theobromine
3,7-dimethylpurine-2,6-dione
Identification
| Name | theobromine |
| IUPAC | 3,7-dimethylpurine-2,6-dione |
| CAS Number | 83-67-0 |
| EINECS | 201-494-2 |
| FDA UNII | OBD445WZ5P |
| Molecular Formula | C7 H8 N4 O2 |
| Molecular Weight | 180.16716000 |
| MDL Number | MFCD00022830 |
| Nikkaji Number | J3.874A |
| Beilstein | 0016464 |
| XlogP3 | -0.80 (est) |
Regulatory
| FDA/DG SANTE Petitions, Reviews, Notices | GRN 340 |
| DG SANTE Food Flavourings | 16.032 theobromine |
| FEMA Number | 3591 |
| FDA | No longer provide for the use of these seven synthetic flavoring substances |
| FDA Mainterm (SATF) | 83-67-0 ; THEOBROMINE |
Physical Properties
| Appearance | white powder (est) |
| Assay | 98.00 to 100.00 |
| Food Chemicals Codex Listed | No |
| Melting Point | 345.00 to 350.00 °C. @ 760.00 mm Hg |
| Flash Point | 32.00 °F. TCC ( 0.00 °C. ) (est) |
| logP (o/w) | -0.780 |
| Shelf Life | 24.00 month(s) or longer if stored properly. |
| Storage | store in cool, dry place in tightly sealed containers, protected from heat and light. |
| Soluble in | alcohol |
| Insoluble in | water |
Cosmetic Information
| CosIng | cosmetic data |
| Cosmetic Uses | fragrance |
Organoleptic Properties
| Taste Description | bitter |
Safety Information
| Preferred SDS | View |
| European information | Most important hazard(s): |
| Oral/Parenteral Toxicity | oral-rat LD50 1265 mg/kg |
| Dermal Toxicity | subcutaneous-rabbit LDLo 1000 mg/kg |
| Inhalation Toxicity | Not determined |
GHS Classification
['GHS Classification in accordance with 29 CFR 1910 (OSHA HCS)', 'GHS Label elements, including precautionary statements']
Safety in Use
| Category | flavoring agents |
| Recommendation for theobromine usage levels up to | not for fragrance use. |
| Maximised Survey-derived Daily Intakes (MSDI-EU) | 30.00 (μg/capita/day) |
| Structure Class | III |
| baked goods | - |
| beverages(nonalcoholic) | - |
| beverages(alcoholic) | - |
| breakfast cereal | - |
| cheese | - |
| chewing gum | - |
| condiments / relishes | - |
| confectionery froastings | - |
| egg products | - |
| fats / oils | - |
| fish products | - |
| frozen dairy | - |
| fruit ices | - |
| gelatins / puddings | - |
| granulated sugar | - |
| gravies | - |
| hard candy | - |
| imitation dairy | - |
| instant coffee / tea | - |
| jams / jellies | - |
| meat products | - |
| milk products | - |
| nut products | - |
| other grains | - |
| poultry | - |
| processed fruits | - |
| processed vegetables | - |
| reconstituted vegetables | - |
| seasonings / flavors | - |
| snack foods | - |
| soft candy | - |
| soups | - |
| sugar substitutes | - |
| sweet sauces | - |
| Dairy products, excluding products of category 02.0 (01.0) | 20.00000 |
| Fats and oils, and fat emulsions (type water-in-oil) (02.0) | - |
| Edible ices, including sherbet and sorbet (03.0) | - |
| Processed fruit (04.1) | - |
| Processed vegetables (incl. mushrooms & fungi, roots & tubers, pulses and legumes), and nuts & seeds (04.2) | - |
| Confectionery (05.0) | - |
| Chewing gum (05.3) | - |
| Cereals and cereal products, incl. flours & starches from roots & tubers, pulses & legumes, excluding bakery (06.0) | - |
| Bakery wares (07.0) | - |
| Meat and meat products, including poultry and game (08.0) | - |
| Fish and fish products, including molluscs, crustaceans and echinoderms (MCE) (09.0) | - |
| Eggs and egg products (10.0) | - |
| Sweeteners, including honey (11.0) | - |
| Salts, spices, soups, sauces, salads, protein products, etc. (12.0) | - |
| Foodstuffs intended for particular nutritional uses (13.0) | - |
| Non-alcoholic ("soft") beverages, excl. dairy products (14.1) | 75.00000 |
| Alcoholic beverages, incl. alcohol-free and low-alcoholic counterparts (14.2) | - |
| Ready-to-eat savouries (15.0) | - |
| Composite foods (e.g. casseroles, meat pies, mincemeat) - foods that could not be placed in categories 01.0 - 15.0 (16.0) | - |
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Potential Uses
Natural Occurrence
Synonyms
3,7-
dihydro-3,7-dimethyl-1H-purine-2,6-dione
2,6-
dihydroxy-3,7-dimethyl purine
2,6-
dihydroxy-3,7-dimethyl-purine
2,6-
dihydroxy-3,7-dimethylpurine
3,7-
dimethyl xanthine
3,7-
dimethyl-1,3,7-trihydropurine-2,6-dione
3,7-
dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
3,7-
dimethyl-3,7-dihydro-1H-purine-2,6-dione
3,7-
dimethyl-xanthine
3,7-
dimethylpurine-2,6-dione
3,7-
dimethylxanthine
diuretin
diurobromine
1H-
purine-2, 3,7-dihydro-3,7-dimethyl-
1H-
purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-
1H-
purine-2,6-dione,3,7-dihydro-3,7- dimethyl-
teobromin
theobromin
theobromine natural
theosalvose
theostene
thesodate
xanthine, 3,7-dimethyl-
US Patents:
4,006,261 - Flavoring with mixtures of theobromine and cyclic dipeptides
PubMed:
Theobromine enhances absorption of cacao polyphenol in rats.
