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Within‐Animal Variation as an Indication of the Minimal Magnitude of the Critical Effect Size for Continuous Toxicological Parameters Applicable in the Benchmark Dose Approach

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  • Susan Dekkers
  • Jan Telman
  • Monique A. J. Rennen
  • Marco J. Appel
  • Cees De Heer

Abstract

In this study, the within‐animal variation in routinely studied continuous toxicological parameters was estimated from temporal fluctuations in individual healthy nonexposed animals. Assuming that these fluctuations are nonadverse, this within‐animal variation may be indicative of the minimal magnitude of the critical effect size (CES). The CES is defined as the breaking point between adverse and nonadverse changes in a continuous toxicological parameter, at the level of the individual organism. The total variation in the data from individual nonexposed animals was divided in variation parts due to known factors (differences in sex, animal, and day) and a residual variation, by means of analysis of variance. Using the residual variation and the estimated analytical measurement error of a toxicological parameter, the within‐animal variation can be estimated. The data showed within‐animal variations ranging between 0.6% and 34% for different clinical chemistry and hematological parameters in 90‐day rat studies. This indicates that different (minimal) CES values may be applicable for different parameters.

Suggested Citation

  • Susan Dekkers & Jan Telman & Monique A. J. Rennen & Marco J. Appel & Cees De Heer, 2006. "Within‐Animal Variation as an Indication of the Minimal Magnitude of the Critical Effect Size for Continuous Toxicological Parameters Applicable in the Benchmark Dose Approach," Risk Analysis, John Wiley & Sons, vol. 26(4), pages 867-880, August.
    • Handle: RePEc:wly:riskan:v:26:y:2006:i:4:p:867-880
    DOI: 10.1111/j.1539-6924.2006.00784.x
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    References listed on IDEAS

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    1. David W. Gaylor & William Slikker, 2004. "Role of the Standard Deviation in the Estimation of Benchmark Doses with Continuous Data," Risk Analysis, John Wiley & Sons, vol. 24(6), pages 1683-1687, December.
    2. W. Slob & M. N. Pieters, 1998. "A Probabilistic Approach for Deriving Acceptable Human Intake Limits and Human Health Risks from Toxicological Studies: General Framework," Risk Analysis, John Wiley & Sons, vol. 18(6), pages 787-798, December.
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