Environment and Breast Cancer: Science Review

Search the Mammary Carcinogens Reviews Database

CAS RN 5522-43-0

Originating list
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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, IARC Monographs, National Toxicology Program 11th Report on Carcinogens, Chemical Carcinogenesis Research Information System
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Associated chemicals
Names of closely related chemicals discussed in the "originating list" are listed here if they were not separately reviewed.
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.
Product of combustion
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.
Diesel exhaust is considered the major source of exposure to nitro-PAHs such as 1-nitropyrene. Monitoring data indicate that the general population may be exposed to 1-nitropyrene and other nitro PAHs via inhalation of ambient air, ingestion of food and drinking water, and dermal contact. 1-nitropyrene is one of the most abundant mononitroarenes detected in ambient air (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.
In studies listed in CPDB and NTP 11th ROC, five of eight studies report increased benign and/or malignant mammary tumors from dosing. NTP 11th ROC: When administered by subcutaneous injections, 1-nitropyrene induced mammary tumors (including adenocarcinomas) in female rats. A study in female rats injected intraperitoneally with 1-nitropyrene showed increased mammary tumors; a second intraperitoneal study demonstrated a nonstatistically significant increase in mammary tumors. Mammary gland tumors were also increased following oral administration of 1-nitropyrene to female rats.
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.
Diesel exhaust is considered the major source of exposure to nitroPAHs such as 1,8-dinitropyrene. Despite the fact that many nitroarenes (as well as PAHs) have been consistently shown to cause mammary gland tumors, the US EPA IRIS record on diesel exhaust(1) does not mention mammary gland tumors or breast cancer and US EPA's 669-page Health Assessment Document for Diesel Exhaust (2) focuses exclusively on lung cancer, not discussing the potential for breast cancer. In contrast, risk assessments by IARC (3), the World Health Organization (4) and the NTP Report on Carcinogens (5) include discussion of mammary gland tumors. A search of PubMed for "diesel exhaust", risk assessment, and "breast cancer" did not produce any articles, and "diesel" with "breast cancer" only brought up two in vitro studies. Cancer risk from diesel exhaust is a major contributor to overall cancer risk from air pollution -- for example the California Air Resources Board has estimated that 70% of cancer risk from toxic air pollution is due to diesel exhaust (focus is lung cancer) (6). Most of the carcinogenic risk of diesel exhaust is estimated to come from PAHs, rather than nitroPAHs (4). 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".
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.
mammary gland, liver, lung
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".
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).
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
Female mice
Male rats
Male mice
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).
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).