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Date: July 11, 2006
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Michelle Strikowsky, Media Relations Assistant
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FOR IMMEDIATE RELEASE
EPA ASSESSMENT OF DIOXIN UNDERSTATES UNCERTAINTY ABOUT HEALTH RISKS AND
MAY OVERSTATE HUMAN CANCER RISK
WASHINGTON -- Although the U.S. Environmental Protection Agency presented a comprehensive review of the scientific literature in its 2003 draft reassessment of the risks of dioxin, the agency did not sufficiently quantify the uncertainties and variabilities associated with the risks, nor did it adequately justify the assumptions used to estimate them, according to a new report from the National Academies' National Research Council. The committee that wrote the report recommended that EPA re-estimate the risks using several different assumptions and better communicate the uncertainties in those estimates. The agency also should explain more clearly how it selects both the data upon which the reassessment is based and the methods used to analyze them.
"Failure to fully characterize uncertainty can convey a false sense of precision in the conclusions of the risk assessment," said committee chair David L. Eaton, a professor and associate vice provost for research at the University of Washington, Seattle. "EPA could improve the transparency and credibility of the assessment by more clearly identifying the assumptions used to support risk estimates and by updating them when significant new findings are made."
Dioxin and related compounds have been a concern since they were found in Agent Orange, a herbicide widely used during the Vietnam War. The chemicals result unintentionally from many industrial processes and persist in the environment, allowing them to build up in the food chain. Humans are exposed to dioxins primarily through the consumption of beef, pork, fish, and dairy products, although occupational or accidental exposure can be higher. Efforts to reduce dioxin and related compounds in the environment in recent years have resulted in lower concentrations of the chemicals in humans.
EPA first assessed the risks of dioxin in 1985. After new scientific data emerged, the agency issued a draft reassessment in 2003. The Interagency Working Group on Dioxin, consisting of representatives of seven federal agencies, recommended further review of the new document.
In its 1985 assessment, EPA classified dioxin as a "probable human carcinogen," but the agency's 2003 reassessment says that dioxin is better characterized as "carcinogenic to humans." Since 2003, however, EPA has issued new guidelines for classifying the carcinogenicity of chemicals. The Research Council committee was split on whether the available evidence met all the criteria for classifying dioxin as "carcinogenic to humans" under the new guidelines, but it was unanimous in agreeing that dioxin should at least be considered "likely to be carcinogenic to humans."
The committee considered the choice of phrasing to be more a question of semantics than science, and said that the public health implications of the two classifications appear to be identical. And although the epidemiological evidence supporting classification of dioxin as a human carcinogen is not strong, occupational studies show a modest association between relatively high concentrations of dioxin in the body and increased mortality from all cancers. Animal studies provide additional support for classifying dioxin as a carcinogen.
The committee did express concern, however, with how EPA estimated cancer risk from dioxin. Because the data indicating cancer risk are from occupational and animal studies where doses of dioxin are much higher than those to which human populations are typically exposed, mathematical models are used to extrapolate the effects of lower doses in order to estimate human risk.
The committee took issue with EPA's decision to rely solely on a "linear" model that assumes the risk of cancer is directly proportional to dose at all levels of exposure, including the levels found in the environment, which are generally much lower than those shown to cause cancer in animals. Such an approach usually results in higher risk estimates than those based on nonlinear assumptions, where biological responses do not vary proportionally with dose. EPA said there was a lack of data to support a nonlinear approach, but the committee said that compelling new animal data from the National Toxicology Program -- released after EPA completed its reassessment -- when combined with substantial evidence that dioxin does not directly damage DNA, is now adequate to justify the use of nonlinear methods for estimating cancer risk at relatively low levels of exposure. Such a nonlinear model would result in a lower estimate of risk. The report recommends that EPA estimate cancer risk using both a nonlinear and linear model and describe the strengths and weaknesses of each.
The agency also should make clear how it chose its "point of departure" dose, which corresponds to the lowest experimental dose associated with adverse health effects; extrapolation is used to estimate the risk at lower doses. The point of departure is typically associated with an incremental effect, such as 5 percent more cancers, which would be expressed as a 5 percent "effective dose." However, very low effective doses, such as the 1 percent effective dose used by EPA in its reassessment, require more supporting data in order to detect such a small increase in effects. The committee said that EPA did not adequately justify its use of a 1 percent effective dose. The report recommends that cancer risks be estimated using a number of points of departure and that the uncertainties associated with each be fully explained, and quantified when possible.
To assess risks other than cancer at very low doses, EPA usually identifies a "reference dose" below which it anticipates no adverse effects. But the agency said that establishing a reference dose in the dioxin reassessment would not provide useful information. The committee, however, said a reference dose would supply valuable information, such as the risks faced by populations, including workers, who may be exposed to more than the reference dose.