PubMed:
Differing chemical compositions of three teas may explain their different effects on acute blood pressure in spontaneously hypertensive rats.
PubMed:
Quantitative analysis of major constituents in green tea with different plucking periods and their antioxidant activity.
PubMed:
Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners.
PubMed:
Identification and determination of synthetic pharmaceuticals as adulterants in eight common herbal weight loss supplements.
PubMed:
Interactions among chemical components of Cocoa tea (Camellia ptilophylla Chang), a naturally low caffeine-containing tea species.
PubMed:
Cocoa phytochemicals: recent advances in molecular mechanisms on health.
PubMed:
Diet of patients after pouch surgery may affect pouch inflammation.
PubMed:
Health benefits of methylxanthines in cacao and chocolate.
PubMed:
Simultaneous determination of caffeine, theophylline and theobromine in food samples by a kinetic spectrophotometric method.
PubMed:
Simultaneous quantification of caffeine and its three primary metabolites in rat plasma by liquid chromatography-tandem mass spectrometry.
PubMed:
Fuzhuanins A and B: the B-ring fission lactones of flavan-3-ols from Fuzhuan brick-tea.
PubMed:
[About flavouring substances and flavouring preparations regulation in the field of manufacturing of flavourings and foodstuffs].
PubMed:
Concentration of biologically active compounds extracted from Ilex paraguariensis St. Hil. by nanofiltration.
PubMed:
Cocoa and human health.
PubMed:
Guarana powder polysaccharides: characterisation and evaluation of the antioxidant activity of a pectic fraction.
PubMed:
Development and validation of a rapid ultra high pressure liquid chromatographic method for the determination of methylxanthines in herbal infusions.
PubMed:
Involvement of a novel intronic microRNA in cross regulation of N-methyltransferase genes involved in caffeine biosynthesis in Coffea canephora.
PubMed:
Diversity of cacao trees in Waslala, Nicaragua: associations between genotype spectra, product quality and yield potential.
PubMed:
Dietary nutrients associated with short and long sleep duration. Data from a nationally representative sample.
PubMed:
The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside.
PubMed:
Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario.
PubMed:
Modification of ginseng flavors by bitter compounds found in chocolate and coffee.
PubMed:
Influence of sugar type on the bioavailability of cocoa flavanols.
PubMed:
Development of a chromatographic low pressure flow injection system: application to the analysis of methylxanthines in coffee.
PubMed:
A general strategy for performing temperature-programming in high performance liquid chromatography--further improvements in the accuracy of retention time predictions of segmented temperature gradients.
PubMed:
Alkaloids in the human food chain--natural occurrence and possible adverse effects.
PubMed:
Comparison of the chemical constituents of aged pu-erh tea, ripened pu-erh tea, and other teas using HPLC-DAD-ESI-MSn.
PubMed:
Erythema multiforme-like eruption from a slimming drug preparation cutaneous adverse drug reaction.
PubMed:
Flavanols and methylxanthines in commercially available dark chocolate: a study of the correlation with nonfat cocoa solids.
PubMed:
Rapid methods to determine procyanidins, anthocyanins, theobromine and caffeine in rat tissues by liquid chromatography-tandem mass spectrometry.
PubMed:
Blood levels of vitamin D in teens and young adults with myopia.
PubMed:
Caffeine, pentoxifylline and theophylline form stacking complexes with IQ-type heterocyclic aromatic amines.
