*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : QB3140000
CHEMICAL NAME           : Monocrotaline
CAS REGISTRY NUMBER     : 315-22-0
BEILSTEIN REFERENCE NO. : 0048732
REFERENCE               : 4-27-00-06660 (Beilstein Handbook Reference)
LAST UPDATED            : 199612
DATA ITEMS CITED        : 44
MOLECULAR FORMULA       : C16-H23-N-O6
MOLECULAR WEIGHT        : 325.40
WISWESSER LINE NOTATION : T55 AN CUTJ FQ D1OV1- ET5OVTJ C1 D1 EQ
COMPOUND DESCRIPTOR     : Tumorigen
                          Drug
                          Mutagen
                          Natural Product
SYNONYMS/TRADE NAMES :
   * Crotaline
   *   (13-alpha,14-alpha)-14,19-Dihydro-12,13-dihydroxy-20-norcrotalanan-11,15
     -dione
   * Monocrotalin
   * NCI-C56462
   * 20-Norcrotalanan-11,15-dione, 14,19-dihydro-12,13-dihydroxy-,  
   (13-alpha,14-alpha)-
   * NSC 28693
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 66 mg/kg
TOXIC EFFECTS :
   Liver - hepatitis (hepatocellular necrosis), diffuse
REFERENCE :
   TXAPA9 Toxicology and Applied Pharmacology.  (Academic Press, Inc., 1 E.
   First St., Duluth, MN 55802) V.1-    1959-  Volume(issue)/page/year:
   18,387,1971
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 130 mg/kg
TOXIC EFFECTS :
   Lungs, Thorax, or Respiration - other changes
   Liver - other changes
REFERENCE :
   CBINA8 Chemico-Biological Interactions.  (Elsevier Scientific Pub. Ireland
   Ltd., POB 85, Limerick, Ireland)  V.1-    1969-  Volume(issue)/page/year:
   12,299,1976
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 60 mg/kg
TOXIC EFFECTS :
   Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
   TXAPA9 Toxicology and Applied Pharmacology.  (Academic Press, Inc., 1 E.
   First St., Duluth, MN 55802) V.1-    1959-  Volume(issue)/page/year:
   23,470,1972
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 92 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
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: 83,265,1945
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Unreported
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 60 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   28,2237,1968
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 259 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:
   59,424,1981
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 261 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
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: 75,78,1942
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Unreported
SPECIES OBSERVED        : Mammal - species unspecified
DOSE/DURATION           : 60 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   PAREAQ Pharmacological Reviews.  (Williams & Wilkins, 428 E. Preston St.,
   Baltimore, MD 21202) V.1-    1949-  Volume(issue)/page/year: 22,429,1970
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 61600 ug/kg/28D-C
TOXIC EFFECTS :
   Lungs, Thorax, or Respiration - changes in lung weight
   Biochemical - Enzyme inhibition, induction, or change in blood or tissue
   levels - other oxidoreductases
   Biochemical - Enzyme inhibition, induction, or change in blood or tissue
   levels - transaminases
REFERENCE :
   TXAPA9 Toxicology and Applied Pharmacology.  (Academic Press, Inc., 1 E.
   First St., Duluth, MN 55802) V.1-    1959-  Volume(issue)/page/year:
   60,193,1981
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 18 mg/kg/10D-C
TOXIC EFFECTS :
   Cardiac - changes in heart weight
   Lungs, Thorax, or Respiration - changes in lung weight
   Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
   JTEHD6 Journal of Toxicology and Environmental Health.  (Hemisphere Pub.,
   1025 Vermont Ave., NW, Washington, DC 20005)  V.1-    1975/76-
   Volume(issue)/page/year: 28,445,1989
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 75600 ug/kg/3W-C
TOXIC EFFECTS :
   Vascular - BP elevation not characterized in autonomic section
   Lungs, Thorax, or Respiration - changes in lung weight
   Cardiac - changes in heart weight
REFERENCE :
   MOPMA3 Molecular Pharmacology.  (Williams & Wilkins Co., 428 E. Preston St.,
   Baltimore, MD 21202) V.1-    1965-  Volume(issue)/page/year: 14,1189,1978
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 288 mg/kg/48W-I
TOXIC EFFECTS :
   Vascular - thrombosis distant from injection site
   Blood - hemorrhage
   Related to Chronic Data - death
REFERENCE :
   BJCAAI British Journal of Cancer.  (Macmillan Press Ltd., Houndmills,
   Basingstoke, Hants. RG21 2XS, UK)  V.1-    1947-  Volume(issue)/page/year:
   9,224,1955
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 1050 mg/kg/14D-I
TOXIC EFFECTS :
   Liver - changes in liver weight
   Endocrine - changes in spleen weight
   Blood - changes in leukocyte (WBC) count
REFERENCE :
   FAATDF Fundamental and Applied Toxicology.  (Academic Press, Inc., 1 E.
   First St., Duluth, MN 55802) V.1-    1981-  Volume(issue)/page/year:
   14,842,1990
 
