3-Nitropropionic acid

119.08

119.08

208-003-0

QY4L0FOX0D

64266

2811

DTXSID1020982

Crystals from chloroform

2915900090

83.12000

-0.08

white to light yellow

1.4±0.1 g/cm3

68-70 °C

222.3°C (rough estimate)

148.4±11.6 °C

1.463

alcohol: 100 mg/mL, may be light yellow

2-8°C

Peritoneal-rat LD50: 68.1 mg/kg; oral-mouse LD50: 67 mg/kg

Combustible; Fire breaks down toxic nitrogen oxide fumes

Water soluble.

Acids, Carboxylic

3-NITROPROPIONIC ACID is incompatible with bases, oxidizing agents and reducing agents. (NTP, 1992)

III

6.1(b)

UN 2811 6.1/PG 3

3

25-36/37/38

26-45

UF6220000

T

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

Stable. Incompatible with strong oxidizing agents, bases, reducing agents.

Missing Phrase - N15.00950417

H301

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

DHEW/NCI; Bioassay of 3-Nitropropionic Acid for Possible Carcinogenicity (1978) Technical Rpt Series No. 52 DHEW Pub No. (NIH) 78-1302

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should keep this material in a tightly closed container under an inert atmosphere, keep it away from oxidizing materials and store it at refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

highly toxic

Systemic administration of 3-nitropropionic acid (3-NPA, a mycotoxin) induces brain damage accompanied by disturbance in the blood-brain barrier (BBB). Since the endothelial cells are important components of the BBB and the first target of a systemic intoxication, in the present study, the effect of 3-NPA on primary cultured rat brain endothelial cells (rBECs) was examined by studying intracellular Ca2+ ([Ca2+]i) response using imaging techniques. Data indicate that a medium to high concentration of 3-NPA induces damage on rBECs as revealed by an accumulation of [Ca2+]i, but the damage was protected by cotreatment with 17 beta-estradiol or tamoxifen, suggesting that estrogen may be protective for the brain vascular damage via estrogen receptor.|The role of impaired mitochondrial function in processes leading to the generation of seizures was studied in mice. An inhibitor of mitochondrial complex III, 3-nitropropionic acid, which is known to evoke convulsions per se, and was used here in subthreshold dose, enhanced seizures generated by electric current and application of 4-aminopyridine. In contrast, 3-nitropropionic acid did not affect convulsions induced by gamma-aminobutyric acid (GABA) receptor antagonists - bicuculline, pentylenetetrazol and picrotoxin, glycine antagonist - strychnine, cholinomimetic drug-pilocarpine, and kynurenine aminotransferase inhibitor - aminooxyacetic acid. It is hypothesised that deranged mitochondrial metabolism renders the central nervous system more susceptible to factors inducing seizures via direct depolarization.|There is currently no effective treatment for Huntington's disease (HD), a progressive, fatal, neurodegenerative disorder characterized by motor & cognitive deterioration. It is well established that Huntington's disease is associated with perturbation of mitochondrial energy metab. Tauroursodeoxycholic acid (TUDCA), a naturally occurring bile acid, can stabilize the mitochondrial membrane, inhibit the mitochondrial permeability transition, decrease free radical formation, & derail apoptotic pathways. Here we report that tauroursodeoxycholic acid significantly reduced 3-nitropropionic acid (3-NPA) mediated striatal neuronal cell death in cell culture, In addition, rats treated with tauroursodeoxycholic acid exhibited an 80% reduction in apoptosis & in lesion volumes associated with 3-nitropropionic acid admin. Moreover, rats which received a combination of tauroursodeoxycholic acid + 3-nitropropionic acid exhibited sensor/motor & cognitive task performance that was indistinguishable from that of controls, & this effect persisted at least 6 months. Bile acids have traditionally been used as therapeutic agents for certain liver diseases. This is the first demonstration, however, that a bile acid can be delivered to the brain & function as a neuroprotectant & thus may offer potential therapeutic benefit in the treatment of certain neurodegenerative diseases.

