*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : US7972100
CHEMICAL NAME : 3,5-Pyridinedicarboxylic acid,
1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-,
2-(benzylmethyl amino)ethyl methyl ester,
monohydrochloride
CAS REGISTRY NUMBER : 54527-84-3
LAST UPDATED : 199703
DATA ITEMS CITED : 25
MOLECULAR FORMULA : C26-H29-N3-O6.Cl-H
MOLECULAR WEIGHT : 516.04
WISWESSER LINE NOTATION : T6M DHJ B1 CVO1 DR CNW& EVO2N1&1R& F1 &GH
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Angioglebil
* Bionicard
* Dafil
* Dagan
* Lincil
* Loxen
* Nicardil
* Nicardipine hydrochloride
* Nicodel
* Perdipina
* Perdipine
* RS-69216
* YC 93
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 26 mg/kg/30D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - urine volume decreased
Kidney, Ureter, Bladder - other changes
REFERENCE :
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N.
Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year:
258,3388,1987
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 1800 ug/kg/36H-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - urine volume decreased
REFERENCE :
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N.
Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year:
258,3388,1987
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 184 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
USXXAM United States Patent Document. (U.S. Patent Office, Box 9,
Washington, DC 20231) Volume(issue)/page/year: #4565823
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 155 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: 6,543,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 606 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
USXXAM United States Patent Document. (U.S. Patent Office, Box 9,
Washington, DC 20231) Volume(issue)/page/year: #4565823
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 15500 ug/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 26,2172,1976
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 322 mg/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
CYLPDN Zhongguo Yaoli Xuebao. Acta Pharmacologica Sinica. Chinese Journal
of Pharmacology. (China International Book Trading Corp., POB 2820,
Beijing, Peop. Rep. China) V.1- 1980- Volume(issue)/page/year:
4,97,1983
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 123 mg/kg
TOXIC EFFECTS :
Behavioral - tremor
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
CYLPDN Zhongguo Yaoli Xuebao. Acta Pharmacologica Sinica. Chinese Journal
of Pharmacology. (China International Book Trading Corp., POB 2820,
Beijing, Peop. Rep. China) V.1- 1980- Volume(issue)/page/year:
4,97,1983
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 540 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: 6,543,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 19900 ug/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - ptosis
Behavioral - ataxia
Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 18,301,1979
TYPE OF TEST : LD - Lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : >60 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
USXXAM United States Patent Document. (U.S. Patent Office, Box 9,
Washington, DC 20231) Volume(issue)/page/year: #4565823
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 5 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
USXXAM United States Patent Document. (U.S. Patent Office, Box 9,
Washington, DC 20231) Volume(issue)/page/year: #4565823
** OTHER MULTIPLE DOSE TOXICITY DATA **
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 - fatty liver degeneration
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - transaminases
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 18,391,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Unreported
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 4550 mg/kg/26W-I
TOXIC EFFECTS :
Behavioral - fluid intake
Cardiac - changes in heart weight
Liver - changes in liver weight
REFERENCE :
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 4,57,1979
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 1050 mg/kg
SEX/DURATION : female 14 day(s) pre-mating
female 1-7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
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: 13,1160,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 2100 mg/kg
SEX/DURATION : female 14 day(s) pre-mating
female 1-7 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)
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: 13,1160,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 2700 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)
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: 13,1160,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 1350 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 :
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: 13,1160,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE : 3360 mg/kg
SEX/DURATION : male 9 week(s) pre-mating
female 2 week(s) pre-mating - 1 week(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)
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: 22,1411,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 110 mg/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Effects on Embryo or Fetus - fetal death
Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4
per # born alive)
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: 20,5419,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 55 mg/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - live birth index (measured after birth)
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: 20,5419,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 30 mg/kg
SEX/DURATION : female 17-22 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - stillbirth
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: 22,1419,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 60 mg/kg
SEX/DURATION : female 17-22 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: 22,1419,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 1650 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 - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Effects on Embryo or Fetus - fetal 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: 13,1160,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rabbit
DOSE : 13 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 - fetal 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: 20,4641,1986
*** END OF RECORD ***