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Many different rock intervals are used for brine disposal injection in the Appalachian Basin. The study area was defined as eastern Kentucky, Ohio, Pennsylvania, and West Virginia. Brine injection in the study area has increased from approximately 6–7 million barrels (bbl) per year in the early 2000s to 17.6 million bbl in 2012, mostly due to shale gas activity. A review of geologic properties and subsurface distribution of rock formations used for injection is useful to understand brine disposal operations in the region. Operational data on injection rates and pressures were compiled for 2008–2012 for more than 300 class II brine disposal wells. Several class II brine disposal wells were monitored with continuous wellhead pressure loggers to estimate reservoir properties and understand injection operations. Project results provide a catalog of injection rates for the various formations, which range from hundreds to more than 100,000 bbl per month per well. Hydrologic analysis of depleted hydrocarbon reservoirs and deep saline formations in the study area indicates that there is a large capacity for brine disposal, but the characteristics of the rock formations may limit injection rates. Based on hydrocarbon production and brine injection volumes from 2008 to 2012, approximately 9984 bbl of brine were routed to class II brine disposal wells per billion cubic feet gas production, which suggests ultimate demand of up to 706–2290 million bbl brine disposal related to unconventional Marcellus and Utica plays. Understanding the geology and operational history of the injection zones is critical to support safe, reliable, and environmentally responsible brine disposal in the region.