This study investigates the RCMD characteristics and toxicity based on the geographic locations. Dissolution experiments in simulated lung fluids (SLFs) and in-vitro response were conducted to determine the toxicity level of samples collected from 5 mines in the Rocky Mountains and Appalachian regions. Dust characteristics were investigated using various dust characterization studies. Inductively coupled plasma mass spectrometry was conducted to determine the concentration of metals dissolved in the SLFs. Finer particle sizes, and higher mineral and elemental contents were found in samples from the Appalachian regions. Si, Al, Fe, Cu, Sr, and Pb were found in dissolution experiments, but no trends were found indicating higher dissolutions in the Appalachian region. The toxicity of the samples based on the metal dissolutions in SLFs and the in-vitro inflammatory response could not be related to the geographic location. Therefore, the higher incidence of lung diseases in the Appalachian region may be related to other factors like the exposure to RCMD, the particle size distribution of the actual RCMD in each mine, and the mineral contributions from the different sources in the mine.