*** 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 ***