*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : DI0250000
CHEMICAL NAME : Benzoic acid, 3,4,5-trimethoxy-, diester with
tetrahydro-1H-1,4-diazepine-1,4(5H)dipropanol,
dihydrochloride
CAS REGISTRY NUMBER : 20153-98-4
LAST UPDATED : 199506
DATA ITEMS CITED : 20
MOLECULAR FORMULA : C31-H44-N2-O10.2Cl-H
MOLECULAR WEIGHT : 677.69
WISWESSER LINE NOTATION : T7N DNTJ A3OVR CO1 DO1 EO1& D3OVR CO1 DO1 EO1 &GH 2
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
SYNONYMS/TRADE NAMES :
* ASTA C
* ASTA C 4898
* N,N'-(Bis-omega-hydroxypropyl)homopiperazine 3,4,5-trimethoxybenzoate
dihydrochloride
* N,N'-Bis(3-(3,4,5-trimethoxybenzoyloxy)propyl)homopiperazine
dihydrochloride
* 1,4-Bis(3-(3,4,5-trimethoxybenzoyloxy)-propyl)perhydro-1,4-diazepine
dihydrochloride
* Comelian
* Cormelian
* Dilazep dihydrochloride
* K-285
* Labitan
* Tetrahydro-1H-1,4-diazepine-1,4(5H)-dipropanol
bis(3,4,5-trimethoxybenzoate) dihydrochloride
*** 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 : >2150 mg/kg
TOXIC EFFECTS :
Peripheral Nerve and Sensation - spastic paralysis with or without sensory
change
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 22,667,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 85200 ug/kg
TOXIC EFFECTS :
Behavioral - tremor
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 22,667,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 369 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - dyspnea
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: 8,2044,1974
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 13700 ug/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - respiratory depression
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: 8,2044,1974
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 2860 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - respiratory depression
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: 8,2044,1974
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 161 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 22,667,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 154 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 22,667,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 16800 ug/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - respiratory depression
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: 8,2044,1974
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : >316 mg/kg
TOXIC EFFECTS :
Cardiac - pulse rate increase, without fall in BP
Gastrointestinal - nausea or vomiting
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 22,667,1972
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 11200 ug/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Gastrointestinal - changes in structure or function of salivary glands
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 22,667,1972
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 156 gm/kg/26W-I
TOXIC EFFECTS :
Liver - other changes
Kidney, Ureter, Bladder - other changes
Nutritional and Gross Metabolic - weight loss or decreased weight gain
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: 8,2062,1974
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 30 gm/kg/30D-C
TOXIC EFFECTS :
Liver - changes in liver weight
Endocrine - changes in adrenal weight
Related to Chronic Data - changes in ovarian 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: 8,2050,1974
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 336 mg/kg/28D-I
TOXIC EFFECTS :
Liver - changes in liver weight
Blood - normocytic anemia
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: 18(Suppl 12),S3091,199
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1456 mg/kg/26W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in bladder weight
Endocrine - changes in adrenal weight
Blood - normocytic anemia
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: 18(Suppl 12),S3155,199
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 84 mg/kg/7D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - urine volume increased
Kidney, Ureter, Bladder - other changes in urine composition
Nutritional and Gross Metabolic - changes in sodium
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: 18(Suppl 12),S3141,199
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 728 mg/kg/26W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition
Blood - changes in platelet count
Nutritional and Gross Metabolic - weight loss or decreased 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: 18(Suppl 12),S3193,199
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 1750 mg/kg
SEX/DURATION : female 7-13 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
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: 8,4368,1974
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 672 mg/kg
SEX/DURATION : male 9 week(s) pre-mating
female 2 week(s) pre-mating - 7 day(s) after
conception
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
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: 18(Suppl 12),S3227,199
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 6 gm/kg
SEX/DURATION : female 7-12 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: 8,2084,1974
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 3 gm/kg
SEX/DURATION : female 7-12 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
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: 8,2084,1974
*** END OF RECORD ***