| GHS-Einstufung | WarningH302: Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Danger |
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| Regulatorische Informationen | List I Chemical: A chemical specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act and is important to the manufacture of a controlled substance. (21 eCFR 1310.02)Status: Active Update: 05-08-2015 https://echa.europa.eu/registration-dossier/-/registered-dossier/11605 |
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| Weitere Sicherheitsinformationen | IMAP assessments - Benzenemethanol, .alpha.-[1-(methylamino)ethyl]-,[R-(R*,S*)]-: Human health tier I assessmentIMAP assessments - Benzenemethanol, .alpha.-[1-(methylamino)ethyl]-,[R-(R*,S*)]-: Environment tier I assessment |
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| FDA-Anforderungen | Dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury under conditions of use recommended or suggested in the labeling, or if no conditions of use are recommended or suggested in the labeling, under ordinary conditions of use. Therefore, dietary supplements containing ephedrine alkaloids are adulterated under section 402(f)(1)(A) of the Federal Food, Drug, and Cosmetic Act.On February 11, 2004, FDA issued a final regulation declaring dietary supplements containing ephedrine alkaloids adulterated under section 402(f)(1)(A) of the Act. FDA took this action because it found that ephedrine alkaloids present an unreasonable risk of illness or injury under the conditions of use recommended or suggested in the labeling, or if no conditions of use are suggested or recommended in labeling, under ordinary conditions of use. The final rule became effective on April 12, 2004.On Aug. 17, 2006, the U.S. Court of Appeals for the Tenth Circuit in Denver upheld the Food and Drug Administration's (FDA) final rule declaring all dietary supplements containing ephedrine alkaloids adulterated, and therefore illegal for marketing in the United States, reversing a decision by the District Court of Utah /made in 2005/.Although synthetic ephedrine (in the form of ephedrine hydrochloride) has been found in products labeled as dietary supplements, ephedrine hydrochloride was approved for use as a human drug as early as the late 1940s and, to the best of /the FDA's/ knowledge there is no evidence that it was marketed prior to that time as a dietary supplement or food. Furthermore, ephedrine hydrochloride and other synthetic sources of ephedrine cannot be dietary ingredients because they are not constituents or extracts of a botanical, nor do they qualify as any other type of dietary ingredient. For these reasons, products containing synthetic ephedrine cannot be legally marketed as dietary supplements |
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| Special Reports | International Programme on Chemical SafetyPoisons Information Monograph: Ephedrine (PIM 209) (2000) This report contains a discussion of the pharmacological and toxicological effects of ephedrine.[Available from, as of March 21, 2014: http://www.inchem.org/documents/pims/pharm/pim209.htm]CANTOXSafety Assessment and Determination of a Tolerable Upper Limit for Ephedra, p. 194 (2000). This very thorough analysis of the information available on ephedra up to 2000 was prepared by CANTOX Health Sciences International, Ontario, for the Council for Responsible Nutrition, Washington, DC, a Washington-based trade association representing ingredient suppliers and manufacturers in the dietary supplement industry.[Available from, as of March 21, 2014: http://www.crnusa.org/pdfs/Cantoxreport.doc]DHHS/NTPToxicology & Carcinogenesis Studies of Ephedrine sulfate in F344/N Rats and B6C3F1 MiceTechnical Report Series No. 307 (1986) NIH Publication No. 86-2563U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709[Available from, as of March 21, 2014: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr307.pdf]Thurn ALp. 189-95 in Encyclopedia of Dietary SupplementsCoates PM et al, eds (2005)A review of Ephedra (Ma Huang) |
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| History and Incidents | Between 1995 and 1997, the FDA received more than 900 reports of possible ephedra toxicity. Serious adverse events such as stroke, heart attack, and sudden death were reported in 37 cases.In 2004, the FDA banned the U.S. sale of dietary supplements containing ephedra. The FDA found that these supplements had an unreasonable risk of injury or illness-particularly cardiovascular complications-and a risk of death. The ban does not apply to traditional Chinese herbal remedies or to products like herbal teas regulated as conventional foods.In July 2003, GAO /US Government Accountability Office/ testified at a House Subcommittee hearing on issues relating to dietary supplements containing ephedrine alkaloids. ... The testimony ... /included/ an evaluation of Metabolife International's records of health-related calls from consumers of Metabolife 356 /a popular weight-loss supplement containing ma-huang, caffeine, and several other active ingredients./. GAO noted that the