*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : UG5700000 CHEMICAL NAME : m-Propionotoluidide, 2-methyl-4'-nitro-alpha,alpha,alpha-triflouro- CAS REGISTRY NUMBER : 13311-84-7 BEILSTEIN REFERENCE NO. : 2157663 LAST UPDATED : 199806 DATA ITEMS CITED : 27 MOLECULAR FORMULA : C11-H11-F3-N2-O3 MOLECULAR WEIGHT : 276.24 WISWESSER LINE NOTATION : FXFFR BNW EMVY1&1 COMPOUND DESCRIPTOR : Tumorigen Drug Mutagen Reproductive Effector Human Hormone SYNONYMS/TRADE NAMES : * Flutamide * Niftholide * Niftolide * 4'-Nitro-3'-trifluoromethylisobutyranilide * Propanamide, 2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)- * Sch 13521 * alpha,alpha,alpha-Trifluoro-2-methyl-4'-nitro-m-propionotoluidide *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 310 mg/kg/31D-I TOXIC EFFECTS : Behavioral - euphoria REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 143,1498,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 787 mg/kg TOXIC EFFECTS : Kidney, Ureter, Bladder - hematuria Kidney, Ureter, Bladder - incontinence 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: 45,135,1993 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 289 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - cyanosis 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: 45,135,1993 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >2 gm/kg TOXIC EFFECTS : Gastrointestinal - nausea or vomiting Gastrointestinal - other changes Liver - other changes REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 45,135,1993 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 700 mg/kg/28D-I TOXIC EFFECTS : Endocrine - androgenic Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) REFERENCE : BJCAAI British Journal of Cancer. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.1- 1947- Volume(issue)/page/year: 60,664,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 27300 mg/kg/52W-I TOXIC EFFECTS : Blood - pigmented or nucleated red blood cells Biochemical - Metabolism (Intermediary) - other proteins 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: 45,163,1993 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2730 mg/kg/1Y-I TOXIC EFFECTS : Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - testicular tumors REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 45,141,1993 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 1050 mg/kg SEX/DURATION : female 14-20 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : AAMMAU Archives d'Anatomie Microscopique et de Morphologie Experimentale. (SPPIF, B.P.22, F-41353 Vineuil, France) V.36-76, 1947-1987. For publisher information, see BSTME2. Volume(issue)/page/year: 64,27,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 150 mg/kg SEX/DURATION : male 30 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 : IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 25,81,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 375 mg/kg SEX/DURATION : male 15 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 : EXCEDS Experimental and Clinical Edocrinology. (Johann Ambrosius Barth Verlag, Postfach 109, Leipzig DDR-7010, Ger. Dem. Rep.) V.81- 1983- Volume(issue)/page/year: 82,140,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 3840 mg/kg SEX/DURATION : male 64 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) 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: 45,187,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 280 mg/kg SEX/DURATION : male 7 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 16,157,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 525 mg/kg SEX/DURATION : female 14-20 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : BIRSB5 Biology of Reproduction, Supplement. (Champaign, IL) No.1-4, 1969-71(?). Discontinued. For publisher information, see BIREBV. Volume(issue)/page/year: 20(Suppl 1),116A,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 275 mg/kg SEX/DURATION : female 11-21 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - Central Nervous System REFERENCE : BRREAP Brain Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1966- Volume(issue)/page/year: 578,69,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 70 mg/kg SEX/DURATION : male 7 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - other effects on male REFERENCE : IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 15,788,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 400 mg/kg SEX/DURATION : female 16-19 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - endocrine system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities REFERENCE : JPDSA3 Journal of Pediatric Surgery. (Grune and Stratton, Inc., Journal Subscription Dept., POB 6280, Duluth, MN 55806) V.1- 1966- Volume(issue)/page/year: 29,836,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE : 65 mg/kg SEX/DURATION : female 10-22 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - delayed effects REFERENCE : ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21203) V.1- 1917- Volume(issue)/page/year: 103,1702,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE : 29040 ug/kg SEX/DURATION : male 17 week(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct REFERENCE : IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 18,1225,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Parenteral SPECIES OBSERVED : Rodent - rat DOSE : 350 mg/kg SEX/DURATION : male 7 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male REFERENCE : ANDRDQ Andrologia. (Grosse Verlag GmbH, Kurfuerstenstr. 112-113, D-1000 Berlin 30, Fed. Rep. Ger.) V.6- 1974- Volume(issue)/page/year: 24,113,1992 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Parenteral SPECIES OBSERVED : Rodent - rat DOSE : 200 mg/kg SEX/DURATION : female 16-17 day(s) after conception TOXIC EFFECTS : Reproductive - Paternal Effects - other effects on male Endocrine - androgenic REFERENCE : JOURAA Journal of Urology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1917- Volume(issue)/page/year: 151,509,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE : 80 mg/kg SEX/DURATION : male 10 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) REFERENCE : ENDKAC Endokrinologie. (Leipzig, Ger. Dem. Rep.) V.1-80, 1928-82. For publisher information, see EXCEDS. Volume(issue)/page/year: 71,135,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE : 400 mg/kg SEX/DURATION : male 10 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : ENDKAC Endokrinologie. (Leipzig, Ger. Dem. Rep.) V.1-80, 1928-82. For publisher information, see EXCEDS. Volume(issue)/page/year: 71,135,1978 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE : 1 gm/kg SEX/DURATION : female 13-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - other postnatal measures or effects REFERENCE : BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W. Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year: 44,707,1991 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE : 300 mg/kg SEX/DURATION : female 14-16 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system REFERENCE : IJANDP International Journal of Andrology. (Scriptor Publisher ApS, 15 Gasvaerksvej, DK-1656 Copenhagen V, Denmark) V.1- 1978- Volume(issue)/page/year: 19,263,1996 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - pig DOSE : 1225 mg/kg SEX/DURATION : female 6 week(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - other effects to embryo REFERENCE : JOURAA Journal of Urology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1917- Volume(issue)/page/year: 156,767,1996 ** MUTATION DATA ** TYPE OF TEST : DNA inhibition TEST SYSTEM : Rodent - rat Liver DOSE/DURATION : 50 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: 13,373,1992 *** STATUS IN U.S. *** EPA GENETOX PROGRAM 1988, Negative: Rodent dominant lethal *** END OF RECORD ***