The Registry of Toxic Effects of Chemical Substances

2H,1,4 - Benzodiazepin - 2 - one, 7 - chloro - 5 - (o - chlorophenyl) - 1,3 - dihydro - 3 - hydroxy -

RTECS #: DF0350000

CAS #: 846-49-1

UPDATE: November 2007 MW: 321.17 MF: C15H10Cl2N2O2


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. REPRODUCTIVE EFFECTS DATA:
  3. ACUTE TOXICITY DATA:
  4. OTHER MULTIPLE DOSE DATA:
  5. REVIEWS:
  6. NIOSH DOCUMENTATION AND SURVEILLANCE:
  7. REFERENCES:

SYNONYMS:

  1. 7 - Chloro - 5 - (o - chlorophenyl) - 1,3 - dihydro - 3 - hydroxy - 2H - 1,4 - benzodiazepin - 2 - one
  2. 7 - Chloro - 5 - (2 - chlorophenyl) - 1,3 - dihydro - 3 - hydroxy - 2H - 1,4 - benzodiazepin - 2 - one
  3. 7 - Chloro - 5 - (2 - chlorophenyl) - 3 - hydroxy - 1H - 1,4 - benzodiazepin - 2 (3H) - one
  4. Almazine
  5. Ativan
  6. Delormetazepam
  7. Demethyllormetazepam
  8. Emotival
  9. Lorax
  1. Lorazepam
  2. Norlormetazepam
  3. Tavor
  4. Temesta
  5. WY 4036
  6. Wypax
  7. o - Chlorooxazepam
  8. o - Chloroxazepam


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
N/R N/R N/R N/R


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lowest published toxic dose: 32 mg/kg (14 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Skin and skin appendages 		PHTOEH 74,228,1994
oral
rat 		lowest published toxic dose: 2,800 µg/kg (9-15 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system JZKEDZ 1,25,1975
oral
woman 		lowest published toxic dose: 2,420 µg/kg (36-39 week pregnant/2 day after birth) Reproductive: Effects on newborn: Other neonatal measures or effects BMJOAE 282,1106,1981
subcutaneous
mouse 		lowest published toxic dose: 16 mg/kg (13-20 day pregnant) Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Behavioral 		NEPHBW 30,53,1991
subcutaneous
mouse 		lowest published toxic dose: 14 mg/kg (14-20 day pregnant) Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Behavioral 		PBBHAU 51,721,1995


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intramuscular
dog 		lethal dose (50 percent kill): >25 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Ataxia

Gastrointestinal: Nausea or vomiting 		ARZNAD 21,1065,1971
intramuscular
human 		lowest published toxic dose: 14.3 µg/kg Behavioral: Antipsychotic NEROEW 26,494,2002
intramuscular
mouse 		lethal dose (50 percent kill): 70 mg/kg Behavioral: Somnolence (general depressed activity) ARZNAD 21,1065,1971
intramuscular
rat 		lethal dose (50 percent kill): 59 mg/kg Behavioral: Somnolence (general depressed activity) ARZNAD 21,1065,1971
intraperitoneal
mouse 		lethal dose (50 percent kill): 1,810 mg/kg N/R JZKEDZ 1,5,1974
intraperitoneal
mouse 		lowest published toxic dose: 1 mg/kg Behavioral: Antianxiety

Behavioral: Change in psychophysiological tests 		JPETAB 298,753,2001
intraperitoneal
mouse 		lowest published toxic dose: 1 mg/kg Ear: Changes in vestibular functions JPETAB 298,753,2001
intraperitoneal
mouse 		lowest published toxic dose: 0.6 mg/kg Behavioral: Muscle weakness JPETAB 298,753,2001
intraperitoneal
mouse 		lowest published toxic dose: 1 mg/kg Behavioral: Anticonvulsant EJPHAZ 519,31,2005
intraperitoneal
mouse 		lowest published toxic dose: 0.52 mg/kg Brain and Coverings: Other degenerative changes JPETAB 316,1378,2006
intraperitoneal
mouse 		lowest published toxic dose: 4.2 mg/kg Behavioral: Convulsions or effect on seizure threshold JPETAB 316,1378,2006
intraperitoneal
rat 		lethal dose (50 percent kill): 870 mg/kg N/R PHMGBN 10,345,1973
intraperitoneal
rat 		lowest published toxic dose: 0.1 mg/kg Brain and Coverings: Changes in surface EEG

