides have a low potential to cause acute or subacute skin toxicity.
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PMID:Cutaneous tolerance to nitroxide free radicals in human skin. 955 76

The attempts to use nitroxide free radicals and nitrone spin traps topically in skin requires analysis of their potential cutaneous adverse effects. The objective of this study was to investigate the skin irritation and sensitizing potential of nitroxides and nitrones in the guinea pig. The following unsubstituted nitroxides were investigated: 2,2,6,6-tetramethyl-1-piperidinoxyl (Tempo), 2,2, 5,5-tetramethyl-3-oxazolidinoxyl (Doxo), 2,2,5,5-tetramethyl-1-dihydro-pyrrolinoxyl (Proxo), 2,2,3,4,5,5-hexamethyl-imidazoline-1-yloxyl (Imidazo) and the nitrones: 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and N-tert.-butyl-phenylnitrone (PBN). Cutaneous irritation was determined following the modified Draize protocol. The response was evaluated clinically as well as by a biophysical method analyzing transepidermal water loss (TEWL). The nitroxides and nitrones were classified clinically from non-irritant (Proxo, Imidazo, DMPO) to slightly irritant (Tempo, Doxo, PBN) according to the Draize protocol. In agreement with the clinical scoring, the TEWL values were significantly increased by Tempo, Doxo and PBN. TOLH, the hydroxylamine of Tempo and its major skin metabolite, did not cause skin irritation. The sensitizing effect was evaluated according to the Magnusson and Kligman test. The results showed no cutaneous hypersensitivity to all nitroxides and nitrones, indicating a weak sensitizing potential. That concludes that the nitroxides and nitrones tested in this study have a low potential of acute skin intolerance.
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PMID:Cutaneous tolerance to nitroxide free radicals and nitrone spin traps in the guinea pig. 958 90

Predictive testing of chemicals to assess their acute skin irritation potential is an important part of the assessment of their toxicological profile. It is possible, where safety and ethical considerations can be met, to do this work in groups of human volunteers. Previously, the relative responsiveness of atopics and non-atopics has been evaluated. The results showed that atopics (defined broadly by high IgE reactivity) were a little more susceptible to skin irritation, but not significantly so. In the present work, the relative reactivity of a skin atopic group versus a non-atopic group was examined in more detail. Sodium lauryl sulfate (SLS) was applied at a range of concentrations and exposure times, such that a fairly constant degree of skin irritation was produced. At various time points, the irritation response was measured by visual assessment, chromametry, laser Doppler flowmetry and transepidermal water loss. Using all of the methods of assessment, the reactions in atopics were similar to or a little less than those seen in non-atopics. The conclusion is that atopics and non-atopics will give similar results in a predictive human test for acute skin irritation. Furthermore, the pattern of response obtained from short duration exposure should be predictive of that following longer durations of (single) exposure.
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PMID:Acute irritant reactivity to sodium lauryl sulfate in atopics and non-atopics. 966 41

Laboratory tests to assess the irritant potential of materials, such as skin cleansers, which are normally used over a long period by humans, fail to mimic actual use. Most washing tests last a few days or at most a few weeks. Skin sites and techniques are often not standardized. The more standardized patch test involves occlusion and results in exaggerated reactions, since even water and blank patches produce visible and pathophysiologic changes. All of these tests rely on visual assessment despite strong evidence that similarly appearing skin can be very different histologically. The primary objective of this study was to use a well-defined animal model to evaluate the cumulative effects of repeated skin exposure to low levels of surfactants of varying skin irritation potential. A secondary aim was to examine whether or not surfactant-induced skin changes were exacerbated by suberythemal UV radiation. Test materials were applied topically, 2x daily to the dorsal areas of normal and low-dose solar simulator exposed mice for 15 weeks. Our results show that, with conditions mimicking typical normal use, these surfactants and skin cleansers produce little or very mild histological changes in the skin. UV irradiation alone produced the greatest change in all histological parameters examined, with no synergistic or additive effects with the topical treatments.
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PMID:The effects of prolonged use of surfactants on the skin of normal and photo-exposed hairless mice. 984 Feb 59

It is well known that cutaneous irritants influence epidermal proliferation but the pathogenesis is poorly understood. Recent investigations have shown that the skin barrier integrity influences the proliferation of the basal keratinocytes. Our question was whether the proliferating activity of keratinocytes is indeed regulated by the degree of skin barrier damage or by a direct toxic action of the irritant on the keratinocytes. Therefore various degrees of skin irritation were induced by the application of 0.1%, 0.5% and 2% sodium lauryl sulphate (SLS) solution to the forearm skin of six healthy volunteers. This experiment was performed to evaluate the relationship between SLS concentration and epidermal proliferation. In a second experiment another 14 volunteers were treated with a single SLS concentration (0.5%) to look for interindividual differences in the patterns of skin reaction and susceptibility to the irritant. Skin barrier function was evaluated by measurements of transepidermal water loss (TEWL) before and after irritation. Punch biopsies were taken after 96 h from exposed areas and from unexposed normal skin. Dividing keratinocytes were identified immunocytochemically using three different monoclonal antibodies: PCNA, MIB 1 and KiS1. Exposure to SLS resulted in concentration-dependent increases in both TEWL and epidermal proliferation. However, no significant correlation could be found between the degree of hyperproliferation and the TEWL changes. The results suggest that epidermal proliferation is modulated by a direct interaction of the surfactant with the keratinocytes and/or by release of mediators rather than the consequence of a barrier disturbance.
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PMID:SLS-irritated human skin shows no correlation between degree of proliferation and TEWL increase. 986 Feb 82

