United States
Environmental Protection
Agency
Perspectives on the Development, Evaluation,
and Application of in Silico Approaches for
Predicting Toxicity
GracePatlewicz
Center for Computational Toxicology and Exposure (CCTE),
US
The views expressed in this presentation are those of the author and
do not necessarily reflect the views or policies of the U.S. EPA
-------
Conflict of Interest Statement
• No conflict of interest declared.
• Disclaimer:
• The views expressed in this presentation are those of the authors
and do not necessarily reflect the views or policies of the U.S. EPA
-------
Outline
• Regulatory Drivers
• Computational (in silico)Toxicology [scope for today's talk]
• Integrated Approaches to Testing and Assessment (IATA) -
definitions and Adverse Outcome Pathway (AOP) informed
• Decision contexts and their impact on the approaches applied
• Risk-based prioritization
• Read-across approaches
- Generalised Read-across (GenRA)
• Summary remarks
• Acknowledgements
-------
Regulatory and Non-Regulatory drivers
• Societal demands for safer and sustainable chemical products are
stimulating changes in toxicity testing and assessment frameworks
• Chemical safety assessments are expected to be conducted faster
and with fewer animals, yet the number of chemicals that require
assessment is also rising with the number of different regulatory
programmes worldwide.
• In the EU, the use of alternatives to animal testing is promoted.
• Animal testing is prohibited in some sectors e.g. EU Cosmetics
regulation
• The European Registration, Evaluation, Authorisation and Restriction
of Chemicals (REACH) legislation lays out specific information
requirements, based on tonnage level triggers. However, the
regulation explicitly expresses the need to use non-testing
approaches to reduce the extent of experimental testing in animals.
-------
Regulatory and Non-Regulatory drivers
• REACH-like schemes also have been established in China, South
Korea, and Turkey.
• In the US, the new Frank Lautenberg Chemical Safety for the 21st
Century Act (LCSA) requires that a risk based prioritisation is
conducted for all substances in commerce, ~40,000, many of which
are lacking sufficient publicly available toxicity information.
• EPA Administrator signed memo 10/9/19 to "direct the agency to
aggressively reduce animal testing, including reducing mammal study
requests and funding 30% by 2025 and completely eliminating them by
2035"
• Risk based prioritisation is also an important aspect of regulatory
frameworks in Canada (the Domestics Substance List), Australia and
the EU.
• Non-testing approaches offer a means of facilitating the regulatory
challenges in chemical safety assessment
-------
Computational (In Silico) Toxicology
• Databases/Dashboards of existing information
Structure-Activity Relationships (SAR)
• Quantitative Structure-Activity Relationships (QSAR)
• Expert Systems
• Category formation (grouping) read-across
• Bioinformatics
• Chemoinformatics
Biokinetics (PBPK)
-------
Integrated Approaches to Testing and Assessment
(IAT A)
Problem formulation. Definition of the regulatory need (e.g. hazard
identification, hazard characterisation, safety assessment etc.) and
the information/parameters that are relevant to satisfy the need
including consideration of existing constraints and, if applicable,
consideration of the level of certainty required.
Gather and evaluate existing information (in vivo, in vitro, in silico
[e.g. (Q)SAR), read across and chemical category data).
Make a weight of evidence assessment or apply predefined decision
criteria (e.g. ITS, STS).
If available information does not provide sufficient, evidence
consider what additional information from non-testing, non-animal
testing methods and, as a last resort., from animal methods would be
needed to generate sufficient evidence.
Make a weight of evidence assessment or apply predefined decision
criteria (i.e. ITS, STS).
Available information
provides sound
conclusive evidence for
the specific regulatory
need
Available information
provides sound
conclusive evidence for
the specific regulatory
need
From OECD
-------
Typical Information within an I AT A:
IATA elements
• Historical information on the chemical of interest
• Non-standard in vivo tests
• Information from "similar" chemicals
• Predictions from other 'non-testing' approaches such as (Q)SAR
• In chemicotests
• In vitro tests
• Molecular biology, -omics
• Exposure, (bio-)kinetics
7
-------
The EPA CompTox Chemicals
Dashboard: An Integration Hub for
Data Supporting Computational
Toxicology
Project Lead: Antony Williams
-------
The CompTox Portal
https ://comptox. epa. gov/
Environmental Topics Laws & Regulations About EPA
Available
JV United Stales
Environmental Protection
Agency
v>EPA
Unriad Sflalax
Erweronmentil Prafesotron
Search EPA.gov
9
-------
v>EPA
Uwittad S«nlos
ERwonmentil Prot«cbon
Af)»ncp
* A publicly accessible website delivering access:
—875,000 chemicals with related property data
- Experimental and predicted physicochemical property data
- Integration to "biological assay data' for 1000s of chemicals
- Information regarding consumer products containing chemicals
- Links to other agency websites and public data resources
- Literature" searches for chemicals using public resources
- "Batch searching" for thousands of chemicals
- DOWNLOADABLE Open Data for reuse and repurposing
CompTox Chemicals Dashboard
10
-------
CompTox Chemicals Dashboard
w
Uniiail StBtas
Ewferonmont»1 Prattcbon
Ag««cv
v>EPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
Chemicals
875 Thousand Chemicals
Product/Use Categories Assay/Gene
Q. Search for chemical by systematic name, synonym. CAS number, DTXSID or InChiK
1 Identifier substring search
See what people are saying, read the dashboard comments!
Cite the Dashboard Publication click here
Latest News
Read more news
New Article regarding the GenRA module
March 9th, 2019 at 1:03:58 PM
A new article regarding "Generalized Read-Across (GenRA): A workflow implemented into the EPA CompTox Chemicals Dashboard" has been
published in the ALTEX (Alternatives to Animal Experimentation) journal. Read the article here.
