Toluene diisocyanate, commercial grade (2,4 (80%)- and 2,6 (20%)-): Carcinogenic Potency Database

Toluene diisocyanate, commercial grade (2,4 (80%)- and 2,6 (20%)-) (CAS 26471-62-5)
Rats and Mice: Cancer Test Summary

Rat Target Sites		Mouse Target Sites		TD₅₀ (mg/kg/day)
Male	Female	Male	Female	Rat	Mouse
pan sub	liv mgl pan sub	no positive	liv vsc	33.7^m	250

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. mgl = mammary gland. pan = pancreas. sub = subcutaneous tissue. vsc = vascular system. 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.

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.

Toluene diisocyanate, commercial grade (2,4 (80%)- and 2,6 (20%)-): 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



TOLUENE DIISOCYANATE, COMMERCIAL GRADE (2,4 (80%)- AND 2,6 (20%)-)   26471-62-5
6114 M f b6c gav 24m25 TR251 :                       0    42.5mg  84.1mg
 MXB MXB        181.mg / P<.0005    97.9mg 612.mg   2/50    4/50   16/50          abc:hes; liv:hes,hpa; ova:hes; spl:hem; sub:hem. C
 liv MXA        215.mg / P<.008     103.mg 5.59gm   4/50    5/50   15/50                                              liv:hpa,hpc. S
 liv hpa        250.mg / P<.005  c  121.mg 2.38gm   2/50    3/50   12/50
 MXA MXA        580.mg * P<.008  c  236.mg 10.7gm   0/50    1/50    5/50              abc:hes; liv:hes; ova:hes; spl:hem; sub:hem.
 MXA hes        1.20gm * P<.04      362.mg n.s.s.   0/50    0/50    3/50                                abc:hes; liv:hes; ova:hes. S
 TBA MXB        305.mg * P<.5       66.0mg n.s.s.  26/50   31/50   30/50
 liv MXB        215.mg / P<.008     103.mg 5.59gm   4/50    5/50   15/50                                          liv:hpa,hpc,nnd.
 lun MXB        815.mg * P<.3       282.mg n.s.s.   0/50    3/50    1/50                                              lun:a/a,a/c.
6115 M m b6c gav 24m25 TR251 :                       0    84.9mg  168.mg
 TBA MXB        253.mg \ P<.3    -  75.0mg n.s.s.  22/50   27/50   (9/50)
 liv MXB        no dre   P=1.       371.mg n.s.s.  11/50   12/50    5/50                                          liv:hpa,hpc,nnd.
 lun MXB        1.92gm * P<.5       416.mg n.s.s.   2/50    5/50    2/50                                              lun:a/a,a/c.
6116 M f cd1 inh 24m24 2178                          0    .112mg  .336mg                                   Loeser;txlt,15,71-81;1983
 lun ade es     no dre   P=1.    -  .422mg n.s.s.  23/90   20/90  (11/89)
 lun car es     no dre   P=1.    -  1.22mg n.s.s.   4/90    2/90   (0/89)
 liv hpc es     no dre   P=1.    -  4.72mg n.s.s.   0/90    1/90    0/89
 liv hpa es     no dre   P=1.    -  6.31mg n.s.s.   5/90    0/90    1/89
 tba mix es     no dre   P=1.    -  .233mg n.s.s.  56/90   50/90  (22/89)
 tba mal es     no dre   P=1.    -  .344mg n.s.s.  30/90   27/90  (10/89)
 tba ben es     no dre   P=1.    -  .389mg n.s.s.  39/90   31/90  (14/89)
6117 M m cd1 inh 24m24 2178                          0    93.3ug  .280mg
 lun ade e      .300mg \ P<.02   -  .136mg n.s.s.  17/90   31/90  (22/90)
 liv hpc e      no dre   P=1.    -  .370mg n.s.s.  24/90   20/90  (12/90)
 liv hpa e      no dre   P=1.    -  .376mg n.s.s.  21/90   18/90   (9/90)
 lun car e      no dre   P=1.    -  2.45mg n.s.s.   6/90    4/90    4/90
 tba mix e      1.63mg \ P<.9    -  96.1ug n.s.s.  64/90   65/90  (43/90)
 tba mal e      no dre   P=1.    -  .186mg n.s.s.  39/90   39/90  (23/90)
 tba ben e      no dre   P=1.    -  1.08mg n.s.s.  38/90   44/90   29/90
6118 R f f34 gav 25m25 TR251 :                       0    42.1mg  83.3mg
 MXB MXB        25.4mg * P<.0005    14.7mg 57.3mg  19/50   26/50   24/50                   liv:nnd; mgl:fba; pni:isa; sub:fbs,fib. C
 mgl fba        33.4mg * P<.0005 c  18.5mg 87.1mg  15/50   21/50   18/50
 liv nnd        92.2mg * P<.0005 c  44.4mg 344.mg   3/50    8/50    8/50
