Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

Abstract

Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits (neurodegeneration, response to stress).

High‐throughput COPAS assay for screening of developmental and reproductive toxicity of nanoparticles using the nematode Caenorhabditis elegans

“…There is an urgent need for consistent and accurate HTS systems for rapid toxicity assessment of emerging NMs (Ban, Zhou, Sun, Mu, & Hu, ). The present study showed that the HTS strategy using C. elegans can be successfully applied for toxicity assessment of ENMs, as has been reported in previous studies on NMs and various environmental toxicants (Hunt et al, ; Jung et al, ; Mashock et al, ; Shin et al, ). The developmental and reproductive toxicity assay described in this study used the COPAS Biosort assay for counting the number and measuring the size of C. elegans at L1 larval and adult stages.…”

ChemFate: A fate and transport modeling framework for evaluating radically different chemicals under comparable conditions

“…3 g L À1 for nano copper oxide (Mashock et al, 2016). Compared to soil bulk concentrations, it is likely that toxic effects may be observed in soil for chlorothalonil and nano copper oxide.…”

Interaction of Copper-Based Nanoparticles to Soil, Terrestrial, and Aquatic Systems: Critical Review of the State of the Science and Future Perspectives

“…In addition, some studies report that Cu-based NPs can also have adverse effects on multicellular soil organisms. For instance, the CuO-NPs affected growth and neuron morphology of a transgenic Caenorhabditis elegans (Mashock et al 2016), and disturbed immunity and reduced population density of a common earthworm…”