*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : ZG0350000 CHEMICAL NAME : 3-beta,20-alpha-Yohimban-16-beta-carboxylic acid, 18-beta-hydroxy-11,17-alpha-dimethoxy-, methyl ester, 3,4,5-trimethoxybenzoate (ester) CAS REGISTRY NUMBER : 50-55-5 BEILSTEIN REFERENCE NO. : 0102014 REFERENCE : 4-25-00-01319 (Beilstein Handbook Reference) LAST UPDATED : 199806 DATA ITEMS CITED : 82 MOLECULAR FORMULA : C33-H40-N2-O9 MOLECULAR WEIGHT : 608.75 WISWESSER LINE NOTATION : T F6 D5 C666 EM ON&&TTTJ HO1 SOVR CO1 DO1 EO1& TO1 UVO1 COMPOUND DESCRIPTOR : Tumorigen Drug Mutagen Reproductive Effector Human Natural Product SYNONYMS/TRADE NAMES : * Anquil * Apoplon * Banasil * Bioserpine * Crystoserpine * Deserpine * Diutensen-R * Elserpine * ENT 50146 * Escaspere * Eserpine * Eskaserp * Gilucard * Hiposerpil * Kitine * Klimanosid * Lemiserp * Loweserp * Mayserpine * Methylreserpate 3,4,5-trimethoxybenzoic acid * Naquival * NCI-C50157 * Quiescin * Raucap * Raulen * Raupasil * Raupoid * Raurine * Rausan * Rau-Sed * Rausedan * Rausedil * Rausedyl * Rauserpol * Rausingle * RCRA waste number U200 * Recipin * Resaltex * Resedril * Resedrex * Rese-Lar * Reser-AR * Reserbal * Resercaps * Resercen * Reserfia * Reserjen * Reserlor * Reserp * Reserpal * Reserpamed * Reserpanca * Reserpene * Reserpex * Reserpidefe * Reserpil * Reserpine * Reserpoid * Reserpur * Resersana * Reserutin * Resiatric * Residine * Resocalm * Resomine * Resperin * Resperine * Respital * Restran * Rezerpin * Riserpa * Rivased * Rivasin * Rolserp * Salupres * Salutensin * Sandril * Sedaraupin * Sedserp * Seominal * Serfin * Serfolia * Serp-AFD * Serpaloid * Serpanray * Serpasil * Serpasil premix * Serpasol * Serpate * Serpatone * Serpazil * Serpazol * Serpedin * Serpen * Serpentina * Serpiloid * Serpine (pharmaceutical) * Serpivite * Serplex K * Serpogen * Serpoid * Serpone * Serpresan * Serpyrit * Sertabs * Sertina * Temposerpine * Triserpin * 3,4,5-Trimethoxybenzoyl methyl reserpate * USAF CB-27 * Vio-Serpine *** 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 : 420 mg/kg TOXIC EFFECTS : Behavioral - antipsychotic REFERENCE : PSSCBG Pesticide Science. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1970- Volume(issue)/page/year: 11,555,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 44 mg/kg TOXIC EFFECTS : Brain and Coverings - recordings from specific areas of CNS REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 110,20,1957 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 25 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944- Volume(issue)/page/year: 56,377,1960 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 15 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,111,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >50 mg/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: -,1453,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 5 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EJMCA5 European Journal of Medicinal Chemistry--Chimie Therapeutique. (Editions Scientifiques Elsevier, 29 rue Buffon, F-75005, Paris, France) V.9- 1974- Volume(issue)/page/year: 10,519,1975 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 5610 ug/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: -,1453,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 21 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Gastrointestinal - hypermotility, diarrhea REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 14,1040,1964 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZIAQ "Drug Dosages in Laboratory Animals - A Handbook," Rev. ed., Barnes, C.D., and L.G. Eltherington, Berkeley, Univ. of California Press, 1973 Volume(issue)/page/year: -,234,1973 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 7 mg/kg TOXIC EFFECTS : Nutritional and Gross Metabolic - body temperature decrease REFERENCE : JDGRAX Journal of Drug Research. (National Organization for Drug Research and Control, POB 29, Cairo, Egypt) V.2- 1969- Volume(issue)/page/year: 6(3),19,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 15 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,111,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 65 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 137,375,1962 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 16 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: 23,600,1973 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Bird - wild bird species DOSE/DURATION : 100 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: 21,315,1972 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 945 mg/kg/75W-C TOXIC EFFECTS : Blood - changes in erythrocyte (RBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases REFERENCE : TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 1,201,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 54 mg/kg/9W-I TOXIC EFFECTS : Related to Chronic Data - death REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 124,237,1960 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 456 ug/kg/Y-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,672,1974 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 54 mg/kg/77W-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Blood - lymphoma, including Hodgkin's disease REFERENCE : COREAF Comptes Rendus Hebdomadaires des Seances, Academie des Sciences. (Paris, France) V.1-261, 1835-1965. For publisher information, see CRASEV. Volume(issue)/page/year: 254,1535,1962 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 132 mg/kg/2.5Y-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Gastrointestinal - tumors Skin and Appendages - tumors REFERENCE : VOONAW Voprosy Onkologii. Problems of Oncology. For English translation, see PONCAU. