Structure of Acetylcysteine
CAS No.: 616-91-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Acetylcysteine is an inhibitor of ROS and the production of TNF. It is a pharmaceutical drug and nutritional supplement used as mucolytic agent.
Synonyms: NAC; N-Acetylcysteine; N-Acetyl-L-cysteine
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Arsenic trioxide-based nanoparticles for enhance chemotherapy by activating pyroptosis
Wang, Shengmei ; Ma, Ding ; Yang, Minghua ; Zhang, Ye ; Wang, Shengfeng ; Zhou, Wenhu
Abstract: Chemotherapy remains a primary treatment option for hepatocellular carcinoma (HCC), yet its clinical benefits are often unsatisfactory. Utilizing arsenic trioxide (ATO) as a model, this study elucidates the role of autophagy inhibition in modulating the cellular response to chemotherapy, shifting cell death from apoptosis to pyroptosis via the caspase-3–GSDME pathway, thereby augmenting the anti-tumor efficacy. Building upon these findings, an ATO nanomedicine delivery system capable of autophagy inhibition to promote pyroptosis for enhanced tumor treatment was developed. Folic acid-modified albumin served as the stabilizer for nano selfassemblies formed through ion pairing between Mn2+ and ATO, encapsulating DNAzyme (Dz) targeting Beclin 1, a key autophagy regulator. Characterization studies confirmed efficient encapsulation of ATO and Dz within nanoparticles, designed to disintegrate in the intracellular microenvironment, releasing the all-active components, i.e., ATO, Mn2+, and Dz. Mn2+ acted as a metal cofactor to activate Dz for Beclin 1 mRNA cleavage, inhibiting autophagy and augmenting ATO-induced cell pyroptosis. Elevated cell pyroptosis levels not only enhance ATO’s direct tumor cell killing capacity but also trigger anti-tumor immune responses, synergistically enhancing efficacy. Upon intravenous injection, the nanomedicine accumulated in tumor tissue and targeted liver cancer cells. Compared to free ATO, the nanomedicine exhibited significantly improved in vivo anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.
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Keywords: Nanoparticles ; Cell death ; Chemotherapy ; Targeting ; Tumor immunity ; Drug delivery ; Arsenic trioxide ; Hepatocellular carcinoma
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Li, Chengyu ; Liu, Zhaojun ; Zhu, Linjie ; Wu, Gang ; Fu, Chen ; Li, Hongmin , et al.
Abstract: HMGB1, one of the most abundant nuclear non-histone proteins, also performs extracellular functions, and its nuclear export mechanisms have been extensively studied. Here, a novel mechanism of nuclear export for HMGB1 driven by lactylation is proposed. In addition, it is revealed that hypoxia-induced lactylation of HMGB1 facilitates its nuclear export in a complex with TIAR, promoting stress granule (SG) formation in the cytosol. Mass spectrometry revealed 12 lysine residues in HMGB1 undergoing lactylation, with K172 and K177 being the most susceptible. Functional studies using lysine-to-arginine mutants (K→R) demonstrated that lactylation at K177 is crucial for HMGB1-TIAR complex export, as K177R mutation completely blocked this export and subsequent SG formation. Notably, this lactylation-mediated mechanism is specific to hypoxic stress, while other stressors, such as sodium arsenite exposure and heat shock, triggered TIAR nuclear export and SG assembly independently of HMGB1. These findings reveal a previously unrecognized role of HMGB1 lactylation in mediating nuclear export and SG formation under hypoxia.
