United States
!¦¦¦ Environmental Protection Agency
EPA Document # EPA-740-R1-8003
June 2018
Office of Chemical Safety and
Pollution Prevention
Supplemental Information for the
Exposure and Use Assessment of Five
Persistent, Bioaccumulative and Toxic
Chemicals
Peer Review Draft
June 2018
-------
Contents
Appendix A. Supplemental Document for Decabromodiphenyl ethers (DecaBDE) 7
A.l Literature Search Strategy 7
A.l.l. Database (Peer-reviewed) Search Strategies 8
A.l.2. Gray Literature Search Strategies 9
A.l.3. Supplemental Search Strategy 15
Backward Search 15
Google Scholar Search 15
A.l.4. Literature Search Results 15
A.2 Literature Screening Strategy 16
A.2.1. Development of the Literature Screening Approach 16
A.2.2. Literature Screening Pilot 17
A.2.3. Literature Screening 17
A.2.4. Prioritization 18
A.3 PECO Statement 20
A.4 PRISMA Diagram 21
A.5 Data Evaluation Criteria 21
A.6 Data Extraction Fields 22
Appendix B. Supplemental Document for Hexachlorobutadiene (HCBD) Literature Search Strategy 23
B.l.l. Database (Peer-reviewed) Search Strategies 23
B.1.2. Gray Literature Search Strategies 24
B.1.3. Supplemental Search Strategy 30
Backward Search 30
Google Scholar Search 30
B.1.4. Literature Search Results 30
B.2 Literature Screening Strategy 31
B.2.1. Development of the Literature Screening Approach 31
B.2.2. Literature Screening Pilot 31
B.2.3. Literature Screening 31
B.3 PECO Statement 32
B.4 PRISMA Diagram 33
B.5 Data Evaluation Criteria 33
B.6 Data Extraction Fields 34
Appendix C. Supplemental Document for Phenol, isopropylated, phosphate (3:1) (ITPP) 35
C.l Literature Search Strategy 35
Page 2 of 94
-------
C.l.l. Database (Peer-reviewed) Search Strategies 35
C.1.2. Gray Literature Search Strategies 38
C.1.3. Supplemental Search Strategy 44
Backward Search 44
Google Scholar Search 44
C.1.4. Literature Search Results 44
C.2 Literature Screening Strategy 45
C.2.1. Development of the Literature Screening Approach 45
C.2.2. Literature Screening Pilot 45
C.2.3. Literature Screening 45
C.2.4. Prioritization 46
C.3 PECO Statement 48
C.4 PRISMA Diagram 49
C.5 Data Evaluation Criteria 49
C.6 Data Extraction Fields 50
Appendix D. Supplemental Document for 2,4,6-Tris(tert-butyl) phenol (TTBP) 51
D.l Literature Search Strategy 51
D.l.l. Database (Peer-reviewed) Search Strategies 52
D.1.2. Gray Literature Search Strategies 54
D.1.3. Supplemental Search Strategy 60
Backward Search 60
Google Scholar Search 60
D.1.4. Literature Search Results 60
D.2 Literature Screening Strategy 61
D.2.1. Development of the Literature Screening Approach 61
D.2.2. Literature Screening Pilot 61
D.2.3. Literature Screening 62
D.2.4. Prioritization 62
D.3 PECO Statement 64
D.4 PRISMA Diagram 65
D.5 Data Evaluation Criteria 65
D.6 Data Extraction Fields 66
Appendix E. Supplemental Document for Pentachlorothiophenol (PCTP) 67
E.l Literature Search Strategy 67
E.l.l. Database (Peer-reviewed) Search Strategies 68
E.1.2. Gray Literature Search Strategies 68
Page 3 of 94
-------
E. 1.3. Supplemental Search Strategy 74
Backward Search 74
Google Scholar Search 74
E.1.4. Literature Search Results 74
E.2 Literature Screening Strategy 74
E.2.1. Development of the Literature Screening Approach 74
E.2.2. Literature Screening Pilot 75
E.2.3. Literature Screening 75
E.3 PECO Statement 76
E.4 PRISMA Diagram 77
E.5 Data Evaluation Criteria 77
E.6 Data Extraction Fields 78
Appendix F. Overall Workflow for Systematic Review 79
Appendix G. Inclusion and Exclusion Criteria for Title/Abstract and Full Text Screening 80
Appendix H. DRAGON Form and Screening Tags 87
H.l DRAGON Screening Form 87
H.2 Peer-Reviewed and Gray Literature Tagging Structures in DRAGON 88
H.3 DRAGON Extraction Form 89
H.4 DRAGON Evaluation Form 90
Appendix I. Data Extraction Fields 91
Appendix J. References 94
Page 4 of 94
-------
Tables
Table A-l. DecaBDE Open Literature Search Strategy 8
Table A-2. PBDE Open Literature Search Strategy 9
Table A-3. Summary of Gray Literature Sources and Search Results for Automated and Manual
Searches for DecaBDE 11
Table A-4. Gray Literature Search Strings 14
Table A-5. Detailed Results from Public Comments Backwards Search for DecaBDE 14
Table A-6. Count of Peer-reviewed Literature Search Results by Search Type for DecaBDE and PBDE 16
Table A-7. Detailed Results of Backwards Search of Frequently Used Sources for DecaBDE 16
Table B-l. HCBD Open Literature Search Strategy 24
Table B-2. Summary of Gray Literature Sources and Search Results for Automated and Manual
Searches for HCBD 26
Table B-3. Gray Literature Search Strings 29
Table B-4. Detailed Results from Public Comments Backwards Search for HCBD 29
Table B-5. Count of Peer-reviewed Literature Search Results by Search Type for HCBD 30
Table B-6. Detailed Results of Backwards Search of Frequently Used Sources for HCBD 30
Table C-l. ITPP Open Literature Search Strategy 36
Table C-2. PIP3 Supplemental Literature Search Strategy 37
Table C-3. Summary of Gray Literature Sources and Search Results for Automated and Manual
Searches for ITPP 39
Table C-4. Gray Literature Search Strings 42
Table C-5. Detailed Results of Public Comments Backwards Search for ITPP 42
Table C-6. Count of Peer-reviewed Literature Search Results by Search Type for ITPP 44
Table C-l. Detailed Results of Backwards Search of Frequently Used Sources for ITPP 44
Table D-l. TTBP Open Literature Search Strategy 52
Table D-2. TTBP Supplemental Literature Search Strategy 52
Table D-3. Summary of Gray Literature Sources and Search Results for Automated and Manual
Searches for TTBP 56
Table D-4. Gray Literature Search Strings 59
