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The Carcinogenic Potency Project

Guide to the Individual Chemical Web Pages of the Carcinogenic Potency Database (CPDB)

This guide to the plot section of the Individual Chemical Web Pages uses an example of one experiment on Phenolphthalein to describe the fields in the plot, the codes and conventions, and pop-up windows that provide definitions of codes.
The plot has 3 sections: 1) chemical information (red), 2) a single line containing information on experimental protocol (black), and 3) for each tissue tumor combination reported, information on tumor incidence, carcinogenic potency, statistical significance and dose response (blue). An experiment is defined in the CPDB as the control and dose groups under a set of experimental conditions that includes one species, sex, and strain of animal that was administered a test agent by a given route for a given experiment length. Experiments are listed under the name of the test chemical, and each experiment is identified by a unique number. The codes in the CPDB are mnemonic for ease of use.
To facilitate the use of this guide, including the pop-up windows, an example of one experiment of Phenolphthalein is repeated at the top of each page.


Chemical (Synonym) CAS
[1]           [2]  [3]
PHENOLPHTHALEIN   77-09-8

# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
[4][5]    [6]   [7]   [8]   [9]    [10]  [11]                  [12]    [13]    [14]                         [15]
4958 M     f    b6c   eat  24m24   TR465   :       0    388.mg  777.mg  1.55gm
Site Path Notes TD50 DR Pval AuOp LoConf UpConf Cntrl 1 Inc 2 Inc 3 Inc Brkly Code [16][17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
MXB MXB 508.mg Z P<.0005 296.mg 1.53gm 15/50 33/50 40/50 (36/50) ---:hcs,lmt,mly; ova:sxb,sxs. C --- mly 748.mg Z P<.003 c 394.mg 4.88gm 15/50 28/50 33/50 (25/50) --- lmt 1.61gm Z P<.003 c 859.mg 8.28gm 1/50 9/50 10/50 (7/50) ova MXA 1.90gm Z P<.003 c 1.00gm 8.68gm 0/50 7/50 6/50 (5/50) ova:sxb,sxs. --- hcs 4.08gm * P<.0005 c 2.27gm 11.7gm 0/50 2/50 7/50 7/50 TBA MXB 1.74gm * P<.2 642.mg n.s.s. 40/50 39/50 47/50 43/50 liv MXB no dre P=1. 3.96gm n.s.s. 21/50 3/50 6/50 (2/50) liv:hpa,hpb,hpc. lun MXB 9.19gm * P<.3 2.56gm n.s.s. 6/50 5/50 6/50 8/50 lun:a/a,a/c.
Using the above example of a single experiment, this guide identifies each field with a set of numbers [1] – [30]. The first line (columns [1] – [3]) provides chemical information, the second line (columns [4] – [15]) provides experimental protocol information and several lines (columns [16] – [30]) provide information on experimental results for each tissue-tumor combination. In the example, as in all Individual Chemical Web Pages, pop-up windows appear when the underlined names of fields in the header lines are clicked, e.g., Species, Strain, DR, Pval. This feature permits you to see all definitions on the computer screen when using an Individual Chemical Web Page or when reading this guide. See Help to improve readability of this Guide by adjusting text size or fittin results onto the screen. It may be useful to print this guide as well, and refer to it when using an Individual Chemical Web Page; in order to fit the plot on a printed page you may need to change your settings in “Page Setup” to landscape and/or a lower scaling value.

Chemical information (red color)
[1], [2] The chemical name is indicated under [1] in the top line for a set of experiments. In the plot, common synonyms can follow the name under [2]. In the example, there is no synonym for Phenolphthalein.
[3] The Chemical Abstracts Service Registry Number (CAS); in the example, the CAS is 77-09-8.

Experimental protocol information (black)
[4] # is the unique plot number for each experiment, i.e., one sex of one species from one research report. In the Phenolphthalein example, the line number is 4958, which corresponds to the number in the plot of all CPDB chemicals combined, including results of 6540 experiments. Each consecutive number in the plot indicates a separate experiment.
[5] The Species (Click for pop-up.) used in the example is indicated under [5] as “M”. The letter “M” refers to mice, “R” to rats, “H” to hamsters, “D” to dogs, “N” to prosimians, and “P” to monkeys.


