Developing a high throughput screening approach to predict the potential toxicity of engineered nanomaterials.

摘要

With rapid expansion in the industrial manufacturing and use of engineered nanomaterials (ENMs), there has come an increased concern for potential adverse effects from exposures to human health and the environment. Consequently, there are critical needs to identify hazards and to evaluate these novel materials so that ENM production and usage can be appropriately regulated. Since the existing toxicity approaches are unable to handle the rapid rate that these materials are being produced, the development of reliable, simple, high throughput toxicity screening approaches capable of predicting potential toxicity of these novel ENMs are needed.;The objects of this proposed study are (1) to develop a high throughput screening technique to predict the potential toxicity of engineered nanoparticles (ENPs) based on their ability to elicit biological oxidative damage (see Chapter II), (2) to utilize an approach that is simultaneously sensitive to multiple physicochemical parameters of ENPs to understand the influence of these factors on biological oxidative damage (see Chapter III), and (3) to evaluate the applicability of a newly optimized simple, robust, cell free approach---using the Ferric Reducing Ability of Serum (ERAS) assay as a nanotoxicity screening test (see Chapter IV).;The results demonstrated that (1) ERAS determined BOD reveals a dose relationship to ENP exposure levels, (2) the FRAS approach appears responsive to multiple determinants of potential toxicity, such as particle chemistry, surface area, crystallinity, morphology, and metal impurities, and (3) FRAS determined BOD shows a high concordance to other positive and negative reports of cytoxicity and inflammatory processes by nanomaterials in higher tier toxicity evaluations.