Environment and Breast Cancer: Science Review
AboutCancer studies: Experimental details
Maltoni C, Conti B, Cotti G, Belpoggi F. Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: current results and ongoing research. Am J Ind Med 1985;7(5-6):415-46
Notes
Numbers seem to show only a marginal increase in mammary tumors. 1st experiment: female rats 4/30, 4/30, 7/35 (or numbers corrected for number of animals alive when first tumor of this type was detected: 4/30, 4/28, 7/28) 2nd experiment: female rats 7/50, 7/40 (or corrected numbers 7/49, 7/40) 3rd experiment: breeders 2/60, 6/54 (corrected is same), embryos are same as controls
Numbers seem to show only a marginal increase in mammary tumors. 1st experiment: female rats 4/30, 4/30, 7/35 (or numbers corrected for number of animals alive when first tumor of this type was detected: 4/30, 4/28, 7/28) 2nd experiment: female rats 7/50, 7/40 (or corrected numbers 7/49, 7/40) 3rd experiment: breeders 2/60, 6/54 (corrected is same), embryos are same as 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).
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.
1st experiment: by gavage, 0, 50, 250 mg/kg body weight in olive oil, 1/day, 4-5/wk, for 52 wks. Animals were 13 wks old. Groups of 35 each sex at highest dose, 30 for lower and control.
2nd experiment: by gavage, 0, 500 mg/kg body weight. 1/day, 4-5 days/wk for 104 wk on 7 wk old
3rd experiment: by inhalation, 13 wk old breeder and 12 day embryos were exposed to 200 ppm for 4 hr/day, 5 days/wk for 7 weeks. One group of mothers and pups were then exposed to 200 ppm for 7 hr/day, 5 days/wk for 12 weeks and then 300 ppm 7 hrs/day, 5 days/wk for 85 wks. Another group of pups had the same prenatal exposure and then 200 ppm for 7 hr/day, 5 days wk for 8 wks. Controls were breeders and embryos for 104 wks.
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.
1st and 2nd experiments: until spontaneous death
3rd experiment: observed until 150th wk
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."
Not noted.
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
1st experiment: female rats 4/30, 4/30, 7/35 (or numbers corrected for number of animals alive when first tumor of this type was detected: 4/30, 4/28, 7/28)
2nd experiment: female rats 7/50, 7/40 (or corrected numbers 7/49, 7/40)
3rd experiment: breeders 2/60, 6/54 (corrected is same), embryos are same as controls
Other tumors
A list of other tumors that developed in the study that were treatment related.
Zymbal gland, oral, blood, skin, nasal, liver
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: 907 overall: 161-8510