The committee agreed with EPA's conclusion that dioxins are probably toxic to the human immune system, but it said that the agency's finding that dioxin-like compounds are immunotoxic at "some dose level" is inadequate. EPA should expand on this issue in its reassessment by discussing the biological mechanisms by which exposure to low doses of dioxins could compromise the immune system. The agency also should more thoroughly address how developmental and reproductive harm caused by dioxins in animals may relate to human risks.
The committee endorsed EPA's use of a "toxic equivalency factor" for estimating the toxicity of dioxin-like compounds relative to dioxin. Toxic equivalency factors assign a percentage of toxicity; for example, a certain dioxin-like compound may present one-tenth the risk of dioxin, which is important when considering the cumulative risks of exposure to multiple dioxin-like compounds in the environment.
Overall, EPA addressed many sources of uncertainty qualitatively, but the committee noted that the report would be substantially strengthened if the agency included more quantifiable measures of both the uncertainty and variability in the available scientific data used to estimate dioxin risks to public health. It recommended that EPA write a more thorough chapter on risk characterization -- a culmination of all the relevant toxicity and exposure data and their relationship to potential health effects -- that includes a comprehensive discussion of uncertainties. The agency also should routinely monitor dioxin-related research and establish criteria for deciding when findings such as the new National Toxicology Program data are compelling enough to revise the most recent dioxin risk assessment.
The committee's report was funded by the U.S. Environmental Protection Agency, U.S. Department of Agriculture, and the U.S. Department of Health and Human Services. The National Research Council is the principal operating arm of the National Academy of Sciences and the National Academy of Engineering. It is a private, nonprofit institution that provides science and technology advice under a congressional charter. A committee roster follows.
Copies of HEALTH RISKS FROM DIOXIN AND RELATED COMPOUNDS: EVALUATION OF THE EPA REASSESSMENT will be available from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at HTTP://WWW.NAP.EDU. Reporters may obtain a pre-publication copy from the Office of News and Public Information (contacts listed above).
[ This news release and report are available at HTTP://NATIONAL-ACADEMIES.ORG ]
NATIONAL RESEARCH COUNCIL
Division on Earth and Life Studies
Board on Environmental Studies and Toxicology
COMMITTEE ON EPA'S EXPOSURE AND HUMAN HEALTH REASSESSMENT OF TCDD
AND RELATED COMPOUNDS
DAVID L. EATON, PH.D. (CHAIR)
Professor of Environmental and Occupational Health Sciences
School of Public Health, and
Associate Vice Provost for Research
University of Washington
DENNIS M. BIER, M.D.
Children's Nutrition Research Center, and
Professor of Pediatrics
Baylor College of Medicine
JOSHUA T. COHEN, PH.D.
Institute for Clinical Research and Health Policy Studies
Tufts New England Medical Center
MICHAEL S. DENISON, PH.D.
Professor of Environmental Toxicology
University of California
RICHARD DI GIULIO, PH.D.
Integrated Toxicology Program;
Superfund Basic Research Center; and
Nicholas School of Environment and Earth Sciences
NORBERT KAMINSKI, PH.D.
Center for Integrative Toxicology, and
Professor of Pharmacology and Toxicology
Michigan State University
NANCY K. KIM, PH.D.
Division of Environmental Health Assessment
New York State Department of Health
ANTOINE KENG DJIEN LIEM, PH.D.
Scientific Coordinator of the Scientific Committee
European Food Safety Authority
THOMAS E. MCKONE, PH.D.
Senior Staff Scientist
Lawrence Berkeley National Laboratory, and
School of Public Health
University of California
MALCOLM C. PIKE, PH.D.
Department of Preventive Medicine
Norris Comprehensive Cancer Center
Keck School of Medicine
University of Southern California
ALVARO PUGA, PH.D.
Professor of Molecular Biology and Environmental Health;
Department of Environmental Health; and
Center for Environmental Genetics
Superfund Basic Research Program
University of Cincinnati Medical Center
ANDREW G. RENWICK, PH.D., D.SC.
University of Southampton
Southampton, United Kingdom
DAVID A. SAVITZ, PH.D.
Department of Community and Preventive Medicine
Mount Sinai School of Medicine
New York City
ALLEN E. SILVERSTONE, PH.D.
Professor of Microbiology and Immunology
Upstate Medical University
State University of New York
PAUL F. TERRANOVA, PH.D.
Center for Reproductive Sciences, and
Professor of Molecular and Integrative Physiology and of Obstetrics and Gynecology
University of Kansas Medical Center
KIMBERLY M. THOMPSON, SC.D.
Operations Management and System Dynamics
Sloan School of Management
Massachusetts Institute of Technology
GARY M. WILLIAMS, M.D.
Director of Environmental Pathology and Toxicology, and
Professor of Pathology
New York Medical College
YILIANG ZHU, PH.D.
University of South Florida
RESEARCH COUNCIL STAFF
SUZANNE VAN DRUNICK, PH.D.
THOMAS BURKE, PH.D.