beta-Estradiol

Estradiol is a steroid sex hormone vital to the maintenance of fertility and secondary sexual characteristics in females.

Signaling Pathways >> Others >> Estrogen Receptor/ERR

Research Areas >> Endocrinology

Natural Products >> Steroids

Human Endogenous Metabolite

Estradiol causes new dendritic spines and synapses in hippocampal CA1 pyramidal cells. Estradiol increases NMDA receptor binding by 46% in parallel with dendritic spine and synapse density. Estradiol also elevates sensitivity of CA1 pyramidal cells to NMDA receptor-mediated synaptic input and such an effect is correlated with the estradiol-induced increase in dendritic spine density in the apical dendritic tree of these cells[1]. Estradiol reduces Ba2+ entry reversibly via Ca2+ channels in acutely dissociated and cultured neostriatal neurons. Estradiol also reduces Ba2+ currents but is significantly less effective than Estradiol in rat neostriatal neurons[2]. Estradiol dose-dependently inhibits IL-1-, TNF-, and IL-1 and TNF-induced production of bioassayable IL-6. Estradiol blocks TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria[3].

Estradiol functions in hippocampal synapse density during the estrous cycle in the adult rat[4]. Estradiol reverses the ovariectomy-induced decrease in spine density. Estradiol in combination with progesterone enhances spine density for 2 to 6 h but decreases following estradiol alone[5].

Briefly, B9 cells (5×103/well of a 96-well plate) are cultured with a series of dilutions of the supernatants in a final volume of 100 mL of RPMI 1640, supplemented with 5×10-5mol/Lof 2-mercaptoethanol, 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin in flat-bottom microtiter plates. After 42 h, 0.5 μCi of [3H]thymidine is added. 6 h later, the cells are harvested and the radioactivity incorporated is determined. IL-6 is quantitated from a standard curve set up with known amounts of recombinant human or mouse IL-6. The anti-IL-6 monoclonal antibody completely inhibited the ability of the B9 cells to proliferate in response to recombinant mouse IL-6. In addition, we determined that B9 cells do not proliferate in response to IL-I or TNF, and that antibodies to these two cytokines did not affect the cell proliferation in response to IL-6. Further, it is established that neither Estradiol (17β-estradiol), nor the 0.01% ethanol used as vehicle in these experiments, has any effect on the bioassay.

Adult female Sprague Dawley rats are housed on a 12 hr light/dark cycle with unlimited access to food and water. These animals are left gonadally intact (intact), ovariectomized and treated with estradiol benzoate (OVX+E), or ovariectomized and treated with sesame oil vehicle (OVX+O). The hormone treatment regimen that is used in these experiments has been shown previously to result in differences in CA1 pyramidal cell dendritic spine and synapse density. Six days before electrophysiological analysis, animals are ovariectomized under Metofane anesthesia using aseptic surgical procedure. After surgery, animals are housed individually. On days 3 and 4 after surgery, OVX+E animals are injected (s.c.) with 10 μg of 17β-estradiol benzoate in 100 μL of sesame oil vehicle; OVX+O animalsreceive oil vehicle at each injection time. Forty-eight hours after the second estradiol or vehicle injection, animals are killed by decapitation and hippocampal slices are prepared from their brains. Gonadally intact animals are killed at random stages of the estrous cycle.

[1]. Woolley CS, et al. Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA receptor-mediated synaptic input: correlation with dendritic spine density. J Neurosci. 1997 Mar 1;17(5):1848-59.

[2]. Mermelstein PG, et al. Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor. J Neurosci. 1996 Jan 15;16(2):595-604.

[3]. Girasole G, et al. 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest. 1992 Mar;89(3):883-91.

[4]. Woolley CS, et al. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci. 1992 Jul;12(7):2549-54.

[5]. Woolley CS, et al. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol. 1993 Oct 8;336(2):293-306.

3-Methyladenine | Hydrocortisone | Acetylcysteine(N-acetylcysteine) | Retinoic acid | Melatonine | Dinoprostone | Nicotinamide | Adenosine triphosphate | 4-Acetamidophenol | Prostaglandin E1 | Dehydroepiandrosterone | Corticosterone | Progesterone | Elacestrant dihydrochloride | Docosahexaenoic Acid

MOLECULAR FORMULA :

C18-H24-O2

MOLECULAR WEIGHT :

272.42

WISWESSER LINE NOTATION :

L E5 B666TTT&J E1 FQ OQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4200 ug/kg/12W-I

TOXIC EFFECTS :

Blood - changes in erythrocyte (RBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in uterine weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1400 mg/kg/13W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Endocrine - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

100 mg/kg/52W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

84 mg/kg/20W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

7 mg/kg/12W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

1200 ug/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Tumorigenic - tumors at site of application

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

360 mg/kg/15W-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Kidney, Ureter, Bladder - Kidney tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

2400 ug/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

58 mg/kg/82W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

40 mg/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - uterine tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

44 mg/kg/52W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Skin and Appendages - tumors Tumorigenic - tumor types after systemic administration not seen spontaneously

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

62500 ug/kg/36W-I

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Endocrine - tumors Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Kidney, Ureter, Bladder - tumors Lungs, Thorax, or Respiration - bronchiogenic carcinoma

