*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : NI3950000 CHEMICAL NAME : Imidazole-4-carboxamide, 5-(3,3-dimethyl-1-triazeno)- CAS REGISTRY NUMBER : 4342-03-4 LAST UPDATED : 199709 DATA ITEMS CITED : 46 MOLECULAR FORMULA : C6-H10-N6-O MOLECULAR WEIGHT : 182.22 WISWESSER LINE NOTATION : T5M CNJ DVZ ENUNN1&1 COMPOUND DESCRIPTOR : Tumorigen Drug Mutagen Reproductive Effector Human SYNONYMS/TRADE NAMES : * Biocarbazine R * Dacarbazine * Deticene * (Dimethyltriazeno)imidazolecarboxamide * 4-(Dimethyltriazeno)imidazole-5-carboxamide * 4-(3,3-Dimethyl-1-triazeno)imidazole-5-carboxamide * 4-(5)-(3,3-Dimethyl-1-triazeno)imidazole-5(4)-carboxamide * 5-(Dimethyltriazeno)imidazole-4-carboxamide * 5-(3,3-Dimethyltriazeno)imidazole-4-carboxamide * 5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide * DTIC-dome * 1H-Imidazole-4-carboxamide, 5-(3,3-dimethyl-1-triazenyl)- * NCI-C04717 * NSC-45388 *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human DOSE/DURATION : 3500 ug/kg TOXIC EFFECTS : Gastrointestinal - nausea or vomiting Blood - leukopenia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - dehydrogenases REFERENCE : CCROBU Cancer Chemotherapy Reports, Part 1. (Washington, DC) V.52(6)-59, 1968-75. For publisher information, see CTRRDO. Volume(issue)/page/year: 57,83,1973 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2147 mg/kg TOXIC EFFECTS : Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,3105,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 350 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARGEAR Archiv fuer Geschwulstforschung. (VEB Verlag Volk und Gesundheit Neue Gruenstr. 18, Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1949- Volume(issue)/page/year: 50,306,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 411 mg/kg TOXIC EFFECTS : Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,3105,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2032 mg/kg TOXIC EFFECTS : Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,3105,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 567 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : CTRRDO Cancer Treatment Reports. (Washington, DC) V.60-71, 1976-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 62,721,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 466 mg/kg TOXIC EFFECTS : Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 9,3105,1981 TYPE OF TEST : LD10 - Lethal Dose ROUTE OF EXPOSURE : Parenteral SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 250 mg/kg TOXIC EFFECTS : Tumorigenic - active as anti-cancer agent REFERENCE : JSONAU Journal of Surgical Oncology. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1969- Volume(issue)/page/year: 15,355,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1568 mg/kg/14D-I TOXIC EFFECTS : Related to Chronic Data - death REFERENCE : CTRRDO Cancer Treatment Reports. (Washington, DC) V.60-71, 1976-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 62,693,1978 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1730 mg/kg/15W-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors REFERENCE : JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8. Volume(issue)/page/year: 54,951,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 25 mg/kg female 20 day(s) after conception TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Brain and Coverings - tumors REFERENCE : ARGEAR Archiv fuer Geschwulstforschung. (VEB Verlag Volk und Gesundheit Neue Gruenstr. 18, Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1949- Volume(issue)/page/year: 50,306,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3900 mg/kg/26W-I TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors REFERENCE : RRCRBU Recent Results in Cancer Research. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1965- Volume(issue)/page/year: 52,1,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1950 mg/kg/26W-I TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors Blood - lymphoma, including Hodgkin's disease REFERENCE : RRCRBU Recent Results in Cancer Research. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1965- Volume(issue)/page/year: 52,1,1975 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3700 mg/kg/14W-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors REFERENCE : PAACA3 Proceedings of the American Association for Cancer Research. (Waverly Press, 428 E. Preston St., Baltimore, MD 21202) V.1- 1954- Volume(issue)/page/year: 11,73,1970 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 50 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 33,2231,1973 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 200 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : ANREAK Anatomical Record. