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Theobromin
3,7-Dimethyl-3,7-dihydro-1H-purine-2,6-dione · 3,7-DIMETHYLXANTHINE · Theobromin · 3,7-dimethyl-1H-purine-2,6(3H,7H)-dione · Caffeine Impurity D · 3,7-dimethylpurine-2,6-dione · 2,6-DIHYDROXY-3,7-DIMETHYL-PURINE · 3,7-dihydro-3,7-dimethyl-1h-purine-6-dione
Identifikatoren & physikalische Daten
| CAS No. | 83-67-0 |
|---|---|
| Summenformel | C7H8N4O2 |
| Durchschnittliche Molmasse | 180,16 g/mol |
| Monoisotopische Masse | 180,0647255 g/mol |
| SMILES | Cn1cnc2c1c(=O)[nH]c(=O)n2C |
| InChIKey | YAPQBXQYLJRXSA-UHFFFAOYSA-N |
| PubChem CID | 5429 |
| ChEMBL | CHEMBL1114 |
| ChEBI | CHEBI:28946 |
| EC No. | 201-494-2 |
| DTXSID | DTXSID9026132 |
| Lokaler Name | Theobromin |
Chemische & physikalische Eigenschaften
| XLogP | -0,8 |
|---|---|
| Polarare Oberfläche (TPSA) | 67,2 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 3 |
| Frei drehbare Bindungen | 0 |
| Schwere Atome | 13 |
| Formalladung | 0 |
| Komplexität | 267 |
| Stoffklassen | Stimulant |
| Arzneimittel | DEA NFLIS-Drug Category -> StimulantsPharmaceuticals -> Metabolite of Caffeine, TheophyllinePharmaceuticals -> BrochodilatorsPharmaceuticals -> Listed in ZINC15 |
| Kosmetika | Cosmetic ingredients (Theobromine) -> CIR (Cosmetic Ingredient Review)Skin conditioning |
| LogP (Verteilungskoeffizient) | log Kow = -0.78 |
| Geschmack | Bitter tasting alkaloid |
| Lebensmittelzusatzstoffe | FLAVORING AGENT OR ADJUVANT -> FDA Substance added to food |
| Dichte | 1.522 g/cu cm at 20 °Crelative density: 1.522 at 20 °C1.50 |
| Aromastoffe | EU Flavoring substances |
| Color/Form | Monoclinic needles (/crystalline structure is/ lamellar twining on 001 /axis/) from waterWhite powder or monoclinic needles |
| Löslichkeit | less than 1 mg/mL at 64 °F (NTP, 1992)In water, 330 mg/L at 25 °CIn water, 500 mg/L, temp not specifiedSlightly soluble in waterOne gram dissolves in about 200 mL water, 150 mL boiling waterH2O: slightly solubleslightly soluble, <0.1 g/100 mL at 18 ºC |
| Human Drugs | Pharmaceuticals |
| Siedepunkt | Sublimes at 554-563 °F (NTP, 1992)Sublimes 290-295 °C312.97°C (rough estimate) |
| Schmelzpunkt | 345-350 °C |
| Brechungsindex | 1.6700 (estimate) |
| FEMA | 3591 | THEOBROMINE |
| Flammpunkt | 290-295°C |
| Lagerbedingungen | Inert atmosphere,Room Temperature |
| Aggregatzustand | solid |
| pKa (Säurekonstante) | 7.89(at 18℃) |
| Farbe | white |
| Geruch | odorless |
| Merck | 14,9282 |
| BRN | 16464 |
| Henry-Konstante | 6.2×105 mol/(m3Pa) at 25℃, HSDB (2015) |
| Hauptanwendungen | clinical testing |
| Kosmetik-Inhaltsstoffe Funktionen | SKIN CONDITIONINGFRAGRANCE |
| InChI | 1S/C7H8N4O2/c1-10-3-8-5-4(10)6(12)9-7(13)11(5)2/h3H,1-2H3,(H,9,12,13) |
| InChIKey | YAPQBXQYLJRXSA-UHFFFAOYSA-N |
| SMILES | [n]1(c2nc[n](c2[c]([nH][c]1=O)=O)C)C |
| LogP (Verteilungskoeffizient) | -0.78 |
| CAS Datenbank | 83-67-0(CAS DataBase Reference) |
| NIST chemische Informationen | 1H-Purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-(83-67-0) |
| EPA chemische Informationen | Theobromine (83-67-0) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH302 (98.6%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P264, P264+P265, P270, P280, P301+P317, P305+P351+P338, P318, P330, P337+P317, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 277 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.DangerH302: Harmful if swallowed [Warning Acute toxicity, oral] |
|---|---|
| Regulatorische Informationen | Chemical: 1H-Purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)Status: Active Update: 30-05-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/178991H-Purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - 1H-Purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-: Human health tier I assessment |
| Brandgefahren | Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992) |
| Gesundheitsgefahren | SYMPTOMS: Ingestion of large doses of this compound may cause nausea and vomiting. Loss of appetite may also occur. Other symptoms may include central nervous system and gastrointestinal changes. |
| FDA-Anforderungen | 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: Theobromine sodium salicylate is included in orally administered menstrual drug products. /Theobromine sodium salicylate/ |
| Reaktive Gruppe | Amides and Imides |
| Reactivity Profile | THEOBROMINE may be sensitive to prolonged exposure to light. This chemical has weakly acidic properties, combining with bases to forms salts. It also has even weaker basic properties, combining with acids to form salts which are decomposed in aqueous solution. (NTP, 1992). |
