Metabolomic analysis to understand the mechanism of Ti3C2Tx (MXene) toxicity in Daphnia magna

Due to their potential release into the environment, the ecotoxicity of Ti3C2Tx (MXene) nanomaterials is a growing concern. Unfortunately, little is known about the toxic effects and mechanisms through which Ti3C2Tx induces toxicity in aquatic organisms. The aim of this study is thus to investigate the toxic effects and mechanisms of Daphnia magna upon exposure to Ti3C2Tx with different sheet sizes (100 nm [Ti3C2Tx-100] and 500 nm [Ti3C2Tx-500]) by employing conventional toxicology and metabolomics analysis. The results showed that exposure to both Ti3C2Tx-100 and Ti3C2Tx-500 at 10 μg/mL resulted in a significant accumulation of Ti3C2Tx in D. magna, but no effects on the mortality or growth of D. magna were observed. However, the metabolomics results revealed that Ti3C2Tx-100 and Ti3C2Tx-500 induced significant changes in up to 265 and 191 differential metabolites in D. magna, respectively, of which 116 metabolites were common for both. Ti3C2Tx-100-induced metabolites were mainly enriched in phospholipid, pyrimidine, tryptophan, and arginine metabolism, whereas Ti3C2Tx-500-induced metabolites were mainly enriched in the glycerol-ester, tryptophan, and glyoxylate metabolism and the pentose phosphate pathway. These results indicated that the toxicity of Ti3C2Tx to D. magna has a size-dependent effect at the metabolic level, and both sheet sizes of Ti3C2Tx can lead to metabolic disturbances in D. magna by interfering with lipid and amino acid metabolism pathways.