US EPA CompTox
Chemicals Dashboard
Antony Williams
US EPA, Center for Computational Toxicology and Exposure
Durham, NC
919-541-1033
williams.antony@epa.gov
-------
Conflict of Interest Statement
This work was reviewed by EPA and approved for presentation but does not
necessarily reflect official Agency policy.
-------
Abbreviations
CompTox - Computational Toxicology
DSSTox - Distributed Structure
Searchable Toxicity DB
CASRN - Chemical Abstracts Registry
Number
InChl - International Chemical
Identifier
QMRF - QSAR Model Report Format
ToxVal - Toxicity Value Database
OPERA - OPEn structure-activity
Relationship App
TEST - Toxicity Estimation Software
Tool
• ToxCAST - Toxicity Forecaster
• CERAPP - Collaborative Estrogen
Receptor Activity Prediction Project
• CoMPARA - Collaborative Modeling
Project for Androgen Receptor Activity
• SDF - Structure data file
-------
CompTox Chemicals Dashboard
https://comptox.epa.gov/dashboard
875k Chemical Substances
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
LAgency
PRQ*^
875 Thousand Chemicals
\
Chemicals
Product/Use Categories
Assay/Gene
I
~ Identifier substring search
See what people are saying, read the dashboard comments!
Cite the Dashboard Publication click here
Latest News
Read more news
Journal of Cheminforrnatics article regarding "MS-Ready structures"
March 9th, 2019 at 1:09:45 PM
A recent article describes "MS-Ready structures", what they are, how they are generated and details regarding the benefits of these structures in navigating structure
relationships across the dashboard. The article is published in the Journal of Cheminforrnatics here.
-------
BASIC Search
Chemicals
Product/Use Categories Assay/Gene
Q, Bisphenol
Eispheno A
DTXSID702Q182
b
Eispheno A bis(2~hydroxyethyl ether] diacrylate
DTXSIDS066991
Eispheno A bis(2-hydroxyethyl ether) dinnethacrylate
DTXS!DiQ66992
Eisphero A bts(2-hydroxypropyl) ether
DTXSID8Q51592
Bisphenol A carbonate polymer
D7XSIDSD2754G
Eispheno A digIycidyl ether
DTXS!D5€24624
Type ahead search using Names,
synonyms and CASRNs
Millions of identifiers
Substring search
Search Results
Searched with 'Synonym Substring': Bisphenol
541 chemicals
Bisphenol A gIycidyl rr ethacry ate
DTXSID7044S41
-------
Detailed Chemical Pages
A United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Down toads
Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANS PORT
HAZARD
~ ADME
~ EXPOSURE
~ BIOACTIVTTY
SIMILAR COMPOUNDS
GENRA (BETA}
RELATED SUBSTANCES
SYNONYMS
~ UTERATURE
UNKS
COMMENTS
^Bisphenol A
80-05-7 I DTXSID7020182
Searched by DSSTox Substance Id.
HjC
CHs
//
\ >
V-
tl
HO
OH
Wikipedia
Bisphenol A (BPA) is an organic synthetic compound with the chemical formula (CHjJjQCgH^QH^ belonging to the group of dSphenylmethane derivatives and
bisphenols. with two hydroxypbenyl groups, t is a colorless solid that is soluble in organic solvents, but poorly soluble in water (0.344 wt % at 33 6C).
BPA is a starting material for the synthesis of plastics, primarily certain polycarbonates
Read more
Linked Substances
Quality Control Notes
Presence in Lists
Record Information
Structural Identifiers
Intrinsic Properties
ft, Molecular Formula: C15H1G02 +. Mol File Q. Find All Chemicals
ft, Average Mass: 228.291 g/mol [jri sotope Mass Distribution
j*, Monoisotopic Mass: 223. T1503 g/mol
Chemical page: Wikipedia snippet when available, intrinsic
properties, structural identifiers, linked substances
-------
it
Executive Summary
;;
Executive Summary
Quantitative Risk Assessment Values
^ IRIS values available G?
Q No PPRTV values
Q EPA RSL values available Gf
0 Minimum RfD: 0.050 mg/kg-day (chronic, IRIS, oral, 8)Gf
Q No RfC calculated
Q IV1VE POD not calculated
Quantitative Hazard Values
Q Minimum oral POD 3.8 mg/kg-day (reproductive HP VIS oral. 6)G?
© >lo inhalation POD values
Q Lowest Observed Bioactivity Equivalent Level: CYP1A1. CYP1A2, Tpo. ESR2. ESR1, ESR1.
NR113. PPARA, NR1I2. Cyp2c11. MMP3. Esrl
Cancer Information
© No cancer slope factor
© No inhalation unit risk value
Q Carcinogenicity data available: University of Maryland carcinogenicity warning Gf
Q Mo genotoxicity findHigs reported
Reproductive Toxicology
Q 200 Reproductive toxicity PODs available Gf
Chronic Toxicology
Q 340 Chronic toxicity PODs available G?
Subchronic Toxicology
Q 12 Subchronic toxicity PODs available Gf
Developmental Toxicology
© 6 Developmental toxicity PODs available Gf
Acute Toxicology
& 391 Acute toxicity PODs available Gf
Subacute Toxicology
@ 1 subacute toxicity PODs available 3"
Neurotoxicology
© No r»eurotoxicology data available.
Endocrine System
Q Endocrine Disruption Potential Significant Estrogen and Androgen Receptor activity seen
Chemical was positive in 21 ER assays (out of 35) and was positive in 9 AR assays (tested in 19).
ADME
O HTTK Css data are available Gf
Fate and Transport
© No bioaccumulatiort concern
©No volatility concern
Biodegradation predictions are available Gf
Q BCF predictions are available Gf
Q Vapor Pressure predictions are available Gf
Exposure
Q Exposure estimates are available based on NHANES and SEEM Gf
AOP Information
Q AOP Links: 13, 33. 36, 58, 50. 61. 66,107. 124,150,163,175.187, 200
Other Notes
Q No water quality values available.
© Mo air quality values available.
Q 14 Occupational exposure values available Gf
POINT-OF-DEPARTURE PLOTS
Class \
THQ
Value
risk-based SSL (mg/kg) \
THQ = 0 1
5.8
GIABS (unspecified)
THQ = 1
1
GIABS (unspecified) N.
THQ = 0.1
1
ABS (unspecified) \
THQ = 0.1
0.1
RFDo (mg/kg-day) \
THQ = 0.1
0.05
screening level (residential Soil) (mg/kg) \
THQ = 0.1
320
screening level (industrial soil) (mg/kg)
TNQ = 0 1
4100
screening»Jevel (tap water) (ug/L)
THQMh4
77
RFDo (mg/kgSsay)
THQ = 1 \
0.05
screening level (residential Soil) (mg/kg)
THQ = 1
53OO
screening level (indusmal soil) (mg/kg)
THQ = 1
41000\.
ABS (unspecified) \
THQ = 1
0 1 ^
risk-based SSL (mg/kg) \
THQ = 1
58
screening level (tap water) (ug/L) \
THQ = 1
770
O PHYSCHEM PARAMETERS
-5 0 5 10 15
logP
-5 0 5\ 10 15
log(BCF)\
Overview of toxicity-related info
• Quantitative values
• Info re. toxicology subsets
• Physchem. and Fate & Transport
• Adverse Outcome Pathway links
• In vitro bioactivity summary plot
Quantitative Risk Assessment Values
(Jp IRIS values available Of
© No PPRTV values
Q EPA RSL values available Gf
Minimum RfD: 0.050 mg/kg-day (chronic, IRIS. oral. 8)Gf
© No RfC calculated
© (VIVE POD not calculated
Quantitative Hazard Values
Minimum oral POD 3.6 mg.'kg-day (reproductive. HPV1S. oral. 6) Gf
© No inhalation POD values
Q Lowest Observed Bioactivity Equivalenl Level: CYP1A1 CYP1A2, Tpo. ESR2 E5R1, ESR1.
NR1I3. PPARA, NR1I2, Cyp2c11. MMP3. Esr1
O ASSAY PLOTS
.J
-------
Experimental and Predicted Data
®Bisphenol A
& H. 80-05-7 | DTXSID7020182
Searched by DSSTox Substance Id.