Table D-5. Detailed Results of Public Comments Backwards Search for TTBP 59
Table D-6. Count of Peer-reviewed Literature Search Results by Search Type for TTBP 61
Table D-7. Detailed Results of Backwards Search of Frequently Used Sources for TTBP 61
Table E-l. PCTP Open Literature Search Strategy 68
Table E-2. Summary of Gray Literature Sources and Search Results for Automated and Manual
Searches for PCTP 70
Table E-3. Gray Literature Search Strings 72
Table E-4. Detailed Results from Public Comments Backwards Search for PCTP 73
Table E-5. Count of Peer-reviewed Literature Search Results by Search Type for PCTP 74
Table G-l. Inclusion/Exclusion Criteria for PBT 5 80
Page 5 of 94
-------
Figures
Figure A-l. Literature Search Strategy Workflow 7
Figure A-2. Ensemble text analytics method for prioritizing studies for screening 19
Figure A-3. PRISMA Diagram for DecaBDE 21
Figure B-l. Literature Search Strategy Workflow 24
Figure B-2. PRISMA Diagram for HCBD 33
Figure C-l. Literature Search Strategy Workflow 36
Figure C-2. Ensemble text analytics method for prioritizing studies for screening 47
Figure C-3. PRISMA Diagram for ITPP 49
Figure D-l. Literature Search Strategy Workflow 51
Figure D-2. Ensemble text analytics methods for prioritizing studies for screening 63
Figure D-3. PRISMA Diagram forTTBP 65
Figure E-l. Literature Search Strategy Workflow 67
Figure E-2. PRISMA Diagram for PCTP 77
Acknowledgement
This report was developed by the United States Environmental Protection Agency (U.S. EPA),
Office of Chemical Safety and Pollution Prevention (OCSPP), Office of Pollution Prevention and
Toxics (OPPT). The OPPTTeam acknowledges support and assistance from EPA contractors ICF
(Contract No. EP-C-14-001).
Disclaimer
Reference herein to any specific commercial products, process or service by trade name,
trademark, manufacturer or otherwise does not constitute or imply its endorsement,
recommendation or favoring by the U.S. Government.
Page 6 of 94
-------
Appendix A. Supplemental Document for Decabromodiphenyl ethers (DecaBDE)
A.l Literature Search Strategy
This document describes the literature search strategy to support the exposure assessments for
five persistent, bioaccumulative, and toxic (PBT) chemicals. The intent of the search is to assess
the likely exposure of the general population, consumers, occupational populations, potentially
exposed or susceptible subpopulations, and the environment to the conditions of use of PBT
chemicals based on the criteria outlined in the Toxic Substances Control Act (TSCA) section 6(h)
(OLRC. 2016). The conditions of use are defined as the circumstances under which a chemical
substance is intended, known or reasonably foreseen to be manufactured, processed,
distributed in commerce, used or disposed of.
Data sources in the peer-reviewed (open) and gray literature were considered as shown in
Figure A-l. In addition to the primary searches of the peer-reviewed literature in Web of
Science, PubMed, and Toxline, there were additional supplemental searches that were used to
complement and/or evaluate the primary peer-reviewed search strategy. These were:
backward searches of frequently used sources1, a Google Scholar search of the top 100 results
by chemical, and public comments and associated references cited in those comments
submitted to the dockets by mid-January 2018.
Peer Reviewed
Database Search
Search peer
reviewed databases:
WoS, PubMed,
Toxine (except
TSCATS) and
compile in Endnote
libraries r~i
Backwards Search
• Conduct
backward
searches from
frequently used
sources and
com pile in
Endnote libraries
Generate Master Libraries
• Remove duplicates
Google Scholar Search (100 hits/chem)
• Remove duplicates captured previously
Evaluate search strategy
Supplemental Public Comments Search
Search docket for public comments and
references cited therein
• Add to HERO b/ docket #
Gray Literature Search
Step 1: Conduct automated
search of approved websites
Step 2: Conduct manual
search of approved websites
(except TSCATS}
Step 3: Compile results in
Excel spreadsheets with mini-
citations
Step 4: Remove duplcates
from gray results
Step 5: Develop full citations
for "on topics"
Submit Citations to HERO for HEROIDs & Addition to SR Database
Figure A-l. Literature Search Strategy Workflow
frequently used sources are sources expected to be of high quality, such as assessments conducted by other
government agencies.
Page 7 of 94
-------
An additional search of the gray literature was conducted as described in the Gray Literature
Search Strategy section and was based off the protocol developed for the Systematic Review of
the "First 10" chemicals under TSCA.
The results of the literature searches were compiled into Endnote libraries (database searches)
and Excel spreadsheets (gray literature.)
A.l.l. Database (Peer-reviewed) Search Strategies
The literature searches for the five PBT chemicals were designed to be as broad as possible,
searching only for the chemical name and synonyms, but not including any limiters such as
terms describing expected uses or dates. For DecaBDE, the chemical class name,
polybrominated diphenyl ethers (PBDE), was also included as a supplementary search. The class
name was included because DecaBDE is expected to behave similarly in the environment as
other PBDEs, as well as degrade to lower-brominated PBDEs. This also follows precedent set by
other DecaBDE assessments previously conducted by EPA and others (see frequently used
sources in Table A-7.) The search strategies are presented in Table A-l and Table A-2.
