Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main goal of the present study was to investigate the response of the human skin equivalent Apligraf in vitro to the application of irritant substances and its predictivity as a screening tool for cumulative skin irritant potential in humans. Vaseline, calcipotriol, trans-retinoic acid, and sodium lauryl sulfate were applied to Apligraf in vitro for 24 h. Cell viability (lactate dehydrogenase leakage), release and mRNA expression of the proinflammatory cytokines IL-1alpha and IL-8, and morphological changes were assessed. The same products were applied to 30 healthy volunteers in a double-blind, randomized, vehicle-controlled within-subject study. The skin reactions after repeated 24-h applications over 3 weeks under Finn chamber patches were monitored by visual scoring and biophysical methods (trans-epidermal water loss, chromametry, and blood flow). Sodium lauryl sulfate was cytotoxic to Apligraf, and increased the release and expression of cytokines at low (0.2%, 0. 4%), but not at high (0.8%, 1%) concentrations. It induced severe irritancy in vivo. Trans-retinoic acid increased the expression and release of cytokines with no detectable cytotoxicity and showed moderate irritancy in humans. Although calcipotriol did neither affect cell viability nor the production of cytokines, it induced morphological signs of irritation and was mildly irritant for healthy volunteers. Vaseline was innocuous in vivo and induced no changes in Apligraf. In conclusion, the cumulative skin irritation potential of the tested products could be predicted with Apligraf in a sensitive and specific manner, by monitoring cytotoxicity, proinflammatory cytokines, and morphological changes.
 ...
PMID:Use of human skin equivalent Apligraf for in vitro assessment of cumulative skin irritation potential of topical products. 1073 42

A structure-activity relationship (SAR) model has been developed to discriminate skin irritant from nonirritant esters. The model is based on the physicochemical properties of 42 esters that were tested in humans for skin irritation. Nineteen physicochemical parameters that represent transport, electronic, and steric properties were calculated for each chemical. Best subsets regression analysis indicated candidate models for further analysis. Regression analyses identified significant models (p < 0.05) that had variables that were also significant (p < 0.05). These candidate models were evaluated using linear discriminant analysis to determine if the irritant esters could be discriminated from nonirritant esters. The stability of the model was evident from the consistency of parameters among ten submodels generated using multiple random sampling of the database. The sensitivity of the ten models, evaluated by "leave-one-out" cross-validation, ranged from 0. 846 to 0.923, with a mean of 0.885 +/- 0.025 (95% CI). The specificity ranged from 0.615 to 0.923, with a mean of 0.738 +/- 0.06 (CI). Compared with nonirritant esters, irritant esters had lower density, lower water solubility, lower sum of partial positive charges, higher Hansen hydrogen bonding parameter, and higher Hansen dispersion parameter. The results indicate that physicochemical features of esters contribute to their ability to cause skin irritation in humans, and that chemical partitioning into the epidermis and intermolecular reactions are likely important components of the response. This model is applicable for prediction of human irritation of esters yet untested.
 ...
PMID:A robust structure-activity relationship (SAR) model for esters that cause skin irritation in humans. 1078 76

Surfactants are known to be skin irritants, but change in their irritant potential due to change in composition during handling and storage has not previously been investigated. The aim of this study was to investigate the influence of oxidation products on the irritant potential of a non-ionic ethoxylated alcohol, C12E5. Pure and oxidized C12E5 were tested, using 2 different patch test procedures; 1 with a single 24 h exposure and 1 with repeated exposures. 18 healthy volunteers participated in each of these studies. Evaluations were made by visual scoring and by measurement of transepidermal water loss and skin blood flow. In the single exposure study, no significant difference in skin irritation was observed between pure C12E5 and a sample of oxidized C12E5 at the concentrations tested (1, 3, 9 and 27%). After repeated exposures, however, the oxidized C12E5 was significantly more irritant than pure C12E5 at the concentrations 9% and 27% (p<0.05). Non-ionic ethoxylated surfactants are known for their weak skin irritant effect and are, due to this, often included in products with prolonged contact with the skin, i.e., skin care products. An increased irritant potential after oxidation might be of importance due to the conditions of use.
