*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : XJ9095080 CHEMICAL NAME : 6H-Thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine, 2-bromo-4-(2-chlorophenyl)-9-methyl- CAS REGISTRY NUMBER : 57801-81-7 BEILSTEIN REFERENCE NO. : 0839277 LAST UPDATED : 199612 DATA ITEMS CITED : 20 MOLECULAR FORMULA : C15-H10-Br-Cl-N4-S MOLECULAR WEIGHT : 393.71 COMPOUND DESCRIPTOR : Tumorigen Drug Reproductive Effector SYNONYMS/TRADE NAMES : * 2-Bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3- a)(1,4)diazepine * 8-Bromo-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo(3,4c)thieno(2,3e)-1,4- diazepine * Brotizolam * Lendorm * Lendormin * WE 941 * WE 941-BS *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3456 mg/kg TOXIC EFFECTS : Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,540,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >20 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: -,1028,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 920 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >20 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: -,1028,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - excitement Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : >2500 ug/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,540,1986 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - cat DOSE/DURATION : >100 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - food intake (animal) Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,540,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic) Behavioral - somnolence (general depressed activity) Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - pig DOSE/DURATION : >10 mg/kg TOXIC EFFECTS : Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic) Behavioral - somnolence (general depressed activity) Behavioral - ataxia REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,540,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 11200 mg/kg/4W-I TOXIC EFFECTS : Liver - changes in liver weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other oxidoreductases REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 40,239,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 35 gm/kg/35D-C TOXIC EFFECTS : Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Blood - changes in erythrocyte (RBC) count 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: 16,281,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 36400 mg/kg/13W-C TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 218 gm/kg/78W-C TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Related to Chronic Data - changes in testicular weight REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 146 gm/kg/2Y-C TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 675 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) 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: 16,818,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 2750 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) 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: 16,818,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 2750 mg/kg SEX/DURATION : multigenerations 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 - other measures of fertility 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: 16,818,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 280 mg/kg SEX/DURATION : female 16-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,592,1986 *** END OF RECORD ***