Environment and Breast Cancer: Science Review

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CAS RN 96-13-9

Cancer studies: Experimental details
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National Toxicology Program Technical Report 400, 1993
Increase of mammary tumors in female rats. Rats: 0,188,375 mg/kg; Female rats: 0/50, 0/50, 5/50 adenocarcinoma. Clear evidence of carcinogenic activity in both sexes of both species (total organs). Mammary tumors listed as cancer type contributing to the determination for female rats. Study ended before 1 yr because of viral infection dangerous to humans.
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).
Topical, subscapular skin
Mostly rat or mouse, though some studies use hamster or monkeys.
Rat, Mouse
F for female, M for male.
F, M
Strain information for the animal species used in the study.
F344/N rats, B6C3F mice
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, 188, 375 mg/kg Mice: 0, 88, 177 mg/kg 5 days/wk 50 per group Study originally designed to last 2 years. Halted prematurely. Rats for 48-51 wks for males, for 52-55 wks for females Mice for 36-39 wks for males, 39-42 wks for females Exposure began around 2 months old for both.
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.
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the same format as for benign, as described above.
Female rats: 0/50, 0/50, 5/50 adenocarcinoma
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 animalís 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 female rats, highest dose has lower weight than controls. Increasing dosage correlated with increasing mortality. Study ended prematurely due to detection of antibodies against lymphocytic choriomeningitis virus in sentinel animals. (The virus also puts humans at risk.) No reviewers desired any changes to conclusions. Includes comparisons to assays of structurally related compounds.
Other tumors
A list of other tumors that developed in the study that were treatment related.
nasal, spleen, skin, oral, forestomach, intestines, liver, kidney, zymbal gland, clitoris, esophagus, lung, nose,
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.
not in CPDB