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

The proliferative responses induced in hairless mouse epidermis after application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the skin irritant cantharidin were investigated. Doses known to give the same degree of hyperplasia were chosen. Mice were pulse-labeled with bromodeoxyuridine (BrdUrd) 30 min prior to or 24 h after a single application of either cantharidin or TPA, and thereafter killed at various time intervals. The basal cells were isolated from epidermis, fixed in 70% ethanol and prepared for bivariate BrdUrd/DNA flow cytometric analysis. Cells pulse-labeled in S phase 30 min prior to treatment with cantharidin or TPA were slightly delayed in their progression through S phase and temporarily blocked in G2 phase. However, they were still able to re-enter S phase 18 h later, indicating a shortening of the G1 phase. Cells pulse-labeled 24 h after treatment had a considerably reduced cell cycle time, i.e. reduced G1 transit time. Hence, the wave of cells entering S phase from 16 h after injury could be explained by an immediate reduction in G1 transit time, without assuming recruitment of temporarily resting G0/G1 cells. Although cantharidin caused the longest initial delay in cell cycle progression, the subsequent proliferative response was less pronounced than that provoked by TPA. Rapid proliferation may allow for clonal expansion of initiated cells. The higher ability of TPA to induce rapid proliferation, apparently without causing any severe initial cell damage, may thus be related to its higher tumor promoting ability.
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PMID:A comparison between the epidermal regenerative responses provoked by a skin irritant and a tumor promoter using anti-BrdUrd/DNA flow cytometry. 202 47

To provide guidelines for handling the very labile phorbol ester, RPA,2 its stability under various laboratory conditions was studied. RPA will remain undecomposed for 8 weeks if stock solutions are made in ethanol, ethyl acetate, or DMSO and stored in absolute darkness at -20 degrees C. When exposed to light RPA readily isomerizes to 13'-cis-RPA. Structure/activity investigations of irritant polyfunctional diterpene esters of phorbol, ingenol, and resiniferonol with saturated and unsaturated aliphatic or with aromatic acids indicate that their irritant activity is a necessary, yet insufficient prerequisite for initiation- (or tumor-) promoting activity (e.g., Refs. 3 and 4). For further testing of this hypothesis, the retinoic acid analogue of the mouse skin irritant and initiation-promoter TPA, i.e., RPA, was designed (7). In initiation/promotion experiments of skin of NMRI mice, it proved to be an irritant almost as active as TPA, but only marginally active as a promoter. In combination with TPA, it turned out to be a "second stage" promoter (PII-promoter) (1, 6) in our strain of mice (2, 7). RPA is a much more labile compound than TPA (5), especially in the solid form. If stored in solution, special precautions have to be taken to ascertain that the concentration or dose intended is represented by undecomposed RPA.
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PMID:Stability of the "second stage" promoter 12-O-retinoylphorbol-13-acetate. 398 82

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.
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PMID:Final report on the safety assessment of Methyl Alcohol. 1135 11

Ocimum spp. (Lamiaceae) and their essential oils have been traditionally used to kill or repel insects, and also to flavor foods and oral products, in fragrances, in folk medicine and as condiments. In Brazil, Ocimum selloi has been used to treat stomachaches and as an anti-inflammatory remedy. This study was performed to provide data on the chemical composition, acute toxicity, mutagenicity, skin irritant potential and mosquito repellency of Ocimum selloi oil. GC/MS analysis of Ocimum selloi oil revealed that its major constituents were methyl-chavicol or estragole (55.3%), trans-anethole (34.2%), cis-anethole (3.9%) and caryophyllene (2.1%). Ocimum selloi oil given by gavage to adult Swiss Webster mice produced no adverse effects at doses as high as 1250 mg/kg body weight. Deaths and symptoms (e.g. hypoactivity, ataxia and lethargy) were observed at doses > or =1500 mg/kg body weight, being females apparently more susceptible than males. Genotoxicity of Ocimum selloi oil was evaluated in the Salmonella/microsome assay without and with S9 mixture. The oil, tested up to the toxicity limit (500-700 microg/plate), was not mutagenic to tester strains TA97a, TA98 and TA100. None of 30 volunteers of either sex exposed to undiluted Ocimum selloi oil (4-h patch test) showed a positive skin irritant reaction. A field test (six volunteers, each individual his/her own control) was carried out to evaluate mosquito (Anopheles braziliensis) repellency of Ocimum selloi oil diluted in ethanol (10% v/v). The median number of mosquito bites on volunteers' skin-recorded for 30 min after application of Ocimum selloi oil (2, range 0-3) was much lower than that noted after application of the solvent alone (19.5, 3-25) (Wilcoxon test, P<0.01). In conclusion, results showed that Ocimum selloi oil is an effective mosquito repellent that presents a low acute toxicity, poses no mutagenic risk and seems not to be irritating to human skin.
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PMID:Chemical composition, toxicity and mosquito repellency of Ocimum selloi oil. 1296 52

Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to "negative" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)
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PMID:Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin. 1736 37

