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Evaluation of Pyrazinamide and Pyrazinoic Acid Analogues for Control of Key Weeds in Multiple Crops
Gregory R. Armel ; James T. Brosnan ; Nilda R. Burgos ; Peter J. Porpiglia ; Jose J. Vargas ;
Abstract: Numerous similarities exist between the structure–activity relationships of pharmaceutical drugs and pesticides, creating the potential for finding new crop management tools with novel mechanisms of action. Analogues of pyrazinamide and its active metabolite pyrazinoic acid were evaluated on a variety of monocot and dicot species to assess their potential as commercial herbicides. Six analogues, applied postemergence at 3 kg ai/ha, controlled yellow nutsedge (Cyperus esculentus) ≥ the commercial standards bentazon or imazethapyr. The compound 5-fluoropyrazine-2-carboxylic acid provided between 71 and 95% control of barnyardgrass (Echinochloa crus-galli) and yellow nutsedge with only modest injury (8–25%) to soybean (Glycine max). A similar compound containing a bromine atom in the 5-position controlled yellow nutsedge greater than bentazon and affected soybean, sweet corn (Zea mays convar. saccharata var. rugosa), and rice (Oryza sativa) in a similar fashion to bentazon as well. The herbicidal sites of action targeted by these analogues of pyrazinamide and pyrazinoic acid are unknown, but it is hypothesized that they may be disrupting targets in the biosynthesis pathways of nicotinamide adenine dinucleotide (NAD) and/or ethylene.
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Keywords: herbicide ; rice ; pyrazinamide ; pharmaceutical ; prodrug ; soybean ; sweet corn
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Purchased from AmBeed: 23688-89-3 ; 86873-60-1 ; 54013-04-6 ; 374068-01-6 ; 40155-43-9 ; 36070-80-1 ; 40155-42-8 ; 312736-49-5 ; 356783-15-8 ; 34604-60-9 ; 27398-39-6 ; 21279-64-1 ; 38275-61-5 ; 1211533-09-3 ; 876161-05-6 ; 5326-23-8 ; 1174321-06-2 ; 5096-73-1 ; 1060814-50-7 ; 1211584-50-7
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CAS No. : | 5326-23-8 |
Formula : | C6H4ClNO2 |
M.W : | 157.55 |
SMILES Code : | O=C(O)C1=CN=C(Cl)C=C1 |
MDL No. : | MFCD00006241 |
InChI Key : | UAWMVMPAYRWUFX-UHFFFAOYSA-N |
Pubchem ID : | 79222 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
With sodium hydrogen sulfate; hydrogen iodide; | 6-Iodonicotinic acid (Compound B) To 27.97 g (186.6 mmol) of sodium iodide cooled to -78 C. was added 121.77 g (71.6 ml, 952.0 mmol) of hydriodic acid (in 57 wt % aqueous solution). The reaction mixture was allowed to warm slightly with stirring for 5 minutes, and then 30 g (190.4 mmol) of 6-chloronicotinic acid was added. The resulting mixture was allowed to warm to room temperature with stirring and then heated at 120-125 C. in an oil bath for 42 hours. A dark brown layer formed above the yellow solid material. The reaction mixture was allowed to cool to room temperature and then poured into acetone (chilled to 0 C.). The resultant yellow solid was collected by filtration, washed with 200 ml of 1N NaHSO3 solution, and dried in vacuum (3 mm Hg) to give the title compound as a pale yellow solid. PMR (DMSO-d6): d 7.90 (1H, dd, J=8.1, 2 Hz), 7.99 (1H, d, J=8.1 Hz), 8.80 (1H, d, J=2 Hz). | |
