4,4'-methylene-bis(2-chloroaniline): Carcinogenic Potency Database

4,4′-Methylene-bis(2-chloroaniline) (CAS 101-14-4)
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
ezy liv lun mgl vsc	liv lun mgl	no test	no test	19.3^m	no test

Dogs: Cancer Test Summary

Target Sites	TD₅₀ (mg/kg/day)
liv ubl	2.12

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: ezy = ear/Zymbal’s gland. liv = liver. lun = lung. mgl = mammary gland. ubl = urinary bladder. 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.

4,4′-Methylene-bis(2-chloroaniline): 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'-METHYLENE-BIS(2-CHLOROANILINE)  (3,3'-dichloro-4,4'-diaminodiphenylmethane, MOCA) 101-14-4
3899 D f beg eat  9y9  1030                          0    7.31mg                                             Stula;jept,1,31-50;1977
 ubl ptc emv    2.12mg   P<.003  +  .586mg 14.8mg   0/6     4/5
 liv hnd emv    3.72mg   P<.02   +  1.04mg n.s.s.   0/6     3/5
 mgl mix emv    no dre   P=1.    -  2.29mg n.s.s.   4/6     2/5
3900 R f cdr eat 67w67 192m                          0    50.0mg                               Stula;txap,31,159-176;1975/pers.comm.
 lun adc ef     42.3mg   P<.003  +  17.1mg 223.mg   0/21    6/21
 mgl adc ef     42.3mg   P<.003  +  17.1mg 223.mg   0/21    6/21
 liv hpa ef     142.mg   P<.1    -  34.9mg n.s.s.   0/21    2/21
 liv hpc ef     291.mg   P<.3    -  47.4mg n.s.s.   0/21    1/21
3901 R f cdr eat 24m24 192n                          0    50.0mg
 lun adc e      34.7mg   P<.0005 +  21.4mg 60.5mg   0/44   27/44
 liv hpc e      467.mg   P<.04   -  141.mg n.s.s.   0/44    3/44
 liv hpa e      708.mg   P<.1    -  174.mg n.s.s.   0/44    2/44
 liv cho e      1.43gm   P<.3    -  233.mg n.s.s.   0/44    1/44
3902 R m cdr eat 67w67 192m                          0    40.0mg
 liv hpc ef     15.3mg   P<.0005 +  7.53mg 38.0mg   0/21   11/21
 liv hpa ef     41.8mg   P<.007  +  15.8mg 498.mg   0/21    5/21
 lun adc ef     41.8mg   P<.007  +  15.8mg 498.mg   0/21    5/21
3903 R m cdr eat 24m24 192n                          0    40.0mg
 lun adc e      42.3mg   P<.0005 +  25.0mg 79.2mg   0/44   21/44
 liv hpc e      388.mg   P<.04   -  117.mg n.s.s.   0/44    3/44
 liv hpa e      388.mg   P<.04   -  117.mg n.s.s.   0/44    3/44
3904 R m cdr eat 18m24 1031m                         0    7.53mg  15.1mg  34.0mg                       Kommineni;jept,2,149-171;1979
 lun neo es     20.8mg * P<.0005 +  15.7mg 28.6mg   1/100  23/100  28/75   35/50
 lun mix es     29.2mg * P<.0005 +  21.5mg 41.1mg   0/100  14/100  20/75   31/50
 mgl adc es     87.6mg * P<.0005 +  53.7mg 174.mg   1/100   5/100   8/75   14/50
 liv hpc es     92.2mg Z P<.0005 +  56.8mg 164.mg   0/100   3/100   3/75   18/50
 zym car es     107.mg * P<.0005 +  61.4mg 288.mg   1/100   8/100   5/75   11/50
 --- ker es     144.mg Z P<.01      63.9mg 6.58gm   1/100   3/100   7/75   (1/50)
 ski sqc es     286.mg * P<.2       109.mg n.s.s.   1/100   4/100   7/75    2/50
 tba mix es     10.4mg * P<.0005    6.48mg 21.1mg  58/100  80/100  61/75   48/50
3905 R m cdr eat 18m24 1031n                         0    3.76mg  7.53mg  15.1mg
 lun neo efs    35.1mg * P<.0005 +  22.7mg 58.9mg   0/100   6/100  11/75   13/50
 lun mix efs    60.9mg * P<.0005 +  35.0mg 127.mg   0/100   3/100   7/75    8/50
 zym car efs    112.mg * P<.0005 +  54.5mg 298.mg   0/100   0/100   4/75    6/50
 liv hpc efs    124.mg Z P<.0005 +  58.3mg 337.mg   0/100   0/100   0/75    9/50
 mgl adc efs    162.mg * P<.006  +  70.1mg 1.51gm   0/100   1/100   3/75    3/50
 --- hes efs    138.mg * P<.02   +  58.8mg n.s.s.   1/100   2/100   4/75    4/50
 ski sqc efs    263.mg * P<.03      90.3mg n.s.s.   1/100   0/100   1/75    4/50
 tba mix efs    14.8mg * P<.0005    8.87mg 37.5mg  37/100  34/100  40/75   36/50
3906 R f wi2 eat 16m28 1018                          0    29.9mg                                        Grundmann;zkko,74,28-39;1970
 liv mix e      15.8mg   P<.0005 +  8.23mg 32.9mg   0/25   18/22
 mgl mix e      51.4mg   P<.003     22.5mg 352.mg   2/25   10/22
 lun mix e      104.mg   P<.005  +  39.4mg 827.mg   0/25    5/22
 tba mix e      11.6mg   P<.0005 +  5.53mg 25.9mg   2/25   20/22
3907 R m wi2 eat 16m30 1018                          0    22.5mg
 liv mix e      10.8mg   P<.0005 +  5.69mg 21.6mg   0/25   22/25
 lun mix e      59.5mg   P<.0005 +  26.8mg 192.mg   0/25    8/25
 tba mix e      9.09mg   P<.0005 +  4.52mg 18.4mg   0/25   23/25

Mutagenicity in Salmonella: positive
SMILES Code for 4,4′-Methylene-bis(2-chloroaniline): ClC1=C(C=CC(=C1)CC2=CC(=C(C=C2)N)Cl)N
InChI Code for 4,4′-Methylene-bis(2-chloroaniline): InChI=1/C13H12Cl2N2/c14-10-6-8(1-3-12(10)16)5-9-2-4-13(17)11(15)7-9/h1-4,6-7H,5,16-17H2
Source for SMILES and InChI: USEPA Distributed Structure-Searchable Toxicity (DSSTox) Database

Chemical Structure for 4,4′-Methylene-bis(2-chloroaniline):

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.

Carcinogenic Potency Database Project (CPDB) Home Page
For more information about this Web Page, contact slone.cpdb@gmail.com.
Last updated: October 3, 2007