| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 96.5% (139 of 144) of all reports.Not ClassifiedAggregated GHS information provided per 144 reports by companies from 6 notifications to the ECHA C&L Inventory. |
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| Regulatorische Informationen | Chemical: Acetamide, N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-Melatonin: Does not have an individual approval but may be used under an appropriate group standard |
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| Weitere Sicherheitsinformationen | IMAP assessments - Acetamide, N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-: Environment tier I assessment |
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| FDA-Anforderungen | Implantation or injectable dosage form new animal drugs. Melatonin implant. ... Indications for use: For use in healthy male and female kit and adult female mink (Mustela vison) to accelerate the fur priming cycle. Limitations: For subcutaneous implantation in mink only. Do not implant potential breeding stock. Do not use in food-producing animals. |
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| Special Reports | Wurtman RJp. 457-464 in Encyclopedia of Dietary SupplementsCoates PM, Blackman MR, eds (2005): A review of pharmacological activity of melatonin. |
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| Hazard Classes and Categories | Not Classified |
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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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| Wechselwirkungen | ... This prospective, randomized, double-blind study included 200 adults with American Society of Anesthesiologists (ASA) physical status I. Patients received either 0.2 mg/kg melatonin or a placebo orally for premedication (n = 100 per group). Approximately 50 min later, subgroups of 10 melatonin and 10 placebo patients were administered various doses of propofol (0.5, 1.0, 1.5, 2.0, or 2.4 mg/kg) or thiopental (2.0, 3.0, 4.0, 5.0, or 6.0 mg/kg) for anesthetic induction. The ability of each patient to respond to the command, "open your eyes," and the disappearance of the eyelash reflex were assessed 60 sec after the end of the injection of propofol or thiopental. Dose-response curves were determined by probit analysis. RESULTS: Melatonin premedication decreased thiopental ED50 values for loss of response to verbal command and eyelash reflex from 3.4 mg/kg (95% confidence interval, 3.2-3.5 mg/kg) and 3.7 mg/kg (3.5-3.9 mg/kg) to 2.7 mg/kg (2.6-2.9 mg/kg) and 2.6 mg/kg (2.5-2.7 mg/kg), respectively (P < 0.05). Corresponding propofol ED50 values decreased from 1.5 mg/kg (1.4-1.6 mg/kg) and 1.6 mg/kg (1.5-1.7 mg/kg) to 0.9 mg/kg (0.8-0.96 mg/kg) and 0.9 mg/kg (0.8-0.95 mg/kg), respectively (P < 0.05). CONCLUSIONS: Melatonin premedication significantly decreased the doses of both propofol and thiopental required to induce anesthesia.Diadenosine tetraphosphate (Ap(4)A, 0.03 nmol) applied topically to the cornea of New Zealand white rabbits, evoked an increase in tear secretion of 9.7 +/- 2.60% (N=7). Melatonin (1 nmol) had no significant effect. Application of Ap(4)A in combination with melatonin, evoked a significantly greater increase in tear secretion of 34.2 +/- 5.8% (N=11). This potentiating effect of melatonin was blocked by pretreating the cornea with a topical application of the melatonin receptor antagonist, luzindole (240 nmol). Melatonin combined with Ap(4)A may be useful for treating dry eye conditions.The present study was designed to investigate the potential protective effect of melatonin against the hepatic and renal toxicity of lead in male rats. Three groups of animals were used in this study (control, lead acetate-treated (100 mg/kg), and lead acetate plus melatonin (10 mg/kg) for 30 days. Levels of lipid peroxidation (LPO) products, superoxide dismutase (SOD) activity, total glutathione (GSH), histopathological changes in the liver and kidneys were investigated. In addition, nuclear area (NA), nuclear volume (NV) and the ratio of nuclear volume/cellular volume (N/C) were measured in the liver. The results revealed increased LPO and decreased SOD, GSH, NA, NV and N/C in the studied organs of lead-treated rats. Histopathological observations showed severe damage in the liver and kidneys. Melatonin co-treatment to the lead-administered rats attenuated the increase of LPO and restored the activity of SOD and levels of GSH as well as the mean values of NA, NV and N/C. Also, the morphological damage in the liver and kidneys was reduced and the tissues appeared like those of controls. The present study suggests that melatonin may be useful in combating free radical-induced damage due to lead toxicity.... In this study, the effect of melatonin against the toxicity of doxorubicin (DOX) was investigated in rats. Hemodynamic function, pathological and biochemical changes were determined in different treated hearts. /The/ findings showed that a significant protection by melatonin (6 mg/kg for 15 days, cumulative dose of 90 mg/kg) against the DOX-induced toxicity was observed. Cardiac function was improved and lipid peroxidation decreased after melatonin treatment. It is concluded that melatonin provides protection against doxorubicin toxicity via an attenuation of lipid peroxidation.For more Interactions (Complete) data for MELATONIN (38 total), please visit the HSDB record page. |
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| Gesundheitliche Auswirkungen | Tolerance can develop, in which the person needs larger doses to achieve the desired effectthis can lead to overdose and death. Accidents or injury can also occur due to the side effects of loss of coordination, slowed reaction time, sleepiness and impaired judgment. Drugs in this category have a high potential for physical and psychological dependence. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. |
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| Hepatotoxicity | In several clinical trials, melatonin was found to be well tolerated and not associated with serum enzyme elevations or evidence of liver injury. Despite wide scale use, melatonin has not been convincingly linked to instances of clinically apparent liver injury. |
