title: An individual-based modeling approach for evaluation of endpoint sensitivity in harpacticoid copepod life-cycle tests and optimization of test design.
abstract: In the present study, an individual-based model for Nitocra spinipes was developed and used to optimize the test design of a proposed Organisation for Economic Co-operation and Development test guideline for harpacticoid copepods. The variability between individuals was taken into account, based on measured data, leading to stochastic model output. Virtual experiments were performed with the model to analyze the endpoint sensitivity and the effect of number of replicates and inspection intervals on statistical power. The impact of mortality was evaluated; most sublethal effects could not be determined if the mortality was ≥70%. Most sensitive to mortality was the determination of effects on brood size, for which the statistical power was reduced at 10% mortality. Our simulations show that increasing the number of replicates from 72 to 96 or 144 has little impact on the statistical power, whereas 25 replicates disallow relevant endpoint detection. Furthermore, it was demonstrated that the proposed 1D inspection interval can be shifted to a 3D interval, without losing statistical power. It was demonstrated that developmental endpoints have a higher statistical power than reproductive endpoints in the current test design. The present study highlights the usefulness of individual-based models for optimizing the experimental design. The use of such models in the development of standard test guidelines will lead to a faster and less resource-demanding process.
authors: RWTH Aachen University, Aachen, Germany. thomas.preuss@bio5.rwth-aachen.de
authors: Thomas G
authors: TG
authors: Preuss
authors: Markus
authors: M
authors: Brinkmann
authors: Elin
authors: E
authors: Lundström
authors: Bengt-Erik
authors: BE
authors: Bengtsson
authors: Magnus
authors: M
authors: Breitholtz
mesh_terms: D000818:Animals; D003198:Computer Simulation; D033342:Copepoda / Q000187:drug effects* / Q000254:growth & development; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D008018:Life Cycle Stages / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D012098:Reproduction / Q000187:drug effects; D012680:Sensitivity and Specificity; D018675:Toxicity Tests / Q000379:methods*