Chemical (Synonym) CAS
[1]           [2]  [3]
PHENOLPHTHALEIN   77-09-8

# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
[4][5]    [6]   [7]   [8]   [9]    [10]  [11]                  [12]    [13]    [14]                         [15]
4958 M     f    b6c   eat  24m24   TR465   :       0    388.mg  777.mg  1.55gm
Site Path Notes TD50 DR Pval AuOp LoConf UpConf Cntrl 1 Inc 2 Inc 3 Inc Brkly Code [16][17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
MXB MXB 508.mg Z P<.0005 296.mg 1.53gm 15/50 33/50 40/50 (36/50) ---:hcs,lmt,mly; ova:sxb,sxs. C --- mly 748.mg Z P<.003 c 394.mg 4.88gm 15/50 28/50 33/50 (25/50) --- lmt 1.61gm Z P<.003 c 859.mg 8.28gm 1/50 9/50 10/50 (7/50) ova MXA 1.90gm Z P<.003 c 1.00gm 8.68gm 0/50 7/50 6/50 (5/50) ova:sxb,sxs. --- hcs 4.08gm * P<.0005 c 2.27gm 11.7gm 0/50 2/50 7/50 7/50 TBA MXB 1.74gm * P<.2 642.mg n.s.s. 40/50 39/50 47/50 43/50 liv MXB no dre P=1. 3.96gm n.s.s. 21/50 3/50 6/50 (2/50) liv:hpa,hpb,hpc. lun MXB 9.19gm * P<.3 2.56gm n.s.s. 6/50 5/50 6/50 8/50 lun:a/a,a/c.
[6] The Sex (Click Sex in header for pop-up of definitions.) is indicated by “f” for female, “m” for male. under [6]. Occasionally an author in the literature reported data only for both sexes together, and in these cases the code “b” used is for both.
[7] The Strain or Stock of animal (Click Strain in header for pop-up of full names.) is reported as a three-letter-code under [7]. In the example, the mouse strain is indicated by b6c for B6C3F1, which is described in the pop-up. Strains are named just as they are in the original publication. No attempt has been made to standardize the strain names; therefore, if different nomenclature is used by two authors who actually tested the same strain, then two different codes are used in the database.
[8] The Route of administration is indicated in the header line by “Route” under [8]. (Click Route in header for pop-up of definitions.) In the Phenolphthalein example, “eat” stands for administration in the diet. Route codes are mnemonic like “gav” for gavage.
[9] The Exposure and Experiment time (Click on Xpo+Xpt for details.) are indicated under [9]. Exposure time is the period over which the test agent is administered; if administration was 5 times a week for 40 weeks, for example, the exposure time is 40 weeks. Experiment time is the total time on test; it is not the age of the animals. It is measured from the start of the experiment to the time of terminal sacrifice or death of the last dosed animal. In the example, the mice were dosed for 24 months, and the experiment ended at 24 months.
[10] The unique Paper Number (under PaperNum) assigned to each research report in the CPDB is indicated under [10]. For NCI/NTP bioassays, this is the Technical Report number, TR465 in the example. See NCI/NTP Bibliography for a list of Technical Reports, with Report Number and year of publication.
[11] Following the PaperNum, codes may appear. In the example, “:” indicates that TD50 is estimated with lifetable data, as in all NCI/NTP bioassays. Other codes are used to indicate pooled controls, kidney step sections, or details of exposure or experiment length. If none of these is relevant for the given experiment, no codes will appear after the paper number. (Click PaperNum in header for descriptions of these codes.)
[12] – [14] Beginning in [12] we report the average daily dose rate (green color) in mg/kg body weight (wt) for the length of the experiment as calculated in the CPDB for each dose group in the experiment. For brevity we have used “mg” instead of “mg/kg bd wt/d.” In the example, there are three dose levels 388 mg/kg, 777 mg/kg, and 1.55 gm/kg. For a description of the standard values and methods used in estimation of the average daily dose-rate, see CPDB Methods.
[15] Literature Reference is an abbreviated citation for the experimental results, listing the first author, journal or book title, volume number, pages, and year of publication. Journal codes on the plot are similar to the journal name and are defined in Journal Codes. For a list of full citations in the CPDB ordered alphabetically by first author, click on Literature Reference. The abbreviation pers.comm. under Literature Reference indicates that we obtained information that is not reported in the published paper, by personal communication with the author, i.e. the CPDB analyses improve upon the published results.
A new citation for a published paper is listed whenever experimental results are from a new paper, i.e. if several experiments are reported consecutively from a single paper, then the citation will not repeat. When the next experiments are from a different paper, a new citation will be reported. If pathology codes appear in the Literature Reference field, as in the Phenolphthalein example, results are for an NCI/NTP bioassay and are discussed under [29] below. The pop-up windows for these codes are Site and Path under [16].