Behavioral: Antianxiety

Behavioral: Change in psychophysiological tests 		JPETAB 298,753,2001
intraperitoneal
rat 		lowest published toxic dose: 0.3 mg/kg Ear: Changes in vestibular functions

Behavioral: Muscle weakness 		JPETAB 298,753,2001
intraperitoneal
rat 		lowest published toxic dose: 0.3 mg/kg Behavioral: Alteration of operant conditioning JOPSEQ 17,293,2003
intraperitoneal
rat 		lowest published toxic dose: 0.6 mg/kg Behavioral: Change in motor activity (specific assay)

Behavioral: Alteration of operant conditioning 		JOPSEQ 17,293,2003
intraperitoneal
rat 		lowest published toxic dose: 0.75 mg/kg Brain and Coverings: Other degenerative changes JPETAB 305,541,2003
intraperitoneal
rat 		lowest published toxic dose: 0.3 mg/kg Behavioral: Change in psychophysiological tests JPETAB 316,1291,2006
intravenous
human 		lowest published toxic dose: 28.6 µg/kg Behavioral: Change in psychophysiological tests JCPCBR 37,858,1997
intravenous
man 		lowest published toxic dose: 0.14 mg/kg Brain and Coverings: Recordings from specific areas of CNS

Behavioral: Change in psychophysiological tests 		PNASA6 99,455,2002
oral
child 		lowest published toxic dose: 1,208 µg/kg Behavioral: Somnolence (general depressed activity)

Vascular: BP lowering not characterized in autonomic section

Lung, Thorax, or Respiration: Pleural thickening 		PECAE5 11,32,1995
oral
child 		lowest published toxic dose: 71 µg/kg Behavioral: General anesthetic

Behavioral: Hallucinations, distorted perceptions

Behavioral: Ataxia 		TOLED5 2,109,1978
oral
dog 		lethal dose (50 percent kill): >2 gm/kg Behavioral: Ataxia

Gastrointestinal: Nausea or vomiting 		ARZNAD 21,1065,1971
oral
human 		lowest published toxic dose: 28 µg/kg Behavioral: Change in psychophysiological tests JCLPDE 46,137,1985
oral
human 		lowest published toxic dose: 21 µg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Alteration of classical conditioning 		CLPTAT 39,526,1986
oral
human 		lowest published toxic dose: 1 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Change in psychophysiological tests 		PSCHDL 165,419,2003
oral
human 		lowest published toxic dose: 0.38 mg/kg Eye: Other eye effects

Behavioral: Somnolence (general depressed activity)

Behavioral: Change in psychophysiological tests 		NEROEW 29,1386,2004
oral
human 		lowest published toxic dose: 0.18 mg/kg Brain and Coverings: Recordings from specific areas of CNS NEROEW 29,1723,2004
oral
human 		lowest published toxic dose: 0.3 mg/kg Eye: Other eye effects

Behavioral: Alteration of operant conditioning

Behavioral: Change in psychophysiological tests 		PSCHDL 170,242,2003
oral
human 		lowest published toxic dose: 0.3 mg/kg Cardiac: Change in rate PSCHDL 170,242,2003
oral
human 		lowest published toxic dose: 0.38 mg/kg Behavioral: Alteration of operant conditioning PSCHDL 172,309,2004
oral
human 		lowest published toxic dose: 0.21 mg/kg Behavioral: Antianxiety

