Structure of 583-55-1
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Inhibiting NOXO1 and CYBA binding to reduce NADPH oxidase I dependent ROS damage in skin explants
Senevirathne, Prasadini ; Sterling, Alyssa ; Anne Refaei, Mary ; Mokhtarpour, Nazanin ; Gutierrez-Rivera, Laura ; Garcia, Joshua , et al.
Abstract: NADPH oxidases (NOXs) are newly identified enzymes that generate intracellular reactive oxygen species (ROS) in skin cells. Recent studies demonstrated that NOX1 holoenzyme is expressed in human keratinocytes and melanocytes, which are implicated in skin photo-carcinogenesis due to the high amounts of ROS produced. Holoenzyme activation requires a ternary complex comprised of NOX1, cytochrome B alpha chain (CYBA), and cytoplasmic NADPH Oxidase Organizer 1 (NOXO1) to properly form. By inhibiting this assembly process, an opportunity for reducing the production of catalytic ROS is possible, especially during high ROS conditions that occur under prolonged UV exposure. We designed a series of small mols. and evaluated their inhibitory effects on NOXO2 using in-silico docking methods in the 1WLP crystal structure. We show that the NOX_inh_5 inhibitor was successful in a variety of experiments using primary skin models from various skin tones. NOX_inh_5 proved to be non-cytotoxic while also improving the viability of primary human skin primary cells under UV exposure. Biophys. studies with NOX_inh_5 using an Isothermal calorimetric (ITC) binding and heteronuclear single quantum coherence (HSQC-NMR) exhibited inhibition of complex formation between NOXO2 and CYBA. Authentic human skin explants, treated with and without NOX_inh_5 and UV exposure, decreased p53 stabilization and decreased UV-induced DNA damage as quantified through cyclobutane dimer formation.
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Keywords: Reactive oxygen species ; Apocynin ; UV ; Melanoma ; Sunscreen ; NOXO1 ; CYBA
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CAS No. : | 583-55-1 |
Formula : | C6H4BrI |
M.W : | 282.90 |
SMILES Code : | IC1=CC=CC=C1Br |
MDL No. : | MFCD00001030 |
InChI Key : | OIRHKGBNGGSCGS-UHFFFAOYSA-N |
Pubchem ID : | 11415 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.86 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.69 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.95 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.47 |
Solubility | 0.0095 mg/ml ; 0.0000336 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.38 |
Solubility | 0.118 mg/ml ; 0.000417 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.2 |
Solubility | 0.0181 mg/ml ; 0.0000638 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.41 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.29 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 12h;Inert atmosphere; Reflux; | 20 g (119.61 mmol) of carbazole, 67.68 g (239.22 mmol) of 2-bromoidobenzene, 11.40 g (59.81 mmol) of copper iodide, and 33.06 g (239.22 mmol) of potassium carbonate were dissolved in xylene in a nitrogen atmosphere, and the mixture was refluxed while stirring. After 12 hours, the mixture was cooled to room temperature, distilled water was added thereto, and the mixture was subjected to extraction using methyl chloride (MC), dried using magnesium sulfate, and distilled under reduced pressure. The resultant was separation-purified using column chromatography to obtain 32.64 g (101.67 mmol, 85% yield) of Intermediate 1-1. |
56% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; for 48h;Inert atmosphere; Reflux; | (1) In the reaction flask carbazole 3.0g, o-bromo-iodobenzene 10.15g, 2.39 g copper iodide, 4.95g of potassium carbonate and 40mL of dry xylene, the reaction was refluxed for 48 hours nitrogen, was added 50mL of water quench off the reaction, extracted with dichloromethane, the solvent was evaporated, purified by column chromatography, a white precipitate was finally obtained 9- (2-bromophenyl) -9H- carbazole 2.5g, 56% yield. |
47% | With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 48h; | Carbazole (1 eq) and o-bromoiodobenzene (3 eq) cuprous iodide (0.05 eq); 11 g potassium carbonate (4 eq) was added to a three-neck bottle.Add anhydrous N,N-dimethylformamide (DMF) and react at 140 C for 48 h.After the reaction was completed, the reaction system was poured into water to precipitate a large amount of solid, and the solid was dissolved in dichloromethane, and the mixture was applied to a white solid (47%); |
