Toxicity assessment of metal oxide nanomaterials using screening and murine acute inhalation studies.

Characterizations and toxicity screening were performed on metal oxide engineered nanomaterials (ENMs) independently comprising ZnO, CuO, CeO, FeO, WO, VO, TiO, AlO and MgO. Nanomaterials that exhibited the highest toxicity responses in the screening assays (ZnO, CuO, and VO) and the lesser explored material WO were tested for acute pulmonary toxicity . Female and male mice (C57Bl/6J) were exposed to aerosolized metal oxide ENMs in a nose-only exposure system and toxicity outcomes (biomarkers of cytotoxicity, immunotoxicity, inflammation, and lung histopathology) at 4 and 24 h after the start of exposure were assessed. The studies were performed as part of the NIEHS Nanomaterials Health Implications Research consortium with the purpose of investigating the effects of ENMs on various biological systems. ENMs were supplied by the Engineered Nanomaterials Resource and Coordination Core. Among the ENMs studied, the highest toxicity was observed for CuO and ZnO NPs in both and acute models. Compared to sham-exposed controls, there was a significant increase in bronchoalveolar lavage neutrophils and proinflammatory cytokines and a loss of macrophage viability at both 4 h and 24 h for ZnO and CuO but not seen for VO or WO. These effects were observed in both female and male mice. The cell viability performed after exposure to ENMs and assessment of lung inflammation after acute inhalation exposure were shown to be sensitive endpoints to predict ENM acute toxicity.