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An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty

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

Abstract

This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No‐Observed‐Adverse‐Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD

Suggested Citation

  • Paul S. Price & Russell E. Keenan & Jeffrey C. Swartout & Carol A. Gillis & Heather Carlson‐Lynch & Michael L. Dourson, 1997. "An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty," Risk Analysis, John Wiley & Sons, vol. 17(4), pages 427-437, August.
    • Handle: RePEc:wly:riskan:v:17:y:1997:i:4:p:427-437
    DOI: 10.1111/j.1539-6924.1997.tb00883.x
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    Cited by:

    1. Paul S. Price & Russ Keenan & Jeff Swartout & Michael Dourson, 1999. "Response to 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. 19(1), pages 7-8, February.
    2. Resha M. Putzrath & James D. Wilson, 1999. "Fundamentals of Health Risk Assessment. Use, Derivation, Validity and Limitations of Safety Indices," Risk Analysis, John Wiley & Sons, vol. 19(2), pages 231-247, April.
    3. 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.
    4. 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.
    5. 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.
    6. Dale Hattis & J Prerna Banati & Rob Goble & David E. Burmaster, 1999. "Human Interindividual Variability in Parameters Related to Health Risks," Risk Analysis, John Wiley & Sons, vol. 19(4), pages 711-726, August.

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