Phenobarbital: Carcinogenic Potency Database

Phenobarbital (CAS 50-06-6)
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	liv	liv	no positive	7.37^m,P,v

Hamsters: Cancer Test Summary

Hamster Target Sites		TD₅₀ (mg/kg/day)
Male	Female	TD₅₀ (mg/kg/day)
no positive	no test	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. 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.

Phenobarbital: 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



PHENOBARBITAL  (phenobarbitone) 50-06-6
4891 H m syg eat 52w52 1804                          0    46.0mg                                       Stenback;jnci,76,327-333;1986
 liv mix er     no dre   P=1.    -  23.7mg n.s.s.   0/5     0/10
4892 M m b6c wat 52w52 1477m                         0    83.3mg                                       Becker;canr,42,3918-3923;1982
 liv mix r      noTD50   P<.006  +  n.s.s. 11.5mg   5/16   16/16
4893 M m b6c eat 96w96 2398                          0    60.0mg                                  Nitta;jtxp,4,55-61;1991/pers.comm.
 liv hpc        20.4mg   P<.0005 +  12.3mg 37.4mg  10/46   43/50
 liv mix        21.1mg   P<.0005 +  12.5mg 40.2mg  12/46   43/50
 lun mix        no dre   P=1.       184.mg n.s.s.   9/46    7/50
4894 M f c3l eat 52w52 235m                          0    65.0mg                                      Peraino;jnci,51,1349-1350;1973
 liv tum r      noTD50   P<.0005 +  n.s.s. 5.36mg   5/39   29/29
4895 M f c3l eat 52w52 235n                          0    65.0mg
 liv tum r      12.2mg   P<.0005 +  5.45mg 46.2mg   1/16   10/16
4896 M m c3l eat 52w52 235m                          0    60.0mg
 liv tum r      4.18mg   P<.0005 +  1.52mg 19.0mg  25/37   35/36
4897 M m c3l eat 52w52 235n                          0    60.0mg
 liv tum r      4.46mg   P<.0005 +  1.56mg 21.4mg   7/17   16/17
4898 M m c5n wat 78w78 1477n                         0    83.3mg                                       Becker;canr,42,3918-3923;1982
 liv tum r      no dre   P=1.    -  155.mg n.s.s.   0/16    0/16
4899 M m cb6 eat 53w53 2084m                         0    60.0mg                                        Diwan;carc,13,1893-1901;1992
 liv hct r      no dre   P=1.       80.3mg n.s.s.   0/25    0/25
4900 M f cd1 wat 78w78 1582                          0    100.mg                                       Miller;canr,43,1124-1134;1983
 liv hpt        559.mg   P<.1       137.mg n.s.s.   0/30    2/30
 lun ade        no dre   P=1.       210.mg n.s.s.   1/30    1/30
4901 M m cen wat 52w52 1477o                         0    83.3mg                                       Becker;canr,42,3918-3923;1982
 liv mix kr     noTD50   P<.3       n.s.s. n.s.s.   5/8     8/8
4902 M m cen wat 52w52 1477r                         0    83.3mg
 liv mix r      noTD50   P<.09   +  n.s.s. n.s.s.  10/16   16/16
4903 M m cen eat 52w52 1992                          0    60.0mg                                    Fullerton;carc,11,1301-1305;1990
 liv mix r      6.67mg   P<.0005 +  3.75mg 13.3mg   2/30   24/30
 liv hpc r      7.78mg   P<.0005 +  4.47mg 14.7mg   0/30   22/30
 lun mix r      139.mg   P<.4       28.5mg n.s.s.   2/30    4/30
 liv hpa r      no dre   P=1.       44.9mg n.s.s.   2/30    2/30
4904 M m chg eat 52w52 1891                          0    24.0mg                                       Mizutani;clet,39,233-237;1988
 liv tum r      5.56mg   P<.002  +  2.31mg 38.5mg  42/139  14/21
4905 M m chh eat 52w52 1891                          0    24.0mg
 liv tum r      noTD50   P<.09      n.s.s. n.s.s.  42/56   31/31
4906 M m d2b eat 26m26 2227                          0    60.0mg                                 Diwan;clet,89,29-35;1995/pers.comm.
 liv hpa er     42.4mg   P<.0005 +  21.0mg 161.mg   9/29   23/30
 liv mix er     42.4mg   P<.0005 +  21.0mg 161.mg   9/29   23/30
 liv hpb er     101.mg   P<.0005 +  50.1mg 250.mg   0/29   11/30
 liv hpc er     199.mg   P<.02   +  78.1mg n.s.s.   1/29    7/30
4907 M m dba eat 53w53 2084n                         0    60.0mg                                        Diwan;carc,13,1893-1901;1992
 liv hpa r      61.2mg   P<.02      21.1mg n.s.s.   0/25    4/25
4908 R f aci eat 67w67 1448                          0    25.0mg                                        Uchida;zkko,100,231-238;1981
 liv tum        no dre   P=1.    -  25.7mg n.s.s.   0/10    0/12
 tba mix        81.7mg   P<.3       13.3mg n.s.s.   0/10    1/12
4909 R m aci eat 67w67 1448                          0    20.0mg