With sodium hydrogen sulfate; hydrogen iodide; | 6-Iodonicotinic acid To 27.97 g (186.6 mmol) of sodium iodide cooled to -78 C. was added 121.77 g (71.6 ml, 952.0 mmol) of hydriodic acid (57 wt %). The reaction mixture was allowed to warm slightly with stirring for 5 minutes, and then 30.00 g (190.4 mmol) of 6-chloronicotinic acid was added. The resulting mixture was allowed to warm to room temperature with stirring and then heated at 120-125 C. in an oil bath for 42 hours. A dark brown layer formed above the yellow solid material. The reaction mixture was allowed to cool to room temperature and then poured into acetone (chilled to 0 C.). The resultant yellow solid was collected by filtration, washed with 200 ml of 1N NaHSO3 solution, and dried in high vacuum (3 mm Hg) to give the title compound as a pale yellow solid. PMR (DMSO-d6): δ 7.90 (1H, dd, J=8.1, 2 Hz), 7.99 (1H, d, J=8.1 Hz), 8.80 (1H, d, J=2.Hz). | |
With sodium hydrogen sulfate; hydrogen iodide; | 6-Iodonicotinic acid To 27.97 g (186.6 mmol) of sodium iodide cooled to -78 C. was added 121.77 g (71.6 ml, 952.0 mmol) of hydriodic acid (in 57 wt % aqueous solution). The reaction mixture was allowed to warm slightly with stirring for 5 minutes, and then 30.00 g (190.4 mmol) of 6-chloronicotinic acid was added. The resulting mixture was allowed to warm to room temperature with stirring and then heated at 120-125 C. in an oil bath for 42 hours. A dark brown layer formed above the yellow solid material. The reaction mixture was allowed to cool to room temperature and then poured into acetone (chilled to 0 C.). The resultant yellow solid was collected by filtration, washed with 200 ml of 1N NaHSO3 solution, and dried in vacuum (3 mm Hg) to give the title compound as a pale yellow solid. PMR (DMSO-d6): d 7.90 (1H, dd, J=8.1, 2 Hz), 7.99 (1H, d, J=8.1 Hz), 8.80 (1H, d, J=2 Hz). |
With hydrogen iodide; sodium iodide; at 100 - 130℃; for 40.0h;Heating / reflux; | A mixture of 15.962 g ((0.106 mol) of sodium iodide in 51 g (30 ml, 40 mmol) of hydriodic acid were stirred for 5 minutes. To the mixture was added 17.184 g (0.109 mol) of 6-chloro-nicotinic acid and the resulting mixture refluxed at 100-130 C. for 40 hours. The dark brown mixture was then taken up in 300 ml of acetone and stirred to dissolve the excess NaI. The product was collected by suction filtration, rinsed with 100 mL in 1N NaHSO3 and dried to give the title compound as a yellow solid. PMR (DMSO-d6): δ 3.36 (1H, s), 7.89 (1H, dd, J=2.5, 8.2 Hz), 8.00 (1H, d, J=7.5 Hz), 8.79 (1H, d, J=2.4 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; borane; In tetrahydrofuran; | EXAMPLE 1 6-Chloronicotinic acid (3.0 g, 18.98 mmol) is dissolved in 30 ml of tetrahydrofuran (THF), with the temperature of the solution maintained below 30. A 1 M solution of borane/TMF (19 ml, 19.0 mmol) is added at a rate to maintain a slow evolution of gas. This mixture is stirred at RT overnight. The reaction is poured onto approximately 50 g ice with 2 ml concentrated hydrochloric acid and is stirred for 1 hour. The pH of the reaction is adjusted to 5. The reaction is then extracted with chloroform, washed with water, dried and stripped to give 6-chloro-3-pyridinemethanol. | |