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Keywords: HMGB1 ; hypoxic stress granules ; lactylation ; nuclear export ; TIAR
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Ievtukhov, Vladyslav ; Zadykowicz, Beata ; Blazheyevskiy, Mykola Ye. ; Krzyminski, Karol ;
Abstract: Biologically active compounds containing sulfhydryl groups (RSHs: N-acetyl-L-cysteine, D-penicillamine, glutathione and acetylthiocholine chloride) were used to develop a luminometric method for their quantification. The title substrate capable of chemiluminescence (CL) was isolated in a highly pure state as a chloride salt (99.9% using RP-HPLC) and identified using mass spectrometry (ESI Q-TOF) and 1H NMR spectroscopy. The cation included in the salt, 9-CMA+, underwent oxidation in an alk. environment containing RSHs by mol. oxygen, generating CL of various intensities, with no need for the use of hydrogen peroxide. The amount of produced light was linearly proportional to the content of investigated analytes in the system over the concentration range ∼0.2-2μM, with the detection limits in the range 0.19-1.73μM. The mechanism of chemiluminogenic oxidation of 9-CMA+ in the presence of RSHs and mol. oxygen is proposed, using computational methods at the d.-functional theory level. The presence of RSHs in an alk. medium seems to be crucial to produce hydroperoxide anions (-OOH), which initiate the 'light path' of 9-CMA+ transformations, ending with the excretion of electronically excited mols. of 10 methyl-acridan-9-one.
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Keywords: 9-cyano-10-methylacridinium cation ; chemiluminescence analysis ; DFT methods ; MS and NMR spectroscopy ; thiol nucleophiles
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| CAS No. : | 616-91-1 |
| Formula : | C5H9NO3S |
| M.W : | 163.19 |
| SMILES Code : | SC[C@@H](C(O)=O)NC(C)=O |
| Synonyms : |
NAC; N-Acetylcysteine; N-Acetyl-L-cysteine
|
| MDL No. : | MFCD00004880 |
| InChI Key : | PWKSKIMOESPYIA-BYPYZUCNSA-N |
| Pubchem ID : | 12035 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
| Target |
|
In Vitro:
|
Cell Line
|
Concentration | Treated Time | Description | References |
| Neutrophils | 1 mM | 30 min | To assess the effect of NAC on NET formation, results showed that NAC reduced PMA-induced NET formation. | Blood Adv. 2020 Jan 28;4(2):312-321. |
| LS174T | 2.5-40 mM | 72 h | Acetylcysteine significantly inhibited the proliferation of LS174T cells, particularly at higher concentrations. | J Exp Clin Cancer Res. 2014 Nov 12;33(1):92. |
| HT29-5M21 | 1-75 mM | 72 h | Acetylcysteine significantly inhibited the proliferation of HT29-5M21 cells, particularly at higher concentrations. | J Exp Clin Cancer Res. 2014 Nov 12;33(1):92. |
| HT29-5F12 | 1-75 mM | 72 h | Acetylcysteine significantly inhibited the proliferation of HT29-5F12 cells, particularly at higher concentrations. | J Exp Clin Cancer Res. 2014 Nov 12;33(1):92. |
| KATO-III | 1-100 mM | 72 h | Acetylcysteine significantly inhibited the proliferation of KATO-III cells, particularly at higher concentrations. | J Exp Clin Cancer Res. 2014 Nov 12;33(1):92. |
| MKN45 | 1-100 mM | 72 h | Acetylcysteine significantly inhibited the proliferation of MKN45 cells, particularly at higher concentrations. | J Exp Clin Cancer Res. 2014 Nov 12;33(1):92. |
| Panc-1 cells | 1 mM | 72 h | To evaluate the effect of NAC/Cu(II) on Panc-1 cells, it was found that NAC/Cu(II) significantly reduced cell viability. | Cancer Lett. 2010 Dec 8;298(2):186-94. |
| T47D cells | 1 mM | 72 h | To evaluate the effect of NAC/Cu(II) on T47D cells, it was found that NAC/Cu(II) significantly reduced cell viability. | Cancer Lett. 2010 Dec 8;298(2):186-94. |
| MDA-MB-231 cells | 1 mM | 72 h | To evaluate the effect of NAC/Cu(II) on MDA-MB-231 cells, it was found that NAC/Cu(II) significantly reduced cell viability. | Cancer Lett. 2010 Dec 8;298(2):186-94. |
| A2780 cells | 1 mM | 72 h | To evaluate NAC as a potential metal ionophore/shuttle, it was found that NAC is cytotoxic only in the presence of copper and inhibits cell growth by inducing apoptosis. | Cancer Lett. 2010 Dec 8;298(2):186-94. |
