Isoniazid: Carcinogenic Potency Database

Isoniazid (CAS 54-85-3)
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 lun	mgl	liv lun mgl(B)	liv lun mgl(B)	150^m	27.1^m,v

Hamsters: Cancer Test Summary

Hamster Target Sites		TD₅₀ (mg/kg/day)
Male	Female	TD₅₀ (mg/kg/day)
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: liv = liver. lun = lung. mgl = mammary gland. (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: 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.

Isoniazid: 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



ISONIAZID  (INH) 54-85-3
3368 H f syg wat 28m28 170                           0    136.mg                                            Toth;ejca,5,165-171;1969
 for pam e      575.mg   P<.02   -  195.mg n.s.s.   2/54    5/22
 liv tum e      no dre   P=1.       1.37gm n.s.s.   0/72    0/36
 lun tum e      no dre   P=1.       1.37gm n.s.s.   0/72    0/36
3369 H m syg wat 30m30 170                           0    120.mg
 liv hem e      no dre   P=1.    -  425.mg n.s.s.   2/25    0/11
 lun tum e      no dre   P=1.       1.51gm n.s.s.   0/67    0/39
3370 M f akr wat 70w70 169                           0    200.mg                                            Toth;ijcn,2,413-420;1967
 lun tum e      89.6mg   P<.4    -  13.2mg n.s.s.   0/1     1/2
 liv tum        no dre   P=1.       560.mg n.s.s.   0/30    0/30
3371 M m akr wat 59w59 169                           0    167.mg
 lun tum e      202.mg   P<.2    -  32.6mg n.s.s.   0/9     1/6
 liv hem e      no dre   P=1.    -  155.mg n.s.s.   1/14    0/14
3372 M m amm gav 79w79 584m                          0    31.4mg  62.9mg                                  Bhide;ijcn,21,381-386;1978
 liv car r      159.mg \ P<.2       48.2mg n.s.s.   0/20    3/40   (0/40)
 lun car r      206.mg * P<.4       64.0mg n.s.s.   1/20    7/40    6/40
 mix car r      219.mg * P<.5    +  55.8mg n.s.s.   1/20   10/40    6/40
3373 M f c3h wat 72w72 1115                          0    200.mg                                       Toth;scie,152,1376-1377;1966a
 lun ade e      755.mg   P<.5       123.mg n.s.s.   0/4     1/12
3374 M m c3h wat 72w72 1115                          0    167.mg
 lun ade e      219.mg   P<.2       71.3mg n.s.s.   1/12    6/21
3375 M f cbc gav 36w84 1074                          0    34.1mg                                    Biancifiori;bjca,18,543-550;1964
 lun mix e      11.2mg   P<.0005 +  5.26mg 29.8mg   4/47   13/17
 liv hpt e      187.mg   P<.4    -  32.3mg n.s.s.   2/47    2/17
3376 M m cbc gav 36w74 1074                          0    32.2mg
 lun mix e      12.2mg   P<.0005 +  5.80mg 32.7mg   1/37   11/18
 liv hpt e      165.mg   P<.6    -  22.1mg n.s.s.   4/37    3/18
3377 M b nss gav 52w52 1425                          0    30.1mg                                       Pershin;vopr,XVIII,50-53;1972
 lun ade e      19.3mg   P<.0005 +  11.1mg 47.4mg   5/94   27/98
 mgl adc e      80.9mg   P<.06   +  30.1mg n.s.s.   2/94    8/98
 tba mix e      14.1mg   P<.0005 +  8.62mg 29.9mg   7/94   35/98
3378 M f swa wat 23m25 169                           0    100.mg  300.mg                                    Toth;ijcn,2,413-420;1967
 lun ade ae     386.mg * P<.0005 +  201.mg 1.37gm  14/108  17/39   13/32
 liv hem ae     no dre   P=1.    -  413.mg n.s.s.   3/88    0/30    0/18
3379 M f swa wat 80w80 1127                          0    200.mg                                         Toth;canr,26,1473-1475;1966
 lun mix e      153.mg   P<.0005 +  82.3mg 426.mg   9/68   23/47
