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Carcinogenic Potency Project

Tamoxifen citrate (CAS 54965-24-1)
SMILES, InChI and Structure are below.
Rats and Mice: Cancer Test Summary
Rat Target Sites Mouse Target Sites TD50 (mg/kg/day)
Male Female Male Female Rat Mouse
liv liv tes ova 3.96m,P,v 4.39m

Key to the Table Above

Positivity: For each chemical with a positive (carcinogenic) experiment in the Carcinogenic Potency Database (CPDB), results are included on carcinogenic potency (TD50) in each species and target sites in males and females. Positivity is determined by an author’s opinion in a published paper. If all experimental results in the CDPB are negative in a sex-species group, “no positive” appears. If the CPDB has no experiments in the sex-species group, “no test” appears. The summary presents the strongest evidence of carcinogenicity in each group. If there are both positive and negative experiments in a sex-species, the negative results are ignored in this Summary Table.
Target Site Codes:   liv = liver. ova = ovary. tes = testes. Target sites are listed if any author of published experimental results concluded that tumors were induced in that organ by the test agent. If there is more than one positive experiment in a sex-species, target sites listed may be from more than one experiment, e.g. if liver and lung are both listed, then liver may have been a target in one experiment and lung in another.
TD50: Our standardized measure of carcinogenic potency, TD50, is the daily dose rate in mg/kg body weight/day to induce tumors in half of test animals that would have remained tumor-free at zero dose. Whenever there is more than one positive experiment in a species, the reported TD50 value is a Harmonic Mean calculated using the TD50 value from the most potent target site in each positive experiment.
Superscripts:   m = There is more than one positive experiment in the species, and TD50 values from each positive experiment are used in the calculation of the reported Harmonic mean of TD50. P = 100% of dosed animals had tumors at a target site in an experiment in this species. v = Variation is greater than ten-fold among statistically significant (two-tailed p<0.1) TD50 values from different positive experiments.

The Carcinogenic Potency Database (CPDB) is a unique and widely used international resource of the results of 6540 chronic, long-term animal cancer tests on 1547 chemicals. The CPDB provides easy access to the bioassay literature, with qualitative and quantitative analyses of both positive and negative experiments that have been published over the past 50 years in the general literature through 2001 and by the National Cancer Institute/National Toxicology Program through 2004. The CPDB standardizes the diverse literature of cancer bioassays that vary widely in protocol, histopathological examination and nomenclature, and in the published author’s choices of what information to provide in their papers. Results are reported in the CPDB for tests in rats, mice, hamsters, dogs, and nonhuman primates.

For each experiment, information is included on species, strain, and sex of test animal; features of experimental protocol such as route of administration, duration of dosing, dose level(s) in mg/kg body weight/day, and duration of experiment; experimental results are provided on target organ, tumor type, and tumor incidence; carcinogenic potency (TD50) and its statistical significance; shape of the dose-response, author’s opinion as to carcinogenicity, and literature citation.

Only tests with dosing for at least ¼ the standard lifespan of the species and experiment length at least ½ the lifespan are included in the CPDB. Only routes of administration with whole body exposure are included. Doses are standardized, average dose rates in mg/kg/day. A description of methods used in the CPDB to standardize the diverse literature of animal cancer tests is presented for: 1) Criteria for inclusion of experiments 2) Standardization of average daily dose levels and 3) TD50 estimation for a standard lifespan. See Methods for other details.

TD50 provides a standardized quantitative measure that can be used for comparisons and analyses of many issues in carcinogenesis. The range of TD50 values across chemicals that are rodent carcinogens is more than 100 million-fold. More than half the chemicals tested are positive in at least one experiment.

A plot of all results on each experiment in the CPDB for this chemical is presented below. These results are the source information for the Cancer Test Summary table above.

