Systemic Toxicity and Teratogenicity of Copper Oxide Nanoparticles and Copper Sulfate

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Abstract
Acceleration in development of metallic nanoparticles for their utility in medical and technological applications due to their unique physicochemical properties has concurrently raised a matter of concern due to their potential toxicity. Of the enormous metallic nanostructures, copper oxide nanoparticles (CuONPs) having optical and electrochemical properties are scrutinized for theranostic applications. Therefore, their safety profile is of a major concern in optimizing a safe dose for its clinical utility. Considering the potency of CuONPs in epitomizing toxicity, we report a dose and time dependent acute, systemic and transgenerational toxicity profile of CuONPs in comparison to the bulk copper as copper sulfate (CuSO4). Acute toxic dose (LD50(14)) of CuONPs (400 mg/kg · b · wt) was found to be three fold higher that of CuSO4(100 mg/kg · b · wt). Comparative steady state evaluation showed that CuONPs (≥5 mg/kg · b · wt.) induce greater dose and time dependent oxidative stress by increase in protein carbonylation and decreased glutathione levels in comparison to the bulk CuSO4. Furthermore, CuONPs were found to disrupt blood brain barrier (BBB) and sneak in to the brain which was quantified by atomic absorption spectroscopy (AAS) and also coax toxicity in liver, kidney and spleen, ascertained by histopathological findings (at ≥5 mg/kg · b · wt.). Considering transgenerational toxicity, CuONPs in comparison to CuSO4 severely affected sperm count and morphology in male animals, though not much teratological effects were observed, except certain extent of embryo resorption. The present study highlights a complete toxicity profile of CuONPs, giving forethought for considering them for clinical applications.