Mapping the Chemical Anatomy of Processed Foods: GRAS Additives, Synergy Networks, and Structural Gaps in U.S. Food Regulation

The U.S. “Generally Recognized as Safe” (GRAS) framework is intended to safeguard the food supply, yet structural gaps have enabled widespread use of food additives with limited oversight. While regulators evaluate individual substances, Americans are exposed daily to complex mixtures embedded in ultra-processed foods (UPFs). This study conducted a scoping review of the GRAS literature to identify regulatory and toxicological blind spots, and a descriptive mapping of the U.S. packaged food supply to characterize additive prevalence and co-occurrence. Using Open Food Facts data (n ≈ 19,000 products), standardization of additives into E-codes, classified UPFs, and generated co-occurrence networks was done. Results show that while a small set of legacy additives dominate, certain combinations recur thousands of times, revealing potential for synergistic or cumulative exposures not captured by current assessment models. Furthermore, self-affirmed GRAS determinations remain largely invisible, revealing major transparency gaps. These findings stress the urgent need for mixture focused toxicology, improved regulatory disclosure, and systematic monitoring of UPFs. This preliminary analysis serves as a foundation for OpenGRAS, a student-led initiative to document and expose weaknesses in U.S. food additive governance.