*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : VH6475000 CHEMICAL NAME : Retinoic acid, all-trans- CAS REGISTRY NUMBER : 302-79-4 BEILSTEIN REFERENCE NO. : 2057223 REFERENCE : 4-09-00-02387 (Beilstein Handbook Reference) LAST UPDATED : 199806 DATA ITEMS CITED : 73 MOLECULAR FORMULA : C20-H28-O2 MOLECULAR WEIGHT : 300.48 WISWESSER LINE NOTATION : L6UTJ A1 B1U1Y1&U2U1Y1&U1VQ C1 C1 COMPOUND DESCRIPTOR : Tumorigen Drug Mutagen Reproductive Effector Primary Irritant SYNONYMS/TRADE NAMES : * Aberel * Airol * Aknoten * Cordes vas * Dermairol * 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid * Effederm * Epi-aberel * Eudyna * 2,4,6,8-Nonatetraenoic acid, 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)- * NSC-122758 * beta-RA * Retin-A * Retinoic acid * beta-Retinoic acid * trans-Retinoic acid * all-trans-Retinoic acid * Tretinoin * beta-all-trans-Retinoic acid * Vitamin A acid *** HEALTH HAZARD DATA *** ** SKIN/EYE IRRITATION DATA ** TYPE OF TEST : Standard Draize test ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Human DOSE/DURATION : 525 mg/21D (Intermittent) REACTION SEVERITY : Mild REFERENCE : AVSUAR Acta Dermato-Venereologica, Supplementum. (Almqvist & Wiksell, POB 45150, S-10430 Stockholm, Sweden) No.1- 1929- Volume(issue)/page/year: 74,128,1975 ** ACUTE TOXICITY DATA ** TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >200 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: -,886,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 96 mg/kg TOXIC EFFECTS : Spinal Cord - other degenerative changes Behavioral - ataxia Blood - normocytic anemia 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: 7,3194,1973 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 53 mg/kg TOXIC EFFECTS : Behavioral - hallucinations, distorted perceptions Lungs, Thorax, or Respiration - respiratory depression Nutritional and Gross Metabolic - weight loss or decreased weight gain 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: 7,3194,1973 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 75 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: -,886,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >500 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: -,886,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 208 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: -,886,1995 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 253 mg/kg TOXIC EFFECTS : Behavioral - sleep Lungs, Thorax, or Respiration - respiratory depression Nutritional and Gross Metabolic - weight loss or decreased weight gain 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: 7,3194,1973 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 92 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: #3878202 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 420 mg/kg/12W-I TOXIC EFFECTS : Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Metabolism (Intermediary) - Plasma proteins not involving coagulation REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 47,359,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1274 mg/kg/13W-C TOXIC EFFECTS : Liver - changes in liver weight Blood - changes in erythrocyte (RBC) count Musculoskeletal - other changes REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 30,115,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1400 mg/kg/28D-C TOXIC EFFECTS : Nutritional and Gross Metabolic - weight loss or decreased weight gain Musculoskeletal - other changes Related to Chronic Data - death REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 96,279,1988 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2100 mg/kg/21D-I TOXIC EFFECTS : Blood - pigmented or nucleated red blood cells Musculoskeletal - other changes Related to Chronic Data - death REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 44,29,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1400 mg/kg/28D-I TOXIC EFFECTS : Musculoskeletal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 96,279,1988 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2100 mg/kg/2W-I TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain 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: 17,331,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 78 mg/kg/26W-I TOXIC EFFECTS : Blood - changes in leukocyte (WBC) count Skin and Appendages - dermatitis, other (after systemic exposure) Nutritional and Gross Metabolic - weight loss or decreased weight gain 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: 7,3247,1973 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 630 mg/kg/21D-I TOXIC EFFECTS : Blood - changes in erythrocyte (RBC) count Musculoskeletal - other changes Related to Chronic Data - death REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 44,29,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 52 mg/kg/30D-I TOXIC EFFECTS : Blood - normocytic anemia Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases 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: 7,3201,1973 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3276 mg/kg/52W-C TOXIC EFFECTS : Blood - hemorrhage Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death REFERENCE : NAIZAM Nara Igaku Zasshi. Journal of the Nara Medical Association. (Nara Igakkai, c/o Narakenritsu Ika Daigaku, Shijo-cho, Kashihara, Nara-ken, Japan) V.1- 1950- Volume(issue)/page/year: 27,437,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 660 mg/kg/22D-I TOXIC EFFECTS : Endocrine - changes in spleen weight Blood - changes in bone marrow (not otherwise