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TOX21S: Tox21 Chemical Inventory for High-Throughput Screening
Structure-Index File

** Version 2a, updated 22 March 2012
Additional QC and corrections of chemical records leading to adjusted count.

Replacement of large number of DSSTox_RIDs already in use in TOXCST.

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blue bullet graphic Description
blue bullet graphic Source Websites & Contacts
blue bullet graphic Main Citations
blue bullet graphic SDF Fields
blue bullet graphic SDF Content Summary
blue bullet graphic Version 2a Update

blue bullet graphic SDF Download Table

blue bullet graphic Acknowledgements, DSSTox Citation & Disclaimer

New Users: For general information, see DSSTox Project Goals and About DSSTox. For additional information on DSSTox SDF (Structure Data Format) files and their use in Chemical Relational Databases, see More on SDF and More on CRDs.

Description: Tox21 is a collaboration among multiple federal Agencies -- EPA's National Center for Computational Toxicology, the National Institutes of Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP) Exit EPA Disclaimer, the National Institutes of Health/National Human Genome Research Institute/NIH Chemical Genomics Center (NCGC) Exit EPA Disclaimer, and the U.S. Food and Drug Administration (FDA) Exit EPA Disclaimer -- working together to develop, validate and translate innovative, high-throughput screening (HTS) chemical testing methods to characterize key steps in toxicity pathways. The goals of the “Tox21 Community” are to investigate the use of these new tools to prioritize substances for further in-depth toxicological evaluation, identify mechanisms of action for further investigation, and develop predictive models for in vivo biological response.  The full Tox21 chemical inventory is currently undergoing screening (as of Nov 2011) at the NCGC's Tox21 HTS Robotics Facility Exit EPA Disclaimer. All HTS assay results are to be publicly released after quality review through various public database venues (EPA ACToR, NIEHS CEBS, NCGC Tox21 Browser Exit EPA Disclaimer, and PubChem Exit EPA Disclaimer). In addition, all parent Tox21 solution plates are undergoing analytical QC (LC MS and follow-up GC MS) in association with testing to assess compound sample purity, identity, concentration, and stability. The Tox21 effort represents the largest and most comprehensive evaluation of the interaction of a wide range of environmental and commercial chemicals with putative and known toxicity pathways. The effort is helping to pave the way for the use of HTS tools in hazard identification, chemical prioritization, and risk assessment. For further information on the Tox21 HTS testing program, see Source Websites.

The Tox21 chemical inventory represents a central pillar of the Tox21 project and is unprecedented in its scope, structural diversity, multiple use-scenarios (pesticides, industrial, food-use, drugs, etc.), and chemical feature characteristics in relation to toxicology. The library consists of approximately equal contributions of more than 3000 physical compound samples mostly procured from commercial sources by each of three Tox21 partners - EPA, NTP, NCGC - for a total of over 10,000 plated compound solutions, spanning more than 8100 unique chemical substances. Tox21 compounds were selected based on a wide range of criteria, including, but not limited to: environmental hazard or exposure concern based on production volume (industrial chemicals) or occurrence data, availability of animal toxicity study data, food-additives, fragrances, toxicity reference chemicals, and drugs or known bioactive compounds. Additional criteria for chemical selection included physical chemical calculated properties suitable for HTS (MW, volatility, solubility, logP), commercial availability and cost, and DMSO (dimethyl sulfoxide) solubility. Resources such as the EPA ACToR database, the DSSTox Master Inventory, and various databases of marketed pharmaceuticals were mined for chemical candidates, and corresponding chemical information and structures. The present Tox21 compound inventory has incorporated and expanded upon the earlier Phase I Tox21 compound libraries compiled by NTP (1408 compounds - see the NTP Tox21 Source Website, and DSSTox NTPHTS), EPA (initially 1408 compounds that included an early version of the ToxCast inventory), and the preliminary NCGC inventory of marketed, withdrawn and investigational drugs (approximately 2800 compounds) – see the NCGC Pharmaceutical Collection (NPC) BrowserExit EPA Disclaimer. In addition, the current EPA ToxCast chemical inventory of over 1060 compounds (see the NCCT ToxCast website) has been incorporated into EPA's contribution to the Tox21chemical inventory to expand Tox21 assay coverage for this high-interest EPA compound set. Within the ToxCast subset, FDA contributed a small number of physical samples of drugs (Weida Tong, National Center for Toxicological Research, FDA), as well as provided lists of food additives with available guideline animal toxicity study data (Kirk Arvidson, Center for Food Safety and Nutrition, FDA). A further unique aspect of the ToxCast chemical inventory portion of the Tox21 inventory is the inclusion of 135 donated "failed drugs" and associated toxicity data from 6 major pharmaceutical companies (see the updated DSSTox TOXCST Download page for a list of these donated pharma compounds). Included among the NTP portion of the Tox21 inventory are compounds that have been tested by the NTP for endpoints such as carcinogenicity, immunotoxicity, genotoxicity, developmental toxicity, and reproductive toxicity; those that have been nominated to the NTP for testing (and structurally related compounds); compounds with regulatory test data identified by the NTP Center for the Evaluation of Alternative Toxicological Methods (NICEATMExit EPA Disclaimer) for evaluating endpoints such as developmental toxicity, endocrine disruption, immunotoxicity, ocular and dermal corrosion/irritation, and oral acute toxicity. Finally, to explore how mixtures might be evaluated in qHTS, 118 formulated mixtures along with each constituent have been included [Note that the current DSSTox TOX21S inventory lists only the individual mixture components; supporting details will be provided at a later date.]

