title: Derivation of the minimal magnitude of the Critical Effect Size for continuous toxicological parameters from within-animal variation in control group data.
abstract: 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.
authors: Food and Chemical Risk Analysis, TNO Quality of Life, Utrechtseweg 48, Zeist 3700 AJ, The Netherlands. harrie.buist@tno.nl
authors: H E
authors: HE
authors: Buist
authors: G Frhr
authors: GF
authors: von Bölcsházy
authors: M
authors: M
authors: Dammann
authors: J
authors: J
authors: Telman
authors: M A J
authors: MA
authors: Rennen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019963:Clinical Chemistry Tests / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D004285:Dogs; D005260:Female; D006403:Hematologic Tests / Q000706:statistics & numerical data; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*; D014116:Toxicology / Q000706:statistics & numerical data*; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D015262:Xenobiotics