|October 19, 2004
Chlorine Chemistry Division of the American
Chemistry Council Staement on Cancer Dose-Additivity Study
of Dioxin-Like Compounds
C. T. "Kip" Howlett, Jr., Executive Director
of the Chlorine Chemistry Division of the American Chemistry
Council, released the following statement today:
"The Chlorine Chemistry Division of the American Chemistry
Council encourages research to understand the toxicity of
mixtures of dioxin-like compounds. Dr. Nigel Walker and his
colleagues have made a significant contribution to this complex
topic by evaluating dose additivity for cancer risk from chronic
exposure to a defined mixture of dioxin-like compounds. The
three compounds combined in this animal study, TCDD, PeCDF
and PCB 126, account for approximately half of the dioxin-like
activity found in human tissue.
Research results include:
- Dose-response curves for each cancer endpoint that are
- The current WHO TEF of 0.5 for PeCDF (2,3,4,7,8-pentachlorodibenzofuran)
overestimates its potency for all cancer endpoints
investigated. The authors state this TEF should be re-evaluated
for its application in quantitative risk assessment.
- A distinction between PeCDF and TCDD in that PeCDF administration
using TEF-adjusted dosages to match the TCDD dosages did
not result in statistically significantly elevated oral
mucousal and lung tumors whereas TCDD treatment did.
- Shapes of dose-response curves for each cancer endpoint
are fundamentally the same, suggesting dose additive effects
for compounds whose primary mechanism of action is via
the Ah receptor. (The research was not designed to address
additivity for compounds that may have multiple modes of
action that are also included in the TEF scheme.)
It is important to note that the dose-response modeling and
relative potency estimates reported by Dr. Walker et al.
reflect dose-comparisons on an administered dosage-basis rather
than the risk assessment metric-body burdens-used by the U.S.
Environmental Protection Agency (EPA) for conducting dioxin
risk assessment. It is our opinion that the risk assessment
policy adopted by the U.S. EPA should harmonize these two
elements. The current hybrid approach, i.e., using toxicity
parameters based on body burden extrapolations coupled to
TEQ estimates based on administered dosage is incongruous
because it ignores important pharmacokinetic differences between
congeners. It is our opinion that the body-burden basis for
relative potency estimates for the 2,3,4,7,8-pentachlorodibenzofuran
is more appropriate and in keeping with the U.S.EPA's current
body burden approach to dioxin risk assessment."
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The Chlorine Chemistry Division of the American Chemistry
Council is a national trade association based in Arlington,
VA representing the manufacturers and users of chlorine and
chlorine-related products. Chlorine is widely used as a disease-fighting
disinfection agent, as a basic component in pharmaceuticals
and myriad other products that are essential to modern life.