*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : XH2275000
CHEMICAL NAME : Theobromine
CAS REGISTRY NUMBER : 83-67-0
BEILSTEIN REFERENCE NO. : 0016464
REFERENCE : 5-26-13-00553 (Beilstein Handbook Reference)
LAST UPDATED : 199701
DATA ITEMS CITED : 40
MOLECULAR FORMULA : C7-H8-N4-O2
MOLECULAR WEIGHT : 180.19
WISWESSER LINE NOTATION : T56 BN DN FNVMVJ B1 F1
COMPOUND DESCRIPTOR : Tumorigen
Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* 3,7-Dihydro-3,7-dimethyl-1H-purine-2,6-dione
* 3,7-Dimethylxanthine
* Diurobromine
* Santheose
* SC 15090
* Teobromin
* Theosalvose
* Theostene
* Thesal
* Thesodate
* Xanthine, 3,7-dimethyl-
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 26 mg/kg
TOXIC EFFECTS :
Behavioral - changes in motor activity (specific assay)
Gastrointestinal - nausea or vomiting
REFERENCE :
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams &
Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
Volume(issue)/page/year: 86,113,1946
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1265 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
GTPZAB Gigiena Truda i Professional'nye Zabolevaniya. Labor Hygiene and
Occupational Diseases. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR)
V.1-36, 1957-1992. For publisher information, see MTPEEI
Volume(issue)/page/year: 26(3),59,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 837 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
GTPZAB Gigiena Truda i Professional'nye Zabolevaniya. Labor Hygiene and
Occupational Diseases. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR)
V.1-36, 1957-1992. For publisher information, see MTPEEI
Volume(issue)/page/year: 26(3),59,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 552 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
ACPHEE Acta Pharmaceutica (Zagreb). (Acta Pharmaceutica, Masarykova 2,
41000 Zagreb, Croatia) V.42- 1992- Volume(issue)/page/year: 46,93,1996
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 530 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 6,601,1956
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 300 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
53,481,1980
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - cat
DOSE/DURATION : 200 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
85JCAE "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J.,
Prague, Czechoslovakia, Avicenum, 1986 Volume(issue)/page/year: -,1372,1986
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : 1 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig,
Ger. Dem. Rep.) Volume(issue)/page/year: 4,1289,1935
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 11596 mg/kg/28D-C
TOXIC EFFECTS :
Endocrine - changes in thymus weight
Related to Chronic Data - changes in testicular weight
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
63,312,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 4172 gm/kg/49D-C
TOXIC EFFECTS :
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Related to Chronic Data - changes in testicular weight
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
58,76,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 23520 mg/kg/7W-C
TOXIC EFFECTS :
Behavioral - food intake (animal)
Endocrine - changes in thymus weight
Related to Chronic Data - changes in testicular weight
REFERENCE :
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House,
Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year:
22,365,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 39900 mg/kg/19W-C
TOXIC EFFECTS :
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Related to Chronic Data - changes in testicular weight
REFERENCE :
JEPTDQ Journal of Environmental Pathology and Toxicology. (Park Forest
South, IL) V.1-5(3), 1977-81(?). For publisher information, see JEPOEC.
