*** 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 ***