Environment and Breast Cancer: Science Review


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nitromethane
CAS RN 75-52-5



Cancer studies: Experimental details
 
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National Toxicology Program Technical Report 461, 1997
Notes
Increases in benign and malignant mammary tumors in female rats. 0, 94, 188, 375 ppm for 6 hrs/d, 5 d/wk for 103 wks for rats. 0, 188, 375, 750 ppm for 6 hrs/d, 5 d/wk for 103 wks for mice. Female rats: 19/50, 21/50, 33/50, 36/50 fibroadenoma Female rats: 2/50, 0/50, 0/50, 2/50 adenoma Female rats: 2/50, 7/50, 1/50, 11/50 carcinoma
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
Species
Mostly rat or mouse, though some studies use hamster or monkeys.
Rat, Mouse
Sexes
F for female, M for male.
F, M
Strain
Strain information for the animal species used in the study.
F344/N rats, B6C3F1 mice
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, 94, 188, 375 ppm for 6 hrs/d, 5 d/wk for 103 wks. 50 rats of both sexes in each dose group. 0, 188, 375, 750 ppm for 6 hrs/d, 5 d/wk for 103 wks. 50 mice of both sexes in each dose group. Rats and mice were 6 weeks old at the beginning of the 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.
1-2 weeks
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: 19/50, 21/50, 33/50, 36/50 fibroadenoma Female rats: 2/50, 0/50, 0/50, 2/50 adenoma
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the same format as for benign, as described above.
Female rats: 2/50, 7/50, 1/50, 11/50 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.
For both rats and mice, no significant differences in survival rates between exposed and unexposed groups. For both rats and mice, no significant differences in body weight between most exposed and unexposed groups (body weight of female rats in the 375 ppm group slightly greater than controls).
Other tumors
A list of other tumors that developed in the study that were treatment related.
harderian gland, liver, lung
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: 40.4-197.0, overall: 40.4-2740.0