HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
5-(Dithiolan-3-yl)valeriansaeure
ALA · THIOCTIC ACID · ALPHA-LIPOIC ACID · DL-THIOCTIC ACID · alpha lipoic acid powder · A-LIPOIC ACID · Thioctic acid CRS · DL-A-LIPOIC ACID
Identifikatoren & physikalische Daten
| CAS No. | 1077-28-7 |
|---|---|
| Summenformel | C8H14O2S2 |
| Durchschnittliche Molmasse | 206,3 g/mol |
| Monoisotopische Masse | 206,04352169 g/mol |
| SMILES | O=C(O)CCCCC1CCSS1 |
| InChIKey | AGBQKNBQESQNJD-UHFFFAOYSA-N |
| PubChem CID | 864 |
| ChEMBL | CHEMBL134342 |
| ChEBI | CHEBI:16494 |
| EC No. | 200-534-6 |
| DTXSID | DTXSID7025508 |
| Lokaler Name | 5-(Dithiolan-3-yl)valeriansaeure |
Chemische & physikalische Eigenschaften
| XLogP | 1,7 |
|---|---|
| Polarare Oberfläche (TPSA) | 87,9 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 5 |
| Schwere Atome | 12 |
| Formalladung | 0 |
| Komplexität | 150 |
| Arzneimittel | Pharmaceuticals |
| Color/Form | Forms yellowish flakes |
| Löslichkeit | Yellow powdersolubility in ethanol: 50 mg/mL /Synthetic, oxidized form/Soluble in methanol, ethanol, diethyl ether and chloroformethanol: 50 mg/mL0.9 g/L (20 ºC) |
| Decomposition | When heated to decomposition, material mits toxic fumes of /sulfur oxides/. |
| Schmelzpunkt | 47.5-48 °C60-62 °C |
| Dissociation Constants | pKa = 5.10 |
| Collision Cross Section | 133.8 Ų [M+H-H2O]+ [CCS Type: DTMethod: single field calibrated with Agilent tune mix (Agilent)] |
| Other Experimental Properties | White powder, soluble in water, pH of aqueous solutions about 7.4 /Thioctic acid, sodium salt/Crystals by vacuum sublimation (at 85-90 °C and 25 micron). MP: 46-48 °C (microblock). Specific optical rotation: + 104 deg at 23 °C/D (c = 0.88 in benzene). UV max (methanol): 333 nm (epsilon 150). pKa = 5.4. Practically insoluble in water. Soluble in fat solvents. /Thioctic acid, d-form/Yellow needles from cyclohexane. MP: 60-61 °C. BP: 160-165 °C. Practically insoluble in watersoluble in fat solvents. Forms a water-soluble sodium salt. /Thioctic acid, dl-form/Crystals from cyclohexane. MP: 45-47.5 °C (microblock). Specific optical rotation: -113 deg at 23 °C/D (c = 1.88 in benzene). UV max (methanol): 330 nm (epsilon 140). /Thioctic acid, l-form/ |
| Siedepunkt | 160-165 °C(lit.) |
| Dichte | 1.2888 (rough estimate) |
| Brechungsindex | 1.5200 (estimate) |
| Flammpunkt | 160-165°C |
| Lagerbedingungen | 2-8°C |
| pKa (Säurekonstante) | 4.75±0.10(Predicted) |
| Aggregatzustand | Crystals or Crystalline Powder |
| Farbe | Yellow |
| Biologische Quelle | synthetic |
| Merck | 14,9326 |
| BRN | 81853 |
| Stabilität | Stable. Incompatible with strong oxidizing agents. |
| Kosmetik-Inhaltsstoffe Funktionen | ANTIOXIDANT |
| InChI | 1S/C8H14O2S2/c9-8(10)4-2-1-3-7-5-6-11-12-7/h7H,1-6H2,(H,9,10) |
| InChIKey | AGBQKNBQESQNJD-UHFFFAOYSA-N |
| SMILES | OC(=O)CCCCC1CCSS1 |
| LogP (Verteilungskoeffizient) | 2.530 (est) |
| CAS Datenbank | 1077-28-7(CAS DataBase Reference) |
| NIST chemische Informationen | Dl-thioctic acid(1077-28-7) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 6.5% (28 of 430) of reports.WarningH302 (93.5%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P272, P273, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P391, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 430 reports by companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.This chemical does not meet GHS hazard criteria for 42.3% (52 of 123) of reports. |
|---|---|
| Regulatorische Informationen | Chemical: 1,2-Dithiolane-3-pentanoic acidStatus: Active Update: 22-07-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/227161,2-Dithiolane-3-pentanoic acid: Does not have an individual approval but may be used under an appropriate group standard |
| Toxic Combustion Products | Emits toxic fumes under fire conditions. |
| Hazard Classes and Categories | Acute Tox. 4 (93.5%)Acute Tox. 4 (57.7%) |
| Skin, Eye, and Respiratory Irritations | Possible eye, skin, gastrointestinal, and/or respiratory tract irritation. |
| Brandbekämpfungsverfahren | Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing. |
| Lagerbedingungen | Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. |
| Reinigungsverfahren | Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site. |
| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash. |
| Preventive Measures | Engineering controls such as exhaust ventilation are recommended.SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling. |
| Personal Protective Equipment (PPE) | Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.Wear approved respiratory protection, chemically compatible gloves, and protective clothing. |
| Treatment | If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally. |
| Gesundheitliche Auswirkungen | Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides. |
| Unerwünschte Wirkungen | ALA is considered a safe supplementation without any adverse effects. One study supports the safety of the drug, and an adult can take up to 2400 mg without experiencing any harmful adverse effects. High doses of ALA are not recommended as higher doses provide no additional benefits. The most common adverse effects reported with ALA are headache, heartburn, nausea, and vomiting. |