 ...
PMID:Skin irritation from air-oxidized ethoxylated surfactants. 1094 46

Aqueous solutions of > or =5% glutaraldehyde (GA) are of moderate acute peroral toxicity and those of < or =2% are of slight toxicity. By single sustained skin contact, aqueous GA solutions of > or =45% are of moderate acute percutaneous toxicity, those of 25% are of slight toxicity and those of </=15% do not present an acute percutaneous hazard. Vapor generated at ambient temperature may cause sensory irritant effects to the eye and respiratory tract, but not acute respiratory tract injury. The 50% decrease in respiratory rate (rd(50)) is 13.86 ppm. A 0.1% solution of GA is not irritating to the eye; the threshold for conjunctival irritation is 0.2% and for corneal injury it is 1.0%. Eye injury is moderate at 2% and severe at > or =5%. Primary skin irritation depends on the duration and contact site, occlusion and solvent. By sustained contact, the threshold for skin irritation is 1%, above which erythema and edema are dose related. With 45% and higher, skin corrosion may occur. There is a low incidence of skin sensitizing reactions, with an eliciting threshold of 0.5% aqueous GA. However, GA is neither phototoxic nor photosensitizing. Subchronic repeated exposure studies by the peroral route show only renal physiological compensatory effects, secondary to reduced water consumption. Repeated skin contact shows only minor skin irritant effects without systemic toxicity. By subchronic vapor exposure, effects are limited to the nasal mucosa at 1.0 ppm, with a no-effect concentration generally at 0.1 ppm. There is no evidence for systemic target organ or tissue toxicity by subchronic repeated exposure by any route. A chronic drinking water study showed an apparent increase, in females only, of large granular cell lymphocytic leukemia but this was not dosage related. This is most likely the result of a modifying effect on the factor(s) responsible for the expression of this commonly occurring rat neoplasm. A chronic (2-year) inhalation toxicity/oncogenicity study showed inflammatory changes in the anterior nasal cavity but no neoplasms or systemic toxicity. In vitro genotoxicity studies--bacterial mutagenicity, forward gene mutation (HGPRT and TK loci), sister chromatid exchange, chromosome aberration, UDS and DNA repair tests--have given variable results, ranging from no effect through to weak positive. In vivo genotoxicity studies--micronucleus, chromosome aberration, dominant lethal and Drosophila tests--generally have shown no activity but one mouse intraperitoneal study showed bone marrow cell chromosome aberrations. Developmental toxicity studies show GA not to be teratogenic, and a two-generation study showed no adverse reproductive effects. Percutaneous pharmacokinetic studies showed low skin penetration, with lowest values measured in vitro in rats and human skin. Overexposure of humans produces typical sensory irritant effects on the eye, skin and respiratory tract. Some reports have described an asthmatic-like reaction by overexposure to GA vapor. In most cases this resembles reactive airways dysfunction syndrome, and the role of immune mechanisms is uncertain. Local mucosal effects may occur if medical instruments or endoscopes are not adequately decontaminated. Protection of individuals from the potential adverse effects of GA exposure requires that there be adequate protection of the skin, eyes and respiratory tract. The airborne concentration of GA vapor should be kept below the recommended safe exposure level (e.g. the threshold limit value) by the use of engineering controls. Those who work with GA should, through a training program, be aware of the properties of GA, its potential adverse effects, how to handle the material safely and how to deal with accidental situations involving GA. If effects develop in exposed workers, the reasons should be determined immediately and corrective methods initiated. (c) 2001 John Wiley & Sons, Ltd.
 ...
