Chairs: Philip Marx-Stoelting & Helena Kandarova
New Approach Methodologies (NAMs) offer significant potential for high-throughput screening and chemical risk assessment of consumer ingredients, industrial chemicals, agrochemicals, and pharmaceuticals. Although the development of NAMs has been rapid, the key challenge is how to keep pace with and increase confidence in these novel methods to translate this new science into practical use, particularly within a regulatory context for decision-making. So far, a comprehensive array of toxicodynamic high-throughput NAMs encompassing relevant human biology, such as transcriptomics and phenotypic profiling applied to various cellular systems, along with targeted biochemical and functional assays, have been utilized to derive points of departure pertaining to hazard identification. These are integrated with high-throughput toxicokinetic models, parameterized with chemical-specific data, to predict exposure levels for typical use cases. However, the development and application of such NAM ‘toolboxes’ for reusable and adaptable safety assessments present challenges that necessitate drawing conclusions from heterogeneous types of source data and communicating associated uncertainties.
This symposium seeks to share extensive experiences from ongoing initiatives in Europe and the United States regarding the development, application, and utility of diverse NAM toolboxes for the characterization of systemic effects. Specifically, five real-world examples demonstrating the feasibility of employing different NAM batteries for safety assessments, derived from applications to numerous case study chemicals, will be presented. Vast experience and recent progress coming from academia, NGOs, the agrochemical, food, cosmetic and chemical industries will be presented. The symposium will be concluded with a discussion on further steps to build scientific confidence in NAM toolboxes for systemic toxicity and future directions to facilitate their regulatory acceptance.
Speakers
- Predrag Kukic – Building confidence in non-animal safety frameworks for systemic toxicity
- Danilo Basili – A NGRA approach to investigate chemical systemic toxicity in the food industry
- Matthias Wehr – Prioritization of ECHA chemicals using high-throughput in vitro screening methods
- Philipp Demuth – ID2STOT – A workflow for the classification of systemic toxicities based on concentrations of bioactivity referenced by internal doses