*** 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 ***