*** 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 ***