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A Probabilistic Framework for the Reference Dose (Probabilistic RfD)

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  • Jeffrey C. Swartout
  • Paul S. Price
  • Michael L. Dourson
  • Heather L. Carlson‐Lynch
  • Russell E. Keenan

Abstract

Determining the probabilistic limits for the uncertainty factors used in the derivation of the Reference Dose (RfD) is an important step toward the goal of characterizing the risk of noncarcinogenic effects from exposure to environmental pollutants. If uncertainty factors are seen, individually, as “upper bounds” on the dose‐scaling factor for sources of uncertainty, then determining comparable upper bounds for combinations of uncertainty factors can be accomplished by treating uncertainty factors as distributions, which can be combined by probabilistic techniques. This paper presents a conceptual approach to probabilistic uncertainty factors based on the definition and use of RfDs by the US. EPA. The approach does not attempt to distinguish one uncertainty factor from another based on empirical data or biological mechanisms but rather uses a simple displaced lognormal distribution as a generic representation of all uncertainty factors. Monte Carlo analyses show that the upper bounds for combinations of this distribution can vary by factors of two to four when compared to the fixed‐value uncertainty factor approach. The probabilistic approach is demonstrated in the comparison of Hazard Quotients based on RfDs with differing number of uncertainty factors.

Suggested Citation

  • Jeffrey C. Swartout & Paul S. Price & Michael L. Dourson & Heather L. Carlson‐Lynch & Russell E. Keenan, 1998. "A Probabilistic Framework for the Reference Dose (Probabilistic RfD)," Risk Analysis, John Wiley & Sons, vol. 18(3), pages 271-282, June.
    • Handle: RePEc:wly:riskan:v:18:y:1998:i:3:p:271-282
    DOI: 10.1111/j.1539-6924.1998.tb01294.x
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    Cited by:

    1. Kevin P. Brand & J Lorenz Rhomberg & John S. Evans, 1999. "Estimating Noncancer Uncertainty Factors: Are Ratios NOAELs Informative?," Risk Analysis, John Wiley & Sons, vol. 19(2), pages 295-308, April.
    2. Michael Pelekis & Mark J. Nicolich & Joseph S. Gauthier, 2003. "Probabilistic Framework for the Estimation of the Adult and Child Toxicokinetic Intraspecies Uncertainty Factors," Risk Analysis, John Wiley & Sons, vol. 23(6), pages 1239-1255, December.
    3. Elizabeth Holman & Royce Francis & George Gray, 2017. "Part I––Comparing Noncancer Chronic Human Health Reference Values: An Analysis of Science Policy Choices," Risk Analysis, John Wiley & Sons, vol. 37(5), pages 861-878, May.
    4. Martí Nadal & Vikas Kumar & Marta Schuhmacher & José L. Domingo, 2008. "Applicability of a Neuroprobabilistic Integral Risk Index for the Environmental Management of Polluted Areas: A Case Study," Risk Analysis, John Wiley & Sons, vol. 28(2), pages 271-286, April.
    5. Scott M. Bartell & Elaine M. Faustman, 1998. "Comments on “An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty” and “A Probabilistic Framework for the Reference Dose (Probabilistic RfD)”," Risk Analysis, John Wiley & Sons, vol. 18(6), pages 663-664, December.
    6. Paul S. Price & Heli M. Hollnagel & Jack M. Zabik, 2009. "Characterizing the Noncancer Toxicity of Mixtures Using Concepts from the TTC and Quantitative Models of Uncertainty in Mixture Toxicity," Risk Analysis, John Wiley & Sons, vol. 29(11), pages 1534-1548, November.
    7. Elizabeth Holman & Royce Francis & George Gray, 2017. "Part II: Quantitative Evaluation of Choices Used in Setting Noncancer Chronic Human Health Reference Values Across Organizations," Risk Analysis, John Wiley & Sons, vol. 37(5), pages 879-892, May.
    8. Roger Cooke, 2010. "Conundrums with Uncertainty Factors," Risk Analysis, John Wiley & Sons, vol. 30(3), pages 330-339, March.

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