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)

As one of the projects in the safety evaluation of chemical constituents in common house-hold products, effects of hexabromocyclododecane (HBCD) were evaluated by primary skin irritation, skin sensitization, phototoxicity and photosensitization using guinea pigs. Primary skin irritation was not observed in HBCD emulsified in distilled water by the Draize test method. Skin sensitization test was carried out according to the maximization test method of Magnusson and Kligman. For this test, HBCD was dissolved in olive oil to give 5, 0.5 and 0.05%. When induction of sensitization occurred, challenged doses of 0.005, 0.05, 0.5 and 5% of HBCD (dissolved in acetone) were applied to its respective sensitized groups. The results showed that the induction dose of greater than 0.5% and the challenge dose of greater than 0.05% elicited a positive response. The increase in the concentration of induction and challenge doses did not further increase the percentage of positive response or the intensity of skin response. Phototoxicity test was carried out with 0, 0.5 and 5% of HBCD dissolved in acetone. Phototoxicity was not observed at all HBCD concentration tested. Photosensitization test was performed according to the Sato's adjuvant-strip method. The skin sensitization and challenge reaction doses were 5 and 0.5% and 0 and 0.5% HBCD (dissolved in acetone), respectively, and no positive reaction was observed. It is clear from the foregoing results that HBCD is a mild skin allergen.
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PMID:[Dermatological evaluation of a flame retardant, hexabromocyclododecane (HBCD) on guinea pig by using the primary irritation, sensitization, phototoxicity and photosensitization of skin]. 792 May 64