Table A-l. DecaBDE Open Literature Search Strategy
Date of Searc
i: December 15, 2017
Database
Search Strategy
PubMed
(1163-19-5[rn] OR BDE-209[tiab] OR DecaBDE[tiab] OR Deca-BDE[tiab] OR Decabromobiphenyl-
ether[tiab] OR Decabromobiphenyl-ether[nm] OR Decabromodiphenylether[tiab] OR
Decabromodiphenyl-ether[tiab] OR Decabromodiphenyl-oxide[tiab] OR PBDE-209[tiab] OR
Pentabromophenyl-ether[tiab])
AND (English[lang])
Web of
Science
("l,r-Oxybis(2,3,4,5,6-pentabromobenzene)" OR '^^'^S'A^^S'^S'-Decabrominated
diphenyl ether" OR '^^'^S'A^^S'^e'-Decabromobiphenyl ether" OR "2,2',3,3',4,4',5,5',6,6'-
Decabromodiphenyl ether" OR "Benzene, l,l'-oxybis(2,3,4,5,6-pentabromo-" OR
"Bis(pentabromophenyl) ether" OR "Bis(pentabromophenyl)ether" OR "Ether,
bis(pentabromophenyl)" OR "Ether, decabromodiphenyl" OR "FR-PE(H)" OR Adine-505 OR AFR-
1021 OR AI3-27894 OR Berkflam-B-lOE OR BR-55N OR BRN-2188438 OR Bromkal-82-0DE OR
Bromkal-83-10DE OR DB-10 OR DB-101 OR DB-102 OR DE-83 OR De-83R OR Decabrom OR
Decabromdiphenyl-oxide OR Decabromobiphenyl-oxide OR Decabromophenyl-ether OR DP-10F
OR EB-10 OR EB-10FP OR EB-10W OR EB-10WS OR EBR-700 OR Fire-Cut-83D OR Flame-Cut-llOR
OR Flame-Cut-Br-100 OR FR-10 OR FR-300 OR FR-300BA OR FR-300-BA OR FRP-53 OR FR-PE OR
Nonnen-DP-10 OR Nonnen-DP-10(F) OR PBED-209 OR Planelon-DB OR Planelon-DB-100 OR
Planelon-DB-101 OR Plasafety-EB-10 OR Plasafety-EBR-700 OR Saytex-102 OR Saytex-102E OR
Tardex-100 OR 1163-19-5 OR BDE-209 OR DecaBDE OR Deca-BDE OR Decabromobiphenyl-ether
OR Decabromodiphenylether OR Decabromodiphenyl-ether OR Decabromodiphenyl-oxide OR
PBDE-209 OR Pentabromophenyl-ether)
AND
English
Toxline
1163-19-5
Include Synonyms
Exclude PubMed
Records from TSCATS and NIH Reporter Database removed in EndNote
Page 8 of 94
-------
Table A-2. PBDE Open Literature Search Strategy
Additional PBDE terms only
Date of Search: December 15, 2017
Database
Search Strategy
PubMed
(PBDE[tiab] OR PBDEs[tiab] OR Halogenated-Diphenyl-Ethers[mh] OR Brominated-Diphenyl-
Ethers[tiab] OR Polybrominated-Diphenyl-Ethers[tiab] OR BDEs[tiab])
AND (English[lang])
NOT (1163-19-5[rn] OR BDE-209[tiab] OR DecaBDE[tiab] OR Deca-BDE[tiab] OR
Decabromobiphenyl-ether[tiab] OR Decabromobiphenyl-ether[nm] OR
Decabromodiphenylether[tiab] OR Decabromodiphenyl-ether[tiab] OR Decabromodiphenyl-
oxide[tiab] OR PBDE-209[tiab] OR Pentabromophenyl-ether[tiab])
Web of
Science
(PBDE OR PBDEs OR Brominated-Diphenyl-Ethers OR Polybrominated-Diphenyl-Ethers OR BDEs)
AND English
NOT ("l,l'-Oxybis(2,3,4,5,6-pentabromobenzene)" OR '^^'^S'A^^S'^S'-Decabrominated
diphenyl ether" OR '^^'^S'A^^S'^e'-Decabromobiphenyl ether" OR "2,2',3,3',4,4',5,5',6,6'-
Decabromodiphenyl ether" OR "Benzene, l,l'-oxybis(2,3,4,5,6-pentabromo-" OR
"Bis(pentabromophenyl) ether" OR "Bis(pentabromophenyl)ether" OR "Ether,
bis(pentabromophenyl)" OR "Ether, decabromodiphenyl" OR "FR-PE(H)" OR Adine-505 OR AFR-
1021 OR AI3-27894 OR Berkflam-B-lOE OR BR-55N OR BRN-2188438 OR Bromkal-82-0DE OR
Bromkal-83-10DE OR DB-10 OR DB-101 OR DB-102 OR DE-83 OR De-83R OR Decabrom OR
Decabromdiphenyl-oxide OR Decabromobiphenyl-oxide OR Decabromophenyl-ether OR DP-10F
OR EB-10 OR EB-10FP OR EB-10W OR EB-10WS OR EBR-700 OR Fire-Cut-83D OR Flame-Cut-llOR
OR Flame-Cut-Br-100 OR FR-10 OR FR-300 OR FR-300BA OR FR-300-BA OR FRP-53 OR FR-PE OR
Nonnen-DP-10 OR Nonnen-DP-10(F) OR PBED-209 OR Planelon-DB OR Planelon-DB-100 OR
Planelon-DB-101 OR Plasafety-EB-10 OR Plasafety-EBR-700 OR Saytex-102 OR Saytex-102E OR
Tardex-100 OR 1163-19-5 OR BDE-209 OR DecaBDE OR Deca-BDE OR Decabromobiphenyl-ether
OR Decabromodiphenylether OR Decabromodiphenyl-ether OR Decabromodiphenyl-oxide OR
PBDE-209 OR Pentabromophenyl-ether)
Toxline
(PBDE OR PBDEs OR Brominated-Diphenyl-Ethers OR Polybrominated-Diphenyl-Ethers OR BDEs)
NOT 1163-19-5
Include Synonyms
Exclude PubMed
Records from TSCATS and NIH Reporter Database removed in EndNote
A.1.2. Gray Literature Search Strategies
The five PBT chemicals searched were targeted to relevant sources and the approach was
adapted from the first 10 chemicals to optimize efficiency by eliminating redundancy. Gray
literature screening criteria excluded peer-reviewed journal articles that were expected to be
caught in the database searches. Mini citations, containing author, title, year, were generated
as a preliminary step to aid in identification and removal of duplicate records prior to tagging.
Automated searches via the Google search Application Programming Interface (API) were
employed where possible in favor of manual search sources. A summary of sources and search
result counts after the removal of duplicates is presented in Table A-3. All results were
Page 9 of 94
-------
reviewed from each source. The search strings used for manual and automated searches are
found in Table A-4.