                          ** TUMORIGENIC DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 130 mg/kg/1Y-I
TOXIC EFFECTS :
   Tumorigenic - Carcinogenic by RTECS criteria
   Lungs, Thorax, or Respiration - tumors
   Liver - 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:
   56,787,1976
 
                            ** MUTATION DATA **
 
TYPE OF TEST            : DNA repair
TEST SYSTEM             : Bacteria - Escherichia coli
DOSE/DURATION           : 1 gm/L
REFERENCE :
   CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House,
   Southfield Road, Eynsham, Oxford OX8 1JJ, UK)  V.1-    1980-
   Volume(issue)/page/year: 2,189,1981
 
TYPE OF TEST            : Specific locus test
ROUTE OF EXPOSURE       : Oral
TEST SYSTEM             : Insect - Drosophila melanogaster
DOSE/DURATION           : 10 umol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 182,243,1987
 
TYPE OF TEST            : Sex chromosome loss and nondisjunction
ROUTE OF EXPOSURE       : Parenteral
TEST SYSTEM             : Insect - Drosophila melanogaster
DOSE/DURATION           : 20 umol/L
REFERENCE :
   ZEVBA5 Zeitschrift fuer Vererbungslehre.  (Berlin, Fed. Rep. Ger.) V.89-98,
   1958-66.  For publisher information, see MGGEAE. Volume(issue)/page/year:
   91,74,1960
 
TYPE OF TEST            : Heritable translocation test
ROUTE OF EXPOSURE       : Parenteral
TEST SYSTEM             : Insect - Drosophila melanogaster
DOSE/DURATION           : 10 mmol/L
REFERENCE :
   JOGNAU Journal of Genetics.  (Belghoria, India)  V.1-63, 1910-77.
   Discontinued.  Volume(issue)/page/year: 59,273,1966
 
TYPE OF TEST            : DNA damage
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - rat
DOSE/DURATION           : 5 mg/kg
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   44,1505,1984
 
TYPE OF TEST            : Unscheduled DNA synthesis
TEST SYSTEM             : Rodent - rat Liver
DOSE/DURATION           : 2 umol/L
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   45,3125,1985
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
ROUTE OF EXPOSURE       : Subcutaneous
TEST SYSTEM             : Rodent - rat
DOSE/DURATION           : 20 mg/kg
REFERENCE :
   RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
   Pub. Ltd., P.O. Box 966, Westbury, NY 11590)  V.1-    1970-
   Volume(issue)/page/year: 5,859,1973
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
ROUTE OF EXPOSURE       : Subcutaneous
TEST SYSTEM             : Rodent - rat
DOSE/DURATION           : 20 mg/kg
REFERENCE :
   RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
   Pub. Ltd., P.O. Box 966, Westbury, NY 11590)  V.1-    1970-
   Volume(issue)/page/year: 5,859,1973
 
