*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : MH6125000
CHEMICAL NAME           : Heliotrine
CAS REGISTRY NUMBER     : 303-33-3
BEILSTEIN REFERENCE NO. : 0292841
LAST UPDATED            : 199803
DATA ITEMS CITED        : 31
MOLECULAR FORMULA       : C16-H27-N-O5
MOLECULAR WEIGHT        : 313.44
WISWESSER LINE NOTATION : T55 AN CUTJ D1OVXQY1&1&Y1&O1 FQ
COMPOUND DESCRIPTOR     : Tumorigen
                          Drug
                          Mutagen
                          Reproductive Effector
                          Natural Product
SYNONYMS/TRADE NAMES :
   * (+)-Heliotrine
   * 7S-Heliotrine
   * Heliotron
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 50 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NATUAS Nature.  (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736)
   V.1-    1869-  Volume(issue)/page/year: 179,361,1957
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 296 mg/kg
TOXIC EFFECTS :
   Gastrointestinal - hypermotility, diarrhea
   Gastrointestinal - other changes
   Kidney, Ureter, Bladder - hematuria
REFERENCE :
   JPBAA7 Journal of Pathology and Bacteriology.  (London, UK)  V.1-96,
   1892-1968.  For publisher information, see JPTLAS. Volume(issue)/page/year:
   75,17,1958
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 274 mg/kg
TOXIC EFFECTS :
   Liver - other changes
REFERENCE :
   AMPLAO AMA Archives of Pathology.  (Chicago, IL)  V.50(4)-69, 1950-60.  For
   publisher information, see APLMAS.  Volume(issue)/page/year: 64,152,1957
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 251 mg/kg
TOXIC EFFECTS :
   Liver - other changes
REFERENCE :
   AMPLAO AMA Archives of Pathology.  (Chicago, IL)  V.50(4)-69, 1950-60.  For
   publisher information, see APLMAS.  Volume(issue)/page/year: 64,152,1957
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Mammal - species unspecified
DOSE/DURATION           : 250 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
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Unreported
SPECIES OBSERVED        : Mammal - species unspecified
DOSE/DURATION           : 260 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       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 900 mg/kg/9D-I
TOXIC EFFECTS :
   Liver - hepatitis (hepatocellular necrosis), zonal
   Blood - macrocytosis
   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:
   101,271,1989
 
                          ** TUMORIGENIC DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 460 mg/kg/6D-I
TOXIC EFFECTS :
   Tumorigenic - equivocal tumorigenic agent by RTECS criteria
   Gastrointestinal - tumors
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   35,2020,1975
 
                          ** 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 10 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
   resorbed implants per total number of implants)
REFERENCE :
   BJEPA5 British Journal of Experimental Pathology.  (Blackwell Scientific
   Pub. Ltd., POB 88, Oxford, UK)  V.1-    1920-  Volume(issue)/page/year:
   42,369,1961
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 100 mg/kg
SEX/DURATION            : female 9 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
   Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
   BJEPA5 British Journal of Experimental Pathology.  (Blackwell Scientific
   Pub. Ltd., POB 88, Oxford, UK)  V.1-    1920-  Volume(issue)/page/year:
   42,369,1961
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 150 mg/kg
SEX/DURATION            : female 16 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Specific Developmental Abnormalities - blood and lymphatic
   systems (including spleen and marrow)
REFERENCE :
   BJEPA5 British Journal of Experimental Pathology.  (Blackwell Scientific
   Pub. Ltd., POB 88, Oxford, UK)  V.1-    1920-  Volume(issue)/page/year:
   42,369,1961
 
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 - homeostasis
   Reproductive - Specific Developmental Abnormalities - craniofacial
   (including nose and tongue)
   Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
   BJEPA5 British Journal of Experimental Pathology.  (Blackwell Scientific
   Pub. Ltd., POB 88, Oxford, UK)  V.1-    1920-  Volume(issue)/page/year:
   42,369,1961
 
                            ** MUTATION DATA **
 
TYPE OF TEST            : Mutation in microorganisms
TEST SYSTEM             : Bacteria - Salmonella typhimurium
DOSE/DURATION           : 1 mg/plate
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 68,211,1979
 