types of adverse events identified in the health-related call records from Metabolife International were consistent with the types of adverse events reported to /FDA/, as well as with the scientifically documented physiological effects of ephedrine alkaloids. GAO also noted that despite the limited information contained in most of the call records, 14,684 call records contained reports of at least one adverse event among consumers of Metabolife 356. The GAO testimony identified 92 serious events that included heart attacks, strokes, seizures, and deaths and emphasized that these findings were similar to other reviews of the call records, including those done by Metabolife International and its consultants. The GAO testimony noted that, in those call records where age was documented, many of the serious adverse events occurred in relatively young consumers, with more than one-third being under the age of 30. Furthermore, for those call records in which quantity of use and/or frequency and duration of use were noted, most of the serious adverse events occurred among Metabolife 356 users who used the product within the recommended guidelines, i.e., they did not take more of the product nor consume it for a longer period of time than the product label recommended. /Metabolife 356/ |
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| Hazard Classes and Categories | Acute Tox. 4 (100%)Skin Corr. 1B (52%)Skin Sens. 1B (52%)Eye Dam. 1 (52%)Acute toxicity - category 4Acute toxicity (Oral) - Category 4Reproductive toxicity - Category 1A, Additional category: Effects on or via lactationSpecific target organ toxicity - Single exposure - Category 2 (heart, nervous system)Specific target organ toxicity - Repeated exposure - Category 2 (heart, nervous system)Acute Tox. 4 * |
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| Lagerbedingungen | ...must be stored in light-resistant containers. Ephedrine base should be stored at or below 8 °C.KEEP WELL CLOSED IN COOL PLACE. |
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| Entsorgungsverfahren | SRP: 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. |
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| Körperbelastung | Three deaths from non-prescription diet aids or stimulants were reportedephedrine concentrations in the blood were 3.5-20.5 mg/Lcorresponding blood caffeine concentrations (130 to 344 mg/L) were sufficient to be lethal. |
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| 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. |
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| Wechselwirkungen | ...A /previously/ healthy 40-year-old man was admitted to our hospital for new-onset congestive heart failure and severe acute hepatitis that developed several months after he began using anabolic-androgenic steroids, ephedra, and gamma-hydroxybutyrate supplements. Analysis with an objective causality assessment scale revealed a probable adverse drug reaction between the patient's use of anabolic steroids, ephedra, and gamma-hydroxybutyrate and the development of his cardiomyopathy and acute liver injury. /Ephedra/Single-dose studies of dietary supplements containing ephedrine alkaloids show that these products cause increases in both heart rate and blood pressure in healthy subjects. In one such study ... the peak increase in blood pressure following a single oral dose of ephedrine alkaloids and caffeine (20 mg/200 mg) was 14 millimeters of mercury (mm Hg) systolic and 6 mm Hg diastolic, occurring about 2 hours after the single dose was taken. The findings ... are complicated by the presence of caffeine in the dietary supplements used because caffeine is also known to have acute effects on blood pressure and heart rate. /Ephedrine alkaloids/A group of healthy subjects received ephedrine (E, 0.1 mg/kilogram (kg) orally), caffeine (C, 4 mg/kg orally), the combination, or a placebo (P). Although caffeine caused a small increase in systolic blood pressure (average 3 to 6 mm Hg), ephedrine alone gave a 12 mm Hg effect, and when added to caffeine, increased systolic blood pressure by an additional 15 mm Hg (C+E = 156 +/- 29 mm HgE = 150 +/- 14C = 141 +/ - 16P = 138 +/- 14).Serious adverse health events have been reported with the use of dietary supplements containing ephedra and guarana. /The authors/ sought to determine whether repeated dosing and multi-ingredient formulations contribute to the adverse effects of these supplements. ... In this study, 16 healthy adults (8 women) took 2 doses each of ephedra-guarana alone, Xenadrine RFA, a multicomponent dietary supplement containing 25 mg ephedra alkaloids and 200 mg caffeine, or placebo 5 hours apart in a randomized, double-blind, 3-arm crossover study. Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared with placebo, Xenadrine and ephedra-guarana significantly increased heart rate (maximum increase, 9.4 +/- 8.6 beats/minP = 0 .002), blood pressure (maximum increase in systolic and diastolic pressure, 11.5 +/- 10.7 mm Hg and 7.3 +/- 7.4 mm Hg, respectivelyP = 0 .015), postprandial glucose concentration (maximum change, 41.0 +/- 18.8 mg/dLP < .0001), and insulin concentration (maximum change, 41.2 +/- 47.8 microIU/mLP = .005). Serum potassium concentrations were significantly decreased by both treatments. Hemodynamic and metabolic changes were observed after both the first and second doses. However, plasma free fatty acid concentrations increased after the first dose only. Xenadrine RFA produced higher increases in glucose concentration than ephedra-guarana, but no other pharmacodynamic differences between the treatments were found. /The authors concluded that/ consumption of 2 doses of ephedra and guarana supplements, per supplement label recommendations, results in persistent increases in heart rate and blood pressure and unfavorable actions on glucose and potassium homeostasis. Such effects could be detrimental in persons with hypertension, atherosclerosis, or glucose intolerance, conditions that are strongly associated with obesity.For more Interactions (Complete) data for (L)-EPHEDRINE (25 total), please visit the HSDB record page. |
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| 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: cholinergi |
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| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 72(SRC), determined from a structure estimation method(2), indicates that (L)-ephedrine is expected to have high mobility in soil(SRC). The pKa of (L)-ephedrine is 9.65(3), indicating that this compound will exist primarily 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 (L)-ephedrine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.7X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(2). (L)-Ephedrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). (L)-Ephedrine is reported to gradually decomposes on exposure to light(5)therefore, (L)-ephedrine may be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC). (L)-Ephedrine has been classified as readily biodegradable by sewage sludge following acclimation(6).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 72(SRC), determined from a structure estimation method(2), indicates that (L)-ephedrine 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 8.7X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 1.4(SRC), from its log Kow of 1.13(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). The rate constant for the reaction of hydroxyl radicals in aqueous solutions at pH 10.5 is 2.3X10+9 L/mol-sec(6)this corresponds to an aquatic half-life of 349 days at an aquatic concentration of 1X10-17 hydroxyl radicals per liter(7). (L)-Ephedrine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). (L)-Ephedrine is reported to decompose gradually on exposure to light(8)therefore, (L)-ephedrine may be susceptible to direct photolysis in natural waters exposed to sunlight(SRC). (L)-Ephedrine has been classified as readily biodegradable by sewage sludge following acclimation(9).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), (L)-ephedrine, which has an estimated vapor pressure of 1.2X10-3 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist solely as a vapor in the ambient atmosphere. Since(L)-ephedrine exists as a solid below its melting point of 38.1 °C(3), occurrence in the particulate-phase may be possible(SRC). Vapor-phase (L)-ephedrine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 4 hours(SRC), calculated from its rate constant of 1.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). (L)-Ephedrine is reported to decompose gradually on exposure to light(3)therefore, (L)-ephedrine may be susceptible to direct photolysis by sunlight(SRC). |
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| Unerwünschte Wirkungen | Ephedrine may produce palpitations, headache, dizziness, nausea, vomiting, restlessness, and anxiety in the conscious patient. Ephedrine is also arrhythmogenic, and clinicians should be cautious when administering patients predisposed to arrhythmias or taking other arrhythmogenic medications, particularly digitalis. When used long-term, the catecholamine excess can result in contraction band necrosis of the myocardium, which predisposes the heart to ventricular arrhythmias.Another common effect of ephedrine is an alteration in the time until the onset and duration of action of other drugs. This effect is most notable during induction when giving ephedrine to a hypotensive patient before rocuronium.Additionally, ephedrine may be hepatotoxic, but there seems to be unclear evidence. This idea stems from case reports where ephedra species containing several compounds resulted in liver damage instead of a direct correlation.A less common effect experienced mostly by illicit users of ephedrine and its derivatives is the development of radiolucent urological ephedrine-containing stones and paranoid schizophrenia.Drug-Drug Interactions* Augmentation of the blood pressure: Clonidine, oxytocin, and propofol can increase blood pressure when administered with ephedrine.* Interactions that antagonize the pressor effect: α-adrenergic antagonists, β-adrenergic antagonists, and reserpine can antagonize the vasopressor effect of ephedrine.* Guanethidine: Ephedrine may inhibit the neuron blockage induced by guanethidine, resulting in loss of antihypertensive efficacy.* Rocuronium: Ephedrine may decrease the onset time of neuromuscular blockade when used with rocuronium for intubation if administered simultaneously. No interventions are needed.* Theophylline: Concomitant use of ephedrine and theophylline may increase nervousness and insomnia.* Cardiac glycosides: Administering ephedrine with a cardiac glycoside, such as digitalis, may increase the likelihood of arrhythmias. Monitor patients on digoxin who are administered ephedrine. |
