Evaluation of Potential Cytotoxicity of Nanoscale Inorganic Oxides Utilized in Semiconductor Manufacturing

Sierra-Alvarez, Reyes; Otero, Lila; Garcia, Antonia Luna-Velasco, Angel Cobo, Jim A Field , Citlali
(University of Arizona, Tucson)

Authors: Reyes Sierra-Alvarez, Lila Otero, Citlali Garcia, Antonia Luna-Velasco, Angel Cobo, Jim A Field The future success of the semiconductor industry is dependent on the capacity to manufacture smaller and smaller devices which requires the use of nanoparticles (NPs). Numerous reports have been published in recent years expressing concern for the potential toxicity of NPs to humans and ecologically important species. The objective of this work was to investigate the potential cytotoxicity of nanoscale inorganic oxides commonly utilized in semiconductor manufacturing (SiO2, Al2O3, CeO2) and emerging inorganic oxide nanoparticles (HfO2). Other commercially-important inorganic oxides (ZnO, TiO2, ZrO2, Mn2O3) were also included in the study for comparison. Nanotoxicity was assessed using several well-established bioassays (e.g., Microtox, yeast respiration measurements, MTT) and a recently developed impedance-based Real Time Cell Assay (RTCA). The target cells in those bioassays included bacteria, yeast, and human cells. Additional assays were performed to evaluate the potential involvement of reactive oxygen species (ROS), toxic soluble species, and/or decrease in cell membrane integrity on cytotoxicity. Furthermote, the particle size distribution and fraction of inorganic oxide effectively dispersed in the various bioassay media was investigated in order to get information on the actual hydrodynamic diameter and state of dispersion of the nanomaterials. With the exception of SiO2 which formed highly stable dispersions, the nanoscale inorganic oxides tested showed a high tendency to aggregate in most biological media resulting in micron-size aggregates that settled out of the dispersion. ZnO and Mn2O3 were the most inhibitory inorganic oxide nanomaterials evaluated with 50% inhibiting concentrations often in the low ppm range. In contrast, CeO2 and HfO2 were nontoxic in most assays at concentrations as high as 1,000 mg L-1. Nanosized SiO2 and Al2O3 showed intermediate to low cytotoxicity. The underlying mechanisms involved in the cytotoxicity of these nanomaterials are currently under investigation. Furthermore, the results obtained indicated the potential of impedance based RTCA to rapidly screen for nanoparticle toxicity. Future research will address validation of the RTCA results using conventional cytotoxicity tests.

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