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| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 904(SRC), determined from a structure estimation method(2), indicates that melatonin is expected to have low mobility in soil(SRC). Melatonin has pKa values of 16.51 and -0.69 and is uncharged in the entire pH-range(3)therefore, sorption in soil will be determined by the neutral form of melatonin(SRC). Volatilization of melatonin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.6X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Melatonin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.4X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Melatonin absorbs at wavelengths >290 nm(4,5) and, therefore, may be susceptible to direct photolysis on soil surfaces exposed to sunlight(SRC). A strain of bacterium (Shewanella putrefaciens) isolated from an estuarine wetland sediment was able to use melatonin as a sole source of carbon and energy under aerobic conditions and completely degrade melatonin at initial of concentrations 25-150 mg/L within a 144-hr incubation period(6).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 904(SRC), determined from a structure estimation method(2), indicates that melatonin is 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 2.6X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of 1.18(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Melatonin absorbs at wavelengths >290 nm(6,7) and, therefore, may be susceptible to direct photolysis in waters exposed to sunlight(SRC). With the exception of the amide function, melatonin does not contain functional groups that hydrolyze under environmental conditions(3), and the amide group of melatonin is expected to have a hydrolysis half-life on the order of years under environmental conditions (pH 5-9)(2,SRC). A strain of bacterium (Shewanella putrefaciens) isolated from an estuarine wetland sediment was able to use melatonin as a sole source of carbon and energy under aerobic conditions and completely degrade melatonin at initial of concentrations 25-150 mg/L within a 144-hr incubation period(8).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), melatonin, which has an estimated vapor pressure of 1.4X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2),will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase melatonin 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 about 2 hours(SRC), calculated from its rate constant of 2.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase melatonin may be removed from the air by wet and dry deposition(SRC). Melatonin absorbs UV light at wavelengths >290 nm(3,4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
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| Lebensmitteluntersuchungswerte | Melatonin concentrations of 2.06 and 13.46 ng/g were detected in Balaton and Montmorency cherries obtained from commercial growers in Tranverse City, MI(1). Melatonin has been detected in bananas, grapes, rice, cereals, herbs, olive oil and wine(2). |
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| Unerwünschte Wirkungen | Melatonin is relatively nontoxic, although some mild adverse effects have been reported with higher doses and extended-release formulations, including drowsiness, daytime sedation, nausea, and headaches. No evidence suggests that patients develop tolerance to melatonin. However, impaired glucose tolerance has been reported in some cases. |
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| Expositionspfade | The absorption and bioavailability of melatonin varies widely. |
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| Milk Concentrations | The pineal hormone melatonin exhibits a circadian rhythm in body fluids. No data are available on melatonin in human milk. The present study was undertaken to determine whether melatonin is detectable in human milk and, if so, whether it exhibits a daily rhythm. Blood and milk were sampled between 1400-1700 h and again between 0200-0400 h from 10 mothers 3-4 days after delivery. Melatonin in both fluids was beyond the limit of detection during the day, whereas during the night, its concentration was 280 pmol/L in serum and 99 pmol/L in milk. Six mothers collected milk after each feeding throughout 1 24-h period within 3 months after delivery. Melatonin in the milk of all subjects exhibited a pronounced daily rhythm, with high levels during the night and undetectable levels during the day. The presence of the rhythm in milk suggests that melatonin fluctuations in milk might communicate time of day information to breast-fed infants. |
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| Toxizitätsübersicht | Toxicity due to melatonin might present as follows:Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body. The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since 1986. It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes.
MT1 receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes.
The binding of melatonin to melatonin receptors activates a few signaling pathways. MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activationstarting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[4] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell. |
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| Plant Concentrations | Melatonin has been identified in many plants including feverfew (Tanacetum parthenium), St John's wort (Hypericum perforatum), rice, corn, tomato and other edible fruits(1). |
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| Signs and Symptoms | Loss of coordination, slowed reaction time, sleepiness and impaired judgment. |
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| Ongoing Test Status | EPA has released the first beta version (version 0.5) of the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The beta version of 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 assaysSee the data in Chemical Explorer/[USEPAICSS Dashboard ApplicationAvailable from, as of March 28, 2014: 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, as of March 19, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=73-31-4] |
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| Alarmwort | Warnung |
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| Gefahrenhinweise | Code Gefahrenhinweise Gefahrenklasse Abteilung Alarmwort Symbol P-Code H302 |
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