Environment and Breast Cancer: Science Review
AboutCancer studies: Experimental details
Conti B, Maltoni C, Perino G, Ciliberti A. Long-term carcinogenicity bioassays on styrene administered by inhalation, ingestion and injection and styrene oxide administered by ingestion in Sprague-Dawley rats, and para-methylstyrene administered by ingestion in Sprague-Dawley rats and Swiss mice. Ann N Y Acad Sci 1988;534:203-34
Notes
Increase in malignant mammary tumors. 6/60, 6/30, 4/30, 9/30, 12/30, 9/30 malignant; 34/60, 24/30, 21/30, 23/30, 24/30, 25/30 malignant and benign [For gavage: The IARC Working Group noted the incomplete reporting and the short duration of treatment.] [By inhalation: The IARC Working Group noted the incomplete reporting of the data and the high incidence of spontaneous mammary tumors in animals of this strainl] [ip injection: The IARC Working Group noted the incomplete reporting of data, the short duration of treatment and the low total dose.] [sc inj: The IARC Working Group noted the incomplete reporting of data and the single low-dose treatment.]
Increase in malignant mammary tumors. 6/60, 6/30, 4/30, 9/30, 12/30, 9/30 malignant; 34/60, 24/30, 21/30, 23/30, 24/30, 25/30 malignant and benign [For gavage: The IARC Working Group noted the incomplete reporting and the short duration of treatment.] [By inhalation: The IARC Working Group noted the incomplete reporting of the data and the high incidence of spontaneous mammary tumors in animals of this strainl] [ip injection: The IARC Working Group noted the incomplete reporting of data, the short duration of treatment and the low total dose.] [sc inj: The IARC Working Group noted the incomplete reporting of data and the single low-dose treatment.]
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, injestion, intraperitoneal inj
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.
Inhalation, 4 hrs/day, 5 days/wk, 52 wks, 0, 25, 50, 100, 200, 300ppm 30 rats/group
Ingestion, 52 wks, once/day: olive oil control(0), 50, 250 mg/kg; 40 rats/group
Intraperitoneal inj, 4 times in 2 m intervals: olive oil(0), 50mg; 40 rats/group
Subcutaneous inj, once; olive oil(0), 50mg; 40 rats/group. Animals were 13 wks old at beginning of experiment.
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 death
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."
see mix with malignant
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the
same format as for benign, as described above.
For inhalation:
6/60, 6/30, 4/30, 9/30, 12/30, 9/30 malignant;
34/60, 24/30, 21/30, 23/30, 24/30, 25/30 malignant and benign
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.
There were no differences in survival related to dosing, except for higher mortality in females treated at the highest dose by ingestion. The authors blame this for not seeing mammary tumors at high doses with injestion. Body weights were similar.
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:23.3-57.1; overall: 12.0-1220