11
-------
Comp I ox Chemicals Dashboard
Chemicals
&EPA
vvEPA
Uniiail StBtas
Ewferonmont»1 Prattcbon
Ag««cv
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
875 Thousand Chemicals
Chemicals
Product/Use Categories Assay/Gene
Q Bisphenol A
fa
£0^
Bisphenol A
DTXSID7020182
Bisphenol A bis(2-hydroxyethyl ether) diacrylate
DTXSID6066991
Bisphenol A bis(2-hydroxyethyl ether) dimethacrylate
DTXSID1066992
Bisphenol A bis(2-hydroxypropyl) ether
DTXSID8051592
Bisphenol A carbonate polymer
DTXSID6027840
Bisphenol A diglycidyl ether
DTXSID6024624
Bisphenol A glycidyl methacrylate
DTXSID 7044841
Bisphenol A propoxylate diglycidyl ether
DTXSID 10399098
12
-------
Comp I ox Chemicals Dashboard
Products and Use Categories
v>EPA
Unriad S«alas
Ewwonmontil Prat«cbon
Ag««cv
*>EPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
875 Thousand Chemicals
Chemicals
Product/Use Categories
Assay/Gene
Q haircolotj
CPDat PRODUCT category: personal care hair color
hair colors and dyes characterized as permanent
CPDat PRODUCT category: personal care hair color
hair colors and dyes characterized as for professional use
CPDat PRODUCT category: personal care hair color
hair colors and dyes characterized as temporary
CPDat PRODUCT category: personal care hair color
hair coloring products not otherwise categorized
CPDat PRODUCT category: personal care hair color activator
chemical activators for hair coloring products
CPDat PRODUCT category: personal care hair color developer
chemical developers for hair coloring products
CPDat PRODUCT category: personal care hair color toner
chemical toners for hair coloring products
00 new chemical substances being added, improved support for Toxcast bioassay available. This short video summarizes the advantages of the dasl
of multiple chemical lists and new user interface enhancements across the targeted analysis. View it here on Youtube. ~
look forward to your feedback.
13
-------
Comp I ox Chemicals Dashboard
Assays and Genes
v>EPA
Ui*t(fiQGl StBtas
Ewferonmont»1 Prattcbon
Ag««cv
v>EPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
875 Thousand Chemicals
Chemicals Product/Use Categories
Assay/Gene
Q ESR
ASSAY: TOX21_ESRE_BLA_ch1
Data from the assay component TOX21_ESRE_BLA_ch 7 was analyzed into 7 a...
ASSAY: TOX21_ESRE_BLA_ch2
Data from the assay component TOX21_ESRE_BLA_ch2 was analyzed into 7 a...
ASSAY: TOX21_ESRE_BLA_ratio
Data from the assay component TOX21_ESRE_BLA_ratio was analyzed into 7...
ASSAY: TOX21_ESRE_BLA_viability
TOX21_ESRE_BLA_viability used a type of growth reporter where loss-of-...
GENE: ESR1
estrogen receptor 7
GENE: esrl.L
estrogen receptor 7 L homeolog
GENE: ESR2
estrogen receptor 2 (ER beta)
GENE: esr2.L
estrogen receptor 2 L homeolog
GENE: esr2a
estrogen receptor 2a
GENE: esr2b
estrogen receptor 2b
14
-------
Detailed Chemical Pages: Landing page
|—r>A United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
LmI M »Agency
Bisphenol A
80-05-7 | DTXS1D7020182
Searched by DSSTox Substance Id.
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
> ADME
> EXPOSURE
> BIOACTIVITY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
SYNONYMS
> LITERATURE
LINKS
COMMENTS
15
-------
An "Executive Summary'
<>EPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
ADME
EXPOSURE
BIOACTIVITY
TOXCAST: SUMMARY
EDSP21
TOXCAST/TOX21
PUBCHEM
Bisphenol A
80-05-7 | DTXSID7020182
Searched by Expert Validated Synonym.
Executive Summary
Quantitative Risk Assessment Values
© IRIS values available C?
© No PPRTV values
© EPA RSL values available G?
© Minimum RfD: 0.050 mg/kg-day (chronic, IRIS, oral, 8)GT
© Mo RfC calculated
© VIVE POD not calculated
Quantitative Hazard Values
© Minimum oral POD: 3.8 mg/kg-day (reproductive, HPVIS, oral, 6)C?
© Mo inhalation POD values
© Lowest Observed Bioactivity Equivalent Level: CYP1A1, CYP1A2, Tpo, ESR2, ESR1,
ESR1, NR1I3, PPARA, NR1I2, Cyp2c11 MMP3, Esr1
Cancer Information
© Mo cancer slope factor
© No inhalation unit risk value
© Carcinogenicity data available: University of Maryland carcinogenicity warning; C?
© No genotoxicity findings reported
Reproductive Toxicology
© 200 Reproductive toxicity PODs available C?
REGIONAL SCREENING
v>EPA
Unriad S«alas
Erweronmentil Prafesotron
I
Class
THQ
Value
5.8
risk-based SSL (mg/kg)
THQ = 0.1
GIABS (unspecified)
THQ = 1
1
GIABS (unspecified)
H
-1
D
ii
o
1
ABS (unspecified)
THQ = 0.1
0.1
RFDo (mg/kg-day)
THQ = 0.1
0.05
screening level (residential Soil) (mg/kg)
—I
X
D
M
p
320
screening level (industrial soil) (mg/kg)
THQ = 0.1
4100
16
-------
An "Executive Summary"
Quick Look Tox Info
Executive Summary
jREENING
Value
41000
Quantitative Risk Assessment Values
Gf IRIS values availaWe G?
Q Mo PPRTV values
Gf EPA RSL values available Gf
Gf Minimum RfD: 0.060 mg/kg-day (chronic, IRIS, oral, 8)Gf
Q No P.fC calculated
© IVTVE POD not calculated
Quantitative Hazard Values
Gf Minimum oral POD 3.8 mg.'kg-day (reproductive. HPVIS, oral, 6) Gf
© No inhalation POD values
Gf Lowest Observed Bioactivity Equivalent Level: CYP1A1. CYP1A2, Tpo. ESR2. ESR1, ESR1.
WRII3. PPARA. MR 112 Cyp2c11 MMP3 Esd
REGIONAL^
Class
risk-based SSL (mg/kg)
GIABS (unspecified)
GIABS (unspecified)
£S (unspecified)
RFD^pig/kg-day)
si (residential Soil) (mg/kg)
screening level (irajustrial soil) (mg/kg)
screening level (tap wanti (ug/L)
RFDo (mg/kg-day)
screening level (residential Soil) (m'
screening level (industrial soil) (mg/kg)
ABS (unspecified)
risk-based SSL (mg/kg)
screening level (tap water) (ug/L)
Cancer Information
Q No cancer slope factor
Q No inhalation unit risk value
Gf Carcinogenicity data available: University of Maryland carcinogenicity warning: C?