Tamoxifen citrate: All Experiments and Citations in CPDB
The definition of each code in the plot below will appear in a pop-up window when the field name in the header line is clicked, e.g., Strain, Site, Path. Each numbered line starts a new experiment and reports protocol information in black. Average daily dose-rates per kg body weight per day are in green. Remaining lines report experimental results in blue.
Abbreviations of fields in header line: # = the line number in the plot of all CPDB chemicals; Xpo = duration of dosing; Xpt = duration of experiment; Site = tissue; Path = tumor type; DR = dose-response; AuOp = author’s opinion about carcinogenicity; LoConf, UpConf = confidence limits (99%) on TD50; Inc = tumor incidence for each dose group.
See Guide to reading the plot for details on each field, using an example of one experiment.
See Help to improve readability, or to fit the plot onto the screen or a printed page.

Chemical (Synonym) CAS
# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
Site Path Notes   TD50  DR Pval    AuOp LoConf UpConf   Cntrl   1 Inc  2 Inc   3 Inc                                                        Brkly Code

TAMOXIFEN CITRATE 54965-24-1 5809 M f aps mix 65w65 2334m 0 5.00mg 50.0mg Tucker;stnd,125-161;1984 ova gca e 3.00mg \ P<.0005 + 1.40mg 8.79mg 0/23 9/25 (9/24) lun ade e no dre P=1. 78.2mg n.s.s. 0/23 1/25 0/24 liv tum e no dre P=1. 9.11mg n.s.s. 0/23 0/25 0/24 5810 M m aps mix 65w65 2334m 0 5.00mg 50.0mg tes ica e 8.18mg * P<.0005 + 4.66mg 15.4mg 0/25 2/24 21/25 liv mhp e no dre P=1. 81.0mg n.s.s. 0/25 1/24 0/25 lun ade e no dre P=1. 60.5mg n.s.s. 1/25 1/24 1/25 liv bhp e no dre P=1. n.s.s. 2/25 1/24 0/25 5811 M m aps mix 56w56 2334n 0 20.0mg tes ict rs 9.80mg P<.08 2.36mg n.s.s. 0/6 2/6 5812 M m aps mix 56w56 2334o 0 20.0mg tes ict rs 9.80mg P<.08 2.36mg n.s.s. 0/6 2/6 5813 M f b6c eat 24m24 2323m 0 21.0mg Martin;carc,18,2209-2215;1997/pers.comm. liv hpa Cv P<.09 - 24.7mg n.s.s. 0/15 2/15 lun alc v no dre P=1. - 64.9mg n.s.s. 0/15 0/15 ute ley v no dre P=1. - 64.9mg n.s.s. 0/15 0/15 5814 M f cb6 eat 52w52 2323n 0 23.8mg liv hpc Crv no dre P=1. - 40.5mg n.s.s. 0/33 0/33 5815 M f dba eat 52w52 2323o 0 23.7mg liv hpc Crv no dre P=1. - 40.3mg n.s.s. 0/33 0/33 5816 R f aap gav 20m25 2044 0 5.00mg 20.0mg 35.0mg Greaves;canr,53,3919-3924;1993 liv hpc e 17.0mg * P<.0005 + 12.7mg 23.4mg 0/104 6/52 37/52 37/52 liv hpa e * P<.0005 + 72.9mg 1/104 2/52 6/52 9/52 liv hcc e * P<.0005 0/104 0/52 4/52 5/52 liv blc e * P<.2 n.s.s. 1/104 0/52 2/52 2/52 liv cho e 2.26gm * P<.4 n.s.s. 0/104 0/52 1/52 0/52 5817 R m aap gav 20m25 2044 0 5.00mg 20.0mg 35.0mg liv hpc e 18.7mg * P<.0005 + 13.8mg 26.0mg 1/102 8/51 34/51 34/51 liv hpa e 47.9mg Z P<.0005 + 26.4mg 1/102 8/51 11/51 (8/51) liv hcc e * P<.0005 1.04gm 0/102 0/51 2/51 5/51 liv blc e 1.10gm * P<.08 n.s.s. 0/102 0/51 1/51 1/51 5818 R f cdr gav 52w52 2049m 0 11.3mg 22.6mg Hard;canr,53,4534-4541;1993/pers.comm. liv mix ek 1.44mg * P<.0005 + .939mg 2.27mg 0/18 24/36 24/24 liv hpa ek 1.68mg * P<.0005 1.10mg 2.65mg 0/18 21/36 24/24 liv hpc ek 2.12mg * P<.0005 + 1.39mg 3.40mg 0/18 16/36 24/24 5819 R f cdr