Environment and Breast Cancer: Science Review
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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.
Industrial chemical
Found in consumer products
"Likely" indicates that the chemical is contained in consumer
products or traces of the chemical are present in products, including food and water, resulting
in likely exposure for the general population. For some chemicals marked as "likely," consumer
product uses have been discontinued, and this will be indicated in the "Use in Consumer
Products" field.
Likely
Food additive in US
Chemicals are classified as "Listed" or "Not listed" in the Everything
Added to Food in the United States database developed by the US Food and Drug
Administration.(22)
Not listed
California Proposition 65
Chemicals are labeled "Listed" or "Not listed" based on the Proposition 65 list of chemicals updated on May 27, 2005. Listed chemicals are "chemicals known by the State of
California to cause cancer or reproductive toxicity"(19).
Not listed
Air pollutant
Chemicals classified as "Likely" air pollutants are those likely to be found in
indoor or outdoor air, including products of combustion and industrial chemicals that may offgas
from consumer products, leading to human exposure.
Likely
Current High Production Volume chemical
Chemicals are classified "Yes" or "No," based on
2002 production volume information submitted to the US EPA: "Yes" for >1 million pounds
produced; "No" for < 1 million pounds produced. Some past production volumes are
referenced, where appropriate, in the HPV comment column (20). In addition, Scorecard.org is
referenced and noted in the HPV comment column when it was inconsistent with current
production volume information obtained from US EPA (21).
Yes
Production volume information
Production volume information is from the US EPA database
on non-confidential production volume information submitted by companies for chemicals
under the 1986-2002 Inventory Update Rule (IUR) using the most updated (2002) values (20).
The Inventory Update Rule requires the submission of basic production data every four years
on chemical substances manufactured (including imported) for commercial purposes in
amounts of 25,000 pounds or more at a single site. Out of over 80,000 chemicals on the TSCA
Chemical Substances Inventory, reports are required for approximately 9,000 substances. For
those substances with annual volumes of 300,000 lbs or more per site, reporters also submit
chemical processing and use information.
>10 - 50 million
General population exposure
This field includes information describing pathways of exposure
for the general population obtained from a variety of sources including: IARC Monographs (9),
NTP 11th ROC on Carcinogens (4), NTP Study Reports and Abstracts (3), Hazardous Substance
Database (10), and other sources located through use of the Google search engine.
Detected in wastewater (IARC 1999 vol.:71 p.1163). The general population may be exposed via inhalation of ambient air, ingestion of food and drinking water, and dermal contact with this compound with other consumer products, such as plastic wrap which contains residual monomer (HSDB). Migration of this chemical into food wrapped in plastic is likely.
Use in consumer products
Summaries of chemical use in consumer products were developed
from information found in US EPA SRD (11), NLM HPD (12), and Scorecard (12). Major uses
were taken from IARC Monographs (9), NTP 11th ROC (4), NTP Study Reports (3), HSDB (10),
and 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.
No consumer products listed in SRD, HPD, or Scorecard. Chemical intermediate; used as a copolymer in various types of saran, in adhesives, and as a component of synthetic fibers (HSDB).
Occupational exposure to women
We extracted the total number of potentially exposed workers and the
number of potentially exposed female workers from the National Occupational Exposure
Survey (NOES) 1981-1983; we listed specific industry classifications if >5,000 women were
potentially exposed in that industry. Note: NOES does not include farm workers.
NOES 1981-1983-Total Exposed: 2,679 Females exposed: 291 Exposure to vinylidene chloride may occur during its production and in the production of copolymers (IARC 1999 vol.:71 p.1163).
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).
C: Possibly Carcinogenic to Humans
US EPA Weight of Evidence narrative
US EPA narrative statement of overall weight of
evidence for carcinogenicity (animal, human, and other supportive data).
"Under the draft revised guidelines for carcinogen risk assessment (1), EPA concludes 1,1-DCE exhibits suggestive evidence of carcinogenicity but not sufficient evidence to assess human carcinogenic potential following inhalation exposure in studies in rodents. Male mice developed kidney tumors at one exposure in a lifetime bioassay, a finding tempered by the absence of similar results in female mice or male or female rats and by the enzymatic differences (i.e., CYP2E1) between male mice and female mice, male and female rats, and human kidney cells. Limited evidence of genotoxicity has been reported in bacterial systems with metabolic activation. The data for 1,1-DCE are inadequate for an assessment of human carcinogenic potential by the oral route, based on the absence of statistically or biologically significant tumors in limited bioassays in rats and mice balanced against the suggestive evidence in male mice in a single bioassay by inhalation and the limited evidence of genotoxicity. The human epidemiological results on the carcinogenicity of 1,1-DCE are too limited to draw useful conclusions. EPA concludes that the results of kidney tumors in one sex and one exposure in a single species of rodents are too limited to support an exposure-response assessment."
US EPA slope factor basis
Lists target organs used for estimating carcinogenic potency of the
chemical (17).
N/A
USA EPA notes
Any Silent Spring Institute notes on treatment of mammary tumors in US EPA
risk assessment.
The US EPA IRIS support document (2) notes lack of dose-response for the increased mammary tumors in Maltoni mouse inhalation study. This document concludes that "data showing equivocal carcinogenicity by the oral route of exposure are not sufficient to justify calculating an oral slope factor under the draft revised cancer guidelines. The suggestive data showing carcinogenicity by the inhalation route of exposure are not considered of sufficient weight to justify calculating an inhalation unit risk." The outcome of this decision is that vinylidene chloride is not considered a carcinogen in quantitative US EPA risk assessments. US EPA notes "one inhalation study in mice provides evidence of a positive carcinogenic effect of increases in renal adenocarcinomas in males. Mammary gland carcinomas and lung tumors were also observed. Other studies, although negative, noted increases in a variety of malignant and benign tumors. These increases were either not statistically significant or judged not exposure-related by the study authors. Study limitations that reduce the sensitivity of these bioassays include less than lifetime exposure, doses below the MTD, small numbers of animals, and limited gross and microscopic tissue examinations" (3).
