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EDCsDATABANK

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Toxicology 327 (2015) 87–94
Contents lists available at ScienceDirect
Toxicology
journal homepage: www.elsevier.com/locate/toxicol
EDCs DataBank: 3D-Structure database of endocrine disrupting
chemicals
Diana Montes-Grajales, Jesus Olivero-Verbel *
Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, University of Cartagena, Campus of Zaragocilla, Cartagena,
Bolivar 130015, Colombia
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 8 August 2014
Received in revised form 31 October 2014
Accepted 23 November 2014
Available online 25 November 2014
Endocrine disrupting chemicals (EDCs) are a group of compounds that affect the endocrine system,
frequently found in everyday products and epidemiologically associated with several diseases. The
purpose of this work was to develop EDCs DataBank, the only database of EDCs with three-dimensional
structures. This database was built on MySQL using the EU list of potential endocrine disruptors and TEDX
list. It contains the three-dimensional structures available on PubChem, as well as a wide variety of
information from different databases and text mining tools, useful for almost any kind of research
regarding EDCs. The web platform was developed employing HTML, CSS and PHP languages, with
dynamic contents in a graphic environment, facilitating information analysis. Currently EDCs DataBank
has 615 molecules, including pesticides, natural and industrial products, cosmetics, drugs and food
additives, among other low molecular weight xenobiotics. Therefore, this database can be used to study
the toxicological effects of these molecules, or to develop pharmaceuticals targeting hormone receptors,
through docking studies, high-throughput virtual screening and ligand-protein interaction analysis. EDCs
DataBank is totally user-friendly and the 3D-structures of the molecules can be downloaded in several
formats. This database is freely available at http://edcs.unicartagena.edu.co.
ã 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords:
Xenobiotic
Endocrine disruptor
Database
Virtual screening
Computational toxicology
1. Introduction
Endocrine disrupting chemicals (EDCs) are environmental
toxicants proposed to cause adverse effects in the body through
disruption of the endocrine system (Stoji
c et al., 2010). These have
been defined by the US Environmental Protection Agency as
exogenous agents that interfere with the synthesis, secretion,
transportation, binding, action, or elimination of natural hormones
Abbreviations: CCRIS, chemical carcinogenesis research information system;
EADB, estrogenic activity database; EDCs, endocrine disrupting chemicals; CID,
PubChem compound identifier; CTD, comparative toxicogenomics database; EDID,
endocrine disrupting chemicals–diet interaction database; EDKB, established
knowledge base for endocrine disrupting chemicals; EDPSD, endocrine disruptor
priority settings database; GENE-TOX, genetic toxicology data bank; HSDB,
hazardous substances data bank; HTML, hypertext markup language; IRIS,
integrated risk information system; ITER, international toxicity estimates for risk;
PCA, principal component analysis; PHP, PHP hypertext preprocessor; POPs,
persistent organic pollutant; log P, octanol–water partition; RBD, development of
the receptor database; SMILES, simplified molecular input line entry specification;
TOXNET, toxicology data network.
* Corresponding author. Tel.: +57 5 6698179/80; fax: +57 5 6698323.
E-mail addresses: [email protected] (D. Montes-Grajales),
[email protected] (J. Olivero-Verbel).
http://dx.doi.org/10.1016/j.tox.2014.11.006
0300-483X/ ã 2014 Elsevier Ireland Ltd. All rights reserved.
in the body that are responsible for the maintenance of
homeostasis, reproduction, development, and/or behavior. EDCs
include a wide range of compounds such as insecticides,
plasticizers and monomers, flame retardants, natural products,
fragrances, industrial chemicals, organic pollutants and food
contact materials, among others (Markey et al., 2002; Mezcua
et al., 2012; Muncke, 2011).
Nowadays, these compounds give reason for growing international concern (Rousselle et al., 2013), due to their widespread
exposure to the general population (Meeker, 2010). Increasing
evidence from both experimental animal and epidemiology
studies suggest that there is a link between exposure to EDCs
and many diseases (Gore et al., 2014). Some of the potential health
problems that have been related to certain EDCs include
reproductive disorders, dysplasia and the development or progression of cancers, such as breast, ovarian, testicular and prostate
cancer (Xi et al., 2013), obesity, diabetes, heart disease, neurodevelopmental and neurodegenerative disorders (Mezcua et al.,
2012). In addition, these chemicals may affect biota, producing
adverse ecological and human health effects (Kumar and
Xagoraraki, 2010).
