*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : EJ9960100
CHEMICAL NAME : Butanedioic acid, compd. with
2-(2,2-diphenylcyclopropyl)-4,5-dihydro-1H-imidazole
(1:1)
CAS REGISTRY NUMBER : 100678-32-8
LAST UPDATED : 199709
DATA ITEMS CITED : 18
MOLECULAR FORMULA : C18-H18-N2.C4-H6-O4
MOLECULAR WEIGHT : 380.48
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
SYNONYMS/TRADE NAMES :
* Cibenzoline succinate (1:1)
* Cifenline succinate
* Cipralan
* 4,5-Dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole succinate
* (+-)-2-(2,2-Diphenylcyclopropyl)-2-imidazoline succinate (1:1)
* 1H-Imidazole, 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-, succinate
* 1H-Imidazole, 2-(2,2-diphenylcyclopropyl)-4,5-dihydro-, (+-)-,
butanedioate (1:1)
* Ritmalan
* Ro 22-7796/001
*** 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 : 359 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - altered sleep time (including change in righting reflex)
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: 22,4485,1988
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 83400 ug/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - altered sleep time (including change in righting reflex)
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: 22,4485,1988
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 156 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - altered sleep time (including change in righting reflex)
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: 22,4485,1988
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 44400 ug/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - altered sleep time (including change in righting reflex)
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: 22,4485,1988
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 180 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - altered sleep time (including change in righting reflex)
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: 22,4485,1988
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 73100 ug/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - altered sleep time (including change in righting reflex)
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: 22,4485,1988
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 83300 ug/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - altered sleep time (including change in righting reflex)
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: 22,4485,1988
TYPE OF TEST : LD - Lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : >56 mg/kg
TOXIC EFFECTS :
Behavioral - tremor
Gastrointestinal - hypermotility, diarrhea
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: 22,4519,1988
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 33300 ug/kg
TOXIC EFFECTS :
Behavioral - altered sleep time (including change in righting reflex)
Cardiac - change in rate
Gastrointestinal - hypermotility, diarrhea
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: 25,3385,1991
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 18250 mg/kg/52W-C
TOXIC EFFECTS :
Kidney, Ureter, Bladder - urine volume increased
Kidney, Ureter, Bladder - 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: 22,4485,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 9100 mg/kg/13W-C
TOXIC EFFECTS :
Behavioral - fluid intake
Kidney, Ureter, Bladder - 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: 22,4485,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 2730 mg/kg/13W-C
TOXIC EFFECTS :
Kidney, Ureter, Bladder - urine volume increased
Kidney, Ureter, Bladder - other changes in urine composition
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: 25,3373,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 2912 mg/kg/13W-I
TOXIC EFFECTS :
Gastrointestinal - nausea or vomiting
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
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: 22,4519,1988
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 1375 mg/kg
SEX/DURATION : female 7-17 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 - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced 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: 22,4527,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 650 mg/kg
SEX/DURATION : female 17-21 day(s) after conception
lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
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: 22,4527,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 2600 mg/kg
SEX/DURATION : female 17-21 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 :
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: 22,4527,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 330 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)
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: 25,3394,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rabbit
DOSE : 130 mg/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
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: 25,3394,1991
*** END OF RECORD ***