Evaluation of food-relevant chemicals in the ToxCast high-throughput screening program.
Thousands of chemicals are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The landscape of the food-relevant chemical universe was evaluated using cheminformatics, and subsequently the bioactivity of food-relevant chemicals across the publicly available ToxCast highthroughput screening program was assessed. In total, 8659 food-relevant chemicals were compiled including direct food additives, food contact substances, and pesticides. Of these food-relevant chemicals, 4719 had curated structure definition files amenable to defining chemical fingerprints, which were used to cluster chemicals using a selforganizing map approach. Pesticides, and direct food additives clustered apart from one another with food contact substances generally in between, supporting that these categories not only reflect different uses but also distinct chemistries. Subsequently, 1530 food-relevant chemicals were identified in ToxCast comprising 616 direct food additives, 371 food contact substances, and 543 pesticides. Bioactivity across ToxCast was filtered for cytotoxicity to identify selective chemical effects. Initiating analyses from strictly chemical-based methodology or bioactivity/cytotoxicity-driven evaluation presents unbiased approaches for prioritizing chemicals. Although bioactivity in vitro is not necessarily predictive of adverse effects in vivo, these data provide insight into chemical properties and cellular targets through which foodrelevant chemicals elicit bioactivity.
ILSI North America Technical Committee on Food and Chemical Safety Summer Fellow, Washington, DC, USA; Oak Ridge Institue for Science and Education (ORISE) Fellow at the US Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC, USA. Electronic address: agnes.karmaus@gmail.com.
Agnes L
AL
Karmaus
Oak Ridge Institue for Science and Education (ORISE) Fellow at the US Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC, USA.
Dayne L
DL
Filer
US Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC, USA.
Matthew T
MT
Martin
US Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC, USA.
Keith A
KA
Houck
D002470:Cell Survival / Q000187:drug effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D005506:Food Contamination / Q000032:analysis*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis*; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency
D004364:Pharmaceutical Preparations
Food additive; Food contact substance; High-throughput screening; Pesticide; ToxCast