EDCs are widely found in various everyday products and have
been detected in waste water treatment plants (Stasinakis et al.,
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D. Montes-Grajales, J. Olivero-Verbel / Toxicology 327 (2015) 87–94
2008). However, the identification of compounds with estrogenic
activity remains a challenge. Although hundreds of these
molecules have been identified – including persistent organic
pollutants (POPs) – the information known about them is just the
tip of the iceberg. Therefore, EDCs are of special interest because of
the large production volumes linked to some of these substances
(Birnbaum, 2013). Exposure to the EDCs is spread in urban areas
through consumer products. In the environment, they are mainly
deposited in sediments and biosolids due to their large octanol–
water partition coefficient (log P) (Stasinakis et al., 2008).
The report from the World Health Organization and UNEP
(http://www.who.int/ceh/publications/endocrine/en/) indicates
that EDCs are a global problem requiring global solutions. These
compounds pollute the planet through the air and water flows.
Hundreds of them have been detected in humans and wildlife,
including even those from remote parts of the world such as the
Arctic. Therefore, it is almost impossible to find a population that is
not exposed to EDCs (Birnbaum, 2013).
EDCs belong to diverse groups of chemicals with very dissimilar
structures, biochemical properties and mechanisms of action
(Stoji
c et al., 2010). The majority of these are still unknown
(Vuorinen et al., 2013). Furthermore, computer-based predictions
of the toxicity of EDCs are increasingly used, due to the growing
need to screen a large number of chemicals in order to determine
their adverse biological activity (Stoji
c et al., 2010). Despite the
efforts that have been made to identify these compounds and
provide experimental data, there was not a repository with threedimensional structures for performing toxicology computational
studies. Therefore, the main purpose of this work was to develop a
database that would provide structural information of these
compounds, open to both the general public and academia.
2. Materials and methods
2.1. Data sources
2.1.1. Molecular structures
In the context of this database, EDCs are those molecules with
the potential to affect the endocrine system with reported data in
the scientific literature. Therefore, the names and CAS numbers of
the EDCs were obtained from the EU list of potential endocrine
disruptors (http://www.mst.dk/English/Chemicals/endocrine_disruptors/the_EU_list_of_potential_endocrine_disruptors/) and the
TEDX list (http://endocrinedisruption.org/endocrine-disruption/
tedx-list-of-potential-endocrine-disruptors/overview). Molecules
stored in these repositories have been cited at least once as
endocrine disruptors in scientific articles. The molecular structures
of the EDCs with three-dimensional structures available in
PubChem (Bolton et al., 2008) were downloaded in 2D- and 3Dsdf formats. These last, were used for building an internal chemical
library in Instant JChem (http://www.chemaxon.com), which was
then saved as a single sdf file containing all the three-dimensional
structures of the EDCs, as well as basic information of each one. The
3D-sdf files were also translated to mol2, pdb and pdbqt format
files employing Sybyl X-2.0 program package (Tripos, St. Louis,
MO), Open Babel (O’Boyle et al., 2011) and AutoDock tools (http://
autodock.scripps.edu/resources/adt), respectively.
health, poisoning, risk assessment and regulations, and toxicology;
ACToR (Judson et al., 2007), a database with structural, toxicological and bioactivity information of environmental chemicals
derived from more than 150 sources of information including
ToxCast (Dix et al., 2007) – a database of activity data for numerous
compounds obtained by high-throughput screening assays; Fable
(http://fable.chop.edu), a fast, automated tool for finding human
genes associated with a keyword and biomedical literature
extraction; and PubMed (http://www.ncbi.nlm.nih.gov/pubmed).
This database has two links to PubMed, the first one is for a
general search of articles containing the name of the compound,
and the second one further includes 40 keywords related with
endocrine disruption in the PubMed query as a filter to present
only the articles associated with endocrine disruption. Those terms
were previously selected using the text mining tool PubMed
PubReMiner (http://hgserver2.amc.nl/cgi-bin/miner/miner2.cgi).