| Air and Water Reactions | Insoluble in water. |
| Hazard Classes and Categories | Acute Tox. 4 (98.6%)Acute toxicity (Oral) - Category 4 |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents |
| Brandbekämpfung | Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992) |
| Erste Hilfe | EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. |
| Brandbekämpfungsverfahren | 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. |
| Lagerbedingungen | Keep container tightly closed in a dry and well-ventilated place. Store under inert gas. Air sensitive. |
| Reinigungsverfahren | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: 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. |
| Freisetung ohne Brand | SMALL SPILLS AND LEAKAGE: If you spill this chemical, dampen the solid spill material with 5% ammonium hydroxide, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% ammonium hydroxide to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% ammonium hydroxide followed by washing 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. |
| Entsorgungsverfahren | SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in air, soil or watereffects on animal, aquatic and plant lifeand conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.Product: Offer surplus and non-recyclable solutions to a licensed disposal companyContaminated packaging: Dispose of as unused product. |
| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: 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.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.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. |
| Personal Protective Equipment (PPE) | RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| Körperbelastung | Following ingestion of 113 g of milk chocolate containing 240 mg theobromine and 16 mg caffeine, theobromine concentration in 6 samples of mother's milk ranged from 3.7 to 7.5 mg/L, mean of 5.3 mg/L, with the concentration max noted at 2.1 to 3.3 hours(1). |
| Wechselwirkungen | Several concentrations of theobromine (TB) and (-)-epicatechin (EC) were coadministered to rats, and plasma EC and its metabolites were determined using ultra-high-performance liquid chromatography-tandem mass spectrometry. It has been demonstrated that TB increases the absorption of EC in a dose-dependent manner. Cocoa powder had a similar effect, and the mechanism involved is not thought to depend on tight junctions.Experiments were designed to determine the effects of feeding the methylxanthines caffeine, theobromine, or theophylline to 4- to 6-week-old males rats at a dietary level of 0.5 % for periods ranging from 14 to 75 weeks. In the first two experiments, Osborne-Mendel rats were fed the test substances alone or in combination with sodium nitrite to test the hypothesis that these amines might nitrosate in vivo to produce toxic nitrosamine compounds. The compounds failed to produce neoplastic or preneoplastic lesions, but a significant positive finding was the occurrence of severe bilateral testicular atrophy with aspermatogenesis or oligospermatogenesis in 85-100 % of the rats fed caffeine or theobromine. ...The effects of allopurinol on the plasma clearance and metabolism of theobromine have been investigated under multiple-dosing conditions. Allopurinol had no effect on the clearance of theobromine, indicating that the elimination of this compound is dependent on enzyme systems other than xanthine oxidase, presumably the hepatic mixed-function oxidases. The excretion of 3-methylxanthine, 6-amino-5-(N-methylformylamino)-1-methyluracil, and unchanged theobromine were similarly unaffected by the allopurinol treatment. Although allopurinol abolished the formation of 7-methyluric acid (7MU) and increased the excretion of 7-methylxanthine (7MX), the metabolic clearance to (7MX + 7MU) was not significantly different with and without allopurinol. It is proposed that the secondary biotransformation of 7MX to 7MU is mediated by xanthine oxidase.The compounds identified in bile of phenobarbital-treated rats were 3,7-dimethyluric acid (64-76% of biliary radioactivity), dimethylallantoin (5-8%), 6-amino-5-(N-methylformylamino)- 1-methyluracil (10-17%) and theobromine (8-10%). In 3-methylcholanthrene-treated rats, urinary elimination of unchanged theobromine was reduced from 23-27% to only 2%, while excretion of 6-amino-5-(N-methylformylamino)-1- methyluracil was significantly