Environment and Breast Cancer: Science Review
Cancer studies: Experimental details
Maltoni C, Cotti G, Perino G. Long-term carcinogenicity bioassays on methylene chloride administered by ingestion to Sprague-Dawley rats and Swiss mice and by inhalation to Sprague-Dawley rats. Ann N Y Acad Sci 1988;534:352-66.
Notes
Gavage: Nonsignificant increase in mammary tumors at highest dose, 500 mg/kg. Inhalation: Slight nonsignificant increase in offspring exposed in utero and afterwards. Authors note the previous, but do not note increase in adult inhalation mammary tumor totals- dosed is higher 24/60, 35/54.
Gavage: Nonsignificant increase in mammary tumors at highest dose, 500 mg/kg. Inhalation: Slight nonsignificant increase in offspring exposed in utero and afterwards. Authors note the previous, but do not note increase in adult inhalation mammary tumor totals- dosed is higher 24/60, 35/54.
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).
gavage, 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.
By inhalation to rats: 0, 100 ppm, 4-7 hours/day, 5 days/wk for 104 wks on 13 wk old breeders and male and female offspring; Other offspring exposed only 15 wks.
By gavage to rats and mice: 0, 100, 500 mg/kg body weight, once daily 4-5 days weekly, for 64 weeks. Rats 12 wks old at start of ingestion experiment; mice 9 wks. For inhalation study, breeders were 13 weeks, embryos at 12 days of gestation at start of experiment. In ingestion study, 50 animals per sex per group in dosed groups of both animals. Rats had 50 animals receiving an olive oil control and 20 m, 26 f in untreated controls. Mice had 60 animals of both sexes for olive oil control. For inhalation study, there were 60 f breeders in control group, 54 in dosed. Embryos exposed for 104 wks: 60 m, 69 f. Embryos exposed for 15 wks: 60 m, 70 f. Control embryos: 158 m, 149 f.
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.
by gavage, 9 months; no followup for inhalation studies
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
2 yr inhalation study: female rats: 24/60, 35/54
64 wk ingestion study: female rats: 4/50, 3/50, 9/50
authors say not significant
"A slight increase (NS) in the percentage of malignant mammary tumors was observed in female offspring exposed for 15 weeks (no dose-response correlation)." 5.4% to 10.0%.
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.
Ingestion experiment had problems with survival: increased mortality for male and female rats at the 500 dose, for both doses for both sexes of mice. Study does not supply actual numbers of animals that survived. Experiment was halted at 64 weeks because of the survival problems. Body weight in rats was unaffected by dosing. Dosed mice of both sexes had decreased body weight.
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: 37.8-1130, overall: 32.1-7050