EPA is aware of information submitted by companies as part of TSCA requirements under
sections 4, 8(d), 8(e) or as part of an FYI ("TSCATS Submissions data"). This information was not
considered as part of the literature search and screening strategy. EPA plans to consider this
information in the future.
Public comments submitted to the Docket (by Docket Number) were captured and HERO
records were created including the title, author and docket number. The results were then
compared to those of other searches to determine whether references cited in those public
comments were already identified by other searches or need to be included. PDFs of the
individual comments were not captured; instead a special "Public Comment" tag in HERO which
specifies the corresponding round of public comments was used. Detailed results of the Public
Comments submitted with the number of cited references for DecaBDE is shown in Table A-5.
Page 10 of 94
-------
Table A-3. Summary of Gray Literature Sources and Search Results for Automated and Manual Searches for DecaBDE
Source
ID1
Source Category
Website
Description
Search type
Search Result
Counts2
6000
US States
Government
Resources
States website custom search engine, see
Summary of State Sources tab
Custom search engine using States sites
Automated
69
1000
US EPA Resources
epa.gov
US Environmental Protection Agency
Automated
124
1150
US EPA Resources
http://aqsdrl.epa.gov/aqsweb/aqstmp/airdata/cl
ownload_files.html#Annual
Office of Air: AQS
Manual
0
1101
US EPA Resources
https://chemview.epa.gov/chemview
ChemView (CDR/IUR)
Manual
29
1083
US EPA Resources
https://actor.epa.gov/cpcat/faces/search.xhtml
CPDat
Manual
1
1154
US EPA Resources
https://comptox.epa.gov/dashboard/
Chemistry Dashboard
Manual
1
1148
US EPA Resources
https://iaspub.epa.gov/oppthpv/existchem_hpv_
prioritizations, report
EPA HPVIS
Manual
0
1001
US EPA Resources
https://www.epa.gov/ground-water-and-drinking-
water/table-regulated-drinking-water-
contaminants
Office of Water: EPA Clean Water Act
Manual
0
1008
US EPA Resources
https://www.waterqualitydata.us/portal/
Office of Water: STORET and WQX
Manual
1
1155
US EPA Resources
https://www.epa.gov/assessing-and-managing-
chemicals-under-tsca/persistent-bioaccumulative-
and-toxic-pbt-chemicals-under
TSCA PBT Use Documents
Manual
1
2150
Other US Agency
Resources
cdc.gov
Centers for Disease Control (includes
NIOSH and ATSDR)
Automated
40
2511
Other US Agency
Resources
energy.gov
Department of Energy
Automated
6
2300
Other US Agency
Resources
fda.gov
US Food and Drug Administration
Automated
4
2050
Other US Agency
Resources
niehs.nih.gov
NIH National Institute of Environmental
Health and Safety
Automated
19
2400
Other US Agency
Resources
osha.gov
OSHA Occupational Safety and Health
Administration
Automated
1
Page 11 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search Result
Counts2
2521
Other US Agency
Resources
pnnl.gov
Pacific Northwest National Laboratory
Automated
1
2509
Other US Agency
Resources
usgs.gov
US Geological Survey
Automated
27
2027
Other US Agency
Resources
https://ntp.niehs.nih.gov/pubhealth/roc/index-
l.html#C
NIH Report on Carcinogens
Manual
1
2414
Other US Agency
Resources
https://www.osha.gov/opengov/healthsamples.ht
ml
OSHA Chemical Exposure Health Data
Manual
(inclusive of all
results; not
limited to first
100)
0
2123
Other US Agency
Resources
https://www2a.cdc.gov/hhe/search.asp
CDC NIOSH Health Hazard Evaluations
Manual and
Automated
(inclusive of all
results; not
limited to first
100)
0
2104
Other US Agency
Resources
www.atsdr.cdc.gov/hac/pha/
CDC ATSDR Health Hazard Consultations
Manual and
Automated
(inclusive of all
results; not
limited to first
100)
1
3160
Other Resources
oecd.org
The Organisation for Economic Co-
operation and Development (OECD)
Automated
20
5000
Other Resources
sustainableproduction.org
Lowell Center for Sustainable
Production
Automated
8
5020
Other Resources
lnfohouse.p2ric.org
Pollution Prevention Infohouse
Automated
17
3600
Other Resources
http://www.spin2000.net/spinmyphp/
Substances in Preparations in Nordic
Countries (SPIN) Database
Manual
1
5027
Other Resources
Kirk Othmer Encyclopedia
Book
Manual
2
5028
Other Resources
Ashford's Dictionary of Industrial Chemicals, 2001
Book
Manual
1
Page 12 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search Result
Counts2
5029
Other Resources
Hawley's Chemical Dictionary, 2016
Book
Manual
0
3425
International
Resources
carexcanada.ca
Carex Canada
Automated
0
3520
International
Resources
env.go.jp
Government of Japan: Ministry of the
Environment
Automated
12
3050
International
Resources
europa.eu
European Union
Automated
164
3057
International
Resources
https://echa.europa.eu/information-on-
chemicals/registered-substances
ECHA
Manual
1
3100
International
Resources
iarc.fr
International Agency for Research on
Cancer
Automated
8
3350
International
Resources
nicnas.gov.au
Australian Government: Department of
Health, National Industrial Chemicals;
NICNAS
Automated
11
3250
International
Resources
who.int
World Health Organization
Automated
18
3421
International
Resources
https://www.canada.ca/en/health-
canada/services/chemical-substances/fact-
sheets/chemicals-glance.html#interest
Canada Chemicals Portal
Manual
12
3450
International
Resources
http://limitvalue.ifa.dguv.de/
GESTIS Database
Manual
0
Total Unique (Duplicates Removed)
601
^'Source ID" refers to an internal ID assigned to each source for tracking purposes.
