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NCTRER: FDA National Center for Toxicological Research Estrogen Receptor Binding
Database File

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** Version 4b, updated 15 February 2008:
Includes 2 new summary activity fields (ActivityOutcome, ActivityScore) to coordinate with PubChem NCTRER Assay deposits.
Includes new InChIKey Standard Chemical Field.

Quick & Easy File Downloads: FTP Download Instructions

blue bullet graphic Description
blue bullet graphic Source Website& Contact
blue bullet graphic Main Citation
blue bullet graphic Guidance for Use
blue bullet graphic Version 4 Update
blue bullet graphic SDF Fields
blue bullet graphic SDF Content Summary

blue bullet graphic SDF Download Table

blue bullet graphic Acknowledgements, DSSTox Citation & Disclaimer

Description: Legislation passed in 1996 mandated that the EPA develop and implement a screening strategy for assessing the risk associated with endocrine disrupting chemicals (EDCs). Recommendations of the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) focused on development of priority-setting approaches and Tier 1 screening methods, initially for assessing estrogenic activity, that would guide the more limited application of Tier 2 animal testing. Priority setting primarily refers to quantitative structure-activity relationship (QSAR) methods for assessing the potential estrogenic activity of chemicals for which test data are unavailable. Included on the list of Tier 1 screening methods is the in vitro estrogen receptor (ER) competitive-binding assay, which provides quantitative assessment of a chemical's ability to bind to the ER. Researchers within FDA's National Center for Toxicological Research (NCTR) generated a database of experimental ER binding results for the express purpose of developing improved QSAR models to predict ER binding affinities. The NCTR ER database consists of 232 chemicals (131 active and 101 inactive) selected a priori based on structural characteristics and tested in a well validated and standardized in vitro rat uterine cytosol ER competitive-binding assay [Blair et al. 2000; Branham et al., 2002]. The database is a structurally diverse set of natural, synthetic, and environmental estrogens covering most known estrogenic classes and spanning a wide range of biological activity. It represents the largest published ER binding database of same-assay results generated in a single laboratory.

The main citation of Fang et al. (2001) surveys the NCTR ER database from a chemical class based, structure-activity relationship (SAR) perspective. Qualitative SAR characteristics of the NCTR ER database are discussed and a set of general hierarchical rules for identifying potential estrogens are presented. For construction of the DSSTox NCTRER SDF, the original NCTR ER database has been augmented with chemical class and SAR information abstracted from Fang et al. (2001). Information on the percent purity and purchasing source for all chemicals are not included in the DSSTox SDF, but can be obtained from the original NCTR ER Source database and Main Citations listed below. For the DSSTox SDF files, we have supplemented the measured ER relative binding affinity for each chemical (LOG_ER_RBA or ER_RBA) with chemical class assignment to one of 6 major estrogenic classes further divided into 20 subclasses (ChemClass_ERB). Mean ER_RBA values for activities within the 6 major estrogenic classes (Mean_ER_RBA_ChemClass) are reported, along with a qualitative activity measure, ActivityCategory_ER_RBA. In addition, log (octanol/water partition coefficient) values (LOGP) are provided. A brief narrative SAR rationale pertaining to ER RBA patterns observed by Fang et al. (2001) for each of the 20 subclasses within the database are provided in the field, ActivityCategory_Rationale_ChemClass_ERB. Finally, we approximate the decision flowchart for identification of ER binders, presented in Fig. 14 of Fang et al. (2001), with 6 indicator (1=yes, 0=no) fields: F1_Ring, F2_AromaticRing, F3_PhenolicRing, F4_Heteroatom, F5_Phenol3nPhenyl, F6_OtherKeyFeatures. Further details on the flowchart rules for predicting ER binding, the criteria for chemical structure class and subclass assignments, corresponding class-based SAR rationales for ER binding, and additional references are provided in the NCTRER Field Definition File offered for download below.

The original NCTR ER database, from which the expanded DSSTox NCTRER was formed, is contained within a larger Endocrine Disruptor Knowledge Base (EDKB) accessible from the FDA Source Website. That website provides online access to an ORACLE-backed relational database comprised of in vitro and in vivo experimental data for about 2000 natural and synthetic compounds, much of this extracted from the literature and representing testing in many laboratories. Data are included for biological assays that measure estrogenic and androgenic activity. Estrogenic endpoints include in vitro assays for estrogen receptor competitive binding affinity, cell proliferation, and reporter-gene assays, and in vivo assays for uterotrophic activity (i.e., uterine weight gain and vaginal cornification). The database also contains a bibliography of over 1200 citations, many of which include abstracts.

