*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : HO9450000
CHEMICAL NAME : 5H-Dibenzo(a,d)cycloheptene-delta(sup
5),gamma-propylamine, 10,11-dihydro-N,N-dimethyl-,
hydrochloride
CAS REGISTRY NUMBER : 549-18-8
LAST UPDATED : 199707
DATA ITEMS CITED : 39
MOLECULAR FORMULA : C20-H23-N.Cl-H
MOLECULAR WEIGHT : 313.90
WISWESSER LINE NOTATION : L C676 BY&T&J BU3N1&1 &GH
COMPOUND DESCRIPTOR : Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Amitriptyline chloride
* Amitriptyline hydrochloride
* Damilen hydrochloride
* Deprex
* Domical
* 10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,d)cycloheptene-delta(sup
5,gamma)-propylamine HCl
* 5-(3-Dimethylaminopropylidene)dibenzo(a,d)(1,4)cycloheptadiene
hydrochloride
* Elavil hydrochloride
* Endep
* Etrafon
* Laroxyl
* Lentizol
* Limbitrol DS
* Miketorin
* Proheptadien monohydrochloride
* 1-Propanamine,
3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-, hcl
* Rantoron
* Saroten
* SK-Amitriptyline
* Triavil
* Tryptizol
* Yamanouchi
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 58 mg/kg
TOXIC EFFECTS :
Behavioral - coma
Vascular - BP lowering not characterized in autonomic section
Lungs, Thorax, or Respiration - respiratory depression
REFERENCE :
SMJOAV Southern Medical Journal. (Southern Medical Assoc., POB 2446,
Birmingham, AL 35205) V.1- 1908- Volume(issue)/page/year: 82,1588,1989
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 714 ug/kg/1D-I
TOXIC EFFECTS :
Behavioral - alteration of operant conditioning
Behavioral - changes in psychophysiological tests
REFERENCE :
HUPSEC Human Psychopharmacology. (John Wiley & Sons Ltd., Baffins Lane,
Chichester, W.Sussex PO19 1UD, United Kingdom) V.1- 1986-
Volume(issue)/page/year: 7,273,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 60 mg/kg/3W-I
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - ataxia
Behavioral - withdrawal
REFERENCE :
JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press,
Inc., POB 240008, Memphis, TN 38124) V.39- 1978-
Volume(issue)/page/year: 53,160,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 10 mg/kg
TOXIC EFFECTS :
Behavioral - hallucinations, distorted perceptions
REFERENCE :
CMAJAX Canadian Medical Association Journal. (Canadian Medical Assoc., POB
8650, Ottawa, ON K1G 0G8, Canada) V.1- 1911- Volume(issue)/page/year:
129,1203,1983
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 62500 ug/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Vascular - BP lowering not characterized in autonomic section
Lungs, Thorax, or Respiration - respiratory depression
REFERENCE :
NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10
Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year:
267,1031,1962
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 4167 ug/kg
TOXIC EFFECTS :
Behavioral - sleep
Behavioral - hallucinations, distorted perceptions
Behavioral - muscle contraction or spasticity
REFERENCE :
NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10
Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year:
267,1031,1962
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 200 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - muscle contraction or spasticity
Behavioral - coma
REFERENCE :
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N.
Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year:
230,1405,1974
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 62500 ug/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - cyanosis
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: 106,501,1963
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 19 mg/kg
TOXIC EFFECTS :
Behavioral - coma
Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823-
Volume(issue)/page/year: 2,543,1963
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 14286 ug/kg
TOXIC EFFECTS :
Behavioral - coma
Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823-
Volume(issue)/page/year: 2,543,1963
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 240 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 67 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: -,49,1990
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 385 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - cyanosis
REFERENCE :
EJPHAZ European Journal of Pharmacology. (Elsevier Science Pub. B.V., POB
211, 1000 AE Amsterdam, Netherlands) V.1- 1967- Volume(issue)/page/year:
32,108,1975
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 14 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: -,61,1972
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 :
WMWOA4 Wiener Medizinische Wochenschrift. (Brueder Hollinek, Gallgasse 40,
A-1130 Vienna, Austria) V.1- 1851- Volume(issue)/page/year: 111,256,1961
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 65 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
JDGRAX Journal of Drug Research. (National Organization for Drug Research
and Control, POB 29, Cairo, Egypt) V.2- 1969- Volume(issue)/page/year:
16,7,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 80 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - cyanosis
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 21 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: 21,808,1971
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 200 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : >27 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,899,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : >23 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,899,1972
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Primate - monkey
DOSE/DURATION : 20300 ug/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - convulsions or effect on seizure threshold
Vascular - BP lowering not characterized in autonomic section
REFERENCE :
IJEBA6 Indian Journal of Experimental Biology. (Publications & Information
Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963-
Volume(issue)/page/year: 22,539,1984
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - cat
DOSE/DURATION : 37 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
DDREDK Drug Development Research. (Alan R. Liss, Inc., 41 E. 11th St., New
York, NY 10003) V.1- 1981- Volume(issue)/page/year: 22,385,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : 9900 ug/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: -,61,1972
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - guinea pig
DOSE/DURATION : 52 mg/kg
TOXIC EFFECTS :
Cardiac - other changes
REFERENCE :
THERAP Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris,
France) V.1- 1946- Volume(issue)/page/year: 20,67,1965
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 3200 mg/kg/32D-C
TOXIC EFFECTS :
Liver - other changes
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Related to Chronic Data - death
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 24640 mg/kg/1Y-I
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 28,1898,1978
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 220 mg/kg
SEX/DURATION : female 1-22 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - stillbirth
Reproductive - Effects on Newborn - behavioral
REFERENCE :
BRBUDU Brain Research Bulletin. (Pergamon Press Inc., Maxwell House,
Fairview Park, Elmsford, NY 10523) V.1- 1976- Volume(issue)/page/year:
24,207,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 70 mg/kg
SEX/DURATION : male 5 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
REFERENCE :
IMSCE2 IRCS Medical Science. (Lancaster, UK) V.12-14, 1984-86. For
publisher information, see MSCREJ. Volume(issue)/page/year: 14,579,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE : 60 mg/kg
SEX/DURATION : female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Effects on Embryo or Fetus - fetal death
Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
DGDFA5 Development, Growth & Differentiation. (Japan Pub. Trading Co.
(USA), 1255 Howard St., San Francisco, CA 94103) V.11- 1969-
Volume(issue)/page/year: 22,61,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE : 60 mg/kg
SEX/DURATION : female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
REFERENCE :
DGDFA5 Development, Growth & Differentiation. (Japan Pub. Trading Co.
(USA), 1255 Howard St., San Francisco, CA 94103) V.11- 1969-
Volume(issue)/page/year: 22,61,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - hamster
DOSE : 60 mg/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System
Reproductive - Specific Developmental Abnormalities - body wall
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
RCPBDC Research Communications in Psychology, Psychiatry and Behavior. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1976-
Volume(issue)/page/year: 5,275,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - hamster
DOSE : 70300 ug/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Specific Developmental Abnormalities - Central Nervous System
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
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: 30,39,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Parenteral
SPECIES OBSERVED : Rodent - hamster
DOSE : 60 mg/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System
Reproductive - Specific Developmental Abnormalities - body wall
REFERENCE :
NRTXDN Neurotoxicology. (Intox Press, Inc., POB 34075, Little Rock, AR
72203) V.1- 1979- Volume(issue)/page/year: 3,83,1982
** MUTATION DATA **
TYPE OF TEST : Sex chromosome loss and nondisjunction
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Insect - Drosophila melanogaster
DOSE/DURATION : 2 mg/2D
REFERENCE :
SOGEBZ Soviet Genetics. English translation of GNKAA5. (Plenum Pub. Corp.,
233 Spring St., New York, NY 10013) V.2- 1966- Volume(issue)/page/year:
11,718,1975
TYPE OF TEST : Sperm Morphology
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 70 mg/kg/5D
REFERENCE :
IMSCE2 IRCS Medical Science. (Lancaster, UK) V.12-14, 1984-86. For
publisher information, see MSCREJ. Volume(issue)/page/year: 14,579,1986
*** REVIEWS ***
TOXICOLOGY REVIEW
IDPYAK Industrial Pharmacology. (Mount Kisco, NY) V.1-3, 1974-79.
Discontinued. Volume(issue)/page/year: 2,209,1975
*** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA ***
NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
NOES - National Occupational Exposure Survey (1983)
NOES Hazard Code - X5594
No. of Facilities: 69 (estimated)
No. of Industries: 1
No. of Occupations: 1
No. of Employees: 514 (estimated)
No. of Female Employees: 266 (estimated)
*** STATUS IN U.S. ***
EPA TSCA Section 8(b) CHEMICAL INVENTORY
*** END OF RECORD ***