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Application of a Biologically‐Based RFD Estimation Method to Tetrachlorodibenzo‐P‐Dioxin (TCDD) Mediated Immune Suppression and Enzyme Induction

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  • Lynne Fahey McGrath
  • Panos Georgopoulos
  • Michael A. Gallo

Abstract

The current methods for a reference dose (RfD) determination can be enhanced through the use of biologically‐based dose‐response analysis. Methods developed here utilizes information from tetrachlorodibenzo‐p‐dioxin (TCDD) to focus on noncancer endpoints, specifically TCDD mediated immune system alterations and enzyme induction. Dose‐response analysis, using the Sigmoid‐Emax (EMAX) function, is applied to multiple studies to determine consistency of response. Through the use of multiple studies and statistical comparison of parameter estimates, it was demonstrated that the slope estimates across studies were very consistent. This adds confidence to the subsequent effect dose estimates. This study also compares traditional methods of risk assessment such as the NOAEL/safety factor to a modified benchmark dose approach which is introduced here. Confidence in the estimation of an effect dose (ED10) was improved through the use of multiple datasets. This is key to adding confidence to the benchmark dose estimates. In addition, the Sigmoid‐Emax function when applied to dose‐response data using nonlinear regression analysis provides a significantly improved fit to data increasing confidence in parameter estimates which subsequently improve effect dose estimates.

Suggested Citation

  • Lynne Fahey McGrath & Panos Georgopoulos & Michael A. Gallo, 1996. "Application of a Biologically‐Based RFD Estimation Method to Tetrachlorodibenzo‐P‐Dioxin (TCDD) Mediated Immune Suppression and Enzyme Induction," Risk Analysis, John Wiley & Sons, vol. 16(4), pages 539-548, August.
    • Handle: RePEc:wly:riskan:v:16:y:1996:i:4:p:539-548
    DOI: 10.1111/j.1539-6924.1996.tb01099.x
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    References listed on IDEAS

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    1. Branden B. Johnson & Paul Slovic, 1995. "Presenting Uncertainty in Health Risk Assessment: Initial Studies of Its Effects on Risk Perception and Trust," Risk Analysis, John Wiley & Sons, vol. 15(4), pages 485-494, August.
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