*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : LV2500000
CHEMICAL NAME           : Furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxol-6(5ah)-one,
                          5,8,8a,9-tetrahydro-9-hydroxy-5-
                          (3,4,5-trimethoxyphenyl)-
CAS REGISTRY NUMBER     : 518-28-5
LAST UPDATED            : 199806
DATA ITEMS CITED        : 36
MOLECULAR FORMULA       : C22-H22-O8
MOLECULAR WEIGHT        : 414.44
WISWESSER LINE NOTATION : T E5 C665 FVO NO PO OHTT&&J DR CO1 DO1 EO1& JQ
COMPOUND DESCRIPTOR     : Drug
                          Mutagen
                          Reproductive Effector
                          Natural Product
SYNONYMS/TRADE NAMES :
   * Condylox
   * NSC 24818
   * Podofilox
   * Podophyllinic acid lactone
   * Podophyllotoxin
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Administration onto the skin
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 500 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   PIXXD2 PCT (Patent Cooperation Treaty) International Application.  (U.S.
   Patent and Trademark Office, Foreign Patents, Washington, DC 20231)
   Volume(issue)/page/year: #86-04062
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 15 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Lungs, Thorax, or Respiration - dyspnea
   Gastrointestinal - nausea or vomiting
REFERENCE :
   FEPRA7 Federation Proceedings, Federation of American Societies for
   Experimental Biology. (Bethesda, MD)  V.1-46, 1942-87.
   Volume(issue)/page/year: 7,249,1948
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 8 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Lungs, Thorax, or Respiration - dyspnea
   Lungs, Thorax, or Respiration - respiratory depression
REFERENCE :
   PSEBAA Proceedings of the Society for Experimental Biology and Medicine.
   (Academic Press, Inc., 1 E. First St., Duluth, MN 55802)  V.1-    1903/04-
   Volume(issue)/page/year: 77,269,1951
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 8700 ug/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Lungs, Thorax, or Respiration - dyspnea
   Gastrointestinal - nausea or vomiting
REFERENCE :
   FEPRA7 Federation Proceedings, Federation of American Societies for
   Experimental Biology. (Bethesda, MD)  V.1-46, 1942-87.
   Volume(issue)/page/year: 7,249,1948
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intramuscular
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 3 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Lungs, Thorax, or Respiration - dyspnea
   Gastrointestinal - nausea or vomiting
REFERENCE :
   FEPRA7 Federation Proceedings, Federation of American Societies for
   Experimental Biology. (Bethesda, MD)  V.1-46, 1942-87.
   Volume(issue)/page/year: 7,249,1948
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 100 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   PIXXD2 PCT (Patent Cooperation Treaty) International Application.  (U.S.
   Patent and Trademark Office, Foreign Patents, Washington, DC 20231)
   Volume(issue)/page/year: #86-04062
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 30 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   ARZNAD Arzneimittel-Forschung. Drug Research.  (Editio Cantor Verlag,
   Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.)  V.1-    1951-
   Volume(issue)/page/year: 11,327,1961
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 24600 ug/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   TOXIA6 Toxicon.  (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW,
   UK)  V.1-    1962-  Volume(issue)/page/year: 8,85,1970
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 56 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   CSLNX* U.S. Army Armament Research & Development Command, Chemical Systems
   Laboratory, NIOSH Exchange Chemicals.  (Aberdeen Proving Ground, MD 21010)
   Volume(issue)/page/year: NX#01679
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 1 mg/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Gastrointestinal - nausea or vomiting
   Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
   AEXPBL Archiv fuer Experimentelle Pathologie und Pharmakologie.  (Leipzig,
   Ger. Dem. Rep.)  V.1-109, 1873-1925.  For publisher information, see NSAPCC.
    Volume(issue)/page/year: 28,32,1891
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Mammal - cat
DOSE/DURATION           : 300 ug/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Gastrointestinal - nausea or vomiting
   Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
   AEXPBL Archiv fuer Experimentelle Pathologie und Pharmakologie.  (Leipzig,
   Ger. Dem. Rep.)  V.1-109, 1873-1925.  For publisher information, see NSAPCC.
    Volume(issue)/page/year: 28,32,1891
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - cat
DOSE/DURATION           : 1700 ug/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Lungs, Thorax, or Respiration - dyspnea
   Gastrointestinal - nausea or vomiting
REFERENCE :
   FEPRA7 Federation Proceedings, Federation of American Societies for
   Experimental Biology. (Bethesda, MD)  V.1-46, 1942-87.
   Volume(issue)/page/year: 7,249,1948