An example of a query search using this link for 3,5-dichlorobiphenyl is presented below:
“3,5-dichlorobiphenyl” and (“androgen” or “androgenic” or
“adrenergic” or “antiadrenergic” or “antiandrogen” or “antiandrogenic” or “antiestrogenic” or “antithyroid” or “aromatase” or
“catecholamines” or “EDCs” or “endocrine” or “ERalpha”
or “estradiol” or “estrogen” or “estrogenic” or “estrogenicity” or
“fertility” or “glucocorticoid” or “hormone” or “proestrogenic” or
“progesterone” or “progesteronic” or “reproductive” or “semen”
or “sperm” or “spermatogenesis” or “steoroids” or “thyroid” or
“urogenital” or “xenoestrogen” or “xenoestrogenic” or “xenoestrogens” or “imposex” or “cancer” or “ovary” or “pregnancy” or
“testosterone” or “uterus” or “tumor”).
2.1.3. Graphics
High quality images of the 2D- and 3D-structures of each
compound were prepared in Marvin Sketch (http://www.chemaxon.com) and PyMol (http://www.pymol.org/), using as input the
obtained 2D- and 3D-sdf files, setting colors by atom type in order
to facilitate their reading. These images are useful for obtaining a
general overview of the geometry of the molecules and possible
sites of interactions. In addition, icons of the different sources of
EDCs were generated as a user-friendly tool that enables a quick
identification of the potential places for greatest risk of exposure,
helping to remember them for educational purposes.
2.2. Data schemes and database implementation
In order to offer a structure for the EDCs DataSheet (page
containing the information for each EDC) in the web development
and database management, all data were organized in the
following sections: name, synonyms, source, identifiers, structural
properties, pharmacophore features, downloads, similarity search,
toxicological information, external links and keywords, as shown
in Table 1.
The EDCs DataBank website was developed from scratch using
HTML (hypertext markup language), CSS, JQuery, JavaScript and
PHP languages (PHP hypertext preprocessor) in a NotePad++ editor.
The database was built on MySQL, the most popular open source
database. The architecture of EDCs DataBank is shown in Fig. 1.
2.3. Quality assurance, validation, completeness and curation
2.1.2. External links, physico-chemical and toxicological information
A wide variety of information for each compound was obtained
from different databases and search engines, such as PubChem
(Bolton et al., 2008), a database of chemical molecules and their
activities against biological assays; TOXNET (toxicology data
network; http://toxnet.nlm.nih.gov/) (Wexler, 2001), a group of
databases covering chemicals and drugs, diseases and the
environment, environmental health, occupational safety and
All the information has been hand cured in order to reduce, as
much as possible, the errors, and the fields of this database have
been completed based on all available information.
Most of the structural information contained in EDCs DataBank
was obtained directly from PubChem (Bolton et al., 2008) and
managed through Instant JChem (http://www.chemaxon.com), for
its inclusion directly in the MySQL database of EDCs DataBank. The
D. Montes-Grajales, J. Olivero-Verbel / Toxicology 327 (2015) 87–94
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Table 1
Structure of the information contained in the EDCs DataSheets.
Field
Description
Name
The most common name for the molecule.
Synonyms
Source
Identifiers
Sructural
properties
Pharmacophore
features
Downloads
Similarity
search
Toxicological
information
External links
Keywords
Source
TEDX list (http://www.endocrinedisruption.com/endocrine.TEDXList.
overview.php) and EU list of potential endocrine disruptors (http://www.
mst.dk/English/Chemicals/endocrine_disruptors/
the_EU_list_of_potential_endocrine_disruptors/).
Alternative names given to the compound.
PubChem (Bolton et al., 2008).
Exposure sources for each EDC.
Internet.
IUPAC name, CAS number, PubChem ID, InChiKey and canonical SMILES. TEDX list (http://www.endocrinedisruption.com/endocrine.TEDXList.
overview.php) and PubChem (Bolton et al., 2008)
It includes molecular formula and molecular weight.
PubChem (Bolton et al., 2008).
Number of bond donors, bond acceptors and atoms different from
hydrogen (heavy atoms).
2D structure (2D-sdf file) and 3D structures (3D-sdf file, mol2, pdb and
pdbqt)
It searches for similar molecules into the database.
PubChem (Bolton et al., 2008).
PubChem (Bolton et al., 2008); the formats mol2, pdb and pdbqt were
obtaining by translation of the original sdf files.
The matrix was generated using the PubChem Score Matrix Service
(http://pubchem.ncbi.nlm.nih.gov//score_matrix/score_matrix.cgi).
