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 highly nonlinear
• 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.