| CF sputum | 2.5 mM | 30 min | To compare the mucolytic effects of MUC-031 and NAC, MUC-031 was more effective in reducing the elastic modulus (G′) of sputum and acted faster. MUC-031 induced mucolysis in 69% of sputum samples within 15 min, compared to 25% for NAC. | Eur Respir J. 2023 May 25;61(5):2202022. |
In Vivo:
|
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
| Mice | JAK2V617F knockin mouse model | Oral | 2 g/L | Starting from 4 to 6 weeks of age, replenished weekly, continuous administration. | To investigate the effect of NAC on thrombosis in MPN mice, results showed that NAC extended the lifespan of JAK2V617F mice and reduced thrombus formation. | Blood Adv. 2020 Jan 28;4(2):312-321. |
| Mice | ΒENaC-Tg mice | Intratracheal instillation (adult mice) or intranasal instillation (neonatal mice) | 131 mg/mL | Three times in one day (acute experiment) or twice daily for two weeks (chronic experiment) | To evaluate the mucolytic efficacy of MUC-031 in βENaC-Tg mice. Acute treatment significantly reduced airway mucus plugging and inflammation; chronic treatment sustained these reductions and improved survival. | Eur Respir J. 2023 May 25;61(5):2202022. |
| BALB/c mice | Hind leg muscle model | Diet | 5% | Daily for 14 days | To investigate the effect of dietary NAC on radical-induced structural changes in DNA, results showed that NAC significantly reduced the concentration of 8-OH-Gua and decreased the variance in the oxidative status of DNA. | Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5937-41 |
| Rats and mice | Early-life stress (ELS) model and EAAC1 knockout mice | Intraperitoneal injection | 50 mg/kg and 150 mg/kg | Once daily for 2 days | NAC injection alleviated depressive-like behaviors in NMS model rats and reduced oxidative stress and neuroinflammation. In EAAC1-/- mice, NAC improved depressive-like behaviors but not impulsive behaviors. | Int J Biol Sci. 2024 Oct 7;20(14):5450-5473 |
Clinical Trial:
| NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
| NCT04278898 | Autism Spectrum Disorder | PHASE2 | RECRUITING | 2025-01-27 | Stanford University School of ... More >>Medicine, Stanford, California, 94305, United States Less << |
| NCT06546475 | Psychosis | PHASE4 | NOT_YET_RECRUITING | 2027-07-31 | - |
| NCT01808521 | Purpura, Thrombotic Thrombocyt... More >>openic|TTP Less << | EARLY_PHASE1 | COMPLETED | 2025-07-17 | Puget Sound Blood Center, Seat... More >>tle, Washington, 98104, United States Less << |
| NCT06260566 | Biliary Atresia | PHASE1 | NOT_YET_RECRUITING | 2025-02-27 | - |
| NCT02094625 | Neuroectodermal Tumors, Primit... More >>ive|Liver Neoplasms|Osteosarcoma|Other Childhood Cancers Using Cisplatin-based Regimens Less << | PHASE1 | COMPLETED | 2025-08-21 | Childrens Hospital Los Angeles... More >>, Los Angeles, California, 90027, United States Less << |
| NCT00211653 | Kidney Failure | PHASE1|PHASE2 | COMPLETED | 2025-11-06 | Veterans Affairs Medical Cente... More >>r, Minneapolis, Minnesota, 55417, United States Less << |
| NCT01896492 | PCOS | PHASE4 | COMPLETED | 2025-06-13 | - |
| NCT00396396 | Creatinine Clearance | UNKNOWN | - | Eastern Virginia Medical Schoo... More >>l/Nephrology Associates, Norfolk, Virginia, 23507, United States Less << | |
| NCT02788292 | Adipose Tissue Atrophy|Deformi... More >>ty of Reconstructed Breast|Graft Loss Less << | PHASE4 | WITHDRAWN | 2020-11-16 | - |
| NCT05123365 | Myeloproliferative Neoplasm|MP... More >>N|Essential Thrombocythemia|Polycythemia Vera|Myelofibrosis Less << | PHASE1|PHASE2 | RECRUITING | 2026-11-15 | University of California, Irvi... More >>ne, Irvine, California, 92617, United States|Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, California, 92868, United States Less << |
| NCT05241262 | Mitochondrial Disease | PHASE1 | RECRUITING | 2025-04-25 | Columbia University Irving Med... More >>ical Center, New York, New York, 10032, United States Less << |
| NCT01800526 | Sickle Cell Disease|Sickle Cel... More >>l Anemia Less << | PHASE1|PHASE2 | COMPLETED | 2020-06-30 | University of Washington, Seat... More >>tle, Washington, 98106, United States Less << |
| NCT00542750 | Cannabis Dependence | PHASE1|PHASE2 | COMPLETED | 2025-12-08 | Medical University of South Ca... More >>rolina, Charleston, South Carolina, 29425, United States Less << |
