化工社化工社 化学情報印刷レポート · 研究参考用
テオフィリン
テオフィリン · テオフォル · ユニコン · テオフルマートL · アーデフィリン · エリクソフィリン · ヌエリン · オプチフィリン
識別子と物理属性
| CAS No. | 58-55-9 |
|---|---|
| 分子式 | C7H8N4O2 |
| 平均分子量 | 180.16 g/mol |
| 単同位体質量 | 180.0647255 g/mol |
| SMILES | Cn1c(=O)c2[nH]cnc2n(C)c1=O |
| InChIKey | ZFXYFBGIUFBOJW-UHFFFAOYSA-N |
| PubChem CID | 2153 |
| ChEMBL | CHEMBL1355736 |
| ChEBI | CHEBI:28177 |
| EC No. | 200-385-7 |
| DTXSID | DTXSID5021336 |
| 現地名 | テオフィリン |
化学・物理的性質
| XLogP | 0 |
|---|---|
| 極性表面積 | 69.3 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 3 |
| 回転可能結合数 | 0 |
| 重原子数 | 13 |
| 形式電荷 | 0 |
| 複雑度 | 267 |
| 物質分類 | StimulantPharmaceutical |
| 医薬品 | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Metabolite of CaffeinePharmaceuticals -> Bronchodilators |
| 化粧品 | Cosmetic ingredients (Theophylline) -> CIR (Cosmetic Ingredient Review)Tonic |
| pH | A saturated solution in water is faintly acid. |
| SpringerMaterials Properties | Fusion temperature |
| LogP（分配係数） | log Kow = - 0.02-0.02-0.02 (estimated)-0.18 |
| 臭い | Odorless |
| 味 | Bitter |
| 密度 | g/cm³1.3640 (rough estimate) |
| Color/Form | White, crystalline alkaloidWhite crystalline powderNeedles or plates (water +1) |
| 溶解度 | 1 to 5 mg/mL at 70.7 °F (NTP, 1992)In water, 7,360 mg/L at 25 °CSlightly soluble in waterSlightly soluble in ethanol, ether, chloroformSlightly soluble in alcoholmore soluble in hot watersoluble in alkaline solutions0.1 M HCl: 可溶8.3g/L(20℃) |
| Human Drugs | Breast FeedingLactationMilk, HumanAnti-Asthmatic AgentsBronchodilator AgentsFDA approved drugs -> Active ingredient |
| 融点 | 271-273 °C |
| 沸点 | 312.97°C (rough estimate) |
| 屈折率 | 1.6700 (estimate) |
| 引火点 | 11 °C |
| 貯蔵条件 | 2-8°C |
| 外観・状態 | 粉 |
| pKa（酸解離定数） | 8.77(at 25℃) |
| 色 | 白い |
| Merck | 14,9285 |
| BRN | 13463 |
| ヘンリー定数 | 5.5×108 mol/(m3Pa) at 25℃, HSDB (2015) |
| BCS Class | 3,1 |
| 安定性 | 安定。強力な酸化剤とは相容れない。 |
| 化粧品成分の機能 | スキンコンディショニング - その他 |
| InChI | 1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9) |
| InChIKey | ZFXYFBGIUFBOJW-UHFFFAOYSA-N |
| SMILES | CN1C(=O)N(C)c2[nH]cnc2C1=O |
| LogP（分配係数） | -0.020 |
| CAS データベース | 58-55-9(CAS DataBase Reference) |
| NISTの化学物質情報 | 1,3-Dimethylxanthine(58-55-9) |
| EPAの化学物質情報 | Theophylline (58-55-9) |
化学的特性
white to light yellow crystal powder
安全性と法規制
| GHS 分類 | DangerH360D: May damage the unborn child [Danger Reproductive toxicity]P203, P280, P318, P405, and P501 (click each P-code to see the statement)This chemical does not meet GHS hazard criteria for 0.3% (1 of 308) of reports.H301 (88%): Toxic if swallowed [Danger Acute toxicity, oral] |
|---|---|
| 規制情報 | Chemical: 1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-Hazard Traits - Reproductive ToxicityStatus: Active Update: 07-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/111721H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-: Does not have an individual approval but may be used under an appropriate group standard |
| その他の安全情報 | Evaluation - 1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl- (theophylline) |
| 輸送ラベル（DOT） | Poison |
| 火災危険 | Flash point data for this chemical are not available, however it is probably combustible. (NTP, 1992)Not combustible. Gives off irritating or toxic fumes (or gases) in a fire. |
| 健康有害性 | SYMPTOMS: Symptoms of exposure to this compound include nausea, vomiting, epigastric pain, hematemesis, diarrhea, headaches, irritability, restlessness, insomnia, reflex hyperexcitability, muscle twitching, clonic and tonic generalized convulsions, palpitations, tachycardia, extrasystoles, potentiation of diuresis, hyperglycemia, flushing, hypotension, tachypnea, albuminuria, inappropriate ADH secretion and rash. Other symptoms include collapse, a fall in blood pressurecoma, hyperreflexia, ventricular arrythmias including fibrillation, hypotension, respiratory arrest, restlessness, fever, agitation and hyperventilation. It may also cause central nervous system stimulation, nervousness, insomnia, tremors, hyperesthesia, stimulation of the medullary respiratory centersapnea, emesis, decreases in peripheral vascular resistanceincreased perfusion of most organs and death. |
| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including theophylline, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: theophylline, anhydroustheophylline calcium salicylateand theophylline sodium glycinate are included in bronchodilator drug products.Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: theophylline is included in orally administered menstrual drug products. |