PMID:Toxicological, medical and industrial hygiene aspects of glutaraldehyde with particular reference to its biocidal use in cold sterilization procedures. 1128 36

Methyl Alcohol is an aliphatic alcohol with use in a few cosmetic formulations as a solvent and denaturant. Concentrations up to 5% are typically used to denature ethyl alcohol in cosmetic products. Methyl Alcohol is readily absorbed through the skin and from the gastrointestinal and respiratory tracts, is distributed throughout all organs and tissues (in direct relation to the body's water distribution), and is eliminated primarily via the lungs. Undiluted Methyl Alcohol is an ocular and skin irritant. Inhalation studies showed a no-effect level for maternal damage of 10,000 ppm and for teratogenic effects of 5,000 ppm. Overall, Methyl Alcohol is not considered mutagenic. Carcinogenicity data were unavailable. The toxicity of Methyl Alcohol in humans results from the metabolism of the alcohol to formate and formic acid through a formaldehyde intermediate. Formate accumulation causes metabolic acidosis and inhibits cellular respiration. Methyl Alcohol toxicity is time and concentration dependent, and its toxic effect is competitively inhibited with ethyl alcohol. Because of the moderating effect of ethyl alcohol, it was concluded that Methyl Alcohol is safe as used to denature ethyl alcohol used in cosmetic products. No conclusion was reached regarding any other use of Methyl Alcohol.
 ...
PMID:Final report on the safety assessment of Methyl Alcohol. 1135 11

One of the in vitro models involved in an ECVAM-sponsored prevalidation study for acute skin irritation is the skin integrity function test (SIFT), which utilises full-thickness mouse skin. We have evaluated nine different skin types in order to identify the most useful model for assessing skin barrier function using transepidermal water loss (TEWL), electrical resistance (ER) and tritiated water flux (TWF) and sodium lauryl sulphate (SLS) as a standard skin irritant. Tissues were: human skin (epidermis and whole), reconstituted human epidermis (RHE), pig (dermatomed and whole), rabbit (whole), rat (epidermis and whole) and mouse (whole). Barrier function was measured following sodium lauryl sulphate (SLS) exposure and expressed as a damage ratio. Human epidermis gave good responses at high doses of SLS only. RHE had abnormally high permeability to water and therefore had little or no response to SLS. Pig skin gave low TEWL ratios and rabbit skin was a poor responder to SLS. Mouse whole skin performed best in this study, giving consistent high damage ratios to TEWL, ER and TWF following SLS treatment. Rat whole skin also performed well but was generally less responsive. We conclude that mouse skin is the best and most practical in vitro model for the SIFT approach for skin irritation prediction.
 ...
PMID:Comparison of tissue sources for the skin integrity function test (SIFT). 1156 97

This report reviews the safety of Aluminum, Calcium, Lithium Magnesium, Lithium Magnesium Sodium, Magnesium Aluminum, Magnesium, Sodium Magnesium, and Zirconium Silicates, Magnesium Trisilicate, Attapulgite, Bentonite, Fuller's Earth, Hectorite, Kaolin, Montmorillonite, Pyrophyllite, and Zeolite as used in cosmetic formulations. The common aspect of all these claylike ingredients is that they contain silicon, oxygen, and one or more metals. Many silicates occur naturally and are mined; yet others are produced synthetically. Typical cosmetic uses of silicates include abrasive, opacifying agent, viscosity-increasing agent, anticaking agent, emulsion stabilizer, binder, and suspending agent. Clay silicates (silicates containing water in their structure) primarily function as adsorbents, opacifiers, and viscosity-increasing agents. Pyrophyllite is also used as a colorant. The International Agency for Research on Cancer has ruled Attapulgite fibers >5 microm as possibly carcinogenic to humans, but fibers <5 microm were not classified as to