Acute toxicities to typical aquatic organisms of synthetic phenolic antioxidants and QSAR study: The vital role of water solubility.

In this paper, the acute toxicities to Scenedesmus obliquus and Danio rerio of 22 Synthetic phenolic antioxidants (SPAs) were investigated in detail. The half-effective concentrations (EC50) of 22 SPAs and half-lethal concentrations (LC50) of 14 SPAs were calculated by the corresponding toxicity effect curves. Results showed that except for 2,4-di-tert-butyl-1,4-benzoquinone (BHT-Q), an important intermediate of 2,6-di-tert-butyl-4-methylphenol (BHT), 4-tert-octylphenol (4-tOP) and dodecyl gallate (DG) with the relative EC50 values of 2.35 and 2.53 mg/L were the most toxic among 22 SPAs. 4-tOP and DG also exhibited high toxicity, ranking within the top three to Danio rerio (LC50: 0.53 and 0.57 mg/L, respectively), while the most toxic SPA was 4,4'-thiobis(6-tert-butyl-m-cresol) (AO44S25). Among these SPAs, they all belonged to toxic ∼ harmful category for green algae, and very toxic ∼ not harmful for zebrafish. Propyl gallate (PG) owned the highest EC50 and LC50 values, namely, PG with the lowest toxicity. Large discrepancy existed between the measured toxicity data and the predicted ones by ECOSAR. Two relatively robust quantitative structure-activity relationship (QSAR) models between EC50 or LC50 and twenty-six typical structural parameters were built using linear-regression analysis. Water solubility (Sw,l) was the vital parameter to determine the acute toxicities of the SPA congeners. Highly toxic BHT and 4-tOP possessed low water solubility and strong cell membrane penetration capacity. They could induce oxidative stress in green algal cells and cause damage to organelles such as mitochondria and chloroplasts, as well as morphological wrinkling and deformation of cells. These data can fill the toxicological knowledge gap for SPA congeners.