Chemical (Synonym) CAS
[1]           [2]  [3]
PHENOLPHTHALEIN   77-09-8

# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
[4][5]    [6]   [7]   [8]   [9]    [10]  [11]                  [12]    [13]    [14]                         [15]
4958 M     f    b6c   eat  24m24   TR465   :       0    388.mg  777.mg  1.55gm
Site Path Notes TD50 DR Pval AuOp LoConf UpConf Cntrl 1 Inc 2 Inc 3 Inc Brkly Code [16][17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
MXB MXB 508.mg Z P<.0005 296.mg 1.53gm 15/50 33/50 40/50 (36/50) ---:hcs,lmt,mly; ova:sxb,sxs. C --- mly 748.mg Z P<.003 c 394.mg 4.88gm 15/50 28/50 33/50 (25/50) --- lmt 1.61gm Z P<.003 c 859.mg 8.28gm 1/50 9/50 10/50 (7/50) ova MXA 1.90gm Z P<.003 c 1.00gm 8.68gm 0/50 7/50 6/50 (5/50) ova:sxb,sxs. --- hcs 4.08gm * P<.0005 c 2.27gm 11.7gm 0/50 2/50 7/50 7/50 TBA MXB 1.74gm * P<.2 642.mg n.s.s. 40/50 39/50 47/50 43/50 liv MXB no dre P=1. 3.96gm n.s.s. 21/50 3/50 6/50 (2/50) liv:hpa,hpb,hpc. lun MXB 9.19gm * P<.3 2.56gm n.s.s. 6/50 5/50 6/50 8/50 lun:a/a,a/c.
Experimental results (blue color)
[16] – [17] The tissue site and histopathology are reported as three-letter codes on this line under [16] and [17]. (Click Site or Path in the header for pop-up of definitions.) The codes are similar to the words they represent; for example, the third line in the plot example reports “ova” which stands for ovary. The nomenclature reflects the terminology used in the Technical Report or the published paper. The operational rule in the CPDB has been to retain the published terms and not reinterpret or rename diagnostic categories. Thus, when various authors use different nomenclature for the same tissue or morphologic type of tumor, two different codes are used in the database.

Some special considerations about reporting Site and Histopathology data from NCI/NTP or literature are as follows:

NCI/NTP Bioassays

In the Phenolphthalein example above, certain tissue and tumor codes are given in capital letters; these denote particular mixes of sites or tumor types from the NCI/NTP bioassays. (Capital letters are not used for papers in the general literature.) When capital letters appear, information about the specific histopathology is presented under column [29]. These special capitalized codes are used for TD50s based on specific mixes of tissue and tumor types from the NCI/NTP bioassays as follows:

