*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : NK7882200
CHEMICAL NAME           : 1H-Indazole-3-carboxamide,
                          1-methyl-N-(9-methyl-9-azabicyclo(3.3.1)non-3-yl)-,
                          monohydrochloride, endo-
CAS REGISTRY NUMBER     : 107007-99-8
LAST UPDATED            : 199612
DATA ITEMS CITED        : 12
MOLECULAR FORMULA       : C18-H24-N4-O.Cl-H
MOLECULAR WEIGHT        : 348.92
COMPOUND DESCRIPTOR     : Drug
                          Mutagen
                          Reproductive Effector
SYNONYMS/TRADE NAMES :
   * BRL 43694A
   * Granisetron hydrochloride
   *   endo-1-Methyl-N-(9-methyl-9-azabicyclo(3.3.1)non-3-yl)-1H-indazole-3-car
     boxamide hydrochloride
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 350 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: 26,740,1995
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 14 mg/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Behavioral - ataxia
   Behavioral - muscle contraction or spasticity
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: 24,4991,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 350 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: 26,740,1995
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 17 mg/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - convulsions or effect on seizure threshold
   Lungs, Thorax, or Respiration - respiratory stimulation
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: 24,4991,1990
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 3 mg/kg
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - effect, not otherwise specified
   Behavioral - tremor
   Gastrointestinal - nausea or vomiting
REFERENCE :
   YKYUA6 Yakkyoku.  Pharmacy.  (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo,
   Japan)  V.1-    1950-  Volume(issue)/page/year: 43,589,1992
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 4500 mg/kg/30D-I
TOXIC EFFECTS :
   Liver - changes in liver weight
   Blood - changes in leukocyte (WBC) count
   Related to Chronic Data - death
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: 23,1239,1995
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 18200 mg/kg/26W-I
TOXIC EFFECTS :
   Liver - changes in liver weight
   Blood - changes in platelet count
   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: 23,1239,1995
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 325 mg/kg/30D-I
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - lacrimation
   Sense Organs and Special Senses (Eye) - ptosis
   Behavioral - tremor
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: 23,1249,1995
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 52 mg/kg
SEX/DURATION            : male 10 week(s) pre-mating
                          female 2 week(s) pre-mating  - 19 day(s) after
                          conception
TOXIC EFFECTS :
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
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: 24,5055,1990
 
                            ** MUTATION DATA **
 
TYPE OF TEST            : Mutation in microorganisms
TEST SYSTEM             : Bacteria - Salmonella typhimurium
DOSE/DURATION           : 5 gm/L
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: 24,6795,1990
 
TYPE OF TEST            : DNA repair
TEST SYSTEM             : Human HeLa cell
DOSE/DURATION           : 500 mg/L
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: 24,6795,1990
 
TYPE OF TEST            : Cytogenetic analysis
TEST SYSTEM             : Human Lymphocyte
DOSE/DURATION           : 1500 mg/L
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: 24,6795,1990
 
                            *** END OF RECORD ***