Volume(issue)/page/year: 2(3),687,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 40320 mg/kg/28D-C
TOXIC EFFECTS :
Endocrine - other changes
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Related to Chronic Data - death
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
49,127,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 4 gm/kg/28D-C
TOXIC EFFECTS :
Cardiac - other changes
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
53,481,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 30400 mg/kg/43W-C
TOXIC EFFECTS :
Cardiac - other changes
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
53,481,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - hamster
DOSE/DURATION : 33600 mg/kg/28D-C
TOXIC EFFECTS :
Behavioral - food intake (animal)
Endocrine - changes in thymus weight
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
49,127,1979
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 7500 mg/kg
SEX/DURATION : male 49 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - testes, epididymis, sperm duct
REFERENCE :
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House,
Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year:
22,365,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 17640 mg/kg
SEX/DURATION : male 49 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - male fertility index (e.g. # males impregnating
females per # males exposed to fertile nonpregnant females)
REFERENCE :
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway,
Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 4,137,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 6300 mg/kg
SEX/DURATION : female 1-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - live birth index (measured after birth)
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
REFERENCE :
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway,
Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 4,191,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE : 500 mg/kg
SEX/DURATION : female 13 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine,
Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14-
1936- Volume(issue)/page/year: 46,167,1969
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE : 500 mg/kg
SEX/DURATION : female 13 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - other developmental
abnormalities
REFERENCE :
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine,
Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14-
1936- Volume(issue)/page/year: 46,167,1969
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 3 gm/kg
SEX/DURATION : female 6-29 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
REFERENCE :
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House,
Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year:
24,363,1986
** MUTATION DATA **
TYPE OF TEST : Mutation in microorganisms
TEST SYSTEM : Bacteria - Escherichia coli
DOSE/DURATION : 150 mg/L
REFERENCE :
CSHSAZ Cold Spring Harbor Symposia on Quantitative Biology. (Cold Spring
Harbor Laboratory, POB 100, Cold Spring Harbor, NY 11724) V.1- 1933-
Volume(issue)/page/year: 16,337,1952
TYPE OF TEST : Mutation test systems - not otherwise specified
TEST SYSTEM : Microorganism - not otherwise specified
DOSE/DURATION : 500 ppm
REFERENCE :
IJEBA6 Indian Journal of Experimental Biology. (Publications & Information
Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963-
Volume(issue)/page/year: 13,387,1975
TYPE OF TEST : Cytogenetic analysis
TEST SYSTEM : Microorganism - not otherwise specified
DOSE/DURATION : 300 ppm
REFERENCE :
IJEBA6 Indian Journal of Experimental Biology. (Publications & Information
Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963-
Volume(issue)/page/year: 13,387,1975
TYPE OF TEST : Mutation in microorganisms
TEST SYSTEM : Protozoa - Euglena gracilis
DOSE/DURATION : 600 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 32,169,1975
TYPE OF TEST : Unscheduled DNA synthesis
TEST SYSTEM : Human Cells - not otherwise specified
DOSE/DURATION : 1 mmol/L
REFERENCE :
BIOJAU Biophysical Journal. (Rockefeller Univ. Press, 1230 York Ave., New
York, NY 10021) V.1- 1960- Volume(issue)/page/year: 35,665,1981
TYPE OF TEST : DNA inhibition
TEST SYSTEM : Human Cells - not otherwise specified
DOSE/DURATION : 4 mmol/L
REFERENCE :
BIOJAU Biophysical Journal. (Rockefeller Univ. Press, 1230 York Ave., New
York, NY 10021) V.1- 1960- Volume(issue)/page/year: 35,665,1981
TYPE OF TEST : Mutation test systems - not otherwise specified
TEST SYSTEM : Human Lymphocyte
DOSE/DURATION : 10 mmol/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 15,197,1972
TYPE OF TEST : Sister chromatid exchange
TEST SYSTEM : Human Lymphocyte
DOSE/DURATION : 100 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 169,105,1986
TYPE OF TEST : Mutation in microorganisms
TEST SYSTEM : Rodent - mouse Lymphocyte
DOSE/DURATION : 1250 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 169,105,1986
TYPE OF TEST : Mutation in mammalian somatic cells
TEST SYSTEM : Rodent - mouse Lymphocyte
DOSE/DURATION : 2 gm/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 169,105,1986
TYPE OF TEST : Sister chromatid exchange
TEST SYSTEM : Rodent - hamster Ovary
DOSE/DURATION : 500 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 169,105,1986
TYPE OF TEST : Sister chromatid exchange
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Rodent - hamster
DOSE/DURATION : 300 mg/kg
REFERENCE :
EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel,
Switzerland) V.1- 1945- Volume(issue)/page/year: 38,600,1982
*** REVIEWS ***
IARC Cancer Review:Human Inadequate Evidence
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 51,421,1991
IARC Cancer Review:Animal No Available Data
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 51,421,1991
IARC Cancer Review:Group 3
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 51,421,1991
TOXICOLOGY REVIEW
JRPMAP Journal of Reproductive Medicine. (2 Jacklynn Ct., St. Louis, MO
63132) V.3- 1969- Volume(issue)/page/year: 12,27,1974
TOXICOLOGY REVIEW
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
13,747,1989
*** STATUS IN U.S. ***
EPA TSCA Section 8(b) CHEMICAL INVENTORY
*** END OF RECORD ***