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Graphene oxide (GO) is widely used in various fields and is considered to be relatively biocompatible. Herein, "indirect" nanotoxicity is first defined as toxic amplification of toxicants or pollutants by nanomaterials. This work revealed that GO greatly amplifies the phytotoxicity of arsenic (As), a widespread contaminant, in wheat, for example, causing a decrease in biomass and root numbers and increasing oxidative stress, which are thought to be regulated by its metabolisms. Compared with As or GO alone, GO combined with As inhibited the metabolism of carbohydrates, enhanced amino acid and secondary metabolism and disrupted fatty acid metabolism and the urea cycle. GO also triggered damage to cellular structures and electrolyte leakage and enhanced the uptake of GO and As. Co-transport of GO-loading As and transformation of As(V) to high-toxicity As(III) by GO were observed. The generation of dimethylarsinate, produced from the detoxification of inorganic As, was inhibited by GO in plants. GO also regulated phosphate transporter gene expression and arsenate reductase activity to influence the uptake and transformation of As, respectively. Moreover, the above effects of GO were concentration dependent. Given the widespread exposure to As in agriculture, the indirect nanotoxicity ofGOshould be carefully considered in food safety. [ABSTRACT FROM AUTHOR]