Property
Sumimary
Physchem and Fate & Transport
experimental and predicted data
Data can be downloaded as Excel, TSV
and CSV files
i. Down oac »
Columns v
Property "
Experimental average *
Predicted average *"
LogP: Octarol-Water
3.32 CI)
3.29
Meltirg Poirt
155 (7)
135
Soi org Point
200 (1)
363
Water Solubility
5.26e-4 (1)
9.62e-4
Vapor Pressure
-
S,37e-7
Flash Point
-
190
• Predictions: multiple algorithms
• EPI Suite: Estimation Program Interface
• ACD/Labs (commercial)
• TEST: Toxicity Estimation Software Tool
• OPERA: OPEn structure-activity/
property Relationship App
-------
Transparency for prediction models
Predicted
¦A- Down oad Predicted Data *
Source ~
Result '
Calculation Details
Jk.
¦w
QMRF '
EPiSUjTE
3,64
Not Aval abie
Not Avai able
NICEATM
2,40
Not Available
Avai able
ACD/Labs Consensus
3,63
Not Available
Not Avai able
ACD/Labs
3.43
Not Available
Not Avai able
OPERA
3,35
OPERA Mode Report [Inside AD]
Avai able
OPERA Models: LogP: Octanol-Water
Bisphenol A
80-05-7 I DTXSID7020182
/sighted KNN model
QMRF-QSAR Model
Report Format details
Applicability Domain
Plots of expt. vs pred.
Nearest-neighbors
toeasurei±3-32
Predicted: 3J3S076
SUTANO/I acip,2 v
• IYDBQXV 3 M£TKV
Predicted: 3.35052
2.2 Diphenvlprqp.onic a:
Measured J.69
Prerictett 2 &4S03
3 OH-2-|4-6iPnENVW:HEXfiMOIC AClO
Mewjred^.75
Predicted: 3.70322
-------
OPERA Standalone Application
Command line
OPERA predictions
available on dashboard
OPERA application
available (from Github)
O OPERA
OPERA models for physchera ar>d environmental fate properties.
Version 1.5 (September 2017)
OPERA is a command line application developed in Wkatlab providing QSAR
models predictions as wall as applicability domain and accuracy assessment.
Developed by:
Kamel Mansouri
mansourikamel§gmail.com
Developed at:
National Center of Computational Toxicology
United States Environmental Protection Agency
Usage: OPERA
Examples:
OPERA -s Sample_50,sdf -o predictions.csv -a -x -v 2
opera -d Sample_5 Download the latest compiled version from the "releases" tab and run the executable installer.
Manage tapirs
® 142 commits p 1 branch
Branch: master - New pull nequest
12 ieleases
H1 contributor
|https://github.com/NIEHS/OPERA
-------
Chemical Hazard Data
ToxVal Database Hazard
DataType
Taxi city Value
v 1
¦fa Download *
Columns v
nb
® ^30k chemic31s ^~
• >770k tox. values
More*
Priority*
Type*
5ubtype *
Risk assessment class *
Value*
Units *
Study type*
Exposure route *
Species*
Subsource *
Source *
h
7
MEG
Short-term Critical Air
short-term
SCO
mg/m3
inhalation
TG 230 Military Exposure Guidelines Table
COD
ft
7
MEG
Short-term Marginal Air
short-term
100
mg/m3
-
inhalation
TG 230 Military Exposure Guidelines Table
COD
• ~30 sources of data
1
7
MEG
Short-term Negligible Air
short-term
15
rng/m3
inhalation
TG 230 Military Exposure Guidelines Table
COD
ft
¦7
MEG
Soil Negligible Soil
chronic
1C6000
mg/kg
-
soil
TG 230 Militaiy Exposure Guidelines Table
DOD
• ~22k sub-sources
ft
7
MEG
Long-Term, 5L/d Negligible Water
chronic
7
mg/'L
oral
TG 230 Military Exposure Guidelines Table
COD
ft
6
RfD
-
chronic
0.05
mg/kg-day
oral
rat
Wignall
Wignall
• ~5k journals cited
ft
5
RfD
-
chronic
0.05
mg/kg-day
MSC Table 5
Pennsylvania DSP ToxVaiues
ft
4
RfD
-
chronic
0.05
mg/lcg-day
chronic
oral
rat
IRIS
Chiu
• ~70k citations
ft
3
RfD
-
chronic
0.6
mg/kg-day
oral
rat
EPA/ORNL/OLEM
HEAST
ft
1
RfD
-
chronic
0.05
mg/kg-day
oral
EPA NCEA
IRJS
-------
In Vitro
Bioassay Screening
ToxCast and Tox21
In vitrobioactivity
4K chemicals (ToxCast)
8k chemicals (Tox21)
/V
2k assay endpoints
Bisphenol A
80-05-7 j DTXSID7020182
Searched by DSSTox Substance Id.
Chemical Activity Summary £)
O TOXCAST DATA
ShciwAl
ccfl cyde
cell morpliatagy
coll adhesarr maecultrs
cytokine
8PCf
o #
• ••
• <* ^v- +
I I I I ITI i f I I
"I 1 i I I III
ACSO (uM)
o ASSAY DETAILS
AC50 (uM): 46.36
Scaled top: 6.19
Assay Endpoint Name; TOX21_CAR_Agocist
Gene Symbol: NR113
Organism: human
Tissue: liver
Assay Format Type cell-based
Biological Process Target regulation of transcription factor activity
Detection Technology: Lutiferase-coupled ATP quantitation
Analysis Direction: positive
Intended Target Family: nuclear receptor
Description: Data from the assay component TOX21_CARwAgonist was
analyzed into 1 assay endpoint This assay end pant
TOX2l_CAR_Agonist, was analyzed in the positive fitting direction
relative to DM SO as the negative control and baseline of activity. Using
a type of indudbie reporter, gain-of-signal activity can be used to
u nderstand changes in the reporter gene as they relate to the gene
NR113. Furthermore, this assay endpoint can be referred to as a primary
readout because the performed assay has only produced 1 assay
endpoint To generalize the intended target to other relatable targets,
this assay endpoint is annotated to the nuclear receptor intended
target family.
-------
In Vitro Bioassay Screening
ToxCast and Tox21
United States
, Environmental Protection
i Agency
EXECUTIVE SUMMARY
PROPERTIES
£WV- FATE/TRANSPORT
HAZARD
~ ADME
~ EXPOSURE
» BIOACTiVlTV
TOXCAST: SUMMARY
EDSP21
PUSCHEM
TOXCAST: MODELS
SIMILAR COMPOUNDS
GENRA CflHAJ
RELATED SUBSTANCES
SYNONYMS
~ LITERATURE
mas
COMMENTS
Advanced Search Batch Search Lists v Predictions Downloads
Bisphenol A
80-05-7 I DTXSID7020182
Searched by Expert Validated Synonym.
Assay Selection 136 Selected
*¦ Active G Inactive ~ All
ToxCast/Tox21
QC Data ID
Grade
Dsscrtptlon
Td*21_202&32
Pass
Purity-'EWk and MW confirmed
Tcc*21_4COOflB
Pass
Purity* 90% and MW confirmed
A Single Assay Can Have Multiple Charts
B Representative Samples Only
u £• oactr.' ty Summary
Number of Charts: 136 I
Ceetox/OpAns {2 of 24 selected)
4
Odyssey Tnera (6 of 17 selected)
4
Attagene (4 of 165 selected)
«1
Tox21 /NCGC (44 of 211 selected)
«
CeilzDirect (3 of 48 selected)
4
B oseek <4 of 174 selected)
4
Apredca (8 of 107 selected)
4
NHEERL Pad ilia Lab (1 of 1 s elected)
4
Novascreen (46 of 167 selected)
4
NHEERL's Hunter Lab (0 of 4 selected)
4
NCCTs Lab {4 of 4 selected)
«1
ACEA Biosciences (4 of 6 selected)
4
Tanguay Lab (9 of 19 selected)
4
NHEERL Stoke' & Laws Lab (1 of 2 selected)
4
TPSHlCrSSGil
or est c=jesb m**
IsfTCMX. ACTIOS
A ,£t-:4-T
DTXaCTOSMOJ
TPaoxntinoi
/I
-------
Sources of Exposure to Chemicals
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
M m Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
~ ADME
~ EXPOSURE
PRODUCT & USE CATEGORIES
CHEMICAL WEIGHT FRACTION
CHEMICAL FUNCTIONAL USE
TOXICS RELEASE INVENTORY
MONITORING DATA
EXPOSURE PREDICTIONS
PRODUCTION VOLUME
Bisphenol A
80-05-7 | DTXSID7020182
Searched by DSSTox Substance Id.
