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Nanotoxicology, is an important field that has started to unravel the adverse effects of nanoparticles. Major emphasis thus is being laid on developing strategies that reduce toxicity of the nanomaterial. Chemical transformations of metal nanoparticles are suggested to be an important way to mitigate nanoparticle toxicity. In the present study, we investigated the toxicity of copper and copper sulfide nanoparticles in a zebrafish model by using a series of biomarkers of toxicity. Exposure of zebrafish to copper nanoparticles enhanced liver oxidative stress, altered detoxification enzymes and affected brain acetylcholinesterase activity. However, exposure of zebrafish to sulfidated copper nanoparticles rescued these parameters. Histopathological analyses of liver and metallothionein levels also support the significance of sulfidation as a potential mechanism for controlling copper nanoparticle toxicity. More importantly, micronucleus formation was shown to be highly reduced in liver of fish that were exposed to sulfidated copper nanoparticle when compared to non-sulfidated nanoparticle. The presented biochemical data provides strong evidence for the reduction in copper nanoparticles toxicity when it undergoes chemical transformation as copper sulfide. 4 human exposure. In spite of the great developments in understanding the toxicity of metal-based nanomaterials, their general mechanism of toxicity, however, remains enigmatic.Of late, green synthesis of metal NPs, that employs biomolecules and organisms, such as bacteria, fungi, proteins, biopolymers and plant extracts, has been receiving widespread attention in order to reduce their potential toxicity. [26][27][28][29] Nevertheless, both biogenic NPs and NPs prepared using synthetic materials exhibit good antibacterial activity. Any unwanted exposure to such an antibacterial agent, thus may produce adverse effect to non-target organisms. To the best of our knowledge, this is the first in vivo report to investigate the toxicity of biogenic CuNPs employing adult zebrafish. Zebrafish is an important model organism in biomedical research, which shares many common biological pathways with humans and is 80% genetically identical to humans. In this paper, we report the synthesis of biogenic CuNPs and copper sulfide (CuS) NPs using guar gum as capping agent and hydrazine as reducing agent. Guar gum is a biocompatible polysaccharide composed of galactomannan. Metal sulfidation has been suggested to be a natural method to minimize the toxicity of silver NPs. 30 To test this concept on CuNPs, we assessed the toxicity of CuNPs and CuS NPs in adult zebrafish employing various complementary biochemical assays that are routinely used in toxicological studies. Our results show that CuNPs enhances liver oxidative stress, alters liver detoxification enzymes, affects brain acetylcholinesterase activity and triggers micronucleus formation in liver; interestingly sulfidation of CuNPs resulted in significant rescue of all the biomarkers studied. In addition, histopathological analyses...