*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : RC8899500
CHEMICAL NAME : 19-Norpregna-4,9-diene-21-nitrile, 17-hydroxy-3-oxo-,
(17-alpha)-
CAS REGISTRY NUMBER : 65928-58-7
LAST UPDATED : 199503
DATA ITEMS CITED : 28
MOLECULAR FORMULA : C20-H25-N-O2
MOLECULAR WEIGHT : 311.46
WISWESSER LINE NOTATION : L E5 B666 OV BU MUTJ E1 FQ F1CN
COMPOUND DESCRIPTOR : Mutagen
Reproductive Effector
Hormone
SYNONYMS/TRADE NAMES :
* 17-alpha-Cyanomethyl-17-beta-hydroxyestra-4,9(10)-diene-3-one
* 17-alpha-Cyanomethyl-17-beta-hydroxy-estra-4,9(10)-dien-3-one
* Dienogest
* STS 557
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 4 gm/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
REFERENCE :
PHARAT Pharmazie. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18,
Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1946- Volume(issue)/page/year:
34,319,1979
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1 gm/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - coma
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: 81,175,1983
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 5 gm/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
REFERENCE :
PHARAT Pharmazie. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18,
Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1946- Volume(issue)/page/year:
34,319,1979
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : 1 gm/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Endocrine - other changes
Nutritional and Gross Metabolic - weight loss or decreased weight gain
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: 81,175,1983
TYPE OF TEST : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : 1500 mg/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Endocrine - other changes
Nutritional and Gross Metabolic - weight loss or decreased weight gain
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: 81,175,1983
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1820 mg/kg/26W-I
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Biochemical - Metabolism (Intermediary) - other proteins
REFERENCE :
PHARAT Pharmazie. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18,
Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1946- Volume(issue)/page/year:
34,319,1979
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 300 mg/kg
SEX/DURATION : male 60 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 :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 36,253,1987
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 1500 mg/kg
SEX/DURATION : male 60 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
Reproductive - Fertility - mating performance (e.g. # sperm positive females
per # females mated; # copulations per # estrus cycles)
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 36,253,1987
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 461 mg/kg
SEX/DURATION : male 21 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 :
IJEBA6 Indian Journal of Experimental Biology. (Publications & Information
Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963-
Volume(issue)/page/year: 27,324,1989
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 8 mg/kg
SEX/DURATION : female 1 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc.,
Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978-
Volume(issue)/page/year: 4,248,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 25 mg/kg
SEX/DURATION : female 1-4 day(s) after conception
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 :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 21,537,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 84 mg/kg
SEX/DURATION : male 21 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - testes, epididymis, sperm duct
Reproductive - Fertility - male fertility index (e.g. # males impregnating
females per # males exposed to fertile nonpregnant females)
REFERENCE :
ARANDR Archives of Andrology. (Elsevier Science Pub. Co., Inc., 52
Vanderbilt Ave., New York, NY 10017) V.1- 1978- Volume(issue)/page/year:
11,157,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 42 mg/kg
SEX/DURATION : male 21 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
REFERENCE :
ARANDR Archives of Andrology. (Elsevier Science Pub. Co., Inc., 52
Vanderbilt Ave., New York, NY 10017) V.1- 1978- Volume(issue)/page/year:
11,157,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 10 mg/kg
SEX/DURATION : female 1 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc.,
Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978-
Volume(issue)/page/year: 4,248,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 500 mg/kg
SEX/DURATION : female 13-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
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: 81,197,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 500 ug/kg
SEX/DURATION : female 3-7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
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: 81,197,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 500 mg/kg
SEX/DURATION : female 8-12 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - abortion
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: 81,197,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE : 200 mg/kg
SEX/DURATION : female 1-4 day(s) after conception
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 :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 21,537,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE : 700 mg/kg
SEX/DURATION : male 35 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
number of implants per female; total number of implants per corpora lutea)
REFERENCE :
ENDKAC Endokrinologie. (Leipzig, Ger. Dem. Rep.) V.1-80, 1928-82. For
publisher information, see EXCEDS. Volume(issue)/page/year: 76,13,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Primate - monkey
DOSE : 80 ug/kg
SEX/DURATION : female 1-4 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: 21,537,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Primate - monkey
DOSE : 600 ug/kg
SEX/DURATION : female 3 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S,
Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 40,688,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Primate - monkey
DOSE : 84 mg/kg
SEX/DURATION : male 7 week(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 37,631,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 80 mg/kg
SEX/DURATION : male 56 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
Reproductive - Fertility - mating performance (e.g. # sperm positive females
per # females mated; # copulations per # estrus cycles)
Reproductive - Fertility - male fertility index (e.g. # males impregnating
females per # males exposed to fertile nonpregnant females)
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 21,641,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 100 ug/kg
SEX/DURATION : female 1 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)
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 21,61,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 13500 ug/kg
SEX/DURATION : female 3 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 :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 21,61,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 4500 ug/kg
SEX/DURATION : female 3 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 21,61,1980
** MUTATION DATA **
TYPE OF TEST : Dominant lethal test
ROUTE OF EXPOSURE : Subcutaneous
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 700 mg/kg/35D
REFERENCE :
ENDKAC Endokrinologie. (Leipzig, Ger. Dem. Rep.) V.1-80, 1928-82. For
publisher information, see EXCEDS. Volume(issue)/page/year: 76,13,1980
*** STATUS IN U.S. ***
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-rabbit
*** END OF RECORD ***