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

30 mg/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Implant

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

34 mg/kg

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4400 ug/kg

SEX/DURATION :

female 31 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 gm/kg

SEX/DURATION :

female 4-8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - abortion

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

750 ug/kg

SEX/DURATION :

female 3 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

875 ug/kg

SEX/DURATION :

female 7 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4195 ng/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1280 ng/kg

SEX/DURATION :

male 8 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - other effects on male Endocrine - changes in luteinizing hormone

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2400 ng/kg

SEX/DURATION :

female 3 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

205 ug/kg

SEX/DURATION :

male 5 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

20 ug/kg

SEX/DURATION :

female 4 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

14400 ng/kg

SEX/DURATION :

female 5-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

10500 ng/kg

SEX/DURATION :

female 7 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

6250 ug/kg

SEX/DURATION :

female 16-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

15300 ng/kg

SEX/DURATION :

female 1-9 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) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

500 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

10 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

2 ug/kg

SEX/DURATION :

female 4 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

60 mg/kg

SEX/DURATION :

female 15-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

60 mg/kg

SEX/DURATION :

female 19-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - endocrine system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

1800 mg/kg

SEX/DURATION :

female 15-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

6720 ng/kg

SEX/DURATION :

male 14 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 Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

70 ug/kg

SEX/DURATION :

female 14 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Maternal Effects - other effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

4 ug/kg

SEX/DURATION :

female 14-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

1600 ug/kg

SEX/DURATION :

male 3 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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

3600 ng/kg

SEX/DURATION :

male 90 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

437 ug/kg

SEX/DURATION :

male 91 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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

262 ug/kg

SEX/DURATION :

male 91 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

5 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intrauterine

DOSE :

25 ng/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

219 mg/kg

SEX/DURATION :

female 52 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

667 ng/kg

SEX/DURATION :

female 3 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

4 mg/kg

SEX/DURATION :

female 5 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

10 mg/kg

SEX/DURATION :

male 5 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 - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1 mg/kg

SEX/DURATION :

male 5 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

20 mg/kg

SEX/DURATION :

female 19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - delayed effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

12 ug/kg

SEX/DURATION :

female 1-3 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

14400 ng/kg

SEX/DURATION :

female 4-6 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

204 ng/kg

SEX/DURATION :

female 3 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

9600 ug/kg

SEX/DURATION :

female 4-6 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

4800 ug/kg

SEX/DURATION :

female 4-6 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

4 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

1720 ug/kg

SEX/DURATION :

female 16-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10 mg/kg

SEX/DURATION :

female 1-6 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

TYPE OF TEST :

TCLo - Lowest published toxic concentration

ROUTE OF EXPOSURE :

Inhalation

DOSE :

30 ug/kg/30M

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 - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

60 ug/kg

SEX/DURATION :

male 8 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

50 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

90 ug/kg

SEX/DURATION :

female 6-11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

45 mg/kg

SEX/DURATION :

female 1-3 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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

45 ug/kg

SEX/DURATION :

female 5-7 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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

30 ug/kg

SEX/DURATION :

female 18-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

5 ug/kg

SEX/DURATION :

female 1-3 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

190 ug/kg

SEX/DURATION :

female 1-19 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) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

7692 ng/kg

SEX/DURATION :

female 9-10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

90 ug/kg

SEX/DURATION :

female 1-9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

900 ug/kg

SEX/DURATION :

female 1-9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

160 mg/kg

SEX/DURATION :

male 50 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

15 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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

14 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

126 ug/kg

SEX/DURATION :

female 48 week(s) pre-mating female 1-28 day(s) after conception

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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

900 ug/kg

SEX/DURATION :

male 26 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

1 mg/kg

SEX/DURATION :

lactating female 26-47 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

147 mg/kg

SEX/DURATION :

male 82 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :

Morphological transformation

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Sister chromatid exchange

TYPE OF TEST :

Sister chromatid exchange

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

DNA damage

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Unscheduled DNA synthesis

MUTATION DATA

TEST SYSTEM :

Bird - chicken

DOSE/DURATION :

25 mg/kg

REFERENCE :

BBRCA9 Biochemical and Biophysical Research Communications. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 112,425,1983 *** REVIEWS *** IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 21,279,1979 IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 6,99,1974 TOXICOLOGY REVIEW CLPTAT Clinical Pharmacology and Therapeutics (St. Louis). (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1960- Volume(issue)/page/year: 5,480,1964 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 TOXICOLOGY REVIEW CANCAR Cancer (Philadelphia). (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1948- Volume(issue)/page/year: 40,1825,1977 TOXICOLOGY REVIEW ACRSAJ Advances in Cancer Research. (Academic Press, Inc., 465 S. Lincoln Dr., Troy, MO 63379) V.1- 1953- Volume(issue)/page/year: 1,173,1953 TOXICOLOGY REVIEW CLECAP Clinical Endocrinology (Oxford). (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1972- Volume(issue)/page/year: 4,551,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 80407 No. of Facilities: 68 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 2770 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 80407 No. of Facilities: 151 (estimated) No. of Industries: 4 No. of Occupations: 5 No. of Employees: 9083 (estimated) No. of Female Employees: 8217 (estimated)