Tamoxifen

Tamoxifen is a selective estrogen receptor modulator (SERM) which blocks estrogen action in breast cells and can activate estrogen activity in other cells, such as bone, liver, and uterine cells.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Others >> Estrogen Receptor/ERR

Research Areas >> Cancer

Estrogen receptor[1]

Tamoxifen shows strong inhibition of MCF-7 cells (EC50=1.41 μM) and to a lesser extent the T47D cells (EC50=2.5 μM) but does not affect the MDA-MB-231 cells[2].

The Tamoxifen-inducible gene knockout strategy has clear advantages in that expression of a gene can be ablated in adult mice at will in a tissue specific manner. To study the role of Med1 in adult heart, 7-week old TmcsMed1-/- mice are given a daily Iintraperitoneal injection of Tamoxifen at a dose of 65 mg/kg for 5 days and killed at selected intervals thereafter. qPCR analysis of RNA shows that the Med1 expression begin to decrease after 3 days of Tamoxifen injection (about 70% decrease), and by 5 days of injection, Med1 expression is almost non-detectable in the heart. Tamoxifen-inducible cardiac-specific disruption of Med1 (TmcsMed1-/-) in adult mice causes dilated cardiomyopathy[3].

Mice[3] Seven-week old TmcsMed1-/- mice and the wild-type littermates are then administered Tamoxifen intraperitoneally at a daily dose of 65 mg/kg body weight for 5 days and then killed at selected intervals after initiation of Tamoxifen treatment. For each experiment 3 to 5 mice for control and csMed1-/- are used. To obtain survival curve 41 csMed1-/- and 41 csMed1fl/fl mice are used. Thirteen TmcsMed-/- mice and the same number of littermates are used for the survival curve experiments using Tamoxifen inducible model. The specific criteria for animal euthanasia included absence of food or water intake, slow or no mobility, weak or absence of heart beat, absence of palpitation of the chest as well as absence of respiratory movement. Mice are euthanized by intraperitoneal pentobarbital injection at the dose of 150mg/kg body weight to minimize suffering.

[1]. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998 Nov 26;339(22):1609-18.

[2]. Hawariah A, et al. In vitro response of human breast cancer cell lines to the growth-inhibitory effects of styrylpyrone derivative (SPD) and assessment of its antiestrogenicity. Anticancer Res. 1998 Nov-Dec;18(6A):4383-6.

[3]. Jia Y, et al. Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal DilatedCardiomyopathy in Mice. PLoS One. 2016 Aug 22;11(8):e0160755.

[4]. Wang Y, et al. Evaluation of the safety and tolerability of tamoxifen for ischemia-incited renal injury in mice. Am J Transl Res. 2018 Jul 15;10(7):2184-2194. eCollection 2018.

Elacestrant dihydrochloride | AZD9496 | Kaempferol | XCT 790 | Estrone | GDC-0810 | (20S)-Protopanaxatriol | 27-Hydroxycholesterol | Diethylstilbestrol | PHTPP | 2,3-bis(4-hydroxyphenyl)propionitrile | 4',7-Isoflavandiol | cholesterol | Chrysin | Endoxifen (Z-isomer hydrochloride)

MOLECULAR FORMULA :

C26-H29-N-O

MOLECULAR WEIGHT :

371.56

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

5600 ug/kg/1W-I

TOXIC EFFECTS :

Skin and Appendages - breast

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

200 ug/kg/D

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Blood - leukopenia Blood - thrombocytopenia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

5600 ug/kg/2W-I

TOXIC EFFECTS :

Blood - normocytic anemia Musculoskeletal - joints

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

700 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2150 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

575 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 :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

330 mg/kg/30D-I

TOXIC EFFECTS :

Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Biochemical - Metabolism (Intermediary) - other proteins

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1001 mg/kg/13W-I

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Biochemical - Metabolism (Intermediary) - other proteins

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6825 mg/kg/65W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4 mg/kg

SEX/DURATION :

lactating female 5 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - postpartum

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2250 ug/kg

SEX/DURATION :

female 1-3 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 :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

6 mg/kg

SEX/DURATION :

female 9-11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - other effects to embryo

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

50 ug/kg

SEX/DURATION :

female 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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2250 ug/kg

SEX/DURATION :

female 1-3 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 :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

100 ug/kg

SEX/DURATION :

female 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 :

500 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 :

Subcutaneous

DOSE :

75 ug/kg

SEX/DURATION :

female 3 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

3500 ug/kg

SEX/DURATION :

female 14 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Maternal Effects - other effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2400 ug/kg

SEX/DURATION :

female 1-3 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 :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 mg/kg

SEX/DURATION :

female 3 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - oogenesis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

50 ug/kg

SEX/DURATION :

female 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 :

7200 ug/kg

SEX/DURATION :

female 1-3 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 :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

25 mg/kg

SEX/DURATION :

female 5 day(s) after conception

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 :

3250 ug/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) 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 :

6 mg/kg

SEX/DURATION :

female 1-3 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 :

Morphological transformation

TYPE OF TEST :

DNA adduct

TYPE OF TEST :

DNA adduct

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Mutation in mammalian somatic cells

TYPE OF TEST :

DNA adduct

MUTATION DATA

TEST SYSTEM :

Rodent - mouse

DOSE/DURATION :

480 umol/kg/4D (Continuous)

REFERENCE :

CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 13,2197,1992 *** 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: 66,253,1996 IARC Cancer Review:Human 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: 66,253,1996 IARC Cancer Review:Group 1 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: 66,253,1996 TOXICOLOGY REVIEW JTEHD6 Journal of Toxicology and Environmental Health. (Hemisphere Pub., 1025 Vermont Ave., NW, Washington, DC 20005) V.1- 1975/76- Volume(issue)/page/year: 4,363,1978 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 : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X7229 No. of Facilities: 9 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 339 (estimated) No. of Female Employees: 170 (estimated)