29% | With tri-tert-butyl phosphine; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In toluene; at 100℃; for 20h;Inert atmosphere; Reflux; | Sigma aldrich in nitrogen (http://www. Sigmaaldrich. Com /) carbazole yarn (50 g, 299. 0 mmol) of toluene 0. 5 L senses a rotation velocity of the disk to, herein 1-bromo-2-iodobenzene sigma aldrich yarn (101. 5 g, 358. 8 mmol), bis (dibenzylideneacetone) palladium (0) (5. 16 g, 8. 97 mmol), tris-tert butylphosphine (3. 02 g, 15. 0 mmol) and sodium tert-butoxide (34. 5 g, 358. 8 mmol) in 100 C sequentially and at the reflux by heating at a 20. Complete after reaction solution at a water doesn't have any error frames, then dichloromethane (DCM) extraction of water to the MgSO4 anhydride after triggers number, filter and was, concentrating it under reduced pressure. Thus-obtained residue number intermediate that is forward separated into flash column chromatography I-3 (27. 9 g, 29%) a obtained. |
25% | With potassium carbonate;copper(l) iodide; In xylene;Heating / reflux; | Carbazole (1.672 g, 10 mmol), l-bromo-2-iodobenzene (1.5 ml, 12 mmol), potassium carbonate (K CO , 2.7646 g, 20 mmol), copper iodide (CuI, 95 mg, 0.5 mmol), and 25 ml of xylene were refluxed in a nitrogen atmosphere. After cooling to normal temperature was conducted, a product was extracted with ethyl acetate, water was removed with anhydrous magnesium sulfate (MgSO ), and the solvent was removed at a reduced pressure. The resulting product was passed through a silica gel column using a hexane solvent to produce a compound, the solvent was removed at a reduced pressure, and vacuum drying was conducted to produce the resulting white solid compound of Formula a (800 mg, yield 25%).[123] MS: [M+H]+ = 323. |
25% | With potassium carbonate;copper(l) iodide; In xylene;Reflux; Inert atmosphere; | Preparation Example 1Preparation of Starting Material Represented by Formula aCarbazole (1.672 g, 10 mmol), 1-bromo-2-iodobenzene (1.5 ml, 12 mmol), potassium carbonate (K2CO3, 2.7646 g, 20 mmol), copper iodide (Cud, 95 mg, 0.5 mmol), and 25 ml of xylene were refluxed in a nitrogen atmosphere. After cooling to normal temperature was conducted, a product was extracted with ethyl acetate, water was removed with anhydrous magnesium sulfate (MgSO4), and the solvent was removed at a reduced pressure. The resulting product was passed through a silica gel column using a hexane solvent to produce a compound, the solvent was removed at a reduced pressure, and vacuum drying was conducted to produce the resulting white solid compound of Formula a (800 mg, yield 25%).MS: [M+H]+=323. |
25% | With potassium carbonate;copper(l) iodide; In xylene;Reflux; Inert atmosphere; | Preparation Example 1Preparation of Starting Material Represented by Formula aCarbazole (1.672 g, 10 mmol), 1-bromo-2-iodobenzene (1.5 ml, 12 mmol), potassium carbonate (K2CO3.2.7646 g, 20 mmol), copper iodide (CuI, 95 mg, 0.5 mmol), and 25 ml of xylene were refluxed in a nitrogen atmosphere. After cooling to normal temperature was conducted, a product was extracted with ethyl acetate, water was removed with anhydrous magnesium sulfate (MgSO4), and the solvent was removed at a reduced pressure. The resulting product was passed through a silica gel column using a hexane solvent to produce a compound, the solvent was removed at a reduced pressure, and vacuum drying was conducted to produce the desired white solid compound (800 mg, yield 25%).MS: [M+H]+=323. |
25% | With copper(l) iodide; potassium carbonate; In N,N-dimethyl acetamide; at 130℃; for 48h;Inert atmosphere; | General procedure: A mixture of carbazole(1.67 g, 10 mmol), 2-bromoiodobenzene (4.2 g, 15 mmol), K2CO3 (2.76 g, 20 mmol), CuI (0.95 g, 5 mmol) and DMA (100 mL) in a 250 mL three-necked flask was heated at 130 C for 48 h under nitrogen. After cooling, it was poured into water (200 mL) and extracted with CH2Cl2, the combined organic phase was washed with water and dried over MgSO4. After workup, the crude product was isolated by column chromatography (PE) to afford white powder (1.5 g, 25 %); Rf = 0.26 (PE); M. p.: 110 - 112 C; 1H NMR (CDCl3, 500 MHz) delta: 8.17(d, J = 7.7 Hz, 2H), 7.88 (d, J = 8.0 Hz, 1H), 7.52 (m, 2H), 7.43 (m, 3H), 7.31 (t, J = 7.33 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H); 13C NMR (CDCl3, 125 MHz) delta: 140.84, 136.77, 134.23, 131.13, 130.14, 128.80, 125.92, 123.85, 123.25, 120.33, 119.98, 110.01. |
25.5% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; at 120℃; | Carbazole (7.39 g, 0.0442 mol), 1-bromo-2-iodobenzene (25 g, 0.0883 mol), CuI (0.421 g, 2.22 mmol), K2CO3 (12.12 g, 0.0883 mol) in a 500 mL 2-neck flask Mol) were dissolved in xylene and refluxed and stirred at 120 C. The mixture was cooled to room temperature, extracted with CH2Cl2, dried over MgSO4, and then the solvent was removed. Hexane solvent to obtain 3.63 g (25.5%) of a white solid. |
25% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Inert atmosphere; Reflux; | Under nitrogen atmosphere, a mixture of carbazole (1.7 g), 1-bromo-2-iodobenzene (1.5 ml), potassium carbonate (2.8 g), copper iodide (95 mg), and xylene (25 ml) was refluxed. After cooling to ordinary temperature, the reaction product was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then, the solvent was removed under reduced pressure. The residue was passed through a silica gel column by using a hexane solvent, and then, the solvent was removed under reduced pressure. The obtained residue was vacuum-dried to obtain the intermediate a as a white solid (800 mg, 25% yield). MS: [M+H]+=323 |
25% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Inert atmosphere; Reflux; | Under nitrogen atmosphere, a mixture of carbazole (1.7 g), 1-bromo-2-iodobenzene (1.5 ml), potassium carbonate (2.8 g), copper iodide (95 mg), and xylene (25 ml) was refluxed. After cooling to ordinary temperature, the reaction product was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and then, the solvent was removed under reduced pressure. The residue was passed through a silica gel column by using a hexane solvent, and then, the solvent was removed under reduced pressure. The obtained residue was vacuum-dried to obtain the intermediate a as a white solid (800 mg, 25% yield). MS: [M+H]+=323 |
25% | With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Reflux; Inert atmosphere; | Carbazole (1.7 g),1-bromo-2-iodobenzene (1.5 ml),Potassium carbonate (2.8 g),Copper iodide (95 mg) and xylene (25 ml) were refluxed under an atmosphere of nitrogen.After cooling to normal temperature, the product was extracted with ethyl acetate.After drying the extract with anhydrous magnesium sulfate,The solvent was removed under reduced pressure.Passed through a silica gel column using a hexane solvent, the solvent was removed under reduced pressure,The obtained residue was dried under vacuum to obtain an intermediate a (800 mg, 25% yield) as a white solid. |
With copper(l) iodide; potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene;Reflux; Inert atmosphere; | 1.672 g of carbazole, 1.6 mL of 1-bromo-2-iodobenzene, 2.7646 g potassium carbonate, 95 mg of copper iodide, and 25 mL of xylene were refluxed in a nitrogen atmosphere. The mixture was cooled to room temperature, extracted with ethyl acetate, and dried with anhydrous magnesium sulfate to remove moisture, and the solvent was removed under reduced pressure. Silica gel column separation using a hexane solvent was conducted, thus obtaining a compound from which the solvent was then removed under reduced pressure, followed by vacuum drying, yielding 9-(2-bromophenyl)-9H-carbazole as a desired white solid intermediate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 48h;Inert atmosphere; | General procedure: To an oven-dry ground test tube equipped with a stir bar were added 1 mmol 2-bromoiodobenzene, 1mmolL-alaninamide, 3 mmol potassium carbonate and 5 mL DMF. The test tube was sealed with a rubber stopperand was evacuated and refilled with argon for three times. Then the test tube was stirred in an oil bathpreheated at 90? C for 48 hours. After the test tube was cooled to room temperature, the reaction wasquenched with water, and the reaction mixture was extracted with 20 mL ethyl acetate for three times. Thecombined organic layer was washed with 10 mL water and then saturated sodium chloride aqueous solution,and dried over anhydrous sodium sulfate. After filtration, the filtrate was condensed on a rotary evaporator invacuum. The resulting crude product was chromatographed on silica gel (300-400 mesh) with a 1:2 volumeratio mixed solution of ethyl acetate and petroleum ether as eluent to give a white solid L-N-phenylalaninamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With copper; potassium carbonate; In neat (no solvent); at 200℃; for 12h; | 9H-carbazole (9.8 g, 58.9 mmol) and 1-bromo-2-iodobenzene (50 g, 177 mmol) were mixed with copper (0.94 g, 14.7 mmol) and potassium carbonate (16.3 g, 118 mmol) and the slurry was heated to 200 °C for 12 hours. After cooling to room temperature, the reaction was filtered through celite, washing with DCM. The DCM was removed under reduced pressure and the excess 1-bromo-2-iodobenzene was removed by Kugelrohr distillation. The residue was then chromatographed