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Effects of the Contaminant Candidate List – 4 (CCL4) on Differentiation and Cytotoxicity in Mouse Embryonic Stem Cells
Citation:
Nichols, H., S. Jeffay, M. Hoopes, AND S. Hunter. Effects of the Contaminant Candidate List – 4 (CCL4) on Differentiation and Cytotoxicity in Mouse Embryonic Stem Cells. 10th. World Congress - Alternatives and Animal Use in the Life Sciences, Seattle, WA, August 20 - 24, 2017. https://doi.org/10.23645/epacomptox.24520984
Impact/Purpose:
Poster presented to the 10th World Congress - Alternatives and Animal Use in the Life Sciences August 2017. The potential for environmental chemicals to produce birth defects is largely unknown. Mouse embryonic stem cells were used to profile the bioactivity of chemicals on the EPA Contaminant Candidate List 4 (CCL4). Differentiation and cytotoxicity were evaluated for 81 non-volatile chemicals on culture days 4 (gastrulation stage) and 9 (cardiomyocyte stage). Stage specific protein markers were used to assess differentiation. Twenty one chemicals were found to have bioactivity on culture day 4, 26 chemicals on day 9, and 20 chemicals had activity on both days. Based on previous work which showed that the combination of cell number on culture day 4 and differentiation on day 9 best correlate to in vivo toxicity, our analysis suggests that, at ≤ 100uM, 24 CCL4 chemicals would be categorized as potential developmental toxicants. These studies provide a basis to prioritize CCL4 chemicals for in-depth assessment. This abstract does not represent EPA policy.
Description:
The potential for environmental chemicals to produce birth defects is largely unknown. Mouse embryonic stem cells were used to profile the bioactivity of chemicals on the EPA Contaminant Candidate List 4 (CCL4). Differentiation and cytotoxicity were evaluated for 81 non-volatile chemicals on culture days 4 (gastrulation stage) and 9 (cardiomyocyte stage). Stage specific protein markers were used to assess differentiation. Twenty one chemicals were found to have bioactivity on culture day 4, 26 chemicals on day 9, and 20 chemicals had activity on both days. Based on previous work which showed that the combination of cell number on culture day 4 and differentiation on day 9 best correlate to in vivo toxicity, our analysis suggests that, at ≤ 100uM, 24 CCL4 chemicals would be categorized as potential developmental toxicants. These studies provide a basis to prioritize CCL4 chemicals for in-depth assessment. This abstract does not represent EPA policy.
URLs/Downloads:
DOI: Effects of the Contaminant Candidate List – 4 (CCL4) on Differentiation and Cytotoxicity in Mouse Embryonic Stem Cells
NICHOLS_2017-08-15.WC10-NEW-HPN_V5.PDF (PDF, NA pp, 1013.999 KB, about PDF)