 Metal oxide nanoparticles, emphies, have been expected to be used in various fields, but their release into the environment and potential toxicity on organisms has become a concern. A comprehensive understanding of their toxic effects is necessary to safely expand their use, and this review uses CUO and Xenoemphies as examples to discuss how key factors such as size, surface characteristics, dissolution, and exposure routes mediate toxic effects and corresponding mechanisms including oxidative stress, coordination effects, and non-homostasis effects. This article was authored by Yanan Chang, Jun Zhang, Geng Mei Xing, and others.