*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : TP2300000
CHEMICAL NAME           : Platinum,
                          diammine(1,1-cyclobutanedicarboxylato(2-)-O,O')-,
                          (SP-4-2)-
CAS REGISTRY NUMBER     : 41575-94-4
OTHER CAS REGISTRY NOS. : 70903-55-8
LAST UPDATED            : 199803
DATA ITEMS CITED        : 33
MOLECULAR FORMULA       : C6-H12-N2-O4-Pt
MOLECULAR WEIGHT        : 371.29
WISWESSER LINE NOTATION : L4TJ AVQ AVQ &Z-PT-Z
COMPOUND DESCRIPTOR     : Drug
                          Mutagen
                          Reproductive Effector
SYNONYMS/TRADE NAMES :
   * Carboplatin
   * Cbdca
   * 1,1-Cyclobutanedicarboxylate diammine platinum(II)
   * cis-(1,1-Cyclobutanedicarboxylato)diammineplatinum(II)
   * Diammine(1,1-cyclobutanedicarboxylato)platinum (II)
   * cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
   * JM 8
   * NSC-241240
   * Paraplatin
   * Platinum (II), (1,1-cyclobutanedicarboxylato)diammine-, cis-
 
                       *** 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           : 343 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,288,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 72 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,288,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 60900 ug/kg
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - effect, not otherwise specified
   Gastrointestinal - hypermotility, diarrhea
   Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
   NTIS** National Technical Information Service.  (Springfield, VA 22161)
   Formerly U.S. Clearinghouse for Scientific & Technical Information.
   Volume(issue)/page/year: PB288-374
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 118 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   EJMCA5 European Journal of Medicinal Chemistry--Chimie Therapeutique.
   (Editions Scientifiques Elsevier, 29 rue Buffon, F-75005, Paris, France)
   V.9-    1974-  Volume(issue)/page/year: 27,611,1992
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 89360 ug/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
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Unreported
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 180 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   RRCRBU Recent Results in Cancer Research.  (Springer-Verlag New York, Inc.,
   Service Center, 44 Hartz Way, Secaucus, NJ 07094)  V.1-    1965-
   Volume(issue)/page/year: 48,12,1974
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : >31200 ug/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,288,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Unreported
SPECIES OBSERVED        : Mammal - species unspecified
DOSE/DURATION           : 158 mg/kg
TOXIC EFFECTS :
   Tumorigenic - active as anti-cancer agent
REFERENCE :
   YHHPAL Yaoxue Xuebao.  Acta Pharmaceutica Sinica.  Pharmaceutical Journal.
   (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep.
   China)  V.1-    1953-    Suspended 1966-78.  Volume(issue)/page/year:
   22,56,1987
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 70 mg/kg/2W-I
TOXIC EFFECTS :
   Lungs, Thorax, or Respiration - changes in lung weight
   Endocrine - changes in spleen weight
   Blood - changes in platelet count
REFERENCE :
   YACHDS Yakuri to Chiryo.  Pharmacology and Therapeutics.  (Raifu Saiensu
   Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan)  V.1-    1972-
   Volume(issue)/page/year: 20(Suppl 3),S721,1992
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 140 mg/kg/26W-I
TOXIC EFFECTS :
   Blood - normocytic anemia
   Blood - changes in bone marrow (not otherwise specified)
   Blood - changes in leukocyte (WBC) count
REFERENCE :
   KSRNAM Kiso to Rinsho.  Clinical Report.  (Yubunsha Co., Ltd., 1-5, Kanda
   Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan)  V.1-    1960-
   Volume(issue)/page/year: 22,3340,1988
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 60 mg/kg/5D-I
TOXIC EFFECTS :
   Gastrointestinal - alteration in gastric secretion
   Gastrointestinal - other changes
   Blood - hemorrhage
REFERENCE :
   NTIS** National Technical Information Service.  (Springfield, VA 22161)
   Formerly U.S. Clearinghouse for Scientific & Technical Information.
   Volume(issue)/page/year: PB81-108912
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 24 mg/kg
SEX/DURATION            : female 6-9 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
   number of implants per female; total number of implants per corpora lutea)
   Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
   e.g., stunted fetus)
   Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
   JTSCDR Journal of Toxicological Sciences.  (Japanese Soc. of Toxicological
   Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku,
   Tokyo 113, Japan)  V.1-    1976-  Volume(issue)/page/year: 14,115,1989
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 24 mg/kg
SEX/DURATION            : female 6-9 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Specific Developmental Abnormalities - Central Nervous System
   Reproductive - Specific Developmental Abnormalities - body wall
   Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
   JTSCDR Journal of Toxicological Sciences.  (Japanese Soc. of Toxicological
   Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku,
   Tokyo 113, Japan)  V.1-    1976-  Volume(issue)/page/year: 14,115,1989
 
                            ** MUTATION DATA **
 
TYPE OF TEST            : Mutation in microorganisms
TEST SYSTEM             : Bacteria - Escherichia coli
DOSE/DURATION           : 300 umol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 173,13,1986
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
TEST SYSTEM             : Bacteria - Escherichia coli
DOSE/DURATION           : 100 mmol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 389,183,1997
 
TYPE OF TEST            : Micronucleus test
TEST SYSTEM             : Human Lymphocyte
DOSE/DURATION           : 500 nmol/L
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 389,183,1997
 