¦ Download
Columns
10
Product and Use Categories (PUCs) Q
Seard
Product or Use Categorization »
Categorization type -
Number of Unique Products
V
manufacturing, metals
CPCat Cassette
17
adhesive
CPCat Cassette
17
paint
CPCat Cassette
16
manufacturing, machines
CPCat Cassette
12
manufacturing, plastics
CPCat Cassette
11
bulldingjnaterial. flooring
CPCat Cassette
8
surfacejreatment, metals
CPCat Cassette
8
construction
CPCat Cassette
8
stabilizer
CPCat Cassette
7
manufacturing, chemical
CPCat Cassette
6
10
» Last
~ BIOACTIVITY
-------
Identifiers to Support Searches
t% J\ United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
I M »Agency
DETAILS
EXECUTI VE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
~ ADME
~ EXPOSURE
~ BIOACTIVITY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
> LITERATURE
LINKS
COMMENTS
Bisphenol A
80-05-7 I DTXSID7020182
Searched by DSSTox Substance Id.
25 v
Synonym
Bisphenol A
Search query
Quality
Valid
4,4'-(Propane-2,2-diyl)diphenol
Phenol, 4,4'-(1-methylethylidene)bis-
80-05-71
BPA
Valid
Valid
Valid
Valid
4.4'-Propane-2,2-diyldiphenol
Phenol, 4,4'-(1-methylethylidene)bis-
4-06-00-06717
(4,4'-Dihydroxydipnenyl)dimethylmethane
2,2-Bis(4'-tiydroxyphenyl) propane
2t2'-Bis(4-hydroxyphenyl)propane
2,2-BIS-(4-HYDROXY-PHENYL)-PROPANE
Valid
Valid
Beilstein
Good
Good
Good
Good
2,2-Bis(4-hydroxyphenyl)propar>e
Good
2,2-Bis(p-hydroxyphenyl)propane
2,2-Di(4-Hydroxyphenyl) Propane
Good
Good
-------
Chemicals Discussed Today
• During talks today we heard about these chemicals. All are on the dashboard.
• 2,4-dihydroxybenzophenone, 131-56-6 (Mark)
• 50-00-0, 6898-97-1, 17804-35-2, 1582-09-8, 789-02-6, 50-06-6, 57-30-7,131-55-5
(Shannon)
• Argatroban, Lepirudin (Thomas)
• Arsenic trioxide, chlorpyrifos, cadmium, phorate, butylate, methyl bromide, Diazinon,
Fonofos, Atrazine, Dichlorvos, Phorate, Parathion, 2-butenal, pyruvaldehyde, nicotine,
formaldehyde, acetaldehyde, acetone, propionaldehyde (Carolyn)
-------
"MODULES"
-------
Literature Searching
Benomyl
17804-35-2 | DTXSID5023900
Searched by Approved Name.
11) Select PubMed starting point query then 2) click on Retrieve. © |
Metabolism/PK/PD ^
Retrieve Articles
Select a Query Term
Hazard
Fate and Transport
Metabolism/PK/PD
Chemical Properties
Exposure
Mixtures
Male Reproduction
Androgen Disruption
Female Reproduction
GeneTox
Cancer
Clinical Trials
Embryo and embryonic development
Child (infant through adolescent)
Dust and Exposure
Food and Exposure
Water and Exposure
Algae
Disaster / Emergency
« 1
Abstract Sifter
Optionally, edit the query before retrieving.
("17804-35-2" OR "Benomyl") AND (metabolism OR metabolite OR tissue distribution OR pharmacokinetics OR
pharmacodynamics)
Real-time retrieval of data from PubMed (>29
million abstracts and growing)
Choose from set of pre-defined queries
Adjust and fine tune queries based on interests
-------
Literature
Searching
"Sifting" of results using
multiple terms
Frequency counting terms
Color highlighting of terms
Download list to Excel
Send list to PubMed for
downloading ref. file
Direct link via PubMed ID
1) Select PubMed starting point query then 2) click on Retrieve. Q
Metabolism/PK/PD v O
To find articles quickly, enter terms to sift abstracts. O
degradation benomyl J N,N'-dibutylurea
714 of 714 articles ioaded
Optionally, edit the query before retrieving.
("17804-35-2" OR "Benomyl") AND (metabolism OR metabolite OR tissue distribution OR pharmacokinetics OR
pharmacodynamics)
Download / Sent
v O
Download Sifter for Excel
LI
Total
PMID
Year
Title
Authors
Journal
Rev
~
1
11
2
14
17493661
2007
Formulation factors that can reduce the formation of the phytotoxic impurity. N,N'-. ..
Ho; Lin; Wang
Chemosphere
4
1
2
7
15356237
2004
Degradation of N,N'-dibutylurea (DBU) in soils treated with only DBU and DBU-for...
Lee; Sassman; Bischoff; Turco
Journal of environmental quality
Q
3
1
1
5
15865150
2005
Accelerated degradation of N, N'-dibutylurea (DBU) upon repeated application.
Bischoff; Lee; Turco
Biodegradation
~
1
1
1
3
8854971
1996
Spontaneous N,N'-dibutylurea (DBU) formation in Benlate DF formulation under el. .
Tang; Song
Archives of environmental contamination and toxico..
~
0
1
0
1
31412509
2019
Arbuscular mycorrhizal fungi alleviate phosphorus limitation by reducing plant N:P ...
Mei; Yang; Zhang; Zhang, Guo
The Science of the total environment
~
0
1
0
1
31190279
2019
Two herbicides, two fungicides and spore-associated bacteria affect Funneliformis...
de Novais: Giovannetti; de Faria; Sbrana
Mycorrhiza
~
0
1
0
1
31146360
2019
Novel Peptide-Based Inhibitors for Microtubule Polymerization in Phytophthora ca...
Lee; Kim; Hoffmeister Yoon; Kim
International journal of molecular sciences
B
0
6
0
31112093
2019
Molecularly imprinted polymers for the detection of benomyl residues in water and..
Guzzella; Casatta; Dahchour; Baggiani; Pozzoni
Journal of environmental science and health. Pari.
O
0
1
0
1
30744902
2019
Benzimidazole- and Qol-resistance in Corynespora cassiicola populations from gr...
Duan; Xin; Lu; Li; Li; Wu: Wang; Zhou
Pesticide biochemistry and physiology
G
0
1
0
1
30673418
2019
Variation in Fungicide Sensitivity Among Rhizoctonia Isolates Recovered from Pot. .
Muzhinji; WoodhaB; Truter van der Waals
Plant disease
~
0
1
0
1
30087309
2018
Synthesis and Spectrum of Biological Activities of Novel N-arylcinnamamides
Pospisilova; Kos; Michnova; Kapustikova; Strharsk.
International journal of molecular sciences
O
0
1
0
1
29984740
2018
Occupational Exposure Limits for ethylidene norbomene, ethyleneimine. benomyl,
Araki; Azuma; Endo; Endo; Fukushima; Hara; Hori;...
Journal of occupational health
o
0
1
0
1
29933012
2018
Bioassay-guided isolation of active substances from Semen Torreyae identifies tw...
Liu; Veryser Lu; Wenseleers: De Borggraeve; Jian
Journal of ethnopharmacoiogy
~
0
1
0
1
29908479
2018
Incident thyroid disease in female spouses of private pesticide applicators.
Shrestha; Parks; Goldner; Kamel; Umbach; Ward; L...
Environment international
o
0
0
0
0
29804677
2018
Purification of kinetochores from the budding yeast Saccharomyces cerevisiae
Gupta; Evans; Koch; Littleton; Biggins
Methods in cell biology
Degradation of N,N'-dibutylurea (DBU) in soils treated with only DBU and DBU-fortified benlate fungicides.
N, N'-dibutylurea (DBU) is a breakdown product of benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazoie carbamate], the active ingredient in Benlate fungicides, and has been proposed to cause crop damage after the use of Benlate 50 DF fungicide (DuPont, Wilmington. DE). Our research
focused on DBU persistence after application into soil. We assessed DBU persistence on direct application of DBU (carbonyl-(l4)C) at too concentrations (0 OS and 0 8 microg DBU kg(-1)) to seven soils and two potting mixes in soil microcosms incubated at various combinations of soil water
potential (-0.03 or -0.1 MPa) and temperature (23.33, 44 degrees C). For two soils at a subset of treatment variables we assessed DBU persistence in the presence of Benlate DF and SP fungicide formulations Parent compounds, metabolites, and (14)CO(2) were tracked using
chromatographic analysis with radioassay and UV detection, liquid scintillation counting, and post-extraction oxidation of the soil. DBU degradation was primarily microbial and for most soil-treatment combinations, half-lives were less than 2 wk. DBU degradation was retarded at the lower soil
water potential and enhanced at 33 degrees C. In the presence of the formulation, DBU degradation was slower for one soil type. The longest half-life observed in any case was less than 7 wk; therefore, long-term persistence of DBU applied to soils through a Benlate application is very
unlikely.
