*** 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 ***