*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : DF1400000
CHEMICAL NAME : 2H-1,4-Benzodiazepin-2-one,
7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-
CAS REGISTRY NUMBER : 604-75-1
OTHER CAS REGISTRY NOS. : 61036-43-9
LAST UPDATED : 199712
DATA ITEMS CITED : 35
MOLECULAR FORMULA : C15-H11-Cl-N2-O2
MOLECULAR WEIGHT : 286.73
WISWESSER LINE NOTATION : T67 GMV JN IHJ CG IQ KR
COMPOUND DESCRIPTOR : Tumorigen
Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Abboxapam
* Adumbran
* Ansioxacepam
* Anxiolit
* Aplakil
* Astress
* Azutranquil
* Bonare
* 7-Chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one
* N-Desmethyltemazepam
* 1,3-Dihydro-7-chloro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one
* Durazepam
* Enidrel
* Hi-Long
* Isodin
* Limbial
* Nesontil
* Noctazepam
* Nortemazepam
* Oxazepam
* Pacienx
* Praxiten
* Propax
* Ro 5-6789
* Rondar
* Serax
* Serenid
* Serenid-D
* Serepax
* Seresta
* Sigacalm
* Sobril
* Tazepam
* Tranquo-buscopan-wirkstoff
* Uskan
* Vaben
* WY-3498
* Zaxopam
* Z10-TR
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - child
DOSE/DURATION : 8 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Behavioral - changes in REM sleep (human)
Behavioral - ataxia
REFERENCE :
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N.
Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year:
196,662,1966
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >8 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
CTCEA9 Current Therapeutic Research, Clinical & Experimental. (Therapeutic
Research Press, Inc., POB 514, Tenafly, NJ 07670) V.1- 1959-
Volume(issue)/page/year: 7,590,1965
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1535 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 : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 3700 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
USXXAM United States Patent Document. (U.S. Patent Office, Box 9,
Washington, DC 20231) Volume(issue)/page/year: #4045569
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 767 mg/kg
TOXIC EFFECTS :
Behavioral - anticonvulsant
REFERENCE :
JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc.,
Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC
20037) V.6- 1963- Volume(issue)/page/year: 11,777,1968
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >400 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
CTCEA9 Current Therapeutic Research, Clinical & Experimental. (Therapeutic
Research Press, Inc., POB 514, Tenafly, NJ 07670) V.1- 1959-
Volume(issue)/page/year: 7,590,1965
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : >2 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
CTCEA9 Current Therapeutic Research, Clinical & Experimental. (Therapeutic
Research Press, Inc., POB 514, Tenafly, NJ 07670) V.1- 1959-
Volume(issue)/page/year: 7,590,1965
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 5250 mg/kg/6W-C
TOXIC EFFECTS :
Liver - changes in liver weight
Kidney, Ureter, Bladder - changes in bladder weight
Endocrine - changes in adrenal weight
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
16,556,1970
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 28224 mg/kg/56W-C
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in bladder weight
Related to Chronic Data - changes in prostate weight
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
16,556,1970
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 9411 mg/kg/30D-I
TOXIC EFFECTS :
Blood - changes in erythrocyte (RBC) count
Blood - changes in leukocyte (WBC) count
REFERENCE :
AGSOA6 Agressologie. Revue Internationale de Physio-Biologie et de
Pharmacologie Appliquees aux Effets de l'Agression. (SPPIF, B.P.22, F-41353
Vineuil, France) V.1- 1960- Volume(issue)/page/year: 22,209,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 7350 mg/kg/14W-C
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Liver - other changes
Liver - changes in liver weight
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
23,280,1994
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 10920 mg/kg/52W-C
TOXIC EFFECTS :
Endocrine - changes in spleen weight
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
16,556,1970
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 26880 mg/kg/4W-C
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Gastrointestinal - changes in pancreatic weight
Liver - changes in liver weight
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
16,556,1970
** TUMORIGENIC DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 219 gm/kg/2Y-C
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Liver - tumors
Endocrine - thyroid tumors
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