-------
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
ADME
~
EXPOSURE
~
BiOACTIVTTY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
SYNONYMS
~
Literature
UNKS
COMMENTS
Generalized Read-Across (GenRA)
2,4-Dihydroxybenzophenone
131 -56-6 I DTXSID8022406
Searched by DSSTox Substance Id.
Step Four: Filter by Endpoint or Analogs
Neighbors by: Cherri: Morgan Fgrprts * Fitter by: inv™0 data
Summary Data Gap Analysis
Group: TcsxRef v
By; Tox Fingerprint v
Generate Data Matrix
fffiifif //''# //•• //
k£- -
Gaiic acid
jcA'
2-8rutno-4-hydr...
' of Analogs [l0 |
~9r°
2.4 BhydnwySie...
/ \
Xl - 06
\
2,4-Dihydroxybenzopbe..
2-Hydroxy-4-mechox-ybe ..
Benzopnenone
2-Chloroacetopherone 20
Pheno) 3
tert-Sutyi perbenzoate 10
& # t
# H #*
20 0
4 ^13 35
2 JQjd 22
14S
Sodium salicylate 6 0 9 57
Resorcino!
2-Bromo-4-hy draxyacet..
o [4U ^3
2' 232| US'
3c*i0
pefbe...
Gallic acid 3 0
Methyl salicylate 6 33 ¦
Sodiun salcvtae
GenRA v
CHRAtxiominaI Cavity
CHR.Ac{ena!_Glaod
CHR:Artery_(GeneralJ
^tarte i?® •
CHRBijeduct
CHR: Blood
CHR Blood vessel
CHREodyJteight
CHR Bone
CHFbBoneMarraw
CHRBrajn
CHR: Bronchus
I ¦
¦ ¦
¦ ¦
¦ ¦
^ ¦ ¦
Min+: G v
1.00© 0.61 y
Min-: 0 v
0.42 V 0.28
-------
GenRA in practice
Analogue identification: based
on Morgan fingerprints and
selecting 10 default analogues
- step by step
Neighbors by; Chem: Morgan Fgrprts v Filler by: invivo data
o
' L I
Methy saliey ate
y
Or
Gal ic acid
2 4-Dihyd'o;tybe...
-•
2-Hydrc«y-4-me...
Seizaoherore
2-Ch oroaoetop
Pbero
JL.
2-Ekoaw-4-hydr...
# of Analogs 10
XX
Resorci -ic
-.ert-Buty pertje..
Sod jm salicylate
-------
GenRA in practice - step by step
Data matrix view of source analogues relative to target chemical
Run Read-Across
GenRA v
Min+: 0 v
CHR:A&doninal Cavity
CHR:Adrenal Gland
CHR:Artery (General
CHR: Auditory Startle Re...
CHR:Bile dud
CHR:BIoq_c
CHR: Blood vessei
C H R: Body Weighl
CHR.Bone
1.00®
2,4-Dihydrcxyb .
0.61 V
Min-: 0 v
0.42 -/ 0.28 •/
Filter:
0.2SV
0.25 V 0.23 -/
Similarity WeightQ
0.23 •/ 0.22 V 0.22 V
Download: Filetype v
0.21 •/
O
W5 o^oo-l
-O - 06 jCX x$r 1^5
2-Kydroxy-4-rr . Benzopherwne 2-Ghtoroacetop .. Phenol tert-Butyi perbe .. Sodium salicylate Rescrc:nol 2-6romo-4-hyd... Gallic acid Methyl salicylate
-------
GenRA in practice - step by step
• Updated Data matrix view with GenRA predictions for target chemical
Run Head-Across
GenRA v
Min+: C
1.00©
0.61 V
Mill-: 0 v Filter:
0.42 -J 0.28 V 0.26 ¦/
Similarity Weights, i Download: Filetype v
0.25 •/ 0.23 -/ 0.23 •/ 0.22 -J 0.22 V 0.21 ¦/
xyo cfo -O >^0 - 06 JX J0r° x£- cS5
2.4-DihydroxyP... 2-tfydroxy-4-rri . Benzcphenone 2-Chtoroaoetop .. Phenol tert-Butyl perbe . Sodtum salicylate Resorcinol 2-6romo-4-hyd... Gallic acid Methyl salicylate
CHR:Abdominal Cavity
CHR:Adrenal Gland
CHR:Artery (General)
CHR:Audiiory Startle Re...
CHR:Bile duct
CHR:BJood
CHR:Blood vessel
CHRjBody Weight
CHR:Bone
• Predictions are binary (yes/no) for toxicity effects
• Predictions summarized on study level basis. Red: ' positive" and Blue:
"negative".
-------
Related Publications
Chemical
Research in
Toxicology
$ OK* TMK Ctiem Res. Taxicot. 2017.30. 2046-2059
pubsjcs.org/crt
Predicting Organ Toxicity Using in Vitro Bioactivity Data and
Chemical Structure
Jie Liu. ; Grace Patlewkz, Antony J. Williams, Russell S. Thomas, and Iniran Shah*
'National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency,
Research Triangle Park, Durham, North Carolina 27711, United States
^Department of Information Science, University of Arkansas at Little Rock, Arkansas 72204, United States
?Oak Ridge Institute for Science Education, National Center for Computational Toxicology, Office of Research and Development,
U.S. Environmental Protection Agency, Research Triangle Park, Durham, North Carolina 27711, United States
ELSEVIER
Computational Toxicology
Available online 23 July 2018
In Press, Corrected Proof©
Extending the Generalised Read-Across approach
(GenRA): A systematic analysis of the impact of
physicochemical property information on read-across
performance
George Helman a- b, Imran Shah b, Grace Pattewicz 'As
Regulatory Toxicology and Pharmacology
Volume 79, August 2016, Pages 12-24
IS
ELSEVIER
IlrtHtlllKll •mil
'=?-
Systematically evaluating read-across prediction and
performance using a local validity approach
characterized by chemical structure and bioactivity
information
Imran Shah 3 A a, Jie Liu b'c Richard S. Judson a, Russell s. Thomas a, Grace Patlewicz a
ELSEVIER
Contents lists available at ScienceDireet
Computational Toxicology
journal homepage: www.elsevier.com
Journal
Cover
Image
Navigating through the minefield of read-across frameworks: A commentary
perspective
Grace Patlewicza-", Mark T.D. Croninb, George Helman11*c, Jason C. Lambertd, Lucina E. Lizarragad, Imran Shah"
1 National Center for Computational Toxicology (NCCT). Office of Research and Development, US Environmental Protection Agency (US EPA), 109 TTV Alexander Dr. Research Triangle Park
(R TP), NC 27711. USA
b School of Pharmacy and BSamokadar Sciences, Liverpool John Moores University, Byront Street Liverpool L3 3AF, UK
c Oak Rids'- Institute for Science and Education (OR1SE), 1299 Bethel Valley Road, Oak Ridge. TN 37830, USA
d National Center for Evaluation Assesstnetu (NCEA), US Environmental Protection Agency (US EPA). 26 Wat Martin Luther King Or. Cincinnati, oH 45268, USA
-------
CHEMICAL LISTS AND
CATEGORIES
-------
EPAHFR: Hydraulic Fracturing
Home Advanced Search Batch Search lists v Predictions Downloads
Lists of Chemicals
Li =t of Assays
b
WATER|EPA; Chemicals associated with hydraulic fracturing
U, Search EPAHFR Chemicals
~ Identifier substring search
~B
AI k>1 benzeries u I forate linear
DTXSID DTXS;D3020C41
PubChem: 0
CPOAT: SB
-O
Anethole
DTXSID DTXS! D4020086
PubChem: 59
CPOAT: 33
Cf
nIh,
Ammonium chloride
DTXSI D: DTXSI D002007E
PubChem: 82
CPDAT: 260
h'^Q>
Aniline
DTXSID: DTXSI D3020090
PubChem: 234
CPDAT: 80
V
V
NH, Mi,
Diammonium citrate
DTXSID: DTXSID5020079
PubChem: 19
CPDAT: 18
Benzidine
DTXSID: DTXSID2020137
PubChem: 112
CPDAT: 15
Ammonium hydroxide
DTXSID: DTXSID4020080
PubChem: 83
CPDAT: 857
C
r
Benzo[a)pyrene
DTXSID: DTXSID2020139
PubChem: 161
CPDAT: 81
-------
PFAS lists of Chemicals
Select List
i Download
Columns
PFAS
Ci Copy Filtered Lists URL
List Acronym List Name "
Last Updated *
Number of Chemicals *
List Description *
EPAPFAS75S1
PFAS|EPA: List of 75 Test
Samples (Set 1)
2018-06-29
74
PFAS list corresponds to 75 samples (Set 1) submitted for initial testing screens
conducted by EPA researchers in collaboration with researchers at the National
Toxicology Program,
EPAPFAS75S2
PFAS|EPA: List of 75 Test
Samples {Set 2)
2019-02-21
75
PFAS list corresponds to a second set of 75 samples (Set 2} submitted for testing
screens conducted by EPA researchers in collaboration with researchers at the
National Toxicology Program.