PubMed:
Theobromine and the pharmacology of cocoa.
PubMed:
Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation.
PubMed:
Energy drinks: a review of use and safety for athletes.
PubMed:
Phenolic acids and methylxanthines composition and antioxidant properties of mate (Ilex paraguariensis) residue.
PubMed:
Rapid determination of methylxanthines in real samples by high-performance liquid chromatography using the new FastGradient narrow-bore monolithic column.
PubMed:
Methylxanthines and phenolics content extracted during the consumption of mate (Ilex paraguariensis St. Hil) beverages.
PubMed:
Natural cocoa as diet-mediated antimalarial prophylaxis.
PubMed:
Identification of a major polyphenol and polyphenolic composition in leaves of Camellia irrawadiensis.
PubMed:
Rapid determination of phenolic compounds and alkaloids of carob flour by improved liquid chromatography tandem mass spectrometry.
PubMed:
Cilostazol: new drug. Intermittent claudication: too little efficacy, too many risks.
PubMed:
Antihypertensive effect of a polyphenol-rich cocoa powder industrially processed to preserve the original flavonoids of the cocoa beans.
PubMed:
Validity and reproducibility of a self-administered semi-quantitative food-frequency questionnaire for estimating usual daily fat, fibre, alcohol, caffeine and theobromine intakes among Belgian post-menopausal women.
PubMed:
Pharmacologic therapy for intermittent claudication.
PubMed:
Safety assessment of kola nut extract as a food ingredient.
PubMed:
Pentoxifylline: a drug with wide spectrum applications in dermatology.
PubMed:
Anti-TNF treatment reduces rat skeletal muscle wasting in monocrotaline-induced cardiac cachexia.
PubMed:
Quantitation of methylxanthinic alkaloids and phenolic compounds in mate (Ilex paraguariensis) and their effects on blood vessel formation in chick embryos.
PubMed:
Protection of human HepG2 cells against oxidative stress by cocoa phenolic extract.
PubMed:
Effects of chronic administration of caffeine and stress on feeding behavior of rats.
PubMed:
Simultaneous HPLC determination of caffeine, theobromine, and theophylline in food, drinks, and herbal products.
PubMed:
Determination of caffeine and associated compounds in food, beverages, natural products, pharmaceuticals, and cosmetics by micellar electrokinetic capillary chromatography.
PubMed:
Short-term toxicity of aristolochic acid, aristolochic acid-I and aristolochic acid-II in rats.
PubMed:
Predictive relationship between polyphenol and nonfat cocoa solids content of chocolate.
PubMed:
Chemical and archaeological evidence for the earliest cacao beverages.
PubMed:
Lipopolysaccharide and trovafloxacin coexposure in mice causes idiosyncrasy-like liver injury dependent on tumor necrosis factor-alpha.
PubMed:
Influence of peptone source on sporulation of Clostridium perfringens type A.
PubMed:
Selective liquid CO2 extraction of purine alkaloids in different Ilex paraguariensis progenies grown under environmental influences.
PubMed:
Simultaneous analysis of catechins, gallic acid, strictinin, and purine alkaloids in green tea by using catechol as an internal standard.
PubMed:
Microbial and dietary factors associated with the 8-prenylnaringenin producer phenotype: a dietary intervention trial with fifty healthy post-menopausal Caucasian women.
PubMed:
Urinary excretion of dietary contaminants in horses.
PubMed:
Development of a biosensor for caffeine.
PubMed:
Infection and anorexia.
PubMed:
Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas.
PubMed:
Molecular definition of the taste of roasted cocoa nibs (Theobroma cacao) by means of quantitative studies and sensory experiments.
PubMed:
Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus.
PubMed:
Pentoxifylline in ALS: a double-blind, randomized, multicenter, placebo-controlled trial.
PubMed:
The pivotal role of cytokines in muscle wasting during cancer.
PubMed:
Sensory-guided decomposition of roasted cocoa nibs (Theobroma cacao) and structure determination of taste-active polyphenols.
PubMed:
Solid-phase ultraviolet sensing system for determination of methylxanthines.
PubMed:
Evaluation of cocoa- and coffee-derived methylxanthines as toxicants for the control of pest coyotes.
PubMed:
Reinforcing effects of caffeine and theobromine as found in chocolate.
PubMed:
Classification of Ilex species based on metabolomic fingerprinting using nuclear magnetic resonance and multivariate data analysis.
PubMed:
Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.
PubMed:
Plant biochemistry: a naturally decaffeinated arabica coffee.
PubMed:
Dietary sources of nutrients among US adults, 1994 to 1996.
