*** 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 ***