on silica with 0-3percent DCM in hetane and recrystallized from heptane to yield 14.4 g of a mixture of 9-(2-bromophenyl)-9H-carbazole (?60percent) and 9-(2-iodophenyl)-9H-carbazole (?40percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; at 80℃; for 53h;Inert atmosphere; | In the nitrogen ambient, after the compound I-1100 g (282 mmol) was melted in the tetrahydrofuran (THF) 1 L here 1- bromo -2-iodobenzene (1-bromo-2-iodobenzene) 95.9 g (339 mmol) and tetrakis(triphenylphosphine) palladium (tetrakis(triphenylphosphine)palladium) 3.26 g(2.82 mmol) were put and it mixed. The saturated potassium carbonate 97.4 g(705 mmol) was put in water and it heated up in 80 for 53 hours and it refluxed. After water was put in into the reaction solutionafter the reaction completion and it extracted in the dichloromethane (DCM)moisture was removed to the anhydrous MgSO4 it filtered and it was concentratedunder reduced pressure. The residue obtained in this way was refined to theflash column chromatography after dividing and the compound I-4 95.1 g (88 %)was obtained |
88% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 80℃; for 53h;Inert atmosphere; | The compound I-1 100 g (282 mmol) in tetrahydrofuran (THF) in a nitrogen environment, was dissolved in 1 L, where the 1-bromo-2-iodo-benzene (1-bromo-2-iodobenzene) 95.9 g (339 mmol) and was stirred into the tetrakis (triphenylphosphine) palladium (tetrakis (triphenylphosphine) palladium) 3.26 g (2.82 mmol).Into a potassium carbonate 97.4 g (705 mmol) in saturated water it was heated to reflux for 53 hours at 80 .After the reaction was completed, the reaction solution into water, extracted with dichloromethane (DCM) and then water was removed with anhydrous MgSO4, filter and was concentrated under reduced pressure.Thus the resulting residue was separated and purified by flash column chromatography to give the compound I-4 95.1 g (88%). |
88% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 53h;Inert atmosphere; Reflux; | in a nitrogen environment,100 g (282 mmol) of compound I-1 was dissolved in 1 L of tetrahydrofuran (THF)95.9 g (339 mmol) of 1-bromo-2-iodobenzene (Sigma-Aldrich Co., Ltd.) and 3.26 g (2.82 mmol) of tetrakistriphenylphosphine palladium were added thereto,And the mixture was stirred.To this was added a saturated aqueous solution of potassium carbonate 97.4 g (705 mmol)The mixture was heated and allowed to reflux for 53 hours at 80 C.When the reaction is complete,Water was added to the reaction solution,And the mixture was extracted with dichloromethane (DCM)Followed by removal of water with anhydrous MgSO4 filtered,And concentrated under reduced pressure.The residue obtained is isolated and purified by column chromatography,95.1 g (88%) of compound I-4 was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Under nitrogen protection, 50.0 mmol of o-iodobromobenzene was dissolved in 100 mL of dry tetrahydrofuran, cooled to 0 C, 52.0 mL of 1M isopropylmagnesium bromide THF solution was added dropwise, and the reaction was stirred for 1 hour, and 48.0 mmol of The solution of 9H-tribenzo[a,c,e][7]cyclorotaxene-9-one (CAS:68089-73-6) dissolved in THF was raised to room temperature and stirred for 2 hours, and 50 mL of 2N diluted The aqueous hydrochloric acid solution was extracted with ethyl acetate, the organic phase was collected, dried, filtered, and the filtrate was concentrated to dryness under reduced pressure, and was separated and purified with a silica gel column to obtain the intermediate Int.-1 with a yield of 94%. | |
94% | Under nitrogen protection, 50.0 mmol of o-iodobromobenzene was dissolved in 100 mL of dry tetrahydrofuran, cooled to 0 C, 52.0 mL of 1M isopropylmagnesium bromide THF solution was added dropwise, and the reaction was stirred for 1 hour, and 48.0 mmol of The solution of 9H-tribenzo[a,c,e][7]cyclorotaxene-9-one (CAS:68089-73-6) dissolved in THF was raised to room temperature and stirred for 2 hours, and 50 mL of 2N diluted The aqueous hydrochloric acid solution was extracted with ethyl acetate, the organic phase was collected, dried, filtered, and the filtrate was concentrated to dryness under reduced pressure, and was separated and purified with a silica gel column to obtain the intermediate Int.-1 with a yield of 94%. |
Tags: 583-55-1 synthesis path| 583-55-1 SDS| 583-55-1 COA| 583-55-1 purity| 583-55-1 application| 583-55-1 NMR| 583-55-1 COA| 583-55-1 structure
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P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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