| 反応性グループ | Amides and Imides |
| UN 分類 | UN Hazard Class: 6.1UN Pack Group: III |
| Special Reports | Upton RAPharmacokinetic Interactions Between Theophylline and Other Medication (Part I)Clin Pharmacokinet 20 (1): 66-80 (1991).Parr MJ et alTheophylline Poisoning -- A Review of 64 CasesIntensive Care Med 16 (6): 394-8 (1990). Sixty-four cases of theophylline poisoning were reviewed. The results support the use of a management regimen which emphasizes intensive supportive therapy and restricts the use of charcoal hemoperfusion.Sessler CNTheophylline Toxicity: Clinical Features of 116 Consecutive CasesAm J Med 88 (6): 567-76 (1990).Boreus LOThe Role of Therapeutic Drug Monitoring in ChildrenClin Pharmacokinet 17 (1): 4-12 (1989).For more Special Reports (Complete) data for THEOPHYLLINE (12 total), please visit the HSDB record page. |
| Reactivity Profile | THEOPHYLLINE neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides. |
| Chemical Dangers | Decomposes on heating. This produces toxic fumes including nitrogen oxides. |
| Packaging and Labelling | Do not transport with food and feedstuffs. |
| 消火 | Fires involving this compound can be controlled using a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)In case of fire in the surroundings, use appropriate extinguishing media. |
| 応急処置措置 | Fresh air, rest.Remove contaminated clothes. Rinse skin with plenty of water or shower.Rinse with plenty of water for several minutes (remove contact lenses if easily possible).Rinse mouth. Give a slurry of activated charcoal in water to drink. Refer for medical attention . |
| 応急処置 | 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. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. |
| 安全保管 | Separated from food and feedstuffs. |
| 消火手順 | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical, or carbon dioxide.Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. |
| 保管条件 | Store at 20 deg -25 °C (68 deg - 77 °F)excursions permitted between 15 deg - 30 °C (59 deg - 86 °F).Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non-combustible, acute toxic Cat.3 / toxic hazardous materials or hazardous materials causing chronic effects. |
| 清掃方法 | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| 非火災時の漏出対応 | 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. |
| 処分方法 | 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.Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubberContaminated packaging: Dispose of as unused product. |
| 漏出処分 | Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into sealable containers. If appropriate, moisten first to prevent dusting. Then store and dispose of according to local regulations. |
| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.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. |
| Isolation and Evacuation | Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]: |
| 相互作用 | Theophylline interacts with a wide variety of drugs. The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to theophylline or another drug or occurrence of adverse effects without a change in serum theophylline concentration. More frequently, however, the interaction is pharmacokinetic, i.e., the rate of theophylline clearance is altered by another drug resulting in increased or decreased serum theophylline concentrations. Theophylline only rarely alters the pharmacokinetics of other drugs. The drugs listed in Table have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with theophylline. The information in the "Effect" column of Table assumes that the interacting drug is being added to a steady-state theophylline regimen. If theophylline is being initiated in a patient who is already taking a drug that inhibits theophylline clearance (e.g., cimetidine, erythromycin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be smaller. Conversely, if theophylline is being initiated in a patient who is already taking a drug that enhances theophylline clearance (e.g., rifampin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be larger. Discontinuation of a concomitant drug that increases theophylline clearance will result in accumulation of theophylline to potentially toxic levels, unless the theophylline dose is appropriately reduced. Discontinuation of a concomitant