“Mandatory sites” are used for all NCI/NTP experiments. They are denoted by “MXB” (for “Mix Berkeley”) to indicate that the site was created especially for the CPDB and is not based upon NCI/NTP evaluations. For every NCI/NTP experiment, the same mandatory sites are given per species: for mice, “liv MXB” (liver mandatory), “lun MXB” (lung mandatory) and “TBA MXB” (all tumor-bearing animals); for rats, “liv MXB” and “TBA MXB”.
As in the Phenolphthalein example, the NCI/NTP mandatory sites are always listed last for the experiment, in the order TBA, liv, and lun. The specific pathology is given for liv MXB and lun MXB under column [29]. (Click Site or Path in header for pop-up.)
“MXA” (for “Mix Author”) is used to denote a combination of sites or tumor types that is taken directly from the Technical Report Tables of Primary Tumors, and denotes a mix of tissues or tumors reported in those tables. In the example, the site and histopathology for “ova MXA” are listed under [29]. Whenever MXA appears under column [17], the sites and or histopathology that were combined are listed under column [29].
“MXB MXB” denotes that a combination of tissues and tumors has been created by our group (MXB for “Mix Berkeley”), which consists of the aggregates of sites and histopathology evaluated in the Technical Report as “carcinogenic” or “clear” or “some” evidence of carcinogenic activity. When “MXB” appears under both columns [16] and [17] a Berkeley Code will be listed under column [30]. (Click Brkly Code [30] in header for pop-up description of the rationale for Berkeley’s combining of tissues and tumors.)


Chemical (Synonym) CAS
[1]           [2]  [3]
PHENOLPHTHALEIN   77-09-8

# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
[4][5]    [6]   [7]   [8]   [9]    [10]  [11]                  [12]    [13]    [14]                         [15]
4958 M     f    b6c   eat  24m24   TR465   :       0    388.mg  777.mg  1.55gm
Site Path Notes TD50 DR Pval AuOp LoConf UpConf Cntrl 1 Inc 2 Inc 3 Inc Brkly Code [16][17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
MXB MXB 508.mg Z P<.0005 296.mg 1.53gm 15/50 33/50 40/50 (36/50) ---:hcs,lmt,mly; ova:sxb,sxs. C --- mly 748.mg Z P<.003 c 394.mg 4.88gm 15/50 28/50 33/50 (25/50) --- lmt 1.61gm Z P<.003 c 859.mg 8.28gm 1/50 9/50 10/50 (7/50) ova MXA 1.90gm Z P<.003 c 1.00gm 8.68gm 0/50 7/50 6/50 (5/50) ova:sxb,sxs. --- hcs 4.08gm * P<.0005 c 2.27gm 11.7gm 0/50 2/50 7/50 7/50 TBA MXB 1.74gm * P<.2 642.mg n.s.s. 40/50 39/50 47/50 43/50 liv MXB no dre P=1. 3.96gm n.s.s. 21/50 3/50 6/50 (2/50) liv:hpa,hpb,hpc. lun MXB 9.19gm * P<.3 2.56gm n.s.s. 6/50 5/50 6/50 8/50 lun:a/a,a/c.

Bioassays in the Published Literature

For site and pathology data from the literature, it is usually not possible to combine tumor incidences for more than one site because, unlike the data available from NCI/NTP bioassays, information is seldom reported about multiple tumor incidence in the same animal. Thus, attempting to combine incidence for different target sites would risk double-counting of animals. When an author does give information about aggregated tissue or tumor types, the code ”mix“ is used in the plot to denote that specific sites and tumors are described in the paper. When the tumor types are not specified in the paper, the code “tum” is used. Mandatory sites from experiments in the literature are included in the database for the same tissues as the NCI/NTP bioassays. A TD50 is calculated for any mix of tumors reported in the mandatory site and for individual tumor types as well. All codes for literature experiments are in lower case letters in the plot.

[18] Notes under column [18], provides many types of information that the published author has provided about the experiment, listed as single-letter-codes. (Click Notes in header for pop-up with details.) This information is helpful in evaluating the experimental data. In the Phenolphthalein example, there are no notecodes. Notecodes indicate such factors as: survival problems (notecode “s”), variable dosing schedule (notecode “v”), serial sacrifice as part of a longer study (notecode “k”), or that histopathological examination or reporting of results was restricted to only a few tissues (notecode “r”). An “h” indicates that the evaluation of carcinogenicity for the tissue-tumor combination was based on a comparison with historical control rates. There are many other notecodes under [18], and these are defined in the Notes pop-up.