specified) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - multiple enzyme effects REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 14,15,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 285 mg/kg/57D-I TOXIC EFFECTS : Endocrine - changes in thymus weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Related to Chronic Data - changes in testicular weight REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 8,517,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 300 mg/kg/10D-I TOXIC EFFECTS : Musculoskeletal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 34,91,1996 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 8400 mg/kg/30W-I TOXIC EFFECTS : Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - photosensitivity (after systemic exposure) Skin and Appendages - tumors REFERENCE : CALEDQ Cancer Letters (Shannon, Ireland). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1975- Volume(issue)/page/year: 7,85,1979 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 15 mg/kg SEX/DURATION : female 11-13 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 : ANESAV Anesthesiology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1940- Volume(issue)/page/year: 64,339,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 15 mg/kg SEX/DURATION : female 14-16 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : ANESAV Anesthesiology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1940- Volume(issue)/page/year: 64,339,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 15 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 - 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: 33,73C,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 120 mg/kg SEX/DURATION : female 11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) 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: 23,25,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 15 mg/kg SEX/DURATION : female 9 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear 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: 33,73C,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rat DOSE : 27500 ug/kg SEX/DURATION : female 6-16 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - other effects Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : JAADDB Journal of the American Academy of Dermatology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) 1979- Volume(issue)/page/year: 36(Suppl),S60,1997 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rat DOSE : 55 mg/kg SEX/DURATION : female 6-16 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : JAADDB Journal of the American Academy of Dermatology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) 1979- Volume(issue)/page/year: 36(Suppl),S60,1997 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 20 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) Reproductive - Specific Developmental Abnormalities - Central Nervous System 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: 28,209,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 40 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) REFERENCE : SJPSEM Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. (Almgvist & Wiksell, POB 638, S-10128 Stockholm, Sweden) V.21- 1987- Volume(issue)/page/year: 24,3,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - rat DOSE : 15 mg/kg SEX/DURATION : female 11-13 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) 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: 25(2),64A,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - rat DOSE : 12 mg/kg SEX/DURATION : female 14-16 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - behavioral 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: 25(2),64A,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 15 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - urogenital 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: 26,11,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 15 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : ANESAV Anesthesiology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1940- Volume(issue)/page/year: 54,505,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 40 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - gastrointestinal 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: 34,37,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 50 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 - Specific Developmental Abnormalities - eye/ear 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: 53,292,1996 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE : 100 mg/kg SEX/DURATION : female 10 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - other effects to embryo REFERENCE : TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 1,181,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 5 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: 32,87,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 20 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous 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: 28,123,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 16 mg/kg SEX/DURATION : female 11 day(s) after conception TOXIC EFFECTS : 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: 32,32A,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 500 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) 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: 40,679,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE : 20 mg/kg SEX/DURATION : female 11 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) 