Q No genotoxtcity findings repotted
Reproductive Toxicology
Gf 200 Reproductive toxicity PODs available Gf
Chronic Toxicology
Gf 340 Chronic toxicity PODs available G?
Subchronic Toxicology
Gf 12 Subchronic toxicity PODs available Gf
Developmental Toxicology
Gf 6 Developmental toxicity PODs available Of
Acute Toxicology
Gf 391 Acute toxicity PODs available Gf
Subacute Toxicology
Gf 1 subacute toxicity PODs available Gf
Neurotoxicology
Q No neurotoxicology 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) ©PHYSCHEM
ADME
Gf HTTK Css data are availaWe Gf
Fate and "Transport
(ji
Q Ho volatility concern
Q Biodegradation predictions are availaWe Gf
Gf BCF predictions are availaWe Gf
Gf Vapor Pressure predictions are available Gf
Exposure
Gf Exposure estimates are availaWe based on NHANES and SEEM Gf
-4-2 0
log(VP)
PARAMETERS
AOP Information
Q AOP Links: t3. 33, 36, 58, 60, 61, 66, 107. 124. 150,163,175.187. 200
Other Notes
Q No water quality values available
Q No air quality values availaWe.
Gf 14 Occupational exposure values available. 'Gf
POINT-OF-DEPARTURE PLOTS
©ASSAY PLOTS
v>EPA
Umloid S«nlas
Environment*! Prafescbon
Aq«*>cy
Quantitative Risk Assessment Values
IRIS values available Gf
Jo PPRTV values
Gf EPA RSL values available Of
Gf Minimum RfD: 0.050 mg/kg-day (chronic. IRIS. oral. 3] 2f
<£} No RfC calculated
Q (VIVE POD nol calculated
Quantitative Hazard Values
Gf Minimum oral POD 3,8 mg.'kg-day (reproductive. HPV15. oral. 6) Gf
© No inhalation POD values
Gf Lowest Observed Bioactivity Equivalent Level: CYP1A1 CYP1A2, Tpo. ESR2. ESR1, ESR1.
NR1I3, PPARA, NR1I2, Cyp2c11. MMP3. Esr1
17
-------
Physicochemical properties
United States
Environmental Protection Home Advanced Search Batch Search Lists V Predictions Downloads
kl M % Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
~ ADME
~ EXPOSURE
t BIOACTIVITY
TOXCAST: SUMMARY
EDSP21
TOXCAST/TOX21
PUBCHEM
TOXCAST: MODELS
SIMILAR COMPOUNDS
Bisphenol A
80-05-7 I DTXSID7020182
Property
Searched by Expert Validated Synonym.
Summary
£a Download ~ Columns ^
Property Experimental average ^ Predicted average
LogP: Octanol-Water 3.32 (1) 3.29
Melting Point 155(7) 139
Boiling Point 200 (1) 363
Water Solubility 5.26e-4 (1) 9.62e-4
Vapor Pressure - 8.37e-7
Flash Point - 190
Surface Tension - 46.0
Index of Refraction - 1.60
Molar Refractivity - 68.2
Polarizability - 27.0
Density I - 1.17
Molar Volume - 200
«»EPA
Uruled SffBtos
E r^»vronment*l Prafescbon
Aq«*>cy
Summary
Experimental median ^ Predicted median ^ Experimental range " Predicted range " Unit
3.43 3.32 2.40 to 3.64
156 138 153 to 156 125 to 157 °C
360 200 343 to 401 DC
1.00e-3 5.26e-4 5.35e-4 to 1.31e-3 mol/L
3.43e-7 - 6.83e-8 to 2.59e-6 mmHg
190 - 188 to 192 °C
46.0 dyn/cm
1.60
68.2 cmA3
27.0 Aa3
1.17 - 1.14 to 1.20 g/cmA3
200 cmA3
18
-------
QSAR Prediction Reporting Format (QPRF):
Standardised template to document a prediction
from a given QSAR model
QSAR Model Reporting Format (QMRF)
Template to document a QSAR model itself
Underpinned by the OECD QSAR Validation
Principles (2004)
ts from
v>EPA
Unriad Syntax
Erwwonmontil Protection
Aljency
OPERA Models: LogP: Octanol-Water
Bisphenol A
80-05-7 I DTXSID7020182
Cx
/>
V-(
HO
\
OH
Predicted value: 3.35
Global applicability domain: | Inside|
Local applicabilitydomain index: 0.877
Confidence level: 0.813
i QMRF
Weighted KNN model
5-fold CV (75%)
Training (75%)
Test (25%)
Q2
RMSE
R2
RMSE
R2
RMSE
0.850
0.690
0.860
0.670
0.860
0.780
Nearest Neighbors from the Training Set
Bisphenol A
Measured:3.32
Predicted: 3.35076
BUTANQIC ACID.2-(4-BIPHENYLYL)-3-
HYDROXY-3-METHY
Measured:3.25
Predicted: 3.39062
Flurbiprofen
Measured:4.16
Predicted: 3.94445
2.2-Diphenvlpropionic acid
Measured:2.69
Predicted: 2.84603
-------
Other Data: Human and Ecological
Chemical Hazard Data
vvEPA
Unriad S«alas
Ewwonmontil Prat«cbon
Ag««cv
t% United States
Environmental Protection Home Advanced Search Batch Search Lists v- Predictions Downloads
* w hI M % Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
~ ADME
~ EXPOSURE
~ BIOACTIVITY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
SYNONYMS
\ LITERATURE
LINKS
COMMENTS
Data Type
Point of Departure v
A Download ~
ijji Human
^Eco
A.