Order of lines within an experiment

The “most potent site” in each experiment is listed first and is determined by ordering the TD50s in each experiment by statistical significance. If any TD50s are significant at the p<0.01 level, then these are listed first, in order of potency (lowest TD50 is most potent). Then follow all TD50s with p<0.10 sorted in order of potency. Last, all other TD50s are listed in order of potency. For literature experiments, we have excluded the category “tba” from this sorting of the target sites, and have listed it last. For the NCI/NTP bioassays, the mandatory sites are excluded from this sorted order, and are listed at the end in the order: TBA MXB, liv MXB, and lun MXB (as in the Phenolphthalein example).
In the example above, there are five TD50s with statistical significance p<0.01. The TD50 for “MXB MXB” is the most potent and thus appears first under column [19]. The estimated TD50 for “--- mly”, appears next and has the opinion “Clear Evidence of Carcinogenic Activity” in the Technical Report (all “c” in AuOp column [22]). These results indicate that 748 mg/kg body wt/day is estimated to induce tumors in half the mice that would otherwise be tumorless survivors at the end of a standard lifespan, for malignant lymphoma in female mice (in the absence of all other causes of death).

[19] The value of each TD50 is presented under column [19], and includes the appropriate units (per kg) of body weight per day. (Click on TD50 in header for a description of how TD50 is estimated.) The symbol “noTD50” appears instead of a numerical value whenever 100% of the dosed animals had the tumor(s) of interest and the TD50 was calculated with summary data. The symbol “no dre”, for “no dose-related effect,” indicates that TD50 is not estimable for some other reason.


Chemical (Synonym) CAS
[1]           [2]  [3]
PHENOLPHTHALEIN   77-09-8

# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
[4][5]    [6]   [7]   [8]   [9]    [10]  [11]                  [12]    [13]    [14]                         [15]
4958 M     f    b6c   eat  24m24   TR465   :       0    388.mg  777.mg  1.55gm
Site Path Notes TD50 DR Pval AuOp LoConf UpConf Cntrl 1 Inc 2 Inc 3 Inc Brkly Code [16][17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
MXB MXB 508.mg Z P<.0005 296.mg 1.53gm 15/50 33/50 40/50 (36/50) ---:hcs,lmt,mly; ova:sxb,sxs. C --- mly 748.mg Z P<.003 c 394.mg 4.88gm 15/50 28/50 33/50 (25/50) --- lmt 1.61gm Z P<.003 c 859.mg 8.28gm 1/50 9/50 10/50 (7/50) ova MXA 1.90gm Z P<.003 c 1.00gm 8.68gm 0/50 7/50 6/50 (5/50) ova:sxb,sxs. --- hcs 4.08gm * P<.0005 c 2.27gm 11.7gm 0/50 2/50 7/50 7/50 TBA MXB 1.74gm * P<.2 642.mg n.s.s. 40/50 39/50 47/50 43/50 liv MXB no dre P=1. 3.96gm n.s.s. 21/50 3/50 6/50 (2/50) liv:hpa,hpb,hpc. lun MXB 9.19gm * P<.3 2.56gm n.s.s. 6/50 5/50 6/50 8/50 lun:a/a,a/c.
[20] The shape of the dose-response curve for each TD50 appears in [20] under the header “DR”. (Click DR in header for pop-up of codes and definitions.) The shape of the dose-response has been determined by a test for departure from linearity. (See Statistical Methods for details.) If there was no significant departure from a linear dose-response, then the curve shape is listed as linear, and the symbol “*” appears. For experiments with three groups of animals including controls, a significant departure from linearity with upward curvature is denoted by the symbol “/”. If there was a significant departure from linearity with downward curvature, then the TD50 is calculated without the data from the highest dose group, and the symbol “\” appears. The groups that are excluded from the reported TD50 calculation are indicated in the plot by parentheses around the tumor incidence data under [27] and [28]. We have adopted this convention to obtain the best estimate of TD50 by using only the linear portion of the dose-response curve in the calculation.
When there are more than three dose groups (including controls) in the TD50 calculation and there is a significant departure from linearity, the symbol “Z” is listed under [20] and the highest dose group(s) is surrounded by parentheses, indicating that the TD50 is calculated without the highest dose group(s). In the Phenolphthalein example the first 4 lines have a “Z” under “DR” and the highest dose group has parentheses around it indicating that the reported TD50 was calculated without the highest dose group. Note that for NCI/NTP bioassays TD50 is estimated with full lifetable data, taking into account survival and tumors in each animal. Lifetable results as well as tumor incidence can affect the shape of the dose response.
When there is a blank space for the shape of the dose-response, there are two possible reasons. First, there may be only one dose group in the experiment, so no dose-response could be determined. Second, there may be no dose-related effect, in which case the code “no dre” appears in [19] for TD50 and “P=1.” appears in [21] for Pval.
[21] The two-tailed p-value appears in [21]. (Click Pval in header for pop-up with details.) This value indicates the statistical significance associated with testing whether the slope of the dose-response is different from zero. All values are given to one significant figure. When there is no dose-related effect or the slope is negative, then “P=1.” appears in [21]. The lowest p-value reported is p<0.0005.
[22] The opinion of the original author, as to the carcinogenicity of the test agent at the particular tissue-tumor site reported on each line, is given under column [22]. Our rule for opinions has been to record all clearly stated evaluations of tumorigenicity at the site. (Click on header on AuOp for codes and definitions.)