2 Search result counts represent totals after removal of duplicate records.
Page 13 of 94
-------
Table A-4. Gray Literature Search Strings
Chemical
Manual Search Terms
Google Search Terms (up to 128 characters)
Decabromodiphenyl ethers
(DecaBDE)
Search database by CAS or chemical
name, or select from a list on the
website
"1163-19-5" OR "DecaBDE" OR "PBDE-209"
OR "Decabromodiphenyl-ether" OR
"Decabromobiphenyl-oxide"
Table A-5. Detailed Results from Public Comments Backwards Search for DecaBDE
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Christina Franz, Senior
Director, Regulatory & Technical Affairs,
American Chemistry Council (ACC)
American
Chemistry Council
(ACC)
EPA-HQ-OPPT-2016-0724-
0006
10
Comment submitted by Patrick Morrison,
Assistant to the General President, Health,
Safety and Medicine, International Association
of Fire Fighters (IAFF)
International
Association of Fire
Fighters (IAFF)
EPA-HQ-OPPT-2016-0724-
0005
6
Comment submitted by Veena Singla, PhD,
Associate Director, Science and Policy, Program
on Reproductive Health and the Environment,
University of California, San Francisco (UCSF) et
al.
UCSF Program on
Reproductive
Health and the
Environment,
academics,
scientists and
clinicians
EPA-HQ-OPPT-2016-0724-
0007
45
Comment submitted by Dianne Barton, Chair,
National Tribal Toxics Council (NTTC)
National Tribal
Toxics Council
(NTTC)
EPA-HQ-OPPT-2016-0724-
0010
18
Comment submitted by Laurie Valeriano,
Executive Director et al., Toxic-Free Future
Toxic-Free Future
EPA-HQ-OPPT-2016-0724-
0009
14
Comment submitted by Elizabeth Hitchcock,
Acting Director, Safer Chemicals Healthy
Families (SCHF) et al.
Safer Chemicals
Healthy Families
(SCHF), Alaska
Community Action
on Toxics, Center
for Environmental
Health,
Earthjustice,
Environmental
Health Strategy
Center, Natural
Resources Defense
Council, Toxic-Free
Future
EPA-HQ-OPPT-2016-0724-
0008
7
Comment submitted by Jyotsna Jagai, Research
Assistant Professor University of Illinois, Chicago
Chair, Environment Section, American Public
Health Association et al.
EPA-HQ-OPPT-2016-0724-
0014
6
Page 14 of 94
-------
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Pamela Miller,
Executive Director, Alaska Community
Action on Toxics (ACAT)
Alaska Community
Action on Toxics
(ACAT)
EPA-HQ-OPPT-2016-0724-
0011
4
Comment submitted by Jessica Helm et al.,
Silent Spring Institute
Silent Spring
Institute
EPA-HQ-OPPT-2016-0724-
0015
13
Comment submitted by Robert Stockman,
Senior Attorney, Environmental Defense Fund
(EDF)
Environmental
Defense Fund
(EDF)
EPA-HQ-OPPT-2016-0724-
0020
8
Comment submitted by Catherine Karr, Sheela
Sathyanarayana and Olivia Halas, Northwest
Pediatric Environmental Health Specialty Unit
Northwest
Pediatric
Environmental
Health Specialty
Unit
EPA-HQ-OPPT-2016-0724-
0018
9
Comment submitted by Leslie Riegle, Director
of Environmental Policy, Aerospace Industries
Association (AIA)
Aerospace
Industries
Association (AIA)
EPA-HQ-OPPT-2016-0724-
0016
0
Comment submitted by Ken Zarker, Section
Manager, Hazardous Waste and Toxics
Reduction Program, State of Washington
Department of Ecology
State of
Washington
Department of
Ecology
EPA-HQ-OPPT-2016-0724-
0017
21
TOTAL
13
161
Total Unique (Duplicates Removed)
138
A.1.3. Supplemental Search Strategy
Backward Search
To both supplement and test the database and gray literature searches, backward searches of
frequently used sources were conducted. These sources consist of previous risk assessments,
systematic reviews, and other assessments, generally conducted by EPA or other government
agencies of the chemicals of interest and presented in Table A-7. The references that are cited
within sections deemed relevant to this assessment were gathered into Endnote libraries for
title abstract review.
Google Scholar Search
To further supplement and test the database searches, a Google Scholar search was conducted
for each of the five PBT chemicals. The top 100 results returned by Google Scholar for each
chemical were exported into Endnote libraries. These results were compared to the references
identified in the database, backward, and gray literature searches to identify references not
found by the previous searches. While Google Scholar results are expected to be primarily peer-
reviewed rather than gray literature, the results were still compared to all searches.
A.1.4. Literature Search Results
The literature searches were conducted, and for PubMed, Web of Science, ToxLine, Backwards
searches, and Google Scholar searches, the results were imported into one Endnote library per
Page 15 of 94
-------
chemical. After the results were combined, duplicates were removed and TSCATS/NIH Reporter
data, a subset of ToxLine, were moved into a separate folder. The resulting counts are
presented in Error! Reference source not found.. Detailed results for the DecaBDE backwards
search are presented in Error! Reference source not found..
Table A-6. Count of Peer-reviewed Literature Search Results by Search Type for DecaBDE and
PBDE
Chemical
PubMed
WoS
ToxLine
TSCATS/ NIH
Reporter
Backwards
Google
Scholar
DecaBDE
1259
995
89
325
694
5
PBDE
3863
3419
8
236
NA
NA
Table A-7. Detailed Results of Backwards Search of Frequently Used Sources for DecaBDE
HERO ID
Document Title
Reference Count
4197019
AN ALTERNATIVES ASSESSMENT FOR THE FLAME RETARDANT
DECABROMODIPHENYL ETHER (DecaBDE)
130
1003344
Ecological State of the Science Report on decabromodiphenyl Ether
(decaBDE)
Bioaccumulation and Transformation
181
4180691
ECHA ANNEX XV RESTRICTION REPORT
PROPOSAL FOR A RESTRICTION
48
4161055
A Human Mixture Risk Assessment for Neurodevelopmental Toxicity
Associated with Polybrominated Diphenyl Ethers Used as Flame
Retardants
43
4180692
Risk profile on decabromodiphenyl ether (commercial mixture,
c-decaBDE)
287
4182591
Environmental risk evaluation report:
Decabromodiphenyl ether
309
956687
An Exposure Assessment of Polybrominated Diphenyl Ethers
364
4182466
VCCEP DecaBDE Assessment
3
TOTAL
1365
Total Unique (Duplicates Removed)
1021
EndNote Library: Total Unique (Duplicates Removed)
694
A.2 Literature Screening Strategy
A.2.1. Development of the Literature Screening Approach
The steps involved in developing the title abstract screening approach are:
1. Define inclusion/exclusion criteria.
2. Conduct the pilot using 10 randomly selected studies for each chemical from both the
peer-reviewed and gray literature that are screened by EPA experts.