EPAPFASCAT
PFAS|EPA Structure-
based Categories
2018-06-29
64
List of registered DSSTox "category substances" representing PFAS categories
created using ChemAxons Markush structure-based query representations.
EPAPFASINSOL
PFAS|EPA: Chemical
Inventory Insoluble in
DMSO
2018-06-29
43
PFAS chemicals included in EPA's expanded ToxCast chemical inventory found to
be insoluble in DMSO above 5mM.
EPAPFASINV
PFAS|EPA: ToxCast
Chemical Inventory
2018-06-29 430
PFAS chemicals included in EPA's expanded ToxCast chemical inventory and
available for testing.
EPAPFASRL
PFAS|EPA: Cross-Agency
Research List
2017-11-16
199
EPAPFASRL is a manually curated listing of mainly straight-chain and branched
PFAS (Per- Si Poly-fluorinated alkyl substances) compiled from various internal,
literature and public sources by EPA researchers and program office
representatives,
PFASKEMI
PFAS: List from the
Swedish Chemicals
Agency (KEMI) Report
2017-02-09 2416
Perfluorinateti substances from a Swedish Chemicals Agency (KEMI) Report on
the occurrence and use of highly fluorinated substances.
PFAS MASTER
PFAS Master List of PFAS
Substances
2018-07-26
5061
PFASMASTER is a consolidated list of PFAS substances spanning and bounded by
the below lists of current interest to researchers and regulators worldwide.
PFASOECD
PFAS: Listed in OECD
Global Database
2018-05-16
4729
OECD released a New Comprehensive Global Database of Per- and
PolyfluoroaHkyl Substances, (PFASs) listing more than 4700 new PFAS
PFASTRIER
PFAS Community-
Compiled List (Trier et al,r
2015)
2017-07-16
597
PFASTRIER community-compiled public listing of PFAS (Trier et al, 2015)
-------
List of Assays
Assay List
A. Download ~ 10 v v Search query (b Copy page URL
ACEA Biosciences
Apred'ca
Assay Component Endpoint Name "
Details
Active Hits '
Description
Gene Symbols
ATG_Ahr_CIS_up
1
573 / 3807
Data from the assay component ATG_.#
endpoint, ATG_Ahr_CIS_up,. was analyz
negative control and baseline of activi
gain-of-signal activity can be used to i
they relate to the gene AhR, Furtberm
readout, because this assay has produ
gene function. To generalize the intern
annotated to the "dna binding ' intend
protein".
Bioseek
Movascreen
Tox21/NCGC
Ceetox/OpArs
CellzDirect
assay endpoint. This assay
ction relative to DMSO as the
reporter, measures of mRNA for
s at the transcription factor-level as
be referred to as a primary
; where this orse serves a reporter
targets., this assay endpoint is
;ubfamily is "basic helix-loop-helix
AHR
ATG_AP_1_CIS_up
K
658 / 3807
Data from the assay component ATG_;
endpoint, ATG_AP_1_CIS_up, was analy
negative control and baseline of activi1
gain-of-signal activity can be used to i
they relate to the gene FOS and JUN, f
readout, because this assay has produi
gene function, To generalize the intern
annotated to the "dna binding'' intend
NGCT's Lab
Tanguay Lab
NHEERL's Hunter Lab
NHEERL Stoker & Laws Lab
NHEERL Med Lab
ea Target ramny, wnere me
atjay endpoint. This assay
ection relative to DMSO as the
reporter, measures of mRNA for
s at the transcription factor-level as
oint can be referred to as a primary
; where this one serves a reporter
targets, this assay endpoint is
subfamily is "basic leucine zipper".
FOSJUN
ATG_AP_2_C IS_u p
fe
47 / 3807
Data from the assay component ATG_AP_2_CiS was analyzed into 1 assay endpoint. This assay
endpoint, ATG_AP_2_CIS_up, was analyzed in the positive fitting direction relative to DMSO as the
negative control and baseline of activity. Using a type of inducible reporter, measures of mRNA for
TFAP2A TFAP2B TFAP2D
-------
From Assay to Chemicals...
Assay Endpoint Name: ACEA_ER_80hr
Assay Details
Assay Endpoint Name: ACEA_ER_3Chr li
Assay Source Description: ACEA Biosciences, Inc. (ACEA) is a privately owned biotechnology company that developed a real-time, label-free, cell-based assay system based on a microelectronic readout called xCELLigence.
425 of 3031 chemicals visible
V
tf
f CASRN X J TOXCAST X J PubMed X
~
:k>i
5-*
NH
b
Acetohexamide
CASRN: 968-81-0
TOXCAST: 4/376
PubMed: 235
o
HtN
H,C
HCI
2-Methoxyaniline hydrochloride
CASRN: 134-29-2
TOXCAST: 17/385
PubMed: 46
-o
HO
Sodium L-ascorbate
CASRN: 134-03-2
TOXCAST: 20/662
PubMed: 38756
$
N=n:
:N
Na
Sodium azide
CASRN: 26628-22-8
TOXCAST: 26/644
PubMed: 1866
-o
-------
Other Searches
Chemicals
Product/Use Categories
Assay/Gene
-------
Product/Use Categories
w
Chemicals
Product/Use Categories
Assay/Gene
Ct lubricant
CPDat PRODUCT category: auto products auto lubricant
engine lubricants and belt dressings, not including motor oils (spray or aerosol formulation specified)
CPDat PRODUCT category: auto products auto lubricant
engine lubricants and belt dressings, not inctuding motor oils
CPDat PRODUCT category: home maintenance lubricant
household maintenance lubricants (spray or aerosol formulation specified)
CPDat PRODUCT category: home maintenance lubricant
household maintenance lubricants
CPDat PRODUCT category: personal care clipper lubricant/cleaner
cleaning and lubricating products for hair clippers
CPCat USE category: lubricant
generic lubricants, lubricants for engines, brake fluids, oils, etc (does not include personal care lubricants)
-------
Lubricant
Searched by Product & Use Categories
Results for CPCat Use Category: CPCat term: Lubricant
173fl chemicals
nmma
| DTXSID * J PubdWKn * J CPDAT *
~
mo
Water
DTXSID: DTXS; D6026296
PubChem: 637
CPDAT: 8270
O
Glycerol
DTXSID: DTXS) D902Q663
PubChem: 13028
CPDAT: 4249
O
HO
XH,
Ethanol
DTXSID: DTX5ID9D2Q5S4
PubChem: 1591
CPDAT: 3635
O
OH
HO.
CH i
1,2-Pnopylene glycol
DTXSJ D: DTXSID0021206
PubChem: 472
CPDAT: 3193
O
HO-
OH
OH
OH
Citric acid
DTXSID: DTXS1D3020332
PubChem: 1516
CPDAT: 2560
O
Tl4+ O2'
Titanium dioxide
DTXSID: DTXSID30213
PubChem: 103
CPDAT: 2519
O
2-Phenoxyethanc
-------
Other Searches
Chemicals
Product/Use Categories
Assay/Gene
Chemical-Biology
-------
Assay/Gene Search
Chemicals Product/Use Categories
Assay/Gene
Q esr|
ASSAY: TOX21_ESRE_BlA_ch1
Data from the assay component T0X21_ESRE_3LA_ch1 was analyzed into 7 a..
ASSAY: TOX21 _ESRE_BLA_ch 2
Data from the assay component TOX21_ESRE_BLA_ch2 was analyzed into 7 a.,
ASSAY: TOX21 _ESRE_BLA_rati o
Date from the assay component TOX21_E5RE_BLA_ratio tvos analyzed into 7.„
ASSAY: TOX21 _ESRE_BLA_vi abi I ity
TOX21_ESRE_BLA_viatsISy used a type of growth reporter where loss-of-.,.
