The Carcinogenic Potency Project

Hydrochlorothiazide (CAS 58-93-5)
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
no positive no positive 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.
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.

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.

Hydrochlorothiazide: 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



HYDROCHLOROTHIAZIDE   58-93-5
3222 M f b6c eat 24m24 TR357 :                       0    320.mg  638.mg
 TBA MXB        no dre   P=1.    -  846.mg n.s.s.  36/50   35/50   27/50
 liv MXB        no dre   P=1.       2.74gm n.s.s.   3/50    5/50    1/50                                          liv:hpa,hpc,nnd.
 lun MXB        no dre   P=1.       3.18gm n.s.s.   4/50    3/50    2/50                                              lun:a/a,a/c.
3223 M m b6c eat 24m24 TR357 :                       0    296.mg  589.mg
 liv MXA        1.23gm * P<.008  e  612.mg 24.4gm   7/50   10/50   21/50                                              liv:hpa,hpc.
 liv hpa        1.49gm * P<.007     747.mg 20.3gm   3/50    8/50   14/50                                                           S
 TBA MXB        3.82gm / P<.7       610.mg n.s.s.  30/50   20/50   34/50
 liv MXB        1.23gm * P<.008     612.mg 24.4gm   7/50   10/50   21/50                                          liv:hpa,hpc,nnd.
 lun MXB        19.8gm * P<.9       1.59gm n.s.s.   8/50    4/50    9/50                                              lun:a/a,a/c.
3224 R f f34 eat 24m25 TR357 :                       0    12.4mg  24.6mg  99.1mg
 TBA MXB        no dre   P=1.    -  88.0mg n.s.s.  49/50   39/50   39/50   37/50
 liv MXB        no dre   P=1.       n.s.s. n.s.s.   0/50    0/50    0/50    0/50                                  liv:hpa,hpc,nnd.
3225 R f f34 eat 24m30 1854                          0    44.0mg                             Lijinsky;txih,3,413-422;1987/pers.comm.
 pit mix        33.9mg   P<.0005    18.4mg 69.4mg   0/24   18/24
 adr phe        100.mg   P<.0005    46.7mg 285.mg   0/24    9/24
 liv hpc        1.11gm   P<.3       180.mg n.s.s.   0/24    1/24
 liv mix        no dre   P=1.       152.mg n.s.s.   4/24    3/24
 liv nnd        no dre   P=1.       194.mg n.s.s.   4/24    2/24
3226 R m f34 eat 24m25 TR357 :                       0    9.91mg  19.8mg  79.2mg
 TBA MXB        214.mg * P<.7    -  29.2mg n.s.s.  50/50   43/50   44/50   45/50
 liv MXB        771.mg * P<.3       143.mg n.s.s.   1/50    0/50    1/50    2/50                                  liv:hpa,hpc,nnd.
3227 R m f34 eat 24m30 1854                          0    46.2mg                             Lijinsky;txih,3,413-422;1987/pers.comm.
 tes car        35.6mg   P<.0005    19.3mg 72.9mg   0/24   18/24
 pit mix        71.3mg   P<.0005    36.1mg 169.mg   0/24   12/24
 adr phe        271.mg   P<.4       64.1mg n.s.s.   6/24    9/24
 liv hpc        no dre   P=1.       357.mg n.s.s.   1/24    0/24
 liv mix        no dre   P=1.       357.mg n.s.s.   3/24    0/24
 liv nnd        no dre   P=1.       357.mg n.s.s.   2/24    0/24
Mutagenicity in Salmonella: negative
SMILES Code for Hydrochlorothiazide: O=S1(=O)C2=C(C=C(C(=C2)S(=O)(=O)N)Cl)NCN1
InChI Code for Hydrochlorothiazide: InChI=1/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database
Chemical Structure for Hydrochlorothiazide: 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
For more information about this Web Page, contact slone.cpdb@gmail.com.
Last updated: October 3, 2007