The DSSTox TOX21S Structure-Index File offers the full complement of DSSTox Standard Chemical Fields for the Tox21 chemical inventory. The DSSTox TOX21S file will be available for structure-searching from the DSSTox Structure-Browser, as well as in association with HTS assay data from various websites: EPA ACToR, NCGC Tox21 Browser Exit EPA Disclaimer, and PubChem Exit EPA Disclaimer.

Source Websites: Tox21 Partner Information Websites: 1) NIH/NHGRI/NCGC Tox21 Initiative; 2) EPA NCCT Tox21 Program; 3) NIEHS/NTP Tox21 High Throughput Screening Initiative; 4) US FDA Tox21 Joint News Release.

Source Contacts:
Tox21 Chemical Workgroup Leads: Ann Richard (EPA) richard.ann@epa.gov; Cynthia Smith (NTP) smith19@niehs.nih.gov; William Leister (NCGC) leisterw@mail.nih.gov; Donna Mendrick (FDA) donna.mendrick@fda.hhs.gov

Tox21 Agency Program Leads: David Dix (EPA) dix.david@epa.gov; Raymond Tice (NTP) tice@niehs.nih.gov; Christopher Austin (NIH/NHGRI - NCGC) austinc@mail.nih.gov.; Thomas Colatsky (FDA) thomas.colatsky@fda.hhs.gov.

For technical questions concerning the DSSTox TOX21S structure-data files, contact Ann Richard (EPA) richard.ann@epa.gov.

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Main Citations: Publications reporting use of the DSSTox TOX21 data files are asked to list the full DSSTox file name, including date stamp, and to cite as primary reference one of the following:

Collins FS, Gray GM, Bucher JR. Transforming environmental health protection. Science. 2008 Feb 15;319(5865):906-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679521/?tool=pubmed Exit EPA Disclaimer

Kavlock RJ, Austin CP, Tice RR. Toxicity Testing in the 21st Century: Implications for Human Health Risk Assessment, Risk Analysis 2009; 29(4):485-487. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202604/?tool=pubmed Exit EPA Disclaimer

A related publication detailing development of the NCGC Pharmaceutical Collection, of which the Tox21 NCGC compound library is a part, is listed below:

R. Huang, N. Southall, Y. Wang, A. Yasgar, P. Shinn, A. Jadhav, D.-T.Nguyen, C. P. Austin, The NCGC Pharmaceutical Collection: A Comprehensive Resource of Clinically Approved Drugs Enabling Repurposing and Chemical Genomics. Sci. Transl. Med. 3, 80ps16 (2011). http://stm.sciencemag.org/content/3/80/80ps16.abstract Exit EPA Disclaimer

TOX21S SDF Fields (20 total):

DSSTox Standard Chemical Fields (19)

Note_TOX21S field added v1b

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TOX21S SDF Content Summary -20 December 2011

TOX21S SDF Content
Totals_v1a
Totals_v1b
Totals_v2a
# Records
8159
8205
8193
DSSTox Standard Chemical Fields
19
19
19
TOX21S Source Fields
0
1
1
Total # Fields
19
20
20
Chemical Content
Counts_v1a Counts_v1b Counts_v2a
     
defined organic
7863
7883
7881
inorganic
106
106
98
organometallic
187
189
187
no structure (blank)
3
26
27
STRUCTURE_TestedForm_
DefinedOrganic
:
     
parent
6251
6268
6314
salt or complex
1612
1615
1567
TestSubstance_Description:      
single chemical compound
7850
7855
7849
macromolecule
29
38
35
mixture or formulation
280*
312*
308*

* Note that, in addition to the mixtures or formulations marked in the current file, 118 defined mixtures with various combinations of single chemical compound constituents are included in the NTP contribution to the Tox21 testing library but are not separately listed in the present DSSTOX TOX21S data file - details to be provided elsewhere.