Behavioral: Change in psychophysiological tests 		JOPSEQ 20,506,2006
oral
man 		lowest published toxic dose: 28.6 µg/kg Behavioral: Antianxiety

Behavioral: Change in psychophysiological tests 		JOPSEQ 19,249,2005
oral
man 		lowest published toxic dose: 0.27 mg/kg Behavioral: Change in psychophysiological tests JOPSEQ 19,614,2005
oral
monkey 		lowest published toxic dose: 0.6 mg/kg Behavioral: Antianxiety JPETAB 303,777,2002
oral
mouse 		lethal dose (50 percent kill): 1,850 mg/kg N/R IYKEDH 8,680,1977
oral
mouse 		lowest published toxic dose: 0.14 mg/kg Behavioral: Anticonvulsant JPETAB 303,777,2002
oral
mouse 		lowest published toxic dose: 10 mg/kg Behavioral: Anticonvulsant

Behavioral: Ataxia 		JPETAB 303,777,2002
oral
mouse 		lowest published toxic dose: 0.3 mg/kg Behavioral: Ataxia JOPSEQ 19,221,2005
oral
rat 		lethal dose (50 percent kill): 4,500 mg/kg N/R IYKEDH 8,680,1977
oral
rat 		lowest published toxic dose: 1 mg/kg Behavioral: Antianxiety

Behavioral: Change in psychophysiological tests 		JPETAB 298,753,2001
oral
rat 		lowest published toxic dose: 0.4 mg/kg Behavioral: Change in motor activity (specific assay) JPETAB 303,777,2002
oral
rat 		lowest published toxic dose: 0.6 mg/kg Behavioral: Change in motor activity (specific assay)

Behavioral: Antianxiety 		JPETAB 303,777,2002
oral
woman 		lowest published toxic dose: 380 µg/kg/19 day- intermittent Blood: Aplastic anemia

Blood: Changes in bone marrow not included in above 		BMJOAE 296,1332,1988
oral
woman 		lowest published toxic dose: 0.5 mg/kg Behavioral: Antianxiety

Behavioral: Change in psychophysiological tests 		PSCHDL 164,262,2002
oral
woman 		lowest published toxic dose: 0.31 mg/kg Behavioral: Change in psychophysiological tests JOPSEQ 19,614,2005
subcutaneous
mouse 		lethal dose (50 percent kill): >10 gm/kg N/R JZKEDZ 1(1),5,1974
subcutaneous
rat 		lethal dose (50 percent kill): >10 gm/kg N/R YKYUA6 28,1475,1977
unreported route
human 		lowest published toxic dose: 0.29 mg/kg Behavioral: Antianxiety

Cardiac: Change in rate

Behavioral: Somnolence (general depressed activity) 		JOPSEQ 21,42,2007


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intramuscular
dog 		lowest published toxic dose: 340 mg/kg/34 day- intermittent Kidney, Ureter, and Bladder: Changes in bladder weight

Endocrine: Changes in spleen weight

Skin: After systemic exposure: Dermatitis, other 		ARZNAD 21,1065,1971
intramuscular
rat 		lowest published toxic dose: 370 mg/kg/37 day- intermittent Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight

Endocrine: Changes in adrenal weight 		ARZNAD 21,1065,1971
intraperitoneal
mouse 		lowest published toxic dose: 63 mg/kg/21 day- intermittent Brain and Coverings: Other degenerative changes

Behavioral: Anticonvulsant 		EJPHAZ 519,31,2005
multiple
rat 		lowest published toxic dose: 420 mg/kg/12 day- intermittent Behavioral: Tolerance