Columns \> 10 v
More ~
Priority ~
Toxval type »
Subtype "
Risk assessment class »
Value
Units '
Study type »
Exposure route ;
Species ~
Subsource »
Source »
i
5
BMDL-10
-
chronic
0.609
mg/kg-day
human
-
mouse
EFSACEF
EFSA
h
5
NOEL
Systemic
repeat dose
3.75
mg/kg-day
repeat dose toxicity : oral
oral
rat
-
ECHA
h
6
NOAEL
-
reproductive
3.75
mg/kg-day
reproductive
oral
rat
-
HPVIS
i
5
NOEL
Systemic
repeat dose
3.75
mg/kg-day
repeat dose toxicity: oral
oral
rat
-
ECHA
K
5
NOEL
Systemic
repeat dose
4.5
mg/kg-day
repeat dose toxicity: oral
oral
mouse
-
ECHA
fe
5
NOEL
Systemic
repeat dose
4.5
rrtg/kg-day
repeat dose toxicity : oral
oral
mouse
-
ECHA
K
7
LEL
-
subchronic
5
mg/kg-day
subchronic
oral
rat
unpublished_submission
ToxRefDB
1
7
nel
-
chronic
5
mg/kg-day
reproductive multigeneration
oral
rat
openjit
ToxRefDB
i
5
NOAEL
-
chronic
5
mg/kg-day
human
-
mouse
EFSAAFC
EFSA
K
7
nel
-
subchronic
5
mg/kg-day
subchronic
oral
rat
unpublished_submission
ToxRefDB
W 1 r
-------
Hazard Data from "ToxVal DB
>-^ERA
Unriad Sflalax
Erweronmentil Prafesotron
Ag«ncy
ToxVal Database contains following structured data:
—30,000 chemicals
—750,000 toxicity values
—30 sources of data
—4500 journals cited
—70,000 literature citations
21
-------
Sources^ of Exposure to Chemicals
v>EPA
Unriad Sflalax
Ewwonmontil Prat«cbon
Ag««cv
oEPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
Bisphenol A
80-05-7 | DTXSID7020182
Searched by DSSTox Substance Id.
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
~ ADME
^ Download ~
Columns v 10 v
P roductor use Categon ration
manufacturing, metals
adhesive
I
- EXPOSURE
PRODUCT & USE CATEGORIES
CHEMICAL WEIGHT FRACTION
CHEMICAL FUNCTIONAL USE
TOXICS RELEASE INVENTORY
MONITORING DATA
Product and Use Categories (PUCs) 0
~ Categorization type
CPCat Cassette
CPCat Cassette
CPCat Cassette
CPCat Cassette
CPCat Cassette
CPCat Cassette
CPCat Cassette
CPCat Cassette
CPCat Cassette
CPCat Cassette
2 3 4 5 6 7
' Nun^®_r-of Unique Products
17
17
16
12
11
8
8
8
7
6
9 10 > » Last
EXPOSURE PREDICTIONS
PRODUCTION VOLUME
22
-------
ADME-IVIVE
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
kl mm Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE,/TRANSPORT
HAZARD
~ ADME
~ EXPOSURE
~ BIOACTIVITY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
Bisphenol A
80-05-7 | DTXSID7Q20182
Searched by Expert Validated Synonym.
Label
© In Vitro Intrinsic Hepatic Clearance
© Fraction Unbound in Human Plasma
© Volume of Distribution
© Days to Steady State
© PK Half Life
© Human Steady-State Plasma Concentration
* Measured
19.29
0.07
Urtrioid Sflnlas
Erv ronmentt) Protection
Aq««>cv
I VIVE
*¦ Predicted
Computed
Unit
uL/m in/mil I ion hepatocytes
29,83
1.98
L/kg
Days
hours
mg/L
23
-------
In VitroBioassay Screening
ToxCast and Tox21
v>EPA
Unriad Sflalax
Ewwonmontil Prat«cbon
Ag««cv
oEPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
t ADME
~ EXPOSURE
~ BIO ACTIVITY
EDSP21
TOXCAST/TOX21
PUBCHEM
TOXCAST: MODELS
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
SYNONYMS
> LITERATURE
LINKS
COMMENTS
J Searched by Expert Validated Synonym.
Chemical Activity Summary©
© TOXCAST DATA
O ASSAY DETAILS
Show All
cell cycle
cell morphology
oell adhesion rootecules
cytokine
gpc*-
maiformaDon
oxsdo'eductase
cyp
nuclear receptor
background measurement
DMA binding
• •
••
• .*
• •!
• <
• •
L %
±.
fc o
%
• •
AC50 (uM)
AC50 (uM): 1.48
Scaled top: 5.48 Mil
Assay Endpoint Name: ATG_PXRE_CIS_up
Gene Symbol: NR1I2
Organism: human
Tissue: liver
Assay Format Type: cell-based
Biological Process Target: regulation of transcription factor activity
Detection Technology: RT-PCR and Capillar/ electrophoresis
Analysis Direction: positive
Intended Target Family: nuclear receptor
Description: Data from the assay component ATG_PXRE_CfS was analyzed into 1 assay endpoint This assay endpoint,
ATG_PXRE_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 NR1I2. 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 "non-steroidal".
185 active of 839 assays
b Download ~ Columns '
cm Show Inactive Show Background
Name *
Modal
SeqaPASS "
AOP "
Event T
Hit Call '
Top
AC50 t
logAC50 '
MaxMed w
Cutoff *
ModlAcc *
Intended Target Family "
OACEA_ER_80hr
II
NP_000116.2 i.
200
1181
ACTIVE
112
0.373
-0.428
113
26.9
-0.686
nuclear receptor
0 APR_HepG2_CellLoss_24h_dn
h
-
ACTIVE
120
106
2.02
1.20
0.663
2.04
cell cycle
O APR_HepG2_MitoMass_24h_dn
h
ACTIVE
0.874
109
2.04
0.867
0.496
2.05
cell morphology
24
-------
In VitroBioassay Screening
ToxCast and Tox21
v>EPA
Unriad Sflalax
Ewwonmontil Prat«cbon
Ag««cv
SEPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
» ADME
~ EXPOSURE
~ BIO ACTIVITY
TOXCAST: SUMMARY
EDSP21
PUBCHEM
TOXCAST: MODELS
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
SYNONYMS
LITERATURE
Bisphenol A
80-05-7 I DTXSID7020182
Searched by Expert Validated Synonym.
Assay Selection 136 Selected
W Active Ll Inactive LJ AH
Ceetox/OpAns (2 of 24 selected)
Odyssey Thera (6 of 17 selected)
Attagene (4 of 165 selected)
Tox21/NCGC {44 of 211 selected)
CellzDirect (3 of 48 selected)
Bioseek (4 of 174 selected)
Apredica (8 of 107 selected)
NHEERL Padilla Lab (1 of 1 selected)
Novascreen (46 of 167 selected)
NHEERL's Hunter Lab (0 of 4 selected)
NCCPs Lab (4 of 4 selected)
ACEA Biosciences (4 of 6 selected)
ToxCast/Tox21
QC Data ID
Grade
Description
Tox21_202992
Pass
Purity>90% and MW confirmed
Tox21_400088
Pass
Purity>90% and MW confirmed
A Single Assay Can Have Multiple Charts
Q Representative Samples Only
i Bioactivity Summary ~
Number of Charts: 136 I
BaphradAlttW)&-/i
TP0001056G66
j
. y
s
1
OT_EH_£RaEFtoJl*!!
| .j*
*
Urn.
