SOT FDA Colloquium: Analysis of In Vitro to In Vivo Concordance Studies for Food Safety Assessment in Humans—October 24, 2017

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 October 24, 2017, SOT and US FDA hosted a colloquium focused on the state-of-the-art in using in vitro technologies for safety assessment and how they are being utilized.

Concordance in safety assessment generally refers to the accuracy of in vitro test results to correctly predict an in vivo response in humans. For food additive ingredients in vivo, animal studies in various targeted areas (e.g., carcinogenicity, neurological disorders, developmental delays and deficits, and reproductive disorders) are typically used. Dietary supplements and cosmetic ingredients, which do not require pre-market approval, still must be safe for consumer use and require safety assessments. Toxicological reviews for safety assessments typically consider in vitro data as one facet of their evaluation but there is increasing emphasis to increase their use and to replace some aspects of in vivo testing. Many challenges remain to be addressed (e.g., metabolic activation of agents in in vitro systems) and there are limitations to the interpretation of the data (e.g., the mechanistic relationship between rapid in vitro responses and more chronic in vivo responses), however, there also are benefits to using in vitro studies to assess safety (e.g., cost, speed of the assay, ability to use high-throughput, and high-output methods to address a large range of potential toxic substances). New and innovative in vitro technologies (e.g., high-throughput sequencing methods for quantifying gene expression, microRNA expression and proteomics) are emerging that may also increase concordance to tissue, organ, and the whole organism effects. However, there is still a need to improve scientific confidence in the utilization of these in vitro tests to replace in vivo testing in safety assessment.