LD50 Rat ip 67 mg/kg|LD50 Mouse iv 50 mg/kg

A bioassay of 3-nitropropionic acid (95% pure) for possible carcinogenicity was conducted by admin the test chemical by gavage to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were admin 3-nitropropionic acid at one of the following doses by gavage 5 days/wk. For male rats, the doses were 0.425 or 0.85 mg/animal/day; for females, they were 0.6 or 1.2 mg/animal/day. For both sexes of mice, the doses were 0.375 or 0.75 mg/animal/day. The rats were admin the test chemical for 110 wk and the mice for 104 wk. The controls consisted of 50 untreated rats and 50 untreated mice of each sex. All surviving rats were /sacrificed/ at 111 wk and all surviving mice at 104-105 wk. Mean body weights and mortality of the dosed animals were not markedly affected by 3-nitropropionic acid under the conditions of this bioassay, indicating that the maximum tolerated dose may not have been reached. The various clinical signs observed were common to both dosed and control groups. In rats, the combination of neoplastic nodule of the liver and hepatocellular carcinoma occurred in the males with a significant dose related trend (p=0.010) and with a higher incidence (p=0.012) in the high dose group of animals than in the controls (controls 0/49, low dose 3/50, high dose 6/49). All but one of these tumors were neoplastic nodules. In the females, only two neoplastic nodules occurred, one in each of the dosed groups. Biliary hyperplasia occurred at a higher incidence in dosed males than in the corresponding controls (controls 19/50, low dose 32/50, high dose 36/50), but the incidence of this lesion in dosed females was not incr as compared with controls. There was also a dose related trend (p=0.033) in the incidence of pancreatic islet cell adenoma in male rats (controls 4/49, low dose 6/50, high dose 11/50); however, direct comparisons of incidences in the dosed and control groups were not statistically significant. The historical incidence of pancreatic islet cell adenoma among 100 control Fischer 344 rats at the laboratory was 7/100 (7%). In addition, focal myocardial fibrosis was observed at a higher incidence in dosed rats than among controls (males: controls 1/4, low dose 17/49, high dose 24/48; females: controls 2/48, low dose 9/46, high dose 9/50. In mice, each type of neoplasm found in the dosed and control mice has been encountered previously as a spontaneous lesion. No specific tumor was found to occur at a statistically higher incidence among dosed mice than among the respective control group. It is concluded that under the conditions of this bioassay, there was an elevated incidence of hepatocellular neoplasms, primarily benign, and of islet cell adenomas of the pancreas in male Fischer 344 rats receiving 3-nitropropionic acid as compared with controls; however, there was no conclusive evidence that 3-nitropropionic acid was carcinogenic in these animals. The chemical was not carcinogenic in female rats or in male or female B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Equivocal; Female Rats: Negative; Male Mice: Negative; Female Mice: Negative.

Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. (See all compounds classified as Convulsants.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

3-Nitropropionic acid (3-NP), a naturally occurring mycotoxin, is an irreversible inhibitor of succinate dehydrogenase that produces adenosine triphosphate (ATP) depletion in cerebral cortical explants and is associated with motor disorders in livestock and humans that have ingested contaminated food.|Previous studies indicate that 3-nitropropionic acid (3-NPA) neurotoxicity involves the excitotoxic activation of N-methyl-D-aspartate (NMDA) receptors. Thus, ... the effect of orphenadrine ... on N-methyl-D-aspartate neurotoxicity in both cultured rat cerebellar granule cells (CGCs) & in rats /was studied/. Orphenadrine protected cerebellar granule cells from N-methyl-D-aspartate induced mortality, as assessed by both the neutral red viability assay & laser scanning cytometry, using propidium iodide staining. For rats, two indirect markers of neuronal damage were used: the binding of ((3)H)-PK 11195 to the peripheral type benzodiazepine receptor (PBR), a microglial marker, & expression of the 27 kD heat shock protein (HSP27), a marker of activated astroglia. Systemic admin of N-methyl-D-aspartate (30 mg/kg/day for 3 days) induced a 170% incr in ((3)H)-PK 11195 binding, & expression of 27 kD heat shock protein. Both the incr in ((3)H)-PK 11195 & HSP 27 expression were prevented by previous admin of 30 mg/kg/day of orphenadrine for 3 days. Lower doses (10 & 20 mg/kg) had no protective effect. Orphenadrine also reduced N-methyl-D-aspartate induced mortality in a dose dependent manner. ... Orphenadrine or orphenadrine like drugs could be used to treat neurodegenerative disorders mediated by overactivation of N-methyl-D-aspartate receptors.|The present study investigated the mechanism of cellular degeneration within the striatum following administration of the mitochondrial toxin, 3-nitropropionic (3-NP) acid. Internucleosomal fragmentation typical of apoptosis was present in the DNA of cells from the striatum of 3-NP-treated rats. DNA fragmentation was also evident in this region by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. The data suggest that striatal cells die by apoptosis following administration of 3-NP.|3-nitropropionic acid blocks energy metabolism prior to exerting neurotoxic damage and the degree of energy depletion determines the detrimental effects of 3-nitropropionic acid. In the present study, we also demonstrate that glutamate and glutamine levels as well as astrocytic functions may play pivotal roles in 3-nitropropionic acid-induced striatal lesions.|For more Mechanism of Action (Complete) data for 3-NITROPROPIONIC ACID (15 total), please visit the HSDB record page.

