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.
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.
authors.affiliation: Food and Chemical Risk Analysis, TNO Quality of Life, P.O. Box 360, Utrechtseweg 48, Zeist, 3700 AJ, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Dekkers
authors.forename: Jan
authors.initials: J
authors.lastname: Telman
authors.forename: Monique A J
authors.initials: MA
authors.lastname: Rennen
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Appel
authors.forename: Cees
authors.initials: C
authors.lastname: de Heer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003627:Data Interpretation, Statistical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D011042:Poisons / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment / Q000706:statistics & numerical data; D014116:Toxicology / Q000706:statistics & numerical data*
chemical_list: D011042:Poisons