Environment and Breast Cancer: Science Review
AboutCancer studies: Experimental details
National Toxicology Program Technical Report 326, 1987
Notes
Malignant mammary tumors increased in female mice, greater at low dose. Female mice: 1/50, 8/50, 6/50 Carcinogenicity refs: Dunkelberg 1982 and 1981, Walpole 1958 (only 12 rats), Snellings 1984, Garman 1985, Lynch 1983 and 1984, NTP TR326 evaluated the Dunkelberg study and only highlighted the stomach tumors, saying "the incidence of tumors in other organs were similar in dosed and control rats"
Malignant mammary tumors increased in female mice, greater at low dose. Female mice: 1/50, 8/50, 6/50 Carcinogenicity refs: Dunkelberg 1982 and 1981, Walpole 1958 (only 12 rats), Snellings 1984, Garman 1985, Lynch 1983 and 1984, NTP TR326 evaluated the Dunkelberg study and only highlighted the stomach tumors, saying "the incidence of tumors in other organs were similar in dosed and control rats"
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, 50, 100 ppm, 6 hours per day, 5 days per week for 102 weeks, 50 mice in each group. Mice were 9 wks old at beginning of exposure.
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.
1 week
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
Female mice: 1/50, 8/50, 6/50
Mammary gland adenocarcinoma and adenosquamous carcinoma in females
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.
Body weights of exposed were similar to controls. Survival was comparable across controls and exposed (with slight increase in survival with higher dose). One reviewer thought higher doses should have been used, since survival was so good. Perhaps the test was not sensitive enough. The PI commented that the dose response curve (for toxicity) is very steep and could result in inadequate survival.The high dose was not considered statistically significant. The study team found it interesting that nasal tumors were lacking.
Other tumors
A list of other tumors that developed in the study that were treatment related.
lung, harderian gland, lymphoma (many sites), uterus
Endocrine related toxicities
This field reports endocrine related toxicities that appeared in the
study such as testicular atrophy.
No nonneoplastic events.
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: 76.3mg, Overall: 39.2-297 mg