*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : KH2387000
CHEMICAL NAME : Ethanamine,
2-(4-(1,2-diphenyl-1-butenyl)phenoxy)-N,N-dimethyl-,
(Z)-, 2-hydroxy- 1,2,3-propanetricarboxylate (1:1)
CAS REGISTRY NUMBER : 54965-24-1
LAST UPDATED : 199703
DATA ITEMS CITED : 39
MOLECULAR FORMULA : C26-H29-N-O.C6-H8-O7
MOLECULAR WEIGHT : 563.70
WISWESSER LINE NOTATION : L6TJ AYR&UY2&R& DO2N1&1 &QV1XQVQ1VQ
COMPOUND DESCRIPTOR : Tumorigen
Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* trans-1-(p-beta-Dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene citrate
* (Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine, citrate
(1:1)
* (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethylamine
citrate (1:1)
* ICI 46,474
* Kessar
* Noltam
* Nolvadex
* Tamofen
* Tamoxasta
* Tamoxifen citrate
* Z-Tamoxifen citrate
* Terimon
* Zynoplex
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 154 mg/kg/1Y-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - visual field changes
Sense Organs and Special Senses (Eye) - retinal changes (pigmentary
depositions, retinitis, other)
REFERENCE :
AJOPAA American Journal of Ophthalmology. (Ophthalmic Pub. Co., 435 N.
Michigan Ave., Suite 1415, Chicago, IL 60611) Series 3: V.1- 1918-
Volume(issue)/page/year: 104,185,1987
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 3600 ug/kg/9D-I
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Gastrointestinal - nausea or vomiting
Nutritional and Gross Metabolic - changes in calcium
REFERENCE :
AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New
York, NY 10022) V.1- 1946- Volume(issue)/page/year: 88,440,1990
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1190 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Lungs, Thorax, or Respiration - respiratory depression
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 575 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Lungs, Thorax, or Respiration - respiratory depression
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >5 gm/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 62500 ug/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
PBPSDY Pharmacological and Biochemical Properties of Drug Substances.
(American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC
20037) V.1- 1977- Volume(issue)/page/year: 2,355,1979
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 3100 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot,
POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
Volume(issue)/page/year: 13,101,1967
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 218 mg/kg
TOXIC EFFECTS :
Skin and Appendages - hair
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >5 gm/kg
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 62500 ug/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
PBPSDY Pharmacological and Biochemical Properties of Drug Substances.
(American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC
20037) V.1- 1977- Volume(issue)/page/year: 2,355,1979
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 2450 ug/kg/5W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in bladder weight
Blood - changes in platelet count
Related to Chronic Data - changes in prostate weight
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 127 mg/kg/26W-I
TOXIC EFFECTS :
Liver - changes in liver weight
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Blood - changes in leukocyte (WBC) count
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
** TUMORIGENIC DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 15512 mg/kg/1Y-I
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Liver - tumors
REFERENCE :
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House,
Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
Volume(issue)/page/year: 14,315,1993
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE : 1216 ug/kg
SEX/DURATION : female 22 week(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - uterus, cervix, vagina
Reproductive - Maternal Effects - menstrual cycle changes or disorders
Reproductive - Maternal Effects - other effects
REFERENCE :
AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co.,
11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920-
Volume(issue)/page/year: 158,1119,1988
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 200 ug/kg
SEX/DURATION : female 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 :
BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W.
Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year:
3,61,1970
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 90 ug/kg
SEX/DURATION : female 2-4 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 :
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot,
POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
Volume(issue)/page/year: 13,101,1967
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 300 ug/kg
SEX/DURATION : female 3 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - uterus, cervix, vagina
REFERENCE :
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot,
POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
Volume(issue)/page/year: 13,101,1967
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 24500 ug/kg
SEX/DURATION : male 35 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 :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
6,1,1980
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 100 ug/kg
SEX/DURATION : female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston
St., Baltimore, MD 21203) V.1- 1917- Volume(issue)/page/year:
87,542,1970
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 500 ug/kg
SEX/DURATION : female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - ovaries, fallopian tubes
Reproductive - Maternal Effects - uterus, cervix, vagina
REFERENCE :
ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston
St., Baltimore, MD 21203) V.1- 1917- Volume(issue)/page/year:
87,542,1970
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
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)
REFERENCE :
JOENAK Journal of Endocrinology. (Biochemical Soc. Book Depot, POB 32,
Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1939-
Volume(issue)/page/year: 37,83,1967
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 500 ug/kg
SEX/DURATION : female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston
St., Baltimore, MD 21203) V.1- 1917- Volume(issue)/page/year:
87,542,1970
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE : 3 ug/kg
SEX/DURATION : female 3 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - uterus, cervix, vagina
REFERENCE :
JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental
Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa,
Takatsu-ku, Kawasaki 211, Japan) V.1- 1975- Volume(issue)/page/year:
5,63,1979
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 5 mg/kg
SEX/DURATION : female 3-7 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)
REFERENCE :
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot,
POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
Volume(issue)/page/year: 13,101,1967
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 34 mg/kg
SEX/DURATION : female 10-26 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 Newborn - live birth index (measured after birth)
REFERENCE :
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot,
POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
Volume(issue)/page/year: 48,367,1976
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 14 mg/kg
SEX/DURATION : female 20-26 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
REFERENCE :
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot,
POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
Volume(issue)/page/year: 48,367,1976
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - rabbit
DOSE : 1500 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)
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
number of implants per female; total number of implants per corpora lutea)
REFERENCE :
BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W.
Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year:
14,451,1976
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - hamster
DOSE : 500 ug/kg
SEX/DURATION : female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
REFERENCE :
ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston
St., Baltimore, MD 21203) V.1- 1917- Volume(issue)/page/year:
87,542,1970
** MUTATION DATA **
TYPE OF TEST : DNA adduct
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - rat
DOSE/DURATION : 60 mg/kg/3D (Continuous)
REFERENCE :
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year:
52,1360,1992
TYPE OF TEST : Cytogenetic analysis
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Rodent - rat
DOSE/DURATION : 35 mg/kg
REFERENCE :
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House,
Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
Volume(issue)/page/year: 17,1051,1996
TYPE OF TEST : Sex chromosome loss and nondisjunction
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Rodent - rat
DOSE/DURATION : 35 mg/kg
REFERENCE :
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House,
Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
Volume(issue)/page/year: 17,1051,1996
TYPE OF TEST : Micronucleus test
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 1 mg/kg/10D (Intermittent)
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 368,109,1996
TYPE OF TEST : Cytogenetic analysis
ROUTE OF EXPOSURE : Oral
TEST SYSTEM : Rodent - mouse
DOSE/DURATION : 1 mg/kg/10D (Intermittent)
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 368,109,1996
TYPE OF TEST : DNA adduct
ROUTE OF EXPOSURE : Intraperitoneal
TEST SYSTEM : Rodent - hamster
DOSE/DURATION : 10 mg/kg
REFERENCE :
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut
Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year:
52,1360,1992
*** 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
PBPSDY Pharmacological and Biochemical Properties of Drug Substances.
(American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC
20037) V.1- 1977- Volume(issue)/page/year: 2,355,1979
*** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA ***
NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
NOES - National Occupational Exposure Survey (1983)
NOES Hazard Code - X4010
No. of Facilities: 66 (estimated)
No. of Industries: 1
No. of Occupations: 2
No. of Employees: 2077 (estimated)
No. of Female Employees: 1054 (estimated)
*** END OF RECORD ***