TYPE OF TEST            : Micronucleus test
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 125 mg/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 285,27,1993
 
TYPE OF TEST            : Micronucleus test
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 60 mg/kg
REFERENCE :
   EMMUEG Environmental and Molecular Mutagenesis.  (Alan R. Liss, Inc., 41 E.
   11th St., New York, NY 10003)  V.10-    1987-  Volume(issue)/page/year:
   26,37,1995
 
TYPE OF TEST            : Unscheduled DNA synthesis
TEST SYSTEM             : Rodent - mouse Liver
DOSE/DURATION           : 20 umol/L
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   45,3125,1985
 
TYPE OF TEST            : DNA inhibition
TEST SYSTEM             : Rodent - mouse Fibroblast
DOSE/DURATION           : 1 mmol/L
REFERENCE :
   JOUOD4 Journal of UOEH (University of Occupational and Environmental
   Health).  (Univ. of Occupational and Environmental Health, 1-1 Iseigaoka,
   Yahata-nishi-ku, Kitakyushu 807, Japan) V.1-    1979-
   Volume(issue)/page/year: 5,147,1983
 
TYPE OF TEST            : Morphological transformation
TEST SYSTEM             : Rodent - hamster Kidney
DOSE/DURATION           : 250 ug/L
REFERENCE :
   CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House,
   Southfield Road, Eynsham, Oxford OX8 1JJ, UK)  V.1-    1980-
   Volume(issue)/page/year: 1,161,1980
 
TYPE OF TEST            : Unscheduled DNA synthesis
TEST SYSTEM             : Rodent - hamster Liver
DOSE/DURATION           : 2 umol/L
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   45,3125,1985
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
TEST SYSTEM             : Rodent - hamster Ovary
DOSE/DURATION           : 2 mmol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 111,209,1983
 
TYPE OF TEST            : Cytogenetic analysis
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 31600 nmol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 282,169,1992
 
TYPE OF TEST            : Cytogenetic analysis
TEST SYSTEM             : Rodent - hamster Ovary
DOSE/DURATION           : 2 mmol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 111,209,1983
 
TYPE OF TEST            : Sister chromatid exchange
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 2500 ug/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 142,209,1985
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
TEST SYSTEM             : Mammal - species unspecified Leukocyte
DOSE/DURATION           : 50 umol/L
REFERENCE :
   CYTBAI Cytobios. (Faculty Press, 88 Regent St., Cambridge, UK)  V.1- 1969- 
   Volume(issue)/page/year: 14,151,1975
 
TYPE OF TEST            : Cytogenetic analysis
TEST SYSTEM             : Mammal - species unspecified Leukocyte
DOSE/DURATION           : 25 umol/L
REFERENCE :
   CYTBAI Cytobios. (Faculty Press, 88 Regent St., Cambridge, UK)  V.1- 1969- 
   Volume(issue)/page/year: 14,151,1975

                              *** 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: 10,291,1976

   IARC Cancer Review:Human No Adequate 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: 10,291,1976

   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:
   7,56,1987

   TOXICOLOGY REVIEW
   FEPRA7 Federation Proceedings, Federation of American Societies for
   Experimental Biology. (Bethesda, MD)  V.1-46, 1942-87.
   Volume(issue)/page/year: 35,89,1976

   TOXICOLOGY REVIEW
   CTRRDO Cancer Treatment Reports.  (Washington, DC)  V.60-71, 1976-87.  For
   publisher information,  see JNCIEQ.  Volume(issue)/page/year: 60,1171,1976

                          *** 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, Negative: TRP reversion
   
   EPA GENETOX PROGRAM 1988, Inconclusive: D melanogaster-reciprocal
   translocation
   
   EPA GENETOX PROGRAM 1988, Inconclusive: Mouse specific locus

 
                            *** END OF RECORD ***