PubMed:
Determination of caffeine, theobromine, and theophylline in standard reference material 2384, baking chocolate, using reversed-phase liquid chromatography.
PubMed:
HPLC-MSn analysis of phenolic compounds and purine alkaloids in green and black tea.
PubMed:
Influence of agronomic variables on the composition of mate tea leaves (Ilex paraguariensis) extracts obtained from CO2 extraction at 30 degrees C and 175 bar.
PubMed:
Lisofylline, a novel anti-inflammatory agent, enhances glucose-stimulated insulin secretion in vivo and in vitro: studies in prediabetic and normal rats.
PubMed:
Metabolite profiling using (1)H NMR spectroscopy for quality assessment of green tea, Camellia sinensis (L.).
PubMed:
Effects of coffee components on the response of GABA(A) receptors expressed in Xenopus oocytes.
PubMed:
Chocolate feeding of pregnant mice influences length of limbs of their progeny.
PubMed:
Producing decaffeinated coffee plants.
PubMed:
[Simultaneous determination of various food additives by high performance liquid chromatography].
PubMed:
The role of Kupffer cells and TNF-alpha in monocrotaline and bacterial lipopolysaccharide-induced liver injury.
PubMed:
Value assignment of nutrient concentrations in standard reference material 2384 baking chocolate.
PubMed:
Inhibition of alkaline phosphatase activity of boar semen by pentoxifylline, caffeine, and theophylline.
PubMed:
Characterization of T lymphocyte subtypes in endotoxin-induced uveitis and effect of pentoxifylline treatment.
PubMed:
Caffeine potentiates the discriminative-stimulus effects of nicotine in rats.
PubMed:
Extraction of methylxanthines from guaraná seeds, maté leaves, and cocoa beans using supercritical carbon dioxide and ethanol.
PubMed:
Cacao usage by the earliest Maya civilization.
PubMed:
Study of catechin and xanthine tea profiles as geographical tracers.
PubMed:
Short-term toxicity of grass carp bile powder, 5alpha-cyprinol and 5alpha-cyprinol sulfate in rats.
PubMed:
Simultaneous determination of artificial sweeteners, preservatives, caffeine, theobromine and theophylline in food and pharmaceutical preparations by ion chromatography.
PubMed:
Food of the gods as mortals' medicine: the uses of choclate and cacao products.
PubMed:
Developmental variation of sugars, carboxylic acids, purine alkaloids, fatty acids, and endoproteinase activity during maturation of Theobroma cacao L. seeds.
PubMed:
Changes of gastric lipase activity after ethanol and indomethacin administration: influence of pretreatment with allopurinol, pentoxifylline and L-DOPA.
PubMed:
Improved high-performance liquid chromatography method to determine theobromine and caffeine in cocoa and cocoa products.
PubMed:
Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease: current and future perspectives.
PubMed:
Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients.
PubMed:
Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.
PubMed:
Medical management of peripheral arterial disease.
PubMed:
Uncertainty factors for chemical risk assessment. human variability in the pharmacokinetics of CYP1A2 probe substrates.
PubMed:
Uncertainty factors for chemical risk assessment: interspecies differences in the in vivo pharmacokinetics and metabolism of human CYP1A2 substrates.
PubMed:
Seizure activity and unresponsiveness after hydroxycut ingestion.
PubMed:
Cytosolic xanthine oxidoreductase mediated bioactivation of ethanol to acetaldehyde and free radicals in rat breast tissue. Its potential role in alcohol-promoted mammary cancer.
PubMed:
Bacterial lipopolysaccharide enhances aflatoxin B1 hepatotoxicity in rats by a mechanism that depends on tumor necrosis factor alpha.
PubMed:
Inhibition of adenosine uptake and augmentation of ischemia-induced increase of interstitial adenosine by cilostazol, an agent to treat intermittent claudication.
PubMed:
Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration.
PubMed:
Caffeine and theobromine levels in selected Nigerian beverages.
PubMed:
Dose independent pharmacokinetics of caffeine after intravenous administration under a chronic food-limited regimen.
PubMed:
Caffeine and theobromine levels in chocolate couverture and coating products.
PubMed:
Application of near-infrared reflectance spectroscopy to the simultaneous prediction of alkaloids and phenolic substances in green tea leaves.
PubMed:
Extraction of purine alkaloids from maté (Ilex paraguariensis) using supercritical CO(2).
PubMed:
Rapid analysis of methylated xanthines in teas by an improved high-performance liquid chromatographic method using a polyvinylpolypyrroridone pre-column.
PubMed:
Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and alpha-tocopherol: an experimental study.
PubMed:
Nutritive value of hot water- or cocoa-pod ash solution-treated cocoa bean cake for broiler chicks.
