*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : NI2922190
CHEMICAL NAME : 4H-Imidazo(1,5-a)(1,4)benzodiazepine,
8-chloro-6-(2-fluorophenyl)-1-methyl-
CAS REGISTRY NUMBER : 59467-70-8
BEILSTEIN REFERENCE NO. : 0625572
LAST UPDATED : 199612
DATA ITEMS CITED : 21
MOLECULAR FORMULA : C18-H13-Cl-F-N3
MOLECULAR WEIGHT : 325.79
WISWESSER LINE NOTATION : T B576 BN DN HN GHJ C1 IR BF& LG
COMPOUND DESCRIPTOR : Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Midazolam
* Ro 21-3981
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 500 ug/kg
TOXIC EFFECTS :
Behavioral - excitement
REFERENCE :
AEMED3 Annals of Emergency Medicine. (American College of Emergency
Physicians, 1125 Executive Circle, Irving, TX 75038)
Volume(issue)/page/year: 24,1173,1994
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 74 ug/kg/1M-C
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
ANZJB8 Australian and New Zealand Journal of Medicine. (Modern Medicine of
Australia Pty., Ltd., 100 Pacific Highway, North Sydney, 2060, Australia)
V.1- 1971- Volume(issue)/page/year: 25,743,1995
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 215 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
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(Suppl 4),S871,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 75 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub.
Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year:
16,37S,1983
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >50 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - lacrimation
Behavioral - somnolence (general depressed activity)
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(Suppl 4),S871,1985
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 500 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - lacrimation
Behavioral - somnolence (general depressed activity)
Behavioral - ataxia
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(Suppl 4),S871,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 50 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub.
Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year:
16,37S,1983
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >50 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - lacrimation
Behavioral - somnolence (general depressed activity)
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(Suppl 4),S871,1985
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 18200 mg/kg/13W-I
TOXIC EFFECTS :
Liver - changes in liver weight
Biochemical - Metabolism (Intermediary) - other proteins
REFERENCE :
BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub.
Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year:
16,37S,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 560 mg/kg/4W-I
TOXIC EFFECTS :
Blood - normocytic anemia
Skin and Appendages - dermatitis, other (after systemic exposure)
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(Suppl 4),S955,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Multiple routes
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1820 mg/kg/13W-I
TOXIC EFFECTS :
Endocrine - changes in thymus weight
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Biochemical - Metabolism (Intermediary) - other proteins
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(Suppl 4),S879,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 4095 mg/kg/13W-I
TOXIC EFFECTS :
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - phosphatases
REFERENCE :
BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub.
Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year:
16,37S,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 910 mg/kg/13W-I
TOXIC EFFECTS :
Liver - changes in liver weight
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - phosphatases
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(Suppl 4),S917,1985
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 220 mg/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - other effects to embryo
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced 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(Suppl 4),S995,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 520 mg/kg
SEX/DURATION : female 17-21 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 - growth statistics (e.g.%, reduced 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(Suppl 4),S1021,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE : 55 mg/kg
SEX/DURATION : female 11-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
Reproductive - Effects on Newborn - behavioral
REFERENCE :
GEPHDP General Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview
Park, Elmsford, NY 10523) V.6- 1975- Volume(issue)/page/year: 22,33,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rabbit
DOSE : 32500 ug/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal 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(Suppl 4),S1011,1985
** MUTATION DATA **
TYPE OF TEST : Mutation test systems - not otherwise specified
TEST SYSTEM : Rodent - hamster Embryo
DOSE/DURATION : 5 mg/L
REFERENCE :
MUTAEX Mutagenesis. (Oxford Univ. Press, Pinkhill House, Southfield Road,
Eynsham, Oxford OX8 1JJ, UK) V.1- 1986- Volume(issue)/page/year: 3,23,1988
TYPE OF TEST : Cytogenetic analysis
TEST SYSTEM : Rodent - hamster Fibroblast
DOSE/DURATION : 7500 ug/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 189,319,1987
TYPE OF TEST : Cytogenetic analysis
TEST SYSTEM : Rodent - hamster Embryo
DOSE/DURATION : 5 mg/L
REFERENCE :
MUTAEX Mutagenesis. (Oxford Univ. Press, Pinkhill House, Southfield Road,
Eynsham, Oxford OX8 1JJ, UK) V.1- 1986- Volume(issue)/page/year: 3,23,1988
TYPE OF TEST : Sex chromosome loss and nondisjunction
TEST SYSTEM : Rodent - hamster Embryo
DOSE/DURATION : 5 mg/L
REFERENCE :
MUTAEX Mutagenesis. (Oxford Univ. Press, Pinkhill House, Southfield Road,
Eynsham, Oxford OX8 1JJ, UK) V.1- 1986- Volume(issue)/page/year: 3,23,1988
*** END OF RECORD ***