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 4h;Reflux; | 2-Ch-oropyridinyI-4-mcthylcncdicthylphbsphonatc. 2-Chloronicotinic acid (3.00 g, 19.0 mmol) was dissolved in dry THF (60 mL) and cooled to 0C. Lithium aluminiumhydride (870 mg, 23.0 mmol) was charged into the stirred reaction (CAUTION: gas evolution) followed by gradual warming to reflux for 4 hours. The reaction was quenched with sequential addition of wet THF (5 mL) and water (50 ml.., cautiously) before filtration through celite and removal of volatilcs in vacuo gave yellow oil that was purified by flash chromatography (Si02, CH2CI2 followed by F,t()Ac). The crystalline alcohol was dissolved in CH2C12 (20 mL) and excess thionylchloride (5-10 mL) before refluxing for 1 hour. On cooling to room temperature, volatiles were removed in vacuo and the residue was neutralised with sat. NallCO before extraction with CH2CI2 (3 x 40 mL). Organics were combined, dried over MgSO^, filtered and concentrated to 3-5 mL before purification through a silica plug (eluting with CH2CI2). Removal of volatiles in vacuo gave yellow oil as the desired 2-chloropyridyl-5-methylcnechloride. The alky chloride was dissolved in triethylphosphite ( 10 mL) and heated to 140C for 2 hours. On cooling to room temperature, volatiles were removed in vacuo and the residue purified by flash chromatography (Si02, CFLC^ followed by EtOAc) to give a light yellow oil (). NMR (500 MHz; CDCI3): S/ppm 8.28-8.26 (m, I II, Vy-H), 7.64 (dl. 1 H, 3./„„ - 8.2, 4Jm = 2.5, Py-//), 7.28 (d, 1 H, 3J,„i - 8.2, Py-H), 4.09-4.02 (m, 4H, 0-C//j), 3.09 (d, 211. 3JHi> = 21.6, 0=?-C/), 1.28- 1.25 (m, 6H, C//3). ,3C{ 'H} NMR (125.7 MHz; CDCIj): S/ppm 150.4 (d, 3Jci> = 7.7, PyCH), 150.3 (d, FontWeight="Bold" FontSize="10" JCP = 4, PyC-Cl), 140.0 (d, 3JCl> - 5.5, PyCH), 127.1 (d, 2Ja> = 9, PyQ, 124.2 (d, VCI> - 2.9, PyCH), 62.6 (d, 2,/a> = 6.8, 0-CH2), 30.5 (d, 'Jcp = 140,0, O-P-CHz), 16.5 (d, = 5.9, CH2-CH3). Λ ,Ρ{} NMR (202.5 MHz; CDCh): S/ppm 24.8 (s, 0=P) | |
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 3h; | To a solution of LiAIH4 (25 g, 0.65 mol) in THF (1500 ml) was added a solution of 6- chloropyridine-3-carboxylic acid (50 g, 0.323 mol) in THF drop-wise at 0C, and the mixture was stirred for 3h at 0C. THF and Na2S04 x 5H2O was added slowly. After stirring for 20 min, the mixture was filtered and the filtrate was concentrated to give crude product (26 g, yield: 57.1 %). |
0.55 g | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 30℃; for 3h;Inert atmosphere; | To a solution of methyl 6-chloronicotinate (1.08 g, 0.009 mole) in THF (30 mL) at 0 C under N2, was added lithium aluminum hydride (1 M in THF, 7.5 mL, 0.0075 mole) drop wise. Reaction mixture was warmed to RT and stirred for 3 hours. The reaction mixture was cooled to 0 C, diluted with ethyl acetate and treated with water (2 mL). The mixture was filtered through celite bed and concentrated under vacuum to obtain the crude compound which was further purified by flash chromatography using ethyl acetate: n-hexane (40: 60) to afford 2-chloro-5-hydroxymethylpyridine. Yield: 0.55 g; lH - NMR (CDC13, 400 MHz) δ ppm: 2.09 (bs, 1H), 4.72 (s, 2H), 7.31 - 7.34 (d, J = 8.1 Hz, 1H), 7.68 - 7.71 (dd, J = 2.2, 8.4 Hz, 1H), 8.36 (s, 1H); Mass (m/z): 144.1, 146.0 (M+H)+. |
