1868

Abstract
Background: More than 8,000 chemical additives are permitted in food in the United States, however, most lack adequate health and safety information. High-throughput screening tools, such as Toxicity Forecaster (ToxCast), provide opportunities to quickly assess and prioritize thousands of food additives for further investigation. Given the significant lack of in vivo data for most chemicals, we aimed to characterize the toxicity data available for chemical food additives using ToxCast.
Methods: We developed an up-to-date inventory of chemical food additives utilizing information from the U.S. Food and Drug Administration, the Environmental Protection Agency, and private manufacturers. We quantified the number of chemicals with ToxCast data available, and conducted a preliminary analysis of toxicity data for selected phthalates and phthalate alternatives (di(2-ethylhexyl) phthalate (DEHP), diisononyl cyclohexane-1,2-dicarboxylate (DINCH), N,N-Diethylhydroxylamine (DEHA), and bis (2-ethylhexyl) terephthalate (DEHT)).
Results: Our updated inventory indicates that there are more than 9,000 chemicals allowed in contact with food, including direct and indirect additives, food packaging chemicals, pesticide residues, and substances generally recognized as safe. Preliminary analyses suggest that approximately 23% of these have ToxCast data available. Comparing bioassay data in ToxCast for selected phthalates and phthalate alternatives, we found DEHP to be the most toxic chemical, with 40 active endpoints related to cell morphology, DNA binding, and nuclear receptors. DEHT had seven bioactive endpoints, followed by DINCH and DEHA each with 3 active endpoints. DEHA was the only plasticizer with no bioactivity for nuclear receptor assays, one important biological pathway for toxicity in humans.
Conclusions: ToxCast may be a useful tool for characterizing the toxicity of chemical food additives. Future analyses will focus on more diverse biological endpoints and compare ToxCast results to available in vivo data. These analyses will help advance understanding on the appropriateness of ToxCast for regulatory decision-making.