Glyceryl Dilaurate, Glyceryl Diarachidate, Glyceryl Dibehenate, Glyceryl Dierucate, Glyceryl Dihydroxystearate, Glyceryl Diisopalmitate, Glyceryl Diisostearate, Glyceryl Dilinoleate, Glyceryl Dimyristate, Glyceryl Dioleate, Glyceryl Diricinoleate, Glyceryl Dipalmitate, Glyceryl Dipalmitoleate, Glyceryl Distearate, Glyceryl Palmitate Lactate, Glyceryl Stearate Citrate, Glyceryl Stearate Lactate, and Glyceryl Stearate Succinate are diacylglycerols (also known as diglycerides or glyceryl diesters) that function as skin conditioning agents - emollients in cosmetics. Only Glyceryl Dilaurate (up to 5%), Glyceryl Diisostearate (up to 43%), Glyceryl Dioleate (up to 2%), Glyceryl Distearate (up to 7%), and Glyceryl Stearate Lactate (up to 5%) are reported to be in current use. Production proceeds from fully refined vegetable oils, which are further processed using hydrogenation and fractionation techniques, and the end products are produced by reacting selected mixtures of the partly hydrogenated, partly fractionated oils and fats with vegetable-derived glycerine to yield partial glycerides. In the final stage of the production process, the products are purified by deodorization, which effectively removes pesticide residues and lower boiling residues such as residues of halogenated solvents and aromatic solvents. Diglycerides have been approved by the Food and Drug Administration (FDA) for use as indirect food additives. Nominally, these ingredients are 1,3-diglycerides, but are easily isomerized to the 1,2-diglycerides form. The 1,3-diglyceride isomer is not a significant toxicant in acute, short-term, subchronic, or chronic animal tests. Glyceryl Dilaurate was a mild primary irritant in albino rabbits, but not a skin sensitizer in guinea pig maximization tests. Diacylglycerol Oil was not genotoxic in the Ames test, in mammalian Chinese hamster lung cells, or in a rodent bone marrow micronucleus assay. An eye shadow containing 1.5% Glyceryl Dilaurate did not induce skin irritation in a single insult patch test, but mild skin irritation reactions to a foundation containing the same concentration were observed. A trade mixture containing an unspecified concentration of Glyceryl Dibehenate did not induce irritation or significant cutaneous intolerance in a 48-h occlusive patch test. In maximization tests, neither an eye shadow nor a foundation containing 1.5% Glyceryl Dilaurate was a skin sensitizer. Sensitization was not induced in subjects patch tested with 50% w/w Glyceryl Dioleate in a repeated insult, occlusive patch test. Glyceryl Palmitate Lactate (50% w/v) did not induce skin irritation or sensitization in subjects patch tested in a repeat-insult patch test. Phototoxicity or photoallergenicity was not induced in healthy volunteers tested with a lipstick containing 1.0% Glyceryl Rosinate. Two diacylglycerols, 1-oleoyl-2-acetoyl-sn-glycerol and 1,2-dipalmitoyl-sn-glycerol, did not alter cell proliferation (as determined by DNA synthesis) in normal human dermal fibroblasts in vitro at doses up to 10 microg/ml. In the absence of initiation, Glyceryl Distearate induced a moderate hyperplastic response in randomly bred mice of a tumor-resistant strain, and with 9,10-dimethyl-1,2-benzanthracene (DMBA) initiation, an increase in the total cell count was observed. In a glyceryl monoester study, a single application of DMBA to the skin followed by 5% Glyceryl Stearate twice weekly produced no tumors, but slight epidermal hyperplasia at the site of application. Glyceryl Dioleate induced transformation in 3-methylcholanthrene-initiated BALB/3T3 A31-1-1 cloned cells in vitro. A tumor-promoting dosing regimen that consisted of multiple applications of 10 mumol of a 1,2-diacylglycerol (sn-1,2-didecanoylglycerol) to female mice twice daily for 1 week caused more than a 60% decrease in protein kinase C (PKC) activity and marked epidermal hyperplasia. Applications of 10 micromol sn-1,2-didecanoylglycerol twice weekly for 1 week caused a decrease in cytosolic PKC activity, an increase in particulate PKC activity, and no epidermal hyperplasia. In studies of the tumor-promoting activity of 1,2-diacylglycerols, dose and the exposure regimen by which the dose is delivered play a role in tumor promotion. The 1,2-diacylglycerol-induced activation of PKC may also relate to the saturation of the fatty acid in the 1 or 2 position; 1,2-Diacylglycerols with two saturated fatty acids are less effective. Also, the activity of 1,2-diacylglycerols may be reduced when the fatty acid moiety in the structure is a long-chain fatty acid. A histological evaluation was performed on human skin from female volunteers (18 to 56 years old) who had applied a prototype lotion or placebo formulation, both containing 0.5% Glyceryl Dilaurate, consecutively for 16 weeks or 21 weeks. Skin irritation was not observed in any of the subjects tested. Biopsies (2 mm) taken from both legs of five subjects indicated no recognizable abnormalities of the skin; the epidermis was normal in thickness, and there was no evidence of scaling, inflammation, or neoplasms in any of the tissues that were evaluated. The Cosmetic Ingredient Review (CIR) Expert Panel considered that the available safety test data indicate that diglycerides in the 1,3-diester form do not present any significant acute toxicity risk, nor are these ingredients irritating, sensitizing, or photosensitizing. Whereas no data are available regarding reproductive or developmental toxicity, there is no reason to suspect any such toxicity because the dermal absorption of these chemicals is negligible. The Panel noted that these nominally 1,3-diglycerides contain 1,2-diglycerides, raising the concern that 1,2-diglycerides could potentially induce hyperplasia. Data regarding the induction of PKC and the tumor promotion potential of 1,2-diacylglycerols increased the level of concern. Most of the diglycerides considered in this safety assessment, however, have fatty acid chains longer than 14 carbons and none have mixed saturated/unsaturated fatty acid moieties. The Panel considered it particularly important that a 21-week use study of a prototype lotion containing 0.5% Glyceryl Dilaurate (a 14-carbon chain fatty acid) indicated no evidence of scaling, inflammation, or neoplasms in biopsy specimens. Also, DNA synthesis assays on Glyceryl Dilaurate and Glyceryl Distearate indicated that neither chemical altered cell proliferation (as determined by DNA synthesis) in normal human dermal fibroblasts in vitro at doses up to 10 microg/ml. The Panel understands that use testing is a common practice in industry and, if histopathology data are collected, the Panel believes that such an approach can demonstrate an absence of epidermal hyperplasia. Because the concentration of these ingredients can vary (up to 43% for Glyceryl Diisostearate in lipstick), the frequency of application can be several times daily, and the proportion of diglycerides that are inactive 1,3 isomers versus potentially biologically active 1,2 isomers is unknown, the Panel believes that each use should be examined to ensure the absence of epidermal hyperplasia during product development and testing. In the absence of inhalation toxicity data on the Glyceryl Diesters in this safety assessment, the Panel determined that these ingredients can be used safely in aerosolized products because they are not respirable. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the CIR Expert Panel considers all ingredients in this group to be safe.
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PMID:Amended final report on the safety assessment of glyceryl dilaurate, glyceryl diarachidate, glyceryl dibehenate, glyceryl dierucate, glyceryl dihydroxystearate, glyceryl diisopalmitate, glyceryl diisostearate, glyceryl dilinoleate, glyceryl dimyristate, glyceryl dioleate, glyceryl diricinoleate, glyceryl dipalmitate, glyceryl dipalmitoleate, glyceryl distearate, glyceryl palmitate lactate, glyceryl stearate citrate, glyceryl stearate lactate, and glyceryl stearate succinate. 1827 50

The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential.
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PMID:Phototoxicity: Its Mechanism and Animal Alternative Test Methods. 2648 92

Phototoxicity occurs when UV irradiation causes otherwise benign compounds to become irritant, sensitizers, or even genotoxic. This toxicity is particularly a concern after topical application and in dermatological programs where skin irritation can be incompatible with the desired therapeutic outcome. This brief article establishes that the intrinsic property forecast index (iPFI) can be used to evaluate the probability of a compound being phototoxic and gives medicinal chemists a practical tool to handle this liability.
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PMID:Intrinsic Property Forecast Index (iPFI) as a Rule of Thumb for Medicinal Chemists to Remove a Phototoxicity Liability. 2954 79