TYPE OF TEST            : Cytogenetic analysis
ROUTE OF EXPOSURE       : Parenteral
TEST SYSTEM             : Insect - Drosophila melanogaster
DOSE/DURATION           : 500 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:
   94,115,1963
 
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            : Sex chromosome loss and nondisjunction
ROUTE OF EXPOSURE       : Oral
TEST SYSTEM             : Insect - Drosophila melanogaster
DOSE/DURATION           : 1 mmol/L
REFERENCE :
   TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis.  (Alan R. Liss, Inc.,
   41 E. 11th St., New York, NY 10003)  V.1-    1980- Volume(issue)/page/year:
   8,205,1988
 
TYPE OF TEST            : Dominant lethal test
ROUTE OF EXPOSURE       : Parenteral
TEST SYSTEM             : Insect - Drosophila melanogaster
DOSE/DURATION           : 1 mmol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 8,139,1969
 
TYPE OF TEST            : Mutation in microorganisms
TEST SYSTEM             : Mold - Aspergillus nidulans
DOSE/DURATION           : 20 mmol/L/4H
REFERENCE :
   NATUAS Nature.  (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736)
   V.1-    1869-  Volume(issue)/page/year: 210,593,1966
 
TYPE OF TEST            : DNA inhibition
TEST SYSTEM             : Human Liver
DOSE/DURATION           : 25 mg/L
REFERENCE :
   IJEVAW International Journal of Environmental Studies.  (Gordon & Breach
   Science Pub. Inc., c/o STBS Ltd., 1 Bedford St., London WCE 9PP, UK)  V.1-
   1970-  Volume(issue)/page/year: 1,107,1971
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
TEST SYSTEM             : Human Liver
DOSE/DURATION           : 10 mg/L
REFERENCE :
   IJEVAW International Journal of Environmental Studies.  (Gordon & Breach
   Science Pub. Inc., c/o STBS Ltd., 1 Bedford St., London WCE 9PP, UK)  V.1-
   1970-  Volume(issue)/page/year: 1,107,1971
 
TYPE OF TEST            : Cytogenetic analysis
TEST SYSTEM             : Human Lymphocyte
DOSE/DURATION           : 100 umol/L
REFERENCE :
   PLMEAA Planta Medica.  (Georg Thieme Verlag, Postfach 732, D-7000 Stuttgart
   1, Fed. Rep. Ger.) V.1-    1953-  Volume(issue)/page/year: 51,89,1985
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
ROUTE OF EXPOSURE       : Unreported
TEST SYSTEM             : Rodent - rat
DOSE/DURATION           : 150 ug/kg
REFERENCE :
   ANYAA9 Annals of the New York Academy of Sciences.  (New York Academy of
   Sciences, 2 E. 63rd St., New York, NY 10021)  V.1-    1877-
   Volume(issue)/page/year: 163,837,1969
 
TYPE OF TEST            : Micronucleus test
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 225 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            : Sister chromatid exchange
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 1200 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            : Cytogenetic analysis
TEST SYSTEM             : Mammal - species unspecified Leukocyte
DOSE/DURATION           : 50 umol/L
REFERENCE :
   AJBSAM Australian Journal of Biological Sciences.  (Commonwealth Scientific
   and Industrial Research Organization, 314 Albert St., E. Melbourne, Vic.
   3002, Australia)  V.6-    1953-  Volume(issue)/page/year: 21,469,1968

                              *** REVIEWS ***
 
   TOXICOLOGY REVIEW
   32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York,
   Springer, 1975  Volume(issue)/page/year: -,49,1975

                          *** STATUS IN U.S. ***
 
   EPA GENETOX PROGRAM 1988, Positive: Aspergillus-forward mutation
   
   EPA GENETOX PROGRAM 1988, Positive: D melanogaster-whole sex chrom. loss
   
   EPA GENETOX PROGRAM 1988, Positive: D melanogaster Sex-linked lethal
   
   EPA GENETOX PROGRAM 1988, Inconclusive: D melanogaster-nondisjunction
   
   EPA GENETOX PROGRAM 1988, Inconclusive: D melanogaster-reciprocal
   translocation

 
                            *** END OF RECORD ***