*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : TW3666000
CHEMICAL NAME : L-Proline,
1-(N-(1-(ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-,
(S)-, (Z)-2- butenedioate (1:1)
CAS REGISTRY NUMBER : 76095-16-4
OTHER CAS REGISTRY NOS. : 77549-59-8
LAST UPDATED : 199709
DATA ITEMS CITED : 28
MOLECULAR FORMULA : C20-H28-N2-O5.C4-H4-O4
MOLECULAR WEIGHT : 492.58
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Enalapril
* Enalapril maleate
* N-((S)-1-Ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline maleate (1:1)
* (S)-1-(N-(1-(Ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline maleate
(1:1)
* MK 421
* MK 421 maleate
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 4 mg/kg/10D-I
TOXIC EFFECTS :
Liver - hepatitis (hepatocellular necrosis), zonal
Liver - liver function tests impaired
REFERENCE :
APHRER Annals of Pharmacotherpy. (Harvey Whitney Books Co., POB 42696,
Cincinnati, OH 45242) V. 26- 1992- Volume(issue)/page/year: 27,1405,1993
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 400 ug/kg/2D-I
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
REFERENCE :
BMJOAE British Medical Journal. (British Medical Assoc., BMA House,
Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year:
294,91,1987
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 357 ug/kg/3D-I
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - acute pulmonary edema
REFERENCE :
AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia,
PA) V.1- 1983- Volume(issue)/page/year: 8,124,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 39500 ug/kg/56W-I
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - acute pulmonary edema
Lungs, Thorax, or Respiration - dyspnea
Lungs, Thorax, or Respiration - cyanosis
REFERENCE :
JFAPDE Journal of Family Practice. (Appleton and Lange, East Norwalk, CT)
V.1- 1974- Volume(issue)/page/year: 34,201,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 143 ug/kg
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
REFERENCE :
BMJOAE British Medical Journal. (British Medical Assoc., BMA House,
Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year:
294,91,1987
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 2800 ug/kg/4W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - renal function tests depressed
Kidney, Ureter, Bladder - other changes in urine composition
REFERENCE :
BMJOAE British Medical Journal. (British Medical Assoc., BMA House,
Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year:
291,450,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 71 ug/kg
TOXIC EFFECTS :
Vascular - BP lowering not characterized in autonomic section
REFERENCE :
BMJOAE British Medical Journal. (British Medical Assoc., BMA House,
Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year:
291,1309,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 5600 ug/kg/4W-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Olfaction) - effect, not otherwise
specified
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823-
Volume(issue)/page/year: 2,1395,1986
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 2973 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - respiratory depression
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: 13,413,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1418 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - respiratory depression
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: 13,413,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 849 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - respiratory depression
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: 13,413,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 3507 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - respiratory depression
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: 13,413,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1160 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - respiratory depression
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: 13,413,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 859 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - ataxia
Lungs, Thorax, or Respiration - respiratory depression
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: 13,413,1985
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 900 mg/kg/30D-C
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Nutritional and Gross Metabolic - changes in potassium
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: 13,425,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 8190 mg/kg/13W-C
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition
Blood - leukopenia
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: 13,425,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 600 mg/kg/4W-C
TOXIC EFFECTS :
Blood - normocytic anemia
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
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: 13,467,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 8190 mg/kg/13W-C
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - transaminases
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: 13,467,1985
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 6800 ug/kg
SEX/DURATION : female 32-34 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system
REFERENCE :
AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200
Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year:
108,215,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 95200 ug/kg
SEX/DURATION : female 1-34 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co.,
11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920-
Volume(issue)/page/year: 162,187,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 95200 ug/kg
SEX/DURATION : female 1-34 week(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - other effects
Reproductive - Specific Developmental Abnormalities - urogenital system
Reproductive - Effects on Newborn - Apgar score (human only)
REFERENCE :
AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co.,
11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920-
Volume(issue)/page/year: 162,187,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 100 mg/kg
SEX/DURATION : female 6-15 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 - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
REFERENCE :
RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970-
Volume(issue)/page/year: 77,347,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 144 mg/kg
SEX/DURATION : female 6-17 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: 13,519,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 100 mg/kg
SEX/DURATION : female 6-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death
Reproductive - Specific Developmental Abnormalities - urogenital system
REFERENCE :
RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970-
Volume(issue)/page/year: 77,347,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 2520 mg/kg
SEX/DURATION : female 15-22 day(s) after conception
lactating female 20 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - weaning or lactation index (e.g., #
alive at weaning per # alive at day 4)
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: 14,43,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 280 mg/kg
SEX/DURATION : female 15-22 day(s) after conception
lactating female 20 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
Reproductive - Effects on Newborn - behavioral
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: 14,43,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 39 mg/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
14,461,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 70 mg/kg
SEX/DURATION : female 14-20 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
14,461,1990
*** END OF RECORD ***