A perspective on enhancing chemical alternative assessments by prioritizing conditions of use

Alternative assessment (AA) for chemical substitution has traditionally been motivated by reducing hazards while minimizing exposure to toxic substances. However, this approach of AA can prematurely eliminate many potential candidate chemicals before considering their technical performance and role. This perspective paper proposes a paradigm shift to prioritize the primary functional requirements of a chemical's given application before adopting the safer and more economical alternative from a life cycle perspective, including raw material extraction and refinement, chemical synthesis, product manufacturing, conditions of use (CoU), and end-of-life management. The adoption of this approach is represented as a mixed-integer nonlinear programming problem, aiming to minimize the differences in the properties of the chemical of interest and the targeted value for a CoU, while considering safety, regulatory limits, and economic feasibility as constraints. If successfully implemented, practical replacements within the acceptable safety parameters set forth by regulatory and nonregulatory entities can be determined to address chemical substitution challenges.