Environment and Breast Cancer: Science Review
About
Originating list
« Place cursor over headings for an explanation of data.
The list(s) or database(s) in which the chemical was identified as showing an
increase in mammary gland tumors. CPDB: Carcinogenic Potency Database, IARC:
International Agency for Research on Chemicals Monographs on the Evaluation of
Carcinogenic Risk of Chemicals to Man summaries, NTP TR: National Toxicology Program
(NTP) Technical Reports, NTP 11ROC: NTP 11th Report on Carcinogens, CCRIS: Chemical
Carcinogenesis Research Information Service.
Carcinogenicity Potency Database, National Toxicology Program studies, IARC Monographs, Chemical Carcinogenesis Research Information System
Image from the National Library of Medicine
Associated chemicals
Names of closely related chemicals discussed in the "originating list" are
listed here if they were not separately reviewed.
none
Major use
We assigned each chemical into one of the following groups based on its major
sources and uses: industrial chemicals, chlorinated solvents, products of combustion,
pesticides, dyes, radiation and drinking water disinfection, pharmaceuticals, hormones, natural
products, and research chemicals.
Chlorinated solvent
Widespread exposure
If a chemical is a High Production Volume chemical, added to food, found in air pollution or consumer products, or causes greater than 5000 women to be exposed occupationally, it was judged to cause a likely widespread exposure to women in the United States.
More Likely
Human exposure summary
Information describing pathways of exposure for the general
population was obtained from a variety of sources, including IARC Monographs (9), NTP 11th
ROC (4), NTP Study Reports (3), and Hazardous Substance Database (10). Summaries of
chemical use in consumer products were developed from information found in US EPA's
Source Ranking Database (SRD) (11), the NLM Household Product Database (HPD)(12),
Scorecard (12), and Pesticide Action Network (PAN) Pesticides Database (13). If a chemical
could not be found in these sources, we searched ToxNet (14), PubChem (15), and The Merck
Index (16), and conducted searches by both name and CAS No. using Google.
Widespread exposure occurs during the production and industrial use of methylene chloride and during the use of a variety of consumer products containing it. Consumer products that may contain the chemical include: fabric cleaners, furniture polish, paint strippers, wood sealant and stains, spray paints, adhesives, shoe polish and art supplies (SRD). Used until 1989 as a propellent for hair spray. Substantial losses to the environment lead to ubiquitous low-level exposures from ambient air and groundwater (IARC 1999 vol.:71 p.25, NTP 11th ROC).
Mammary gland tumor summary
A summary of findings related to mammary gland tumors, most
often excerpted from IARC Monographs or the NTP 11th ROC, and, in some cases,
supplemented by our evaluation of individual studies and reviews, is available for the priority
chemicals and 67 others.
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.
Risk assessment summary
For 11 chemicals that are of particular interest because of recent
regulatory attention, a Silent Spring Institute summary of how the evidence on mammary gland
tumors and the potential for breast cancer was considered in major governmental risk
assessments and regulations is available.
US EPA and Canadian regulatory agencies have focused on mouse liver and lung tumors to estimate the carcinogenic potency of methylene chloride (1), with little discussion of rat mammary gland tumors except in the US OSHA 1997 regulation (2) lowering exposure levels for workers. Industry groups have argued that mouse tumors are not relevent to humans, and also that the rat mammary gland tumors are not relevent to humans because they are related to prolactin secretion; and the Netherlands and IPCS have adopted these arguments in their risk assessments despite the fact that only limited data support this hypothesis (3,4). In fact, a recent article shows that prolactin plays a major role in human breast cancer and that prolactin-mediated mammary carcinogenesis in rodents is likely to be relevent to humans (5). US OSHA proposed mammography for exposed women as part of required medical surveillance, but this breast cancer screening was dropped from the final regulation following objections from Eli Lilly and others (6). References
International Agency for Research on Cancer evaluation
IARC classification
Overall evaluation: Group 1: The agent is carcinogenic to humans.
Group 2A: The agent is probably carcinogenic to humans. Group 2B: The agent is
possibly carcinogenic to humans. Group 3: The agent is not classifiable as to
carcinogenicity in humans. Group 4: The agent is probably not carcinogenic to humans.
NA: not evaluated by IARC (9).
2B: Possibly carcinogenic to humans
Evidence in humans
Strength of the evidence in humans
(summary of epidemiologic evidence) and animals: sufficient, limited, or inadequate. If
IARC has not reviewed the chemical, this field will be labeled "NA".
inadequate
Tumor sites identified in IARC Monographs
If tumors were found in humans, the entry
in this field will be labeled "(human)." Unlabeled terms are from animal studies. Tumor
sites are abbreviated and can be referenced in the key (Table 1). NA: not evaluated by
IARC.
pancreas (human), liver (human), biliary tract (human), prostate (human), mammary gland (human), gynecological (human), cervix (human), rectal(human), (all not consistent risk across studies), lung, liver, mammary gland
Evidence in animals
Strength of the evidence in humans
(summary of epidemiologic evidence) and animals: sufficient, limited, or inadequate. If
IARC has not reviewed the chemical, this field will be labeled "NA".
sufficient
US EPA cancer classification
The US EPA Weight of Evidence Characterization of the
chemical’s carcinogenic potential is listed: Group A: Carcinogenic to humans; Group B:
Probably carcinogenic to humans. Group C: Possibly carcinogenic to humans. Group D: Not
classifiable as to human carcinogenicity. Group E: Evidence of non-carcinogenicity for
humans. NA: Not evaluated by US EPA (17).
B2: Probably Carcinogenic to Humans, inadequate evidence
National Toxicology Program Study Conclusions
The National Toxicology Program Technical
Reports include a determination of the carcinogenicity of the test chemical in each sex and
species tested. Designations prior to 1983 are "positive" or "negative". After 1983, NTP
assigned designations of "clear evidence of carcinogenicity," "some evidence of
carcinogenicity," "equivocal evidence of carcinogenicity," "no evidence of carcinogenicity," or "inadequate study of carcinogenicity." The words "of carcinogenicity” are removed from the
field in this database to conserve space. "NA" indicates no NTP technical report for the
chemical (3).
Female rats
Clear Evidence
Clear Evidence
Female mice
Clear Evidence
Clear Evidence
Male rats
Some Evidence
Some Evidence
Male mice
Clear Evidence
Clear Evidence
Mutagenicity from CPDB
This summary of evidence from the Carcinogenic Potency
Database is labeled “Yes” if the agent is mutagenic or weakly mutagenic in the Salmonella assay
and “No” if not. NA: Not listed in CPDB. NA-S: Listed in CPDB, but no assessment of
mutagenicity in Salmonella is included (1).
Mutagenic
Mutagenicity from RTECS
This summary of evidence from the Registry of Toxic Effects of
Chemical Substances database (NIOSH 2005) is labeled “Yes” if the agent is listed as mutagenic,
“No” if not. NA: Not listed in RTECS (18).
Mutagenic