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intramuscular
SPECIES OBSERVED        : Mammal - cat
DOSE/DURATION           : 4 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Lungs, Thorax, or Respiration - dyspnea
   Skin and Appendages - cutaneous sensitization, experimental (after topical
   exposure)
REFERENCE :
   FEPRA7 Federation Proceedings, Federation of American Societies for
   Experimental Biology. (Bethesda, MD)  V.1-46, 1942-87.
   Volume(issue)/page/year: 7,249,1948
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Administration onto the skin
SPECIES OBSERVED        : Rodent - rabbit
DOSE/DURATION           : 200 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   PIXXD2 PCT (Patent Cooperation Treaty) International Application.  (U.S.
   Patent and Trademark Office, Foreign Patents, Washington, DC 20231)
   Volume(issue)/page/year: #86-04062
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rabbit
DOSE/DURATION           : 5 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Lungs, Thorax, or Respiration - dyspnea
   Skin and Appendages - cutaneous sensitization, experimental (after topical
   exposure)
REFERENCE :
   FEPRA7 Federation Proceedings, Federation of American Societies for
   Experimental Biology. (Bethesda, MD)  V.1-46, 1942-87.
   Volume(issue)/page/year: 7,249,1948
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Bird - pigeon
DOSE/DURATION           : 10 mg/kg
TOXIC EFFECTS :
   Behavioral - muscle contraction or spasticity
   Gastrointestinal - hypermotility, diarrhea
REFERENCE :
   AEXPBL Archiv fuer Experimentelle Pathologie und Pharmakologie.  (Leipzig,
   Ger. Dem. Rep.)  V.1-109, 1873-1925.  For publisher information, see NSAPCC.
    Volume(issue)/page/year: 28,32,1891
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Bird - chicken
DOSE/DURATION           : 6250 ug/kg
TOXIC EFFECTS :
   Behavioral - muscle contraction or spasticity
   Gastrointestinal - hypermotility, diarrhea
REFERENCE :
   AEXPBL Archiv fuer Experimentelle Pathologie und Pharmakologie.  (Leipzig,
   Ger. Dem. Rep.)  V.1-109, 1873-1925.  For publisher information, see NSAPCC.
    Volume(issue)/page/year: 28,32,1891
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Parenteral
SPECIES OBSERVED        : Amphibian - frog
DOSE/DURATION           : 152 mg/kg
TOXIC EFFECTS :
   Behavioral - stiffness
REFERENCE :
   AEXPBL Archiv fuer Experimentelle Pathologie und Pharmakologie.  (Leipzig,
   Ger. Dem. Rep.)  V.1-109, 1873-1925.  For publisher information, see NSAPCC.
    Volume(issue)/page/year: 28,32,1891
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 11690 ug/kg/7D-I
TOXIC EFFECTS :
   Gastrointestinal - other changes
   Liver - other changes
REFERENCE :
   TOXID9 Toxicologist.  (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway,
   Akron, OH 44311) V.1-    1981-  Volume(issue)/page/year: 15,291,1995
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 500 mg/kg
SEX/DURATION            : female 1-5 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - female fertility index (e.g. # females pregnant
   per # sperm positive females; # females pregnant per # females mated)
REFERENCE :
   JRPFA4 Journal of Reproduction and Fertility.  (Biochemical Soc. Book Depot,
   POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK)  V.1-    1960-
   Volume(issue)/page/year: 14,534,1967
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 10 mg/kg
SEX/DURATION            : female 15-16 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
   Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
   PSEBAA Proceedings of the Society for Experimental Biology and Medicine.
   (Academic Press, Inc., 1 E. First St., Duluth, MN 55802)  V.1-    1903/04-
   Volume(issue)/page/year: 113,124,1963
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 10 mg/kg
SEX/DURATION            : female 11-12 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
   resorbed implants per total number of implants)
REFERENCE :
   PSEBAA Proceedings of the Society for Experimental Biology and Medicine.
   (Academic Press, Inc., 1 E. First St., Duluth, MN 55802)  V.1-    1903/04-
   Volume(issue)/page/year: 113,124,1963
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 500 mg/kg
SEX/DURATION            : female 1-5 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - female fertility index (e.g. # females pregnant
   per # sperm positive females; # females pregnant per # females mated)
REFERENCE :
   JRPFA4 Journal of Reproduction and Fertility.  (Biochemical Soc. Book Depot,
   POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK)  V.1-    1960-
   Volume(issue)/page/year: 14,534,1967
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE                    : 250 ug/kg
SEX/DURATION            : female 3 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - female fertility index (e.g. # females pregnant
   per # sperm positive females; # females pregnant per # females mated)
REFERENCE :
   NATUAS Nature.  (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736)
   V.1-    1869-  Volume(issue)/page/year: 176,249,1955
 
