Environment and Breast Cancer: Science Review
Cancer studies: Experimental details
National Toxicology Program Technical Report 162, 1979
Notes
Increases in malignant mammary tumors in female rats and benign tumors in female rats. Time weighted average dose was 79 ppm (low-dose males and females) for 103 wks, 176 ppm (high dose males) for 79 wks, 171 ppm (high dose females) for 84 wks. Female rats: 0/20, 9/50, 8/50 carcinoma Female rats: 0/20, 1/50, 1/50 other malignant tumors Authors acknowledge poor survival rates in rats may have resulted in fewer metastases of mammary tumors.
Increases in malignant mammary tumors in female rats and benign tumors in female rats. Time weighted average dose was 79 ppm (low-dose males and females) for 103 wks, 176 ppm (high dose males) for 79 wks, 171 ppm (high dose females) for 84 wks. Female rats: 0/20, 9/50, 8/50 carcinoma Female rats: 0/20, 1/50, 1/50 other malignant tumors Authors acknowledge poor survival rates in rats may have resulted in fewer metastases of mammary tumors.
Route
Route of chemical administration: dermal, inhalation, gavage (delivery directly into the
stomach), in feed, subcutaneous injection (under the skin), or intraperitoneal injection (into the
cavity that contains the abdominal organs).
In feed
Doses
Dosage, frequency, and duration of treatment; the sizes of the groups of animals
involved and what age the animals were at the beginning of the study.
Rats: 0, 125, 250 ppm for 40 weeks then 0, 50, 100 for 63 wks (low dose) or 39 wks(high dose males) or 44 wks (high dose females). Time weighted average dose was 79 ppm (low-dose males and females) for 103 wks, 176 ppm (high dose males) for 79 wks, 171 ppm (high dose females) for 84 wks. 20 rats of each sex in control group and 50 rats of each sex in dose groups.
Mice: 0, 100, 200 ppm for 101 wks. 20 mice each sex in control group and 50 mice of each sex in dose groups.
Feed provided ad libitum 7 d/wk.
Animals 6 wks old at beginning of study.
Time after cessation of dosing
How long the animals were observed after the chemical was no
longer being administered and before death of the animals.
none
Mammary tumors, benign
Development of benign mammary tumors, reported as a series of
fractions. The numerators represent the number of animals that developed benign mammary
tumors and the denominators represent the total number of animals receiving the particular
dose of chemical. Where available, the denominator will reflect the number of animals alive
when the first tumor developed. Otherwise, it will reflect the number of animals examined. The
order of the fractions reflects the level of chemical treatment, from no dose (controls) on the left
to the highest dose on the right. Where available, the histological type of the tumors will be
indicated, i.e. adenoma or fibroadenoma.
Additional information, in development, includes statistical significance and trend information.
We plan to indicate whether a particular treatment group’s ratio of mammary tumors related to
the control is statistically significantly elevated, as determined by the author. This is indicated
with an asterisk (*). We will also include information indicating whether there was an
increasing, statistically significant dose response trend reported by CPDB. Results that are
statistically significant at p < 0.05 are labeled "T+" and statistical significance between 0.05 and
1.0 is labeled "T~". Where there is no dose-related effect or the trend is identified as decreasing
with dose, results are labeled here as "Tna."
Male rats: 0/20, 3/50, 4/50 fibroadenoma
Male rats: 0/20, 1/50, 1/50 other adenomas
Female rats: 1/20, 26/50, 29/50 fibroadenoma
Female rats: 0/20, 13/50, 18/50 other adenomas
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
Male rats: 0/20, 1/50, 0/50 carcinoma
Male rats: 0/20, 2/50, 0/50 other malignant tumors
Female rats: 0/20, 9/50, 8/50 carcinoma
Female rats: 0/20, 1/50, 1/50 other malignant tumors
Comments
This field contains information on the survival rates of the animals and the body
weight trends in order to evaluate whether these factors were likely to have affected the
generation of mammary gland tumors. Mammary gland tumors tend to develop later in an
animal’s life, so studies with lowered survival could mean that animals died before mammary
gland tumors could develop. Decreased weight (perhaps due to toxicity of the chemical) can
decrease the development of tumors. This field may also contain other comments about the
design or outcome of the study.
In response to severely decreased body weight in dosed rat groups, dose levels were lowered. Significantly higher mortality for low and high dose rat groups as compared to controls. Female mice had decreased body weight compared to controls. Survival rates in mice were similar to controls.
Other tumors
A list of other tumors that developed in the study that were treatment related.
liver, subcutaneous tissue, lymphomas
Endocrine related toxicities
This field reports endocrine related toxicities that appeared in the
study such as testicular atrophy.
none
CPDB TD50 (mg/kg-d)
Data excerpted from the CPDB database that is defined as the "dose-rate in
mg/kg body wt/day which, if administered chronically for the standard lifespan of the species,
will halve the probability of remaining tumorless throughout that period". The CPDB
calculated values for all tumor endpoints listed as well as for total tumors. The range of
mammary gland tumors TD50s is provided, as well as an overall range.
Mammary: 1.46-8.98, overall: 0.991-105.0