(1319-D) Identifying potential adverse health effects of chemicals by screening on a panel of safety-related biological targets
Tuesday, February 6, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: Numerous chemicals in foods and dietary supplements have unknown effects on human health. Since traditional toxicology testing (animal testing) is not always feasible due to high cost and labor, rapid and higher-throughput methods are needed. To rapidly identify potential chemical hazards, in silico models and in vitro assays were used to predict and measure binding between chemicals and safety-related biological targets (e.g., receptors, ion channels, transporters, and enzymes). A collection of food-related, structurally similar chemicals was evaluated, most of which have no human or animal toxicology data available. Target binding profiles were predicted by a commercial in silico model that is based upon quantitative structure-activity relationship (QSAR) models. Target binding was also measured in vitro by biochemical assays (competitive binding and enzyme inhibition). Generally, predicted binding to serotonin, norepinephrine, and dopamine transporters agreed with binding measured in vitro. These targets are associated with adverse health effects in the heart and nervous system. Additionally, some in silico target predictions were false positives including serotonin, adrenergic, and histamine receptors. The in vitro target binding profiles for analogues having no in vivo toxicology data were compared to a chemical in the collection that adversely affects the heart and nervous system in vivo. Methyl analogues, for example, had similar target binding profiles (nanomolar) as the chemical studied in vivo, indicating a potential for the analogues to cause similar adverse health effects. However, formyl analogues exhibited weak binding (micromolar) to these targets. Biological target profiling is an important initial step to identify potential adverse health effects. Ultimately, the integration of target profiles with pharmacokinetics and human exposure levels can serve as a holistic approach to help identify adverse health effects of structurally analogous chemicals.