*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : HQ4375000 CHEMICAL NAME : Dibenz(b,e)oxepin-delta(sup 11(6H),gamma)-propylamine, N,N-dimethyl-, hydrochloride CAS REGISTRY NUMBER : 1229-29-4 LAST UPDATED : 199706 DATA ITEMS CITED : 29 MOLECULAR FORMULA : C19-H21-N-O.Cl-H MOLECULAR WEIGHT : 315.87 WISWESSER LINE NOTATION : T C676 IO&T&J B3N1&1 &GH COMPOUND DESCRIPTOR : Drug Reproductive Effector Human SYNONYMS/TRADE NAMES : * Adapin * Cidoxepin hydrochloride * Curatin * 11-Dimethylamino propylidene 6H-dibenz(b,e)oxepin * 11-(3-(Dimethylamino)propylidene)-6,11-dihydrodibenz(b,e)oxepin hydrochloride * N,N-Dimethyldibenz(b,e)oxepin-delta(sup 11(6H),gamma)-propylamine hydrochloride * Doxepin hydrochloride * NSC-108160 * P-3693A * P-4599 * 1-Propanamine, 3-dibenz(b,e)oxepin-11(6H)ylidene-N,N-dimethyl-, hydrochloride * Sinequan *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 357 ug/kg TOXIC EFFECTS : Behavioral - muscle weakness Behavioral - coma Vascular - BP lowering not characterized in autonomic section REFERENCE : JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 7,161,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 112 mg/kg/4W-I TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions REFERENCE : JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 44,106,1983 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 90 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - coma Blood - hemorrhage REFERENCE : JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 2,18,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 9300 ug/kg TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions Behavioral - muscle contraction or spasticity Cardiac - change in rate REFERENCE : JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 237,2632,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 141 mg/kg/12W-I TOXIC EFFECTS : Sense Organs and Special Senses (Ear) - tinnitus REFERENCE : SMJOAV Southern Medical Journal. (Southern Medical Assoc., POB 2446, Birmingham, AL 35205) V.1- 1908- Volume(issue)/page/year: 76,1204,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 357 ug/kg TOXIC EFFECTS : Liver - hepatitis (hepatocellular necrosis), zonal Liver - jaundice (or hyperbilirubinemia) hepatocellular REFERENCE : ANZJB8 Australian and New Zealand Journal of Medicine. (Modern Medicine of Australia Pty., Ltd., 100 Pacific Highway, North Sydney, 2060, Australia) V.1- 1971- Volume(issue)/page/year: 23,523,1993 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 147 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: -,72,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 84 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia 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 : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 155 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold 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 - rat DOSE/DURATION : 13 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: -,72,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 180 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia 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 - mouse DOSE/DURATION : 79 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: -,72,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 160 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: -,72,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse 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: -,72,1972 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 300 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting 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 : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting 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 : Intramuscular SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 40 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting 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 : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 20400 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 : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 11 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: -,72,1972 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 14560 mg/kg/26W-C TOXIC EFFECTS : Cardiac - changes in heart weight Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,929,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3300 mg/kg/33D-C TOXIC EFFECTS : Gastrointestinal - 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 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 1620 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 1620 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 60 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 540 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 210 mg/kg SEX/DURATION : female 8-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - live birth index (measured after birth) REFERENCE : DPTHDL Developmental Pharmacology and Therapeutics. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 8,17,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE : 900 mg/kg SEX/DURATION : female 8-16 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,905,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE : 45 mg/kg SEX/DURATION : female 8-16 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,905,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3181 No. of Facilities: 140 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 2633 (estimated) No. of Female Employees: 1442 (estimated) *** END OF RECORD ***