615 mg (75%) | With BH3; In tetrahydrofuran; ethyl acetate; | 9-Chloro-5-{3-[2-(6-chloropyridin-3-yl)-2-hydroxyethylamino]cyclohexyl}-3-methyl-5H-isoxazolo[4,3-c]quinolin4one To a stirred solution of 6-chloronicotinic acid (900 mg, 5.7 mmol) in THF (7 mL) was added BH3 (16 mL, 17.1 mmol, 1M in THF) under N2 atmosphere. The reaction mixture was stirred for 5 h. It was quenched with methanol (5 mL) and then concentrated. The crude was dissolved in EtOAc (30 mL), washed with 1N NaOH (15 mL*3), brine, dried and concentrated. Yield: 615 mg (75%) of 6-chloro-pyridin-3-yl-methanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 46 N-t-Butyl-6-chloro-3-pyridinecarboxamide The title compound was prepared by the same method as that described in Example 26, using 6-chloronicotinic acid and t-butylamine. 1H-NMR(270 MHz, CDCl3) 8.67 (d, J=2.6 Hz, 1H), 8.03 (dd, J=8.3, 2.6 Hz, 1H), 7.39 (dd, J=8.3, 0.7 Hz, 1H), 5.88 (br, 1H), 1.48 (s, 9H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium iodide; | 6-iodonicotinic acid Sodium iodide (20.59 g, 137.40 mmol) was cooled to -78 C. under argon and then hydriodic acid (97.13 g, 759.34 mmol) was added. The cooling bath was removed and the suspension was stirred for 5 minutes. To this mixture was added 6-chloronicotinic acid (22.09 g, 140.20 mmol) and the resulting mixture was slowly warmed to ambient temperature with stirring. The mixture was heated to reflux at 125 C. for 24 hours, cooled to ambient temperature and poured into acetone (500 ml) at 0 C. The yellow solid was collected by filtration and washed with 200 ml of 1N aqueous NaHSO3 solution. Recrystallization from methanol (crystals were washed with ethyl ether) afforded the title compound as white crystals: mp 177-179 C. ›lit. mp 187-192, Newkome et al. "Reductive Dehalogenation of Electron-Poor Heterocycles: Nicotinic Acid Derivatives" J. Org. Chem. 51: 953-954 (1986). 1H NMR (DMSO-d6): δ 8.81 (1H, dd, J=0.8, 2.4 Hz), 8.01 (1H, dd, J=0.8, 8.2 Hz), 7.91 (1H, dd, J=2.4, 8.2 Hz). | |
With sodium iodide; | 6-iodonicotinic acid Sodium iodide (20.59 g, 137.40 mmol) was cooled to -78 C. under argon and then hydriodic acid (97.13 g, 759.34 mmol) was added. The cooling bath was removed and the suspension was stirred for 5 minutes. To this mixture was added 6-chloronicotinic acid (22.09 g, 140.20 mmol) and the resulting mixture was slowly warmed to ambient temperature with stirring. The mixture was heated to reflux at 125 C. for 24 hours, cooled to ambient temperature and poured into acetone (500 ml) at 0 C. The yellow solid was collected by filtration and washed with 200 ml of 1N aqueous NaHSO3 solution. Recrystallization from methanol (crystals were washed with ethyl ether) afforded the title compound as white crystals: mp 177-179 C. ›lit. mp 187-192, Newkome et al. "Reductive Dehalogenation of Electron-Poor Heterocycles: Nicotinic Acid Derivatives" J. Org. Chem. 51: 953-954 (1986). 1H NMR (DMSO-d6): δ 8.81 (1H, dd, J=0.8, 2.4 Hz), 8.01 (1H, dd, J=0.8, 8.2 Hz), 7.91 (1H, dd, J=2.4, 8.2 Hz). | |
