2019 SOT FDA Colloquium: In Silico Modeling and Methods for Food Ingredient, Dietary Supplement, and Cosmetic Safety

The Society of Toxicology in conjunction with the US FDA Center for Food Safety and Applied Nutrition (CFSAN) have partnered to provide this colloquia series. The series presents scientific information that is high-quality, cutting-edge, future-oriented toxicological science to provide a well-grounded foundation to inform the work of US FDA employees.

On May 15, 2019, SOT and the US FDA hosted a colloquium that featured the science behind new international trends in the in silico safety assessment of chemical exposure.

Two common themes shared by international regulatory bodies are the critical issues involved in alternative methods to animal testing and the rigorous treatment of uncertainties to obtain reproducible and transparent weight-of-evidence approaches to decision making. For alternative methods to repeated-dose toxicity, toxicokinetics and metabolism are emphasized to understand chemical exposure and bioavailability. Biokinetics is further being applied to data-waiving methods such as the Threshold of Toxicological Concerns (TTC). Internal TTC is a TTC concept for situations of low internal exposure, where this value is more relevant than the external exposure. Development of internal TTCs requires a significant amount of data and computational tools (e.g., PBPK modeling) to convert the chemical specific external doses (i.e., NOAELs) in the TTC databases into an estimate of the internal exposure. The common concerns related to the relevance of in silico chemical safety assessment that may hinder its adoption if not properly addressed will be discussed.