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

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

Dekkers, S.
Telman, J.
Rennen, M.A.J.
Appel, M.J.
de Heer, C.
TNO Industrie en Techniek TNO Kwaliteit van Leven

2006

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.

Biology
Food and Chemical Risk Analysis
Adverse effect
Benchmark approach
Critical effect size
Within-animal variation
Benchmarking
Biodiversity
Data reduction
Error analysis
Parameter estimation
Risk assessment
Adverse effects
Benchmark approach
Critical effect size (CES)
Within-animal variation
Toxicity
Intraspecific variation
Rodent
Temporal variation
Toxicity
Variance analysis
Analysis of variance
Animal experiment
Circadian rhythm
Clinical chemistry
Controlled study
Effect size
Female
Hematology
Male
Nonhuman
Rat
Review
Sex difference
Toxicity testing
Toxicological parameters
Analysis of Variance
Animals
Data Interpretation, Statistical
Dogs
Dose-Response Relationship, Drug
Female
Male
Poisons
Rats
Rats, Wistar
Risk Assessment
Toxicology
Animalia

http://resolver.tudelft.nl/uuid:a13930cc-a979-4011-86ed-7a5781eb6a14

https://doi.org/10.1111/j.1539-6924.2006.00784.x

239402

0272-4332

Risk Analysis, 26 (4), 867-880

article