*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : DF2368000
CHEMICAL NAME : 2H-1,4-Benzodiazepin-2-one,
1,3-dihydro-7-chloro-1-(cyclopropylmethyl)-5-phenyl-
CAS REGISTRY NUMBER : 2955-38-6
BEILSTEIN REFERENCE NO. : 0895797
REFERENCE : 5-24-04-00304 (Beilstein Handbook Reference)
LAST UPDATED : 199703
DATA ITEMS CITED : 28
MOLECULAR FORMULA : C19-H17-Cl-N2-O
MOLECULAR WEIGHT : 324.83
WISWESSER LINE NOTATION : T67 GNV JN IHJ CG KR& G1- AL3TJ
COMPOUND DESCRIPTOR : Tumorigen
Drug
Reproductive Effector
SYNONYMS/TRADE NAMES :
* 7-Chloro-1-(cyclopropylmethyl)-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin
-2-one
* 7-Chloro-1-cyclopropylmethyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one
* Demetrin
* K-373
* Lysanxia
* Prazepam
* Verstran
* W 4020
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >4 gm/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - lacrimation
Behavioral - ataxia
Nutritional and Gross Metabolic - body temperature decrease
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,241,1978
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >2 gm/kg
TOXIC EFFECTS :
Behavioral - ataxia
Lungs, Thorax, or Respiration - dyspnea
Nutritional and Gross Metabolic - body temperature decrease
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,241,1978
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >2 gm/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,241,1978
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 2300 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JKXXAF Japanese Kokai Tokyo Koho Patents. (U.S. Patent and Trademark
Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year:
#79-92631
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1020 mg/kg
TOXIC EFFECTS :
Behavioral - ataxia
Lungs, Thorax, or Respiration - dyspnea
Nutritional and Gross Metabolic - body temperature decrease
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,241,1978
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >2 gm/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,241,1978
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : >4 gm/kg
TOXIC EFFECTS :
Behavioral - food intake (animal)
Behavioral - ataxia
Nutritional and Gross Metabolic - body temperature decrease
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,759,1978
** OTHER MULTIPLE DOSE TOXICITY DATA **
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 - other changes
Kidney, Ureter, Bladder - other changes
Related to Chronic Data - changes in testicular weight
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,247,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 930 mg/kg/31W-I
TOXIC EFFECTS :
Liver - changes in liver weight
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - phosphatases
Related to Chronic Data - changes in prostate weight
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,777,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 40500 mg/kg/27W-I
TOXIC EFFECTS :
Liver - changes in liver weight
Kidney, Ureter, Bladder - changes in bladder weight
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,269,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Mammal - dog
DOSE/DURATION : 1200 mg/kg/30D-C
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - phosphatases
Related to Chronic Data - changes in prostate weight
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,759,1978
** TUMORIGENIC DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 5284 mg/kg/2Y-C
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria
Endocrine - tumors
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
57,39,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 14 gm/kg/80W-C
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria
Blood - lymphoma, including Hodgkin's disease
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
57,39,1981
TYPE OF TEST : TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 55 gm/kg/2Y-C
TOXIC EFFECTS :
Tumorigenic - active as anti-cancer agent
Skin and Appendages - tumors
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year:
57,39,1981
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 21 gm/kg
SEX/DURATION : female 14 day(s) pre-mating
female 1-7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - female fertility index (e.g. # females pregnant
per # sperm positive females; # females pregnant per # females mated)
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,813,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 250 mg/kg
SEX/DURATION : female 8-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight
gain)
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,797,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 2500 mg/kg
SEX/DURATION : female 8-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
number of implants per female; total number of implants per corpora lutea)
Reproductive - Effects on Newborn - stillbirth
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,797,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 10 gm/kg
SEX/DURATION : female 8-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Specific Developmental Abnormalities - homeostasis
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 15,797,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 135 mg/kg
SEX/DURATION : female 17-22 day(s) after conception
lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - behavioral
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 17,833,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 624 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 : 1656 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 : 800 mg/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
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 504 mg/kg
SEX/DURATION : female 1-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - behavioral
REFERENCE :
PLRCAT Pharmacological Research Communications. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1969- Volume(issue)/page/year:
9,325,1977
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 650 mg/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 17,673,1979
*** REVIEWS ***
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: 66,143,1996
IARC Cancer Review:Animal 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: 66,143,1996
IARC Cancer Review:Group 3
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: 66,143,1996
*** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA ***
NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
NOES - National Occupational Exposure Survey (1983)
NOES Hazard Code - X5481
No. of Facilities: 16 (estimated)
No. of Industries: 1
No. of Occupations: 1
No. of Employees: 94 (estimated)
No. of Female Employees: 62 (estimated)
*** END OF RECORD ***