GENE: ESR1
estrogen receptor J
GENE: esrl.L
estrogen receptor 1 i homeolog
GENE: ESR2
estrogen receptor 2 (ER beta)
GENE: esrZL
estrogen receptor 2 L homeolog
-------
Assay/Gene Search
Assay List
± Download ~ 10 v Filter by vendor v ESR1 Ci Copy Filtered Lists URL
Assay Component Endpoint Name "
Details
Active Hits
* Description
Gene Symbols
ACEA_ER_80hr
ft
425 / 3031
Data from the assay component ACEA_ER_80hr was analyzed into 2 assay endpoints. This assay endpoint,
ACEA_ER_flOhr_Positive, was analyzed in the positive fitting direction relative to DMSO as the negative
control and baseline of activity. Using a type of growth reporter, measures of the cells for gain-of-signal
activity can be used to understand the signaling at the pathway-level as they relate to the gene ESR1,
Furthermore, this assay endpoint can be referred to as a primary readout because this assay has produced
multiple assay endpoints where this one serves a signaling function. To generalize the intended target to
other relatable targets, this assay endpoint is annotated to the 'nuclear receptor" intended target family,
where the subfamily is "steroidal",
ESR1
ATG_ERE_CIS_up
ft
992 / 3807
Data from the assay component ATG_ERE_CIS was analyzed into 1 assay endpoint, This assay endpoint,
ATG_ERE_CIS_up, was analyzed in the positive fitting direction relative to DMSO as the negative control and
baseline of activity. Using a type of inducible reporter, measures of mRNA for gain-of-signal activity can be
used to understand the reporter gene at the transcription factor-level as they relate to the gene ESR1.
Furthermore, this assay endpoint can be referred to as a primary readout, because this assay has produced
multiple assay endpoints where this one serves a reporter gene function, To generalize the intended target
to other relatable targets, this assay endpoint is annotated to the "nuclear receptor" intended target family,
where the subfamily is "steroidal",
ESR1
< < < 2 3 4 > > >
Showing 1 to 10 of 32 records
-------
Mass/Formula
Searching
-------
Advanced Searches
Mass Search
Mass Search ©
± Mir/Max
Adduct
All Adducts
Neutral v
Choose adduct from dropdown
191.131
Da ± 5
Da
Search Q.
-------
Advanced Searches
Mass Search
Search Results
Searched by Mass: 191.131 +/- 5,0 ppm.
329 of 329 chemicals visible
~
| DTXSID * J CASRN * J TOXCAST 11 J Mais Dttt tt
1 MuKkzvnportffit Chemicals *
~
o
o
-Q
Q
O
O
H.C H»C
//
D£ET
DTXS! D: DTXSi D2D21995
CAS FIN: 134-62-3
TOXCAST: 12,763
Mass Diff: 0.000014
-O
Phendimesrazine
DTXSI D: DTXSi D1023447
CASRN: 634-03-7
TOXCAST: -
Mass Diff: 0.000014
-O
N-Buryiacetanilide
~TXS! D: DTXS! D2042197
CASRN: 91-49-6
TOXCAST: -
Mass Diff: 0.OD0014
-O
Berczaldehyde, 4-(diethylaminoj-2-m€th...
DTXSiD: DTXSIQ4059041
CASRN: 92-14-S
TOXCAST: -
\fess Diff: Q.G00014
o
A,
CMj
Acetanilide. 2'G'-diethyl-
DTXSJ D: DTXSI D90163148
CASRN: 16565-89-7
TOXCAST: -
Mass Diff: O.OG0O14
X)
o
I
CH,
Azstidire. 1,3-di methyl -3 -(m-roethoxyp...
DTXSI D: DTXSID40173 560
CASRN: 19B32-26-9
TOXCAST: -
Mass Diff. 0.000014
O
Benzamid-e, N-pent/I -
DTXSi Dc DTXS D20174196
CASRN: 20308-43-4
TOXCAST: -
CHj CM,
p-t-3utylacetanilide
DTXSi D: DTXS DSD174238
CASRN: 20330-45-4
TOXCAST: -
n;ff
N. N- Disthytphenyi acetam ids
DTXSi D: DTXS: D00179048
CASRN: 2431-96-1
TOXCAST:-
«| dare r
3-(0imethylammo}-2-methyl prcpiopfren..
DTXSi D: DTXSi D60180796
CASRN: 26171-50-5
TOXCAST: -
HiC
'V
°wNH^
But/ramide. 2-ethyl-2-phervy1-
DTXSID: DTXS! D60184653
CASRN: 30568-39-9
TOXCAST: -
1 -Heptanone, 1 -(4-pyridyl)-
DTXSl D: DTXS; D4018659d
CASRN: 32S41-30-3
TOXCAST: -
mourn
-------
Mass Spec Focused Applications
Analytical and Bioanalytical Chemistry (2019) 411:853-866
https://doi.Org/10.1007/500 216 -018-143 5-6
RESEARCH PAPER
I CreesMark
s
EPA's non-targeted analysis collaborative trial (ENTACT): genesis,
design, and initial findings
Elin M. Ulrich1 • Jon R.Sobus1 • Christopher M. Grulke2 ¦ Ann M. Richard2* Seth R. Newton1 ¦ Mark J. Strynar1 •
Kamel Mansouri3,4 • Antony J. Williams2
Analytical and Bioa nalytical Chemistry (2019) 411:835-851
https://dd.Org/10.1007/sOO 216 -018 -1526-4
RESEARCH PAPER
<8>
CrossMark
Using prepared mixtures of ToxCast chemicals to evaluate non-targeted
analysis (NTA) method performance
Jon R.Sobus1 C • Jarod N. Grossman2 3 * AlexChao2 • Randolph Singh4 ¦ Antony J. Williams5 ¦ Christopher M. Grulkes
Ann M. RichardJ • Seth R. Newton 1 • Andrew D. McEachran4 * Elin M. Ulrich1
-------
Mass Spec Focused Applications
Journal of Exposure Science & Environmental Epidemiology (2018) 28:411-426
https://doi.org/10.! 038/ s41370-017-0012-y
REVIEW ARTICLE
Integrating tools for non-targeted analysis research and chemical
safety evaluations at the US EPA
Jon R. Sobus1 - John F. Wambaugh2 ¦ Kristin K. Isaacs1 • Antony J. Williams2 ¦ Andrew D. McEachran3 *
Ann M. Richard2 * Christopher M. Grulke2 • Elin M. Ulrich1 ¦ Julia E. Rager3,4* Mark J. Strynar1 * Seth R. Newton1
Article
pubs.acs.org/est
© Cite This: Environ. Sci. Technol. 2018, 52, 3125-3135
Suspect Screening Analysis of Chemicals in Consumer Products
Kathcrine A. Phillips/ Alice Yau/ Kristin A Favela/ Kristin K. Isaacs," Andrew McEachran,'
Christopher Grulke," Ann M. Richard," Antony J. Williams," [on R. Sobus," Russell S. Thomas,"
and John F. Wambaugh*'" j
-------
Batch Searching
-------
Batch Searching
• Singleton searches are great but...
• ...we generally want data on LOTS of chemicals!
• Typical questions
• What are the structures for a set of chemical names? Set of CASRNs?
• Can I get chemical lists in Excel files? As a list of SMILES strings? Can I
get an SDF file?
• Can I include predicted properties in the download file? OPERA? TEST?
• Are "these chemicals" screened in Toxcast?
• I'm a mass spectrometrist and need masses and formulae for a list of
chemicals
-------
Chemicals Discussed Today
• During talks today we heard about....
• 2,4-dihydroxybenzophenone, 131-56-6 (Mark)
• 50-00-0, 6898-97-1, 17804-35-2, 1582-09-8, 789-02-6, 50-06-6, 57-30-7,131-55-5
(Shannon)
• Argatroban, Lepirudin (Thomas)
• Arsenic trioxide, chlorpyrifos, cadmium, phorate, butylate, methyl bromide, Diazinon,
Fonofos, Atrazine, Dichlorvos, Phorate, Parathion, 2-butenal, pyruvaldehyde, nicotine,
formaldehyde, acetaldehyde, acetone, propionaldehyde (Carolyn)
• What information can we find and how fast???
