*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : XZ5660000 CHEMICAL NAME : s-Triazolo(4,3-a)pyridin-3(2H)-one, 2-(3-(4-(m-chlorophenyl)-1-piperazinyl)propyl)-, monohydrochloride CAS REGISTRY NUMBER : 25332-39-2 LAST UPDATED : 199706 DATA ITEMS CITED : 29 MOLECULAR FORMULA : C19-H22-Cl-N5-O.Cl-H MOLECULAR WEIGHT : 408.37 WISWESSER LINE NOTATION : T56 ANVNNJ C3- AT6N DNTJ DR CG &GH COMPOUND DESCRIPTOR : Drug Reproductive Effector Human SYNONYMS/TRADE NAMES : * AF 1161 * 2-(3-(4-(3-Chlorophenyl)-1-piperazinyl)propyl)-s-triazolo(4,3-a)pyridin- 3(2H)-one HCl * Desyrel * KB-831 * Molipaxin * Pragmazone * Thombran * Tombran * Trazodone hydrochloride * Trittico *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 5714 ug/kg/4D-I TOXIC EFFECTS : Behavioral - euphoria Behavioral - excitement REFERENCE : BJPYAJ British Journal of Psychiatry. (Headley Brothers, Ltd., Ashford, Kent TN24 8HH, UK) V.109- 1963- Volume(issue)/page/year: 158,275,1991 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 43 mg/kg/30D-I TOXIC EFFECTS : Blood - agranulocytosis Blood - other changes REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 150,1563,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 750 ug/kg TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 141,434,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 720 mg/kg/34W-I TOXIC EFFECTS : Liver - hepatitis (hepatocellular necrosis), zonal Liver - jaundice (or hyperbilirubinemia) hepatocellular Kidney, Ureter, Bladder - other changes in urine composition REFERENCE : AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 118,791,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 46 mg/kg/8D-I TOXIC EFFECTS : Behavioral - excitement Cardiac - pulse rate increase, without fall in BP Kidney, Ureter, Bladder - urine volume increased REFERENCE : JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 6,117,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 667 ug/kg TOXIC EFFECTS : Cardiac - cardiomyopathy including infarction REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 141,1472,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 80 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - respiratory depression REFERENCE : JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 8,91,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 690 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 178 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2729 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 91 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 584 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 : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 255 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPMSAE Journal of Pharmaceutical Sciences. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.50- 1961- Volume(issue)/page/year: 81,99,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,967,1991 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 91 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 500 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Behavioral - aggression REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >40 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 25 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands REFERENCE : PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 3,94,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 560 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 52 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands REFERENCE : MPPPBK Modern Problems of Pharmacopsychiatry. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) V.1- 1968- Volume(issue)/page/year: 9,76,1974 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 66175 mg/kg/78W-C TOXIC EFFECTS : Endocrine - changes in adrenal weight Endocrine - changes in thyroid weight Related to Chronic Data - changes in testicular weight 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: 23,5865,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2730 mg/kg/13W-I TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17(Suppl 5),S1259,1989 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE : 159 mg/kg SEX/DURATION : male 7 week(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - impotence REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 140,1256,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE : 112 mg/kg SEX/DURATION : male 6 week(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - other effects on male REFERENCE : JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 45,232,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE : 667 ug/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - other effects on male REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 142,142,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 3300 mg/kg SEX/DURATION : female 7-17 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 - musculoskeletal system REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17(Suppl 5),1283,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 1100 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - physical REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17(Suppl 5),1283,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 750 mg/kg SEX/DURATION : female 7-20 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 17(Suppl 5),1301,1989 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5669 No. of Facilities: 24 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 333 (estimated) No. of Female Employees: 219 (estimated) *** END OF RECORD ***