Environment and Breast Cancer: Science Review
Cancer studies: Experimental details
National Toxicology Program Technical Report 210, 1982
Notes
Increases in malignant mammary tumors in female mice and benign tumors in female rats. 0, 10, 40 ppm for 6 hrs/d, 5d/wk for 78 weeks-103 weeks Female mice: 2/50, 14/50*, 8/50* adenocarcinoma T+ Female rats: 4/50, 29/50*, 24/50* fibroadenoma T+ Female rats: 1/50, 0/50, 4/50 adenocarcinoma T+ Has a second NTP Technical Report: TR86, 1978 which used gavage instead of inhalation.
Increases in malignant mammary tumors in female mice and benign tumors in female rats. 0, 10, 40 ppm for 6 hrs/d, 5d/wk for 78 weeks-103 weeks Female mice: 2/50, 14/50*, 8/50* adenocarcinoma T+ Female rats: 4/50, 29/50*, 24/50* fibroadenoma T+ Female rats: 1/50, 0/50, 4/50 adenocarcinoma T+ Has a second NTP Technical Report: TR86, 1978 which used gavage instead of inhalation.
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).
Inhalation
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.
0, 10, 40 ppm for 6 hrs/d, 5d/wk for 78 weeks-103 weeks. 50 animals of each species and sex in each dose group. Rats were 6 weeks old and mice 5 weeks 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."
Female rats: 4/50, 29/50, 24/50 fibroadenoma
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
Female rats: 1/50, 0/50, 4/50 adenocarcinoma
Female mice: 2/50, 14/50, 8/50 adenocarcinoma
Female mice: 0/50, 4/50, 1/50 adenosquamous carcinoma
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.
High dose rats had lowered survival compared to low dose and controls. High dose female mice had lowered survival compared to low dose and control. Low dose survival was also lower than controls. Early death in male mice of all dosages caused by urinary tract infection. High dose rats and mice of either sex had lower weight than controls.
Other tumors
A list of other tumors that developed in the study that were treatment related.
nasal, circulatory system, testes, lung, subcutaneous,
Endocrine related toxicities
This field reports endocrine related toxicities that appeared in the
study such as testicular atrophy.
testicular degeneration and atrophy
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: 3.6-98.8 , overall: 1.10-470