gav 52w65 2049n 0 9.04mg 18.1mg liv mix e 3.86mg * P<.0005 + 2.56mg 6.23mg 0/21 16/30 22/33 liv hpa e 4.35mg * P<.0005 2.84mg 7.11mg 0/21 13/30 22/33 liv hpc e 4.62mg * P<.0005 + 3.01mg 7.77mg 0/21 14/30 20/33 5820 R f cdr gav 52w52 2116m 0 2.80mg 11.3mg 45.2mg Williams;carc,14,315-317;1993/pers.comm. liv hpa ekr 5.80mg * P<.002 + 2.43mg 29.2mg 0/10 0/10 5/10 2/4 liv hpc ekr 10.3mg * P<.002 + 3.43mg 59.0mg 0/10 0/10 1/10 3/4 5821 R f cdr gav 51w65 2116n 0 2.24mg 9.04mg 45.2mg liv hpa aer 7.77mg Z P<.002 + 2.93mg 35.9mg 0/12 0/27 5/12 (7/22) liv hpc aer 7.77mg Z P<.002 + 2.93mg 35.9mg 0/12 0/27 5/12 (6/22) 5822 R f f3t eat 86w86 2250r : 0 21.0mg Carthew;carc,16,1299-1304;1995/pers.comm. liv hpc Cr 4.18mg P<.0005 + 1.96mg 12.8mg 0/10 10/10 5823 R f lew eat 48w48 2250u : () 0 21.0mg liv hpc Cr 1.38mg P<.0005 + .658mg 3.59mg 0/10 10/10 5824 R f sda gav 39m39 BT5T 0 2.83mg Maltoni;anya,837,469-512;1997 liv hpc P<.05 49.7mg n.s.s. 0/100 3/100 ute fib P<.1 60.9mg n.s.s. 0/100 2/100 ute sar P<.7 58.6mg n.s.s. 2/100 3/100 liv hpa P<.3 81.0mg n.s.s. 0/100 1/100 vag sqc P<.3 81.0mg n.s.s. 0/100 1/100 ute sqc P<.3 81.0mg n.s.s. 0/100 1/100 ute esp no dre P=1. n.s.s. 13/100 0/100 ute car no dre P=1. 91.9mg n.s.s. 1/100 1/100 ute agf no dre P=1. 91.9mg n.s.s. 1/100 1/100 ute adc no dre P=1. n.s.s. 1/100 0/100 pit ade no dre P=1. n.s.s. 16/100 2/100 mam mal no dre P=1. n.s.s. 9/100 0/100 mam fbs no dre P=1. n.s.s. 1/100 0/100 mam ben no dre P=1. n.s.s. 36/100 0/100 mam adc no dre P=1. n.s.s. 8/100 0/100 adr phe no dre P=1. 46.5mg n.s.s. 17/100 12/100 tba mal 88.7mg P<.6 16.7mg n.s.s. 27/100 31/100 tba ben no dre P=1. 59.8mg n.s.s. 57/100 26/100 5825 R f sda gav 52w52 2043m 0 11.3mg 45.0mg Hirsimaki;artx,67,49-54;1993/pers.comm. liv hpc ekr 11.8mg * P<.02 + 3.43mg n.s.s. 0/5 0/5 3/5 5826 R f sda gav 52w65 2043n 0 9.04mg 36.0mg liv hpc er 18.9mg * P<.002 + 7.04mg 95.0mg 0/10 0/10 5/10 5827 R f sda gav 52w52 2159m 0 11.3mg 45.0mg Ahotupa;carc,15,863-868;1994 liv hpc er 7.56mg * P<.003 + 2.40mg 52.5mg 0/5 0/5 4/5 5828 R f sda gav 52w65 2159n 0 9.04mg 36.0mg liv hpc er 6.00mg * P<.0005 + 1.88mg 27.3mg 0/5 0/5 5/5 5829 R f sda gav 52w52 2633m 0 45.0mg Karki;artx,74,249-256;2000/pers.comm. liv mix Cer noTD50 P<.009 + n.s.s. 10.7mg 0/5 5/5 liv hpc Cer 4.79mg P<.005 + 1.33mg 42.7mg 0/5 4/5 5830 R f sda gav 52w65 2633n 0 36.0mg liv hpc Cer noTD50 P<.009 + n.s.s. 13.3mg 0/5 5/5 5831 R m sda gav 39m39 BT5T 0 2.83mg Maltoni;anya,837,469-512;1997 mam ben 96.4mg P<.05 34.8mg n.s.s. 1/100 6/100 liv hpc P<.1 60.9mg n.s.s. 0/100 2/100 mam adc P<.1 60.9mg n.s.s. 0/100 2/100 liv hpa P<.3 81.0mg n.s.s. 0/100 1/100 adr phe no dre P=1. 35.4mg n.s.s. 19/100 16/100 pan isa no dre P=1. n.s.s. 7/100 1/100 pit ade no dre P=1. 76.0mg n.s.s. 11/100 5/100 tes ldc no dre P=1. n.s.s. 4/100 0/100 tba mal P<.8 20.4mg n.s.s. 24/100 26/100 tba ben no dre P=1. 25.3mg n.s.s. 33/100 29/100 5832 R f sls gav 52w52 2247 0 2.86mg Machishi;carc,16,2965-2971;1995 liv hpc Cr no dre P=1. 1.18mg n.s.s. 0/8 0/8 5833 R f wil eat 49w49 2250s : () 0 21.0mg Carthew;carc,16,1299-1304;1995/pers.comm. liv hpc Cr 1.36mg P<.0005 + .637mg 4.18mg 0/10 10/10