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Source Website: For further information on the original NCTR ER database and to gain relational database access to a wider body of information on EDCs, users are encouraged to visit the NCTR Endocrine Disruptor Knowledge Base website at http://edkb.fda.gov/index.htmlexit EPA

Source Contact: Weida Tong and Hong Fang, National Center for Toxicological Research, Jefferson, Arkansas; email: wtong@nctr.fda.gov, hfang@nctr.fda.gov

 

Main Citation: Publications reporting use of DSSTox SDF file for the NCTRER are asked to list the full DSSTox file name(s), including date stamp, and to cite as primary references the following:

Fang, H., W. Tong, L.M. Shi, R. Blair, R. Perkins, W. Branham, B.S. Hass, Q. Xie, S.L. Dial, C.L. Moland, and D.M. Sheehan (2001) Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens. Chem. Res. Tox., 14:280-294.

Blair, R.M., H. Fang, W.S. Branham, B.S. Hass, S.L. Dial, C.L. Moland, W. Tong, L. Shi, R. Perkins, and D.M. Sheehan (2000) The estrogen receptor relative binding affinities of 188 natural and xenochemicals: Structural diversity of ligands. Toxicol. Sci., 54:138-153.

W.S. Branham, S.L. Dial, C.L. Moland, B.S. Hass, R.M. Blair, H. Fang, L. Shi, W. Tong, R.G. Perkins, and D.M. Sheehan (2002) Binding of phytoestrogens and mycoestrogens to the rat uterine estrogen receptor. J. Nutr., 132:658-664.

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Guidance for Use: A user of the DSSTox NCTRER SDF files is encouraged to consult the NCTR EDC Source Website http://edkb.fda.gov/index.htmlexit EPA and the main and supporting literature citations provided therein and above. Some discrepancies were noted in ER binding values reported in the earlier publications compared to those listed at the NCTR EDC website; the latter values are the most current and accurate and are those included in the DSSTox NCTRER SDF files. Although not reported in the original publications, three compounds were tested in citrate form and one was tested in a salt form. We represent information on the tested forms of the chemicals in the main NCTRER file. The NCTRER Field Definition File contains essential documentation and should be downloaded with, and accompany any use of the DSSTox NCTRER SDF file. The NCTRER Log File provides database summary information (field, chemical counts, etc.) and a description of procedures and quality assurance checks used in SDF file creation. In addition, the Log File documents modifications incorporated into version/revision updates of the DSSTox NCTRER SDF file. For additional information on DSSTox SDF files and their use in Chemical Relational Databases, see More on SDF and More on CRDs. To report errors in any NCTRER documentation or SDF data file, click on File Error Report here or below.

Version 4 Update: NCTRER_v4 has no new chemical records but has several minor QA corrections, field entry revisions, field changes, new CASRN, etc. Changes to DSSTox Standard Chemical Fields include new ID fields: DSSTox_RID, DSSTox_Generic_SID and DSSTox_FileID (replacing DSSTox_SID and DSSTox_ID_FileName) (see More on Standard Chemical Fields), and entries in theTestSubstance_Description field have been simplified. NCTRER-specific chemical information has been removed from the ChemicalNote field and moved to new Source-specific field, Note_NCTRER. Finally, text entries in field Mean_ER_RBA_ChemClass have been converted to a pure numeric field.

Version 4b Update: NCTRER_v4b includes minor structure changes/modifications and two new summary activity fields for use in PubChem and structure-activity relationship studies: ActivityOutcome_NCTRER (entries of active, inactive, or inconclusive) and ActivityScore_NCTRER (INTEGER[0-100]). In addition, the new STRUCTURE_InChIKey field (25 character abbreviated InChI for use in structure-indexing applications) has been added as a DSSTox Standard Chemical Field to all DSSTox files.

For more information and version history, consult the NCTRER_LogFile in the Download Table below.