-------
Batch Search Identifiers
2j4-dihydroxybenzophenone
50-00-0
6898-97-1
17804-35-2
1582-09-8
789-02-6
50-06-6
57-30-7
131-55-5
Argatroban
Lepirudin
Arsenic trioxide
chlorpyrifos
cadmium
phorate
butylate
methyl bromide
Diazinon
Fonofos
Atrazine
Dichlorvos
Phorate
Parathion
2-butenal
pyruvaldehyde
nicotine
formaldehyde
acetaldehyde
acetone
propionaldehyde
Step 1
Step 2
Batch Search©
Step 3
Step 4
Step 5
Step Four: Select Data Output Format and Choose Data Fields to Download
Please enter one identifier per line
Select Input Type(s)
M Identifiers
Chemical Name ©
Isfi CASRN ©
~ I rich I Key©
0 DSSTox Substance ID ©
1 DSSTox Compound ID ©
i—I inChlKey Skeleton ©
MS-Ready Formulate) ©
U Exact Formula(e) ©
1 Monoisotopic Mass©
<9> Display All Chemicals
Select Output Format:
Excel
Customize Results
~ Select All
~ Select All in Lists
Chemical Identifiers
* DTXSID©
' chemical Name ©
Download Chemical Data
Excel
Download
Enter Identifiers to Search (searches should be limited to <5000 identifiers)
2,4-d i hy d roxy benzo p h e no ne
50-00-0
6898-97-1
17804-35-2
1582-09-8
789-02-6
50-06-6
57-30-7
131-55-5
Argatroban
I
1 | INPUT FOUND_BY | DTXSID
2 2.4-dihydroxyber Approved Name
50-00-0
6898-97-1
17804-35-2
1582-09-8
789-02-6
50-06-6
57-30-7
131-55-5
Argatroban
Lepirudin
CAS-RN
CAS-RN
CAS-RN
CAS-RN
CAS-RN
CAS-RN
CAS-RN
CAS-RN
Approved Name
Approved Name
Arsenic trioxide Synonym
chlorpyrifos Approved Name
cadmium Approved Name
phorate Approved Name
17 butylate Approved Name
18 methyl bromide Approved Name
DTXSID8022406
DTXSID7020637
DTXSID3040770
DTXSID5023900
DTXSID4021395
DTXSID6022345
DTXSID5021122
DTXSID0021123
DTXSID5041306
DTXSID7046467
DTXSID50160461
DTXSID0074007
DTXSID4020458
DTXSID1023940
DTXSID4032459
DTXSID7023936
DTXSID8020832
1preferred_name
2,4-Di hyd roxy be nzoph e n one
Formaldehyde
(Z.E)-Diethylstilbestrol
Benomyl
Trifluralin
o,p"-DDT
Phenobarbital
Phenobarbital sodium
2.2\4.4'-Tetrahydroxybenzopherf
Argatroban
Lepirudin
Arsenite
Chlorpyrifos
Cadmium
Phorate
Butylate
Methyl bromide
Quantities C
-------
Include Data of Interest - then dive deeper
Chemical Identifiers
* DTXSID0
* Chemical Name a
~ DTXCID ©
' CAS-RN 0
~ Inch I Key 0
~ IUPAC Name©
Structures
Mol File O
L J SMILES ©
InChl String ©
MS-Ready SMILES 0
L QSAR-Ready SMILES O
Intrinsic And Predicted Properties
1 Molecular Formula 0
1 Average Mass 0
1 Monoisotopic Mass 0
LJ TEST Model Predictions 0
' OPEFIA Model Predictions 0
Metadata
~ Curation Level Details 0
^ NHANES/Predicted Exposure 0
LJ Data Sources 0
' Include ToxVal Data Availability 0
' Assay Hit Count 0
® Number of PubMed Articles 0
D PubChem Data Sources 0
LJ CPDat Product Occurrence Count I
' IRISJ
f DTXSID PREFERRED N/
CASRN
EXPOCAS1
EXPOCAS1
NHANES
TOXVAL DATA
TOXCAST PERCENT
TOXCAST NUMBER
NUMBER OF PUBMED ARTICL
IRIS LINJ^
DTXSIDBO; 2.4-Dihydroxyber
131-56-6
¦5.786-07
Y
-
Y
r14.02
92/656
25
c
DTXSID70; Formaldehyde
50-00-0
r1.32e-06
Y
-
Y
-
-
19234
Y t
DTXSID30* (Z.E)-Diethylstilb
6898-97-1
r1.65e-07
Y
-
-
25.1
62/247
8326
DTXSID50; Benomyl
17804-35-i
r1.11e-07
Y
-
Y
"l 1.23
96/855
476
y c
DTXSID40. T rifluralin
1582-09-8
r1.57e-06
Y
-
Y
H 0.44
87/833
259
Y \
DTXSID60I o,p"-DDT
789-02-6
r1.16e-07
Y
-
Y
"52.87
239/727
125
DTXSID50; Phenobarbital
50-06-6
2.57e-08
Y
-
Y
r1.7
4/235
18244
{f
DTXSIDOOIPhenobarbital so
57-30-7
r1.66e-07
Y
-
Y
2.15
15/698
17600
-
DTXSID50^2,2\4.4'-Tetrahyd
131-55-5
2.31e-07
Y
-
Y
r18.31
139/759
25
Ji
DTXSID70' Argatroban
74863-84-E2.3e-07
Y
-
-
2.43
1/235
868
DTXSID50' Lepirudin
138068-37
-
-
-
-
-
-
354
w
DTXSIDOO" Arsenite
15502-74-f
-
-
-
-
-
4003
1
DTXSID40; Chlorpyrifos
2921-88-2
2.3e-08
Y
Y
Y
r18.73
124/662
2387
y A
DTXSID10; Cadmium
7440-43-9
-
-
-
Y
-
-
29395
Y ^
DTXSID40; Phorate
298-02-2
r1.23e-08
Y
Y
Y
"5.26
36/685
113
DTXSID70; Butylate
200841-5
"&.43e-08
Y
-
Y
*1.14
9/790
17
Y |
DTXSID30; Methyl bromide
74-83-9
-
-
-
Y
-
-
500
Y '
DTXSID90; Diazinon
33341-5
r1.02e-07
Y
Y
Y
"&.9
59/855
890
-
DTXSID20;Fonofos
944-22-9
7.86e-08
Y
-
Y
2.13
5/235
41
y J
DTXSID90I Atrazirie
1912-24-9
2.56e-08
Y
Y
Y
^.62
40/866
14356
Y #
DTXSID50,'Dichlorvos
62-73-7
r1.37e-08
Y
Y
Y
7.13
58/814
1106
y ^
DTXSID40; Phorate
298-02-2
r1.23e-08
Y
Y
Y
"5.26
36/685
113
T
DTXSID70; Parathion
56-38-2
2.36e-08
Y
Y
Y
r13.05
116/889
2213
y j
(DTXSID30; Crotonaldehyde
4170-30-3
2.64e-07
Y
-
Y
2.0
0/235
172
/
(DTXSIDOO; Methyl glyoxal
78-98-8
-
-
-
Y
"Q 72
2/277
1553
/
DTXSID10; Nicotine
54-11-5
7.08e-07
Y
-
Y
2.39
17/711
22837
i
DTXSID70; Formaldehyde
50-00-0
r1.32e-06
Y
-
Y
-
-
19234
y ^
DTXSID50; Acetaldehyde
75-07-0
2.57e-06
Y
-
Y
25.5
142/400
5568
y T
DTXSID80; Acetone
67-64-1
^.72e-05
Y
-
Y
2.43
1/235
7176
y J
t DTXSID20U^ropanal^^
123-38^
,^.7M5
Y .
Y -
Su _
0/235 r-
1219
Y
-------
Batch collection of data for a
set of pesticides
-------
Curated List of Pesticides
United States
Environmental Protection Home Advanced Search Batch Search Lists V Predictions Downloads
kAgency
Find list of interest
Select List
PESTICIDES|EPA: Pesticide Chemical Search Database
1 i Identifier substring search
List details
DescriptioraKhe entries in this list have been classified in the U.S. as pesticidat "active ingredients" (conventional, antimicrobial, or biopesticidal agents), and were sourced from the Pesticide Chemical Search database
(https://iaspub^arinv/aDex/Desticides/f?p=chemicalsearch:1) created by EPA's Office of Pesticide Programs. Chemical Search provides a single point of reference for easy access to information previously published in a variety of locations,
including various Ef^^eb pages and Regulations.gov. Chemical search contains the following: 1) More than 20,000 regulatory documents; 2) Links to over 800 dockets in Regulations.gov B) Links to pesticide tolerance (or maximum residue
levels) information; 4) Al^iety of web services providing easy access to other scientific and regulatory information on particular chemicals from other EPA programs and federal government sources.
Number of Chemicals; 401;
Select list and
send to batch
Send to Batch Search
CASRN X I DTXSID X I MonoMass X
Hide chemicals that are: v
-O
-o
-o
x^/
Y y
Jih cr
Lf*
1 -Acetyl-6-(1,1, l,2,3,3,3-heptafluoro-2-p...