DupWrQ A183-06-71
DIX3iD>«»Ue
TP0OM)r6i601
! / i
25
-------
Bioactivity: Downloadable Data
https://www.epa.gov/chemical-research/exploring-toxcast-data-download
Unriad S«alas
Ewwonmontil Prat«cbon
Ag««cv
Exploring ToxCast Data: Downloadable Data
The results after processing through the Pipeline are available on the ToxCast Dashboard, and for
most users EPA recommends accessing the data there.
Resources
ToxCast Chemicals
ToxCast Assays
ToxCast Data and Information
Toxicity Forecaster i'ToxCast)
Fact Sheet
ToxCast Publications
ToxCast Citation
About ToxCast
• ToxCast & Tox21 Summary Files. Data for a single chemical endpoint pair forthousands of
chemicals and assay endpointsfor 20 variables such as the activity or hit call, activity
concentrations, whether the chemical was tested in a specific assay, etc.
o Download ToxCast Summary Information
o Download Read Me
• ToxCast & Tox21 Data Spreadsheet. A spreadsheet of EPA's analysis of the chemicals screened through ToxCast and the Tox21
collaboration which includes EPA's activity calls from the screening of over 1,800 chemicals.
o Download Data
o Download ReadMe
• ToxCast Data Pipeline R Package. The R computer programming package used to process and model all EPA ToxCast and Tox21
chemical screening data. The files include the R programming package as well as documents that provide overviews of the data analysis
pipeline used and the R package. Users will need experience with R to use these files.
o Download Package
o TCPL Overview
26
-------
BUILT-IN "MODULES"
27
-------
Landing page
J\ United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
m * Agency
Bisphenol A
80-05-7 | DTXS1D7020182
Searched by DSSTox Substance Id.
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
\ ADME
> EXPOSURE
> BIOACTIVITY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
SYNONYMS
> LITERATURE
LINKS
COMMENTS
«»EPA
Wikipedia
Bisphenol A (BPA) is an organic synthetic compound with the chemical formula {CHs^CfCghUOHfe belonging to the group of dlphenylmethane
derivatives and bisphenols, with two hydroxyphenyl groups. It is a colorless solid that is soluble in organic solvents, but poorly soluble in water. It has
been in commercial use since 1957.
BPA is a starting material for the synthesis of plastics, primarily
Read more
Intrinsic Properties
Structural Identifiers
Linked Substances
Presence in Lists
Record Information
Quality Control Notes
28
-------
Related Publications
8
jk
Regulatory Toxicology and Pharmacology
Volume 79, August 2016, Pages 12-24
KritiiiMiin
lirtktwkie? .it'll
I1U llltfl »kMO
ELSEVIER
Systematically evaluating read-across prediction and
performance using a local validity approach
characterized by chemical structure and bioactivity
information
Short Communication
Generalized Read-Across (GenRA):
A Workflow Implemented into the EPA
CompTox Chemicals Dashboard
George Hehnanu, Imran Shah'-, Antony J. Ff 7/jEkwe -, Jeff Edwards^, Jeremy Dunne* and Grace Patlewicz *
'Ciko:i»e Znrjtxe far kieice ad Ed.zsLDii i'OSISIi OikRida, IN, USA; *Nniiad Ciuter fox Compumtnnal Tasimln^v fNCCT], Office of
* Ug^d^-tas^«-dsabi£r&v" "T;i
v>ERAk
Unriad Sflalax
Ewwonmontil Prot«cbon
Ag««cv
Concha *v*il*bk as SdcrwKsDjrc«
Computational Toxicology
journal Swrwpase; httpe/Zee* clsevi ts. eora
Contents lists available at SdenceDirect
Computational Toxicology
ELSEVIER
journal homepage: v
v.elsevier.com
Journal
Image
Navigating through the minefield of read-across frameworks: A commentary
perspective
Grace Patlewicz3' \ Mark T.D. Croninb. George I Jelrjair' Jason C. Lambert11, Lucina E. Lizarraga*1, Imran Shah"
a National Center for Computational Toxicology (NCCT), Office of Research und Development, US Environmental Protection Agency (US EPA), 109 TW Alexander Br, Research Triangle Park
(RTP), NC 27711, USA
b school of Pharmacy and Riomolecnlar Sciences, Liverpool .lohn Moons University, Byrom Street, Liverpool 1.13AF, UK
r Oak, Ridge Institute for Science arid Education (ORISE), 1299 Bethel Vulley Roud, Oak Ridge, TN 37830, USA
National Center for Evaluation Assessment (NChA), US Environmental Protection Agency (US EPA), 26 West Martin Luther King Dr, Cincinnati. Off 4i>268, USA
ELSEVIER
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 Patlewicz b A e
Transitioning the generalised read-across approach (GenRA) to quantitative
predictions: A case study using acute oral toxicity data
George HeJman"*b, Imran shahb, Grace patlewieib'*
¦ odt Kidft fa* Sdei&t ezd ziL^amn. (OMOZ}, oak
* Ctrnrffo* CMfMBtiOMf EMtariqy QtGCTX, Cgfltt iftL
37711. VSA
ARTICLE INFO
JQgiwanJi
lt*d-.b£r-a» (OwSAJl
Am oral uMCbiary
'0uUC.UCi»4
AB!
RA*d-
Or tti
set
dooel
»
to lootirity aiudk* Hm, wc WKlLn»f*J c;ceHA to > 4rvdopntnal» (rv*pfc*li**tiw. aod fluiliii^ccrau* effcm- Tb* moan UME2. for
carfi chemical were convoietl Id lux nv -lnr equivalent Applying CcrtRA 1o ill chraiicak Willi a minimum
-------
Generalised Read-Across (GenRA)
v>EPA
OETAILS
EXECUTrVT SUMMARY
PROPERTIES
ENV. FATE'TRANSPORT
~ EXPOSURE
B1QACTIVITY
TOXCAST- SUMMARY
PUBCHEM
TOXCAST. DATA
TOXCAST. MODELS
SIMILAR COMPOU NDS
RELATED SUBSTANCES
SYNONYMS
> LITERATURE
LINKS
COMMENTS
Unriad Sflalax
Ewwonmontil Prat«cbon
Ag««cv
Bisphenol A
80-05-7 | DTXSID7020182
Searched by Expert Validated Synonym.