23,280,1994
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 219 gm/kg/2Y-C
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Liver - tumors
REFERENCE :
NTPTR* National Toxicology Program Technical Report Series. (Research
Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-443,1993
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 120 gm/kg/57W-C
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria
Liver - tumors
REFERENCE :
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway,
Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 13,373,1993
TYPE OF TEST : TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 65 gm/kg/52-C
TOXIC EFFECTS :
Tumorigenic - neoplastic by RTECS criteria
Liver - tumors
REFERENCE :
RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970-
Volume(issue)/page/year: 8,481,1974
TYPE OF TEST : TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 239 gm/kg/57W-C
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Liver - tumors
REFERENCE :
RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970-
Volume(issue)/page/year: 8,481,1974
TYPE OF TEST : TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 219 gm/kg/2Y-C
TOXIC EFFECTS :
Tumorigenic - neoplastic by RTECS criteria
Endocrine - thyroid tumors
REFERENCE :
RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970-
Volume(issue)/page/year: 8,481,1974
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 150 mg/kg
SEX/DURATION : female 12-16 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - behavioral
REFERENCE :
NETEEC Neurotoxicology and Teratology. (Pergamon Press Inc., Maxwell House,
Fairview Park, Elmsford, NY 10523) V.9- 1987- Volume(issue)/page/year:
13,75,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 400 mg/kg
SEX/DURATION : female 14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
25,453,1973
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 1560 mg/kg
SEX/DURATION : female 26 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
REFERENCE :
RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970-
Volume(issue)/page/year: 11,155,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 4140 mg/kg
SEX/DURATION : male 5 day(s) pre-mating
female 3 week(s) pre-mating - 3 week(s) post-birth
TOXIC EFFECTS :
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 :
PLRCAT Pharmacological Research Communications. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1969- Volume(issue)/page/year:
9,187,1977
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 2 gm/kg
SEX/DURATION : male 5 day(s) pre-mating
female 15 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - mating performance (e.g. # sperm positive females
per # females mated; # copulations per # estrus cycles)
REFERENCE :
RCOCB8 Research Communications in Chemical Pathology and Pharmacology. (PJD
Pub. Ltd., P.O. Box 966, Westbury, NY 11590) V.1- 1970-
Volume(issue)/page/year: 13,601,1976
** MUTATION DATA **
TYPE OF TEST : Mutation in microorganisms
TEST SYSTEM : Bacteria - Salmonella typhimurium
DOSE/DURATION : 5200 pmol/plate
REFERENCE :
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year:
38,4478,1978
*** REVIEWS ***
IARC Cancer Review:Animal Limited Evidence
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 13,57,1977
IARC Cancer Review:Animal Sufficient Evidence
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 66,115,1996
IARC Cancer Review:Human No Adequate Data
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 13,57,1977
IARC Cancer Review:Human Inadequate Evidence
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 66,115,1996
IARC Cancer Review:Group 3
IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49
Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year:
7,56,1987
IARC Cancer Review:Group 2B
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 66,115,1996
TOXICOLOGY REVIEW
INTEAG Internist. (Springer-Verlag New York, Inc., Service Center, 44 Hartz
Way, Secaucus, NJ 07094) V.1- 1960- Volume(issue)/page/year: 15,7,1974
*** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA ***
NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
NOES - National Occupational Exposure Survey (1983)
NOES Hazard Code - X3707
No. of Facilities: 37 (estimated)
No. of Industries: 2
No. of Occupations: 3
No. of Employees: 2657 (estimated)
No. of Female Employees: 1586 (estimated)
*** STATUS IN U.S. ***
NTP Carcinogenesis studies (feed);clear evidence:mouse,rat
NTPTR* National Toxicology Program Technical Report Series. (Research
Triangle Park, NC 27709) No.206- Volume(issue)/page/year: NTP-TR-443,93
NTP Carcinogenesis studies; test completed (post peer review), October 1997
*** END OF RECORD ***