Use of Mode of Action in the Risk Characterization of Dioxins

1
Use of Mode of Action in the Risk
Characterization of Dioxins L Birnbaum1, D
Cleverly2, M DeVito1, W Farland1, B Gullett3, M
Lorber2, B Rodan2, J Schaum2, L Tuxen2, D
Winters4 U.S. EPA, ORD, 1NHEERL, 2NCEA, 3NRML
4Office of Pollution Prevention and Toxic
Substances
Results/Conclusions
The USEPAs Dioxin Reassessment was the impetus
for developing a research program on dioxins and
related chemicals. This integrated research
effort developed data, models and methods that
provided the scientific basis for the Dioxin
Reassessment. The major route of exposure to
dioxins to the general population is through
microcontamination of the diet. Dioxins are
largely the product of industrial activities,
although small amounts are produced naturally.
Over the past 20 years, emissions from industrial
sources have decreased over 90 and is reflected
in lower environmental contamination and human
body burdens. Estimates of the margin of
exposure for a variety of adaptive and adverse
effects of dioxins range from less than 1 to 10.
In addition, based on some
Science Question
Can the common mode of action of TCDD and related
chemicals be used to reduce uncertainty an better
characterize the health risk from these
contaminants? How can all the components of the
risk assessment paradigm be integrated to provide
a comprehensive risk characterization based on
this common mode of action?
Research Goals

• To develop methods, models and measurements to
  predict the relationships between sources to
  exposure to effects that incorporate information
  on the mode of action of dioxins in order to
  characterize the risk.

Impact and Outcomes
The research from ORD has not only provided the
scientific basis for the EPAs Dioxin
Reassessment, it has also provided the basis for
risk assessments and risk characterizations of
other public health organizations including
Japan, WHO and several European countries. For
example, WHO, Japan and several European
countries use steady-state body burden as the
dose metric of choice. In addition, the WHO
recommends exposure assessment methodologies for
dioxins that were developed by ORD researchers.

• The risk characterization for dioxinlike
  chemicals uses mode of action information for
• Species extrapolation
• Cumulative risk assessment
• Dose Response Modeling
• Margin of Exposure Estimates

Cumulative Risk Assessment
Future Directions
The Dioxin Reassessment is presently under review
by the National Academy of Sciences (NAS). This
review should be completed within the next year.
Following the completion of the NAS review, ORD
scientists will revise the Dioxin Reassessment
based on the NAS comments
References
NAS Review Draft of EPAs Exposure and Human
Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-
p-dioxin (TCDD) and Related Compounds.
http//cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?de
id87843
Dioxin-like Compounds and Human Carcinogenicity