drug that inhibits theophylline clearance will result in decreased serum theophylline concentrations, unless the theophylline dose is appropriately increased.Cimetidine, high-dose allopurinol (e.g., 600 mg daily), oral contraceptives, propranolol, ciprofloxacin, erythromycin, and troleandomycin may increase serum theophylline concentrations by decreasing theophylline's hepatic clearance.Methotrexate may decrease clearance of theophyllineplasma theophylline concentrations should be monitored in patients receiving theophylline concomitantly with methotrexate.Rifampin may decrease serum theophylline concentrations by increasing theophylline's hepatic clearance.For more Interactions (Complete) data for THEOPHYLLINE (19 total), please visit the HSDB record page. |
| Hepatotoxicity | Prospective studies have shown that ALT elevations occur in less than 1% of patients receiving long term oral therapy with theophylline, making it unlikely that such elevations are more common than might occur by chance. No instances of clinically apparent liver injury have been convincingly linked to theophylline use. Liver injury may occur as a part of generalized toxicity from high doses of theophylline probably as a result of hepatic complications of hypotension or anoxia from seizures or cardiac arrhythmias caused by the drug. Theophylline actually has been shown to attenuate several forms of experimental acute liver injury, and chronic caffeine (another xanthine) intake has been associated with decreased rates of chronic liver disease, cirrhosis and liver cancer. |
| 生態毒性値 | LC50Species: Streptocephalus proboscideus (Fairy Shrimp)Conditions: freshwaterConcentration: 2360 umol/L for 24 hr /97->99% purity/Species: Artemia salina (Brine Shrimp)Conditions: saltwaterConcentration: 45800 umol/L for 24 hr /97->99% purity/EC50Species: Daphnia pulex (Water Flea) age <24 hrConditions: freshwater, static, 20 °C, pH 7.6Concentration: 1.82 mM for 24 hrEffect: intoxication, immobilization /formulation/Species: Daphnia magna (Water Flea) age <24 hr neonateConditions: freshwater, static, 21 °C, pH 7.6Concentration: 0.861 mM for 24 hrEffect: intoxication, immobilization |
| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that theophylline is expected to have very high mobility in soil(SRC). The pKa of theophylline is 8.81(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species of theophylline from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.8X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Theophylline is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.1X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Theophylline has been categorized as readily biodegradable in screening tests(6), suggesting that biodegradation may be an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that theophylline is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.8X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 0.02(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Theophylline has been categorized as readily biodegradable in screening tests(7), suggesting that biodegradation may be an important environmental fate process in water(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), theophylline, which has an estimated vapor pressure of 5.1X10-19 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase theophylline may be removed from the air by wet and dry deposition(SRC). Theophylline contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| 食品調査値 | Theophylline occurrence in plants(1).[Table#4567] |
| 有害作用 | Theophylline has a very narrow therapeutic window, and its interaction with various other drugs has led to the limitation of its use. The serum theophylline concentrations require monitoring directly to avoid toxicity as the adverse effects of theophylline are related to its plasma concentration and have been observed when plasma concentrations exceed 20 mg/L. Some patients have also experienced adverse effects at low plasma concentrations. The dose gradually increases until achieving therapeutic plasma concentrations. This approach reduces side effects. |
| 暴露経路 | The substance can be absorbed into the body in hazardous amounts by ingestion.Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. |