TYPE OF TEST            : DNA inhibition
TEST SYSTEM             : Human Cells - not otherwise specified
DOSE/DURATION           : 225 umol/L
REFERENCE :
   BCPCA6 Biochemical Pharmacology.  (Pergamon Press Inc., Maxwell House,
   Fairview Park, Elmsford, NY 10523)  V.1-    1958-  Volume(issue)/page/year:
   42,357,1991
 
TYPE OF TEST            : DNA inhibition
TEST SYSTEM             : Human Cells - not otherwise specified
DOSE/DURATION           : 225 umol/L
REFERENCE :
   BCPCA6 Biochemical Pharmacology.  (Pergamon Press Inc., Maxwell House,
   Fairview Park, Elmsford, NY 10523)  V.1-    1958-  Volume(issue)/page/year:
   42,357,1991
 
TYPE OF TEST            : Cytogenetic analysis
TEST SYSTEM             : Human Lymphocyte
DOSE/DURATION           : 675 ug/L
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: 22,821,1991
 
TYPE OF TEST            : DNA inhibition
TEST SYSTEM             : Rodent - rat Kidney
DOSE/DURATION           : 25 umol/L
REFERENCE :
   PHTOEH Pharmacology and Toxicology (Copenhagen).  (Munksgaard International
   Pub., POB 2148, DK-1016 Copenhagen K, Denmark)  V.60-    1987-
   Volume(issue)/page/year: 70,143,1992
 
TYPE OF TEST            : Micronucleus test
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 75 mg/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 322,55,1994
 
TYPE OF TEST            : DNA damage
TEST SYSTEM             : Rodent - mouse Leukocyte
DOSE/DURATION           : 200 umol/L
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   45,4043,1985
 
TYPE OF TEST            : DNA damage
ROUTE OF EXPOSURE       : Intravenous
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 128 mg/kg
REFERENCE :
   INNDDK Investigational New Drugs. The Journal of New Anticancer Agents.
   Kluwer Academic Pub., POB 358, Accord Stn., Hingham, MA 02018)  V.1- 1983- 
   Volume(issue)/page/year: 8,17,1990
 
TYPE OF TEST            : DNA inhibition
ROUTE OF EXPOSURE       : Intravenous
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 60 mg/kg
REFERENCE :
   CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
   Sts., Philadelphia, PA 19106)  V.1-    1941-  Volume(issue)/page/year:
   49,6629,1989
 
TYPE OF TEST            : Mutation test systems - not otherwise specified
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 75 mg/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 322,55,1994
 
TYPE OF TEST            : Cytogenetic analysis
ROUTE OF EXPOSURE       : Intravenous
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 18800 ug/kg
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: 22,821,1991
 
TYPE OF TEST            : Micronucleus test
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 8250 nmol/L
REFERENCE :
   NEOLA4 Neoplasma.  (Karger-Libri, P.O. Box, CH-4009 Basel, Switzerland) V.4-
      1957-  Volume(issue)/page/year: 31,655,1984
 
TYPE OF TEST            : Cytogenetic analysis
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 4400 nmol/L
REFERENCE :
   ZYYZEW Zhongguo Yaolixue Yu Dulixue Zazhi.  (Chinese Pharmacological
   Society, 27 Tai-Ping Road, Beijing 100850, China)  V.1-    1986-
   Volume(issue)/page/year: 5,217,1991
 
TYPE OF TEST            : Sister chromatid exchange
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 8250 nmol/L
REFERENCE :
   NEOLA4 Neoplasma.  (Karger-Libri, P.O. Box, CH-4009 Basel, Switzerland) V.4-
      1957-  Volume(issue)/page/year: 31,655,1984
 
TYPE OF TEST            : Mutation in mammalian somatic cells
TEST SYSTEM             : Rodent - hamster Lung
DOSE/DURATION           : 100 umol/L
REFERENCE :
   EJCODS European Journal of Cancer and Clinical Oncology.  (Pergamon Press,
   c/o Elsevier Science, 660 White Plains Rd., Tarrytown, NY 10591)  V.17(7)-
   25, 1981-89.  For publisher information, see EJCAEL Volume(issue)/page/year:
   25,27,1989
 
TYPE OF TEST            : Mutation in mammalian somatic cells
TEST SYSTEM             : Rodent - hamster Ovary
DOSE/DURATION           : 250 mg/L
REFERENCE :
   CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House,
   Southfield Road, Eynsham, Oxford OX8 1JJ, UK)  V.1-    1980-
   Volume(issue)/page/year: 13,15,1992
 
TYPE OF TEST            : Morphological transformation
TEST SYSTEM             : Rodent - hamster Kidney
DOSE/DURATION           : 25 umol/L
REFERENCE :
   EJCODS European Journal of Cancer and Clinical Oncology.  (Pergamon Press,
   c/o Elsevier Science, 660 White Plains Rd., Tarrytown, NY 10591)  V.17(7)-
   25, 1981-89.  For publisher information, see EJCAEL Volume(issue)/page/year:
   25,27,1989

                              *** REVIEWS ***
 
   TOXICOLOGY REVIEW
   JPMSAE Journal of Pharmaceutical Sciences.  (American Pharmaceutical Assoc.,
   2215 Constitution Ave., NW, Washington, DC 20037)  V.50-    1961-
   Volume(issue)/page/year: 65,315,1976

 
                            *** END OF RECORD ***