The AOP concept was used to translate ToxCast high-throughput screening data into a ToxPi matrix of 1058 chemicals x 24 features ordered by predicted potential to disrupt angiogenesis. This dataset is associated with the following publication: Saili, K., J. Franzosa, N. Baker, R. Ellis-Hutchings, R. Settivari, E. Carney, R. Spencer, T. Zurlinden, N. Kleinstreuer, S. Li, M. Xia, and T. Knudsen. Systems Modeling of Developmental Vascular Toxicity. Current Opinion in Toxicology. Elsevier BV, AMSTERDAM, NETHERLANDS, 15(1): 55-63, (2019).

The AOP concept was used to translate ToxCast high-throughput screening data into a ToxPi matrix of 1058 chemicals x 24 features ordered by predicted potential to disrupt angiogenesis. This dataset is associated with the following publication: Saili, K., J. Franzosa, N. Baker, R. Ellis-Hutchings, R. Settivari, E. Carney, R. Spencer, T. Zurlinden, N. Kleinstreuer, S. Li, M. Xia, and T. Knudsen. Systems Modeling of Developmental Vascular Toxicity. Current Opinion in Toxicology. Elsevier BV, AMSTERDAM, NETHERLANDS, 15(1): 55-63, (2019).

In zebrafish, 161 compounds were screened and 34 were identified by visual inspection as VDCs, of which 28 were confirmed as VDCs by quantitative image analysis. Testing of the zebrafish VDCs for their capacity to inhibit endothelial tube formation in the murine yolk-sac-derived endothelial cell line C166 identified 22 compounds that both disrupted zebrafish vascular development and murine endothelial in vitro tubulogenesis. This dataset is associated with the following publication: McCollum, C., J. Conde Vancells, C. Hans, M. Vazquez-Chantada, N. Kleinstreuer, T. Tal , T. Knudsen, S. Shah, F. Merchant, R. Finnell, J. Gustafsson, R. Cabrera, and M. Bondesson. (Reproductive Toxicology) Identification of vascular disruptor compounds by a tiered analysis in zebrafish embryos and mouse embryonic endothelial cells. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 70: 60-69, (2017).

In zebrafish, 161 compounds were screened and 34 were identified by visual inspection as VDCs, of which 28 were confirmed as VDCs by quantitative image analysis. Testing of the zebrafish VDCs for their capacity to inhibit endothelial tube formation in the murine yolk-sac-derived endothelial cell line C166 identified 22 compounds that both disrupted zebrafish vascular development and murine endothelial in vitro tubulogenesis. This dataset is associated with the following publication: McCollum, C., J. Conde Vancells, C. Hans, M. Vazquez-Chantada, N. Kleinstreuer, T. Tal , T. Knudsen, S. Shah, F. Merchant, R. Finnell, J. Gustafsson, R. Cabrera, and M. Bondesson. (Reproductive Toxicology) Identification of vascular disruptor compounds by a tiered analysis in zebrafish embryos and mouse embryonic endothelial cells. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 70: 60-69, (2017).

A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit. This dataset is not publicly accessible because: this paper uses EPA public data to build new datasets and analysis by non-EPA authors. It can be accessed through the following means: EPA data is publicly accessible. Format: N/A. This dataset is associated with the following publication: Theunissen, P., S. Beken, B. Beyer, W. Breslin, G.D. Cappon, C. Chen, G. Chmielewski, L. De Schaepdrijver, B. Enright, J. Foreman, W. Harrouk, K. Hew, A. Hoberman, J. Hui, T. Knudsen , S. Laffan, S. Makris , and M. Martin. (Crit. Rev. Tox.) Comparing rat and rabbit embryo-fetal developmental toxicity studies for 379 pharmaceuticals: On systemic dose and developmental effects. CRITICAL REVIEWS IN TOXICOLOGY. CRC Press LLC, Boca Raton, FL, USA, 1-13, (2016).

The data presented here support the application of the Stemina devTOXqP platform for predictive toxicology and further demonstrate its value in ToxCast as a novel resource that can generate testable hypotheses aimed at characterizing potential pathways for teratogenicity and HTS prioritization of environmental chemicals for an exposure-based assessment of developmental hazard. The dataset from the Stemina (STM) assay is annotated in the ToxCast portfolio as STM. Major findings from the analysis of ToxCast_STM dataset include (1) 19% of 1065 chemicals yielded a prediction of developmental toxicity, (2) assay performance reached 79%-82% accuracy with high specificity (> 84%) but modest sensitivity (< 67%) when compared with in vivo animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain. The results of this study will be useful to improving our ability to predict in vivo developmental toxicants based on in vitro data and in silico models. This dataset is associated with the following publication: Zurlinden, T., K. Saili, N. Rush, P. Kothiya, R. Judson, K. Houck, E. Hunter, N. Baker, J. Palmer, R. Thomas, and T. Knudsen. Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 174(2): 189-209, (2020).

The data presented here support the application of the Stemina devTOXqP platform for predictive toxicology and further demonstrate its value in ToxCast as a novel resource that can generate testable hypotheses aimed at characterizing potential pathways for teratogenicity and HTS prioritization of environmental chemicals for an exposure-based assessment of developmental hazard. The dataset from the Stemina (STM) assay is annotated in the ToxCast portfolio as STM. Major findings from the analysis of ToxCast_STM dataset include (1) 19% of 1065 chemicals yielded a prediction of developmental toxicity, (2) assay performance reached 79%-82% accuracy with high specificity (> 84%) but modest sensitivity (< 67%) when compared with in vivo animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain. The results of this study will be useful to improving our ability to predict in vivo developmental toxicants based on in vitro data and in silico models. This dataset is associated with the following publication: Zurlinden, T., K. Saili, N. Rush, P. Kothiya, R. Judson, K. Houck, E. Hunter, N. Baker, J. Palmer, R. Thomas, and T. Knudsen. Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 174(2): 189-209, (2020).

This dataset includes data used to generate Figures 4C, 5B, 5C, and 5D in Tal et al. Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity. Reproductive Toxicology. 2017. Data underlying all other figures shown in the manuscript are included in the Supplemental Tables published with the original article. This dataset is associated with the following publication: Tal , T., C. Kilty, A. Smith, C. LaLone , B. Kennedy, A. Tennant , C. McCollum, M. Bondesson, T. Knudsen , S. Padilla , and N. Kleinstreuer. Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 70: 70-81, (2017).

Previous work identified a ‘cytotoxic burst’ (CTB) phenomenon wherein large numbers of the ToxCast assays begin to respond at or near test chemical concentrations that elicit cytotoxicity, and a statistical approach to defining the bounds of the CTB was developed. To focus AOP development on the molecular targets corresponding to ToxCast assays indicating pathway-specific effects, we conducted a meta-analysis to identify which assays most frequently respond at concentrations below the CTB. A preliminary list of potentially important, target-specific assays was determined by ranking assays by the fraction of chemical hits below the CTB compared to the number of chemicals tested. Additional priority assays were identified using a diagnostic-odds-ratio approach which gives greater ranking to assays with high specificity but low responsivity. Combined, the two prioritization methods identified several novel targets (e.g., peripheral benzodiazepine and progesterone receptors) to prioritize for AOP development, and affirmed the importance of a number of existing AOPs aligned with ToxCast targets (e.g., thyroperoxidase, estrogen receptor, aromatase). This dataset is associated with the following publication: Fay, K., J. Swintek, D. Villeneuve, S. Edwards, M. Nelms, B. Blackwell, and G. Ankley. Differentiating pathway-specific from non-specific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 163(2): 500-515, (2018).