increased. Only 3,7-dimethyluric acid was produced by liver microsomal incubation in control rats while phenobarbital and 3-methylcholanthrene pretreatment enhanced the biotransformation resulting in the production of all metabolites found in vivo as well as unknown polar compounds. |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that theobromine is expected to have very high mobility in soil(SRC). Volatilization of theobromine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.6X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Theobromine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Using an acclimated sewage sludge inoculum, theobromine reached 100% of its Theoretical BOD in 28 days(4), suggesting that biodegradation may be an important environmental fate process in soil previously exposed to this compound(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 theobromine 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 1.6X10-11 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 -0.78(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Using an acclimated sewage sludge inoculum, theobromine reached 100% of its Theoretical BOD in 28 days(7), suggesting that biodegradation may be an important environmental fate process in water previously exposed to this compound(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), theobromine, which has an estimated vapor pressure of 1.1X10-11 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 theobromine may be removed from the air by wet and dry deposition(SRC). Theobromine does not absorb light at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). |
| Lebensmitteluntersuchungswerte | Theobromine levels of 0.15-0.20% have been reported in manufactured tea and 0.3% in dried mate(1). Theobromine has been found in blended black tea at a level of 0.69% dry extractable solids present(1).Theobromine is the predominant alkaloid in coca and chocolate products(1). The theobromine content of finished chocolate products were reported as follows: baking chocolate, 1.386%chocolate flavored syrup, 0.242%cocoa, 15% fat, 2.598%dark sweet chocolate, 0.474%, and milk chocolate, 0.197%(1). An average level of 1.89% was found in eight commercial brands of cocao powder. Hot chocolate beverages contain average levels of 65 mg/5-oz serving. Chocolate milk samples from instant, cold, sweetened cocoa mixes had an average level of 58 mg theobromine per serving, 62 mg per serving for hot cocoa. Theobromine levels in dark eating chocolate were 0.36 to 0.63% with one 1-oz bar of dark chocolate containing 130 mg theobrominea one 1-oz bar of milk chocolate contained 44 mg theobromine. Chocolate frostings have a higher theobromine content (0.055-0.213%) than chocolate cakes(2). |
| Milk Concentrations | Theobromine is readily absorbed from food and evenly distributed in body fluidsthe half-times in plasma and saliva are highly correlated. Theobromine has been reported to pass into the breast milk of nursing mothers(1). Following ingestion of 113 g of milk chocolate containing 240 mg theobromine and 16 mg caffeine, theobromine concentration in 6 samples of mother's milk ranged from 3.7 to 7.5 mg/L, mean of 5.3 mg/L, with the concentration max noted at 2.1 to 3.3 hours(2).Six nursing mothers ingested 113 gm of Hershey's milk chocolate containing 240 mg of theobromine. Samples of plasma, saliva, and breast milk were assayed for theobromine by high pressure liquid chromatography. Peak theobromine concentrations of 3.7 to 8.2 mg/L were found in all fluids at 2 to 3 hour after ingestion of chocolate. ... Body clearance was 65 +/- 20 mL/hour/kilogram ... Theobromine is only slightly bound to plasma and milk proteins and concentrations in milk and saliva matched plasma data closely. The mean concentration ratios were 0.82 +/- 0.17 for milk/plasma and 0.92 +/- 0.17 for saliva/plasma. |