Page 16 of 94
-------
3. Use the results of the pilot to refine the inclusion/exclusion criteria.
4. Use the refined pilot to train screeners in applying the tags.
The overall workflow of the systematic review process including the literature screening is
presented in Appendix F.
In these assessments, the results of the title/abstract literature screening will be used to
develop the PECO statement. The PECO statement is included in Appendix A.3. Four tags were
used at the title-abstract phase: Peer On Topic, Peer Off Topic, Gray On Topic, and Gray Off
Topic and recorded on the HERO project pages. Title abstract screening was conducted in
DRAGON2. A screenshot of the DRAGON form and all DRAGON tags is presented in Appendix H.
The inclusion/exclusion criteria for title/abstract and full text screening are included in
Appendix F. During full text screening, studies were also screened for "Red Flag Criteria," which
represent the "Unacceptable" criteria from the Data Evaluation criteria (U.S. EPA. 2018).
A.2.2. Literature Screening Pilot
A pilot with 100 results representative of the five chemicals and the peer, backwards, and gray
literature search results was developed by EPA. Two exposure experts scored the pilot, and met
with EPA to refine the criteria and application of the criteria.
Before screening, all screeners were required to meet a 90% accuracy in tagging the pilot
screening studies. Screeners who met this level of proficiency could begin title abstract
screening. Screeners who do not meet this level of proficiency, continued to train, using the
studies screened by screeners who had passed the pilot as additional training studies.
Documentation of all pilot tagging results was maintained in Excel spreadsheets for both the
peer-reviewed and gray literature.
A.2.3. Literature Screening
Title abstract screening of the peer-reviewed and gray literature occurred in DRAGON, an
online tool for systematic review. Results of the DecaBDE search were manually screened with
one screener who has been trained via the pilot process. Additionally, a subject matter expert
reviewed 10% of the references deemed to be On Topic and Off Topic as a quality assurance
check to ensure that they have been categorized appropriately.
For gray literature, title/abstract and full text screening was done simultaneously, and tags for
screening are included in Appendix H. For peer-reviewed literature, title/abstract and full text
screening were done separately, and tags for each stage are included in Appendix H.2.
2DRAGON is an online tool for systematic review developed by ICF that stores qualitative and quantitative data
from literature to help scientists implement the elements of systematic review, including problem formulation,
literature screening, risk of bias evaluation, and data integration.
Page 17 of 94
-------
A.2.4. Prioritization
The database search strategy for DecaBDE is returned approximately 2,500 results. Adding
search terms for the chemical class PBDEs to the DecaBDE search increased the number of
results to approximately 13,000. Few of the results added by including terms for chemical class
are likely to be relevant to an exposure assessment of DecaBDE; therefore, the results of the
title abstract screening of the DecaBDE search results were used to prioritize the results added
by including chemical class search terms using text analytics in the DoCTER tool and
SWIFTActive.
For prioritization, multiple text analytic algorithms can be used to find studies with titles and
abstracts similar to seed studies previously identified as On Topic by EPA experts. DoCTER
employs two main metrics, ensemble clustering and machine learning, including active machine
learning. Ensemble clustering uses multiple algorithms in Varghese et al. (2017) to prioritize
references for review. The prioritization strategy is shown in Figure A-2Error! Reference source
not found, and presented in Varghese et al. (2017). These algorithms create a user-defined
number of clusters based on similarities in the text of the title and abstract, and each algorithm
is broadly-accepted in the text analytics scientific field, as described in Varghese et ai. (2017).
The clusters are populated by the algorithms that first convert the text in each title and abstract
into a numerical matrix (using binary or 0s and Is to represent the text) and then identifies
similarities or similar numerical strings between each matrix representation of a title and
abstract. Based on the similarities, the reference is assigned to a cluster. In the example, each
of the algorithms was used to bin the studies into 10, 20, or 30 clusters, for a total of six
different cluster analyses (six large circles in the figure). A random sample of studies identified
as relevant serve as "tracer" or "seed" studies (pink circles in the figure). The tracer method
involves following these relevant studies and determining the clusters the majority occur in;
these clusters are then deemed more likely to contain other (as-yet unidentified) relevant
studies. Off topic references, or negative seeds, can be used to estimate performance of the
tool using the metric of precision, but are not required for clustering.
To identify these high-priority clusters, the clusters containing a given fraction (75% in the
example) of the relevant tracer studies are identified for each of the six analyses and termed
"high concentration of tracer" clusters. All non-tracer studies in those high-concentration
clusters can then be marked as "high priority" for further screening. This ensemble method is
used to increase confidence in the selection of prioritized studies by mitigating uncertainty
from each individual analysis. Additionally, studies in the "low priority" clusters can be further
analyzed using machine learning algorithms that also use the "tracer" studies in conjunction
with Off Topic references, or negative seeds, and assign a probability score to each of the
remaining studies as likely to be On Topic.
DoCTER also employs machine learning, which uses a training data set of studies identified as
both On and Off Topic, to identify studies that are most likely to be On Topic. This data set can
be identified prior to conducting prioritization in traditional machine learning or can be
conducted as part of the prioritization process, as in active machine learning.
Page 18 of 94
-------
K-Means
Algorithm
NMF
Algorithm
> » H
¦hmooch
aeeeoo
¦COO^O
looooe
moocm
Q Algorithm/number of
clusters combination
0 Cluster identified by
algorithm
# Tracer study (identified
as relevant during
Round 1 screening)
# Studies to be
prioritized
O Prioritized clusters for
each analysis (have up
to 75% of tracers)
10 20 30
clusters clusters clusters
Figure A-2. Ensemble text analytics method for prioritizing studies for screening.
Studies were also prioritized independently using SWIFT-Review. The same training data of On
Topic and Off Topic studies used in DoCTER were also used for prioritization in SWIFT-Review,
Using the training set, SWIFT-Review builds a statistical log-linear model that is used to
estimate the probability that an unlabeled document is relevant (Howard et al.. 2016).
