1. 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
- Author
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Monique Rennen, Marco J Appel, Jan Telman, Cees de Heer, Susan Dekkers, and TNO Industrie en Techniek TNO Kwaliteit van Leven
- Subjects
Male ,Magnitude (mathematics) ,Review ,Adverse effect ,Residual ,Toxicology ,Poisons ,Clinical chemistry ,Statistics ,Analysis of variance ,Safety, Risk, Reliability and Quality ,Critical effect size (CES) ,Rodent ,Data reduction ,Circadian rhythm ,Estimation theory ,Breaking point ,Biodiversity ,Hematology ,Temporal variation ,Benchmarking ,Variation (linguistics) ,Error analysis ,Toxicological parameters ,Data Interpretation, Statistical ,Variance analysis ,Female ,Food and Chemical Risk Analysis ,Benchmark approach ,Effect size ,Biology ,Intraspecific variation ,Risk Assessment ,Dogs ,Physiology (medical) ,Parameter estimation ,Animalia ,Animals ,Animal experiment ,Rats, Wistar ,Analysis of Variance ,Observational error ,Toxicity ,Dose-Response Relationship, Drug ,Adverse effects ,Data interpretation ,Nonhuman ,Sex difference ,Rats ,Within-animal variation ,Toxicity testing ,Rat ,Critical effect size ,Controlled study - 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. © 2006 Society for Risk Analysis.
- Published
- 2006