Environment and Breast Cancer: Science Review

Originating list
Carcinogenicity Potency Database, National Toxicology Program studies, IARC Monographs, Chemical Carcinogenesis Research Information System

Mammary gland tumor summary
High levels of methylene chloride were associated with benign mammary tumors in rats as well as an increase in the number of mammary tumors per animal. Four studies reported mammary turmors. NTP 11th ROC: Methylene chloride inhalation increased the incidence of fibroadenoma of the mammary gland in female rats. There is some evidence of the carcinogenicity of methylene chloride in male rats, as shown by an increased incidence of fibroadenomas of the mammary gland.

Citations to review sources and individual studies reporting mammary gland tumors are listed below.

Citation

Notes

International Agency for Research on Cancer, Monographs on the evaluation of carcinogenic risk of chemicals to man.VOL.: 71 (1999) (p. 251). Dichloromethane.

Review

Inhalation studies with mammary tumors.: Burek et al. (1984) and US EPA (1985), NTP (1986), Nitschke et al. (1988)

http://monographs.iarc.fr/ENG/Monographs/vol71/volume71.p...

Carcinogenic Potency Database 2005. Gold LS ST, Manley NB, Garfinkel GB, Ames BN. Summary Table by Chemical of Carcinogenicity Results in CPDB on 1485 Chemicals. 2005

Review

Four of six studies reported mammary turmors. Studies that reported mammary tumors: Nitschke 1988, Burek 1984, Maltoni 1988, and NTP TR306. Studies that did not report mammary tumors: Serota 1986, Kari 1993.

http://potency.berkeley.edu/pdfs/ChemicalTable.pdfpotency...

National Toxicology Program 11th Report on Carcinogens.

Review

References NTP TR306 1986 and IARC 1987.

http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s066di...

Burek JD, Nitschke KD, Bell TJ, Wackerle DL, Childs RC, Beyer JE, et al. Methylene chloride: a two-year inhalation toxicity and oncogenicity study in rats and hamsters. Fundam Appl Toxicol 1984;4(1):30-47.

Primary Literature

experimental details

Number of mammary tumor bearing rats did not have an increasing trend, but the total number of mammary tumors per rat did increase in a dose dependant manner (though not evaluated for statistical significance.)

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.

Primary Literature

experimental details

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.

National Toxicology Program Technical Report 306, 1986

Primary Literature

experimental details

"Clear evidence" in rats is based on the mammary tumors. Rats: 0, 1000, 2000, 4000 ppm:benign mammary tumors in female rats: 5/50, 11/50, 13/50, 22/50. In male rats, they looked at the combined benign mammary tumors and the integumentary ones, for significant increase. In Discussion, for mammary tumors they note Burek 1980 and 1984 for mammary tumors, Nitschke 1982. For"negative" they note National Coffee Association studies of 1982 and 1983 in which much lower levels were used (highest was 250 mg/kg).

http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr306.pdf

Nitschke KD, Burek JD, Bell TJ, Kociba RJ, Rampy LW, McKenna MJ. Methylene chloride: a 2-year inhalation toxicity and oncogenicity study in rats. Fundam Appl Toxicol 1988;11(1):48-59.

Primary Literature

experimental details

See a nonsignificant increase in benign mammary tumors. See significant increase in benign mammary tumors/per tumor bearing rat at 500 ppm level. Despite this, they declare a no adverse effect level of 200ppm. They also talk extensively about historical controls (from only 2 studies) which are higher than the concurrent controls.

Kari FW, Foley JF, Seilkop SK, Maronpot RR, Anderson MW. Effect of varying exposure regimens on methylene chloride-induced lung and liver tumors in female B6C3F1 mice. Carcinogenesis 1993;14(5):819-26.

Primary Literature

A study listed by CPDB 2005 that did not report mammary tumors. Focused on lung and liver tumor outcomes.

Serota DG, Thakur AK, Ulland BM, Kirschman JC, Brown NM, Coots RH, et al. A two-year drinking-water study of dichloromethane in rodents. I. Rats. Food Chem Toxicol 1986;24(9):951-8.

Primary Literature

A study listed by CPDB 2005 that did not report mammary tumors. From abstract: Administered in water to 500 rats over 2 years, at 5-250 mg/kg body weight. No focus on a particular tumor outcome. Seems likely they should have been able to detect mammary tumors.

Serota DG, Thakur AK, Ulland BM, Kirschman JC, Brown NM, Coots RH, et al. A two-year drinking-water study of dichloromethane in rodents. II. Mice. Food Chem Toxicol 1986;24(9):959-63.

Primary Literature

A study listed by CPDB 2005 that did not report mammary tumors. Administered in water to 1000 mice for 2 years, at 5-250 mg/kg body weight. No focus on a particular tumor outcome. Seems likely they should have been able to detect mammary tumors, although mammary tumors have generally only been found in rats with this chemical.

US EPA. Health Assessment Document for Dichloromethane (Methylene Chloride). Final Report (EPA/600/8-82/004F). In: Office of Health and Environmental Assessment; 1985.

Primary Literature

From IARC, review postponed.