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The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined. Clustering of the assays based on frequency of affected assays resulted in a ranking of the test compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We conclude that the combination of ESC- and zebrafish-based assays provides a valuable platform for the prioritization of pharmaceutical and industrial chemicals for further testing of developmental toxicity in rodents., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Environmental factors affecting nutrient availability during development can cause predisposition to diseases later in life. To identify chemicals in the environment capable of altering nutrient mobilization, we analyzed yolk malabsorption in the zebrafish embryo, which relies on maternally-derived yolk for nutrition during its first week of life. Embryos of the transgenic zebrafish line HGn50D, which fluoresce in the yolk syncytial layer, were exposed from two to five days post fertilization to different chemicals. We developed a software package to automatically and accurately segment and quantify the area of the fluorescing yolk in images captured at the end of the treatment period. Based on this quantification, we found that prochloraz decreased yolk absorption, while butralin, tetrabromobisphenol A, tetrachlorobisphenol A and tributyltin increased yolk absorption. Given the number and variety of industrial chemicals in commerce today, development of automated image processing to perform high-speed quantitative analysis of biological effects is an important step for enabling high throughput screening to identify chemicals altering nutrient absorption., (Copyright © 2014 Elsevier Inc. All rights reserved.)