*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : HO9275000 CHEMICAL NAME : 5H-Dibenzo(a,d)cycloheptene-delta(sup 5),gamma-propylamine, 10,11-dihydro-N,N-dimethyl- CAS REGISTRY NUMBER : 50-48-6 BEILSTEIN REFERENCE NO. : 2217885 LAST UPDATED : 199706 DATA ITEMS CITED : 31 MOLECULAR FORMULA : C20-H23-N MOLECULAR WEIGHT : 277.44 WISWESSER LINE NOTATION : L C676 BY&T&J BU3N1&1 COMPOUND DESCRIPTOR : Drug Reproductive Effector Human SYNONYMS/TRADE NAMES : * Adepress * Adepril * Amitriptilina * Amitriptylin * Amitriptyline * Damilan * Damitriptyline * 3-(10,11-Dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-1-pr opanamine * 10,11-Dihydro-5-(gamma-dimethylaminopropylidene)-5H-dibenzo(a,d)cyclohep tene * 10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-delta(sup 5),gamma-propylamine * 5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatr iene * 5-(3'-Dimethylaminopropylidene)-dibenzo-(a,d)(1,4)-cycloheptadiene * 5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene * 5-(gamma-Dimethylaminopropylidene)-5H-dibenzo(a,d)-10,11-dihydrocyclohep tene * 5-(gamma-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cyclohep tene * 5-(3-Dimethylpropylidene)dibenzo(a,d)(1,4)cycloheptadiene * Elavil * Flavyl * Lantron * MK 230 * Proheptadiene * Ro 4-1575 * Seroten * Triptanol * Triptisol *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 84 mg/kg TOXIC EFFECTS : Cardiac - EKG changes not diagnostic of specified effects REFERENCE : JJTOEX Japanese Journal of Toxicology. (Yakugyo Jihosha, Hokushin Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo, 101, Japan) V.1- 1988- Volume(issue)/page/year: 5,69,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 60 mg/kg TOXIC EFFECTS : Cardiac - arrhythmias (including changes in conduction) Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section REFERENCE : JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 19,67,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - child DOSE/DURATION : 4500 ug/kg TOXIC EFFECTS : Behavioral - sleep REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 3,663,1967 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 16800 ug/kg/2W-I TOXIC EFFECTS : Peripheral Nerve and Sensation - paresthesis Behavioral - headache REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,426,1968 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 14 mg/kg TOXIC EFFECTS : Cardiac - other changes REFERENCE : PSDTAP Proceedings of the European Society for the Study of Drug Toxicity. (Princeton, NJ 08540) V.1-15, 1963-74. For publisher information, see PESTD5. Volume(issue)/page/year: 6,171,1965 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - infant DOSE/DURATION : 50 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Cardiac - change in rate Behavioral - muscle contraction or spasticity 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: 130,507,1976 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 29 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HETOEA Human & Experimental Toxicology. (Macmillan Press Ltd., Brunel Road, Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990- Volume(issue)/page/year: 9,257,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 13500 ug/kg/3D-C TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - excitement REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,390,1968 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Human - woman DOSE/DURATION : 240 ug/kg/36H-C TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,390,1968 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - man DOSE/DURATION : 45 mg/kg/21D TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Cardiac - change in rate REFERENCE : LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 2,1202,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 320 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - ataxia Gastrointestinal - changes in structure or function of salivary glands REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 72 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : PJPPAA Polish Journal of Pharmacology and Pharmacy. (ARS Polona, POB 1001, 00-068 Warsaw 1, Poland) V.25- 1973- Volume(issue)/page/year: 27,503,1975 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 140 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : THERAP Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris, France) V.1- 1946- Volume(issue)/page/year: 26,459,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 48400 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 53(4),19,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 100 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4605673 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 16 mg/kg TOXIC EFFECTS : Behavioral - changes in motor activity (specific assay) 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: 17,65,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 80 mg/kg TOXIC EFFECTS : Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic) 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: 10,418,1967 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 50 mg/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - spastic paralysis with or without sensory change Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - other changes REFERENCE : PHMCAA Pharmacologist. (American Soc. for Pharmacology and Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20014) V.1- 1959- Volume(issue)/page/year: 11,283,1969 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 58700 ug/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - cyanosis REFERENCE : JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 19,321,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 8600 ug/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: 15,863,1965 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 35 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 8,949,1983 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5760 mg/kg/22W-I TOXIC EFFECTS : Cardiac - EKG changes not diagnostic of specified effects Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,1709,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 62500 ug/kg/30D-I TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other Enzymes REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 75,63,1992 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 75 mg/kg SEX/DURATION : female 4-18 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : JNMDBO Journal of Medicine (Westbury, NY). (PJD Pub., Ltd., POB 966, Westbury, NY 11590) V.1- 1970- Volume(issue)/page/year: 2,271,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 504 mg/kg SEX/DURATION : female 6-14 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 - other developmental abnormalities REFERENCE : PSDTAP Proceedings of the European Society for the Study of Drug Toxicity. (Princeton, NJ 08540) V.1-15, 1963-74. For publisher information, see PESTD5. Volume(issue)/page/year: 10,235,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 252 mg/kg SEX/DURATION : female 6-14 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) REFERENCE : PSDTAP Proceedings of the European Society for the Study of Drug Toxicity. (Princeton, NJ 08540) V.1-15, 1963-74. For publisher information, see PESTD5. Volume(issue)/page/year: 10,235,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE : 540 mg/kg SEX/DURATION : female 8-16 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - other developmental abnormalities Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : PSDTAP Proceedings of the European Society for the Study of Drug Toxicity. (Princeton, NJ 08540) V.1-15, 1963-74. For publisher information, see PESTD5. Volume(issue)/page/year: 10,235,1969 *** REVIEWS *** TOXICOLOGY REVIEW DICPBB Drug Intelligence and Clinical Pharmacy. (POB 42435, Cincinnati, OH 45242) V.3- 1969- Volume(issue)/page/year: 8,690,1974 TOXICOLOGY REVIEW CLCHAU Clinical Chemistry (Winston-Salem, NC). (American Assoc. for Clinical Chemistry, 1725 K St., NW, Washington, DC 20006) V.1- 1955- Volume(issue)/page/year: 19,361,1973 TOXICOLOGY REVIEW CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 2,403,1969 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3816 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 8 No. of Employees: 3157 (estimated) No. of Female Employees: 1154 (estimated) *** END OF RECORD ***