[occ-env-med-l] NPR/NAS: TCDD risk assessment may overstate risk (fwd)

[Guest guest]

Environment

Panel: EPA Should Reassess Dioxin Threat

by

Morning Edition, July 12, 2006 · Despite decades of work, the

Environmental Protection Agency still needs to redo its assessment of

one of the most notorious chemicals in the world: dioxin. A committee

convened by the National Academy of Sciences says the EPA's methods

are flawed and need to be reworked. The report, published Tuesday, is

the latest turn in a decades-long saga involving dioxin.

Listen (3.5 min)

http://www.npr.org/templates/story/story.php?storyId=5550093

= -- = -- = -- = -- = -- = -- = -- = -- = --

http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=11688

Date: July 11, 2006

Contacts: Bill Kearney, Director of Media Relations

Strikowsky, Media Relations Assistant

Office of News and Public Information

202-334-2138; e-mail <news@...>

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 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)

University of Washington

DENNIS M. BIER, M.D.

Baylor College of Medicine

JOSHUA T. COHEN, PH.D.

Tufts New England Medical Center

MICHAEL S. DENISON, PH.D.

University of California,

RICHARD DI GIULIO, PH.D.

School of Environment and Earth Sciences, Duke University

NORBERT KAMINSKI, PH.D.

Michigan State University

NANCY K. KIM, PH.D.

New York State Department of Health

ANTOINE KENG DJIEN LIEM, PH.D.

European Food Safety Authority

THOMAS E. MCKONE, PH.D.

Lawrence Berkeley National Laboratory, and

University of California, Berkeley

MALCOLM C. PIKE, PH.D.

Keck School of Medicine, UCLA

ALVARO PUGA, PH.D.

University of Cincinnati Medical Center

ANDREW G. RENWICK, PH.D., D.SC.

University of Southampton, United Kingdom

DAVID A. SAVITZ, PH.D.

Mount Sinai School of Medicine

ALLEN E. SILVERSTONE, PH.D.

Upstate Medical University

PAUL F. TERRANOVA, PH.D.

University of Kansas Medical Center

KIMBERLY M. THOMPSON, SC.D.

Sloan School of Management, Massachusetts Institute of Technology

GARY M. WILLIAMS, M.D.

New York Medical College

YILIANG ZHU, PH.D.

University of South Florida

= -- = -- = -- = -- = -- = -- = -- = -- = --

http://www.nap.edu/catalog/11688.html

Table of Contents

Front Matter

Public Summary

Summary

1 Introduction

2 General Considerations of Uncertainty and Variability, Selection of

Dose Metric, and Dose-Response Modeling

3 Toxic Equivalency Factors

4 Exposure Assessment

5 Cancer

6 Noncancer End Points

7 Review of Risk Characterization

8 Conclusions and Recommendations

References

Appendix A Biographical Information on Committee Members

Appendix B EPA's 2005 Guidelines for Carcinogen Risk Assessment

Description

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 this 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.