In silico identification of protein targets for chemical neurotoxins using ToxCast in vitro data and read-across within the QSAR toolbox† †Electronic supplementary information (ESI) available: Tables S1–S4. See DOI: 10.1039/c7tx00268h

This study evaluates the application of QSAR Toolbox and ToxCast screening data to identify neurological targets for pyrethroids.

[1]  C. Austin,et al.  Improving the Human Hazard Characterization of Chemicals: A Tox21 Update , 2013, Environmental health perspectives.

[2]  K. Crofton,et al.  Putative adverse outcome pathways relevant to neurotoxicity , 2015, Critical reviews in toxicology.

[3]  Timothy J Shafer,et al.  Multi-well microelectrode array recordings detect neuroactivity of ToxCast compounds. , 2014, Neurotoxicology.

[4]  G. Conductier,et al.  The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases , 2010, Journal of Neuroimmunology.

[5]  B. Roth,et al.  The Multiplicity of Serotonin Receptors: Uselessly Diverse Molecules or an Embarrassment of Riches? , 2000 .

[6]  Baskar Mohana Krishnan,et al.  In vitro evaluation of pyrethroid-mediated changes on neuronal burst parameters using microelectrode arrays. , 2016, Neurotoxicology.

[7]  Igor V. Tetko,et al.  ToxCast EPA in Vitro to in Vivo Challenge: Insight into the Rank-I Model , 2016, Chemical research in toxicology.

[8]  Weida Tong,et al.  Versatility or Promiscuity: The Estrogen Receptors, Control of Ligand Selectivity and an Update on Subtype Selective Ligands , 2014, International journal of environmental research and public health.

[9]  E. Benfenati.  In Silico Methods for Predicting Drug Toxicity , 2016, Methods in Molecular Biology.

[10]  D. Dix,et al.  The ToxCast program for prioritizing toxicity testing of environmental chemicals. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[11]  Christophe Tzourio,et al.  Association between Parkinson's disease and the HLA‐DRB1 locus , 2012, Movement disorders : official journal of the Movement Disorder Society.

[12]  S D Dimitrov,et al.  QSAR Toolbox – workflow and major functionalities* , 2016, SAR and QSAR in environmental research.

[13]  David S. Wishart,et al.  DrugBank: a knowledgebase for drugs, drug actions and drug targets , 2007, Nucleic Acids Res..

[14]  E Benfenati,et al.  ToxRead: A tool to assist in read across and its use to assess mutagenicity of chemicals£ , 2014, SAR and QSAR in environmental research.

[15]  J. V. D. van den Bercken,et al.  Neurotoxicological effects and the mode of action of pyrethroid insecticides. , 1990, Critical reviews in toxicology.

[16]  D. Istance.  Organization for Economic Co-operation and Development , 1966, Nature.

[17]  Imran Shah,et al.  Systematically evaluating read-across prediction and performance using a local validity approach characterized by chemical structure and bioactivity information. , 2016, Regulatory toxicology and pharmacology : RTP.

[18]  M. Nagarkatti,et al.  Estrogen receptor agonists for attenuation of neuroinflammation and neurodegeneration , 2014, Brain Research Bulletin.

[19]  D. Blacker,et al.  Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database , 2007, Nature Genetics.

[20]  Nina Jeliazkova,et al.  Toxmatch--a chemical classification and activity prediction tool based on similarity measures. , 2008, Regulatory toxicology and pharmacology : RTP.

[21]  S. Bose,et al.  Role of chemokine CCL2 and its receptor CCR2 in neurodegenerative diseases , 2013, Archives of pharmacal research.

[22]  Ruili Huang,et al.  CERAPP: Collaborative Estrogen Receptor Activity Prediction Project , 2016, Environmental health perspectives.

[23]  A. Calhoun,et al.  Migraine and estrogen. , 2014, Current opinion in neurology.

[24]  Grace Patlewicz,et al.  Current and Future Perspectives on the Development, Evaluation, and Application of in Silico Approaches for Predicting Toxicity. , 2016, Chemical research in toxicology.

[25]  Guidance on information requirements and chemical safety assessment , 2008 .

[26]  Michael B. Black,et al.  A comprehensive statistical analysis of predicting in vivo hazard using high-throughput in vitro screening. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[27]  Huixiao Hong,et al.  Predicting hepatotoxicity using ToxCast in vitro bioactivity and chemical structure. , 2015, Chemical research in toxicology.

[28]  Mathieu Vinken,et al.  The adverse outcome pathway concept: a pragmatic tool in toxicology. , 2013, Toxicology.

[29]  David M. Reif,et al.  Profiling 976 ToxCast Chemicals across 331 Enzymatic and Receptor Signaling Assays , 2013, Chemical research in toxicology.

[30]  S. Gabriel,et al.  Risk alleles for multiple sclerosis identified by a genomewide study. , 2007, The New England journal of medicine.