Version 2a Update: Completing a final round of chemical information review resulted in changes yielding a net count of 12 fewer unique substances across the entire inventory. Changes to Standard Chemical Field entries from v1b to v2a are documented in the Note_TOX21S field. In addition, a large number of DSSTox_RIDs for TOX21S were replaced due to already being in use in the related TOXCST inventory. 

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File Download Notes: The following files are offered in the DownLoad table below:

green bullet Log File (PDF) provides SDF data file version history and summary information (field, chemical counts, etc.), and a description of procedures and quality assurance checks used in SDF file creation;
Structure Data File (SDF) is the main DSSTox product, providing the complete inventory of chemical structures, DSSTox Standard Chemical Fields, and all Source-specific data fields [Note: the structure field is blank for all records containing complex mixtures or undefined substances];
Data Table MS Excel (MS Office 2007) file contains the full SDF data contents in spreadsheet table form, minus the chemical structure field.

You will need Adobe Acrobat Reader, available as a free download, to view the Adobe PDF files on this page. See EPA's PDF page to learn more about PDF, and for a link to the free Acrobat Reader.

Zip files may be decompressed using a utility such as JZip. Exit EPA Disclaimer
File Types   Description File Size Format

Documentation Files: TOX21S
Log File  
75KB
pdf document icon
Data Files: TOX21S
SDF Structure Data File  
*.zip
4.9MB
sdf document icon
• Data Table
(no structures)
  excel document icon
file error report graphic link to submit error report form      

These files constitute the main DSSTox products. Documentation Files use standard templates, and DSSTox Structure Data Files and DSSTox File Names adhere to strict formatting standards and conventions. For additional information, see More on DSSTox Standard Chemical Fields, Known Problems & Fixes, Chemical Information Quality Review Procedures, and How to Use DSSTox Files.

Quick & Easy File Downloads: FTP Download

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Acknowledgements: The DSSTox SDF file of the Tox21 chemical inventory was compiled over the course of more than 2 years, resulting from careful review of chemical supplier documentation accompanying chemical sample procurements (i.e., mainly Certificates of Analysis and Material Safety Data Sheets), as well as consultation of public and commercial sources of chemical structures. The EPA ACToR database (developed by Richard Judson) was heavily relied upon for construction of EPA's Tox21 chemical inventory contribution. Initial chemical structure annotation and quality control (QC) review were carried out and overseen by teams within NTP (Cynthia Smith, Brad Collins) and NCGC (Ruili Huang, Tom Daniel, Paul Shinn, William Leister, Noel Southall, Adam Yasgar, Dac-Trung Nguyen, Yuhong Wang, Danielle Van Leer, Heather Baker, David Maloney). Final QA review and registration of structures into the DSSTox Master inventory was performed by Maritja Wolf (Lockheed Martin Contractor to the EPA), with assistance of Inthirany Thillainadarajah (EPA SEE grant program) and Patra Volarath (EPA). Assistance with further structure QC and annotations was kindly provided by Chihae Yang and Daniel Kromer (Altimira). Initial feedback and error reports on the SDF file were kindly provided by Antony Williams (RSC, ChemSpider) and Evan Bolton (PubChem). EPA and NTP thank the staff at Compound Focus, Inc. (contractor to the US EPA) and MRIGlobal (contractor to the NIH/NTP) for expert assistance in the procurement, information processing, and plating of the EPA and NTP Tox21 compound libraries. Finally, we thank all members of the Tox21 Workgroups across EPA, NTP, NCGC and FDA, members of the ToxCast team within EPA NCCT (in particular, Richard Judson, David Dix, Keith Houck, Robert Kavlock), as well as outside Tox21 partners for their myriad contributions to the entire Tox21 community effort.

DSSTox Citation: M.A. Wolf, I. Thillainadarajah, P. Volarath, C. Smith, B. Collins, R. Huang, W. Leister, P. Shinn, T. Daniel, R. Judson, R. Tice, R. Kavlock, C. Austin, D. Dix, A. Richard (2011) DSSTox EPA Tox21S Chemical Inventory for High Throughput Screening Structure-Index File: SDF File and Documentation, Updated version: TOX21S_v2a_8193_22Mar2012, www.epa.gov/ncct/dsstox/sdf_tox21s.html

Disclaimer: Every effort is made to ensure that DSSTox SDF files and associated documentation are error-free, but neither the DSSTox Source collaborators nor the EPA DSSTox project team make guarantees of accuracy, nor are any of these persons to be held liable for any subsequent use of these public data. The contents of this webpage and supporting documents have been subjected to review by the EPA National Center for Computational Toxicology and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. See additional disclaimers.

EPA/600/C-06/012

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