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A Parametric Model for Detecting Hormetic Effects in Developmental Toxicity Studies

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  • Daniel L. Hunt
  • Dale Bowman

Abstract

Hormetic effects have been observed at low exposure levels based on the dose‐response pattern of data from developmental toxicity studies. This indicates that there might actually be a reduced risk of exhibiting toxic effects at low exposure levels. Hormesis implies the existence of a threshold dose level and there are dose‐response models that include parameters that account for the threshold. We propose a function that introduces a parameter to account for hormesis. This function is a subset of the set of all functions that could represent a hormetic dose‐response relationship at low exposure levels to toxic agents. We characterize the overall dose‐response relationship with a piecewise function that consists of a hormetic u‐shape curve at low dose levels and a logistic curve at high dose levels. We apply our model to a data set from an experiment conducted at the National Toxicology Program (NTP). We also use the beta‐binomial distribution to model the litter response data. It can be seen by observing the structure of these data that current experimental designs for developmental studies employ a limited number of dose groups. These designs may not be satisfactory when the goal is to illustrate the existence of hormesis. In particular, increasing the number of low‐level doses improves the power for detecting hormetic effects. Therefore, we also provide the results of simulations that were done to characterize the power of current designs in detecting hormesis and to demonstrate how this power can be improved upon by altering these designs with the addition of only a few low exposure levels.

Suggested Citation

  • Daniel L. Hunt & Dale Bowman, 2004. "A Parametric Model for Detecting Hormetic Effects in Developmental Toxicity Studies," Risk Analysis, John Wiley & Sons, vol. 24(1), pages 65-72, February.
  • Handle: RePEc:wly:riskan:v:24:y:2004:i:1:p:65-72
    DOI: 10.1111/j.0272-4332.2004.00412.x
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    References listed on IDEAS

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    1. Edward J. Calabrese & Linda A. Baldwin & Charles D. Holland, 1999. "Hormesis: A Highly Generalizable and Reproducible Phenomenon With Important Implications for Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 19(2), pages 261-281, April.
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    Cited by:

    1. Steven Kim & Jeffrey Wand & Christina Magana‐Ramirez & Jenel Fraij, 2021. "Logistic Regression Models with Unspecified Low Dose–Response Relationships and Experimental Designs for Hormesis Studies," Risk Analysis, John Wiley & Sons, vol. 41(1), pages 92-109, January.
    2. Víctor Casero-Alonso & Andrey Pepelyshev & Weng K. Wong, 2018. "A web-based tool for designing experimental studies to detect hormesis and estimate the threshold dose," Statistical Papers, Springer, vol. 59(4), pages 1307-1324, December.
    3. Dette, Holger & Scheder, Regine, 2008. "A finite sample comparison of nonparametric estimates of the effective dose in quantal bioassay," Technical Reports 2008,05, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    4. Holger Dette & Andrey Pepelyshev & Weng Kee Wong, 2011. "Optimal Experimental Design Strategies for Detecting Hormesis," Risk Analysis, John Wiley & Sons, vol. 31(12), pages 1949-1960, December.

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