their carcinogenicity to humans. Likewise, Clinoptilolite, Phillipsite, Mordenite, Nonfibrous Japanese Zeolite, and synthetic Zeolites were not classified as to their carcinogenicity to humans. These ingredients are not significantly toxic in oral acute or short-term oral or parenteral toxicity studies in animals. Inhalation toxicity, however, is readily demonstrated in animals. Particle size, fibrogenicity, concentration, and mineral composition had the greatest effect on toxicity. Larger particle size and longer and wider fibers cause more adverse effects. Magnesium Aluminum Silicate was a weak primary skin irritant in rabbits and had no cumulative skin irritation in guinea pigs. No gross effects were reported in any of these studies. Sodium Magnesium Silicate had no primary skin irritation in rabbits and had no cumulative skin irritation in guinea pigs. Hectorite was nonirritating to the skin of rabbits in a Draize primary skin irritation study. Magnesium Aluminum Silicate and Sodium Magnesium Silicate caused minimal eye irritation in a Draize eye irritation test. Bentonite caused severe iritis after injection into the anterior chamber of the eyes of rabbits and when injected intralamellarly, widespread corneal infiltrates and retrocorneal membranes were recorded. In a primary eye irritation study in rabbits, Hectorite was moderately irritating without washing and practically nonirritating to the eye with a washout. Rats tolerated a single dose of Zeolite A without any adverse reaction in the eye. Calcium Silicate had no discernible effect on nidation or on maternal or fetal survival in rabbits. Magnesium Aluminum Silicate had neither a teratogenic nor adverse effects on the mouse fetus. Female rats receiving a 20% Kaolin diet exhibited maternal anemia but no significant reduction in birth weight of the pups was recorded. Type A Zeolite produced no adverse effects on the dam, embryo, or fetus in either rats or rabbits at any dose level. Clinoptilolite had no effect on female rat reproductive performance. These ingredients were not genotoxic in the Ames bacterial test system. In primary hepatocyte cultures, the addition of Attapulgite had no significant unscheduled DNA synthesis. Attapulgite did cause significant increases in unscheduled DNA synthesis in rat pleural mesothelial cells, but no significant increase in sister chromosome exchanges were seen. Zeolite particles (<10 microm) produced statistically significant increase in the percentage of aberrant metaphases in human peripheral blood lymphocytes and cells collected by peritoneal lavage from exposed mice. Topical application of Magnesium Aluminum Silicate to human skin daily for 1 week produced no adverse effects. Occupational exposure to mineral dusts has been studied extensively. Fibrosis and pneumoconiosis have been documented in workers involved in the mining and processing of Aluminum Silicate, Calcium Silicate, Zirconium Silicate, Fuller's Earth, Kaolin, Montmorillonite, Pyrophyllite, and Zeolite. The Cosmetic Ingredient Review (CIR. The Cosmetic Ingredient Review (CIR) Expert Panel concluded that the extensive pulmonary damage in humans was the result of direct occupational inhalation of the dusts and noted that lesions seen in animals were affected by particle size, fiber length, and concentration. The Panel considers that most of the formulations are not respirable and of the preparations that are respirable, the concentration of the ingredient is very low. Even so, the Panel considered that any spray containing these solids should be formulated to minimize their inhalation. With this admonition to the cosmetics industry, the CIR Expert Panel concluded that these ingredients are safe as currently used in cosmetic formulations. The Panel did note that the cosmetic ingredient, Talc, is a hydrated magnesium silicate. Because it has a unique crystalline structure that differs from ingredients addressed in this safety assessment, Talc is not included in this report.
 ...
