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Topic: Celebrating Children’s Health Month - Researching Developmental Toxicity Models

Who: Dr. Thomas Knudsen, Developmental Systems Biologist , Center for Computational Toxicology and Exposure

When: October 22, 2020 from 11:00 AM- 12:00 PM EST

Where: Register for webinar using EventbriteExit and check the confirmation email for webinar information.

Topic overview:

High-throughput in vitro assays offer a promising alternative to pregnant animal studies for assessing developmental toxicity of chemicals. Varying cells used in high-throughput screening assays have unique properties of self-renewal, pluripotency, and self-organization which help them to be excellent models of the developing embryo. Many studies have shown positive predictive value (PPV) of these cell lines for detecting developmental toxicity potential; however, translatability to pregnancy and development will require integrative computational models that recapitulate the full complementation of developmental pathways, maternal-placental toxicokinetics, and toxicodynamics of an exposed embryo.

Research under EPA’s Virtual Tissues Models is investigating the translatability of diverse cell-based platforms and computer models to evaluate effects of thousands of chemicals. A commercial platform was used to evaluate 1065 chemicals on a metabolic biomarker a cell line [Zurlinden et al. 2020]. A second platform evaluated 1047 chemicals using another cell line for a biomarker of gastrulation [Hunter et al., manuscript under review]. A challenge for science and technology is to gain a holistic understanding of the applicability domain and blind spots of cell platforms, as well as outcomes against which a PPV may be qualified. Advanced computer models and micropatterned in vitro platforms will enable recoding of cell-based data into the genomic blueprint of early development.

This abstract does not necessarily reflect U.S. EPA policy.

For more information visit the EPA's Computational Toxicology Communities of Practice webpage