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1-10, 1928-37; V.1- 1955- Volume(issue)/page/year: 32(7),76,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 433 mg/kg/2Y-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-193,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 200 mg/kg/2Y-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors Skin and Appendages - tumors REFERENCE : VOONAW Voprosy Onkologii. Problems of Oncology. For English translation, see PONCAU. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1-10, 1928-37; V.1- 1955- Volume(issue)/page/year: 32(7),76,1986 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 216 mg/kg/2Y-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Endocrine - adrenal cortex tumors Skin and Appendages - tumors REFERENCE : NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-193,1980 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 73 mg/kg/2Y-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,672,1974 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 24 mg/kg/13Y-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Brain and Coverings - tumors REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,672,1974 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 16 mg/kg/3Y-C TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,672,1974 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 340 mg/kg/3Y-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Gastrointestinal - tumors Endocrine - thyroid tumors REFERENCE : VOONAW Voprosy Onkologii. Problems of Oncology. For English translation, see PONCAU. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1-10, 1928-37; V.1- 1955- Volume(issue)/page/year: 32(7),76,1986 TYPE OF TEST : TD - Toxic dose (other than lowest) ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1120 mg/kg/2Y-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Blood - tumors Skin and Appendages - tumors REFERENCE : VOONAW Voprosy Onkologii. Problems of Oncology. For English translation, see PONCAU. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1-10, 1928-37; V.1- 1955- Volume(issue)/page/year: 32(7),76,1986 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Human - woman DOSE : 200 ug/kg SEX/DURATION : female 39 week(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - other neonatal measures or effects REFERENCE : AJDCAI American Journal of Diseases of Children. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-80(3), 1911-50; V.100- 1960- Volume(issue)/page/year: 90,286,1955 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - woman DOSE : 4800 ug/kg SEX/DURATION : female 32-39 week(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth REFERENCE : AGPSA3 AMA Archives of General Psychiatry. (Chicago, IL) V.1-2, 1959-60. For publisher information, see ARGPAQ. Volume(issue)/page/year: 2,606,1960 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 11130 ug/kg SEX/DURATION : male 21 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles) REFERENCE : NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 200,585,1963 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 17500 mg/kg SEX/DURATION : female 3-9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) 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: 100,555,1959 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 6 mg/kg SEX/DURATION : female 60 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - menstrual cycle changes or disorders REFERENCE : CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 156,587,1962 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 21217 ug/kg SEX/DURATION : female 30 week(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 156,587,1962 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 2 mg/kg SEX/DURATION : female 2 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes REFERENCE : TJXMAH Tokushima Journal of Experimental Medicine. (Univ. of Tokushima, School of Medicine, 3, Kuramoto-cho, Tokushima, Japan) V.1- 1954- Volume(issue)/page/year: 23,1,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 700 ug/kg SEX/DURATION : female 8-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral REFERENCE : PEDIAU Pediatrics. (American Academy of Pediatrics, P.O. Box 1034, Evanston, IL 60204) V.1- 1948- Volume(issue)/page/year: 27,318,1961 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 2500 ug/kg SEX/DURATION : female 19 