Environment and Breast Cancer: Science Review
Cancer studies: Experimental details
Komulainen H, Kosma VM, Vaittinen SL, Vartiainen T, Kaliste-Korhonen E, Lotjonen S, et al. Carcinogenicity of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the rat. J Natl Cancer Inst 1997;89(12):848-56.
Notes
Statistically signifant increase of adenocarcinomas: 3/50, 2/50, 5/50, 11/50 Tumors occurred in all dose groups at subtoxic levels. Updated with information from McDonald, as listed on CPDB.
Statistically signifant increase of adenocarcinomas: 3/50, 2/50, 5/50, 11/50 Tumors occurred in all dose groups at subtoxic levels. Updated with information from McDonald, as listed on CPDB.
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).
drinking water
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.
For females:0, 0.6, 1.9, 6.6mg/kg
For males: 0.4, 1.3, 5.0 mg/kg
For 2 years, 50 rats per group. Rats were 5 wks old at start 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."
23/50, 25/50, 32/50, 34/50 fibroadenomas
0/50, 0/50, 3/50, 1/50 adenomas
in female rats
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
3/50, 2/50, 5/50, 11/50 adenocarcinoma in female rats
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.
"it causes tumors at doses that are not overtly toxic to rats" Survival was 42-70% in dose groups vs. 60-72% in control groups. High dose had lowered survival: 42% in female rats and 54% in male rats. Authors state survival rates were not statistically significantly different. Dosed animals drank less water in correlation with conc of MX. Body weights of the high dose animals of both sexes was lower (8.8% f, 9.8% m). The authors also tested the thyroid hormone and TSH levels. They saw no statistical difference between dosed animals and controls.
Other tumors
A list of other tumors that developed in the study that were treatment related.
thyroid, liver, adrenal, leukemia and lymphoma, pancreas, lungs
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 5.13-14.0, overall 0.532-122mg