*** 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 ***