Step Two: Data Gap Analysis & Generate Data Matrix
Ne^gfiBora by: Chem: Morgan Fgrprta ~
Fi ler by: mvlvodata ~ O
Summary Data Gap Analyse 0 Group: TaxRef ~
By: Tok Fingerprint ~
Generate Data Matrix H
0
-O-fc-
&-42-Me0ivfcula -yxx
«-(1,tA3-T«ra_
g/ a-.
-$/ V
-Of
Btypafatan
/
"CW - ^
BSshcnol A
\v
Dclif-KTocstrcJ
mo
-
1f 234
K>-
V
Bir.pherv.il A 23
4 ^2 Meftiylbutan 2-yl)pb 5
4-<1.1.33Te*snuslhylfcw. 15
DelhyWtibeslrtjl S3
Mcfrytparaben 7
led ButyPiytirDqunane 12
AcptamincqriKi 4
4 Nilraphend 15
Phend 3
4 !4 HySnxYabeny |buL 14 0 16 165
Eihylparabcn 3
CfrW: Adrenal Gla-icB
|
CHRiBkwd v
6 95
* cr Analogs 10
iVflann-xWr
CMR:Bone|
CHR: Bane .Ma rraiiv J
CHR.Brair j
CHR.Bronc+iLsB
Min+: 0 ~
1.00 0
Min-: 0 ~ Fitter: |
Q.4S / 0.45 y 0.29 V 0.28 >/ 0.28 •/ 0.28 V 0.2S ~ 0.26 •/
¦ /¦ ,
/ i/j
/ //'
/j?
& /¦ /¦¦ f-
af.' *i: .f: /:
fy j; &
' >>¦ # /'
' -r'' V
'
-J
///
*'//
V/ <2?-'
¦
¦
¦
¦
¦¦
¦
¦ ¦
¦
¦
¦
¦
¦ ¦
¦ ¦
¦ ¦
¦
m
¦ ¦
Similarity Weight:
Download:
020 V 0.25 7
r-T
£?Q \ -O-G 1, ~-Q\ jav K>- —o
Bisphenti A i (2 Metttytbut. 4-<1.1^3,JT«-a DieSiyf&iiLu&ui Methytparsben tesl 3u!/hycrj Acctmnaatien J *trt-opne!>d ^HcrcJ 4 V4 Hydranyph Ethytccrafoen
CH:R:A:domin3l Cayfy
CHR Adren3[ Gj _ _
CHR Artery (General}
CH itoryjS^rtte Re _
CHR.Bile duct
CHR: Bfood
CHR ^3 sood _ve5_ss_
CKRJktfy Weight
CHR:Ekwe
30
-------
Read-across
• Read-across describes the method of filling a data gap whereby a
chemical with existing data values is used to make a prediction for a
'similar' chemical.
• A target chemical is a chemical which has a data gap that needs to be
filled i.e. the subject of the read-across.
• A source analogue is a chemical that has been identified as an
appropriate chemical for use in a read-across based on similarity to
the target chemical and existence of relevant data.
Known to be harmful Predicted to be harmful
-------
Read-across workflow in GenRA vl.O
Decision
Context
Screening level assessment
of hazard based on
toxicity effects from
ToxRefDB vl
Uncertainty
assessment
Assess prediction and
uncertainty using AUC and
p value metrics
Analogue
identification
Similarity context is based
on structural
characteristics
Read-across
Similarity weighted
average - many to one
read-across
*
Data gap
analysis for
target and
source analogues
Analogue
evaluation
Evaluate consistency and
concordance of
experimental data of
source analogues across
and between endpoints
-------
GenRA tool in practice
• Structured as a workflow
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
ADME
> EXPOSURE
> BIOACTIVITY
SIMILAR COMPOUNDS
RELATED SUBSTANCES
SYNONYMS
> LITERATURE
LINKS
COMMENTS
Fluconazole
86386-73-4 | DTXSID3020627
Searched by DSSTox Substance Id
r
Neighbors b^^ Chem: Morgan Fgrprfly ~ Filter by: invivo data ~ ©
-Oiv
/ %
Similarity context
Bromuconazole
V
/ \
Fyrasuifotote m...
# of Analogs 10
cp-p-
Tetraconazole
$
Fenaucorazole
Step One: Analog Identification and Evaluation
4
J
y
r
9
k
J
i
4
4
-------
GenRA tool in practice
GenRA
Neighbors by: Chem: Morgan Fgrprts *
Butanal oxime
jj-r
-
Ethoprop
Fosamine amm...
# of Analogs 10
Ethylene glycol..
Acrolein diethyl...
Filter by: invivo data
i
Elhion
-C
Methyleugenol
•JCX.
bis(2-Chl oro-1 -
2-Elhoxyethyl a..
Step Two: Data Gap Analysis & Generate Data Matrix
Sumrwsry Data Gap Analysis
a
V-
$ 4
Group: ToxRef
By: Tox Fingerprint
Generate Data Matrix
^rd/=C
Myrcene
¥
Chlorethoxyfos
^Fluconazole
3
ra
"
i:
Hexaconazole
43
18 I
Flusilazole
28
9
Cyproconazole
14
,0
Pyrasulfotole metabolite ...
0
0
18
234
Myclobutanil
15
a
15 I
Fenbuconazole
34
17 I
Tetraconazole
35
~
20 |
Metconazole
35
215
15
82
Ipconazole
46
232
16
180
Bromuconazole
24
277
13 I
m
£/
/ / /
^
-------
GenRA tool in practice
GenRA
Step Three: Run GenRA Prediction
Neighbors by: Chem: Morgan Fgrprts »
Filter by: invivo data ~
Summary Data Gap Analysis Group: ToxRef ~
By: Tox Fingerprint T
M Run Read-Across 1
Run GenRA
A <$¦
#' # r
Acrolein diethylacetal 14 0 4 0
Ethylene glycol diethyl e . 7 0 4 95
CHR:Body Weight
CHR:Bone Marrow
CHR:Brain
/ ^ ^
rT Qi _0 i*.
