*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : JF8259000
CHEMICAL NAME : 18,19-Dinorpregn-4-en-20-yn-3-one,
13-ethyl-17-hydroxy-,
(8-alpha,9-beta,10-alpha,13-alpha, 14-beta)-
CAS REGISTRY NUMBER : 797-64-8
LAST UPDATED : 199606
DATA ITEMS CITED : 28
MOLECULAR FORMULA : C21-H28-O2
MOLECULAR WEIGHT : 312.49
WISWESSER LINE NOTATION : L E5 B666 OV MUTJ E2 FQ F1UU1
COMPOUND DESCRIPTOR : Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Levonorgestrel
* l-Norgestrel
* levo-Norgestrel
* Norplant
*** 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 : >5 gm/kg
TOXIC EFFECTS :
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1470 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - effect, not otherwise specified
Behavioral - altered sleep time (including change in righting reflex)
Behavioral - ataxia
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >5 gm/kg
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >5 gm/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: 41,295,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 2990 mg/kg
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - lacrimation
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: 41,295,1991
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >5 gm/kg
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 9100 mg/kg/52W-C
TOXIC EFFECTS :
Liver - changes in liver weight
Endocrine - changes in adrenal weight
Nutritional and Gross Metabolic - other changes
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,291,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Primate - monkey
DOSE/DURATION : 910 mg/kg/1Y-C
TOXIC EFFECTS :
Nutritional and Gross Metabolic - other changes
REFERENCE :
OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180,
Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,301,1991
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE : 2607 ug/kg
SEX/DURATION : male 52 week(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
Reproductive - Paternal Effects - other effects on male
Endocrine - androgenic
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 21,631,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 219 ug/kg
SEX/DURATION : female 52 week(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: 25,243,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Implant
SPECIES OBSERVED : Human - woman
DOSE : 875 ug/kg
SEX/DURATION : female 35 week(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: 22,71,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Implant
SPECIES OBSERVED : Human - man
DOSE : 3171 ug/kg
SEX/DURATION : male 60 day(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: 25,591,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Implant
SPECIES OBSERVED : Human - woman
DOSE : 110 ug/kg
SEX/DURATION : female 52 week(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - menstrual cycle changes or disorders
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: 18,151,1978
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Implant
SPECIES OBSERVED : Human - woman
DOSE : 4080 ug/kg
SEX/DURATION : female 52 week(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: 27,473,1983
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravaginal
SPECIES OBSERVED : Human - woman
DOSE : 102 ug/kg
SEX/DURATION : female 17 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - uterus, cervix, vagina
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 22,71,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intracervical
SPECIES OBSERVED : Human - woman
DOSE : 12 ug/kg
SEX/DURATION : female 30 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - menstrual cycle changes or disorders
REFERENCE :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 23,473,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intracervical
SPECIES OBSERVED : Human - woman
DOSE : 36 ug/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 :
CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1-
1970- Volume(issue)/page/year: 23,473,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 250 mg/kg
SEX/DURATION : female 1-4 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: 21,537,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 2800 ug/kg
SEX/DURATION : male 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - testes, epididymis, sperm duct
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 : Rodent - mouse
DOSE : 500 mg/kg
SEX/DURATION : female 8-12 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Effects on Embryo or Fetus - fetal death
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 : 50 mg/kg
SEX/DURATION : female 3-7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
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 : 5 mg/kg
SEX/DURATION : female 8-12 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - stillbirth
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 : 5 gm/kg
SEX/DURATION : female 3-7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced 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: 81,197,1983
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 - 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 : Oral
SPECIES OBSERVED : Primate - monkey
DOSE : 80 ug/kg
SEX/DURATION : female 1 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 : Rodent - rabbit
DOSE : 80 mg/kg
SEX/DURATION : male 56 day(s) pre-mating
TOXIC EFFECTS :
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: 21,641,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 500 ug/kg
SEX/DURATION : female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 33,231,1983
*** STATUS IN U.S. ***
EPA GENETOX PROGRAM 1988, Negative: Sperm morphology-rabbit
*** END OF RECORD ***
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