*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : TH9203900
CHEMICAL NAME           : 1(2H)-Phthalazinone,
                          4-((4-chlorophenyl)methyl)-2-(hexahydro-1-methyl-1H-a
                          zepin-4-yl)-, monohydrochloride
CAS REGISTRY NUMBER     : 79307-93-0
LAST UPDATED            : 199206
DATA ITEMS CITED        : 21
MOLECULAR FORMULA       : C22-H24-Cl-N3-O.Cl-H
MOLECULAR WEIGHT        : 418.40
WISWESSER LINE NOTATION : T66 BVNNJ E1R DG& C- DT7NTJ A1 &GH
COMPOUND DESCRIPTOR     : Drug
                          Reproductive Effector
SYNONYMS/TRADE NAMES :
   * A 5610
   * Azelastine hydrochloride
   * Azeptin
   *   4-(p-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalaz
     inone HCl
   * E-0659
   * W-2979M
 
                       *** 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           : 580 mg/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 80500 ug/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 24600 ug/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intramuscular
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 115 mg/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 143 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - convulsions or effect on seizure threshold
   Gastrointestinal - changes in structure or function of salivary glands
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 59600 ug/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - convulsions or effect on seizure threshold
   Gastrointestinal - changes in structure or function of salivary glands
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 25400 ug/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - convulsions or effect on seizure threshold
   Gastrointestinal - changes in structure or function of salivary glands
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intramuscular
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 57200 ug/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - ataxia
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 107 mg/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Behavioral - ataxia
   Gastrointestinal - nausea or vomiting
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: 20,5235,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 126 mg/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 37300 ug/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 23 mg/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intramuscular
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 46200 ug/kg
TOXIC EFFECTS :
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
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: 20,5231,1986
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 1050 mg/kg/5W-C
TOXIC EFFECTS :
   Liver - changes in liver weight
   Kidney, Ureter, Bladder - urine volume increased
   Biochemical - Enzyme inhibition, induction, or change in blood or tissue
   levels - phosphatases
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: 20,5238,1986
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 5460 mg/kg/26W-C
TOXIC EFFECTS :
   Liver - changes in liver weight
   Kidney, Ureter, Bladder - urine volume increased
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: 20,5273,1986
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 10920 mg/kg/52W-C
TOXIC EFFECTS :
   Liver - changes in liver weight
   Kidney, Ureter, Bladder - other changes in urine composition
   Kidney, Ureter, Bladder - changes in bladder 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: 20,5287,1986
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 700 mg/kg/5W-C
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Behavioral - excitement
   Related to Chronic Data - death
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: 20,5251,1986
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 6729 mg/kg
SEX/DURATION            : male 11 week(s) pre-mating
                          female 2 week(s) pre-mating  - 7 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 - Fertility - other measures of fertility
REFERENCE :
   ARZNAD Arzneimittel-Forschung. Drug Research.  (Editio Cantor Verlag,
   Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.)  V.1-    1951-
   Volume(issue)/page/year: 31,1225,1981
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 330 mg/kg
SEX/DURATION            : female 7-17 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
   ARZNAD Arzneimittel-Forschung. Drug Research.  (Editio Cantor Verlag,
   Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.)  V.1-    1951-
   Volume(issue)/page/year: 31,1225,1981
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 755 mg/kg
SEX/DURATION            : female 7-17 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
   resorbed implants per total number of implants)
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
   Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
   ARZNAD Arzneimittel-Forschung. Drug Research.  (Editio Cantor Verlag,
   Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.)  V.1-    1951-
   Volume(issue)/page/year: 31,1225,1981
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE                    : 390 mg/kg
SEX/DURATION            : female 6-18 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - abortion
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
   Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
   ARZNAD Arzneimittel-Forschung. Drug Research.  (Editio Cantor Verlag,
   Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.)  V.1-    1951-
   Volume(issue)/page/year: 31,1225,1981
 
                            *** END OF RECORD ***