*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : DF0350000
CHEMICAL NAME : 2H,1,4-Benzodiazepin-2-one,
7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-
CAS REGISTRY NUMBER : 846-49-1
BEILSTEIN REFERENCE NO. : 0759084
REFERENCE : 5-25-02-00248 (Beilstein Handbook Reference)
LAST UPDATED : 199801
DATA ITEMS CITED : 31
MOLECULAR FORMULA : C15-H10-Cl2-N2-O2
MOLECULAR WEIGHT : 321.17
WISWESSER LINE NOTATION : T67 GMV JN IHJ CG IQ KR BG
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Almazine
* Ativan
* 7-Chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2
-one
* 7-Chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2
-one
* 7-Chloro-5-(2-chlorophenyl)-3-hydroxy-1H-1,4-benzodiazepin-2(3H)-one
* o-Chlorooxazepam
* o-Chloroxazepam
* Delormetazepam
* Demethyllormetazepam
* Emotival
* Lorax
* Lorazepam
* Norlormetazepam
* Tavor
* Temesta
* WY 4036
* Wypax
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 28 ug/kg
TOXIC EFFECTS :
Behavioral - changes in psychophysiological tests
REFERENCE :
JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press,
Inc., POB 240008, Memphis, TN 38124) V.39- 1978-
Volume(issue)/page/year: 46,137,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 1208 ug/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Vascular - BP lowering not characterized in autonomic section
Lungs, Thorax, or Respiration - pleural thickening
REFERENCE :
PECAE5 Pediatric Emergency Care. (Williams & Wilkins, 428 E. Preston St.,
Baltimore, MD 21202) V.1- 1985- Volume(issue)/page/year: 11,32,1995
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 71 ug/kg
TOXIC EFFECTS :
Behavioral - general anesthetic
Behavioral - hallucinations, distorted perceptions
Behavioral - ataxia
REFERENCE :
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 2,109,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 380 ug/kg/19D-I
TOXIC EFFECTS :
Blood - aplastic anemia
Blood - changes in bone marrow (not otherwise specified)
REFERENCE :
BMJOAE British Medical Journal. (British Medical Assoc., BMA House,
Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year:
296,1332,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 21 ug/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - alteration of classical 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: 39,526,1986
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 4500 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: 8,680,1977
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 870 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
PHMGBN Pharmacology: International Journal of Experimental and Clinical
Pharmacology. (S. Karger AG, Postfach CH-4009 Basel, Switzerland) V.1-
1968- Volume(issue)/page/year: 10,345,1973
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >10 gm/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: 28,1475,1977
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 59 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 21,1065,1971
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1850 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: 8,680,1977
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1810 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
1,5,1974
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >10 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
1(1),5,1974
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 70 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 21,1065,1971
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 - ataxia
Gastrointestinal - nausea or vomiting
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 21,1065,1971
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : >25 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - ataxia
Gastrointestinal - nausea or vomiting
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 21,1065,1971
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 2800 mg/kg/4W-I
TOXIC EFFECTS :
Liver - changes in liver weight
Kidney, Ureter, Bladder - urine volume increased
Endocrine - changes in adrenal weight
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
1,5,1974
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 18720 mg/kg/13W-C
TOXIC EFFECTS :
Liver - other changes
Kidney, Ureter, Bladder - changes in bladder weight
Related to Chronic Data - changes in prostate 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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 43680 mg/kg/26W-C
TOXIC EFFECTS :
Liver - changes in liver weight
Kidney, Ureter, Bladder - changes in bladder 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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 161 gm/kg/80W-C
TOXIC EFFECTS :
Endocrine - changes in adrenal weight
Endocrine - changes in thyroid weight
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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 370 mg/kg/37D-I
TOXIC EFFECTS :
Liver - changes in liver weight
Kidney, Ureter, Bladder - changes in bladder weight
Endocrine - changes in adrenal 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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 2100 mg/kg/6W-I
TOXIC EFFECTS :
Liver - changes in liver 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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 16800 mg/kg/12W-I
TOXIC EFFECTS :
Liver - changes in liver 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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 87360 mg/kg/26W-I
TOXIC EFFECTS :
Endocrine - changes in spleen 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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 43800 mg/kg/1Y-I
TOXIC EFFECTS :
Endocrine - changes in spleen weight
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: 21,1065,1971
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 340 mg/kg/34D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in bladder weight
Endocrine - changes in spleen weight
Skin and Appendages - dermatitis, other (after systemic exposure)
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 21,1065,1971
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 2420 ug/kg
SEX/DURATION : female 36-39 week(s) after conception
lactating female 2 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - other neonatal measures or effects
REFERENCE :
BMJOAE British Medical Journal. (British Medical Assoc., BMA House,
Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year:
282,1106,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 2800 ug/kg
SEX/DURATION : female 9-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
1,25,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE : 32 mg/kg
SEX/DURATION : female 14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
Reproductive - Specific Developmental Abnormalities - skin and skin
appendages
REFERENCE :
PHTOEH Pharmacology and Toxicology (Copenhagen). (Munksgaard International
Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.60- 1987-
Volume(issue)/page/year: 74,228,1994
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE : 16 mg/kg
SEX/DURATION : female 13-20 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - biochemical and metabolic
Reproductive - Effects on Newborn - behavioral
REFERENCE :
NEPHBW Neuropharmacology. (Pergamon Press Ltd., Headington Hill Hall,
Oxford OX3 OBW, UK) V.9- 1970- Volume(issue)/page/year: 30,53,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE : 14 mg/kg
SEX/DURATION : female 14-20 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - biochemical and metabolic
Reproductive - Effects on Newborn - behavioral
REFERENCE :
PBBHAU Pharmacology, Biochemistry and Behavior. (ANKHO International Inc.,
P.O. Box 426, Fayetteville, NY 13066) V.1- 1973-
Volume(issue)/page/year: 51,721,1995
*** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA ***
NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
NOES - National Occupational Exposure Survey (1983)
NOES Hazard Code - X6070
No. of Facilities: 34 (estimated)
No. of Industries: 1
No. of Occupations: 3
No. of Employees: 1530 (estimated)
No. of Female Employees: 1062 (estimated)
*** END OF RECORD ***