 lun ade e      189.mg   P<.0005 +  97.3mg 635.mg   8/68   20/47
 lun adc e      435.mg   P<.01      165.mg 27.1gm   1/48    6/32
 liv hem e      no dre   P=1.    -  534.mg n.s.s.   3/48    1/32
3380 M m swa wat 86w87 169                           0    83.3mg  250.mg                                    Toth;ijcn,2,413-420;1967
 lun ade aes    104.mg \ P<.0005 +  49.2mg 437.mg  10/90   15/38   (3/14)
 liv mix aes    no dre   P=1.       555.mg n.s.s.   2/85    1/38    0/10
3381 M m swa wat 80w80 1127                          0    167.mg                                         Toth;canr,26,1473-1475;1966
 lun ade e      124.mg   P<.0005 +  67.5mg 311.mg   8/80   21/44
 liv hem e      no dre   P=1.    -  203.mg n.s.s.   2/35    0/10
3382 M b swi gav 97w97 1525                          0    27.6mg                                             Maru;clet,17,75-80;1982
 lun tum r      24.5mg   P<.0005 +  13.0mg 55.8mg   1/47   15/30
 liv tum r      no dre   P=1.       116.mg n.s.s.   7/47    1/30
3383 M b swi gav 95w95 1552                          0    27.6mg                                         Menon;zkko,105,258-261;1983
 lun adc r      28.8mg   P<.0005 +  17.2mg 80.7mg   1/20   27/60
3384 M f swi gav 83w83 584m                          0    37.7mg                                          Bhide;ijcn,21,381-386;1978
 lun car r      53.1mg   P<.0005    23.9mg 174.mg   0/30    8/30
 mix car r      53.1mg   P<.0005 +  23.9mg 174.mg   0/30    8/30
 liv car r      no dre   P=1.       149.mg n.s.s.   0/30    0/30
3385 M f swi gav 81w83 584n                          0    37.0mg
 mix car gr     39.9mg   P<.0005 +  19.3mg 105.mg   0/30   10/30
 lun car gr     88.6mg   P<.008     33.6mg 1.32gm   0/30    5/30
 liv car gr     88.6mg   P<.008     33.6mg 1.32gm   0/30    5/30
3386 M m swi gav 85w85 584m                          0    15.7mg  31.4mg
 mix car r      24.0mg * P<.0005 +  13.9mg 53.4mg   1/30    6/30   16/30
 lun car r      28.9mg * P<.0005    16.2mg 70.0mg   1/30    4/30   15/30
 liv car r      211.mg * P<.3       63.8mg n.s.s.   0/30    2/30    1/30
3387 M m swi gav 79w79 584o                          0    15.7mg  31.4mg
 mix car fr     25.7mg * P<.003  +  14.1mg 107.mg   0/15    6/25    9/25
 lun car fr     41.1mg * P<.007     20.0mg 420.mg   0/15    3/25    7/25
 liv car fr     88.8mg * P<.3       33.7mg n.s.s.   0/15    3/25    2/25
3388 M m swi gav 79w79 584r                          0    31.4mg
 mix car br     21.2mg   P<.005  +  10.1mg 158.mg   1/15   12/25
 lun car br     39.2mg   P<.05      15.4mg n.s.s.   1/15    8/25
 liv car br     71.3mg   P<.05      24.6mg n.s.s.   0/15    4/25
3389 R f cbs wat 48w64 157                           0    149.mg                                         Severi;jnci,41,331-349;1968
 mgl fba s      120.mg   P<.002  +  60.1mg 399.mg   0/22   11/40
 lun tum s      no dre   P=1.       465.mg n.s.s.   0/22    0/40
 liv tum s      no dre   P=1.       465.mg n.s.s.   0/22    0/40
3390 R m cbs wat 48w84 157                           0    99.4mg
 liv tum es     199.mg   P<.07   +  32.1mg n.s.s.   0/21    1/5
 lun mix s      1.07gm   P<.2    +  262.mg n.s.s.   0/28    2/49

Mutagenicity in Salmonella: positive
SMILES Code for Isoniazid: O=C(C1=CC=NC=C1)NN
InChI Code for Isoniazid: InChI=1/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10)
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database

Chemical Structure for Isoniazid:

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.

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Last updated: October 3, 2007