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : NISFAY Nippon Sanka Fujinka Gakkai Zasshi. Journal of the Japan Society of Obstetrics and Gynecology. (Nippon Sanka Fujinka Gakkai Zasshi, Hoken Kaikan Bekkan, 1-1 Sadohara-cho, Ichigaya, Shijuku-ku, Tokyo 162, Japan) V.1- 1949- Volume(issue)/page/year: 30,161,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 1 mg/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - menstrual cycle changes or disorders REFERENCE : ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21203) V.1- 1917- Volume(issue)/page/year: 65,563,1959 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 1250 ug/kg SEX/DURATION : male 5 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands 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: 28,177,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 400 ug/kg SEX/DURATION : female 11-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - behavioral REFERENCE : EXNEAC Experimental Neurology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 6,263,1962 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 3 mg/kg SEX/DURATION : female 12-15 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Effects on Newborn - physical REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 13,652,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 1500 ug/kg SEX/DURATION : female 12-15 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - biochemical and metabolic Reproductive - Effects on Newborn - physical REFERENCE : NETEEC Neurotoxicology and Teratology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.9- 1987- Volume(issue)/page/year: 11,515,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 2 mg/kg SEX/DURATION : female 12-17 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes REFERENCE : PRGLBA Prostaglandins. (Geron-X, Inc., P.O. Box 1108, Los Altos, CA 94022) V.1- 1972- Volume(issue)/page/year: 9,75,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 400 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility REFERENCE : ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21203) V.1- 1917- Volume(issue)/page/year: 78,225,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 4 mg/kg SEX/DURATION : female 16-19 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Effects on Newborn - biochemical and metabolic REFERENCE : TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968- Volume(issue)/page/year: 27,35A,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE : 800 ug/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear 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 : 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: 118,857,1965 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE : 800 ug/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Maternal Effects - other effects Nutritional and Gross Metabolic - weight loss or decreased weight gain 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: 118,857,1965 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE : 1 mg/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system 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: 118,857,1965 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE : 1500 ug/kg SEX/DURATION : female 10 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System 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: 118,857,1965 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Parenteral SPECIES OBSERVED : Rodent - rat DOSE : 9 mg/kg SEX/DURATION : female 1-9 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) REFERENCE : 15QWAW "Agents Affecting Fertility, a Symposium, 1964," Austin, C.R., and J.S. Perry, eds., Boston, Little, Brown & Co., 1965 Volume(issue)/page/year: -,290,1965 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - rat DOSE : 3750 ug/kg SEX/DURATION : male 15 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles) REFERENCE : ANENAG Annales d'Endocrinologie. (Masson Editeur, 120 Blvd. Saint-Germain, F-25280 Paris Cedex 06, France) V.1- 1939- Volume(issue)/page/year: 23,281,1962 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - rat DOSE : 50 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : AKGIAO Akushcherstvo i Ginekologiya (Moscow). (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) No.1- 1936- Volume(issue)/page/year: 43(12),10,1967 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 600 ug/kg SEX/DURATION : female 7-12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 4,2937,1970 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 10 mg/kg SEX/DURATION : female 1 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility 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: 13,345,1967 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE : 120 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility REFERENCE : JOENAK Journal of Endocrinology. