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This study models emissions quantities and neighboring exposure concentrations of six airborne pollutants, including PM10, PM2.5, crystalline silica, arsenic, uranium, and barium, which resulted from the disposal of Marcellus shale drill cuttings waste during the 2011–2017 period. Using these predicted exposures, this study evaluates current setback distances required in Pennsylvania from waste facilities. For potential residents living at the perimeter of the current setback distance, 274 m (900 ft), a waste disposal rate of 612.4 metric tons per day at landfills (the 99th percentile in record) does not result in exceedances of the exposure limits for any of the six investigated pollutants. However, the current setback distance can result in exceedance with respect to the 24-hr daily concentration standards for PM10 and PM2.5 established in the National Air Ambient Quality Standards (NAAQS), if daily waste disposal rate surpasses 900 metric tons per day. Dry depositions of barium-containing and uranium-containing particulate matter should not be a danger to public health based on these results. To investigate the air quality impacts of waste transportation and the potential for reductions, this article describes an optimization of landfill locations in Pennsylvania indicating the potential benefits in reduced environmental health hazard level possible by decreasing the distance traveled by waste disposal trucks. This strategy could reduce annual emissions of PM10 and PM2.5 by a mean of 64% and reduce the expected number of annual fatal accidents by nearly half, and should be considered a potential risk management goal in the long run. Therefore, policy to limit or encourage reduction of distances traveled by waste removal trucks and manage setback distances as a function of delivered waste quantities is merited. This study shows the necessity of reviewing current setback distance required in Pennsylvania, which might not ensure 24-hr mean PM10 and PM2.5 levels below the values stated in National Ambient Air Quality Standards for the residents living at the perimeter. Furthermore, this study also reveals potential tremendous benefits from optimizing location of landfills accepting drill cuttings within Pennsylvania, with PM10 and PM2.5 emission, total distance traveled shrinking, and number of fatal accidents shrinking by nearly half. [ABSTRACT FROM AUTHOR]