cell culture information with toxicity and proteomic changes. This dataset is associated with the following publication: VanEmon, J., P. Pan, and F. Van Breukelen. Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney cells. CHEMOSPHERE. Elsevier Science Ltd, New York, NY, USA, 191: 537-547, (2018).

General toxicology, clinical chemistry, complete blood counts, histopathology, gene expression. This dataset is associated with the following publication: Chernoff, N., D. Hill, I. Chorus, D. Diggs, H. Huang, D. King, J. Lang, T. Le, J. Schmid, G. Travlos, E. Whitley, R. Wilson, and C. Wood. Cylindrospermopsin toxicity in mice following a 90-d oral exposure. ENVIRONMENTAL TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, USA, 549-566, (2018).

General toxicology, clinical chemistry, complete blood counts, histopathology, gene expression. This dataset is associated with the following publication: Chernoff, N., D. Hill, I. Chorus, D. Diggs, H. Huang, D. King, J. Lang, T. Le, J. Schmid, G. Travlos, E. Whitley, R. Wilson, and C. Wood. Cylindrospermopsin toxicity in mice following a 90-d oral exposure. ENVIRONMENTAL TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, USA, 549-566, (2018).

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).

Raw data file outputs of serum and urine measurements of GenX in dosed rodents. This dataset is associated with the following publication: Rushing, B., Q. Hu, J. Franklin, R. McMahen, S. Dagnino, C. Higgins, M. Strynar, and J. DeWitt. Evaluation of the Immunomodulatory Effects of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (“GenX”) in C57BL/6 Mice. ENVIRONMENTAL TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, USA, 156(1): 179-189, (2017).

Abstract CI-994 (acetyldinaline) is an investigational anticancer drug currently in clinical trials. In preclinical safety studies in rats and dogs, CI-994 resulted in significant toxicity to bone marrow and lymphoid tissue. To determine if apoptosis was involved in CI-994 toxicity, peripheral blood lymphocytes were isolated from untreated male Wistar rats and exposed to CI-994 (1, 3, 10, or 30 μM) in vitro for up to 24 hours. Morphological and biochemical features of apoptosis were evaluated using several techniques, and lactate dehydrogenase (LDH) release was measured as an indicator of cell necrosis. No evidence of apoptosis or necrosis was detected in lymphocytes exposed to CI-994 for 4 hours. After 24 hours, concentration-dependent increases in apoptosis characterized by DNA condensation, DNA fragmentation, and/or externalization of phosphatidyl serine were seen at CI-994 concentrations as low as 1 μM and were statistically significant beginning at 10 μM. Ultrastructural analysis confirmed the presence of DNA condensation, DNA fragmentation, cell shrinkage, and membrane blebbing in cells exposed to 30 μM CI-994. After 24 hours, the percent of maximum LDH release from lymphocytes treated with 10 and 30 μM CI-994 was 7% and 15%, respectively, compared with 0% in the controls. In comparison, morphological changes of apoptosis detected by fluorescent microscopy were observed in 79% of the lymphocytes at these two concentrations. Additionally, apoptosis was seen in more than 24% of lymphocytes exposed to 1 and 3 μM CI-994, whereas maximum LDH release was less than or equal to 1% at these concentrations. These results show that apoptosis is the primary mode of cell death in rat lymphocytes exposed to CI-994 in vitro.

This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. This dataset is not publicly accessible because: no EPA data; all the data generated by external organizations; EPA coauthors. It can be accessed through the following means: Data generated by external organizations. Format: N/A. This dataset is associated with the following publication: Ellis-Hutchings, R., R. Settivari, A. McCoy, N. Kleinstreuer, J. Franzosa, T. Knudsen, and E. Carney. (REPRODUCTIVE TOXICOLOGY) EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 70: 82-96, (2017).

This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. This dataset is not publicly accessible because: no EPA data; all the data generated by external organizations; EPA coauthors. It can be accessed through the following means: Data generated by external organizations. Format: N/A. This dataset is associated with the following publication: Ellis-Hutchings, R., R. Settivari, A. McCoy, N. Kleinstreuer, J. Franzosa, T. Knudsen, and E. Carney. (REPRODUCTIVE TOXICOLOGY) EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 70: 82-96, (2017).

This paper uses EPA public data to build new datasets and analysis by non-EPA authors. This dataset is not publicly accessible because: Data was not collected in EPA labs or paid for by EPA. It can be accessed through the following means: This paper uses EPA public data to build new datasets and analysis by non-EPA authors. Format: N/A. This dataset is associated with the following publication: Theunissen, P., S. Beken, B. Beyer, W. Breslin, G. 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 , M. Martin , M. McNerney, C. Siezen, D. Stanislaus, J. Stewart, K. Thompson, B. Tornesi, G. Weinbauer, S. Wood, J. Van der Laan, and A. Piersma. (Crit. Rev. Tox.) Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects. CRITICAL REVIEWS IN TOXICOLOGY. CRC Press LLC, Boca Raton, FL, USA, 1-11, (2016).

This paper uses EPA public data to build new datasets and analysis by non-EPA authors. This dataset is not publicly accessible because: Data was not collected in EPA labs or paid for by EPA. It can be accessed through the following means: This paper uses EPA public data to build new datasets and analysis by non-EPA authors. Format: N/A. This dataset is associated with the following publication: Theunissen, P., S. Beken, B. Beyer, W. Breslin, G. 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 , M. Martin , M. McNerney, C. Siezen, D. Stanislaus, J. Stewart, K. Thompson, B. Tornesi, G. Weinbauer, S. Wood, J. Van der Laan, and A. Piersma. (Crit. Rev. Tox.) Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects. CRITICAL REVIEWS IN TOXICOLOGY. CRC Press LLC, Boca Raton, FL, USA, 1-11, (2016).