| NCT05081479 | Lymphoma | PHASE1 | RECRUITING | 2025-10-21 | Memorial Sloan Kettering Baski... More >>ng Ridge (Limited Protocol Activities), Basking Ridge, New Jersey, 07920, United States|Memorial Sloan Kettering Monmouth (Limited Protocol Activities), Middletown, New Jersey, 07748, United States|Memorial Sloan Kettering Bergen (Limited Protocol Activities), Montvale, New Jersey, 07645, United States|Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities), Commack, New York, 11725, United States|Memorial Sloan Kettering Westchester (Limited Protocol Activities), Harrison, New York, 10604, United States|Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States|Memorial Sloan Kettering Nassau (Limited Protocol Activities), Uniondale, New York, 11553, United States Less << |
| NCT01424033 | Interstitial Lung Disease|Conn... More >>ective Tissue Disease Less << | PHASE2|PHASE3 | TERMINATED | - | University of Michigan, Ann Ar... More >>bor, Michigan, 48109, United States Less << |
| Bio Calculators | ||||
| Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
|
1 mM 5 mM 10 mM |
6.13mL 1.23mL 0.61mL |
30.64mL 6.13mL 3.06mL |
61.28mL 12.26mL 6.13mL |
|
| Dissolving Methods |
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
|
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Tags: Acetylcysteine | N-Acetylcysteine | N-Acetyl-L-cysteine | NAC | Reactive Oxygen Species | Antioxidant | disulphide breaking agent | glutathione precursor | oxidative stress | LNAC | Acetadote | Mucomyst | glutathione precursor | ROS | antioxidant therapy | mucolytic agent | acetaminophen overdose | reactive oxygen species | intracellular glutathione | mucus viscosity reduction | oxidative stress | 616-91-1
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| P221 | Take any precaution to avoid mixing with combustibles |
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| P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
| P230 | Keep wetted |
| P231 | Handle under inert gas. |
| P232 | Protect from moisture. |
| P233 | Keep container tightly closed. |
| P234 | Keep only in original container. |
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| P240 | Ground/bond container and receiving equipment. |
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| P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
| P262 | Do not get in eyes, on skin, or on clothing. |
| P263 | Avoid contact during pregnancy/while nursing. |
| P264 | Wash hands thoroughly after handling. |
| P265 | Wash skin thouroughly after handling. |
| P270 | Do not eat, drink or smoke when using this product. |
| P271 | Use only outdoors or in a well-ventilated area. |
| P272 | Contaminated work clothing should not be allowed out of the workplace. |
| P273 | Avoid release to the environment. |
| P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
| P281 | Use personal protective equipment as required. |
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Response | |
| Code | Phrase |
| P301 | IF SWALLOWED: |
| P304 | IF INHALED: |
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| P332 | IF SKIN irritation occurs: |
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| P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
| P337 | If eye irritation persists: |
| P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
| P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| 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. |
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| 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 | |
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| P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
| P411 + P235 | Keep cool. |
Disposal | |
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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 |
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Health hazards | |
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| H302 | Harmful if swallowed |
| H303 | May be harmful if swallowed |
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| 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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