# Presentation: 683952

## THE USE OF THE TOXIC EQUIVALENCY FACTOR (TEF) METHODOLOGY FOR CUMULATIVE RISK FOR DIOXINS

**Research Goals**

**Impact and Outcomes**

**Results/Conclusions**

**Future Directions**

**Science Questions**

**References**

- What are the uncertainties in the use of the TEF methodology for dioxin risk assessment?

- There are a number of assumptions and uncertainties in the TEF methodology:
- 1.	The toxicity of all chemicals included in the 	TEF methodology is mediated by the Ah 	receptor.
- 2.	The relative potency (REP) of a chemical is 	equivalent across all endpoints.
- 3.	The REP of a chemical is equivalent across all 	species
- 4.	The REP of a chemical is equivalent 	across 	exposure scenarios.
- 5.	The chemicals interact in a dose additive manner.
- Research in ORD has focused on examining several of these assumptions in order to better characterize the uncertainty in the use of the TEF method.
**STUDY GOALS**
**Project: 1  **
- 1.	To determine if the REPs are equivalent across 	endpoints in a single species
- 2.	To determine if mixtures of dioxins act in a dose 	additive manner
- 3.	To determine if REPs from mice can predict 	responses in rats.
**Project 2**
- 1.	To determine if the WHO TEFs can predict 	responses of a laboratory defined mixture
**Project 3**
- 1. 	To determine if the WHO TEFs can predict 	responses in Aroclor 1254 mixtures
- .

- The TEF methodology provides a reasonable approximation of the toxic effects of a mixture of dioxin-like chemicals.  With the following caveats:
- The predictions are best for effects strictly mediated by the Ah receptor (enzyme induction).
- Effects that occur through multiple pathways maybe under predicted the response (thyroid hormones).
- A separate set of TEF values for administered dose and tissue concentrations may be of value in applying this methodology.

- The data examining the TEF methodology was used in the USEPA Dioxin Reassessment and in the Risk Assessment Form document on developing a framework for the application of TEFs in ecological risk assessment.  In addition, the WHO is sponsoring a meeting re-evaluating the 1998 WHO TEF values for dioxins.  Members of ORD are actively involved in this meeting as participants

- While there is no longer an active research component to this work, ORD staff continue to participate in writing framework documents for the use of TEFs and working with WHO on the 2005 TEF Workshop

- Johnson CW, Williams WC, Copeland CB, DeVito MJ, Smialowicz RJ. Sensitivity of the SRBC PFC assay versus ELISA for detection of immunosuppression by TCDD and TCDD-like congeners. Toxicology. 2000 Dec 7;156(1):1-11.
- DeVito MJ, Diliberto JJ, Ross DG, Menache MG, Birnbaum LS. Dose-response relationships for polyhalogenated dioxins and dibenzofurans following subchronic treatment in mice. I. CYP1A1 and CYP1A2 enzyme activity in liver, lung, and skin. Toxicol Appl Pharmacol. 1997 Dec;147(2):267-80.
- DeVito, MJ, Diliberto, JJ, Ross, DG, Menache, MG, and Birnbaum, LS.  Dose-response relationships for polychlorinated biphenyls following subchronic treatment in mice: CYP1A1 and CYP1A2 enzyme activity in liver, lung and skin.  *Toxicol Appl. Pharmacol. *167(3):157-72, 2000.
- USEPA.  Chapter 9. Toxic Equivalency Factors (TEF) for Dioxin and Related Compounds:  Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-*p*-Dioxin (TCDD) and Related Compounds.  Part II: Health Assessment for 2,3,7,8-Tetrachlorodibenzo-*p*-dioxin (TCDD) and Related Compounds. 2004.
- Framework for Application of the Toxicity Equivalence Methodology for Polychlorinated Dioxins, Furans and Biphenyls in Ecological Risk Assessment (External Review Draft). U.S. Environmental Protection Agency, Risk Assessment Forum, Washington, DC, 630/P-03/002A, 2003.

**THE USE OF THE TOXIC EQUIVALENCY FACTOR (TEF) METHODOLOGY FOR CUMULATIVE RISK FOR DIOXINS**
- M DeVito, JJ Diliberto, LS Birnbaum
- U.S. Environmental Protection Agency, Office of Research and Development, Experimental Toxicology Division