PMID:Final report on the safety assessment of aluminum silicate, calcium silicate, magnesium aluminum silicate, magnesium silicate, magnesium trisilicate, sodium magnesium silicate, zirconium silicate, attapulgite, bentonite, Fuller's earth, hectorite, kaolin, lithium magnesium silicate, lithium magnesium sodium silicate, montmorillonite, pyrophyllite, and zeolite. 1285 Nov 64

To evaluate the effects of the occupational exposure to rayon manufacturing chemicals (RMC, containing predominantly carbon disulfide (CS(2)) and minor sulfuric acid) in a rayon factory on the basal transepidermal water loss (TEWL), barrier integrity (BI), and sequential increasing TEWL profiles. Six Thais and five Chinese workers in the spinning department of a rayon manufacturing plant and five healthy unexposed controls were recruited as the test subjects. An area of 4.5 x 5.5 cm on the mid-side of the volar forearm on the right hand was stripped by means of moderate pressure with commercially available adhesive tape by the same technician throughout the experiment. The skin was progressively stripped until glistening. TEWL was measured at every three and five tape strips on the right hand. The corresponding site on the left hand was measured parallel as the self-control. We found significant differences in basal TEWL and in BI between Chinese workers and Chinese controls, and between Thai workers and Chinese workers, respectively. Two-stage patterns of progressive TEWL profiles were found in such a chronic and repeated occupational exposure to RMC containing CS(2). The occupational exposure to RMC could result in the perturbation of the skin barrier function. Basal TEWL might be more sensitive to chronic skin irritant exposure. The TEWL profile achieved to the glistening stage might be necessary to avoid erroneous pattern estimation. Due to the lack of Thais control in this study, the racial difference in response to the RMC warrants further study.
 ...
PMID:Effect of occupational exposure to rayon manufacturing chemicals on skin barrier to evaporative water loss. 1549 59

Potassium Silicate, Sodium Metasilicate, and Sodium Silicate combine metal cations with silica to form inorganic salts used as corrosion inhibitors in cosmetics. Sodium Metasilicate also functions as a chelating agent and Sodium Silicate as a buffering and pH adjuster. Sodium Metasilicate is currently used in 168 formulations at concentrations ranging from 13% to 18%. Sodium Silicate is currently used in 24 formulations at concentrations ranging from 0.3% to 55%. Potassium Silicate and Sodium Silicate have been reported as being used in industrial cleaners and detergents. Sodium Metasilicate is a GRAS (generally regarded as safe) food ingredient. Aqueous solutions of Sodium Silicate species are a part of a chemical continuum of silicates based on an equilibrium of alkali, water, and silica. pH determines the solubility of silica and, together with concentration, determines the degree of polymerization. Sodium Silicate administered orally is readily absorbed from the alimentary canal and excreted in the urine. The toxicity of these silicates has been related to the molar ratio of SiO2/Na2O and the concentration being used. The Sodium Metasilicate acute oral LD50 ranged from 847 mg/kg in male rats to 1349.3 mg/kg in female rats and from 770 mg/kg in female mice to 820 mg/kg in male mice. Gross lesions of variable severity were found in the oral cavity, pharynx, esophagus, stomach, larynx, lungs, and kidneys of dogs receiving 0.25 g/kg or more of a commercial detergent containing Sodium Metasilicate; similar lesions were also seen in pigs administered the same detergent and dose. Male rats orally administered 464 mg/kg of a 20% solution containing either 2.0 or 2.4 to 1.0 ratio of sodium oxide showed no signs of toxicity, whereas doses of 1000 and 2150 mg/kg produced gasping, dypsnea, and acute depression. Dogs fed 2.4 g/kg/day of Sodium Silicate for 4 weeks had gross renal lesions but no impairment of renal function. Dermal irritation of Potassium Silicate, Sodium Metasilicate, and Sodium Silicate ranged from negligible to severe, depending on the species tested and the molar ratio and concentration tested. Sodium Metasilicate was negative in the local lymph node assay (LLNA), but a delayed-type hypersensitivity response was observed in mice. Potassium Silicate was nonirritating in two acute eye irritation studies in rabbits. Sodium Metasilicate (42.4% H2O) was corrosive