Print Email Facebook Twitter 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 Title 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 Dekkers, S. Telman, J. Rennen, M.A.J. Appel, M.J. de Heer, C. TNO Industrie en Techniek TNO Kwaliteit van Leven Publication year 2006 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. Subject BiologyFood and Chemical Risk AnalysisAdverse effectBenchmark approachCritical effect sizeWithin-animal variationBenchmarkingBiodiversityData reductionError analysisParameter estimationRisk assessmentAdverse effectsBenchmark approachCritical effect size (CES)Within-animal variationToxicityIntraspecific variationRodentTemporal variationToxicityVariance analysisAnalysis of varianceAnimal experimentCircadian rhythmClinical chemistryControlled studyEffect sizeFemaleHematologyMaleNonhumanRatReviewSex differenceToxicity testingToxicological parametersAnalysis of VarianceAnimalsData Interpretation, StatisticalDogsDose-Response Relationship, DrugFemaleMalePoisonsRatsRats, WistarRisk AssessmentToxicologyAnimalia To reference this document use: http://resolver.tudelft.nl/uuid:a13930cc-a979-4011-86ed-7a5781eb6a14 DOI https://doi.org/10.1111/j.1539-6924.2006.00784.x TNO identifier 239402 ISSN 0272-4332 Source Risk Analysis, 26 (4), 867-880 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.