*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : WG9800000 CHEMICAL NAME : Spiro(benzofuran-2(3H),1'-(2)cyclohexene)-3,4'-dione, 7-chloro-2'4,6-trimethoxy-6'-beta- methyl- CAS REGISTRY NUMBER : 126-07-8 BEILSTEIN REFERENCE NO. : 0095226 REFERENCE : 5-18-05-00150 (Beilstein Handbook Reference) LAST UPDATED : 199801 DATA ITEMS CITED : 53 MOLECULAR FORMULA : C17-H17-Cl-O6 MOLECULAR WEIGHT : 352.79 WISWESSER LINE NOTATION : T56 BOXVJ FO1 HO1 IG C-& DL6V DX BUTJ CO1 E1 COMPOUND DESCRIPTOR : Agricultural Chemical Tumorigen Drug Mutagen Reproductive Effector Natural Product SYNONYMS/TRADE NAMES : * Amudane * Biogrisin-FP * 7-Chloro-4,6,2'-trimethoxy-6'-methylgris-2'-en-3,4'-dione * Curling factor * Delmofulvina * Fulcin * Fulcine * Fulvican grisactin * Fulvicin * Fulvicin-P/G * Fulvicin-U/F * Fulvina * Fulvistatin * Fungivin * Greosin * Gresfeed * Gricin * Grifulvin * Grifulvin V * Grisactin * Griscofulvin * Grisefuline * Griseo * Griseofulvin * (+)-Griseofulvin * Griseofulvin-forte * Griseofulvinum * Griseomix * Grisetin * Grisofulvin * Grisovin * Gris-PEG * Grysio * Guservin * Lamoryl * Likuden * Murfulvin * Neo-fulcin * NSC 34533 * Poncyl * Spirofulvin * Sporostatin * USAF SC-2 *** 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 : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,215,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/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: 2,44,1960 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 400 mg/kg TOXIC EFFECTS : Blood - changes in cell count (unspecified) Blood - changes in bone marrow (not otherwise specified) REFERENCE : NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 182,1320,1958 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >50 gm/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: 2,44,1960 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: AD277-689 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >12 gm/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: 2,44,1960 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 280 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: 2,44,1960 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 109 gm/kg/52W-C 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: 2,44,1960 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 462 gm/kg/2Y-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Blood - lymphoma, including Hodgkin's disease REFERENCE : BJCAAI British Journal of Cancer. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.1- 1947- Volume(issue)/page/year: 38,237,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 440 gm/kg/52W-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Liver - tumors REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 26,721,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 120 mg/kg/49W-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Liver - tumors REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 27,1900,1967 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 730 gm/kg/52W-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Liver - tumors REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 26,721,1966 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 1250 mg/kg SEX/DURATION : female 6-15 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) REFERENCE : SCIEAS Science. (American Assoc. for the Advancement of Science, 1333 H St., NW, Washington, DC 20005) V.1- 1895- Volume(issue)/page/year: 175,1483,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 2 gm/kg SEX/DURATION : female 11-14 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : ANTBAL Antibiotiki. (Moscow, USSR) V.1-29, 1956-84. For publisher information, see AMBIEH. Volume(issue)/page/year: 14,44,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 12500 mg/kg SEX/DURATION : female 6-15 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : SCIEAS Science. (American Assoc. for the Advancement of Science, 1333 H St., NW, Washington, DC 20005) V.1- 1895- Volume(issue)/page/year: 175,1483,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 500 mg/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - eye/ear REFERENCE : ANTBAL Antibiotiki. (Moscow, USSR) V.1-29, 1956-84. For publisher information, see AMBIEH. Volume(issue)/page/year: 14,44,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 10 gm/kg SEX/DURATION : female 8-9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : 40YJAX "Evaluation of Embryotoxicity, Mutagenicity and Carcinogenicity Risks In New Drugs, Proceedings of the Symposium on Toxicological Testing for Safety of New Drugs, 3rd, Prague, 1976," Benesova, O., et al., eds., Prague, Czechoslovakia, Univerzita Karlova, 1979 Volume(issue)/page/year: -,161,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - domestic DOSE : 1 gm/kg SEX/DURATION : female 48-52 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : VEQUDU Veterinary Quarterly. (Kluwer Academic Publishers, POB 322, 3300 AH Dordrecht, Netherlands) V.1- 1979-d/* Volume(issue)/page/year: 19,58,1997 ** MUTATION DATA ** TYPE OF TEST : Mutation test systems - not otherwise specified TEST SYSTEM : Microorganism - not otherwise specified DOSE/DURATION : 10 mg/L REFERENCE : AMICCW Archives of Microbiology. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secacus, NJ 07094) V.95- 1974- Volume(issue)/page/year: 95,57,1974 TYPE OF TEST : Specific locus test ROUTE OF EXPOSURE : Oral TEST SYSTEM : Insect - Drosophila melanogaster DOSE/DURATION : 2 gm/L REFERENCE : GNKAA5 Genetika (Moscow). For English translation, see SOGEBZ. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) No.1- 1965- Volume(issue)/page/year: 30(6),796,1994 TYPE OF TEST : DNA repair ROUTE OF EXPOSURE : Oral TEST SYSTEM : Insect - Drosophila melanogaster DOSE/DURATION : 3 gm/L REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 343,229,1995 TYPE OF TEST : Mutation in microorganisms TEST SYSTEM : Mold - Aspergillus nidulans DOSE/DURATION : 17 umol/L REFERENCE : PHYTAJ Phytopathology. (American Phytopathological Soc., 3340 Pilot Knob Rd., St. Paul, MN 55121) V.1- 1911- Volume(issue)/page/year: 66,217,1976 TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Mold - Aspergillus nidulans DOSE/DURATION : 400 mg/L REFERENCE : CJMIAZ Canadian Journal of Microbiology. (National Research Council of Canada, Publication Sales and Distribution, Ottawa ON K1A OR6, Canada) V.1- 1954- Volume(issue)/page/year: 18,683,1972 TYPE OF TEST : Sex chromosome loss and nondisjunction TEST SYSTEM : Mold - Aspergillus nidulans DOSE/DURATION : 6 mg/L REFERENCE : JOBAAY Journal of Bacteriology. (American Soc. for Microbiology, 1913 I St., NW, Washington, DC 20006) V.1- 1916- Volume(issue)/page/year: 119,334,1974 TYPE OF TEST : Cytogenetic analysis ROUTE OF EXPOSURE : Oral TEST SYSTEM : Insect - grasshopper DOSE/DURATION : 5 mg REFERENCE : PISCAD Proceedings of the Indian Science Congress. (Indian Science Congress Assoc., 14, Dr. Biresh Guha St., Calcutta, 700017, India) 1st- 1914- Volume(issue)/page/year: 59(Pt 3),410,1972 TYPE OF TEST : Micronucleus test TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 5 mg/L REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 322,151,1994 TYPE OF TEST : DNA inhibition TEST SYSTEM : Human Fibroblast DOSE/DURATION : 20 mg/L/3D (Continuous) REFERENCE : KAMJDW Kawasaki Medical Journal. (Kawasaki Medical School, Kurashiki 701-01, Japan) V.1- 1975- Volume(issue)/page/year: 2,127,1976 TYPE OF TEST : DNA inhibition TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 20 mg/L/3D (Continuous) REFERENCE : KAMJDW Kawasaki Medical Journal. (Kawasaki Medical School, Kurashiki 701-01, Japan) V.1- 1975- Volume(issue)/page/year: 2,127,1976 TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 40 mg/L/3D REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 25,123,1974 TYPE OF TEST : Sex chromosome loss and nondisjunction TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 5 mg/L REFERENCE : MUTAEX Mutagenesis. (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1986- Volume(issue)/page/year: 4,165,1989 TYPE OF TEST : Cytogenetic analysis ROUTE OF EXPOSURE : Intravenous TEST SYSTEM : Rodent - rat DOSE/DURATION : 200 mg/kg REFERENCE : NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 182,1320,1958 TYPE OF TEST : Micronucleus test TEST SYSTEM : Rodent - mouse Cells - not otherwise specified DOSE/DURATION : 10 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 : Cytogenetic analysis TEST SYSTEM : Rodent - mouse Embryo DOSE/DURATION : 50 mg/L REFERENCE : NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 253,361,1975 TYPE OF TEST : Sister chromatid exchange ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 100 mg/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 137,111,1984 TYPE OF TEST : Sex chromosome loss and nondisjunction ROUTE OF EXPOSURE : Oral TEST SYSTEM : Rodent - mouse DOSE/DURATION : 1 gm/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 300,155,1993 TYPE OF TEST : Sperm Morphology ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 29750 mg/kg/5D (Intermittent) REFERENCE : CMMUAO Chemical Mutagens. Principles and Methods for Their Detection. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) V.1- 1971- Volume(issue)/page/year: 5,257,1978 TYPE OF TEST : Morphological transformation TEST SYSTEM : Rodent - hamster Embryo DOSE/DURATION : 8 mg/L REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 343,7,1995 TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Rodent - hamster Embryo DOSE/DURATION : 50 mg/L REFERENCE : NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 253,361,1975 TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Rodent - hamster Fibroblast DOSE/DURATION : 10 mg/L REFERENCE : CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 3,499,1982 TYPE OF TEST : Cytogenetic analysis TEST SYSTEM : Bird - chicken Fibroblast DOSE/DURATION : 50 mg/L REFERENCE : NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 253,361,1975 *** REVIEWS *** IARC Cancer Review:Animal Sufficient Evidence IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,391,1987 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: 7,391,1987 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 LLOYA2 Lloydia. (Cincinnati, OH) V.1-41, 1938-78. For publisher information, see JNPRDF. Volume(issue)/page/year: 38,21,1975 TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 TOXICOLOGY REVIEW ARMIAZ Annual Review of Microbiology. (Annual Reviews, Inc., POB 10139, Palo Alto, CA 94303) V.1- 1947- Volume(issue)/page/year: 26,279,1972 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3685 No. of Facilities: 58 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 1656 (estimated) No. of Female Employees: 774 (estimated) *** STATUS IN U.S. *** EPA GENETOX PROGRAM 1988, Positive: Aspergillus-aneuploidy; Sperm morphology-mouse EPA GENETOX PROGRAM 1988, Positive/limited: Carcinogenicity-mouse/rat EPA GENETOX PROGRAM 1988, Negative: S cerevisiae-homozygosis EPA GENETOX PROGRAM 1988, Inconclusive: Aspergillus-recombination; Mammalian micronucleus EPA GENETOX PROGRAM 1988, Inconclusive: B subtilis rec assay; E coli polA without S9 EPA GENETOX PROGRAM 1988, Inconclusive: Histidine reversion-Ames test *** END OF RECORD ***