| Toxizitätsübersicht | 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: Theobromine is a white powder. It is an alkaloid found in cocoa and chocolate products. Theobromine is used principally to make caffeine . Formerly, theobromine and its derivatives were used in diuretics, myocardial stimulants, vasodilators and smooth muscle relaxants. Theobromine salts (calcium salicylate, sodium salicylate and sodium acetate) were used previously to dilate coronary arteries at doses of 300 to 600 mg per day. There is no current therapeutic use of theobromine. HUMAN EXPOSURE AND TOXICITY: It has been stated that "in large doses" theobromine may cause nausea and anorexia and that daily intake of 50-100 g cocoa (0.8-1.5 g theobromine) by humans has been associated with sweating, trembling and severe headache. Theobromine responses differed according to doseit showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In other studies, theobromine increased HDL-cholesterol concentrations by 0.16 mmol/L. Furthermore, there was a significant theobromine effect on increasing apolipoprotein A-I and decreasing apolipoprotein B and LDL-cholesterol concentrations. In human lymphocyte cultures, theobromine did not significantly increase the number of sister chromatid exchanges per cell, but, in another experiment using higher doses, the numbers of sister chromatid exchanges per cell were increased in the absence of an exogenous metabolic system. Theobromine induced breaks in human lymphocytes in culture, contrary to the results with rodent cells. ANIMAL STUDIES: High doses 250-300 mg/kg bw (mature animals) and 500 mg/kg bw (immature animals) have been shown to cause complete thymic atrophy in male and female rats. This effect was seen in hamsters only at a level of 850 mg/kg bw and in mice at levels of 1840-1880 mg/kg bw. Theobromine administration in rabbits resulted in marked changes in thymus and testes and the severity of lesions appeared to be related to the amounts of the ingested methylxanthine. Other experiments in rats also found the toxic effects of theobromine on the testis. In rats fed diets containing theobromine (daily doses, 53 or 99 mg/kg bw) on gestation days 6-19, no maternal toxicity was observed. Although no malformation occurred, slight decreases in fetal body weight were observed with the high dose, and a significant increase was seen in the frequency of skeletal variations. In rabbits, decreased fetal body weight and malformations were seen at doses of 125 or 200 mg/kgthe incidence of skeletal variations was increased with 75 mg/kg and over. Theobromine was mutagenic to Escherichia coli under conditions in which a constant growth rate and cell population density were maintained, but it was not mutagenic to Salmonella typhimurium. Theobromine induced mutations in a lower eukaryote, Euglena gracilis. Theobromine did not induce chromosomal aberrations in plants (Vicia faba). It was reported in an abstract that chromosomal aberrations were not observed in Drosophila melanogaster treated with 0.45% theobromine in feeding experiments. Chromosomal aberrations were not induced by theobromine in Chinese hamster cells. |
| Average Daily Intake | The daily per-capita intake in the US of theobromine from food and beverages was estimated to be 39.05 mg(1). |
| Plant Concentrations | Theobromine concentration in whole cacao husks and beans are 0.7-1.2% and 1.5-3%, respectively(1). Levels of 20 mg/kg have been reported in green coffee beans(1). The concentration of theobromine in cocoa beans varies widely depending on country of origin, i.e., Trinidad, 1.730 and New Guinea, 0.818% total alkaloid(2). The quantity in fresh tea leaves has been reported as 0.2 weight% on a dry weight basis(3).Theobromine occurrence in plants(1).[Table#6919] |
| 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 September 8, 2016: http://actor.epa.gov/dashboard/] |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of theobromine can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that theobromine is expected to have very high mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(3,4), suggesting that mobility may be much lower in some soils(SRC). |
| Natural Pollution Sources | Theobromine is the principal alkaloid of the cacao bean(1). It also occurs in tea and cola nuts and is a purine base closely related to caffeine(2). |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Theobromine, a methylxanthine-related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to doseit showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative./HUMAN EXPOSURE STUDIES/ Evidence from clinical studies has suggested that cocoa may increase high-density lipoprotein (HDL)-cholesterol concentrations. However, it is unclear whether this effect is attributable to flavonoids or theobromine, both of which are major cocoa components. We investigated whether pure theobromine increases serum HDL cholesterol and whether there is an interaction effect between theobromine and cocoa. The study had a 2-center, double-blind, randomized, placebo-controlled, full factorial parallel design. After a 2-wk run-in period, 152 healthy men and women (aged 40-70 