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This report addresses scientific issues and provides guidance on the conduct of the Environmental Protection Agency's (EPA) studies on Controlled Human Inhalation Exposure (CHIE). This report assesses the utility of CHIE studies to inform and reduce uncertainties in setting air-pollution standards to protect public health and assess whether continuation of such studies is warranted. It also evaluates the potential health risks to test subjects who participated in recent studies of air pollutants at EPA’s clinical research facility.