NIOSH Pocket Guide - potential carcinogen?
This field indicates whether NIOSH identifies the chemical as a potential
carcinogen for workers (yes/no) (24).
yes
NIOSH Pocket Guide - cancer sites
Lists target organs from animal cancer bioassays (24).
liver, kidney
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.
Despite evidence of mutagenicity and limited evidence of carcinogenicity, including mammary gland carcinomas, and despite its structural similarity to other mammary carcinogens that form epoxides, vinylidene chloride is not considered a carcinogen in quantitative risk assessments by US EPA and other regulatory bodies.
Other governmental risk assessment documents
For 11
chemicals that are of particular interest because of recent regulatory attention, we identified and
summarized risk assessment materials developed by a wide range of agencies and groups. We
specifically searched for documents by the following organizations: California EPA Office of
Health Hazard Assessment, Health Canada, IARC, International Program on Chemical Safety
(IPCS), World Health Organization, RIVM (Dutch chemical standards agency), Toxicology
Excellence for Risk Assessment ITER database and Peer Consultation documents, and by
searching PubMed, ToxLine, the National Library of Medicine, and Google for documents
related to “risk assessment” and the CAS No. or chemical name.
The abstract of the Concise International Chemical Assessment Document (4) does not mention mammary tumors but does discuss male mouse kidney tumors. The 1990 WHO criteria document abstract (5) notes that "statistically increased incidences of lung tumours (mainly adenomas in mice of both sexes) and mammary carcinomas (in females) were observed, but no dose-response relationships were found. California EPA (6) notes that 1) in only 1 of 18 oncogenicity studies is there suggestive evidence that DCE may be a carcinogen (7,8) and 2) significantly elevated mammary tumors in rats were not treatment related based on lack of dose-response. IARC says in mice, treatment-related increases in the incidence of kidney adenocarcinomas were observed in male mice, as were increases in mammary carcinomas in females and pulmonary adenomas in male and female mice (9).
Non-governmental risk assessment documents
For 11
chemicals that are of particular interest because of recent regulatory attention, we identified and
summarized risk assessment materials developed by a wide range of agencies and groups. We
specifically searched for documents by the following organizations: California EPA Office of
Health Hazard Assessment, Health Canada, IARC, International Program on Chemical Safety
(IPCS), World Health Organization, RIVM (Dutch chemical standards agency), Toxicology
Excellence for Risk Assessment ITER database and Peer Consultation documents, and by
searching PubMed, ToxLine, the National Library of Medicine, and Google for documents
related to “risk assessment” and the CAS No. or chemical name.
In an article on risk from foam insulation boards, authors said "vinylidene chloride was associated with an increase in tumor incidence (kidney tumors in mice) in a single study out of 19 in which its carcinogenicity has been investigated (10). In its VCCEP submission (11), authors did not mention mammary gland tumors. However, they did include a study in a table that showd an increase in leukemia in rats exposed in utero (12). It is interesting that no other risk assessment or regulatory documents we located mentioned this leukemia finding in the only available study of in utero exposure.
(1) - US Environmental Protection Agency. Chemical Hazard Data Availability Study, 1998. - Link
(2) - US Environmental Protection Agency. Toxicological review of 1,1-dichloroethylene (CAS No. 75-35-4)
in support of summary information on the Integrated Risk Information System (IRIS). Washington, D.C., 2002. - Link
(3) - US Environmental Protection Agency. Voluntary Children's Chemical Evaluation Program: Data Needs Decision Document of Vinylidene Chloride. Office of Pollution Prevention and Toxics, 2005. - Link
(4) - US Environmental Protection Agency. Concise International Chemical Assessment Document (CICAD) for 1,1-Dichloroethene; Vinylidene Chloride. Concise International Chemical Assessment Document, Vol:51. World Health Organization: 35 p, 2003. - Link
(5) - World Health Organization Working Group. Environmental Health Criteria: Vinylidene chloride. Environmental Health Criteria. Vol:100. 187 p, 1990. - Link
(6) - California Environmental Protection Agency. Public Health Goal for 1,1-Dichloroethylene In Drinking Water. In: Office of Environmental Health Hazard Assessment, ed., 1999. - Link
(7) - Maltoni C, Cotti G, Chieco P. Chronic toxicity and carcinogenicity bioassays of vinylidene chloride. Acta oncol 1984;5:91-145. - Link
(8) - Maltoni C. Recent findings on the carcinogenicity of chlorinated olefins. Environ Health Perspect 1977;21:1-5. - Link
(9) - International Agency for Research on Cancer. Vinylidene Chloride. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Summaries, vol. 71. Re-Evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. World Health Organization, 1994:106. - Link
(10) - Turnbull D, Machado RJ, Boberg RE. Safety assessment of HCFC-141b: use as a blowing agent for insulation in building construction and refrigeration. Regul Toxicol Pharmacol 1994;19(3):282-96. - Link
(11) - The Dow Chemical Company, Vinylidene Chloride VCCEP Submission. Toxicology Excellence for Risk Assessment, 2002. - Link
(12) - Cotti G, Maltoni C, Lefemine G. Long-term carcinogenicity bioassay on vinylidene chloride administered by inhalation to Sprague-Dawley rats. New results. Ann N Y Acad Sci 1988;534:160-8. - Link