^ 4
? <4°
I I
# / -4? / / /^° ry9 ^
^ 0" <\! *&/ tfFf 0J
iletype
Target
Min-: 0
Source analogues
Similarity Weight: Q
o ?1 J a ?i J
Download: Filetype
v£o\ ^ pb -^5 xh® o
~x_
$>p~
Fluconazole Hexaconazole Flualazole Cyproconazole Pyrasulfotoie m... Mydobutanil Fenbuconazoie Tetraconazole Metoonazoie ipconazoSe Bromuconazole
_CHR:Abdomtnal Cavity
CHR Adrenal Gland
CHRMery .(General)
CHR.Auditory Startle Re..
CHRBileduct
CHRjBlood
CHR: BJood vessel
CHR Body Weight
CHRBone
-------
Names and CASRNs to
Support Searches
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
i Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
~ ADME
~ EXPOSURE
~ BIOACTIVITY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
~ LITERATURE
LINKS
COMMENTS
Bisphenol A
80-05-7 | DTXSID7020182
Searched by DSSTox Substance Id.
25 v
Synonym
Bisphenol A
4,4'-(Propane-2,2-diyl)diphenol
Phenol, 4.4'-(1 -methylethylidene)bis-
80-05-7
BPA
4,4'-Propane-2,2-diyldiphenol
Phenol, 4,4'-(1 -methylethylidene)bis-
4-06-00-067171
Beilstein Registry N
(4,4 '-DiHydroxydiphenyl)dimethylmethane
2.2-Bis(4'-hydroxyphenyl) propane
2!2'-Bis(4-nydroxyphenyl)propane
2.2-BIS-(4-HYDROXY-PHENYL)-PROPANE
2,2-Bis(4-hydroxyphenyl)propane
2,2-Bis(p-hydroxyphenyljpropane
2,2-Di(4-Hydroxyphenyi) Propane
«»EPA
Umloid SXnlas
E r^»vronment*l Prafescbon
Aq«*>cy
~ Quality
Valid
Valid
Valid
Valid
Valid
Valid
Valid
Beilstein
Good
Good
Good
Good
Good
Good
Good
36
-------
Literature Searching
v>EPA
Unriad Sflalax
Ewwonmontil Prat«cbon
Ag««cv
1 * 1 _-rv.
XX
\
r,—
HO
Morphine
57-27-2 | DTXSID9023336
Searched by Approved Name.
Abstract Sifter
1) Select PubMed starting point query then 2) click on Retrieve. ©
Select a Query Term
Select a Query Term
Hazard
Fate and Transport
M eta bo I is m/P K/P D
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
Retrieve Articles
Optionally, edit tihe query before retrieving,
"57-27-2" OR "Morphine"
37
-------
Literature Searching
Lnna Liniam inrougn aaoiescenij
Dust and Exposure
Food and Exposure
Water and Exposure
¦ i
Algae
Disaster / Emergency
Optionally, edit the query before retrieving,
C57-27-2" OR "Morphine") AND ([water CR groundwater OR drinking
water) AND Environmental Exposure)
38
-------
Literature Searching
v>EPA
Unriad Sflalax
Ewwonmontil Prat«cbon
Ag««cv
37 of 37 articles loaded...
wastewater
Spectrometry
epa|
Clear Terms
Spectrometry 1
EPA
Total
PMID
Year
Title
Authors
Journal
Rev
~
4
2
0
6
29274731
2017
Simultaneous analysis of opioid analgesics and thei.
Krizman-Matasic: Kostanjevecki. Ahel; Terac
Journal of chromatography A
~
0
1
0
1
25768972
2015
Evaluating external contamination of polybrominate...
Poon: Aleksa. Carnevale: Kapur. Goodyer; Koren
Therapeutic drug monitoring
~
0
1
0
1
22544551
2012
Spatial distribution of illicit drugs in surface waters o...
Vazquez-Roig, Andreu; Blasco: Morillas: Pico
Environmental science and pollution research inter...
~
1
1
0
2
20801467
2010
Analysis of llicit and illicit drugs in waste, surface an...
Berset: Brenneisen: Mathieu
Chemosphere
~
1
1
0
2
17935751
2007
Illicit drugs, a novel group of environmental contami...
Zuccato: Castiglioni; Bagnati: Chiabrando; Grassi: ...
Water research
~
2
1
1
4
17607391
2007
Using environmental analytical data to estimate lev...
Bones: Thomas: Paull
Journal of environmental monitoring : JEM
~
3
1
2
6
17180984
2006
Simultaneous determination of psychoactive drugs . ..
Hummel; Loffler Fink; Ternes
Environmental science & technology
~
6
0
0
6
305831S9
2018
Assessment of drugs of abuse in a wastewater trea...
Kumar: Tscharke: O'Brien; Mueller: Wilkins. Padhye
The Science of the total environment
~
0
0
3
3
30488421
2018
Effect of enriched environment during adolescence ...
Mohammadian: Najafi Miladi-Gorji
Developmental psychobiology
~
3
0
0
3
29574368
2018
Estimation of the consumption of illicit drugs during ...
Foppe Hammond-Weinberger: Subedi
The Science of the total environment
~
1
0
0
1
28787791
2017
Evaluation of in-sewer transformation of selected illi. ..
Gao: Banks: Li: Jiang: Lai Mueller; Thai
The Science of the total environment
~
9
0
0
9
28472697
2017
Occurrence and fate of illicit drugs and pharmaceutic.
Causanilles: Ruepert; Ibafiez: Emke; Hernandez: d...
The Science of the total environment
~
0
0
0
0
28010888
2016
Dose-dependent effects of morphine on lipopolysac ..
Mottaz: Schonenberger; Fischer: Eggen: Schirmer ...
Environmental pollution (Barking. Essex : 1987)
~
0
0
0
0
27746311
2016
Effects of voluntary exercise on the viability, prolifer...
Haydari: Safari; Zarbakhsh: Bandegi Miladi-Gorji
Neur ©science letters
~
0
0
0
0
27261879
2016
Genotoxic effects induced by the exposure to an en...
Parolini: Magni: Castiglioni: Binelli
Ecotoxicology and environmental safety
~
3
0
0
3
27179320
2016
Temporal trends in drug use in Adelaide. South Aus ..
