Linking algal growth inhibition to chemical activity: Excess toxicity below 0.1% of saturation

Chemical activity quantifies the energetic level of an organic compound relative to its pure liquid [0–1], and several studies have reported that baseline toxicity generally requires chemical activities of 0.01–0.1. The first aim was to challenge this chemical activity range for baseline toxicity. Algal growth inhibition data (median effective concentrations, EC₅₀) were compiled from two recent studies and included 108 compounds categorised as non-polar (mode of action, MOA1) and polar (MOA2) narcotics. These data were linked to chemical activity by (1) plotting them relative to a regression for (subcooled) liquid solubility (SL), which served as visual reference for chemical activity of unity and (2) determining EC₅₀/SL ratios that essentially equal median effective chemical activity (Ea₅₀). Growth inhibition required chemical activity >0.01 for MOA1 and >0.001 for MOA2 compounds. The second aim was to identify compounds exerting excess toxicity, i.e., when growth inhibition occurred at chemical activity <0.001. From a recent review with 2323 data entries, 315 EC₅₀ values passed our selection criteria. 280 of these EC₅₀ values were within or near the baseline toxicity range (Ea₅₀>0.001), and 25 compounds were found to exert excess toxicity (Ea₅₀<0.001). Of these compounds, 16 are pesticides or precursors. Methodologically, this study includes two methods for translating EC₅₀ values into the chemical activity framework, each having advantages and limitations. Scientifically, this study confirms that baseline toxicity generally requires chemical activities of 0.01–0.1 and extends the application of the chemical activity approach beyond baseline toxicity, by demonstrating its utility to identify compounds that exert excess toxicity.