Most studies of nanomaterial
environmental impacts have focused
on relatively simple first-generation nanomaterials, including metals
or metal oxides (e.g., Ag, ZnO) for which dissolution largely accounts
for toxicity. Few studies have considered nanomaterials with more
complex compositions, such as complex metal oxides, which represent
an emerging class of next-generation nanomaterials used in commercial
products at large scales. Importantly, many nanomaterials are not
colloidally stable in aqueous environments and will aggregate and
settle, yet most studies use pelagic rather than benthic-dwelling
organisms. Here we show that exposure of the model benthic species Chironomus riparius to lithium cobalt oxide (Li
x
Co1–x
O2, LCO) and lithium nickel manganese cobalt oxide (Li
x
Ni
y
Mn
z
Co1–y–z
O2, NMC) at 10 and 100 mg·L–1 caused 30–60% declines in larval growth and a delay of 7–25
d in adult emergence. A correlated 41–48% decline in larval
hemoglobin concentration and related gene expression changes suggest
a potential adverse outcome pathway. Metal ions released from nanoparticles
do not cause equivalent impacts, indicating a nanospecific effect.
Nanomaterials settled within 2 days and indicate higher cumulative
exposures to sediment organisms than those in the water column, making
this a potentially realistic environmental exposure. Differences in
toxicity between NMC and LCO indicate compositional tuning may reduce
material impact.
Growing evidence across organisms points to altered energy metabolism as an adverse outcome of metal oxide nanomaterial toxicity, with a mechanism of toxicity potentially related to the redox chemistry of processes involved in energy production. Despite this evidence, the significance of this mechanism has gone unrecognized in nanotoxicology due to the field's focus on oxidative stress as a universalbut nonspecific nanotoxicity mechanism. To further explore metabolic impacts, we determined lithium cobalt oxide's (LCO's) effects on these pathways in the model organism Daphnia magna through global gene-expression analysis using RNA-Seq and untargeted metabolomics by direct-injection mass spectrometry. Our results show that a sublethal 1 mg/L 48 h exposure of D. magna to LCO nanosheets causes significant impacts on metabolic pathways versus untreated controls, while exposure to ions released over 48 h does not. Specifically, transcriptomic analysis using DAVID indicated significant enrichment (Benjamini-adjusted p ≤0.0.5) in LCO-exposed animals for changes in pathways involved in the cellular response to starvation (25 genes), mitochondrial function (70 genes), ATP-binding (70 genes), oxidative phosphorylation (53 genes), NADH dehydrogenase activity (12 genes), and protein biosynthesis (40 genes). Metabolomic analysis using MetaboAnalyst indicated significant enrichment (γ-adjusted p <0.1) for changes in amino acid metabolism (19 metabolites) and starch, sucrose, and galactose metabolism (7 metabolites). Overlap of significantly impacted pathways by RNA-Seq and metabolomics suggests amino acid breakdown and increased sugar import for energy production. Results indicate that LCO-exposed Daphnia respond to energy starvation by altering metabolic pathways, both at the gene expression and metabolite levels. These results support altered energy production as a sensitive nanotoxicity adverse outcome for LCO exposure and suggest negative impacts on energy metabolism as an important avenue for future studies of nanotoxicity, including for other biological systems and for metal oxide nanomaterials more broadly.
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