A Semenov-type analysis is made of the conditions for an exothermic runaway reaction in an "organic phase" (or "red oil") made up of tri-n-butyl phosphate (TBP) saturated with nitric acid (HNO3). Also, a theoretical framework is developed to predict the critical organic layer depth above which a runaway will occur when the organic layer rests on a layer of aqueous nitric acid ("aqueous phase"). Available calorimetry data on peak pressurization rates during vented TBP/HNO3 reactions are rationalized using orifice flow theory, which provides a simple criterion for the required vent area for vessel pressure relief during a red oil runaway. Finally, it is shown that the Tomsk-7 accident can be explained by a combination of weak reaction tempering at the vessel relief valve set pressure and insufficient venting capacity. The formulations for determining the onset of a TBP/HNO3 runaway outlined in this paper rely heavily on the empirical and semiempirical equations developed in the companion paper "Thermal Stability and Safe Venting of the Tri-N-Butyl Phosphate-Nitric Acid-Water ("Red Oil") System - II: Experimental Data on Reaction Self-Heat Rates and Gas Production and Their Correlation," Nuclear Technology, Vol. 163, p. 294 (2008), which deals with the chemical self-heat rate in the organic phase, the gas production rate in the organic phase, and the superficial gas velocity across the aqueous-organic interface of a two-layer organic over aqueous configuration.