*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : DJ2275000 CHEMICAL NAME : 3H-2-Benzopyran-7-carboxylic acid, 4,6-dihydro-8-hydroxy-3,4,5-trimethyl-6-oxo-, (3R-trans)- CAS REGISTRY NUMBER : 518-75-2 BEILSTEIN REFERENCE NO. : 0088597 REFERENCE : 5-18-09-00061 (Beilstein Handbook Reference) LAST UPDATED : 199709 DATA ITEMS CITED : 41 MOLECULAR FORMULA : C13-H14-O5 MOLECULAR WEIGHT : 250.27 WISWESSER LINE NOTATION : T66 CO HV AUT&J D1 E1 G1 IVQ JQ COMPOUND DESCRIPTOR : Agricultural Chemical Tumorigen Drug Mutagen Reproductive Effector Primary Irritant SYNONYMS/TRADE NAMES : * Citrinin * (-)-Citrinin * (3R,4S)-4,6-Dihydro-8-hydroxy-3,4,5-trimethyl-6-oxo-3H-2-benzopyran-7-ca rboxylic acid *** HEALTH HAZARD DATA *** ** SKIN/EYE IRRITATION DATA ** TYPE OF TEST : Standard Draize test ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 40 mg/24H REACTION SEVERITY : Severe REFERENCE : JANCA2 Journal of the Association of Official Analytical Chemists. (Assoc. of Official Analytical Chemists, 1111 N. 19th St., Suite 210, Arlington, VA 22209) V.49- 1966- Volume(issue)/page/year: 57,1121,1974 ** ACUTE TOXICITY DATA ** TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 50 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PHBUA9 Pharmaceutical Bulletin. (Tokyo, Japan) V.1-5, 1953-57. For publisher information, see CPBTAL. Volume(issue)/page/year: 3,337,1955 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 67 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - respiratory stimulation Blood - other changes 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: 88,173,1946 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 112 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: 37,139,1976 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 35 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - respiratory stimulation 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: 88,173,1946 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 73 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 15,29,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 134 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) REFERENCE : FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 21,487,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 50 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) REFERENCE : FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 21,487,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 19 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - changes in structure or function of salivary glands 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: 88,173,1946 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 37 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - respiratory stimulation 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: 88,173,1946 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 75 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 16,355,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 66 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 16,355,1978 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 240 mg/kg/6W-I TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - dehydrogenases Biochemical - Metabolism (Intermediary) - lipids including transport REFERENCE : INJPD2 Indian Journal of Pharmacology. (Dept. of Pharmacology, Baranas Hindu Univ., Varanasi 221 005, India) V.1- 1968(?)- Volume(issue)/page/year: 16,238,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 539 mg/kg/7D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes Related to Chronic Data - death REFERENCE : FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 21,487,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 780 mg/kg/8W-I TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - miosis (pupillary constriction) Gastrointestinal - changes in structure or function of salivary glands Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) 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: 88,173,1946 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 630 mg/kg/14D-I TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from large intestine Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Related to Chronic Data - death REFERENCE : FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 15,553,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 700 mg/kg/7D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) REFERENCE : FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 16,355,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 385 mg/kg/7D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) REFERENCE : FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 16,355,1978 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 25200 mg/kg/60W-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors REFERENCE : CALEDQ Cancer Letters (Shannon, Ireland). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1975- Volume(issue)/page/year: 17,281,1983 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 13 gm/kg/32W-C TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors REFERENCE : FGIGDO Fujita Gakuen Igakkaishi. Journal of the Fujita Gakuen Medical Society. (Nagoya Hoken Eisei Daigaku Fujita Gakuen Igakkai, 1-98 Dengakuga, Kubo, Kutsukake-Cho, Toyoake, Aichi-Ken 470-11, Japan) V.1- 1977- Volume(issue)/page/year: 5,77,1981 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 30 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) 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: 13,553,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 35 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) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 25,151,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 35 mg/kg SEX/DURATION : female 11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 25,151,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 35 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 25,151,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 35 mg/kg SEX/DURATION : female 15 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 25,151,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 20 mg/kg SEX/DURATION : female 10 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : 85EGD4 "Toxins: Animal, Plant and Microbial; Proceedings of the International Symposium," Rosenberg, P., ed., New York, Pergamon Press Inc., 1978 Volume(issue)/page/year: -,739,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 30 mg/kg SEX/DURATION : female 10 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 14,175,1976 ** MUTATION DATA ** TYPE OF TEST : DNA damage TEST SYSTEM : Bacteria - Escherichia coli DOSE/DURATION : 100 mg/L REFERENCE : AEMIDF Applied and Environmental Microbiology. (American Soc. for Microbiology, 1913 I St., NW, Washington, DC 20006) V.31- 1976- Volume(issue)/page/year: 52,1273,1986 TYPE OF TEST : Phage inhibition capacity TEST SYSTEM : Bacteria - Escherichia coli DOSE/DURATION : 300 mg/L REFERENCE : AEMIDF Applied and Environmental Microbiology. (American Soc. for Microbiology, 1913 I St., NW, Washington, DC 20006) V.31- 1976- Volume(issue)/page/year: 52,1273,1986 TYPE OF TEST : DNA repair TEST SYSTEM : Bacteria - Bacillus subtilis DOSE/DURATION : 20 ug/disc REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 36,445,1976 TYPE OF TEST : DNA inhibition TEST SYSTEM : Human HeLa cell DOSE/DURATION : 300 umol/L REFERENCE : CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 13,2389,1992 TYPE OF TEST : DNA damage TEST SYSTEM : Rodent - rat Fibroblast DOSE/DURATION : 200 mg/L REFERENCE : FOBLAN Folia Biologica (Prague). (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1955- Volume(issue)/page/year: 32,128,1986 TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - rat Fibroblast DOSE/DURATION : 100 mg/L REFERENCE : FOBLAN Folia Biologica (Prague). (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1955- Volume(issue)/page/year: 32,128,1986 TYPE OF TEST : DNA damage TEST SYSTEM : Rodent - hamster Ovary DOSE/DURATION : 200 mg/L REFERENCE : FOBLAN Folia Biologica (Prague). (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1955- Volume(issue)/page/year: 32,128,1986 TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - hamster Ovary DOSE/DURATION : 100 mg/L REFERENCE : FOBLAN Folia Biologica (Prague). (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1955- Volume(issue)/page/year: 32,128,1986 *** REVIEWS *** IARC Cancer Review:Animal Limited 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: 40,67,1986 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: 40,67,1986 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,56,1987 *** STATUS IN U.S. *** EPA GENETOX PROGRAM 1988, Positive: B subtilis rec assay EPA GENETOX PROGRAM 1988, Negative: S cerevisiae-homozygosis EPA GENETOX PROGRAM 1988, Inconclusive: Histidine reversion-Ames test *** END OF RECORD ***