SYMPTOMS: Symptoms of exposure to this chemical may include irritation of the skin, eyes, mucous membranes and upper respiratory tract. ACUTE/CHRONIC HAZARDS: This compound may be harmful by inhalation or ingestion. It is an irritant of the skin, eyes, mucous membranes and upper respiratory tract. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide and nitrogen oxides. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Generally, the induction of vomiting is NOT recommended outside of a physician's care due to the risk of aspirating the chemical into the victim's lungs. However, if the victim is conscious and not convulsing and if medical help is not readily available, consider the risk of inducing vomiting because of the high toxicity of the chemical ingested. Ipecac syrup or salt water may be used in such an emergency. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

IF METHEMOGLOBINEMIA OCCURS & IS SEVERE, THEN TREAT WITH METHYLENE BLUE & OXYGEN.|Basic Treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . /Etiological Agents/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in respiratory arrest. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Proparacaine hydrochloride should be used to assist eye irrigation ... . /Etiological Agents/

/HUMAN EXPOSURE STUDIES/ 3-Nitropropionic acid (3-NP), a naturally occurring mycotoxin... is associated with motor disorders in livestock and humans that have ingested contaminated food.|/HUMAN EXPOSURE STUDIES/ 3-Nitropropionic acid (3-NPA) - a suicide inhibitor of succinate dehydrogenase - is a widely distributed plant and fungal neurotoxin known to induce damage to basal ganglia, hippocampus, spinal tracts and peripheral nerves in animals. Recent reports from Northern China indicate that 3-NPA is also likely to be responsible for the development of putaminal necrosis with delayed dystonia in children after ingestion of mildewed sugar cane. This article discusses the role of 3-NPA in the causation of the disease in China, its neurotoxic effects in animals and the potential role for this compound as a probe of selective neuronal vulnerability.|/EPIDEMIOLOGY STUDIES/ There have been 217 outbreaks of acute mildewed sugar cane poisoning between 1972 & 1989 in China resulting in 884 patients & 88 deaths. Epidemiologic & experimental studies have found that 3-nitropropionic acid , a mycotoxin produced by Arthrinium-contaminated sugar canes, is the probable etiologic factor of the disease. ... Initial symptoms were nausea, vomiting, abdominal pain without diarrhea, & anorexia that followed headache & dizziness. Coma & convulsions develop within 3-18 hr after onset. Coma lasted 20 days in one case. Following the coma motor aphasia, inability of voluntary movement, & urinary & fecal incontinence appeared. There was no fever. The focal cerebral impairments were reversible. Dystonia began 11-60 days after the coma. CT scans indicated bilateral lenticular lesions in the putanes & pallidum.

3-nitropropanoic acid

BETA-NITROPROPIONIC ACID IS DETECTED IN CRUDE BIOLOGICAL SYSTEMS USING TECHNIQUE OF THIN-LAYER CHROMATOGRAPHY. METHOD CAN DETECT AS LITTLE AS 30 MICROGRAMS.