Step 3 Resources
Below you will find information pertaining to tools and resources that can be used to link a characterized chemical to MIEs, KEs, or AOs.
Step 3 Overview
ToxCast (Toxicity Forecaster)
The ToxCast Dashboard helps users examine high-throughput assay data to inform chemical safety decisions. To date, the ToxCast Dashboard has data on over 9,000 chemicals and information from more than 1,000 high-throughput assay endpoint components. Once the user selects the chemicals and assays of interest, they can then explore the biological activity for the chemical-assay combinations. Results from the selections are shown with tables, graphs and charts that can be downloaded by the user.
Using the VEGA platform, you can access a series of QSAR (quantitative structure-activity relationship) models for regulatory purposes, or develop your own model for research purposes. QSAR models are models linking a property or effect, such as boiling point or toxicity, to parameters associated with chemical structure, such as certain molecular descriptors. They can be used to assess chemical substances within the so-called in silico approach (as an analogy to the in vitro and in vivo approach).
EPA’s Aggregated Computational Toxicology Online Resource (ACToR) aggregates data from thousands of public sources on over 500,000 chemicals. ACToR is also the data and web applications warehouse for EPA’s computational toxicology information which includes high-throughput screening, chemical exposure, sustainable chemistry (chemical structures and physicochemical properties) and virtual tissues data. ACToR is the warehouse for EPA web applications which can be used to explore and visualize complex computational toxicology information.
ATSDR Toxic Substances Portal
The ATSDR Toxic Substances Portal provides access to important information about toxic substances and how they affect our health. Information about toxic substances includes: characteristics, exposure risks, associated health effects, and related CDC and ATSDR health studies and assessments.
Pharos Chemical and Material Library
Pharos is an independent database of chemicals, polymers, metals, and other substances that includes 88,024 records and counting. Using dozens of scientific lists for specific human and environmental health hazards, it aggregates a vast array of information used for analyzing chemicals of concern. The tool also provides a wealth of information on certifications and standards used to measure the health impacts of products, including VOC content and emissions, recycled and bio-based content, and much more.
Beginning in 2012, the Endocrine Disruptor Screening Program (EDSP) began a multi-year transition to validate and more efficiently use computational toxicology methods and high throughput screens that will allow EPA to more quickly and cost-effectively assess potential chemical toxicity. The initiative, referred to as EDSP21 – or EDSP in the 21st century – aims to use computational or in silico models and molecular based in vitro high-throughput screening (HTS) assays to prioritize and screen chemicals to determine their potential to interact with the estrogen, androgen or thyroid (E, A, or T) bioactivity.
Reactome is an open-source, open access, manually curated and peer-reviewed pathway database. Reactome's goal is to provide intuitive bioinformatics tools for the visualization, interpretation and analysis of pathway knowledge to support basic and clinical research, genome analysis, modeling, systems biology and education.
OECD QSAR Toolbox
The OECD QSAR Toolbox is a software application intended for use by governments, the chemical industry and other stakeholders to fill gaps in (eco)toxicity data needed for assessing the hazards of chemicals. The Toolbox incorporates information and tools from various sources into a logical workflow. Crucial to this workflow is grouping chemicals into chemical categories. The seminal features of the Toolbox are identification of relevant structural characteristics and potential mechanism or mode of action of a target chemical; identification of other chemicals that have the same structural characteristics and/or mechanism or mode of action; and use of existing experimental data to fill the data gap(s). The toolbox also provides an approach to predict skin sensitisation based on the concept of Adverse Outcome Pathways.
Toxicity Estimation Software Tool (TEST)
TEST allows a user to estimate toxicity without requiring any external programs. Users input a chemical to evaluate by drawing it in an included chemical sketcher window, entering a structure text file, or importing it from an included database of structures. Once entered, the toxicity is estimated using one of several advanced QSAR methodologies. The required molecular descriptors are calculated within TEST.
EPA's New Chemical Categories Document
EPA groups Premanufacture Notice (PMN) chemicals with shared chemical and toxicological properties into categories, enabling both PMN submitters and EPA reviewers to benefit from the accumulated data and past decisional precedents allowing reviews to be facilitated. Currently, there are a total of 56 categories. Establishing these categories has streamlined the process for Agency review of new chemical substances. This document describes the molecular structure a new chemical must have to be included in the category, boundary conditions such as molecular weight, equivalent weight, the log of the octanol/water partition coefficient (log P), or water solubility, that would determine inclusion in (or exclusion from) a category, and standard hazard and fate tests to address concerns for the category.
WikiPathways is an open, collaborative platform that includes a graphical pathway editing tool and integrated databases covering major gene, protein, and small-molecule systems.
The ChemView database contains information on chemical health and safety data received by EPA and EPA's assessments and regulatory actions for specific chemicals under the Toxic Substances Control Act (TSCA). ChemView contains no confidential business information (CBI).
The OncoLogic™ model is a predictive system that mimics the judgment of human experts by following sets of knowledge rules based on studies of how chemicals cause cancer in animals and humans. OncoLogic™ asks for chemical and use information from the user, and following the knowledge rules incorporated into the system, uses the responses to construct an estimation of the carcinogenicity potential of the chemical.
Mcule is an online drug discovery platform. It offers a unique solution for pharma and biotech companies by providing the highest quality purchasable compound database and molecular modeling tools. Applications include: 1-Click Docking, 1-Click Scaffold Hop, Property calculator, and Toxicity checker.
MOL-Instincts is a database containing property data and molecular information of chemical compounds for industrial applications. It is also meant to be used for research and development in the many fields of science and engineering. The database includes thermodynamic properties, physico-chemical properties, transport properties, quantum-related information, molecular descriptors, drug-related properties, spectra information, optimized 3D structure, and orbital information.
