Derivation of the minimal magnitude of the Critical Effect Size for continuous toxicological parameters from within-animal variation in control group data

Derivation of the minimal magnitude of the Critical Effect Size for continuous toxicological parameters from within-animal variation in control group data

Buist, H.E.
von Bölcsházy, G.Frhr.
Dammann, M.
Telman, J.
Rennen, M.A.J.
TNO Kwaliteit van Leven

2009

Assuming that temporal fluctuations in physiological parameters (e.g. haematology, biochemistry) in individual healthy non-exposed animals are non-adverse, the minimal magnitude of the Critical Effect Size (CES) for a number of continuous parameters of toxicity studies was derived. A total of 36 studies (19 pharmaceutical preclinical studies in dogs and 17 chemical risk assessment studies in rats) were analysed to determine within-animal variation in their control groups. Minimal CES-values were derived for each group of studies, differentiating where necessary between strains and sexes, using the 2.5 percentile (lower limit) and/or 97.5 percentile (upper limit) of the distribution of the within-animal variation around the mean of each parameter. We concluded that minimal CES-values for continuous clinical chemistry and haematology parameters should be established separately per species, strain, sex and study duration investigated. Grouping of minimal CES-values, leading to more or less "general" values, seems possible for those parameters that are subject to tight homeostatic control and consequently show little within-animal variation. Nearly a quarter of the proposed CES-values is ≤5%, nearly a quarter range from 6% to 10%, a quarter is 15% or 20%, and nearly 30% of the proposed values is ≥20% of the mean of the control animals. © 2009 Elsevier Inc. All rights reserved.

Toxicology
Food and Chemical Risk Analysis
Adverse effect
Benchmark approach
Critical Effect Size
Repeated dose toxicity studies
Within-animal variation

http://resolver.tudelft.nl/uuid:fb45177c-ad15-4705-a8b0-8f5a894636aa

https://doi.org/10.1016/j.yrtph.2009.06.009

242128

0273-2300

Regulatory Toxicology and Pharmacology, 55 (2), 139-150

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