Nanomaterials (NMs), including nanoparticles (NPs), offer promising potential in achieving the European Commission's Green Deal goals of climate-neutral, zero-pollution and circular economy. Metal oxide NPs display antimicrobial properties, with efficacy also towards antimicrobial-resistant bacteria. Nevertheless, the increasing manufacture, use and unintended release of NMs particularly in aquatic compartments, raises concerns about their environmental sustainability and safety towards non-target organisms. Within the Safe and Sustainable by Design framework, this study compares toxicity and environmental impacts of sonochemically synthesized water-based CuO and Zn-doped CuO NPs. Zebrafish embryos were exploited in a high-throughput developmental and behavioral screening to investigate nanosafety. The Fish Embryo acute Toxicity test was used to assess the NPs aquatic toxicity potential, while behaviour was addressed by tracking embryos activity. The Life Cycle Assessment (LCA) methodology was implemented through the OpenLCA software to evaluate the environmental footprint of the NPs synthesis. Our findings showed no significative lethality at the tested concentrations (0.01-100 mg/L) (LC