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 influence of the amounts of additives including 1-O-ethyl-3-n-butylcyclohexanol (OEBC), diisopropyl adipate (DIA), and isopropanol (IPA) on the penetration rate (R(p)) of ketoprofen from hydrogels through rat skin in vivo was investigated. Skin irritation evoked by the application of hydrogels was evaluated based on a microscopic observation of skin cross-sections. Both optimization techniques incorporating an artificial neural network (ANN) and a second-order polynomial regression analysis were applied to the optimization of ketoprofen hydrogel formulations. Findings indicated that the R(p) and total irritation score (TIS) of the skin were predicted quantitatively as a function of quantities of OEBC, DIA, and IPA, employing ANN. In contrast, the prediction ability of the polynomial regression equation was somewhat poorer compared with that of ANN. The observed results of R(p) and TIS in the optimal formulation coincided well with the predictions in the simultaneous optimization technique incorporating ANN.
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PMID:Simultaneous optimization based on artificial neural networks in ketoprofen hydrogel formula containing O-ethyl-3-butylcyclohexanol as percutaneous absorption enhancer. 1153 4

Stearamide DIBA-Stearate is a substituted dihydroxyisobutylamine (DIBA) that functions in cosmetic formulations as an opacifying agent, a surfactant-foam booster, and a viscosity increasing agent. Stearamide DIBA-Stearate was reportedly used in four cosmetic formulations, at concentrations of 1% to 3%. Few data on this ingredient were available. Data on related ingredients, including Dibutyl Adipate, Diisopropyl Adipate, Stearamide DEA, and Stearamide MEA, were considered in the assessment of safety. A formulation containing 1.3% Stearamide DIBA-Stearate (further diluted to 4% of the formulation) was mildly irritating but nonsensitizing in an repeated-insult patch test (RIPT). The same dilution was noncomedogenic. At a concentration of 20%, Dibutyl Adipate had an oral LD50 of 2 g/kg. Subchronic dermal exposure of rabbits (1.0 ml/kg/day) caused a reduction in weight gain that was not observed at a dose of 0.5 ml/kg/day. In studies using rabbits, undiluted Dibutyl Adipate caused mild to moderate skin irritation and minimal ocular irritation. When pregnant rats were treated intraperitoneally with approximately 1.75 ml/kg Dibutyl Adipate during gestation, the incidence of fetal gross abnormalities was increased. No effect was observed at smaller doses. Diisopropyl Adipate had low acute oral and percutaneous toxicity, and was only a very mild ocular irritant. In skin irritation studies using rabbits, 5.0% to 100% Diisopropyl Adipate caused minimal to mild irritation; these results were also seen in clinical testing with only moderate cumulative irritation, and no sensitization or photosensitization. A formulation containing 5.27% Stearamide MEA was not toxic to rats when applied topically daily for 13 weeks. In studies using rabbits, Stearamide DEA (35% to 40%) was not a skin or ocular irritant, and Stearamide MEA (5.27%) was not an ocular irritant. At 17%, Stearamide MEA was not irritating to the skin, but caused minimal to moderate irritation to the eyes of rabbits. Stearamide MEA (5.27%) did not cause sensitization during a clinical study. It was not possible, however, to determine the relevance of these data on related ingredients. Therefore, it was concluded that the available data are insufficient. Additional data needs are (1) method of manufacture; (2) chemical characterization, including impurities; (3) dermal absorption; if significantly absorbed, then a 28-day dermal toxicity study and a reproductive and developmental toxicity study may be needed; (4) two genotoxicity assays, at least one in a mammalian system; if positive, then a 2-year dermal carcinogenesis study using National Toxicology Program (NTP) methods may be needed; (5) ultraviolet (UV) absorption data; if significant absorption occurs in the UVA or UVB range, photosensitization data are needed. Absent these data, it was concluded that the available data are insufficient to support the safety of Stearamide DIBA-Stearate as used in cosmetic products.
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PMID:Final report on the safety assessment of Stearamide DIBA-Stearate. 1176 36

Adipic acid has very low acute toxicity in rats with an LD50 > 5000 mg/kg. Adipic acid produced mild to no skin irritation on intact guinea pig skin as a 50% concentration in propylene glycol; it was not a skin sensitizer. Adipic acid caused mild conjunctival irritation in washed rabbit eyes; in unwashed rabbit eyes, there was mild conjunctival irritation, minimal iritis, but no corneal effects. Adipic acid dust may irritate the mucous membranes of the lungs and nose. In a 2-year feeding study, rats fed adipic acid at concentrations up to 5% in the diet exhibited only weight loss. Adipic acid is not genetically active in a wide variety of assay systems. Adipic acid caused no developmental toxicity in mice, rats, rabbits, or hamsters when administered orally. Adipic acid is partially metabolized in humans; the balance is eliminated unchanged in the urine. Adipic acid is slightly to moderately toxic to fish, daphnia, and algae in acute tests.
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PMID:Toxicity of adipic acid. 1202 2