A clinical study was performed to determine the effects of patch testing human skin with four industrially used surfactants on erythema formation, transepidermal water loss, and the contents in suction blister fluids of primary proinflammatory mediators including arachidonic acid, eicosanoids, and IL-1 alpha, which were analyzed by quantitative gas chromatography/negative ion chemical ionization mass spectrometry and by an enzyme-immunoassay, respectively. Benzalkonium chloride (BKCI) and sodium lauryl sulfate (SLS) elicited erythema and caused increased transepidermal water loss, indicating a disturbance of the epidermal barrier. Triethanolamine (TEA) and Tween 80 did not evoke these gross symptoms of inflammation. Suction blister fluids collected after a 24-h application of BKCl, SLS, and Tween 80 contained significantly increased amounts of individual eicosanoids whereas TEA induced no response. The induced eicosanoid profile was characteristic for each compound, pointing to different cell types of skin to be involved in their production. The elevation of prostaglandin and LTB4 contents correlated with the induction of erythema and the impairment of the epidermal barrier as shown for BKCl and SLS and preceded the maximum of erythema formation. IL-1 alpha contents did not correlate with these gross symptoms of inflammation. The results of this in vivo study support those of a previous study using human keratinocytes in culture indicating the release of arachidonic acid and prostaglandins to be an early event involved in the interaction of keratinocytes with surfactants. Moreover, the in vivo data with human skin underscore the mechanistic relationship to the in vitro model and support the concept that arachidonic acid and eicosanoid release from keratinocytes can be used as a marker of primary skin irritation.
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PMID:Arachidonic acid metabolism in primary irritant dermatitis produced by patch testing of human skin with surfactants. 987

Topical application of a skin permeation enhancer such as oleic acid (OA) can result in: (i) higher skin permeability for many exogenous substances (ii) an irritation reaction. Laser Doppler velocimetry (LDV) is one of few techniques which can assess both effects using appropriate protocols. Direct LDV measurement, measuring cutaneous blood flow, has been preferred as a tool to evaluate skin irritation. By comparing the LDV value of an irritant-treated site with an untreated site, an irritation index for the irritant can be obtained. Occlusive application of 0.16 M OA in propylene glycol (PG) for either 3 or 24 h produced irritation in form of redness and slight swelling. Using LDV, we obtained an irritation index of 2 and 4, respectively. The vehicle, PG alone, produced an index of around 1, which corresponded well to the slight to almost no irritation observed visually. The duration of the high irritation index assessed by LDV after OA-PG application is comparable to the duration of the increase in transepidermal water loss following the same application. This indicates a correlation between skin irritation and barrier perturbation caused by OA. LDV can also be used to elucidate the effect of enhancers on skin using hexyl nicotinate (HN) as a model drug, since its vasodilative effect can be clearly assessed by LDV. Pre-treatment of PG for 3 h significantly reduced the t0 and tmax of HN. No further reduction could be observed when OA was added into PG, suggesting that OA-PG is not more effective than PG alone in enhancing the permeation of HN.
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PMID:In vivo human skin permeability enhancement by oleic acid: a laser Doppler velocimetry study. 1002 93

We have used microdialysis in the dermis for assessing penetration kinetics of salicylic acid (SA) in healthy volunteers (n = 18), following application on the volar aspect of the left forearm. Penetration was monitored at four locations: in normal (unmodified) skin and in skin with perturbed barrier function from (i) repeated tape stripping (ii) irritant dermatitis from 1 or 2% sodium lauryl sulphate (SLS) for 24 h and (iii) delipidization by acetone. The order of the treatments was randomized according to a latin square design. Epidermal barrier function and skin irritation were assessed in each location using evaporimetry and colorimetry. Transepidermal water loss (TEWL) values confirmed that both mild (acetone), moderate (1% SLS) and severe barrier damage (tape stripping and 2% SLS) had occurred. Microdialysis sampling with two parallel probes in the dermis was performed in each of the four treatment areas for every subject. SA (5% in ethanol) was applied in a chamber glued to the skin overlying the microdialysis probes and sampling was continued for 4 h. SA was detectable in all samples and measurable in all samples from penetration through perturbed skin. Comparing the SA penetration in barrier-perturbed skin with the penetration in unmodified skin in the same subject, the mean SA penetration increase was 2.2-fold in acetone-treated skin (P = 0.012), 46-fold in mild dermatitis and 146- and 157-fold in severe dermatitis and tape stripped skin, respectively (P < 0.001). The penetration of SA significantly correlated with the measurements of barrier perturbation by TEWL (P = 0.01) and erythema (P = 0.02) for each individual. Microdialysis sampling of SA penetration was more sensitive than non-invasive measuring techniques in detecting significant barrier perturbation in acetone-treated skin. A positive dose-response relationship for the percutaneous penetration of SA in response to increasing SLS pretreatment concentrations and thus the degree of irritant dermatitis was found. When analysing data by location on the forearm, a tendency towards an intraregional variation in the reactivity to barrier damage was found, with the most proximal location displaying higher reactivity scores than the most distal location in response to the same barrier perturbation procedures. The penetration of SA was not significantly different between locations. In conclusion, using microdialysis in the dermis to obtain real-time dermal pharmacokinetics in the target organ, this study demonstrates highly increased and differentiated cutaneous penetration of SA in barrier-perturbed skin. The measured drug penetration was demonstrated to correlate with non-invasive quantification of barrier damage.
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PMID:Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function. 1023 34


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