Distributed Structure-Searchable Toxicity Database Network (DSSTox)
DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. A distinguishing feature of this effort is the accurate mapping of bioassay and physicochemical property data associated with chemical substances to their corresponding chemical structures.
EURL ECVAM JRC QSAR Model Database
Quantitative Structure-Activity relationship (QSAR) models can be used to predict properties needed for hazard and risk assessment and for which data gaps exist. The JRC QSAR Model Database provides information on the validity of QSAR models that have been submitted to the JRC. The database is intended to help to identify valid QSARs.
EPA's Virtual Tissue Models (Embryo, Blood Vessel Development, Developmental Toxicity, and Thyroid)
Virtual tissue models use new computational methods to construct advanced computer models capable of simulating how chemicals may affect human development. Virtual Embryo models simulate biological interactions observed during development and predict when chemicals disrupt key biological events in pathways that are thought to lead to adverse effects. The goal of the Virtual Thyroid is to model the potential impact of chemical disruption of thyroid function and subsequent adverse impacts on brain development.
The OpenFoodTox database gives information on over 4,000 chemical substances, related EU legislation, the EFSA output identifying their critical effects, and the safe levels set by EFSA scientific panels, such as tolerable or acceptable daily intakes.
NICEATM Integrated Chemical Environment (ICE)
The Integrated Chemical Environment (ICE) provides high-quality, curated data from NICEATM and its partners as well as other data resources and tools to support development of new approaches for assessing chemical safety. ICE allows users to easily query and integrate data streams that can then be explored interactively via table or graphic formats. The Integrator currently provides access to data for about 10,000 chemicals; endpoints include acute oral toxicity, skin and eye irritation, skin sensitization, and endocrine activity.
Comparative Toxicogenomics Database (CTD)
CTD is a robust, publicly available database that aims to advance understanding about how environmental exposures affect human health. It provides manually curated information about chemical–gene/protein interactions, chemical–disease and gene–disease relationships. These data are integrated with functional and pathway data to aid in development of hypotheses about the mechanisms underlying environmentally influenced diseases.
Chemical Carcinogenesis Research Information System (CCRIS)
The CCRIS database contains chemical records with carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition test results. It was developed by the National Cancer Institute (NCI). Data are derived from studies cited in primary journals, current awareness tools, NCI reports, and other sources. Test results have been reviewed by experts in carcinogenesis and mutagenesis.
Literature Search - Supporting Resources
Chemistry Dashboard ("CompTox")
The Chemistry Dashboard is part of a suite of dashboards developed by EPA to help evaluate the safety of chemicals. The Chemistry Dashboard provides access to a variety of information on over 700,000 chemicals currently in use. Within the Chemistry Dashboard, users can access chemical structures, experimental and predicted physicochemical and toxicity data, and additional links to relevant websites and applications. It maps curated physicochemical property data associated with chemical substances to their corresponding chemical structures.
ChemSpider is a free chemical structure database providing fast access to over 63 million structures, properties, and associated information. By integrating and linking compounds from ~280 data sources, ChemSpider enables researchers to discover the most comprehensive view of freely available chemical data from a single online search. It is owned by the Royal Society of Chemistry. ChemSpider offers text and structure searching to find compounds of interest and provides unique services to improve this data by curation and annotation, and to integrate it with users’ applications.
eChemPortal provides free public access to information on properties of chemicals: physical chemical properties, ecotoxicity, environmental fate and behavior, and toxicity. eChemPortal allows simultaneous searching of reports and datasets by chemical name and number, by chemical property, and by GHS classification.
QuickGO is a web interface developed by the European Molecular Biology Laboratory - European Bioinformatics Institute (EMBL-EBI). QuickGO is a fast web-based browser of the Gene Ontology and Gene Ontology annotation data.
AmiGO 2 is a project to create the next generation of AmiGO--the current official web-based set of tools for searching and browsing the Gene Ontology database.
International Toxicity Estimates for Risk (ITER)
ITER contains data in support of human health risk assessments. It is compiled by Toxicology Excellence for Risk Assessment (TERA) and contains data from CDC/ATSDR, Health Canada, RIVM, U.S. EPA, IARC, NSF International and independent parties offering peer-reviewed risk values. ITER provides comparison charts of international risk assessment information and explains differences in risk values derived by different organizations.
Literature Search - TOXNET
GENE-TOX provides genetic toxicology (mutagenicity) test data from expert peer review of open scientific literature for more than 3,000 chemicals from the United States Environmental Protection Agency (EPA). GENE-TOX was established to select assay systems for evaluation, review data in the scientific literature, and recommend proper testing protocols and evaluation procedures for these systems.
Hazardous Substances Data Bank (HSDB)
HSDB is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel.
TOXLINE is a bibliographic database with an assortment of citations from specialized journals and other sources. It provides references covering the biochemical, pharmacological, physiological, and toxicological effects of drugs and other chemicals. Most of TOXLINE's bibliographic citations contain abstracts and/or indexing terms and Chemical Abstract Service (CAS) Registry Numbers.
LactMed (Drugs and Lactation DB)
The LactMed® database contains information on drugs and other chemicals to which breastfeeding mothers may be exposed. It includes information on the levels of such substances in breast milk and infant blood, and the possible adverse effects in the nursing infant. Suggested therapeutic alternatives to those drugs are provided, where appropriate. All data are derived from the scientific literature and fully referenced. A peer review panel reviews the data to assure scientific validity and currency.
DART (Developmental and Reproductive Toxicology DB)
DART provides more than 400,000 journal references covering teratology and other aspects of developmental and reproductive toxicology. DART is funded by the U.S. Environmental Protection Agency, the National Institute of Environmental Health Sciences, the National Center for Toxicological Research of the Food and Drug Administration, and the NLM.