*** 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 ***