Environment and Breast Cancer: Science Review
AboutCancer studies: Experimental details
Maltoni C, Lefemine, G., Cotti, G., Chieco, P., and Patella, V. Experimental research on vinylidene chloride carcinogenesis. Arch. Res. Ind. Carcinog. 1985;3:1-229.
Notes
Increased malignant mammary tumors in mice inhalation experiments and in mixed mammary tumors in rat inhalation studies. Gavage studies and hamster studies showed no increase in mammary tumors. Exp 1: females: 61/98, 28/30, 21/30, 23/30, 25/30, 44/59 (T not calc by CPDB); males 11/83, 4/29, 4/27, 7/30, 5/30, 8/59 (T not calculated by CPDB) mixed mammary tumors Exp 3: lower than controls Exp 4: same levels as controls, females ~ 46% Exp 5: no mammary tumors in hamsters noted Exp 6: female embryos, same as or less than controls; male embryos 11/156, 3/59 (15 wks), 7/61 (104 wks); female breeders 24/60, 29/54 (104 wks) (T not calc by CPDB) mixed Exp 2a, females: 2/98, 6/30*, 4/30* (T not calc by CPDB) mixed, mostly adenocarcinoma Exp 2b, females: 1/89, 12/119* T+ mixed. Mostly adenocarcinomas
Increased malignant mammary tumors in mice inhalation experiments and in mixed mammary tumors in rat inhalation studies. Gavage studies and hamster studies showed no increase in mammary tumors. Exp 1: females: 61/98, 28/30, 21/30, 23/30, 25/30, 44/59 (T not calc by CPDB); males 11/83, 4/29, 4/27, 7/30, 5/30, 8/59 (T not calculated by CPDB) mixed mammary tumors Exp 3: lower than controls Exp 4: same levels as controls, females ~ 46% Exp 5: no mammary tumors in hamsters noted Exp 6: female embryos, same as or less than controls; male embryos 11/156, 3/59 (15 wks), 7/61 (104 wks); female breeders 24/60, 29/54 (104 wks) (T not calc by CPDB) mixed Exp 2a, females: 2/98, 6/30*, 4/30* (T not calc by CPDB) mixed, mostly adenocarcinoma Exp 2b, females: 1/89, 12/119* T+ mixed. Mostly adenocarcinomas
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, gavage
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.
Exp 1: rat, inhalation: 0, 10, 25, 50, 100, 150-200 ppm, 4hr/d, 4-5 d/wk for 52 wks. 60 animals of each sex in the highest dose group, 30 of each in other doses, and 100 of each in the control groups. Animals were 16 wks old at start.
Exp 2a: mouse, inhalation: 0, 10, 25 ppm for 4 hr/d, 4-5 d/wk for 52 wks. 30 animals of each sex were in the dosed groups and 100 animals of each sex were in the controls. Animals were 16 wks old at start.
Exp 2b: mouse, inhalation: 0, 25 ppm for 4 hr/d, 4-5 d/wk for 52 wks. 120 animals of each sex in dosed group, 90 animals of each for controls. Animals were 9 wks old at start.
Exp 3: rat, gavage: 0, 5, 10, 20 mg/ kg body weight, 1/d, 4-5 d/wk for 52 wks. 50 animals of each sex were in the dosed groups and 100 of each in the controls. Animals were 9 wks old at start.
Exp 4: rat, gavage: 0, 0.5 mg/kg body weight, 1/d, 4-5 d/wk for 52 wks. 50 animals of each sex dosed, and 75 of each in control group. Animals were 10 wks old at start.
Exp 5: hamster, inhalation: 0, 25 ppm, 4 hr/d, 4-5 d/wk for 52 wks. 30 animals of each sex were dosed, 18 males and 17 females were in the control groups. Animals were 28 wks old at start.
Exp 6: rat, inhalation: 0, 100 ppm for 4hr/d for 4-5 d/wk for 7 wks and then 7 hr/d for 4-5 d/wk for 8 wks or 97 wks, breeders and embryos. Number of animals: 54 exposed breeders for 104 wks, 60-62 embryos of each sex for 15 wk and 104 wk exposures, 60 breeder controls, 158 male and 149 female embryo controls. Breeders were 13 wks old and embryos were 12 days old at start.
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.
followed until end of life
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."
Exp 1, females: 61/98, 28/30, 21/30, 23/30, 25/30, 44/59 ; males 11/83, 4/29, 4/27, 7/30, 5/30, 8/59 mixed mammary tumors
Exp 3: lower than controls
Exp 4: same levels as controls, females ~ 46%
Exp 5: no mammary tumors in hamsters noted
Exp 6: female embryos, same as or less than controls; male embryos 11/156, 3/59 (15 wks), 7/61 (104 wks); female breeders 24/60, 29/54 (104 wks) (T not calc by CPDB) mixed
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
Exp 2a, females: 2/98, 6/30, 4/30 mixed, mostly adenocarcinoma
Exp 2b, females: 1/89, 12/119 mixed. Mostly adenocarcinomas
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.
In rat and hamster experiments, survival was comparable between dosed animals and controls. In mouse experiments, the mice had slightly higher survival. Weights were similar to controls except for decreases seen in Exp 2a (mice, inhalation) and Exp 6 (rats, inhalation, breeders and embryos.)
Other tumors
A list of other tumors that developed in the study that were treatment related.
kidney, lung, leukemia
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: 80.9, overall: 0.5- 858