A systematic procedure to select solvents in mass separating agent (MSA) driven technologies so as to account for plant-wide point source or post-release environmental interactions is presented in this paper. A three step procedure is proposed involving identification of all agent-based operations within the process of interest, determination of a list of candidate solvents satisfying separation task operational and environmental constraints, and selection of an optimal solvent candidate based on global plant-wide process and environmental constraints. Environmental impact assessment techniques including post-release environmental damage are also incorporated in the solvent selection framework. Two examples are presented to illustrate the viability of the approach; trade-offs are discussed regarding cost and environmental impact objectives.