Characterization of 100 chemicals for electrophillic potential using Hard and Soft Acid and Bases theory. The chemicals were ranked for electrophillic potential and a group of chemicals within a range of electrophillic values were identified as having properties similar to other neurotoxicants. This dataset is associated with the following publication: Melnikov, F., B. Geohagen, T. Gavin, R. LoPachin, P. Anastas, P. Coish, and D. Herr. Application of the Hard and Soft, Acids and Bases (HSAB) Theory as a Method to Predict Cumulative Neurotoxicity. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, NETHERLANDS, 79: 95-103, (2020).

This file contains the data on apoptosis, neurite outgrowth, synaptogenesis and proliferation. This dataset is associated with the following publication: Harrill, J., T. Freudenrich, K. Wallace, K. Ball, T. Shafer, and W. Mundy. Testing for developmental neurotoxicity using a battery of in vitro assays for key cellular events in neurodevelopment. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, USA, 354(1): 24-39, (2018).

Background T-cells extravasation and CNS parenchyma infiltration during autoimmune neurodegenerative disease can be evoked by local antigen presenting cells. Studying the chemoattracting potential of spinal perivascular macrophages (SPM) during experimental allergic encephalomyelitis (EAE), we observed numerous infiltrates of densely-packed mononuclear cells. Apart from the poor spatial and optical resolution, no differentiation between the resident SPM (mabs ED1+, ED2+) and the just recruited monocytes/macrophages (mab ED1+) was possible. Results This is why we labeled SPM by injections of different fluoresecent dyes into the lateral cerebral ventricle before induction of active EAE. Within an additional experimental set EAE was induced by an intraperitoneal injection of T-cells specifically sensitized to myelin basic protein (MBP) and engineered to express the green fluorescent protein (GFP). In both experiments we observed a strong activation of SPM (mabs OX6+, SILK6+, CD40+, CD80+, CD86+) which was accompanied by a consistently increased expression of ICAM-1, VCAM-1, and the chemokines MCP-1 and MIP-1α. Conclusion These observations indicate that SPM play a role in promoting lymphocyte extravasation.

This data file contains the full raw parameter data for the 86 compounds tested in the developmental MEA assay, as well as Area Under the Curve (AUC) calculations and plate normalized data.

These data are the individual parameter and well-level data that were support the conclusions in Brown et al. Note: the parameters CVtime and CVnetwork were not used. This dataset is associated with the following publication: Brown, J., D. Hall, C. Frank, K. Wallace, W. Mundy, and T. Shafer. Editor's highlight: Evaluation of a Microelectrode Array-based Assay for Neural Network Ontogeny using Training Set Chemicals. TOXICOLOGICAL SCIENCES. Society of Toxicology, 154(1): 126-139, (2016).

This study looked at functional endpoints in adult offspring of rats exposed in utero and postnatally to an environmentally relevant mixture of PCBs, Fox River blend. A model of neural plasticity and epilepsy, electrical kindling, was examined. Animals exposed to PCBs had slower kindling rates suggesting impaired plasticity mechanisms, consistent with previous work with PCBs where deficits were seen in another plasticity model, long-term potentiation. This dataset is associated with the following publication: Bandara, S., R. Sadowski, S. Schantz, and M. Gilbert. Developmental Exposure to an Environmental PCB Mixture Delays the Propagation of Kindling in the Amygdala. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, NETHERLANDS, n/a, (2016).

Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures and decline in serum TH resulting in neurodevelopmental impairment is poorly understood. The present study developed a quantitative adverse outcome pathway (qAOP) where serum thyroxin (T4) reduction following inhibition of thyroperoxidase in the thyroid gland are described and related to deficits in fetal brain TH and the development of a brain malformation, subcortical band heterotopia. Pregnant dams were exposed to 6-propylthiouracil (PTU 0, 0.1, 0.5, 1, 2, or 3 ppm) from gestational day 6-20, increasing PTU concentrations in maternal thyroid gland and serum as well as in fetal serum. Dams exposed to 0.5 ppm PTU and higher exhibited dose-dependent decreases in thyroidal T4. Serum T4 levels in the dam were significantly decreased with exposure to 2 and 3 ppm PTU. In the fetus, T4 decrements were first observed at a lower dose of 0.5 ppm PTU. Based on these data, fetal brain T4 levels were estimated from published literature sources, and quantitatively linked to increases in the size of the heterotopia present in the brains of offspring. These data show the potential of in vivo assessments and computational descriptions of biological responses to predict the development of this structural brain malformation and use of qAOP approach to evaluate brain deficits that may result from exposure to other TH disruptors. This dataset is associated with the following publication: Hassan, I., H. El-Masri, P. Kosian, J. Ford, S. Degitz, and M. Gilbert. Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework. TOXICOLOGICAL SCIENCES. Society of Toxicology, 57-73, (2017).