*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : OP2800000 CHEMICAL NAME : Mannitol, 1,6-dibromo-1,6-dideoxy-, D- CAS REGISTRY NUMBER : 488-41-5 BEILSTEIN REFERENCE NO. : 1721919 REFERENCE : 3-01-00-02373 (Beilstein Handbook Reference) LAST UPDATED : 199707 DATA ITEMS CITED : 36 MOLECULAR FORMULA : C6-H12-Br2-O4 MOLECULAR WEIGHT : 308.00 WISWESSER LINE NOTATION : E1YQYQYQYQ1E COMPOUND DESCRIPTOR : Tumorigen Drug Mutagen Reproductive Effector SYNONYMS/TRADE NAMES : * 1,6-Dibrom-1,6-didesoxy-D-mannit * Dibromannit * 1,6-Dibromo-1,6-dideoxy-D-mannitol * 1,6-Dibromo-1,6-D-didesoxymannitol * Dibromomannitol * D-Dibromomannitol * 1,6-Dibromomannitol * Mieobromol * Mitobronitol * Myebrol * Myelobromol * NCI-C04762 * NSC-94100 * R 54 *** 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 : 1500 mg/kg TOXIC EFFECTS : Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes Blood - normocytic anemia REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 900 mg/kg TOXIC EFFECTS : Blood - normocytic anemia Blood - thrombocytopenia REFERENCE : EJCAAH European Journal of Cancer. (Oxford, UK) V.1-17(6), 1965-1981. For publisher information, see EJCODS. Volume(issue)/page/year: 4,617,1968 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1240 mg/kg TOXIC EFFECTS : Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes Blood - normocytic anemia REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1370 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value 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: 8,680,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1380 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - ataxia Skin and Appendages - hair REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 900 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - ataxia Skin and Appendages - hair REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2200 mg/kg TOXIC EFFECTS : Behavioral - tremor Behavioral - ataxia Skin and Appendages - hair REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value 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: 8,680,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 1080 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 4950 mg/kg/33D-I TOXIC EFFECTS : Behavioral - ataxia Liver - other changes Blood - changes in leukocyte (WBC) count REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 28,1587,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5460 mg/kg/26W-I TOXIC EFFECTS : Endocrine - changes in thymus weight Blood - normocytic anemia Related to Chronic Data - death REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 10920 mg/kg/26W-C TOXIC EFFECTS : 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: 6,831,1972 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9750 mg/kg/26W-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors Tumorigenic - tumors at site of application 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: 52,1,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 7000 mg/kg/26W-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors Blood - lymphoma, including Hodgkin's disease 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: 52,1,1975 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 300 mg/kg SEX/DURATION : female 9-14 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) 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: 6,30,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 3900 mg/kg SEX/DURATION : female 26 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 500 mg/kg SEX/DURATION : female 13 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) 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: 6,30,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 500 mg/kg SEX/DURATION : female 10 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : HYDKAK Hoshi Yakka Daigaku Kiyo. Bulletin of the Hoshi College of Pharmacy. (2-4-41 Ebara, Shinagawa-ku, Tokyo 142, Japan) No.1- 1951- Volume(issue)/page/year: 17,67,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 300 mg/kg SEX/DURATION : female 9 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 - fetal death 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: 6,30,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 3900 mg/kg SEX/DURATION : male 26 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,831,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 150 mg/kg SEX/DURATION : female 11 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 - Effects on Embryo or Fetus - fetal death 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: 6,30,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 150 mg/kg SEX/DURATION : female 11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system 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: 6,30,1972 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 300 mg/kg SEX/DURATION : female 12 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear 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: 6,30,1972 ** MUTATION DATA ** TYPE OF TEST : Mutation in microorganisms TEST SYSTEM : Bacteria - Salmonella typhimurium DOSE/DURATION : 1 mg/plate REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,4530,1983 TYPE OF TEST : Mutation in microorganisms TEST SYSTEM : Bacteria - Salmonella typhimurium DOSE/DURATION : 667 ug/plate REFERENCE : ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG. Volume(issue)/page/year: 8(Suppl 7),1,1986 TYPE OF TEST : DNA repair TEST SYSTEM : Microorganism - not otherwise specified DOSE/DURATION : 15400 ug/plate REFERENCE : BIZNAT Biologisches Zentralblatt. (VEB Georg Thieme, Postfach 946, Leipzig DDR-7010, Ger. Dem. Rep.) V.1- 1881- Volume(issue)/page/year: 95,463,1976 TYPE OF TEST : Sex chromosome loss and nondisjunction ROUTE OF EXPOSURE : Oral TEST SYSTEM : Insect - Drosophila melanogaster DOSE/DURATION : 1 ppb REFERENCE : EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987- Volume(issue)/page/year: 23,208,1994 TYPE OF TEST : Heritable translocation test ROUTE OF EXPOSURE : Oral TEST SYSTEM : Insect - Drosophila melanogaster DOSE/DURATION : 1 ppb REFERENCE : EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987- Volume(issue)/page/year: 23,208,1994 TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Human Lymphocyte DOSE/DURATION : 10 nmol/L REFERENCE : NGCJAK Nippon Gan Chiryo Gakkai-shi. Journal of Japan Society for Cancer Therapy. (Nippon Gan Chiryo Gakkai, Kinki Chiho Hatsumei Senta, 14 Kawara-machi, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.1- 1966- Volume(issue)/page/year: 15,1085,1980 TYPE OF TEST : Cytogenetic analysis ROUTE OF EXPOSURE : Intravenous TEST SYSTEM : Rodent - mouse DOSE/DURATION : 90 mg/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 60,329,1979 TYPE OF TEST : Sister chromatid exchange ROUTE OF EXPOSURE : Intravenous TEST SYSTEM : Rodent - mouse DOSE/DURATION : 90 mg/kg REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 60,329,1979 TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Rodent - hamster Cells - not otherwise specified DOSE/DURATION : 1300 ng/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,4530,1983 TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - rabbit Bone marrow DOSE/DURATION : 730 umol/L REFERENCE : BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 25,1705,1976 *** REVIEWS *** TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 1(1),93,1971 TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 2,159,1973 *** STATUS IN U.S. *** NCI Carcinogenesis Studies (ipr);clear evidence:mouse,rat 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: 52,1,75 *** END OF RECORD ***