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1939- Volume(issue)/page/year: 35,161,1966 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Parenteral SPECIES OBSERVED : Rodent - mouse DOSE : 400 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 12,346,1961 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Parenteral SPECIES OBSERVED : Rodent - mouse DOSE : 3200 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 12,346,1961 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE : 1600 ug/kg SEX/DURATION : female 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - other measures of fertility REFERENCE : AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 83,1405,1962 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE : 32 ug/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - other effects on male REFERENCE : NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944- Volume(issue)/page/year: 80,239,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Primate - monkey DOSE : 100 mg/kg SEX/DURATION : female 14 week(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - menstrual cycle changes or disorders REFERENCE : SCIEAS Science. (American Assoc. for the Advancement of Science, 1333 H St., NW, Washington, DC 20005) V.1- 1895- Volume(issue)/page/year: 124,726,1956 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - guinea pig DOSE : 170 ug/kg SEX/DURATION : female 35-68 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) REFERENCE : AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 92,711,1965 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - guinea pig DOSE : 340 ug/kg SEX/DURATION : female 35-68 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - other neonatal measures or effects Reproductive - Effects on Newborn - biochemical and metabolic REFERENCE : AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 92,711,1965 ** MUTATION DATA ** TYPE OF TEST : Unscheduled DNA synthesis TEST SYSTEM : Bacteria - Salmonella typhimurium DOSE/DURATION : 1 ug REFERENCE : ECEBDI Experimental Cell Biology. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.44- 1976- Volume(issue)/page/year: 50,271,1982 TYPE OF TEST : DNA adduct TEST SYSTEM : Bacteria - Escherichia coli DOSE/DURATION : 20 umol/L REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 89,95,1981 TYPE OF TEST : Morphological transformation TEST SYSTEM : Rodent - rat Embryo DOSE/DURATION : 2200 ng/plate REFERENCE : JJATDK JAT, Journal of Applied Toxicology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK) V.1- 1981- Volume(issue)/page/year: 1,190,1981 TYPE OF TEST : Micronucleus test ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 2 mg/kg REFERENCE : BPBSDA Bulletin of the Philippine Biochemical Society. (Philippine Biochemical Soc., POB 593, Manila, Philippines) V.1- 1978- Volume(issue)/page/year: 2,52,1979 TYPE OF TEST : Cytogenetic analysis ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 30 mg/kg/48H REFERENCE : PCJOAU Pharmaceutical Chemistry Journal (English Translation). Translation of KHFZAN. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No.1- 1967- Volume(issue)/page/year: 12,298,1978 TYPE OF TEST : Dominant lethal test ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - mouse DOSE/DURATION : 200 ug/kg REFERENCE : KHFZAN Khimiko-Farmatsevticheskii Zhurnal. Chemical Pharmaceutical Journal. For English translation, see PCJOAU. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1967- Volume(issue)/page/year: 12(3),19,1978 TYPE OF TEST : Morphological transformation TEST SYSTEM : Rodent - hamster Embryo DOSE/DURATION : 4 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: 15,11,1994 TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Rodent - hamster Ovary DOSE/DURATION : 2 mg/L REFERENCE : EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987- Volume(issue)/page/year: 13,133,1989 TYPE OF TEST : Sex chromosome loss and nondisjunction ROUTE OF EXPOSURE : Intraperitoneal TEST SYSTEM : Rodent - hamster DOSE/DURATION : 4 ng/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 *** 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: 24,211,1980 IARC Cancer Review:Human Inadequate 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: 24,211,1980 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: 7,330,1987 TOXICOLOGY REVIEW CLPTAT Clinical Pharmacology and Therapeutics (St. Louis). (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1960- Volume(issue)/page/year: 5,480,1964 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84711 No. of Facilities: 68 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 2770 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84711 No. of Facilities: 142 (estimated) No. of Industries: 2 No. of Occupations: 10 No. of Employees: 5611 (estimated) No. of Female Employees: 2414 (estimated) *** STATUS IN U.S. *** EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat EPA GENETOX PROGRAM 1988, Inconclusive: Aspergillus-aneuploidy EPA TSCA Section 8(b) CHEMICAL INVENTORY NCI Carcinogenesis Bioassay (feed);clear evidence:mouse,rat NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*. Volume(issue)/page/year: NCI-TR-193,80 NTP 7th Annual Report on Carcinogens, 1992 : anticipated to be carcinogen *** END OF RECORD ***