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In Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles
Citation:
Cupi, D. AND K. L. DREHER. In Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
Abstract describes research to develop rapid predictive alternative pulmonary toxicity testing methods for engineered nanoparticles.
Description:
Nanomaterials (NMs) encompass a diversity of materials with unique physicochemical characteristics which raise concerns about their potential risk to human health. Rapid predictive testing methods are needed to characterize NMs health effects as well as to screen and prioritize NMs for comprehensive toxicological assessments. BEAS2B human bronchial epithelial cells were employed to assess the in vitro pulmonary toxicity of 4 Ti02 and 4 Ce02 particles varying is size (6 -1288nm), morphology and crystalline structure. Exposures were conducted over several concentrations for each endpoint examined. No BEAS2B cytotoxicity was observed for any particle following a 24 hr exposure to concentrations up t0 100 ug/ml.The ability of Ti02 and Ce02 particles to induce inflammation and oxidative stress was assessed by gene induction using RT-PCR. At 50 ug/ml maximal lL-8 and IL-6 gene induction by 6nm Ti02 and 8nm Ce02 NMs was observed at 6hr and 24hr post-exposure, respectively, with 8nm Ce02 NMs producing the greatest induction of cytokine mRNA levels. Smaller Ti02 and Ce02 NMs produced greater induction of IL-8 and IL-6 mRNA levels compared to their larger sized counterparts. At 50 ug/ml all Ti02 and Ce02 particles induced similar increases in HO-1 mRNA levels at 6hr and 24hr post-exposure, respectively. The pattern of HO-1 gene induction was inconsistent with a role of oxidative stress in metal oxide induced BEAS2B cytokine gene expression. Pretreatment of BEAS2B cells with IKK inhibitor III BMS-345541 completely inhibit 25nm Ti02 and 69nm Ce02 NM induction of IL-8, IL-6 and HO-1 gene expression indicating a role of NFkB in these responses. A cell-based ELISA for NFKB p65 phosphorylation revealed rapid Ser536 phosphorylation in BEAS2B cells following exposure to 50 ug/ml of Ti02 and Ce02 NMs with sizes ≥25nm. Results demonstrate the ability to employ in vitro methods to assess NM induced pulmonary toxicity. Some responses were found not to be totally dependent on NM size/surface area indicating composition and surface properties playa role in mediating NM toxicity. This abstract does not reflect EPA policy.