Some special considerations about assigning the author’s opinion in the CPDB are as follows:

NCI/NTP Bioassays

The Author’s opinions from NCI/NTP are based on the text and the statistical analysis tables in the Technical Report. An author’s opinion is listed for all sites on the plot except Berkeley Mixes (MXB) and the statistically significant sites that were not considered evidence of carcinogenicity. For these sites, the opinion column is blank, e.g., in the Phenolphthalein example the last 3 lines are mandatory sites and are blank in the opinion column [22].
A ”c“ opinion for NCI Reports indicates that the Report stated that the compound was carcinogenic at that site under the conditions of the bioassay. For NTP a “c” indicates that the Abstract reported “clear evidence of carcinogenic activity” at the site, e.g. for Phenolphthalein, the sites “--- mly”, “--- lmt”, “ova MXA” and “--- hcs” have a “c” opinion. For NCI Reports, an “a” indicates tumors at that site(s) were evaluated as associated with administration of the compound or that the evidence for carcinogenicity was suggestive. For NTP we report all sites listed in the summary table in the Abstract with an opinion for carcinogenic activity: “c” for clear, “p” for some, and “e” for equivocal (Click AuOp for pop-up with details).


Chemical (Synonym) CAS
[1]           [2]  [3]
PHENOLPHTHALEIN   77-09-8

# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
[4][5]    [6]   [7]   [8]   [9]    [10]  [11]                  [12]    [13]    [14]                         [15]
4958 M     f    b6c   eat  24m24   TR465   :       0    388.mg  777.mg  1.55gm
Site Path Notes TD50 DR Pval AuOp LoConf UpConf Cntrl 1 Inc 2 Inc 3 Inc Brkly Code [16][17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
MXB MXB 508.mg Z P<.0005 296.mg 1.53gm 15/50 33/50 40/50 (36/50) ---:hcs,lmt,mly; ova:sxb,sxs. C --- mly 748.mg Z P<.003 c 394.mg 4.88gm 15/50 28/50 33/50 (25/50) --- lmt 1.61gm Z P<.003 c 859.mg 8.28gm 1/50 9/50 10/50 (7/50) ova MXA 1.90gm Z P<.003 c 1.00gm 8.68gm 0/50 7/50 6/50 (5/50) ova:sxb,sxs. --- hcs 4.08gm * P<.0005 c 2.27gm 11.7gm 0/50 2/50 7/50 7/50 TBA MXB 1.74gm * P<.2 642.mg n.s.s. 40/50 39/50 47/50 43/50 liv MXB no dre P=1. 3.96gm n.s.s. 21/50 3/50 6/50 (2/50) liv:hpa,hpb,hpc. lun MXB 9.19gm * P<.3 2.56gm n.s.s. 6/50 5/50 6/50 8/50 lun:a/a,a/c.
The symbol “–” appears in the opinion column of the first line of an NCI/NTP bioassay when the evaluation was “not carcinogenic” in that sex-species. For experiments evaluated as inadequate by NCI/NTP, an “i” appears in the opinion column in the first line.
For some cases a “–” appears for a statistical site, i.e., one not evaluated as evidence for carcinogenicity in the Report, but which are included in the CPDB because the results were statistically significant according to the statistical tables in the Report, and also had a TD50 significance level of p<0.05.
For bioassays in which some target sites were evaluated as treatment-related, the statistical sites are also reported but the opinion column is left blank. In order to make it clear that NCI/NTP did not evaluate these statistical sites as evidence of carcinogenicity, we put an “S” for “statistical” in column [30]. (Click on Brkly Code in header for pop-up.)