to the rabbit eye. Sodium Silicate was a severe eye irritant in some eye irritation studies, but was irritating or nonirritating in others. A skin freshener containing Sodium Silicate was nonirritating. Sodium Metasilicate was nonmutagenic in bacterial cells. Rats given Sodium Silicate (600 and 1200 ppm of added silica) in the drinking water in reproductive studies produced a reduced number of offspring: to 67% of controls at 600 ppm and to 80% of controls at 1200 ppm. Three adult rats injected intratesticularly and subcutaneously with 0.8 mM/kg of Sodium Silicate showed no morphological changes in the testes and no effect on the residual spermatozoa in the ductus deferens. Sodium Metasilicate (37% in a detergent) mixed with water was a severe skin irritant when tested on intact and abraded human skin, but 6%, 7%, and 13% Sodium Silicate were negligible skin irritants to intact and abraded human skin. Sodium Silicate (10% of a 40% aqueous solution) was negative in a repeat-insult predictive patch test in humans. The same aqueous solution of Sodium Silicate was considered a mild irritant under normal use conditions in a study of cumulative irritant properties. The Cosmetic Ingredient Review (CIR) Expert Panel recognized the irritation potential of these ingredients, especially in leave-on products. However, because these ingredients have limited dermal absorption and Sodium Metasilicate is a GRAS direct food substance, the Panel deemed the ingredients safe for use in cosmetic products in the practices of use and concentration described in this safety assessment, when formulated to avoid irritation.
 ...
PMID:Final report on the safety assessment of potassium silicate, sodium metasilicate, and sodium silicate. 1598 34

Phytantriol is an alcohol used in around 100 cosmetic products at concentrations ranging from 0.0002% to 1.0%, although uses at concentrations up to 3% are under development. Phytanriol is supplied at 95.2% and 96.0% purity. Impurities include water, sulphated ash, heavy metals, and a diastereomer of Phytantriol, 3,7,11,15-tetramethyl-1,2,3,4-tetrahydroxyhexadecane. Dermal penetration is low; skin permeability was calculated as log Kp = - 1.734. Oral LD50 values in mice and rats were reported to be > 5000 mg/kg. Ocular application of 100% Phytantriol did cause severe corneal damage in some animals, at 23% in diethyl phthalate only slight corneal opacity was seen, and at 10% transient opacity was seen, which resolved by 48 h. Phytantriol at 100% was a severe skin irritant in animal tests. Phytantriol at 3% and 10% in diethyl phthalate produced only slight erythema, which cleared by 48 h. Phytantriol, in the Longhorn egg chorioallantoic membrane assay, was found to have almost no irritation potential when tested at 3% concentration in corn oil. Phytantriol at 25% did produce sensitization in a maximization test, but concentrations of 1% and lower did not cause a sensitization response. Phytantriol is neither phototoxic nor photoallergenic. Phytantriol did not induce aberrations in cultured human lymphocytes, when tested within cytotoxicity limits, nor was it mutagenic in Ames tests, with or without metabolic activation. None of 101 human volunteers reacted initially or to challenge patches of 3% Phytantriol in corn oil. In another investigation of 227 volunteers induced and challenged with 3% Phytantriol in 70:30 ethyl alcohol/water, one person had a mild reaction to the first induction patch; this was the only positive reaction during the induction and challenge phases for all of the volunteers. Phytantriol had no adverse effects in any of 206 volunteer subjects in a repeat insult patch test at 5%. Although data were not available with which to assess reproductive and developmental toxicity and carcinogenic potential, there were no structural alerts suggesting that these end points should be of concern. Dermal penetration is low, and Phytantriol is not genotoxic. Although products containing this ingredient may be aerosolized, typical particle sizes for cosmetic aerosol products are larger than are respirable. Although this ingredient can be irritating and produce sensitization reactions at high concentrations, such effects are absent at lower concentrations. The Panel concluded that cosmetic products could be formulated at concentrations as high as 3% without significant irritation or sensitization.
 ...
PMID:Final report on the safety assessment of phytantriol. 1736 38


<< Previous 1 2 3 Next >>