| Toxizitätsübersicht | ALA is generally considered a safe drug. A daily dose of 200 mg/day to 2400 mg/day of ALA is deemed safe without significant adverse effects. However, there is no reported safe dose in children.(R)-lipoic acid is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen. |
| Signs and Symptoms | Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result. |
| Natural Pollution Sources | Growth factor for many bacteria and protozoaprosthetic group, coenzyme, or substrate in plants, microorganisms, and animal tissues ... The dl-form is naturally occurring. /Thioctic acid/alpha-Lipoic acid is found in plants such as spinach and broccoli(1).alpha-Lipoic acid is a naturally occurring compound that is synthesized in small amounts by plants and animals. Animal tissues shown to contain this compound are the kidney, heart, and liver(1). |
| Human Toxicity Excerpts | /CASE REPORTS/ Insulin Autoimmune Syndrome (IAS) is a rare disease characterized by hypoglycemia and autoantibodies to insulin without prior insulin administration. Here, we report a case of IAS associated with alpha lipoic acid. The patient is a 55-year-old man. He began to complain of hypoglycemic symptoms after taking alpha lipoic acid. He lost consciousness in the late postprandial period and blood glucose was found to be 27 mg/dl. A high insulin level and high titers of insulin antibodies were detected. His HLA genotype contains DRB1* 0406. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Alpha-lipoic acid, also referred to as thioctic acid, has been demonstrated to exhibit strong anti-oxidant properties. In order to test the long-term toxicity of alpha-lipoic acid, groups of 40-50 male and female, 5-6-week-old, Sprague-Dawley rats were subjected to oral administration of 20, 60, or 180 mg/kg body weight (bw)/day alpha for 24 months. There was no significant difference between control animals and treated animals at 20 or 60 mg/kg bw/day with respect to body weight gain, food consumption, behavioral effects, hematological and clinical chemistry parameters, and gross and histopathological findings. In all treatment groups, mortality was slightly lower as compared to the control. The absolute weights of the heart (high-dose males), thymus (high-dose males), and left adrenal (mid-dose males), liver (high-dose females), and lungs (high-dose females) were decreased in comparison to controls. These changes were of no toxicological significance. The only notable finding in rats of both sexes dosed at 180 mg/kg bw/day was a reduction in food intake relative to the controls and a concomitant decrease in body weight. This decrease in body weight led to significant differences between the control and high-dose rats with respect to the absolute weights of certain organs. However, no gross or histopathological changes were associated with these findings. The no-observed-adverse-effect level (NOAEL) is considered to be 60 mg/kg bw/day./VETERINARY CASE REPORTS/ Suspected alpha lipoic acid (ALA) toxicity was diagnosed based on clinical history and compatible laboratory findings in 2 dogs. Case 1 was presented within 10 hours of ALA ingestion, with initial behavioral changes likely due to hypoglycemia. During the course of hospitalization, hypoglycemia persisted and evidence of acute hepatic insult developed. With aggressive supportive care (including IV fluids with dextrose supplementation, hepatoprotective medications, and a plasma transfusion), he made a full recovery. Case 2 was presented approximately 60 hours after ALA ingestion, and was found to be in oliguric renal failure. She was treated with IV fluids, gastroprotective medications, and furosemide, but her condition deteriorated and she was ultimately euthanized within 16 hours of admission to the hospital. |
| Antidote and Emergency Treatment | /SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B//SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). 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. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B//SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/ |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 29349990 |
| RTECS-Nr. | JP1192000 |
| R-Sätze (R) | 22-20/21/22 |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 37/39-26-24/25-36-36/37/39 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 1077-28-7(Hazardous Substances Data) |
| Gefahrenklasse | Acute Tox. 4 OralAquatic Chronic 2Eye Irrit. 2Skin Irrit. 2Skin Sens. 1 |
Anwendungen & Verwendung
Beschreibung
DL-α-Lipoic acid is a cyclic disulfide antioxidant that interconverts with its reduced dithiol form. It is an essential cofactor for decarboxylation reactions of the citric acid cycle, and acts as a general antioxidant. DL-α-lipoic acid can act as a direct radical scavenger, as a cofactor to regenerate reduced glutathione, and as a metal chelator.
Verwenden
(±)-α-Lipoic acid has been used in in vitro lipoylation studies and in the pyruvate dehydrogenase complex (PDC)-pyruvate dehydrogenase kinase (PDHK) functional assay. It has also been used to investigate its antioxidative effect on developing cerebellum of rats exposed to arsenic during postnatal period.