Bioassays in the Published Literature

The author’s opinion in [22] for literature experiments reflects what the author actually stated or we were able to obtain through personal communication. Sites evaluated as positive are given a “+”. Sites evaluated as negative are given a “–”. The symbol “+” is used for “tba” when the compound was evaluated as positive, but the author did not evaluate any specific target site as positive. For all other opinions the author’s opinion column is blank. If additional information about evaluations was obtained directly from the author, then “pers.comm.” appears after the citation under column [15].
A “+” opinion for literature experiments is given when the author uses evaluations such as “positive,” “arcinogenic,” “induced,” “treatment-related,” or “tumorigenic.” The opinion column contains a “–” only when either (1) the author stated an opinion that there was no carcinogenic effect at the particular sites included in the TD50, or (2) the author concluded that there was no treatment-related effect in the experiment, in which case all sites reported for the experiment have a “–” in the opinion column. (Click on AuOp in the header.)
Sites which an author did not evaluate as positive are included in the database only when the statistical significance associated with an increased percentage of dosed animals with tumors is p<0.05 (standard chi-square, one-sided p-value), or when the tissue is a mandatory site. When no opinion about carcinogenicity is stated in the published paper for sites that are reported in the plot, the author’s opinion column is left blank. This may occur either for mandatory sites, or for included sites that were not unequivocally evaluated by the author.
[23], [24] The Lower and Upper 99% confidence limits for each TD50 are presented in [23] and [24] respectively. (Click on LoConf or UpConf in the header for pop-up description.) The abbreviation “n.s.s.” denotes “not statistically significant.” Whenever the statistical significance of TD50 is p>0.01, then the upper 99% confidence limit cannot be calculated. When the lower confidence limit is “n.s.s.” this usually indicates that there were no tumors or only one tumor at the site, and the lower confidence limit was not estimable; most often this occurs for mandatory sites.


