Environment and Breast Cancer: Science Review


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MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5h)-furanone)
CAS RN 77439-76-0



Cancer studies: Experimental details
 
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Komulainen H, Kosma VM, Vaittinen SL, Vartiainen T, Kaliste-Korhonen E, Lotjonen S, et al. Carcinogenicity of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in the rat. J Natl Cancer Inst 1997;89(12):848-56.
Notes
Statistically signifant increase of adenocarcinomas: 3/50, 2/50, 5/50, 11/50 Tumors occurred in all dose groups at subtoxic levels. Updated with information from McDonald, as listed on CPDB.
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).
drinking water
Species
Mostly rat or mouse, though some studies use hamster or monkeys.
Rat
Sexes
F for female, M for male.
F, M
Strain
Strain information for the animal species used in the study.
Wistar
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.
For females:0, 0.6, 1.9, 6.6mg/kg For males: 0.4, 1.3, 5.0 mg/kg For 2 years, 50 rats per group. Rats were 5 wks old at start of study.
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
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."
23/50, 25/50, 32/50, 34/50 fibroadenomas 0/50, 0/50, 3/50, 1/50 adenomas in female rats
Mammary tumors, malignant
Development of malignant mammary gland tumors follows the same format as for benign, as described above.
3/50, 2/50, 5/50, 11/50 adenocarcinoma in female rats
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.
"it causes tumors at doses that are not overtly toxic to rats" Survival was 42-70% in dose groups vs. 60-72% in control groups. High dose had lowered survival: 42% in female rats and 54% in male rats. Authors state survival rates were not statistically significantly different. Dosed animals drank less water in correlation with conc of MX. Body weights of the high dose animals of both sexes was lower (8.8% f, 9.8% m). The authors also tested the thyroid hormone and TSH levels. They saw no statistical difference between dosed animals and controls.
Other tumors
A list of other tumors that developed in the study that were treatment related.
thyroid, liver, adrenal, leukemia and lymphoma, pancreas, lungs
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 5.13-14.0, overall 0.532-122mg