The overall correlation between DoCTER and SWIFT-Review scoring and percentile rank was
very high and any reference that was flagged as high priority by either DoCTER or SWIFT-Review
was loaded into DRAGON for title abstract screening.
After full-text screening was complete, EPA prioritized the following studies with the following
criteria;
- Sample size of >10
- Study published after 2000
- Quantitative data was available in a table, rather than graph or chart.
Using these criteria, approximately 150 studies were not prioritized for data extraction and data
evaluation. Due to the large number of studies, it is likely the overall magnitude and trends of
reported exposure are well represented by the studies that were evaluated and extracted.
Any reference that was flagged as high priority by either DoCTER or SWIFT was loaded into
DRAGON for title abstract screening.
move®
eooee
eooeo
Page 19 of 94
-------
A.3 PECO Statement
PECO statements were written after full-text screening and informed how articles were
identified for inclusion in the exposure characterization.
Chemical
DecaBDE
PECO Element
Evidence
Population
Human: Children; infants; pregnant women; lactating women; women of childbearing
age; general population; consumers and bystanders in residential settings; workers and
occupational non-users; near-facility populations (including industrial and commercial
facilities manufacturing, processing, or using DecaBDE); populations exposed from
transfer from workplaces through take home exposures; populations in co-located
residences or businesses. No chemical-specific exclusions are suggested at present.
Ecological: Aauatic organisms (edible and nonedible fish, aauatic invertebrates
(daphnia), amphibians); terrestrial organisms (plants, soil invertebrates (worms), birds,
mammals). No chemical specific exclusions are suggested at present.
Exposure
Expected Exposure Sources, Pathways, Routes
Source: Indoor sources/materials that are abraded during use or have high potential for
direct contact; industrial activities (manufacturing, processing, recycling, treatment,
disposal of products); commercial and consumer uses of consumer products containing
decaBDE and associated releases to air, dust, water, or wastes (wastewater/liquid
wastes, solid wastes).
Pathwav: dust; contact with products; indoor air; food (breastmilk. fish. meat. eggs,
dairy); waste streams (landfills, biosolids); outdoor air (fugitive/stack emissions);
soil/sediment contact.
Routes: inhalation (indoor air and dust); oral (dietarv ingestion of breastmilk. food,
incidental ingestion of contaminated soil and dust); mouthing of consumer articles;
dermal (contact with dust, soil, consumer products containing DecaBDE); hand-to-mouth
contact, ingestion of suspended particles.
Comparator
(Scenario)
Human: Populations in alternative geographic regions and differing age groups.
Populations at different distances from industrial and recycling sites. Populations
occupationally exposed. Populations with alternative diets.
Ecological: Receptors in alternative geographical locations. Receptors with differing
levels of proximity to sources and releases.
Outcomes for
Exposure
Concentration or
Dose
Human: Acute, subchronic. and/or chronic external dose estimates (mg/kg/dav); acute,
subchronic, and/or chronic internal dose based on biomonitoring and reverse dosimetry
(mg/kg/day); acute, subchronic, and/or chronic air, soil, dust, water and biomonitoring
concentration estimates (mg/m3 or mg/L).
Ecological: A wide range of ecological receptors will be considered using surface water,
sediment, soil, and air concentrations. Targeted use of wildlife biomonitoring data will
also be explored.
Page 20 of 94
-------
A.4 PRISMA Diagram
The PRISMA Diagram for DecaBDE, including literature counts from search, screening and
included phases from all sources, is presented in Figure A-3. A subset of studies that passed the
screening phase were not extracted or evaluated due to the ready availability of the full text
and supplemental information. Due to time constraints, studies that did not include data in text
or tables, and studies that had fewer than 10 observations were not extracted or evaluated.
DECABDE
n
Data sources identified
through open literature,
backward searching, and
public comments n = 3,640
Data sources identified
through gray literature
n = 601
~
On-topic after title-
abstract screen n= 2,383
Data sources identified
through open lit from
similar chemicals
n = 7,388
On-topic after full-text
screen n= 1,740
On-topic after combined
title-abstract—full-text
screen n= 121
On-topic after machine
learning n= 512
On-topic after full-text
screen n= 374
Total On-topic
Core n= 1,705
Total On-topic
Supplemental n= 1,064
Total on
topic
= 2,235
Total Studies that were able to
be extracted n= 525
Total Studies that were
extracted and passed
evaluation criteria n= 478
Total
included
= 478
Figure A-3. PRISMA Diagram for DecaBDE
A.5 Data Evaluation Criteria
Core exposure data includes the following exposure data types:
Total
Searched =
11,629
Did not meet
evaluation
criteria screen
n = 246
Not on Topic-
Did not meet
full text tag
criteria
n = 9,394
Excluded -
Were not able
to be
extracted n =
424
Excluded - Did
not meet full
evaluation
criteria n = 47
- Environmental monitoring
- Biomonitoring
- Database Sources
- Completed Assessments
- Modeling
Page 21 of 94
-------
Assessors evaluated the extracted core exposure data for evaluation criteria specific to the data
type. The data evaluation criteria are included in (U.S. EPA. 2018).
A.6 Data Extraction Fields
Core exposure data, including monitoring data and modeled estimates of concentration or
dose, was extracted in DRAGON. The data extraction fields are included in Appendix I.
Page 22 of 94
-------
Appendix B. Supplemental Document for Hexachlorobutadiene (HCBD)
Literature Search Strategy
This document describes the literature search strategy to support the exposure assessments for
five persistent, bioaccumulative, and toxic (PBT) chemicals. The intent of the search is to assess
the likely exposure of the general population, consumers, occupational populations, potentially
exposed or susceptible subpopulations, and the environment to the conditions of use of PBT
chemicals based on the criteria outlined in the Toxic Substances Control Act (TSCA) section 6(h)
(OLRC, 2016). The conditions of use are defined as the circumstances under which a chemical
substance is intended, known or reasonably foreseen to be manufactured, processed,
distributed in commerce, used or disposed of.