yr) were randomly allocated to consume one 200-mL drink/d for 4 wk that contained 1) cocoa, which naturally provided 150 mg theobromine and 325 mg flavonoids [cocoa intervention (CC)], 2) 850 mg pure theobromine [theobromine intervention (TB)], 3) cocoa and added theobromine, which provided 1000 mg theobromine and 325 mg flavonoids [theobromine and cocoa intervention (TB+CC)], or 4) neither cocoa nor theobromine (placebo). Blood lipids and apolipoproteins were measured at the start and end of interventions. In a 2-factor analysis, there was a significant main effect of the TB (P < 0.0001) but not CC (P = 0.1288) on HDL cholesterol but no significant interaction (P = 0.3735). The TB increased HDL-cholesterol concentrations by 0.16 mmol/L (P < 0.0001). Furthermore, there was a significant main effect of the TB on increasing apolipoprotein A-I (P < 0.0001) and decreasing apolipoprotein B and LDL-cholesterol concentrations (P < 0.02). Theobromine independently increased serum HDL-cholesterol concentrations by 0.16 mmol/L. The lack of significant cocoa and interaction effects suggested that theobromine may be the main ingredient responsible for the HDL cholesterol-raising effect. This trial was registered at clinicaltrials.gov as NCT01481389./HUMAN EXPOSURE STUDIES/ Like caffeine, theobromine crosses the blood-brain barrier and binds to adenosine receptors, suggesting it might share caffeine's beneficial effects on mood and vigilance. Therefore, the purpose of this study was to assess the effect of theobromine doses commonly found in foods on mood and vigilance parameters sensitive to caffeine. Caffeine was tested as a positive control. Twenty-four men (age, 23 [3] years) completed 6 double-blind trials during which they consumed experimental beverages, assessed their mood using standardized self-report questionnaires, and completed a 2-hour visual vigilance task. Three experimental doses (100, 200, and 400 mg theobromine) were delivered in a cocoa-based beverage3 matched control treatments (0 mg theobromine, 400 mg theobromine, and 100 mg caffeine) were delivered in a non-cocoa beverage. Mean salivary concentrations of theobromine exhibited significant dose-dependent differences (400 mg trials > 200 mg trial > 100 mg trial > 0 mg trialsP < 0.005). At every dose tested, theobromine failed to consistently affect mood state or vigilance (P > 0.05), but 100-mg caffeine significantly decreased lethargy/fatigue and increased vigor (P = 0.006 and 0.011, respectively). These findings indicate theobromine does not influence mood and vigilance when administered in nutritionally relevant doses, despite sharing many of caffeine's structural characteristics./SIGNS AND SYMPTOMS/ It has been stated that "in large doses" theobromine may cause nausea and anorexia and that daily intake of 50-100 g cocoa (0.8-1.5 g theobromine) by humans has been associated with sweating, trembling and severe headache.For more Human Toxicity Excerpts (Complete) data for 3,7-Dimethylxanthine (7 total), please visit the HSDB record page. |
| F | 10-23 |
| Wassergefährdungsklasse (WGK) | 1 |
| TSCA-Inventar-Status | TSCA listed |
| UN-Transportnummer | UN1230 - class 3 - PG 2 - Methanol, solution |
| Zollcode | 29399990 |
| RTECS-Nr. | XH2275000 |
| R-Sätze (R) | 22-36/37/38-39/23/24/25-23/24/25-11 |
| Gefahrensymbole | Xn,Xi,T,F |
| Sicherheitshinweise (S) | 22-24/25-36-26-45-36/37-16-7 |
| Lagerklasse | 3 - Flammable liquids |
| Gefahrstoffdaten | 83-67-0(Hazardous Substances Data) |
| Gefahrenklasse | Acute Tox. 4 OralEye Irrit. 2Flam. Liq. 2 |
Anwendungen & Verwendung
Beschreibung
Theobromine is a methylxanthine alkaloid and derivative of caffeine that has been found in cocoa beans and has diverse biological activities. It is an adenosine A1 receptor antagonist (IC50s = 200-280 μM in radioligand binding assays using rat brain membranes). Theobromine (150 μg/ml) increases AMPK phosphorylation and inhibits adipocyte differentiation, ERK and JNK phosphorylation, and IL-6 and TNF-α production in 3T3-L1 preadipocytes cultured in differentiation medium. It inhibits decreases in renal cortex SIRT1 activity and increases in NADPH oxidase-dependent reactive oxygen species (ROS) production, as well as reduces kidney hypertrophy and albuminuria in a spontaneously hypertensive rat model of streptozotocin-induced diabetes when administered at a dose of 5 mg/kg per day. Theobromine is toxic to dogs with an LD50 value of 250 to 500 mg/kg.
Occurrence
Reported found in cocoa bean, cocoa powder, cola nut and tea.