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Metal nanoparticles (NPs), such as TiO2 NPs, have been extensively researched for their potential use in aquaculture. One of the main uses of TiO2 NPs in aquaculture is as a natural water purifier. TiO2 has photocatalytic properties that make it highly effective in breaking down organic pollutants and toxic substances in water. Additionally, TiO2 NPs have been used to improve the efficiency of aquaculture feed. However, it is important to note that while the use of TiO2 NPs in aquaculture holds promise, there are also some concerns about their safety and environmental impact. Therefore, in this study, we sought to ascertain whether penicillamine and ethylenediaminetetraacetic acid (EDTA), two compounds used in the treatment of heavy metal poisoning and whose efficacy has been demonstrated in both warm-blooded animals and humans, may lessen the toxicity of TiO2 NPs in Nile tilapia. In this study, 280 Nile tilapia fries (3.20±0.12 g) were split into four treatments over the course of three replications. Following that, the OECD Guidelines for the Testing of Chemicals was used to evaluate and compare the acute toxicity of TiO2 NPs. In all stages of toxicity determination, the data demonstrated that the toxicity of TiO2 NPs in the control treatment was significantly higher than that of the treatments given penicillamine and EDTA. Finally, the efficiency of penicillamine is more than that of EDTA, and both of these drugs can be used orally to prevent and treat seafood poisoning caused by TiO2 NPs. [ABSTRACT FROM AUTHOR]