                            ** MUTATION DATA **
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
TEST SYSTEM             : Non-mammalian species Cells - not otherwise specified
DOSE/DURATION           : 50 nmol/L
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   37,3071,1977
 
TYPE OF TEST            : DNA inhibition
TEST SYSTEM             : Human HeLa cell
DOSE/DURATION           : 10 umol/L
REFERENCE :
   BICHAW Biochemistry.  (American Chemical Soc., Distribution Office Dept.
   223, POB 57136, West End Stn., Washington, DC 20037)  V.1-    1962-
   Volume(issue)/page/year: 15,5435,1976
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
TEST SYSTEM             : Human HeLa cell
DOSE/DURATION           : 5 umol/L
REFERENCE :
   BICHAW Biochemistry.  (American Chemical Soc., Distribution Office Dept.
   223, POB 57136, West End Stn., Washington, DC 20037)  V.1-    1962-
   Volume(issue)/page/year: 15,5435,1976
 
TYPE OF TEST            : Micronucleus test
TEST SYSTEM             : Rodent - mouse Cells - not otherwise specified
DOSE/DURATION           : 1 mg/L
REFERENCE :
   JNCIAM Journal of the National Cancer Institute.  (Washington, DC)  V.1-60,
   1940-78.  For publisher information, see JJIND8.  Volume(issue)/page/year:
   56,357,1976
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
TEST SYSTEM             : Rodent - mouse Cells - not otherwise specified
DOSE/DURATION           : 10 umol/L
REFERENCE :
   JMCMAR Journal of Medicinal Chemistry.  (American Chemical Soc.,
   Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC
   20037)  V.6-    1963-  Volume(issue)/page/year: 19,148,1976
 
TYPE OF TEST            : Micronucleus test
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 250 nmol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 392,151,1997
 
TYPE OF TEST            : Sex chromosome loss and nondisjunction
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - hamster
DOSE/DURATION           : 160 ug/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 327,237,1995
 
TYPE OF TEST            : DNA inhibition
TEST SYSTEM             : Mammal - species unspecified Ascites tumor
DOSE/DURATION           : 50 umol/L
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: 24,309,1983

                              *** REVIEWS ***
 
   TOXICOLOGY REVIEW
   PMDCAY Progress in Medical Chemistry.  (Elsevier Science Pub. Co., Inc., 52
   Vanderbilt Ave., New York, NY 10017)  V.1-    1961- Volume(issue)/page/year:
   10,85,1974

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

   TOXICOLOGY REVIEW
   ARVPAX Annual Review of Pharmacology.  (Palo Alto, CA)  V.1-15, 1961-75. For
   publisher information, see ARPTDI.  Volume(issue)/page/year: 5,447,1965

                          *** STATUS IN U.S. ***
 
   EPA GENETOX PROGRAM 1988, Inconclusive: CHO gene mutation

 
                            *** END OF RECORD ***