| 毒性の概要 | Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.orgIDENTIFICATION AND USE: Theophylline is a white, crystalline alkaloid. It is used as bronchodilator agent. Theophylline is an old drug experiencing a renaissance owing to its beneficial antiinflammatory effects in chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. HUMAN EXPOSURE AND TOXICITY: Theophylline has a low therapeutic index. Theophylline toxicity is most likely to occur when serum concentrations exceed 20 ug/mL and becomes progressively more severe at higher serum concentrations. Tachycardia, in the absence of hypoxia, fever, or administration of sympathomimetic drugs, may be an indication of theophylline toxicity. Anorexia, nausea and occasional vomiting, diarrhea, insomnia, irritability, restlessness, and headache commonly occur. Other symptoms of toxicity may include agitated maniacal behavior, frequent vomiting, extreme thirst, slight fever, tinnitus, palpitation, and arrhythmias, delirium, muscle twitching, severe dehydration, albuminuria, emesis of a "coffee ground" material, hyperthermia, and profuse diaphoresis. Seizures may occur even without other preceding symptoms of toxicity and often result in death. Fatalities in adults have generally occurred during or following IV administration of large doses of aminophylline in patients with renal, hepatic, or cardiovascular complications. In other patients, the rapidity of the injection, rather than the dose used, appears to be the more important factor precipitating acute hypotension, seizures, coma, cardiac standstill, ventricular fibrillation, and death. IV theophylline should therefore be given slowly. In children, fatalities usually are a result of overdosage and marked sensitivity to the CNS stimulation of theophylline. Acute single overdose is usually a result of a suicide attempt or accidental childhood ingestion but may also be caused by accidental or iatrogenic misuse (therapeutic overdose). Usual manifestations include vomiting (sometimes with hematemesis), tremor, anxiety, and tachycardia. Metabolic effects include pronounced hypokalemia, hypophosphatemia, hyperglycemia, and metabolic acidoses. With serum levels above 90-100 mg/L, hypotension, ventricular arrhythmias, and seizures are commonstatus epilepticus is frequently resistant to anticonvulsant drugs. Seizures and other manifestations of severe toxicity may be delayed 12-16 hr or more after ingestion, in part owing to delayed absorption of drug from sustained-release preparations. Theophylline also inhibited DNA synthesis in human fibroblastoid EUE cells, and the shape of the dose-response curves and the absence of theophylline-induced DNA strand breaks indicated that theophylline does not directly damage the DNA but acts as a metabolic inhibitor. The results of a study with synchronized HeLa S3 cells exposed to theophylline indicate that the block in DNA replication results from inhibition of histone 1 phosphorylation, which prevents the normal release of chromatin structure between G1 and S phases. ANIMAL STUDIES: In tests performed in rabbits, undiluted theophylline induced mean scores of 0.6 for cornea opacity, 1.8 for conjunctival redness, and 0.6 for swelling. On day 8, one of 3 animals showed opacity grade 1 and conjunctivitis grade 2. The animal showing slight corneal opacity had also keratitis. The effects could possibly be due to mechanical irritation by the crystalline test substance. A single oral dose of 400 mg/kg bw theophylline was acutely toxic to rats and mice. Administration of the same daily dose as two separate doses of 200 mg/kg bw was acutely toxic to rats but not to mice. In dogs, the minimal oral toxic concentration of theophylline appears to be higher (37-60 ug/mL plasma) than in man ( > 20 g/mL). Theophylline has been reported to be more toxic than caffeine or theobromine to the heart, bronchi and kidneys. Groups of female mice 25 days of age, received a single subcutaneous injection of 0.1 mg/g bw urethane followed immediately by seven intraperitoneal injections (0.05 umol/g bw) of theophylline at 6-hr intervals up to 36 hr after urethane treatment, to give a total dose of 63 ug/g bw theophylline. Mice were killed five months after urethane treatment. No significant difference was noted in the numbers of mice with lung tumors or in the numbers of tumors/lung. In a reproductive study, mice were administered 0.075, 0.15 or 0.30% theophylline in the diet (average daily doses, 125, 265 or 530 mg/kg bw) for one week before mating