Retinoids (vitamin A and derivatives) are of great commercial potential in cosmetics and pharmaceuticals such as skin care products. However, the clinical effectiveness of these retinoids is limited by skin irritation, water insolubility, and except for retinyl-esters, extreme instability. In this paper, an enzymatic method for preparing water-soluble retinol derivatives catalyzed by immobilized lipase is described. The synthesis is based on a unique strategy of two-step enzymatic acylation. Among the different synthesized compounds, the most water-soluble are the disaccharide derivatives such as saccharose retinyl adipate (nonionic water-soluble retinol derivative) and the sodium salt of retinyl diacids such as retinyl succinate sodium salt (ionic water-soluble retinol derivative).
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PMID:Synthesis of water-soluble retinol derivatives by enzymatic method. 1205 54

Dibutyl Adipate, the diester of butyl alcohol and adipic acid, functions as a plasticizer, skin-conditioning agent, and solvent in cosmetic formulations. It is reportedly used at a concentration of 5% in nail polish and 8% in suntan gels, creams, and liquids. Dibutyl Adipate is soluble in organic solvents, but practically insoluble in water. Dibutyl Adipate does not absorb radiation in the ultraviolet (UV) region of the spectrum. Dibutyl Adipate is not toxic in acute oral or dermal animal toxicity tests. In a subchronic dermal toxicity study, 1.0 ml/kg day-1 caused a significant reduction in body weight gain in rabbits, but 0.5 ml/kg/day1 was without effect. In a study with dogs, no adverse effects were observed when an emulsion containing 6.25% Dibutyl Adipate was applied to the entire body twice a week for 3 months. Dibutyl Adipate was tested for dermal irritation using rabbits and mice and a none to minimal irritation was observed. Dibutyl Adipate at a concentration of 25% was not a sensitizer in a guinea pig maximization study. Undiluted Dibutyl Adipate was minimally irritating to the eyes of rabbits and 0.1% was nonirritating. A significant increase in fetal gross abnormalities was observed in rats given intraperitoneal injections of Dibutyl Adipate at 1.75 ml/kg on 3 separate days during gestation, but no effect was seen in animals given 1.05 ml/kg. Dibutyl Adipate was not genotoxic in either bacterial or mammalian test systems. Clinical patch tests confirmed the absence of skin irritation found in animal tests. Clinical phototoxicity tests were negative. Dibutyl Adipate at 0.1% was not an ocular irritant in two male volunteers. In a clinical test of comedogenicity, Dibutyl Adipate produced no effect. The Cosmetic Ingredient Review (CIR) Expert Panel recognized that use of Dibutyl Adipate in suntan cosmetic products will result in repeated, frequent exposure in a leave-on product. The available data demonstrate no skin sensitization or cumulative skin irritation, no comedogenicity, and no genotoxicity. Combined with the data demonstrating little acute toxicity, no skin or ocular irritation, and no reproductive or developmental toxicity, these data form an adequate basis for reaching a conclusion that Dibutyl Adipate is safe as a cosmetic ingredient in the practices of use and concentrations as reflected in this safety assessment.
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PMID:Amended final report of the safety assessment of dibutyl adipate as used in cosmetics. 1683 33

The aim of this study was to prepare a transdermal therapeutic formulation of CNS5161, an NMDA receptor antagonist developed as a drug for neuropathic pain. Since a silicone pressure-sensitive adhesive (PSA) was found to be the best PSA for CNS5161 among six different PSAs examined in our previous study, the effects of the loading concentration of CNS5161 on release and rat skin permeability were investigated using silicone PSAs. The release of CNS5161 was elevated with an increase in the drug concentration from 1% to 14%. The transdermal flux at the steady state reached a plateau at 8% and over, while crystallization of CNS5161 was not observed for any formulation even at high drug concentrations. The drug concentration in rat skin at the steady state was also saturated at 8% and over, which correlated well with the transdermal flux at the steady state. Therefore, skin permeation clearance defined to the skin concentration at the steady state was almost constant at 0.21/h from 2% to 14% of CNS5161, which suggests that drug concentrations in the skin would be a driving force for transport of the drug to the receptor side. Since increasing the concentration of CNS5161 in the PSA patch was not able to elevate the transdermal flux, 12 formulations containing several permeation enhancers were examined to improve the transdermal transport of CNS5161. Among them, the formulation containing propylene glycol, diisopropyl adipate, and polyvinylpyrrolidone significantly increased the transdermal flux by approximately 1.8-fold by improving the diffusivity of CNS5161 in the skin, and also significantly enhanced the analgesic effect of CNS5161. This formulation caused only slight skin irritation, which indicated that it would be a promising transdermal therapeutic system for CNS5161.
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PMID:Development of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor antagonist, by utilizing pressure-sensitive adhesives II: improved transdermal absorption and evaluation of efficacy and safety. 2421 37