Environment and Breast Cancer: Science Review
AboutCancer studies: Experimental details
Nitschke KD, Burek JD, Bell TJ, Kociba RJ, Rampy LW, McKenna MJ. Methylene chloride: a 2-year inhalation toxicity and oncogenicity study in rats. Fundam Appl Toxicol 1988;11(1):48-59.
Notes
See a nonsignificant increase in benign mammary tumors. See significant increase in benign mammary tumors/per tumor bearing rat at 500 ppm level. Despite this, they declare a no adverse effect level of 200ppm. They also talk extensively about historical controls (from only 2 studies) which are higher than the concurrent controls.
See a nonsignificant increase in benign mammary tumors. See significant increase in benign mammary tumors/per tumor bearing rat at 500 ppm level. Despite this, they declare a no adverse effect level of 200ppm. They also talk extensively about historical controls (from only 2 studies) which are higher than the concurrent controls.
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, 200, 500ppm 6 hr/day, 5 days/wk for24 months (f) or 20 months (m) or same exposure for only 12 months of the study either first or last. For the 2 year exposures, groups of 90 male and 108 female rats were used. (Subgroups were removed for interim kills, resulting in 70 rats for final oncogenic analysis.) For the 1 yr exposure, 1 yr controls, groups of 30 female rats were used. (One subgroup interim kill, resulting in 25 final rats.) Animals were 8-10 wks old when dosing began.
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 for most rats; 1 yr for some rats after one year of exposure.
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."
Authors break out into 10 categories- many more than other studies.
Fibroadenoma: 51/69, 57/69, 60/69, 55/69
Number of benign mt/tumor bearing rat: 2.0, 2.3, 2.2, 2.7
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
Adenocarcinoma 3/69, 5/69, 4/69, 3/69- no trend
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.
Purpose was to look at lower concentrations in order to determine the no-adverse effect level. All animals palpated monthly. Body weight and mortality not affected by dosing. They create a 'benign' mt category that doesn't add up to the individual benign cancers- in ANY combination. At 200 ppm it is stat sig different from controls in Table 3, but then they never talk about this in the text and say there were no stat sig differences.Compare results to historical controls which were higher than the current controls. The "historical range" is based on 2 studies.
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: 631-1550 Overall: 631-9520