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1906/08- Volume(issue)/page/year: 186,461,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 100 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 33,2231,1973 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 400 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 33,2231,1973 ** MUTATION DATA ** TYPE OF TEST : Mutation in microorganisms TEST SYSTEM : Bacteria - Salmonella typhimurium DOSE/DURATION : 100 ug/plate REFERENCE : CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 3,467,1982 TYPE OF TEST : Mutation in microorganisms TEST SYSTEM : Bacteria - Escherichia coli DOSE/DURATION : 100 ug/plate REFERENCE : CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 3,467,1982 TYPE OF TEST : DNA repair TEST SYSTEM : Bacteria - Escherichia coli DOSE/DURATION : 600 pg/plate REFERENCE : NULSAK Nucleus (Calcutta). (Dr. A.K. Sharma, Centre of Advanced Studies in Cell and Chromosome Research, Calcutta, 35 Baliygunge Circular Rd., Calcutta 700 019, India) V.1- 1958- Volume(issue)/page/year: 28,159,1985 TYPE OF TEST : Sex chromosome loss and nondisjunction ROUTE OF EXPOSURE : Oral TEST SYSTEM : Insect - Drosophila melanogaster DOSE/DURATION : 500 umol/L/3D REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 202,251,1988 TYPE OF TEST : Gene conversion and mitotic recombination TEST SYSTEM : Yeast - Saccharomyces cerevisiae 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: 204,239,1988 TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - mouse Fibroblast DOSE/DURATION : 10 umol/L REFERENCE : BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 24,615,1975 TYPE OF TEST : Mutation test systems - not otherwise specified TEST SYSTEM : Rodent - mouse Fibroblast DOSE/DURATION : 100 umol/L REFERENCE : BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 24,615,1975 TYPE OF TEST : DNA damage ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - rat DOSE/DURATION : 6 mg/kg REFERENCE : CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 12,285,1991 TYPE OF TEST : DNA inhibition ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - rat DOSE/DURATION : 37500 ug/kg REFERENCE : BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 21,2817,1972 TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - rat Cells - not otherwise specified DOSE/DURATION : 1 mmol/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 36,2827,1976 TYPE OF TEST : Mutation test systems - not otherwise specified TEST SYSTEM : Rodent - rat Cells - not otherwise specified DOSE/DURATION : 1 mmol/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 36,2827,1976 TYPE OF TEST : Micronucleus test ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 225 mg/kg/48H (Intermittent) REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 389,3,1997 TYPE OF TEST : Mutation in microorganisms TEST SYSTEM : Rodent - mouse Lymphocyte DOSE/DURATION : 75 mg/L REFERENCE : DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 1,277,1978 TYPE OF TEST : Mutation test systems - not otherwise specified ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 9 mg/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 223,259,1989 TYPE OF TEST : Cytogenetic analysis ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 9 mg/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 223,259,1989 TYPE OF TEST : Mutation in mammalian somatic cells TEST SYSTEM : Rodent - mouse Lymphocyte DOSE/DURATION : 75 mg/L REFERENCE : DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 1,277,1978 TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Rodent - hamster Ovary DOSE/DURATION : 200 mg/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,577,1983 TYPE OF TEST : Mutation in mammalian somatic cells TEST SYSTEM : Rodent - hamster Lung DOSE/DURATION : 20 mg/L REFERENCE : CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 3,467,1982 TYPE OF TEST : Mutation in mammalian somatic cells TEST SYSTEM : Rodent - hamster Ovary DOSE/DURATION : 400 mg/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,577,1983 *** REVIEWS *** IARC Cancer Review:Animal Sufficient 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: 26,203,1981 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: 26,203,1981 IARC Cancer Review:Group 2B IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,184,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3246 No. of Facilities: 412 (estimated) No. of Industries: 1 No. of Occupations: 9 No. of Employees: 17273 (estimated) No. of Female Employees: 12863 (estimated) *** STATUS IN U.S. *** EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat EPA GENETOX PROGRAM 1988, Positive: D melanogaster Sex-linked lethal EPA GENETOX PROGRAM 1988, Positive: CHO gene mutation NCI Carcinogenesis Studies (ipr);clear evidence:mouse,rat RRCRBU Recent Results in Cancer Research. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1965- Volume(issue)/page/year: 52,1,75 NTP 7th Annual Report on Carcinogens, 1992 : anticipated to be carcinogen *** END OF RECORD ***