With hydrogen iodide; | 6-Iodonicotinic acid (Compound B) To 27.97 g (186.6 mmol) of sodium iodide cooled to -78 C. was added 121.77 g (71.6 ml, 952.0 mmol) of hydriodic acid (in 57 wt % aqueous solution). The reaction mixture was allowed to warm slightly with stirring for 5 minutes and then 30.00 g (190.4 mmol) of 6-chloronicotinic acid was added. The resulting mixture was allowed to warm to room temperature with stirring and then heated at 120-125 C. in an oil bath for 42 hours. A dark brown layer formed above the yellow solid material. The reaction mixture was allowed to cool to room temperature and then poured into acetone (chilled to 0 C.). The resultant yellow solid was collected by filtration, washed with 200 ml of 1 N aqueous NaHSO3 solution, and dried in vacuum (3 mm Hg) to give the title compound as a pale yellow solid. PMR (DMSO-d6):d 7.90 (1H, dd, J=8.1, 2 Hz), 7.99 (1H, d, J=8.1 Hz), 8.80 (1H, d, J=2 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogen sulfate; | 6-Iodonicotinic acid To 27.97 g (186.6 mmol) of sodium iodide cooled to -78 C. was added 121.77 g (71.6 ml, 952.0 mmol) of hydroiodic acid (57 wt %). The reaction mixture was allowed to warm slightly with stirring for 5 minutes, and then 30.00 g (190.4 mmol) of 6-chloronicotinic acid was added. The resulting mixture was allowed to warm to room temperature with stirring and then heated at 120-125 C. in an oil bath for 42 hours. A dark brown layer formed above the yellow solid material. The reaction mixture was allowed to cool to room temperature and then poured into acetone (chilled to 0 C.). The resultant yellow solid was collected by filtration, washed with 200 ml of 1N NaHSO3 solution, and dried in high vacuum (3 mmHg) to give the title compound as a pale yellow solid. PMR (DMSO-D6): δ 7.90 (1H, dd, J=8.1, 2 Hz), 7.99 (1H, d, J=8.1 Hz), 8.80 (1H, d, J=2.Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.6%; 41.3% | With lithium hydroxide; In ethanol; water; at 21 - 32℃; for 0.00555556h;Sonication; | To a mixture of 6-chloro-pyridine-3-carbaldehyde (0.46 g, 3.2 mmol), and lithium hydroxide (0.08 g, 3.2 mmol), in a 10 mL of a solution of ethanol in water (1/1), at room temperature, was applied an ultrasonic agitation for 20 seconds (amplitude = 0.3; ti = 21C, tf = 32C; E = 709 J). The solvents were evaporated under reduced pressure and the resulting mixture was solved in CH2Cl2 and washed with water. The organic layer was collected and dried under reduced pressure to obtain 6 (0.19 g, 1.3 mmol, 41.3% yield) as a yellow oil that crystalizes within 10 minutes to become a yellow solid, with the same physicochemical properties as in the literature.11 The aqueous layer was evaporated under reduced pressure to obtain a white powder containing 6 (20%) and 7. The powder was washed with EtOAc and filtered to provide 7 (0.22 g, 1.4 mmol, 43.6% yield) as a white powder, with the same physicochemical properties as in the literature.12 6: mp 46-49 C (CH2Cl2); Rf (CH2Cl2:MeOH = 99:1) = 0.6; 1H NMR (CDCl3, 400 MHz) δ ppm 1.80 (t, J = 5.7 Hz, 1H, CH2OH), 4.74 (d, J = 5.7 Hz, 2H, CH2OH), 7.34 (d, J = 8.0 Hz, 1H, ArH), 7.70 (dd, J = 8.0, 2.4 Hz, 1H, ArH), 8.38 (d, J = 2.4 Hz, 1H, ArH); 13C NMR (CDCl3, 100 MHz) δ ppm 61.7 (CH2), 124.2 (CH), 135.3 (C), 137.8 (CH), 148.1 (CH), 150.4 (C); IR ν (cm-1): 3290, 1569, 1453, 1101, 819. |
Tags: 6-Chloropyridine-3-carboxylic acid | Pyridines | Chlorides | Insecticide | Organic Building Blocks | Heterocyclic Building Blocks | Pesticide Composition | Other Inhibitors/Agonists | 5326-23-8
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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 |
Sorry,this product has been discontinued.
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