Meta-Analysis of Fish Early Life Stage Tests - Association of Toxic Ratios and Acute-To-Chronic Ratios with Modes of Action

Fish early life stage (FELS) tests (OECD test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stage. In order to analyse whether certain modes of action are related to high toxic ratios (TR, i.e., ratios between experimental effect and baseline toxicity) and/or acute-to-chronic ratios (ACR) in the FELS test effect concentrations for 183 compounds were extracted from the US EPA ecotoxicity database. Analysis of effect concentration of narcotic compounds indicated that baseline toxicity could be observed in the FELS test at similar concentrations as in acute fish toxicity test. All non-narcotic modes of action were associated with higher TRs with median values ranging from 4 to 9.3*104 (uncoupling < reactivity < neuromuscular toxicity < methemoglobin formation < endocrine disruption < extracellular matrix formation inhibition). Four modes of action (were also found to be associated with high ACRs: (1) lysyl oxidase inhibition leading to notochord distortion, (2) putative methemoglobin formation or haemolytic anemia, (3) endocrine disruption, and (4) compounds with neuromuscular toxicity. It was discussed that for the prediction of effect concentrations in the FELS test with alternative test systems, endpoints targeted to the modes of action of compounds with enhanced TR or ACR could be used to trigger FELS tests or even replace these tests.