Abstract
The increasing regulatory safety demands for the submission and registration of chemicals, pesticides, or pharmaceuticals as well as tightening animal protection legislation have exacerbated the dilemma of regulatory toxicology, where on the one hand the required scientific contributions for the protection of workers, consumers, or patients are constantly augmented while on the other hand the number of experimental animal studies should be reduced.
One way to resolve this dilemma could be the use of computer-assisted systems to predict toxic effects. These so-called “in silico” tools have experienced improvements in their performance and predictive power over the past three decades. They are therefore able to contribute to hazard identification and risk assessment at least for some toxicological endpoints. However, knowledge of how these systems work, the importance of the underlying data quality, and their respective limitations are prerequisites for a sensible application.
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Appendices
Resources
List of noncommercial toxicological internet data sources including a short description:
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CTD (Comparative Toxicogenomics database; a publicly available database focusing on gene expression data that aims to advance understanding about how environmental exposures affect human health. Structure-based searches are not possible): http://ctdbase.org/
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COSMOS (toxicological data and information from regulatory submissions and the literature, focusing on chronic toxicity assessment. The database was developed in the framework of the European SEURAT project. Structure-based searches are possible): http://www.cosmostox.eu/what/COSMOSdb/
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DrugBank (a chem- and bioinformatics resource supported by the Canadian Institutes of Health Research that combines drug (i.e., chemical, pharmacological and pharmaceutical. Structure-based searches are not possible) data with drug target information): https://www.drugbank.ca/
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DSSTox (Distributed Structure-Searchable Toxicity Database; a resource for public chemistry data, including bioassay and physicochemical data maintained by US EPA. Structure-based searches are not possible): https://www.epa.gov/chemical-research/distributed-structure-searchable-toxicity-dsstox-database Chemicals from the DSSTox can be either downloaded as sd files or accessed via the two dashboards:
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ToxCast (EPA’s ToxCast data can be queried for assays and chemical names or CAS numbers): https://actor.epa.gov/dashboard/
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Chemistry Dashboard: https://comptox.epa.gov/dashboard
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eTOXsys (user interface of the IMI eTOX project containing a sample set of systemic toxicity studies and predictive tools developed in the project): https://etoxsys.eu/etoxsys.v3-demo-bk/dashboard/
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IUCLID (REACH study results; a collection of nonconfidential substance data that was submitted to ECHA under the REACH regulation): https://iuclid6.echa.europa.eu/reach-study-results
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LiverTox (a database hosted by the US National Library of Medicine providing information about drug-induced liver injury caused by prescription and nonprescription drugs, herbals, and dietary supplements): https://livertox.nih.gov/
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Liver Toxicity Knowledge Base (LTKB) (a database hosted by the FDA containing drugs whose potential to cause DILI (Drug-Induced Liver Injury) in humans has been established using the FDA-approved prescription drug labels): https://www.fda.gov/ScienceResearch/BioinformaticsTools/LiverToxicityKnowledgeBase/default.htm
National Toxicology Program
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Tox21 Toolbox (tools for visualizing dose-response curves or profiling activities of the compounds tested within the Tox21 program): https://ntp.niehs.nih.gov/results/tox21/tbox/
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Tox21 Data Browser: https://tripod.nih.gov/tox21/index
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Drug Matrix Database (toxicogenomic reference resource for drugs and environmental chemicals): https://www.niehs.nih.gov/drug_matrix
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TG-GATES database (public toxicogenomics database supported by the National Institutes of Biomedical Innovation, Health and Nutrition containing data on gene expression and detailed toxicity data from rats and the primary cultured hepatocytes of rats and humans): http://toxico.nibiohn.go.jp/english/index.html
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ToxNet (resources for searching databases on toxicology, hazardous chemicals, environmental health, and toxic releases maintained by the US National Library of Medicine. Structure-based searches are not possible): https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm
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Subsets of mutagenicity and reproductive toxicity data (DART) can be found:
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Toxic Exposome Database (formerly called T3DB, a database supported by the Canadian Institutes of Health Research with a focus on providing mechanisms of toxicity and target proteins for chemical compounds. Structure-based searches are possible): http://www.t3db.ca/
Selection of Freely Available Software and Tools
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OECD toolbox: http://www.oecd.org/chemicalsafety/risk-assessment/oecd-qsar-toolbox.htm
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ToxAlerts: https://ochem.eu/alerts
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VEGAHUB: https://www.vegahub.eu/
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Steger-Hartmann, T., Boyer, S. (2020). Computer-Based Prediction Models in Regulatory Toxicology. In: Reichl, FX., Schwenk, M. (eds) Regulatory Toxicology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36206-4_36-2
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DOI: https://doi.org/10.1007/978-3-642-36206-4_36-2
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