Chemical (Synonym) CAS
[1]           [2]  [3]
PHENOLPHTHALEIN   77-09-8

# Species Sex Strain Route Xpo+Xpt PaperNum        0 Dose  1 Dose 2 Dose  3 Dose          Literature Reference or NCI/NTP:Site Path
[4][5]    [6]   [7]   [8]   [9]    [10]  [11]                  [12]    [13]    [14]                         [15]
4958 M     f    b6c   eat  24m24   TR465   :       0    388.mg  777.mg  1.55gm
Site Path Notes TD50 DR Pval AuOp LoConf UpConf Cntrl 1 Inc 2 Inc 3 Inc Brkly Code [16][17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30]
MXB MXB 508.mg Z P<.0005 296.mg 1.53gm 15/50 33/50 40/50 (36/50) ---:hcs,lmt,mly; ova:sxb,sxs. C --- mly 748.mg Z P<.003 c 394.mg 4.88gm 15/50 28/50 33/50 (25/50) --- lmt 1.61gm Z P<.003 c 859.mg 8.28gm 1/50 9/50 10/50 (7/50) ova MXA 1.90gm Z P<.003 c 1.00gm 8.68gm 0/50 7/50 6/50 (5/50) ova:sxb,sxs. --- hcs 4.08gm * P<.0005 c 2.27gm 11.7gm 0/50 2/50 7/50 7/50 TBA MXB 1.74gm * P<.2 642.mg n.s.s. 40/50 39/50 47/50 43/50 liv MXB no dre P=1. 3.96gm n.s.s. 21/50 3/50 6/50 (2/50) liv:hpa,hpb,hpc. lun MXB 9.19gm * P<.3 2.56gm n.s.s. 6/50 5/50 6/50 8/50 lun:a/a,a/c.
[25] – [28] Beginning in [25] and extending through [28], we report the proportion of animals with tumors corresponding to the tissue-tumor combination reported in [16] and [17]. Column [25], Cntrl, is for the control group and columns [26] – [28] correspond to the dose groups with the dose levels reported in columns [12] – [14]. Tumor incidence is reported under 1 Inc 2 Inc 3 Inc. The tumor incidence data for TD50s that have been calculated with lifetable data i.e. NCI/NTP studies, are presented in the plot in summary form, and the denominator reflects the starting number in each group. When parentheses surround the tumor incidence as in the first 4 lines of the Phenolphthalein plot above, the reported TD50 was calculated without the data from those dose group(s) because there was a significant downward departure from linearity. See [20] in this guide for details. (Click on DR for the pop-up.)

NCI/NTP Bioassays

For the proportion of animals with tumors, the number of animals reported in each group is the number at the start of the experiment; the TD50 was estimated with lifetable data. In the example, there were 50 in each group. For some early NCI experiments pooled controls were used in evaluating evidence for carcinogenicity in the Technical Report, and we have calculated TD50s with those pools as well as the matched controls. Data using the pooled controls are indicated by the word “pool” under column [11], and by reporting the pooled results as a separate experiment with a different line number.

Bioassays in the Published Literature

The proportion of animals with tumors presented for papers from the general literature is the number of animals used in the TD50 calculation. Many authors have reported only the starting number of animals. Whenever the published paper had additional information, i.e., the number of animals alive at the time of appearance of the first tumor, or if that was not reported, then the number examined histologically at the site, this number is used in the denominator of the tumor incidence data. This is a more accurate description of the number of animals at risk of tumor. These data were used in the TD50 calculation and are reflected in columns [25] – [28]. In these cases, the notecode “e” for “effective number” appears in column [18] under Notes. (Click Notes in header.) Otherwise, the data reflect the number of animals that started in each group. Since experimental designs vary in the literature, the incidence and dose-rate data may include a control and only one dose group or perhaps, a control and several dose groups. We have corresponded with about half the published authors about their results and evaluations, we are sometimes able to report tumor incidence data that is not given in the publication but improves the estimate of TD50, e.g., number of animals alive at the first tumor in the denominator.
Whenever vehicle control data were available, either in NCI/NTP or general literature, they were used in the CPDB.
[29] For the NCI/NTP, we present the three-letter-codes in [29] for all sites and histopathology which are an “Author’s Mix” (MXA) or “Berkeley Mix” (MXB). This includes the MXB mandatory liver and lung sites, our combinations of sites that were individually evaluated as positive in the Technical Report (MXB), the “statistical sites”, and any combination of sites evaluated as treatment-related in the Technical Report (MXA). The three-letter-code for each tissue in the TD50 calculation is reported, and a “:” separates the tissues and tumors for each category of neoplasm included in the calculation. A “.” follows the last three letter tumor code in each mix. (Click on Site and Path for pop-up of definitions for each code.)
[30] The last column of the plot, is used only for NCI/NTP bioassays. Under the header “Brkly Code”, we indicate that a TD50 has been included in the database because of a decision rule of the CPDB (Berkeley) rather than because the sites were evaluated as treatment-related or combined in the NCI/NTP Technical Report. The capital letters “C”, “M” and “P” are used in the Berkeley Code column for Berkeley Mixes (MXB). (Click on Brkly Code [30]) for pop-up description of each Berkeley Code.)

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Last updated: August 27, 2007
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