Tscharke. Chen Gerber; White
The Science of the total environment
39
-------
External Links to ~80 websites
vvEPA
United States
Environmental Protection
Agency
DETAILS
EXECUTIVE SUMMARY
PROPERTIES
ENV. FATE/TRANSPORT
HAZARD
» ADME
~ EXPOSURE
> BIOACTIVITY
SIMILAR COMPOUNDS
GENRA (BETA)
RELATED SUBSTANCES
SYNONYMS
~ LITERATURE
Home Advanced Search Batch Search Lists v Predictions Downloads
Bisphenol A
80-05-7 I DTXSID7020182
Searched by Approved Name-
General
• EPA Substance Registry Service
Household Products Database
¦Chemical Entities of Biological Interest
(ChEBI)
i PubChem
© Chemspicer
'CPCat
• DrjgBank
*nv HMDB
W IMtapecfca
Q MSDS Lookup
ChEMBL
Q 'Chemical Vendors
If CalEPA Office of Environmental Health
Hazard Assessment
23 NiOSH Chemical Safety' Cards
"oxPlanet
~ ACS Reagent Chemicals
W Wiksdata
~ ChemHat: Hazards and Alternatives
Toolbox
4£ Wolfram Alpha
• i ScrubChem
[J] ECHA Brie-" Profi e
ECHA Fnfocard
BB ChemAgcra
Teleology
Q AC I gR
3H: DrugPoda
y
, *
CCRIS
ChennView
@CTD
• eChemPo'tal
y Gene-Tax
ynsDE
v/crrv
Unriad S«alas
Erweronrnentil Prafesotron
Analytical
Ith Perspectives
• Program
I NEMI: National Environmental Methods
Index
3 RSC Analytical Abstracts
^ Tox21 Analytical Data
m MONA" MassBank North America
^ mzCloud
NET MIST IR Spectrum
NET NIST MS Spectrum
Prediction
£ 2D NMR HSQO'HMBC Prediction
^ Carbon-13 NMR Prediction
Proton NMR Prediction
ChemRTP Predictor
0 LSERD
ue
Search Engine
aarch
40
-------
CHEMICAL LISTS AND
CATEGORIES
41
-------
An Example List
v>EPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
Search all data
Hepatic metabolic clearance and plasma protein binding data PHASE 1
Q. Search WETMORE2012 Chemicals
U Identifier substring search
List Details
Description: Data from the Wetmore et ai paper Integration of dosimetry, exposure, and high-throuahput screening data in chemical toxicity assessment. Hepatic metabolic clearance and plasma protein binding data were experimentally
measured for ca. 240 ToxCast Phase I chemicals. The experimental data were used in a population-based in vitro-\o-in vivo (IVIVE) extrapolation model to estimate the daily human oral dose, called the oral equivalent dose, necessary to
produce steady-state in vivo blood concentrations equivalent to in vitro AC(50) (concentration at 50% of maximum activity) or lowest effective concentration values across more than 500 in vitro assays. The work was split into two phases.
This is phase 1 (2012) and the second phase is available here (2015).
Number of Chemicals: 238
238 chemicals
Download * I Send to Batch Search I Default v ft
CASRN X I DTXS1D X
-Q
Acifluorfen
CASRN: 50594-66-6
DTXSID: DTXSID0020022
Mass: 360.996485
O
AA
Anilazine
CASRN: 101-05-3
DTXSID: DTXSID9020089
Mass: 273.957979
Hide chemicals that are: v
_ri.
«-<¦=<
CH,
Atrazine
CASRN: 1912-24-9
DTXSID: DTXSID9020112
Mass: 215.093773
Azinphos-methyl
CASRN: 86-50-0
DTXSID: DTXSID3020122
Mass: 317.005771
-------
BATCH
SEARCHING
43
-------
v>EPA
U nil ad Syntax
L nv ro n me n t»1 Pratection
Aq«*>cv
• Singleton searches are useful but what if
you need data on LOTS of chemicals at
the same time...
• Typical questions
- What is the list of chemicals for the formula CxHyOz
- Can I get chemical lists in Excel files? In SOF files?
- Can I include properties in the download file?
Batch Searching
44
-------
REAL-TIME
PREDICTIONS
-------
Real-Time Predictions
v>EPA
Unriad Sflalax
Ewwonmontil Prat«cbon
Ag««cv
oEPA
United States
Environmental Protection Home Advanced Search Batch Search Lists v Predictions Downloads
Agency
Atrazine
DBQa
j 0 ^ ^ |™» T1 li A
V © & V
0 0 9
*
0
O,
[ 1
%
4
OOOOADOO o
I Crwsl |
Sefect properties to predict
H
C
N
O
S
P
F
Br
® Toxicological properties
® 96 hour fathead minnow LC50
® 48 hour D. magna LC50
48 hour T. pyriformis IGC50
® Oral rat LD50
Is?1 B'oaccumulatior factor
<1 Developmental toxicity
0 Ames mutagenicity
£3 Estrogen Receptor RBA
B Estrogen Receptor Binding
® Physical properties
Normal boiling point
® Melting point
0 Flash point
@ Vapor pressure
® Density
® Surface tension
® Thermal conductivity
0 Viscosity
/I Water solubility
46
-------
Conclusions
v>ERAk
Unriad Sflalax
Ewwonmontil Prot«cbon
Ag««cv
Computational toxicology encompasses many types of data
streams that are integrated together to address different
decision contexts both regulatory and non regulatory
The EPA CompTox Chemicals Dashboard provides access to
data for ~875,000 chemicals that addresses many of these
data streams
47
-------
Acknowledgements
«»EPA
LhnltMl SffBtos
E r^»vronment*l Prafescbon
Aq«*>cy
EPA-RTP
• An enormous te
contributors fr
especially the XT
development te
• Our curation te
care and focus
• Multiple centers
laboratories acr
• Many public dom
and open data contributors
-------
Contact for the CompTox Chemicals
Dashboard ——-
v>EPA
Unriad S«alas
Ewwonmontil Prat«cbon
Ag««cv
Antony Williams
CCTE, US EPA Office of Research and Development,
Wi 11 iams. Antony@epa.gov
ORCID: https://orcid.org/0000-0002-2668-4821
Williams et at. J Cheminform (2017)9:6}
DO110.1186/513321-017-0247-6
0 Journal of Cheminformatics
DATABASE
Open Access
#
CrossMark
The CompTox Chemistry Dashboard: a
community data resource for environmental
chemistry
Antony J. Williams1*®, Christopher M. Grulke1, Jeff Edwards', Andrew D. McEachran2, Karnel Man sou ri1,2,4,
Nancy C. Baker3, Grace Patlewicz1, Imran Shah1, John F. Wambaugh', Richard S. Judson1 and Ann M. Richard1
https://doi.org/10.1186/sl3321-017-0247-6
------- |