University of California Berkeley seal E. O. Lawrence Berkeley National Laboratory seal
The Carcinogenic Potency Project

4,4′-Methylenedianiline.2HCl (CAS 13552-44-8)
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 thy thy adr liv thy hmo liv thy 20m 32.4m

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:   adr = adrenal gland. hmo = hematopoietic system. liv = liver. thy = thyroid gland. 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.

4,4′-Methylenedianiline.2HCl: 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

4,4'-METHYLENEDIANILINE.2HCl 13552-44-8 3946 M f b6c wat 24m24 TR248 : 0 29.4mg 59.1mg MXB MXB 32.6mg * P<.0005 19.1mg 95.5mg 16/50 36/50 44/50 ---:mlh,mlm,mlu,mno; liv:hpa,hpc; thy:fca. C liv MXA 59.3mg * P<.0005 c 35.2mg 4/50 15/50 23/50 liv:hpa,hpc. --- MXA 64.7mg * P<.007 c 32.7mg 1.16gm 13/50 28/50 29/50 ---:mlh,mlm,mlu,mno. thy MXA / P<.0005 71.6mg 0/50 1/50 15/50 thy:fca,fcc. S liv hpc * P<.002 c 72.0mg 1/50 6/50 11/50 thy fca / P<.0005 c 80.7mg 0/50 1/50 13/50 liv hpa * P<.02 c 65.1mg n.s.s. 3/50 9/50 12/50 lun MXA * P<.04 n.s.s. 2/50 3/50 8/50 lun:a/a,a/c. S lun a/a * P<.04 n.s.s. 1/50 2/50 6/50 S TBA MXB 52.1mg * P<.05 22.1mg n.s.s. 32/50 47/50 47/50 liv MXB 59.3mg * P<.0005 35.2mg 4/50 15/50 23/50 liv:hpa,hpc,nnd. lun MXB * P<.04 n.s.s. 2/50 3/50 8/50 lun:a/a,a/c. 3947 M m b6c wat 24m24 TR248 : 0 24.5mg 49.5mg liv MXA 17.0mg \ P<.0005 9.07mg 65.8mg 17/50 43/50 (37/50) liv:hpa,hpc. S liv hpc 22.3mg \ P<.0005 c 12.1mg 75.5mg 10/50 33/50 (29/50) MXB MXB 28.7mg * P<.0005 17.1mg 78.7mg 12/50 36/50 34/50 adr:phe; liv:hpc; thy:fca. C adr phe 70.0mg * P<.0005 c 39.7mg 2/50 12/50 14/50 thy fca 88.4mg / P<.0005 c 51.4mg 0/50 3/50 16/50 TBA MXB 47.4mg * P<.07 19.1mg n.s.s. 37/50 47/50 45/50 liv MXB 17.0mg \ P<.0005 9.07mg 65.8mg 17/50 43/50 (37/50) liv:hpa,hpc,nnd. lun MXB no dre P=1. n.s.s. 13/50 12/50 4/50 lun:a/a,a/c. 3948 R f f34 wat 24m24 TR248 : 0 8.41mg 16.7mg thy MXB 22.0mg * P<.0005 13.9mg 38.4mg 0/50 5/50 22/50 thy:cca,fca. C thy MXA 27.2mg * P<.0005 16.6mg 50.3mg 0/50 4/50 19/50 thy:fca,fcc. S thy fca 33.5mg / P<.0005 c 19.5mg 66.1mg 0/50 2/50 17/50 thy cca 73.7mg * P<.007 c 34.7mg 0/50 3/50 6/50 thy MXA 70.0mg * P<.04 30.6mg n.s.s. 1/50 5/50 7/50 thy:cca,ccr. S TBA MXB * P<1. 10.6mg n.s.s. 43/50 48/50 49/50 liv MXB * P<.4 31.5mg n.s.s. 4/50 8/50 8/50 liv:hpa,hpc,nnd. 3949 R m f34 wat 24m24 TR248 : 0 7.36mg 14.7mg MXB MXB 12.5mg * P<.0005 8.33mg 22.0mg 1/50 12/50 29/50 liv:nnd; thy:fcc. C liv nnd 14.3mg * P<.0005 c 9.35mg 27.1mg 1/50 12/50 25/50 thy MXA 49.5mg * P<.006 24.4mg 1/50 4/50 10/50 thy:fca,fcc. S thy fcc 85.4mg * P<.003 c 36.9mg 0/50 0/50 7/50 TBA MXB no dre P=1. 15.3mg n.s.s. 45/50 42/50 40/50 liv MXB 14.1mg * P<.0005 9.22mg 26.6mg 1/50 13/50 25/50 liv:hpa,hpc,nnd.

Mutagenicity in Salmonella: positive
SMILES Code for 4,4′-Methylenedianiline.2HCl: C(C1=CC=C(C=C1)N)C2=CC=C(C=C2)N.[HCl].[HCl]
InChI Code for 4,4′-Methylenedianiline.2HCl: InChI=1/C13H14N2.2ClH/c14-12-5-1-10(2-6-12)9-11-3-7-13(15)8-4-11;;/h1-8H,9,14-15H2;2*1H
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database
Chemical Structure for 4,4′-Methylenedianiline.2HCl: 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 Specialized Information Services (
Last updated: October 3, 2007

PDF documents are best viewed with the free Adobe® Reader
Excel documents are best viewed with the free Excel® Viewer