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| Expositionspfade | Oralparenteral (intramuscular or intravenous injection). 85%. |
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| Milk Concentrations | Ephedrine is distributed into breast milk...use of ephedrine in nursing mothers is not recommended because of the risk for infants. |
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| Toxizitätsübersicht | IDENTIFICATION: Ephedrine is a colorless or white solid powder or crystals. It has a bitter taste and is odorless or slight aromatic odor. It is soluble in water, alcohol, chloroform, ether, glycerol, olive oil and in liquid paraffin. Ephedrine and its optical isomer pseudoephedrine are structurally very similar to methamphetamine. In illicit drug laboratories simple dehydrogenation is used to make methamphetamine from ephedrine. Indications: The most important uses are: as a bronchodilatornasal decongestantand treatment for syndrome of Stokes-Adamsas a mydriatic and hypertensor in the spinal anesthesia. It is also used as an herbal diet supplement under the name Ma-huang as an anorectic and CNS stimulant. HUMAN EXPOSURE: Contraindications: Cardiovascular diseasehypertensionhyperthyroidismpheochromocytoma and closed angle glaucoma. Ephedrine should not be given in patients being treated with MAOI (or have stopped treatment in the last 14 days). It should be used with caution in patients with prostatic enlargement or with renal impairment. Routes of exposure: Oral: Abuse of ephedrine-containing diet pills is a common occurrence. Inhalation: Ephedrine salts are used as nasal drops or sprays in the relief of nasal congestion associated with cold or rhinitis. Ephedrine can be abused by the nasal route by subjects who have developed dependence to its vasoconstrictive effect. Dermal: As an ointment is well absorbed. Eye: Eye-drops at 0.1% are effective in congestion of conjunctival allergy. Parenteral: Subcutaneous or intramuscular injections. Kinetics: Absorption by route of exposure: Ephedrine is readily and completely absorbed from the gastrointestinal tractplasma peak concentrations are reached an hour after ingestion. Biological half-life by route of exposure: It has a plasma half-life ranging from 3 to 6 hours depending on urinary pH. No change in half-life from that seen with therapeutic dosing was observed in an otherwise healthy patient wiAccording to the manufacturer's prescribing information, an overdose of ephedrine can cause a rapid rise in blood pressure. In the case of an overdose, careful blood pressure monitoring is recommended. If blood pressure rises to an unacceptable level, parenteral antihypertensive agents can be administered at the clinician's discretion.Signs and Symptoms: The principal manifestation of ephedrine poisoning is hypertension and convulsions. A case report of cardiomyopathy and spinal artery vasospasm leading to quadriplegia has been noted.Treatment: If respirations are shallow or cyanosis is present, secure the airway and provide mechanical ventilation.Antidote: For hypertension, 5 mg phentolamine mesylate diluted in saline may be administered slowly intravenously, or clinicians may give 100 mg orally. Convulsions may be controlled by benzodiazepines.Ephedrine 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. |
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| Plant Concentrations | (L)-Ephedrine occurrence in plants(1).[Table#4381]Ephedrine occurrence in plants(1). /Ephedrine/[Table#4382] |
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| Signs and Symptoms | Side-effects can include sweating, dry mouth, blurred vision, insomnia, loss of appetite, and dizziness. In addition users can feel restless, anxious and moody, become excitable and have a false sense of power and security. Amphetamine overdose can also cause cardiac arrhythmias, headaches, convulsions, hypertension, rapid heart rate, coma and death. Amphetamines are psychologically and physically addictive. |
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| Ongoing Test Status | 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, as of March 19, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=299-42-3]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. /Ephedrine sulfate/[Available from, as of March 19, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=134-72-5] |
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