Propyl Gallate is the n-propyl ester of gallic acid (3,4,5-trihydroxybenzoic acid). It is soluble in ethanol, ethyl ether, oil, lard, and aqueous solutions of polyethylene glycol (PEG) ethers of cetyl alcohol, but only slightly soluble in water. Propyl Gallate currently is used as an antioxidant in a reported 167 cosmetic products at maximum concentrations of 0.1%. Propyl Gallate is a generally recognized as safe (GRAS) antioxidant to protect fats, oils, and fat-containing food from rancidity that results from the formation of peroxides. Data on dermal absorption are not available, but Propyl Gallate is absorbed when ingested, then methylated, conjugated, and excreted in the urine. The biological activity of Propyl Gallate is consistent with its free-radical scavenging ability, with effects that include antimicrobial activity, enzyme inhibition, inhibition of biosynthetic processes, inhibition of the formation of nitrosamines, anesthesia, inhibition of neuromuscular response to chemicals, ionizing/ultraviolet (UV) radiation protection, chemoprotection, antimutagenesis, anticarcinogenesis and antitumorigenesis, antiteratogenesis, and anticariogenesis. Animal toxicity studies indicate that Propyl Gallate was slightly toxic when ingested, but no systemic effects were noted with dermal application. Propyl Gallate is a strong sensitizer when tested intradermally, less sensitizing when tested topically, and nonsensitizing topically at 0.1% in one study. In a second study, Propyl Gallate (15 mg dissolved in 8 ml vehicle) was sensitizing to guinea pigs. Acute eye irritation tests conducted on nine cosmetic formulations, each containing less than 1% Propyl Gallate, were negative. A phototoxicity study conducted on a cosmetic formulation containing 0.003% Propyl Gallate determined that the product was not phototoxic to guinea pigs. In one study, female rats fed 0.5 g Propyl Gallate had substantially increased fetal resorption rates when compared to controls, but in four other studies, Propyl Gallate at doses up to 2.04 g/kg was nonteratogenic in rats, rabbits, mice, and hamsters. In clinical cumulative irritancy tests, Propyl Gallate was nonirritating at concentrations up to 10%. Patch tests at concentrations less than 1% yielded positive elicitation responses. Repeat-insult patch tests using cosmetic formulations with 0.003% Propyl Gallate produced no irritation or sensitization. Propyl Gallate at a concentration of 10% in alcohol was nonphototoxic in 25 subjects. Cosmetic formulations, each containing 0.003% Propyl Gallate, produced no signs of photosensitization or phototoxicity in a total of 371 subjects. Although Propyl Gallate is not a skin irritant in clinical tests, the available data demonstrate that it is a skin sensitizer and that it may be a sensitizer at lower concentrations than originally thought, i.e., at concentrations less than 1%. In actual practice, cosmetic formulations contain Propyl Gallate at concentrations up to 0.1% and usage has increased over the past 20 years. In spite of the increased exposure associated with increased use, it is the clinical experience of the Panel that the use of Propyl Gallate in cosmetics has not resulted in sensitization reactions. Therefore, the Panel believes that a concentration limitation of 0.1% in cosmetics is necessary (given the evidence of sensitization at concentrations less than 1%) and sufficient (given that current products are not producing adverse reactions).
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PMID:Final report on the amended safety assessment of Propyl Gallate. 1808 Aug 74

The bioactivity of four flavonoid compounds, namely poncirin, rhoifolin, naringin and marmesin, from Poncirus trifoliata was studied against the Aedes aegypti. Larvicidal assays were conducted to evaluate the 24 h LC(50) and LC(90) values of the flavonoid compounds. The lethal concentration (LC(50) and LC(90)) values ranged from 0.082 to 0.122 mg/l and 0.152 to 0.223 mg/l, respectively. The result of ovicidal test suggests that the ovicidal activity of the flavonoid compounds was influenced by the concentration of flavonoid compounds and age of the eggs. The result of oviposition test showed that the four flavonoid compounds exhibited oviposition-deterrent activity against gravid female mosquitoes. Oviposition decreased with an increase in concentration of flavonoid compounds. A laboratory test was carried out to evaluate protection period and percentage of repellency of four compounds diluted in ethanol (10 mg/l). The compound rhoifolin provided maximum 365.0 +/- 12.0 min protection and also 100.0% +/- 0.0 repellency against mosquito bite followed by poncirin, marmesin and naringin. None of the 25 volunteers of either sex exposed to 10% (w/v) flavonoid compounds (4-h patch test) showed a positive skin irritant reaction. All of the tested compounds proved to have various activities against different life stages of A. aegypti. Therefore, flavonoid compounds from P. trifoliata can be a potential candidate for use in the development of commercial mosquitocidal products that may be an alternative to conventional synthetic chemicals, particularly in integrated vector control applications.
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PMID:Bioactivity of flavonoid compounds from Poncirus trifoliata L. (Family: Rutaceae) against the dengue vector, Aedes aegypti L. (Diptera: Culicidae). 1881 Apr 94