PubMed:
Inhibition of tumor necrosis factor alpha alters resistance to Mycobacterium avium complex infection in mice.
PubMed:
Nitric oxide deficiency, leukocyte activation, and resultant ischemia are crucial to the pathogenesis of diabetic retinopathy/neuropathy--preventive potential of antioxidants, essential fatty acids, chromium, ginkgolides, and pentoxifylline.
PubMed:
Liquid chromatographic determination of methylxanthines and catechins in herbal preparations containing guaraná.
PubMed:
Determination of caffeine and its metabolites by micellar electrokinetic capillary electrophoresis.
PubMed:
Recent advances in caffeine and theobromine toxicities: a review.
PubMed:
Oxidation of caffeine and related methylxanthines in ascorbate and polyphenol-driven Fenton-type oxidations.
PubMed:
Protein profiles and organoleptic properties of bread from wheat flour and full-fat or defatted fermented cocoa bean powder.
PubMed:
Oral and IP caffeine pharmacokinetics under a chronic food-limitation condition.
PubMed:
Analysis of the potential carcinogenicity of coffee and its related compounds in a medium-term liver bioassay of rats.
PubMed:
Green tea composition, consumption, and polyphenol chemistry.
PubMed:
Breast cancer and methylxanthine consumption.
PubMed:
Urinary excretion of theobromine in horses given contaminated pelleted food.
PubMed:
The effect of methylxanthines on milk volume and composition, and growth of rat pups.
PubMed:
The excretion of theobromine in Thoroughbred racehorses after feeding compounded cubes containing cocoa husk--establishment of a threshold value in horse urine.
PubMed:
Effect of methylxanthines on lactational performance of rats.
PubMed:
Use of flavor-amplified foods to improve nutritional status in elderly patients.
PubMed:
Methylxanthines: toxicity to humans. 3. Theobromine, paraxanthine and the combined effects of methylxanthines.
PubMed:
Methylxanthines: toxicity to humans. 1. Theophylline.
PubMed:
Variability in caffeine consumption from coffee and tea: possible significance for epidemiological studies.
PubMed:
The effect of nutritional factors on sex hormone levels in male twins.
PubMed:
Genotoxicity and carcinogenicity assessments of caffeine and theobromine.
PubMed:
Effect of pentoxifylline on Wrb antigen.
PubMed:
Evaluation of the genotoxicity of theobromine and caffeine.
PubMed:
Evaluation of the perinatal, postnatal and teratogenic effects of cocoa powder and theobromine in Sprague-Dawley/CD rats.
PubMed:
Evaluation of the teratogenic potential of cocoa powder and theobromine in New Zealand White rabbits.
PubMed:
Modulation of the behavioral effects of chlordiazepoxide by methylxanthines and analogs of adenosine in squirrel monkeys.
PubMed:
The fate of chronically consumed caffeine in the monkey (Macaca fascicularis).
PubMed:
Pentoxifylline: a new agent for intermittent claudication.
PubMed:
Antagonism of the behavioral effects of L-phenylisopropyladenosine (L-PIA) by caffeine and its metabolites.
PubMed:
High-performance liquid chromatographic determination of theobromine, theophylline and caffeine in food products.
PubMed:
Comparative toxicities of dietary caffeine and theobromine in the rat.
PubMed:
Tea: the plant and its manufacture; chemistry and consumption of the beverage.
PubMed:
Analytical methods for quantitation of methylxanthines.
PubMed:
Methylxanthine composition and consumption patterns of cocoa and chocolate products.
PubMed:
Central nervous system pharmacology of the dietary methylxanthines.
PubMed:
Theobromine metabolism.
PubMed:
[Effect of the harvest season on the composition of raw and fermented cotyledons of 2 varieties of cacao and shell fractions].
PubMed:
Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats.
PubMed:
Genotoxicity of cocoa examined by microbial and mammalian systems.
PubMed:
[Effect of methylxanthines on urinary prostaglandin E excretion of rats acutely loaded with salt and water (author's transl)].
PubMed:
The biochemistry and technology of tea manufacture.
PubMed:
Metabolic pathway of theobromine in the rat and identification of two new metabolites in human urine.
PubMed:
Effects on plasma and brain tryptophan in the rat of drugs and hormones that influence the concentration of unesterified fatty acid in the plasma.
PubMed:
Effect on hamster caries by purine derivatives vanillin and some tannin-containing materials. Caries in relation to food consumption and animal growth.
PubMed:
[Determination of Theobromine and its metabolites in urine].
PubMed:
VITAMIN E CONTENT OF VEGETABLE OILS AND FATS.