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 TD
50 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 TD
50 is calculated without the data from the highest
dose group, and the symbol “\” appears. The groups that
are excluded from the reported TD
50 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 TD
50 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.)
Carcinogenic Potency Database Project (CPDB)
Home Page
Last updated: August 27, 2007
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