*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : US5676200
CHEMICAL NAME : 3-Pyridinecarboxylic acid,
1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-1,3,2-dioxap
hosphorinan- 2-yl)-4-(3-nitrophenyl)-,
2-(phenyl(phenylmethyl)amino)ethyl ester, P-oxide,
monohydrochloride
CAS REGISTRY NUMBER : 111011-76-8
LAST UPDATED : 199512
DATA ITEMS CITED : 17
MOLECULAR FORMULA : C34-H38-N3-O7-P.Cl-H.C2-H6-O
MOLECULAR WEIGHT : 714.26
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
SYNONYMS/TRADE NAMES :
* Efonidipine hydrochloride ethanolate
* NZ 105 ethanolate
* NZ-105
*** 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 : >5 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 161 mg/kg
TOXIC EFFECTS :
Behavioral - altered sleep time (including change in righting reflex)
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - dyspnea
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >5 gm/kg
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 43 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - dyspnea
Nutritional and Gross Metabolic - body temperature decrease
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1805 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - dyspnea
Nutritional and Gross Metabolic - body temperature decrease
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 365 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Lungs, Thorax, or Respiration - dyspnea
Nutritional and Gross Metabolic - body temperature decrease
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >5 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 77 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - convulsions or effect on seizure threshold
Skin and Appendages - hair
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: 19(Suppl 6),S1333,1991
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 3 gm/kg
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - emphysema
Kidney, Ureter, Bladder - other changes
Blood - other changes
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: 19(Suppl 6),S1341,1991
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 10950 mg/kg/1Y-C
TOXIC EFFECTS :
Cardiac - changes in heart weight
Liver - changes in liver weight
Endocrine - changes in thyroid weight
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: 19(Suppl 6),S1411,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 2730 mg/kg/13W-I
TOXIC EFFECTS :
Cardiac - changes in heart weight
Liver - other changes
Liver - changes in liver weight
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: 19(Suppl 6),S1349,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 7300 mg/kg/1Y-C
TOXIC EFFECTS :
Cardiac - changes in heart weight
Kidney, Ureter, Bladder - proteinuria
Blood - leukopenia
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: 19(Suppl 6),S1433,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 9100 mg/kg/13W-I
TOXIC EFFECTS :
Cardiac - changes in heart weight
Endocrine - adrenal cortex hyperplasia
Blood - other changes
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: 19(Suppl 6),S1377,1991
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 30 gm/kg
SEX/DURATION : male 9 week(s) pre-mating
female 2 week(s) pre-mating - 3 week(s) after
conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
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: 19(suppl 6),1465,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 36 gm/kg
SEX/DURATION : male 9 week(s) pre-mating
female 2 week(s) pre-mating - 3 week(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
Reproductive - Effects on Newborn - delayed effects
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: 19(Suppl 6),S1465,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 7800 mg/kg
SEX/DURATION : female 17-21 day(s) after conception
lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
Reproductive - Effects on Newborn - behavioral
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: 19(Suppl 6),S1527,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 11700 mg/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
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: 19(Suppl 6),S1517,1991
*** END OF RECORD ***