Behavioral: Withdrawal 		PBBHAU 66,361,2000
oral
dog 		lowest published toxic dose: 2,100 mg/kg/6 week- intermittent Liver: Changes in liver weight ARZNAD 21,1065,1971
oral
dog 		lowest published toxic dose: 16,800 mg/kg/12 week- intermittent Liver: Changes in liver weight ARZNAD 21,1065,1971
oral
dog 		lowest published toxic dose: 87,360 mg/kg/26 week- intermittent Endocrine: Changes in spleen weight ARZNAD 21,1065,1971
oral
dog 		lowest published toxic dose: 43,800 mg/kg/1 year- intermittent Endocrine: Changes in spleen weight

Related to Chronic Data: Changes in testicular weight 		ARZNAD 21,1065,1971
oral
rat 		lowest published toxic dose: 2,800 mg/kg/4 week- intermittent Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Urine volume increased

Endocrine: Changes in adrenal weight 		JZKEDZ 1,5,1974
oral
rat 		lowest published toxic dose: 18,720 mg/kg/13 week- continuous Liver: Other changes

Kidney, Ureter, and Bladder: Changes in bladder weight

Related to Chronic Data: Changes in prostate weight 		ARZNAD 21,1065,1971
oral
rat 		lowest published toxic dose: 43,680 mg/kg/26 week- continuous Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight 		ARZNAD 21,1065,1971
oral
rat 		lowest published toxic dose: 161 gm/kg/80 week- continuous Endocrine: Changes in adrenal weight

Endocrine: Changes in thyroid weight

Related to Chronic Data: Changes in testicular weight 		ARZNAD 21,1065,1971


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
TOXICOLOGY REVIEW
MUREAV 488,151,2001
TOXICOLOGY REVIEW
TPHSDY 24,542,2003
TOXICOLOGY REVIEW
AINCM* 7,63,2006


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
N/R N/R N/R


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X6070;
Number of Industries 1;
Total Number of Facilities 34;
Number of Occupations 3;
Total Number of Employees Exposed 1,530;
Total Number of Female Employees Exposed 1,062


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
N/R


REFERENCES:

CODEN
REFERENCE
AINCM* Anaesthesia and Intensive Care Medicine (Abingdon: Medicine Pub. Co.) V.1- 2000-
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857-
CLPTAT Clinical Pharmacology and Therapeutics. (American Society for Clinical Pharmacology and Therapeutics, St. Louis Mo Mosby-Year Book) V.1- 1960-
EJPHAZ European Journal of Pharmacology. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1967-
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978-
JCPCBR Journal of Clinical Pharmacology. (Hall Assoc., PO Box 482, Stamford, CT 06904) V.13- 1973-
JOPSEQ Journal of Psychopharmacology (Oxford). (Oxford University Press, Great Clarendon St., Oxford OX2 6DP, UK) V.1- 1987-
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
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-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NEPHBW Neuropharmacology. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.9- 1970-
NEROEW Neuropsychopharmacology. (Elsevier Science, 655 Avenue of the Americas, New York, NY 10010) V.1- 1987-
PBBHAU Pharmacology, Biochemistry and Behavior. (ANKHO International Inc., P.O. Box 426, Fayetteville, NY 13066) V.1- 1973-
PECAE5 Pediatric Emergency Care. (Williams & Wilkins, 428 E. Preston St., Baltimore, MD 21202) V.1- 1985-
PHMGBN Pharmacology: International Journal of Experimental and Clinical Pharmacology. (S. Karger AG, Postfach CH-4009 Basel, Switzerland) V.1- 1968-
PHTOEH Pharmacology and Toxicology (Copenhagen). (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.60- 1987-
PNASA6 Proceedings of the National Academy of Sciences of the United States of America. (National Academy of Sciences, Printing & Pub. Office, 2101 Constitution Ave., Washington, DC 20418) V.1- 1915-
PSCHDL Psychopharmacology (Berlin). (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.47- 1976-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TPHSDY Trends in Pharmacological Sciences. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1979-
YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950-

Used as an anticonvulsant and tranquilizer

FDA-proprietary drug

RTECS Compound Description:
   Drug
   Reproductive Effector
   Human Data

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