A hierarchical approach to estimate the sustainability-potential of the alternative synthetic routes for the manufacture of vinyl chloride is presented. All the individual alternative synthetic routes (reaction paths) are identified by the graph-theoretic method based on P-graphs (process graphs). Subsequently, the individual alternative synthetic routes are sequentially assessed in descending order of quantifiability in terms of available energy, or exergy, dissipation the possible profit, and the toxicity index, respectively. Each of the synthetic routes surviving the scrutiny in light of available energy or exergy dissipation is subsequently assessed by evaluating its potential profit (gross profit). The toxicity of every synthetic route surviving the scrutiny in light of exergy dissipation and potential profit can be evaluated subsequently in terms of various toxicological properties from various existing databases. The toxicity index of a reacting species unlisted in the database can be estimated from those of similar chemicals already in the database. The overall toxicity index of synthetic route is computed as the sum of the toxicity indexes of all reacting species involved in its overall reaction. The efficacy of the approach is demonstrated with the manufacture of vinyl chloride. This is an abstract of a paper presented at the AIChE Annual Meeting (Salt Lake City, UT 11/4-9/2007).