*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : TU4157070 CHEMICAL NAME : 17-alpha-Pregna-2,4-dien-20-yno(2,3-d)isoxazol-17-ol CAS REGISTRY NUMBER : 17230-88-5 LAST UPDATED : 199609 DATA ITEMS CITED : 39 MOLECULAR FORMULA : C22-H27-N-O2 MOLECULAR WEIGHT : 337.50 WISWESSER LINE NOTATION : T G5 E6 B665 HON EU&TTTTJ M1 Q1 RQ R1UU1 COMPOUND DESCRIPTOR : Tumorigen Drug Mutagen Reproductive Effector Human Hormone SYNONYMS/TRADE NAMES : * Danazol * Danocrine * Danol * Pregna-2,4-dien-20-yno(2,3-d)isoxazol-17-ol, (17-alpha)- * 17-alpha-2,4-Pregnadien-20-yno(2,3-d)isoxazol-17-ol * 17-alpha-Pregn-4-en-20-yno(2,3-d)isoxazol-17-ol * WIN 17757 *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 274 mg/kg/32D-I TOXIC EFFECTS : Liver - jaundice, cholestatic Liver - other changes Skin and Appendages - dermatitis, other (after systemic exposure) REFERENCE : PGMJAO Postgraduate Medical Journal. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1925- Volume(issue)/page/year: 69,237,1993 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 120 mg/kg/10D-I TOXIC EFFECTS : Skin and Appendages - dermatitis, allergic (after systemic exposure) REFERENCE : AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 145,2251,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 1029 mg/kg/17W-I TOXIC EFFECTS : Liver - jaundice, cholestatic REFERENCE : PGMJAO Postgraduate Medical Journal. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1925- Volume(issue)/page/year: 68,984,1992 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >17 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959- Volume(issue)/page/year: 25,691,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959- Volume(issue)/page/year: 25,691,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959- Volume(issue)/page/year: 25,691,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 4830 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ZYZAEU Zhongguo Yaoxue Zazhi. Chinese Pharmacuetical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. China) V.24- 1989- Volume(issue)/page/year: 25,55,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 6770 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: 14,484,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959- Volume(issue)/page/year: 25,691,1983 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 5(Suppl 3),1,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 5(Suppl 3),1,1977 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2500 mg/kg/10D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - changes in bladder weight REFERENCE : ZYZAEU Zhongguo Yaoxue Zazhi. Chinese Pharmacuetical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. China) V.24- 1989- Volume(issue)/page/year: 25,55,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 91 gm/kg/26W-I TOXIC EFFECTS : Liver - fatty liver degeneration Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase REFERENCE : JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year: 15,29,1989 ** TUMORIGENIC DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 2920 mg/kg/2Y-C TOXIC EFFECTS : Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors REFERENCE : JSONAU Journal of Surgical Oncology. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1969- Volume(issue)/page/year: 28,114,1985 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE : 1064 mg/kg SEX/DURATION : female 1-19 week(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Effects on Newborn - germ cell effects (in offspring) Reproductive - Effects on Newborn - physical REFERENCE : MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 143,410,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE : 120 mg/kg SEX/DURATION : female 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - other effects REFERENCE : INJFA3 International Journal of Fertility. (Allen Press, 1041 New Hampshire, St., Lawrence, KS 66044) V.1- 1955- Volume(issue)/page/year: 25,75,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE : 1028 mg/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 - impotence REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 7,357,1973 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE : 16 ug/kg SEX/DURATION : female 5 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 27,39,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE : 90 mg/kg SEX/DURATION : female 90 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - other measures of fertility REFERENCE : JRPMAP Journal of Reproductive Medicine. (2 Jacklynn Ct., St. Louis, MO 63132) V.3- 1969- Volume(issue)/page/year: 17,98,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE : 430 mg/kg SEX/DURATION : male 21 week(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - other effects on male REFERENCE : JCEMAZ Journal of Clinical Endocrinology and Metabolism. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.12- 1952- Volume(issue)/page/year: 32,522,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 600 mg/kg SEX/DURATION : female 6 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) REFERENCE : JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 5(Suppl 3),1,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 462 mg/kg SEX/DURATION : male 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 25,367,1974 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 5600 mg/kg SEX/DURATION : female 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes REFERENCE : JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 5(Suppl 3),1,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 1400 mg/kg SEX/DURATION : male 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 25,367,1974 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 37500 ug/kg SEX/DURATION : female 3 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 25,367,1974 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 56 mg/kg SEX/DURATION : male 14 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 : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 22,9,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 140 mg/kg SEX/DURATION : female 14 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 22,9,1971 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 520 mg/kg SEX/DURATION : male 39 day(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 : JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960- Volume(issue)/page/year: 77,233,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE : 93 mg/kg SEX/DURATION : male 7 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - other effects on male REFERENCE : JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960- Volume(issue)/page/year: 77,233,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE : 880 mg/kg SEX/DURATION : male 22 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 : FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 26,68,1975 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE : 3 gm/kg SEX/DURATION : female 15 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina REFERENCE : AEFTAA Acta Europaea Fertilitatis. (COFESE Eds., Piazzale Ungheria 73, 90141 Palermo, Italy) V.1- 1969- Volume(issue)/page/year: 7,243,1976 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Mammal - dog DOSE : 600 mg/kg SEX/DURATION : male 30 day(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 : AEFTAA Acta Europaea Fertilitatis. (COFESE Eds., Piazzale Ungheria 73, 90141 Palermo, Italy) V.1- 1969- Volume(issue)/page/year: 8,167,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intratesticular SPECIES OBSERVED : Mammal - dog DOSE : 18 mg/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : 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: 17,937,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE : 1800 mg/kg SEX/DURATION : female 90 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated) REFERENCE : JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 5(Suppl 3),1,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE : 3600 mg/kg SEX/DURATION : female 90 day(s) pre-mating TOXIC EFFECTS : Reproductive - Maternal Effects - menstrual cycle changes or disorders REFERENCE : JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 5(Suppl 3),1,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Primate - monkey DOSE : 1920 mg/kg SEX/DURATION : male 48 day(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 : ANDRDQ Andrologia. (Grosse Verlag GmbH, Kurfuerstenstr. 112-113, D-1000 Berlin 30, Fed. Rep. Ger.) V.6- 1974- Volume(issue)/page/year: 13,314,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - gerbil DOSE : 880 mg/kg SEX/DURATION : male 22 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 : JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960- Volume(issue)/page/year: 61,217,1981 ** MUTATION DATA ** TYPE OF TEST : Mutation test systems - not otherwise specified ROUTE OF EXPOSURE : Intratesticular TEST SYSTEM : Mammal - dog DOSE/DURATION : 13 mg/kg REFERENCE : FOBGA8 Folia Biologica (Krakow). (Ars Polona, POB 1001, 00-068 Warsaw 1, Poland) V.1- 1953- Volume(issue)/page/year: 23.305,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5831 No. of Facilities: 9 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 339 (estimated) No. of Female Employees: 170 (estimated) *** END OF RECORD ***