 pni MXA        115.mg * P<.0005    51.9mg 383.mg   0/50    7/50    2/50                                              pni:isa,isc. S
 pni isa        135.mg * P<.002  c  58.3mg 523.mg   0/50    6/50    2/50
 adr phe        143.mg * P<.007     58.4mg 2.25gm   2/50    5/50    4/50                                                           S
 adr coa        174.mg * P<.007     67.1mg 3.51gm   2/50    3/50    5/50                                                           S
 sub fib        256.mg * P<.004     87.6mg 1.88gm   0/50    1/50    3/50                                                           S
 pit cra        77.3mg * P<.03      32.1mg n.s.s.  25/50   15/50   16/50                                                           S
 pit MXA        86.9mg * P<.05      33.7mg n.s.s.  27/50   15/50   16/50                                              pit:cra,crc. S
 sub MXA        206.mg / P<.02   c  73.7mg 43.3gm   2/50    1/50    5/50                                              sub:fbs,fib.
 cli adn        260.mg * P<.03      87.3mg n.s.s.   0/50    4/50    0/50                                                           S
 TBA MXB        25.1mg * P<.0005    13.6mg 82.8mg  45/50   36/50   34/50
 liv MXB        92.2mg * P<.0005    44.4mg 344.mg   3/50    8/50    8/50                                          liv:hpa,hpc,nnd.
6119 R m f34 gav 25m25 TR251 :                       0    21.0mg  41.7mg
 tes MXA        13.6mg * P<.002     6.93mg 71.9mg  48/50   35/50   30/50                                              tes:ict,itm. S
 MXB MXB        27.3mg * P<.0005    14.9mg 65.4mg   4/50    8/50   14/50                                     pan:ana; sub:fbs,fib. C
 sub MXA        34.1mg * P<.0005 c  18.0mg 88.4mg   3/50    6/50   12/50                                              sub:fbs,fib.
 pan ana        51.6mg * P<.0005 c  23.2mg 183.mg   1/50    3/50    7/50
 sub fib        56.0mg * P<.0005    25.2mg 239.mg   3/50    3/50    9/50                                                           S
 pit cra        76.4mg * P<.005     32.2mg 732.mg   3/50    4/50    7/50                                                           S
 sub fbs        92.4mg * P<.002     36.9mg 421.mg   0/50    3/50    3/50                                                           S
 pit MXA        83.7mg * P<.02      33.6mg 12.8gm   4/50    4/50    7/50                                              pit:cra,crc. S
 sub MXA        103.mg * P<.02      39.2mg n.s.s.   1/50    4/50    3/50                                          sub:fbs,ost,srn. S
 pni MXA        201.mg * P<.03      57.7mg n.s.s.   1/50    0/50    4/50                                              pni:isa,isc. S
 TBA MXB        18.4mg * P<.002     9.29mg 94.4mg  40/50   24/50   29/50
 liv MXB        196.mg * P<.4       42.4mg n.s.s.   7/50    3/50    4/50                                          liv:hpa,hpc,nnd.
6120 R f cdr inh 25m25 2178                          0    26.7ug  80.0ug                                   Loeser;txlt,15,71-81;1983
 liv hpc e      8.24mg * P<.3    -  1.34mg n.s.s.   0/104   0/105   1/105
 tba mal e      1.09mg * P<.5    -  .247mg n.s.s.  21/104  18/105  25/105
 tba ben e      no dre   P=1.    -  80.1ug n.s.s. 102/104  94/105  96/105
 tba mix e      no dre   P=1.    -  46.5ug n.s.s. 104/104  98/105 101/105
6121 R m cdr inh 26m26 2178                          0    18.7ug  56.0ug
 liv hpc e      no dre   P=1.    -  1.03mg n.s.s.   0/104   1/104   0/104
 tba mix e      no dre   P=1.    -  76.3ug n.s.s.  86/104  67/104  81/104
 tba ben e      no dre   P=1.    -  .103mg n.s.s.  77/104  64/104  71/104
 tba mal e      6.18mg * P<1.    -  .263mg n.s.s.  17/104  14/104  17/104

Mutagenicity in Salmonella: positive

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