This is a resource that presents the available toxicological information in ACToR (Judson et al., 2007), TEDX list (http://www.endocrinedisruption.
the databases ACToR, hazardous substances data bank (HSDB), chemical com/endocrine.TEDXList.overview.php) and TOXNET (Wexler, 2001).
carcinogenesis research information system (CCRIS), GENE-TOX,
comparative toxicogenomics database (CTD), integrated risk information
system (IRIS), international toxicity estimates for risk (ITER) and TEDX list.
These are links to other databases and search engines.
PubChem (Bolton et al., 2008), PubMed (http://www.ncbi.nlm.nih.gov/
pubmed), PhysProp (http://esc.syrres.com/fatepointer/search.asp) and
Fable (http://fable.chop.edu).
Words related to each EDC. The words with the largest letters represent a LigerCat (Sarkar et al., 2009).
major association.
theoretical models of the three-dimensional structures were also
obtained directly from PubChem (Bolton et al., 2008; https://
pubchem.ncbi.nlm.nih.gov/release3d.html), leading the file names
as default, and translated to several formats using standardized
protocols in order to avoid typing errors.
All the information contained in each EDC DataSheet was
carefully revised. The whole texts of each datasheet were revised
three times by a Ph.D. student and an undergraduate student, the
correct functioning of the external links and toxicological
information iframes was also checked. The concordance between
the name, 2D structure, 3D structure and Jmol interactive
molecular viewer (http://jmol.sourceforge.net/index.en.html/)
was examined; and each 2D and 3D structure was downloaded
and the geometry was checked using pymol in order to be sure that
the 3D-structures contain three-dimensional features, expected
connectivity and normal bond lengths. These revisions will be
performed systematically and regularly in order to keep the
database updated and curated. Users are also encouraged to
suggest improvements to the database through the “questions and
comments” form, located in the Contact us option of the main
menu.
The website of EDCs DataBanks is hosted as a subdomain of the
University of Cartagena website (http://edcs.unicartagena.edu.co/),
which contributes to its permanency and continuous development
Fig. 1. EDCs DataBank arquitecture.
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D. Montes-Grajales, J. Olivero-Verbel / Toxicology 327 (2015) 87–94
by the students of the Ph.D. Program in Environmental Toxicology of
this University, working in the research line of the endocrine
disruptors and environmental pollutants. Additional information
and new molecules will be included in the database, in accordance
with the information available and the new discoveries in this field.
3. Results
3.1. Data sources
3.1.1. Molecular structures
EDCs DataBank currently contains 615 molecules. This database
allows the download of the whole 2D and 3D structures stored on
it, in several formats (mol2, pdb, pdbqt, sdf). This can be executed
from the download section of each EDC DataSheet or from the
download option of the main menu. This possibility contributes to
an easy use of these compounds in docking, QSAR and virtual
screening studies.
3.1.2. External links, physico-chemical and toxicological information
The EDCs belonging to EDCs DataBank include pesticides,
flavonoids and medicinal plants; as well as compounds used in
cosmetics, plastics and pharmaceutical industry, among others.
Many of them also correspond to environmental pollutants, or are
components of everyday goods, such as household and personal
care products. A broad diversity of data regarding each compound
is available in the DataSheet of each compound, organized in the
following sections: name, synonyms, source, identifiers, structural properties, pharmacophore features, downloads, similarity
search and keywords. In addition, this database is hyperlinked to
other important databases in the field of toxicology and literature
search such as PubMed, PubChem (Bolton et al., 2008), ACToR
(Judson et al., 2007), LigerCat (Sarkar et al., 2009), PhysProp and
TOXNET – HSDB (hazardous substances data bank), CCRIS
(chemical carcinogenesis research information system),
GENE-TOX (genetic toxicology data bank), CTD (comparative
toxicogenomics database), IRIS (integrated risk information
system) and ITER (international toxicity estimates for risk). These
links are present as a section on toxicological information,
external links and keywords of the DataSheet for each compound.
In the case of the items of the toxicological information and
physical properties hyperlink, its availability depends of the
existence of the information in the source database. The number
of molecules in EDCs DataBank with available data in those fields
is presented in Fig. 2.
3.1.3. Graphics
Fig. 2. Number of molecules with toxicological and physicochemical data available
in EDCs DataBank.
