*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : XZ5472500 CHEMICAL NAME : 4H-s-Triazolo(4,3-a)(1,4)benzodiazepine, 8-chloro-6-(o-chlorophenyl)-1-methyl- CAS REGISTRY NUMBER : 28911-01-5 BEILSTEIN REFERENCE NO. : 1226643 LAST UPDATED : 199806 DATA ITEMS CITED : 26 MOLECULAR FORMULA : C17-H12-Cl2-N4 MOLECULAR WEIGHT : 343.23 WISWESSER LINE NOTATION : T B576 BN DNN HN GHJ C1 IR BG& LG COMPOUND DESCRIPTOR : Drug Reproductive Effector Human SYNONYMS/TRADE NAMES : * 8-Chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo(4,3-a)(1,4)benzodiaze pine * Halcion * Novidorm * Songar * Triazolam * 4H-(1,2,4)Triazolo(4,3-a)(1,4)benzodiazepine, 8-chloro-6-(2-chlorophenyl)-1-methyl- * U-33,030 *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 3289 ng/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - alteration of operant conditioning REFERENCE : CLPTAT Clinical Pharmacology and Therapeutics (St. Louis). (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1960- Volume(issue)/page/year: 49,581,1991 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 7 ug/kg TOXIC EFFECTS : Behavioral - coma Lungs, Thorax, or Respiration - acute pulmonary edema Lungs, Thorax, or Respiration - respiratory obstruction REFERENCE : JTCTDW Journal of Toxicology, Clinical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.19- 1982- Volume(issue)/page/year: 33,185,1995 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 100 ug/kg TOXIC EFFECTS : Behavioral - coma Lungs, Thorax, or Respiration - cyanosis Lungs, Thorax, or Respiration - other changes REFERENCE : AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 3,210,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 114 ug/kg/4D-I TOXIC EFFECTS : Behavioral - toxic psychosis REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 304,1178,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 357 ug/kg TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions Behavioral - coma Behavioral - irritability REFERENCE : HETOEA Human & Experimental Toxicology. (Macmillan Press Ltd., Brunel Road, Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990- Volume(issue)/page/year: 11,289,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 100 ug/kg TOXIC EFFECTS : Behavioral - sleep Behavioral - ataxia Cardiac - pulse rate REFERENCE : JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 47,50,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 7 ug/kg TOXIC EFFECTS : Brain and Coverings - changes in surface EEG Behavioral - sleep Behavioral - hallucinations, distorted perceptions REFERENCE : JCPCBR Journal of Clinical Pharmacology. (Hall Assoc., PO Box 482, Stamford, CT 06904) V.13- 1973- Volume(issue)/page/year: 14,102,1974 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 107 ug/kg TOXIC EFFECTS : Behavioral - coma REFERENCE : AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 145,663,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 1786 ng/kg TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions REFERENCE : SMJOAV Southern Medical Journal. (Southern Medical Assoc., POB 2446, Birmingham, AL 35205) V.1- 1908- Volume(issue)/page/year: 80,1425,1987 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >7500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 35,1074,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >3300 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: -,860,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959- Volume(issue)/page/year: 25,499,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1080 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic) REFERENCE : CKFRAY Ceskoslovenska Farmacie. (PNS-Ustredni Expedice a Dovoz Tisku, Kafkova 19, 160 00 Prague 6, Czechoslovakia) V.1- 1952- Volume(issue)/page/year: 37,443,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1625 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 14,484,1983 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 : YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959- Volume(issue)/page/year: 25,499,1983 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5600 mg/kg/35D-C TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) 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: 20,8557,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 1500 mg/kg/30D-C TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes in urine composition Endocrine - 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: 20,8597,1986 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE : 50 ug/kg SEX/DURATION : female 33 week(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Effects on Newborn - Apgar score (human only) Reproductive - Effects on Newborn - behavioral REFERENCE : EJPEDT European Journal of Pediatrics. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.121- 1975- Volume(issue)/page/year: 155,1065,1996 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 8100 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) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,52,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 810 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 : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,52,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 3300 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,52,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 4400 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,765,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 4400 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,765,1985 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 - 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 - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 10,52,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE : 91 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,819,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE : 195 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,819,1985 *** END OF RECORD ***