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NCTRER SDF Fields (38 total)*

DSSTox Standard Chemical Fields (19) * STRUCTURE_InChIKey field added in v4b

DSSTox Standard Toxicity Fields (3)

ChemClass_ERB
ER_RBA
LOG_ER_RBA
ActivityCategory_ER_RBA
ActivityOutcome_NCTRER *new to v4b
ActivityScore_NCTRER *new to v4b
Mean_ER_RBA_ChemClass

ActivityCategory_Rationale_ChemClass_ERB
F1_Ring
F2_AromaticRing
F3_PhenolicRing
F4_Heteroatom
F5_Phenol3nPhenyl
F6_OtherKeyFeatures
LOGP
Note_NCTRER

* Note: For detailed information on SDF content, see NCTRER_FieldDefinitionFile in Download Table below.

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NCTRER SDF Content Summary - 15 February 2008

NCTRER SDF Content
Totals_v3b Totals_v4a Totals_v4b
# Records
232
232
232
DSSTox Standard Chemical Fields
18
18
19
DSSTox Standard Toxicity Fields
3
3
3
NCTRER Source Fields
13
14
16
Total # Fields
34
35
38
Chemical Content
Counts_v3b Counts_v4a Counts_v4b
     
defined organic
230
230
230
inorganic
0
0
0
organometallic
2
2
2
no structure
0
0
0
STRUCTURE_TestedForm_
DefinedOrganic
:
     
parent
226
226
226
complex
3
3
3
salt
1
1
1
salt complex
0
0
0
TestSubstance_Description:
single chemical compound
225
225
225
defined mixture or formulation
7
* (NA)
* (NA)
undefined mixture
0
* (NA)
* (NA)
macromolecule
0
0
0
mixture or formulation
* (NA)
7
7

* (NA) = field entry not applicable for DSSTox file version indicated

Note: For SDF content summary information on previous versions of NCTRER, view NCTRER_LogFile in Download Table below.

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

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;
Field Definition File (PDF or MS Word doc file) provides field definitions and essential documentation, and should be downloaded with and accompany any use of the DSSTox SDF file;
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 mixtures or undefined substances];
Data Table MS Excel (MS Office 2003) file contains the full SDF data contents in spreadsheet table form, minus the chemical structure field [file created with CambridgeSoft ChemFinder plug-in to MS Excel 2003];
Structures Table (PDF) file contains a tiled format graphical view of all chemical structures contained in the SDF file, annotated with TestSubstance_CASRN and truncated TestSubstance_ChemicalName field entries for the tested form of the chemical [file created with ACD ChemFolder, ver. 10.01, ACD Labs].

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.

File Types   Description File Size Format

Document Files
Log File  
40KB
pdf document icon
Field Definition File  
168KB
pdf document icon
   
288KB
ms word document icon
Data Files: NCTRER
SDF Structure Data File  
776KB
sdf document inside zip file
• Data Table
(no structures)
 
175KB
excel document iside zip file
• Structures Table  
984KB
pdf document icon
file error report graphic link to submit error report form      

These files constitute the main DSSTox products. DSSTox 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 original DSSTox SDF file for the NCTRER was expanded from an original SDF file kindly provided by the NCTR Source, Weida Tong. The file was converted to DSSTox format by ClarLynda Williams (EPA/NC Central Univ Student COOP; EPA) with the assistance of Jamie Burch (EPA/NC Central Univ Student COOP) and Ann Richard (EPA). Additional ER-related data fields were added by Ann Richard (EPA) in collaboration with Weida Tong and Hong Fang, both of NCTR. Finally, we thank Rob Dewoskin (EPA) for review of all documentation and Stephen Little (EPA) for providing a few missing CAS numbers, and for his careful review of the documentation and helpful suggestions. All subsequent QA review and structure modifications to NCTRER_v2 and later versions were carried out by Maritja Wolf (Lockheed Martin, Contractor for EPA).

DSSTox Citation: Tong, W., H. Fang, C.R. Williams, J.M. Burch, and A.M. Richard (2008) DSSTox FDA National Center for Toxicological Research Estrogen Receptor Binding Database (NCTRER): SDF files and website documentation, Updated version: NCTRER_v4b_232_15Feb2008, www.epa.gov/ncct/dsstox/sdf_nctrer.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 National Health and Environmental Effects Research Laboratory 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.

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