 liv tum        no dre   P=1.    -  20.5mg n.s.s.   0/10    0/12
 tba mix        no dre   P=1.       15.3mg n.s.s.   4/10    1/12
4910 R f f34 wat 76w76 1689                          0    28.6mg                                        Diwan;jnci,75,1099-1105;1985
 liv hpa er     99.2mg   P<.3       16.1mg n.s.s.   0/10    1/10
4911 R f f34 eat 89w91 2219                          0    24.4mg                         Zavanella;carc,15,2531-2539;1994/pers.comm.
 liv hct r      46.5mg   P<.06      12.5mg n.s.s.   1/24    3/11
4912 R m f34 wat 76w76 1689                          0    25.0mg                                        Diwan;jnci,75,1099-1105;1985
 liv hpa er     86.8mg   P<.3       14.1mg n.s.s.   0/10    1/10
4913 R m f34 wat 72w72 1690                          0    25.0mg                                          Diwan;jnci,74,509-516;1985
 liv hpa e      45.0mg   P<.08      11.0mg n.s.s.   0/13    2/12
4914 R m f34 eat 17m24 1803                          0    14.0mg                                     Shivapurkar;carc,7,547-550;1986
 liv nnd e      no dre   P=1.    -  38.2mg n.s.s.   2/28    2/28
4915 R m f34 eat 52w52 1834                          0    20.0mg                           Leonard;jnci,79,1313-1319;1987/pers.comm.
 liv mix er     no dre   P=1.    -  20.6mg n.s.s.   0/20    0/20
4916 R m f34 eat 71w71 1951                          0    20.0mg                                          Diwan;carc,10,189-194;1989
 liv hpt e      no dre   P=1.       28.8mg n.s.s.   0/15    0/15
4917 R m f34 eat 71w71 2084m                         0    20.0mg                                        Diwan;carc,13,1893-1901;1992
 liv hpa        76.6mg   P<.1       18.8mg n.s.s.   0/25    2/25
4918 R m f34 eat 71w71 2109                          0    20.0mg                                          Diwan;artx,66,413-422;1992
 liv hpa e      44.6mg   P<.04      11.0mg n.s.s.   0/27    2/15
4919 R m f34 eat 89w91 2219                          0    19.6mg                         Zavanella;carc,15,2531-2539;1994/pers.comm.
 liv hct r      328.mg   P<.8       22.7mg n.s.s.   1/21    1/13
4920 R m f34 eat 72w72 2322                          0    20.0mg                                            Diwan;carc,17,37-43;1996
 liv hpa        115.mg   P<.3       18.7mg n.s.s.   0/18    1/18
4921 R m f34 eat 78w78 2535                          0    20.0mg                             Allen;carc,18,1103-1107;1997/pers.comm.
 liv tum e      no dre   P=1.    -  64.9mg n.s.s.   0/28    0/28
4922 R m f34 eat 72w72 2657                          0    20.0mg                                            Diwan;ijtx,20,81-87;2001
 liv hpa        75.5mg   P<.3    -  12.3mg n.s.s.   0/12    1/12
4923 R m f3d wat 40w78 2565                          0    14.7mg                           Hasegawa;clet,123,185-191;1998/pers.comm.
 liv tum e      no dre   P=1.    -  25.5mg n.s.s.   0/10    0/15
4924 R m fis eat 39w78 1653                          0    10.0mg                                          Carr;carc,5,1583-1590;1984
 liv tum e      no dre   P=1.    -  6.96mg n.s.s.   0/12    0/6
 tba tum e      no dre   P=1.    -  6.96mg n.s.s.   0/12    0/6
4925 R f sda ipj 24m24 1134                          0    .286mg                                          Schmahl;zkko,86,77-84;1976
 tba mal es     no dre   P=1.    -  1.25mg n.s.s.   3/33    1/30
4926 R m sda ipj 24m24 1134                          0    .286mg
 liv hae es     no dre   P=1.       1.88mg n.s.s.   1/36    0/32
 tba mal es     54.7mg   P<1.    -  n.s.s. n.s.s.   1/36    1/32
4927 R m wis eat 59w59 2155                          0    50.0mg                        Kraupp-Grasl;canr,51,666-671;1991/pers.comm.
 liv mix e      303.mg   P<.4       49.4mg n.s.s.   0/18    1/28
 tba tum e      9.22mg   P<.0005    5.07mg 20.4mg   1/18   20/28
4928 R f wsh wat 56w56 2659                          0    57.1mg                                          White;carc,22,553-557;2001
 liv tum Cr     no dre   P=1.    -  34.1mg n.s.s.   0/10    0/10

Mutagenicity in Salmonella: positive
SMILES Code for Phenobarbital: O=C1C(C2=CC=CC=C2)(C(=O)NC(=O)N1)CC
InChI Code for Phenobarbital: InChI=1/C12H12N2O3/c1-2-12(8-6-4-3-5-7-8)9(15)13-11(17)14-10(12)16/h3-7H,2H2,1H3,(H2,13,14,15,16,17)
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database

Chemical Structure for Phenobarbital:

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