*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : XZ5472500
CHEMICAL NAME           : 4H-s-Triazolo(4,3-a)(1,4)benzodiazepine,
                          8-chloro-6-(o-chlorophenyl)-1-methyl-
CAS REGISTRY NUMBER     : 28911-01-5
BEILSTEIN REFERENCE NO. : 1226643
LAST UPDATED            : 199806
DATA ITEMS CITED        : 26
MOLECULAR FORMULA       : C17-H12-Cl2-N4
MOLECULAR WEIGHT        : 343.23
WISWESSER LINE NOTATION : T B576 BN DNN HN GHJ C1 IR BG& LG
COMPOUND DESCRIPTOR     : Drug
                          Reproductive Effector
                          Human
SYNONYMS/TRADE NAMES :
   *   8-Chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo(4,3-a)(1,4)benzodiaze
     pine
   * Halcion
   * Novidorm
   * Songar
   * Triazolam
   * 4H-(1,2,4)Triazolo(4,3-a)(1,4)benzodiazepine,  
   8-chloro-6-(2-chlorophenyl)-1-methyl-
   * U-33,030
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 3289 ng/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - alteration of operant conditioning
REFERENCE :
   CLPTAT Clinical Pharmacology and Therapeutics (St. Louis).  (C.V. Mosby Co.,
   11830 Westline Industrial Dr., St. Louis, MO 63146)  V.1-    1960-
   Volume(issue)/page/year: 49,581,1991
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 7 ug/kg
TOXIC EFFECTS :
   Behavioral - coma
   Lungs, Thorax, or Respiration - acute pulmonary edema
   Lungs, Thorax, or Respiration - respiratory obstruction
REFERENCE :
   JTCTDW Journal of Toxicology, Clinical Toxicology.  (Marcel Dekker, 270
   Madison Ave., New York, NY 10016)  V.19-    1982-  Volume(issue)/page/year:
   33,185,1995
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - woman
DOSE/DURATION           : 100 ug/kg
TOXIC EFFECTS :
   Behavioral - coma
   Lungs, Thorax, or Respiration - cyanosis
   Lungs, Thorax, or Respiration - other changes
REFERENCE :
   AJEMEN American Journal of Emergency Medicine.  (WB Saunders, Philadelphia,
   PA)  V.1-    1983-  Volume(issue)/page/year: 3,210,1985
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human
DOSE/DURATION           : 114 ug/kg/4D-I
TOXIC EFFECTS :
   Behavioral - toxic psychosis
REFERENCE :
   BMJOAE British Medical Journal.  (British Medical Assoc., BMA House,
   Tavistock Sq., London WC1H 9JR, UK)  V.1-    1857- Volume(issue)/page/year:
   304,1178,1992
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 357 ug/kg
TOXIC EFFECTS :
   Behavioral - hallucinations, distorted perceptions
   Behavioral - coma
   Behavioral - irritability
REFERENCE :
   HETOEA Human & Experimental Toxicology.  (Macmillan Press Ltd., Brunel Road,
   Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990-
   Volume(issue)/page/year: 11,289,1992
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 100 ug/kg
TOXIC EFFECTS :
   Behavioral - sleep
   Behavioral - ataxia
   Cardiac - pulse rate
REFERENCE :
   JCLPDE Journal of Clinical Psychiatry.  (Physicians Postgraduate Press,
   Inc., POB 240008, Memphis, TN 38124)  V.39-    1978-
   Volume(issue)/page/year: 47,50,1986
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human
DOSE/DURATION           : 7 ug/kg
TOXIC EFFECTS :
   Brain and Coverings - changes in surface EEG
   Behavioral - sleep
   Behavioral - hallucinations, distorted perceptions
REFERENCE :
   JCPCBR Journal of Clinical Pharmacology.  (Hall Assoc., PO Box 482,
   Stamford, CT 06904) V.13-    1973-  Volume(issue)/page/year: 14,102,1974
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 107 ug/kg
TOXIC EFFECTS :
   Behavioral - coma
REFERENCE :
   AIMDAP Archives of Internal Medicine.  (AMA, 535 N. Dearborn St., Chicago,
   IL 60610)  V.1-    1908-  Volume(issue)/page/year: 145,663,1985
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 1786 ng/kg
TOXIC EFFECTS :
   Behavioral - hallucinations, distorted perceptions
REFERENCE :
   SMJOAV Southern Medical Journal.  (Southern Medical Assoc., POB 2446,
   Birmingham, AL 35205) V.1-    1908-  Volume(issue)/page/year: 80,1425,1987
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : >7500 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   YKYUA6 Yakkyoku.  Pharmacy.  (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo,
   Japan)  V.1-    1950-  Volume(issue)/page/year: 35,1074,1984
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : >3300 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: -,860,1995
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : >5 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   YAKUD5 Gekkan Yakuji.  Pharmaceuticals Monthly.  (Yakugyo Jihosha, Inaoka
   Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan)  V.1-   1959-
   Volume(issue)/page/year: 25,499,1983
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 1080 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Autonomic Nervous System - smooth muscle relaxant (mechanism undefined,
   spasmolytic)
REFERENCE :
   CKFRAY Ceskoslovenska Farmacie.  (PNS-Ustredni Expedice a Dovoz Tisku,
   Kafkova 19, 160 00 Prague 6, Czechoslovakia)  V.1-    1952-
   Volume(issue)/page/year: 37,443,1988
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 1625 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: 14,484,1983
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : >5 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   YAKUD5 Gekkan Yakuji.  Pharmaceuticals Monthly.  (Yakugyo Jihosha, Inaoka
   Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan)  V.1-   1959-
   Volume(issue)/page/year: 25,499,1983
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 5600 mg/kg/35D-C
TOXIC EFFECTS :
   Liver - other changes
   Kidney, Ureter, Bladder - other changes
   Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
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: 20,8557,1986
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 1500 mg/kg/30D-C
TOXIC EFFECTS :
   Liver - other changes
   Kidney, Ureter, Bladder - other changes in urine composition
   Endocrine - other changes
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: 20,8597,1986
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - woman
DOSE                    : 50 ug/kg
SEX/DURATION            : female 33 week(s) after conception
TOXIC EFFECTS :
   Reproductive - Specific Developmental Abnormalities - respiratory system
   Reproductive - Effects on Newborn - Apgar score (human only)
   Reproductive - Effects on Newborn - behavioral
REFERENCE :
   EJPEDT European Journal of Pediatrics.  (Springer-Verlag New York, Inc.,
   Service Center, 44 Hartz Way, Secaucus, NJ 07094)  V.121-    1975-
   Volume(issue)/page/year: 155,1065,1996
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 8100 mg/kg
SEX/DURATION            : female 17-22 day(s) after conception
                          lactating female 21 day(s) post-birth
TOXIC EFFECTS :
   Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4
   per # born alive)
   Reproductive - Effects on Newborn - weaning or lactation index (e.g., #
   alive at weaning per # alive at day 4)
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: 10,52,1979
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 810 mg/kg
SEX/DURATION            : female 17-22 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 :
   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: 10,52,1979
 
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 - Specific Developmental Abnormalities - musculoskeletal system
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: 10,52,1979
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 4400 mg/kg
SEX/DURATION            : female 7-17 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Maternal Effects - ovaries, fallopian tubes
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
   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: 30,765,1985
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 4400 mg/kg
SEX/DURATION            : female 7-17 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4
   per # born alive)
   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: 30,765,1985
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE                    : 39 mg/kg
SEX/DURATION            : female 6-18 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
   number of implants per female; total number of implants per corpora lutea)
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
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: 10,52,1979
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE                    : 91 mg/kg
SEX/DURATION            : female 6-18 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: 30,819,1985
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE                    : 195 mg/kg
SEX/DURATION            : female 6-18 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
   before birth)
REFERENCE :
   OYYAA2 Oyo Yakuri.  Pharmacometrics.  (Oyo Yakuri Kenkyukai, CPO Box 180,
   Sendai 980-91, Japan) V.1-    1967-  Volume(issue)/page/year: 30,819,1985
 
                            *** END OF RECORD ***