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Evaluation of an adherent mouse embryonic stem cell in vitro assay to predict developmental toxicity of ToxCast chemicals.
Citation:
Jeffay, S., H. Nichols, M. Hoopes, Mitch Rosen, M. Barrier, AND S. Hunter. Evaluation of an adherent mouse embryonic stem cell in vitro assay to predict developmental toxicity of ToxCast chemicals. 10th World Congress Alternatives and Animal Use in the Life Sciences, Seattle, Washington, August 20 - 24, 2017.
Impact/Purpose:
The potential for most environmental chemicals to produce developmental toxicity is unknown. Mouse embryonic stem cell (mESC) assays are an alternative in vitro model to assess chemicals. The chemical space evaluated using mESC and compared to in vivo is limited. We used an adherent mESC assay to evaluate ToxCast Phase I and II chemicals at 2 time points and 4 concentrations ≤ 25uM. We monitored cell number and differentiation; goosecoid (GSC) and myosin heavy chain (MHC) protein biomarkers of day 4 gastrulation and day 9 cardiomyocytes, respectively. At day 4 of the 1078 chemicals evaluated, 114 affected GSC, 95 cell number and 173 both endpoints. At day 9 of the 320 chemicals evaluated, 34 affected MHC, 111 cell number and 60 both endpoints. For chemicals affecting mESC at both time points, 68% are reported as rodent developmental toxicants in EPA’s Toxicity Reference Database. mESCs can be used to prioritize potential developmental toxicants. This abstract does not reflect EPA Policy
Description:
The potential for most environmental chemicals to produce developmental toxicity is unknown. Mouse embryonic stem cell (mESC) assays are an alternative in vitro model to assess chemicals. The chemical space evaluated using mESC and compared to in vivo is limited. We used an adherent mESC assay to evaluate ToxCast Phase I and II chemicals at 2 time points and 4 concentrations ≤ 25uM. We monitored cell number and differentiation; goosecoid (GSC) and myosin heavy chain (MHC) protein biomarkers of day 4 gastrulation and day 9 cardiomyocytes, respectively. At day 4 of the 1078 chemicals evaluated, 114 affected GSC, 95 cell number and 173 both endpoints. At day 9 of the 320 chemicals evaluated, 34 affected MHC, 111 cell number and 60 both endpoints. For chemicals affecting mESC at both time points, 68% are reported as rodent developmental toxicants in EPA’s Toxicity Reference Database. mESCs can be used to prioritize potential developmental toxicants. This abstract does not reflect EPA Policy