Each EDC has images of its 2D- and 3D-structures in
high-quality. In addition, a Jmol application (http://jmol.sourceforge.net/index.en.html/) was included to the EDCs DataSheet,
which allows the interaction with the three-dimensional structure
and simple calculations by right-clicking on the image. In order to
use this applet, an updated version of Java is required. The 51 icons
regarding the different sources of EDCs are also available as a
search tool in the home page, and for information in the EDCs
DataSheets.
3.2. Data schemes and database implementation
3.2.1. EDCs DataBank description
EDCs DataBank is a unique database with three-dimensional
structures of EDCs for virtual screening. It includes compounds
utilized in pesticides, cosmetics, gasoline and food, health care and
household products, among others. It is suitable for virtual
screening because each molecule is presented in several formats
(mol2, pdb, pdbqt, sdf), allowing the use of different computer
aided tools for their analysis. Consequently, EDCs DataBank is a
valuable repository to study the interactions of these compounds
with macromolecules involved in several diseases, such as breast
cancer, obesity and diabetes. The databank also benefits the
community and students, since it contains possible sources of
exposure to EDCs, toxicological information and links to different
databases in a user-friendly environment.
3.2.2. Website map
At the top of the page is the main menu of the EDCs DataBank.
The user can find the search bar and access the advanced search.
The website of the database possesses a download page in which
the user can obtain the 3D structures of all molecules stored in
EDCs DataBank in different formats, as well as images regarding
statistical information of all compounds. This page also contains a
questions and comments form in the contact us button, in which
the user can communicate their inquiries and suggestions. The
website includes an about and help links with detailed information
regarding EDCs DataBank and its use. The map of the website is
shown in Fig. 3.
3.2.3. Search and advanced search
This database is fully searchable. The general searcher (Fig. 4A),
located at the top of the website home page, allows the user to seek
expressions found in the category name, synonyms and the IUPAC
name. The searcher considers many options to call a molecule,
facilitating the searching and identification of the compounds. The
advanced search (Fig. 4B) generates a query according to the search
parameter selected by the users. Compounds may be searched in a
range of molecular weight, number of bond donors, number of
heavy atoms (atoms different from hydrogen), number of bond
acceptors, and a multiple entry search. The search by source
(Fig. 4C), found at the home page below the search box, consists of
51 icons representing the possible sources of exposure to
endocrine disruptors. This tool helps to make our database more
user-friendly and useful to the general public, by showing the
compounds that may be found on certain elements or products to
which people could be exposed.
3.2.4. EDCs DataSheet
EDCs DataBank is a non-redundant database built on MySQL.
The identifier InChIKey has been used as a primary key, in order to
make it not redundant. In addition, given the current state of
information and the difficulty of handling it, especially in terms of
codes of molecules, we decided not to incorporate a new identifier
of molecules for our database. Therefore, we use the existing and
widely recognized PubChem compound identifier (CID) (Bolton
D. Montes-Grajales, J. Olivero-Verbel / Toxicology 327 (2015) 87–94
Fig. 3. Map of EDCs DataBank website.
Fig. 4. Screenshot of search of (A) search, (B) advanced search and (C) source.
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D. Montes-Grajales, J. Olivero-Verbel / Toxicology 327 (2015) 87–94
Fig. 5. EDCs DataSheet screenshot for methyl-paraben.
D. Montes-Grajales, J. Olivero-Verbel / Toxicology 327 (2015) 87–94
et al., 2008), which is shown in identifiers and utilized to name the
2D- and 3D-structure files and images in the different formats
offered by this database.
All the information stored in the MySQL database is presented
in a user-friendly web environment in the EDCs DataSheets (Fig. 5).
The website has been developed utilizing HTML, PHP, CSS, JQuery
and JavaScript languages using an appropriately graphic design in
order to simplify the process of finding and reading data.
EDCs DataSheets show the information for each single compound
selected by the user. The data is presented in 10 main categories:
name, synonyms, source, identifiers, structural properties, pharmacophore features, downloads, search similar structures, toxicological
information, external links and keywords, which are accompanied
by source icons, 2D- and 3D-structure figures and an interactive
three-dimensional view of each compound by Jmol (http://jmol.
sourceforge.net/index.en.html/), allowing to perform simple calculations such as van der Waal surface, distances, angles, dihedral
angles, among other. Another interesting tool in the EDCs DataSheet
is its capability of searching for similar molecules. The tool was
created by employing a similarity matrix calculated in the PubChem
Score Matrix Service (https://pubchem.ncbi.nlm.nih.gov/score_matrix/score_matrix-help.html). The 2D similarity (substructure keys)
between molecules was used as a scoring method, so that the client
only has to include the range of similitude percentage for the search.