SMILES Code for Tamoxifen citrate: O=C(O)CC(C(O)=O)(O)CC(O)=O.CN(C)COC3=CC=C(C=C3)\C(C2=CC=CC=C2)=C(CC)/C1=CC=CC=C1
InChI Code for Tamoxifen citrate: InChI=1/C25H27NO.C6H8O7/c1-4-24(20-11-7-5-8-12-20)25(21-13-9-6-10-14-21)22-15-17-23(18-16-22)27-19-26(2)3;7-3(8)1-6(13,5(11)12)2-4(9)10/h5-18H,4,19H2,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/b25-24-;
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database
Chemical Structure for Tamoxifen citrate: Chemical Structure
Source for structure: National Library of Medicine ChemIDPlus

See full CPDB Summary Table on 1547 chemicals. See Full CPDB for all results on 6540 experiments of 1547 chemicals.

A complete list of CPDB chemicals, which is searchable by name or by CAS number, is available here.

For a compendium of CPDB results organized by target organ, which lists all chemicals in each species that induced tumors in each of 35 organs, see Summary Table by Target Organ.

The CPDB is available in several formats that permit printing and downloading into spreadsheets and statistical databases.

  1. A plot of the CPDB presents results of 1547 experiments on 6540 chemicals in an easily readable format that has been used in publications of the CPDB.
  2. A Screen version plot for use on a single computer screen, with the same data.
  3. Excel version of the same data.
  4. Tab-separated versions of the same data, which can be easily read into databases.

A Supplementary Dataset gives details on dosing and survival for each experiment.

Relatively precise estimates of the lower confidence limit on the TD10 (LTD10) are readily calculated from the TD50 and its lower confidence limit, which are reported in the CPDB. For researchers and regulatory agencies interested in LTD10 values, we provide them in an Excel spreadsheet.

PDF versions of our publications of analyses using the CPDB are available, organized by year and by research topic.

Carcinogenic Potency Database Project (CPDB) Home Page
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Last updated: October 3, 2007

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