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As nanotechnology progresses from research and development to commercialization and use, it is likely that manufactured nanomaterials and nanoproducts will be released into the environment. EPA is charged with protecting human health and the environment, as well as ensuring that the application of engineered nanotechnology products occur without unreasonable harm to human health or the environment. The unique features of manufactured nanomaterials and a lack of experience with these materials hinder the risk evaluation that is needed to inform decisions about pollution prevention, environmental clean-up and other control measures, including regulation. Beyond the usual concerns for most toxic materials, such as physical and chemical properties, uptake, distribution, absorption, and interactions with organs, the immune system and the environment, the adequacy of current toxicity tests for chemicals needs to be assessed to develop an effective approach for evaluating the toxicity of nanomaterials. To the extent that nanoparticles are redox active or elicit novel biological responses, these concerns need to be accounted for in toxicity testing to provide relevant information needed for risk assessment to inform decision making.