CASRN: NOCAS_920532
DTXSID: DTXSID00920532
Mono.Mass: 468.114807
>-(2,6-Diethyl-4-methylphenyl)-8-hydro...
CASRN: NOCASJ920508
DTXSID: DTXSID10920508
Mono.Mass: 332.173607
5-({I(Methylamino)(nitroamino)methylen...
CASRN:
DTXSID:
Mono.Mass:
NOCAS_912338
DTXSID20912338
295.004511
Sodium 3,4,4-trifluoro-3-butene-1 -sulfo...
CASRN: NOCAS_912336
DTXSID: DTXSID00912336
Mono.Mass: 211.973094
-------
Send to batch and select....
Intrinsic And Predicted Properties
Molecular Formula e
Average Mass ©
Monoisotopic Mass ©
TEST Model Predictions ©
OPERA Model Predictions ©
Metadata
Curation Level Details©
NHANES/Predicted Exposure ©
Data Sources o
Include ToxVal Data Availability ©
Assay Hit Count ©
Number of PubMed Articles ©
PubChem Data Sources o
CPDat Product Occurrence Count ©
~ IRIS©
PPRTV ©
A few seconds to assemble
• ToxCast data - #actives/#assays and % active
• # articles in PubMed
• Links to IRIS or PPRTV reports
• TEST or OPERA predictions
• Exposure data: predictions and CPDat
A
B
C
D
E
F
G
H
I J
K
L
M
DTXSID
PREFERREDNAME
EXPOCAST
_MEC EXPOCASTNHANES
TOXVALDATA
TOXCAST % ACT TOXCAST
#PUBMED
PUBCHEM,
CPDAT_COUHRIS_LINK
PPRTVJJNK
DTXSID2021105
Pentachloronitrobenzener1.14e-07
Y
Y
Y
r11.8
99/839
69
96"
164
Y
-
DTXSID4022527
Propylparaben
1 4e-05
Y
Y
Y
r13.77
99/719
201
121
1476
-
DTXSID4024064
Dinex
r8.29e-08
Y
-
Y
r42.13
99/235
-
35
5
Y
DTXSID0032493
Triadimenol
r1 73e-08
Y
-
Y
"10.54
98/930
163
74
83
-
-
DTXSID4032667
Esfenvalerate
r1,7e-06
Y
-
Y
"11.45
98/856
483
45
198
-
-
DTXSID6020561
Endrin
r1,29e-07
Y
-
Y
r14.02
98/699
284
16
98
Y
Y
DTXSID6025355
Glutaraldehyde
r2.03e-05
Y
-
Y
*14.35
98/683
6515
139
1144
-
-
DTXSID8032417
Isofenphos
r1.87e-08
Y
-
Y
r16.28
98/602
30
42
60
-
DTXSID6032352
Chlorpyrifos-methyl
r1,07e-07
Y
Y
Y
"11.27
97/861
72
50
116
-
DTXSID8020620
Fenthion
r8.99e-08
Y
Y
Y
'l 1.56
97/839
354
100
99
-
DTXSID2020189
FD&C Blue No. 1
*0.000178
Y
-
Y
r13.72
97/707
174
49
672
-
DTXSID7044843
Erythrosin B
r6.3e-07
Y
-
-
"54.25
97/400
14843
51
7
-
DTXSID5041778
Chloropropylate
r1,05e-07
Y
-
Y
r40.93
97/237
-
36
12
-
DTXSID5023900
Benomyl
r1.11e-07
Y
-
Y
"11.23
96/855
476
91
105
Y
DTXSID9020247
Carbaryl
r5.61e-08
Y
Y
Y
"i 1.51
96/834
1135
117
245
Y
DTXSID8024109
Flutolanil
r1,63e-08
Y
Y
r11.4
95/833
6
59
80
]-
DTXSID1023998
Cypermethrin
r1,62e-06
Y
Y
Y
"10.78
94/872
1148
148
246
-
-
~TXSID2024242
Paclobutrazol
r9.19e-08
Y
-
Y
"11.11
94/846
139
-
40
Y
-
DTXSID1020807
2-Mercaptobenzothiazole 4.7e-05
Y
_
Y
"12.82
94/733
111
181
86
Y
-------
Real-Time Predictions
United States
Environmental Protection Home Advanced Search Batch Search Lists* Predictions Downloads
L Agency
Atrazine
Input structure
using sketcher
Edit chemical
Select endpoints
for prediction
J | 100» T | (A
f © & >>
o © o
A
Select properties to predict
® Toxico logical properties
® 96 hour fathead minnow LC50
kfi 48 hour D. magna LC50
® 48 hourT. piriformis IGC50
0 Oral rat LD50
® Bfoaccumulatior factor
9 Developmental toxicity
@ Ames mutagenicity
^ Estrogen Receptor RBA
^ Estrogen Receptor Binding
® Physical properties
81 Normal boiling point
0 Meiting point
9 Flash point
® Vapor pressure
9 Density
9 Surface tension
@ Thermal conductivity
0 Viscosity
bfi Water solubility
OOOOADOO o
I cmi I
49
-------
Real-Time Predictions with detailed calculation reports
¦
Environmental Protection Home Advanced Search Batch Search lists v Predictions Downloads
Provider: T.E.S.T.
i Download Summary
A II
Property Experimental Value
Consensus
Hierarchical clustering
Single model
Group contribution
Nearest neighbor
96 hour fathead minnow LC50
4.951 -logtO(molA)
3.425 mg/L
5,198 -LoglO(molA)
1,943 mg/L
5.257 -LoglO(moH)
1.693 mg/L
5.287 -Log10(mo|/L)
1.581 mg/L
4,064 -LoglOjmol/L)
26.452 mg/'L
4S hour D, magna LC50
4.430 -Lc
-------
Real-Time Predictions with detailed calculation reports
Predicted Vapor pressure at 25°C for C1C=1N=C(N=C(N1)NC(C)CCC(C1)C)NC(C)C from Consensus method
Prediction results
Endpoint
Expei'imetita] value
Predicted value
Vapor pressure at 25=C Log lOtromHs}
M'A
-6.B5
Vapor preiiure at 25°C onrUg
NA
1.42E-07
Individual Predictions
Method
Predicted value
L»glO(mmHg)
Hierarchical cjustaruiH
-6.47
Group contribution
-7.62
Nearast neighbor
-6.46
Predictions for the test chemical and for the most similar chemicals in the external test set
If the predicted value matches the experimental values for similar chemicals in the test set (and the similar chemicals were predicted well), one
Prediction results (collars defined in table below}
-iOr
-5 5
MAE
= 0.67
o
~
o
Chemicals
MAE*
Entire =et
0.47
Similarity coefficient > 0.5
0.67
xMaan absolute error in LoslGCmmHs)
IS -MO -JS -7 0 -CS -40 -SS -So
Fwp. Vapor iprr-ssurr at ?S*C I agl DfmmHg|>
CAS
Structure
Similarity"
Coefficient
Experimental value
LoglO
-------
Summary and Conclusion
%
%
cnerT1
j.
***
ERA'S CompTox
icalS Dashboard/
>oard ^
Chemistry Dashboard
f List...n }Q^cr Lists (User Interactions)
-------
Acknowledgements
EPA-RTP
• An enormous team
Center for Computational
Exposure, especially
• Multiple centers and
• Special Mentions:
• Dashboard: Jeff
• GenRA: Imron S
• Abstract Sifter:
• InvitroDB: Katie
Credit: the Research Triangle Foundation
-------
References
The CompTox Chemistry Dashboard: a community data resource for environmental
chemistry, J. Cheminformotics, 9, 61 (2017)
EPA's DSSTox database: History of development of a curated chemistry resource
supporting computational toxicology research, Comp. Tox. 12,100096 (2019)
OPERA models for predicting physicochemical properties and environmental fate
endpoints, J. Cheminformatics, 10,10 (2018)
Screening Chemicals for Estrogen Receptor Bioactivity Using a Computational Model,
Environ. Sci. Technol. 49, 8804-8814 (2015)
ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology, Chem. Res.
Toxicol. 29, 1225-51 (2016)
Development and Validation of a Computational Model for Androgen Receptor Activity,
Chem. Res. Toxicol. 30, 946-964 (2017)
CERAPP: Collaborative Estrogen Receptor Activity Prediction Project, Environ. Health
Perspect. 124,1023 (2016)
Abstract Sifter: a comprehensive front-end system to PubMed, F1000, 6, 2164 (2017)
-------
LIVE DEMO
IF TIME
55
------- |