Cyclophosphamide: Carcinogenic Potency Database

Cyclophosphamide (CAS 50-18-0)
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
hmo(B) nrv(B) tba ubl(B)	hmo(B) nrv(B) tba ubl(B)	lun	hmo lun	2.21^m,v	5.96^i,m

Monkeys: Cancer Test Summary

Monkey Target Sites		TD₅₀ (mg/kg/day)
Rhesus	Cynomulgus	Rhesus	Cynomulgus
no positive	no positive	no positive	no positive

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: hmo = hematopoietic system. lun = lung. nrv = nervous system. tba = all tumor bearing animals. ubl = urinary bladder. (B) = experimental results were reported only for both sexes together. 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: i = Intraperitoneal or intravenous injection are the only routes of administration with positive tests in the CPDB. 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. 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.

Cyclophosphamide: 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



CYCLOPHOSPHAMIDE  (endoxan) 50-18-0
1657 M f swi ipj 26w79 1336                          0    1.69mg  3.52mg   Skipper;srfr;1976/Weisburger;canc;1977/Prejean pers.comm.
 --- lys e      7.09mg * P<.003  +  2.50mg 61.3mg   3/154   1/19    4/16
 ski sqc e      11.1mg * P<.002     3.35mg 81.6mg   0/154   1/19    2/16
 lun mix e      6.15mg * P<.06   +  1.97mg n.s.s.  20/154   4/19    5/16
 liv lys e      no dre   P=1.       2.43mg n.s.s.   1/154   0/19    0/16
 tba mal e      1.78mg * P<.0005    .858mg 5.93mg  29/154   7/19   11/16
 tba mix e      1.78mg * P<.0005    .815mg 8.25mg  42/154   9/19   11/16
 tba ben e      no dre   P=1.       6.99mg n.s.s.  13/154   2/19    0/16
1658 M m swi ipj 26w79 1336                          0    1.72mg  3.52mg
 --- leu e      8.69mg * P<.004     2.63mg 84.8mg   0/101   2/22    1/9
 lun mix e      5.78mg * P<.07   +  1.78mg n.s.s.   9/101   5/22    2/9
 liv mix e      40.9mg * P<.5       4.60mg n.s.s.   2/101   0/22    1/9
 tba mix e      3.66mg * P<.09      1.15mg n.s.s.  28/101   8/22    5/9
 tba mal e      3.77mg * P<.05      1.27mg n.s.s.  19/101   7/22    4/9
 tba ben e      no dre   P=1.       4.42mg n.s.s.   9/101   1/22    1/9
1659 P b cym eat 11y13 2003 :                        0    3.46mg           Adamson;ossc,129-156;1982/Thorgeirsson 1994/Dalgard 1997/
                                                                                                      Thorgeirsson&Seiber pers.comm.
 bre pam w      1.04mg   P<.002     .245mg 16.0mg   0/32    2/3
 hea car w      8.30mg   P<.08      1.35mg n.s.s.   0/33    1/8
 lun car w      8.30mg   P<.08      1.35mg n.s.s.   0/33    1/8
 ute ley Ww     8.30mg   P<.08      1.35mg n.s.s.   0/33    1/8
 tba mix Ww     .818mg   P<.0005    .234mg 4.62mg   0/33    4/8
 tba ben Ww     .922mg   P<.0005    .240mg 7.54mg   0/33    3/8
 tba mal Ww     8.30mg   P<.08      1.35mg n.s.s.   0/33    1/8
1660 P b rhe eat 11y13 2003 :                        0    2.94mg
 liv fbl w      .436mg   P<.007     71.0ug 82.2mg   0/42    1/1
 liv hem w      .436mg   P<.007     71.0ug 82.2mg   0/42    1/1
 bre pam Ww     5.67mg   P<.05      .923mg n.s.s.   0/51    1/7
 ubl tcc w      8.28mg   P<.04      1.35mg n.s.s.   0/93    1/10
 tba mix Ww     1.75mg   P<.03      .341mg n.s.s.   5/108   3/12
 tba ben Ww     2.29mg   P<.08      .337mg n.s.s.   4/108   2/12
 tba mal Ww     6.54mg   P<.3       .769mg n.s.s.   2/93    1/10
1661 R m b46 ivj 12m24 1017                          0    .929mg                                      Schmahl;arzn,20,1461-1467;1970
 tba mix es     3.01mg   P<.04   +  1.12mg n.s.s.   7/65   10/36
 tba mal es     5.36mg   P<.1    +  1.62mg n.s.s.   4/65    6/36
 tba ben es     9.02mg   P<.3       2.12mg n.s.s.   3/65    4/36
1662 R b sda wat 32m36 1705                          0    .221mg  .450mg  .893mg  1.79mg                Schmahl;ijcn,23,706-712;1979
 ubl tcc ae     21.4mg * P<.0005 +  12.1mg 70.4mg   0/74    2/77    2/78    5/73    8/72
 --- mix ae     34.9mg * P<.2    +  12.1mg n.s.s.   0/74    3/77    6/78    6/73    4/72
 vse hms ae     65.6mg * P<.3       17.1mg n.s.s.   1/74    4/77    2/78    7/73    3/72
 liv tum ae     189.mg * P<.3       46.4mg n.s.s.   0/74    0/77    1/78    0/73    1/72
 ner ngs ae     no dre   P=1.    +  29.6mg n.s.s.   1/74    7/77    5/78    6/73    1/72
 tba mal ae     12.8mg * P<.05   +  5.20mg n.s.s.   9/74   22/77   27/78   26/73   22/72
1663 R f sda ipj 24m24 1134                          0    .571mg                                          Schmahl;zkko,86,77-84;1976
 mam mal es     1.70mg   P<.05      .660mg n.s.s.   3/33   10/36
 tba mal es     1.26mg   P<.02   +  .549mg n.s.s.   3/33   12/36
1664 R m sda ipj 25m25 1134                          0    .571mg
 liv hae es     no dre   P=1.       3.91mg n.s.s.   1/36    0/32
 tba mal es     2.87mg   P<.06   +  .956mg n.s.s.   1/36    5/32
1665 R m sda ivj 12m24 1703                          0    .929mg                                        Schmahl;zkko,81,211-215;1974
 mix hae e      3.38mg   P<.007     1.29mg 65.1mg   1/52    6/32
 tba mal e      1.41mg   P<.002  +  .656mg 6.75mg   6/52   14/32

Mutagenicity in Salmonella: positive
SMILES Code for Cyclophosphamide: ClCCN(CCCl)[P]1(=O)NCCCO1
InChI Code for Cyclophosphamide: InChI=1/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database

Chemical Structure for Cyclophosphamide:

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.

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.
A Screen version plot for use on a single computer screen, with the same data.
Excel version of the same data.
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