雌二醇

Estradiol 是一种类固醇性激素,对维持女性的生育能力和第二性征至关重要。

信号通路 >> 其他 >> 雌激素受体/ERR

研究领域 >> 内分泌

天然产物 >> 类固醇

Human Endogenous Metabolite

雌二醇在海马CA1锥体细胞中引起新的树突棘和突触。与树突棘和突触密度平行,雌二醇使NMDA受体结合增加46％。雌二醇还提高了CA1锥体细胞对NMDA受体介导的突触输入的敏感性,这种效应与雌二醇诱导的这些细胞顶端树突树中树突棘密度的增加相关[1]。雌二醇在急性解离和培养的新纹状体神经元中通过Ca2 +通道可逆地减少Ba2 +进入。雌二醇也可降低Ba2 +电流,但在大鼠新纹状体神经元中的效果明显低于雌二醇[2]。雌二醇剂量依赖性地抑制IL-1,TNF-α和IL-1以及TNF诱导的生物可测定的IL-6的产生。雌二醇阻断TNF诱导的IL-6产生和来自新生小鼠颅骨的原代骨细胞培养物中的破骨细胞发育[3]。

雌二醇在成年大鼠动情周期中在海马突触密度中起作用[4]。雌二醇可逆转卵巢切除引起的脊柱密度降低。雌二醇与黄体酮联合使用可提高脊柱密度2至6小时,但单独使用雌二醇可降低脊柱密度[5]。

简而言之，用一系列稀释的上清液培养B9细胞（5×103 /孔的96孔板），最终体积为100mL RPMI 1640，补充有5×10-5mol / L的2-巯基乙醇。在平底微量滴定板中，10％FBS，100U / mL青霉素和100μg/ mL链霉素。 42小时后，加入0.5μCi的[3H]胸苷。 6小时后，收获细胞并测定掺入的放射性。从用已知量的重组人或小鼠IL-6建立的标准曲线定量IL-6。抗IL-6单克隆抗体完全抑制B9细胞响应重组小鼠IL-6而增殖的能力。此外，我们确定B9细胞不响应IL-1或TNF而增殖，并且针对这两种细胞因子的抗体不响应IL-6对细胞增殖的影响。此外，确定雌二醇（17β-雌二醇）和在这些实验中用作载体的0.01％乙醇都不会对生物测定产生任何影响。

将成年雌性Sprague Dawley大鼠圈养在12小时光照/黑暗循环中，无限制地获取食物和水。将这些动物保持性腺完整（完整），卵巢切除并用苯甲酸雌二醇（OVX + E）处理，或切除卵形并用芝麻油载体（OVX + O）处理。先前已经显示在这些实验中使用的激素治疗方案导致CA1锥体细胞树突棘和突触密度的差异。在电生理学分析前6天，使用无菌外科手术在Metofane麻醉下对动物进行卵巢切除术。手术后，将动物单独圈养。在手术后第3天和第4天，在100μL芝麻油载体中向OSX注射（sc）10μg17β-雌二醇苯甲酸酯;每次注射时OVX + O动物接收油类载体。在第二次雌二醇或载体注射后48小时，通过断头处死动物并从其脑中制备海马切片。性腺完整的动物在动情周期的随机阶段被杀死。

[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-甲基腺嘌呤 | 氢化可的松 | N-乙酰半胱氨酸 | 维生素A酸； 视黄酸 | 褪黑素 | 地诺前列酮 | 烟酰胺 | 5'-三磷酸腺苷 | 对乙酰氨基苯酚 | 列腺素 E1 | 去氢表雄酮 | 肾上腺酮 | 孕酮； 黄体素； 黄体酮 | Elacestrant dihydrochloride | 二十二碳六烯酸

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)