Comparison of false-positive rates of 2 hypothesis-test approaches in relation to laboratory toxicity test performance.

We compared 2 statistical hypothesis-test approaches (no-observed-effect concentration [NOEC] and test of significant toxicity [TST]) to determine the influence of laboratory test performance on the false-positive error rate using the US Environmental Protection Agency's Ceriodaphnia dubia reproduction whole-effluent toxicity (WET) test endpoint. Simulation and power calculations were used to determine error rates based on observed control coefficients of variation (CV) for 8 laboratories over a range of effect levels. Average C. dubia control reproduction among laboratories was 20 to 40 offspring per female, and the 75th percentile CV was 0.10 to 0.31, reflecting a range in laboratory performance. The 2 approaches behave similarly for CVs of 0.2 to 0.3. At effects <10%, as CV decreases, TST is less likely to declare toxicity and NOEC is more likely to do so. Laboratory performance affects whether a sample is declared toxic and influences the probability of false-positive (and -negative) error rates using either approach. At the 75th percentile control CV observed for each laboratory, 4 laboratories would achieve approximately a 5% false-positive rate using 13 or fewer replicates for this test method. For the remaining 4 laboratories, more replicates would be needed to achieve a 5% false-positive rate. The present analyses demonstrate how false-positive rates are influenced by laboratory performance and WET test design. Environ Toxicol Chem 2019;38:511-523. Published 2019 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.