Currently, EDCs DataBank is the unique database of endocrine
disruptors with three dimensional structures available for virtual
screening, with a complete repository of information regarding
EDCs and their molecular structures. Therefore, it will have an
impact in the study of these compounds through bioinformatics
and computational toxicology strategies.
3.3. Quality assurance, validation, completeness and curation
The data contained in EDCs DataBank has been revised and
hand curated, diminishing the possible errors. All the fields of this
database are fully complete with exception of external links and
toxicological information that depend on the availability of the
data in the source databases. In addition, this database uses
PubChem as primary source for the three-dimensional structures,
which is one of the most recognized and used databases for getting
chemical structures of low molecular weight compounds (Bolton
et al., 2008).
93
the receptor database), which can assist with the problem of
endocrine disruptors, presenting information about steroid
hormone receptors to which endocrine disruptors could join
(Nakata et al., 1999); EDID (endocrine disrupting chemicals–diet
interaction database) has information about the possible interactions between diet and endocrine disruptors, allowing the search
for scientific papers, showing this information by entering words
found in the article title, keywords, and/or publication year (Baldi
and Mantovani, 2008); EDPSD (endocrine disruptor priority
settings database), a useful database which ranks priority chemical
parameters for screening and testing endocrine disruptors (http://
www.epa.gov/endo/pubs/prioritysetting/finalarch.htm);
and
EADB (estrogenic activity database), contains information of
estrogenic activity for 8212 chemicals in in vitro and in vivo assays
of different species (Shen et al., 2013).
However, there was not a database of EDCs with threedimensional structures available for virtual screening. This
database is a valuable repository to study the interactions of
these compounds with macromolecules involved in several
diseases, such as breast cancer, obesity and diabetes, among
others. In addition, it was created in a very user-friendly
environment that makes it helpful for community information
regarding EDCs exposure in everyday products and their eventual
toxicity impact in environmental and human health.
5. Conclusions
EDCs DataBank is the unique database with three-dimensional
structures of EDCs for virtual screening, freely available on
http://edcs.unicartagena.edu.co. It is also suitable for its use with
other computational approaches as all molecular structures stored
in it can be downloaded in several formats. Therefore, it is a
valuable repository to study the molecular basis of the interaction
between these molecules and macromolecules involved in diverse
pathologies. In addition, EDCs DataBank has been developed in a
user-friendly environment and provides a vast amount of
structural and toxicological information of each compound that
can be used for research, academia and general population.
Conflict of interest
The authors declare that there are no conflicts of interest.
4. Discussion
Historically, the public, scientific and regulatory concerns
regarding the potential adverse health effects of exposure to EDCs
were initiated in the early 1990s (Safe, 2000). Since then,
numerous efforts have been made to compile information related
to these compounds. In 1988, before the term was coined
“endocrine disruptor”, Dr. Theo Colborn began the search for
compounds with potential to interfere with the endocrine system.
These compounds were consolidated in the TEDX list of potential
endocrine disruptors (http://endocrinedisruption.org/endocrinedisruption/tedx-list-of-potential-endocrine-disruptors/overview).
Another interesting project started in mid-1990s, was EDKB
(established knowledge base for endocrine disrupting chemicals),
which consists of a database with information on the chemical
structure, name, testing and supply of the experiment, containing
more than 3257 records and about 1800 EDCs (Ding et al., 2010). In
2010, Nashev et al. created an internal database of endocrine
disruptors which was used to perform virtual screening studies
with protein 17b dehydrogenase type 3 (Nashev et al., 2010). Later,
in 2012, the database was employed for the identification of
xenobiotics as potential disruptors of corticosteroid action (Nashev
et al., 2012). Other databases in this field are RBD (development of
Transparency document
The Transparency document associated with this article can be
found in the online version.
Acknowledgments
The authors wish to thank the Administrative Department of
Science, Technology and Innovation of Colombia, Colciencias
(Grants 567-2012 to D.M.-G., 1107-519-29058, 1107-459-21616;
CENIVAM, RC 0572-2012) and the University of Cartagena
(0342010) for the financial support; and the Novation Program
and Division of Communications and Public Relations of the
University of Cartagena for their technical assistance.
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