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: 25(2),57A,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE : 80 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) 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: 25(2),57A,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE : 40 mg/kg SEX/DURATION : female 11 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: 25(2),57A,1982 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE : 40 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous 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: 36,441,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE : 188 mg/kg SEX/DURATION : female 20-44 day(s) after conception TOXIC EFFECTS : 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: 21,29,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE : 250 mg/kg SEX/DURATION : female 20-44 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) 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: 22,87,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE : 250 mg/kg SEX/DURATION : female 20-44 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital 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: 22,87,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE : 170 mg/kg SEX/DURATION : female 10-24 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) 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: 45,65,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rabbit DOSE : 6500 ug/kg SEX/DURATION : female 7-19 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 - abortion Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : JAADDB Journal of the American Academy of Dermatology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) 1979- Volume(issue)/page/year: 36(Suppl),S67,1997 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE : 40 mg/kg SEX/DURATION : female 7 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) 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: 21,193,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE : 12500 ug/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 72,689,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE : 60 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material) 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: 28,341,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE : 25 mg/kg SEX/DURATION : female 8 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 72,689,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Mammal - species unspecified DOSE : 12500 ug/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) REFERENCE : ENMEE9 Environmental Medicine. (Nagoya University, Research Insitute of Environmental Medicine, Furo-cho, Chikusa-ku, Nagoya, 464, Japan) V.26- 1982- Volume(issue)/page/year: 36,75,1992 ** MUTATION DATA ** TYPE OF TEST : DNA inhibition TEST SYSTEM : Microorganism - not otherwise specified DOSE/DURATION : 1 umol/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 45,2098,1985 TYPE OF TEST : DNA inhibition TEST SYSTEM : Human Leukocyte DOSE/DURATION : 1 umol/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 46,1388,1986 TYPE OF TEST : Mutation test systems - not otherwise specified TEST SYSTEM : Human Leukocyte DOSE/DURATION : 1 umol/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 46,1388,1986 TYPE OF TEST : Mutation test systems - not otherwise specified ROUTE OF EXPOSURE : Administration onto the skin TEST SYSTEM : Human DOSE/DURATION : 1000 ppm REFERENCE : 26UYA8 "Psoriasis, Proceedings of the International Symposium, Stanford, CA, 1971," Farber, E.M., and A.J. Cox, eds., Stanford, CA, Stanford Univ. Press, 1971 Volume(issue)/page/year: -,335,1971 TYPE OF TEST : Sister chromatid exchange TEST SYSTEM : Human Fibroblast DOSE/DURATION : 5 mg/L REFERENCE : MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 58,317,1978 TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - rat Mammary gland DOSE/DURATION : 3 umol/L REFERENCE : JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 70,949,1983 TYPE OF TEST : Unscheduled DNA synthesis ROUTE OF EXPOSURE : Administration onto the skin TEST SYSTEM : Rodent - mouse DOSE/DURATION : 4 umol/kg REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,5174,1983 TYPE OF TEST : Mutation test systems - not otherwise specified TEST SYSTEM : Rodent - mouse Embryo DOSE/DURATION : 10 umol/L REFERENCE : CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 42,4918,1982 TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - mouse Lymphocyte DOSE/DURATION : 1 umol/L REFERENCE : ONCOBS Oncology. (S. Karger AG, Postfach CH-4009 Basel, Switzerland) V.21- 1967- Volume(issue)/page/year: 44,356,1987 TYPE OF TEST : DNA inhibition TEST SYSTEM : Mammal - cattle Lymphocyte DOSE/DURATION : 8 umol/L REFERENCE : CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 3,409,1982 *** REVIEWS *** TOXICOLOGY REVIEW BCSTB5 Biochemical Society Transactions. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1973- Volume(issue)/page/year: 2,695,1974 TOXICOLOGY REVIEW APJUA8 Acta Pharmaceutica Jugoslavica. (FDH, Masarykova 2, 41000 Zagreb, Yugoslavia) V.1-41, 1951-1991. Volume(issue)/page/year: 41,79,1991 TOXICOLOGY REVIEW DDREDK Drug Development Research. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1981- Volume(issue)/page/year: 30,244,1993 *** STATUS IN U.S. *** EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro SCE-human EPA TSCA Section 8(b) CHEMICAL INVENTORY EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JUNE 1998 *** END OF RECORD ***