and during 13 weeks of cohabitation. Among all treated groups, there was a dose-related decrease in the number of live pups per litterin the high-dose groups, there was a significant decrease in the number of litters per breeding pair and a significant decrease in live pup weight. In the high- and mid-dose groups, a significant decrease in the percentage of pups born alive was observed. Only mild toxicity was observed in adults at these doses. In a cross-over mating trial at the end of a 19-week exposure to 0.3% theophylline, animals of each sex were found to be affected, although females were more severely affected than males. Feeding theophylline to immature (five to six weeks old) rats at 0.5% in the diet (approximately 300 mg/kg bw per day) for 75 weeks produced severe testicular atrophy in 50% of animals, oligo-spermatogenesis and aspermatogenesis. Theophylline has been studied in Ames Salmonella test, in vivo and in vitro cytogenetics, micronucleus and Chinese hamster ovary test systems and has not been shown to be genotoxic.As with other methylxanthines, theophylline toxicity can lead to gastrointestinal distress, insomnia, and tremor. Reports also exist of severe nausea and vomiting, cardiac arrhythmias, hypotension, and convulsions, more commonly in cases of overdosage. Very large overdoses, such as those during suicide attempts, could potentially be lethal because of the development of arrhythmias and convulsions.Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin. |
| Signs and Symptoms | See Ingestion.Headache. Nausea. Vomiting. Irritability. Palpitations. Convulsions.Symptoms of overdose include seizures, arrhythmias, and GI effects. |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of July 7, 2016: http://actor.epa.gov/dashboard/]The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=58-55-9] |
| Effluent Concentrations | Theophylline has been reported in final effluent water samples from wastewater treatment plants the UK at a range of 1,220-3,169 ng/L. Influent concentrations ranged from 9,467-20,400, indicating a >80% treatment removal(1). |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of theophylline can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that theophylline is expected to have very high mobility in soil. The pKa of theophylline is 8.81(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). |
| F | 10-23 |
| 水環境危害等級（WGK） | 1 |
| TSCA 収載状態 | TSCA listed |
| RTECS 番号 | XH3850000 |
| 輸送番号（UN） | UN 2811 6.1/PG 3 |
| 毒性 | LD50 oral in rabbit: 350mg/kg |
| 税関コード | 29395900 |
| 危険文句（R） | 22-39/23/24/25-23/24/25-11-36/37/38 |
| 危険表示 | Xn,T,F,Xi |
| 安全措置（S） | 7-16-36/37-45-36-26-24/25 |
| 危険等級 | 6.1(b)Acute Tox. 3 OralRepr. 1B |
| 包装等級 | III |
| 貯蔵分類 | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| 有害物質データ | 58-55-9(Hazardous Substances Data) |
用途
解説
テオフィリン,無色の針状晶．融点270～274 ℃．pKa 8.77(25 ℃)．昇華性がある．酸やアルカリに可溶，アルコール類に微溶，エーテルに不溶．N-メチル化によりカフェインとなる．利尿薬として使われるが，その作用はテオブロミンやカフェインより強い．森北出版「化学辞典（第2版）
用途
ホスホジエステラーゼ阻害作 用を示します。
用途
気管支拡張薬 強心薬 血管拡張薬 抗喘息薬 利尿薬
説明
Theophylline is a methylxanthine that acts as a weak bronchodilator. It is useful for chronic therapy and is not helpful in acute exacerbations.Theophylline is a methylxanthine alkaloid that is a competitive inhibitor of phosphodiesterase (PDE; Ki = 100 μM). It is also a non-selective antagonist of adenosine A receptors (Ki = 14 μM for A1 and A2). Theophylline induces relaxation of feline bronchiole smooth muscle precontracted with acetylcholine (EC40 = 117 μM; EC80 = 208 μM). Formulations containing theophylline have been used in the treatment of asthma and chronic obstructive pulmonary disease (COPD).
使用
theophylline is tonic and skin conditioning. Its cosmetic activity is not clearly or definitively established. It is most often found in anti-cellulite products. Theophylline is in the same family of bio chemicals as caffeine. It is naturally occurring in tea.
一般的な説明
Odorless white crystalline powder. Odorless. Bitter taste.
製法・合成法
純化方法
It crystallises from H2O as the monohydrate which becomes anhydrous above 100o. It is freely soluble in hot H2O, but its solubility at 15o is 0.44%. It complexes with heavy metals. It is a diuretic, vasodilator and a cardiac stimulant. [Lister Purines Part II, Fused Pyrimidines Brown Ed, Wiley-Interscience pp253-254 1971, ISBN 0-471-38205-1, Beilstein 26 H 455, 26 I 134, 26 II 263, 26 III/IV 2331.]