*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : TL6400000
CHEMICAL NAME : 2,6-Piperazinedione, 4,4'-propylenedi-, (+-)-
CAS REGISTRY NUMBER : 21416-87-5
BEILSTEIN REFERENCE NO. : 5759130
LAST UPDATED : 199612
DATA ITEMS CITED : 19
MOLECULAR FORMULA : C11-H16-N4-O4
MOLECULAR WEIGHT : 268.31
WISWESSER LINE NOTATION : T6VMV ENTJ E3- ET6VMV ENTJ
COMPOUND DESCRIPTOR : Tumorigen
Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* (+,-)-1,2-Bis(3,5-dioxopiperazine-1-yl)propane
* (+-)-1,2-Bis(3,5-dioxopiperazinyl)propane
* ICRF-159
* NCI-C01627
* NSC-129943
* 2,6-Piperazinedione, 4,4'-(1-methyl-1,2-ethanediyl)bis-, (+-)-
* 2,6-Piperazinedione-4,4'-propylene dioxopiperazine
* Propane, (+-)-1,2-bis(3,5-dioxopiperazin-1-yl)-
* Razoxane
* Tepirone
* (+-)-(3,5,3',5'-Tetraoxo)-1,2-dipiperazinopropane
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 81 mg/kg/3D-I
TOXIC EFFECTS :
Gastrointestinal - nausea or vomiting
Blood - leukopenia
Blood - thrombocytopenia
REFERENCE :
CCROBU Cancer Chemotherapy Reports, Part 1. (Washington, DC) V.52(6)-59,
1968-75. For publisher information, see CTRRDO. Volume(issue)/page/year:
57,185,1973
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 500 mg/kg
TOXIC EFFECTS :
Gastrointestinal - nausea or vomiting
Blood - leukopenia
Blood - thrombocytopenia
REFERENCE :
CTRRDO Cancer Treatment Reports. (Washington, DC) V.60-71, 1976-87. For
publisher information, see JNCIEQ. Volume(issue)/page/year: 62,465,1978
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 861 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NCISP* National Cancer Institute Screening Program Data Summary,
Developmental Therapeutics Program. (Bethesda, MD 20205)
Volume(issue)/page/year: JAN1986
** TUMORIGENIC DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 7488 mg/kg/52W-I
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Reproductive - Tumorigenic effects - uterine tumors
REFERENCE :
NCITR* National Cancer Institute Carcinogenesis Technical Report Series.
(Bethesda, MD) No.0-205. For publisher information, see NTPTR*.
Volume(issue)/page/year: NCI-TR-78,1978
TYPE OF TEST : TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 15 gm/kg/Y-I
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Reproductive - Tumorigenic effects - uterine tumors
REFERENCE :
NCITR* National Cancer Institute Carcinogenesis Technical Report Series.
(Bethesda, MD) No.0-205. For publisher information, see NTPTR*.
Volume(issue)/page/year: NCI-TR-78,1978
TYPE OF TEST : TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 12 gm/kg/Y-I
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Blood - lymphoma, including Hodgkin's disease
REFERENCE :
NCITR* National Cancer Institute Carcinogenesis Technical Report Series.
(Bethesda, MD) No.0-205. For publisher information, see NTPTR*.
Volume(issue)/page/year: NCI-TR-78,1978
TYPE OF TEST : TD - Toxic dose (other than lowest)
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1 gm/kg/8W-I
TOXIC EFFECTS :
Tumorigenic - equivocal tumorigenic agent by RTECS criteria
Lungs, Thorax, or Respiration - tumors
REFERENCE :
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year:
33,3069,1973
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 37500 ug/kg
SEX/DURATION : female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Specific Developmental Abnormalities - eye/ear
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 11,119,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 37500 ug/kg
SEX/DURATION : female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - body wall
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 11,119,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 30 mg/kg
SEX/DURATION : female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 11,119,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE : 37500 mg/kg
SEX/DURATION : female 6-8 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 - other developmental
abnormalities
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 11,119,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 10 mg/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 11,119,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 15 mg/kg
SEX/DURATION : female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 11,119,1975
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Unreported
SPECIES OBSERVED : Rodent - mouse
DOSE : 2520 mg/kg
SEX/DURATION : male 42 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - testes, epididymis, sperm duct
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823-
Volume(issue)/page/year: 1,840,1972
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 105 mg/kg
SEX/DURATION : female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 11,119,1975
** MUTATION DATA **
TYPE OF TEST : DNA inhibition
TEST SYSTEM : Rodent - mouse Embryo
DOSE/DURATION : 20 mg/L
REFERENCE :
IJCNAW International Journal of Cancer. (International Union Against
Cancer, 3 rue du Conseil- General, 1205 Geneva, Switzerland) V.1- 1966-
Volume(issue)/page/year: 5,47,1970
TYPE OF TEST : Mutation in mammalian somatic cells
TEST SYSTEM : Rodent - mouse Lung
DOSE/DURATION : 200 ug/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 157,199,1985
*** STATUS IN U.S. ***
EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat; V79 cell
culture-gene mutation
NCI Carcinogenesis Bioassay (ipr);clear evidence:mouse,rat
NCITR* National Cancer Institute Carcinogenesis Technical Report Series.
(Bethesda, MD) No.0-205. For publisher information, see NTPTR*.
Volume(issue)/page/year: NCI-TR-78,78
*** END OF RECORD ***