Data sources in the peer-reviewed (open) and gray literature were considered as shown in
Figure B-l. In addition to the primary searches of the peer-reviewed literature in Web of
Science, PubMed, and Toxline, there were additional supplemental searches that were used to
complement and/or evaluate the primary peer-reviewed search strategy. These were:
backward searches of frequently used sources3, a Google Scholar search of the top 100 results
by chemical, and public comments and associated references cited in those comments
submitted to the dockets by mid-January 2018.
An additional search of the gray literature was conducted as described in the Gray Literature
Search Strategy section and was based off the protocol developed for the Systematic Review of
the "First 10" chemicals under TSCA.
The results of the literature searches were compiled into Endnote libraries (database searches)
and Excel spreadsheets (gray literature).
B.l.l. Database (Peer-reviewed) Search Strategies
The literature searches for the five PBT chemicals were designed to be as broad as possible,
searching only for the chemical name and synonyms, but not including any limiters such as
terms describing expected uses or dates. For HCBD, no chemical category name was included in
the search. The search strategy for HCBD is presented in Table B-l.
3 Frequently used sources are sources expected to be of high quality, such as assessments conducted by other
government agencies.
Page 23 of 94
-------
Peer Reviewed
Database Search
• Search peer
reviewed databases:
WoS, PubMed,
Toxlne (except
TSCATS) and
comipile in Endnote
at
Backwards Search
• Conduct
backward
searches from
frequently used
sources and
com pile in
Endnote libraries
i
Generate Master Libraries
• Remove duplicates
Google Scholar Search (100 hits/chem)
Rem ove du plicates ca pt u re d previously
• Evaluate search strategy
ir
Supplemental Public Comments Search
Search docket for public comments and
references cited therein
Add to HERO by docket #
\7
Gray Literature Search
Step 1: Conduct automated
search of approved websites
Step2: Conduct manual
search of approved websites
(except TSCATS)
Step 3: Compile results in
Excel spreadsheets with mini-
citations
Step 4: Remove dupficates
from gray results
Step 5: Develop full citations
for "on topics"
< 7
Submit Citations to HERO for HEROIDs & Addition to SR Database
Figure B-l. Literature Search Strategy Workflow
Table B-l. HCBD Open Literature Search Strategy
Date of Search: December 15, 2017
Database
Search Strategy
PubMed
("l,l,2,3,4,4-Hexachloro-l,3-butadiene"[tiab] OR "l,3-Hexachlorobutadiene"[tiab] OR "Hexachloro-
l,3-butadiene"[tiab] OR "Hexachlorobuta-l,3-diene"[tiab] OR 87-68-3[rn] OR Dolen-pur[tiab] OR
HCBD[tiab] OR Hexachlorobutadiene[tiab] OR Hexachlorobutadiene[nm] OR
Perchlorobutadiene[tiab])
AND (English[lang])
Web of
Science
("1,l,2,3,4,4-Hexachloro-l,3-butadien" OR "l,l,2,3,4,4-Hexachlorobuta-l,3-diene" OR "1,3-
Butadiene, 1,1,2,3,4,4-hexachloro-" OR "1,3-Butadiene, hexachloro-" OR "BUTADIENE,
HEXACHLORO-" OR "Hexachior-l,3-butadien" OR "Hexachlorbuta-l,3-dien" OR "Hexacloro-1,3-
butadieno" OR "hexaclorobuta-l,3-dieno" OR "Perchloro-l,3-butadiene" OR "1,1,2,3,4,4-
Hexachloro-l,3-butadiene" OR "1,3-Hexachlorobutadierie" OR "Hexachloro-1,3-butadierie" OR
"Hexachlorobuta-l,3-diene" OR 87-68-3 OR Dolen-pur OR HCBD OR Hexachlorobutadiene OR
Perchlorobutadierie)
AND English
Toxline
87-68-3
Include Synonyms
Exclude PubMed
Records from TSCATS and NIH Reporter Database removed in EndNote
B.1.2. Gray Literature Search Strategies
The five PBT chemicals searched were targeted to relevant sources and the approach was
adapted from the first 10 chemicals to optimize efficiency by eliminating redundancy. Gray
literature screening criteria excluded peer-reviewed journal articles that were expected to be
caught in the database searches. Mini citations, containing author, title, year, were generated
Page 24 of 94
-------
as a preliminary step to aid in identification and removal of duplicate records prior to tagging.
Automated searches via the Google search API were employed where possible in favor of
manual search sources. A summary of sources and search result counts after the removal of
duplicates is presented in Table B-2.AII results were reviewed from each source. The search
strings used for manual and automated searches are found in Table B-3.
EPA is aware of information submitted by companies as part of TSCA requirements under
sections 4, 8(d), 8(e) or as part of an FYI ("TSCATS Submissions data"). This information was not
considered as part of the literature search and screening strategy. EPA plans to consider this
information in the future.
Public comments submitted to the Docket (by Docket Number) were captured and HERO
records were created including the title, author and docket number. The results were then
compared to those of other searches to determine whether references cited in those public
comments were already identified by other searches or need to be included. PDFs of the
individual comments were not captured; instead a special "Public Comment" tag in HERO which
specifies the corresponding round of public comments was used. Detailed results of the Public
Comments submitted with the number of cited references for HCBD is shown in Table B-4.
Page 25 of 94
-------
Table B-2. Summary of Gray Literature Sources and Search Results for Automated and Manual Searches for HCBD
Source
ID1
Source Category
Website
Description
Search type
Search Result
Counts2
6000
US States
Government
Resources
States website custom search engine,
see Summary of State Sources tab
Custom search engine using States sites
Automated
97
1000
US EPA Resources
epa.gov
US Environmental Protection Agency
Automated
283
1150
US EPA Resources
http://aqsdrl.epa.gov/aqsweb/aqstmp/
airdata/download_files.html#Annual
Office of Air: AQS
Manual
1
1101
US EPA Resources
https://chemview.epa.gov/chemview
ChemView (CDR/IUR)
Manual
1
1083
US EPA Resources
https://actor.epa.gov/cpcat/faces/searc
h.xhtml
CPDat
Manual
1
1154
US EPA Resources
https://comptox.epa.gov/dashboard/
Chemistry Dashboard
Manual
1
1148
US EPA Resources
https://iaspub.epa.gov/oppthpv/existch
em_hpv_prioritizations. report
EPA HPVIS
Manual
0
1001
US EPA Resources
https://www.epa.gov/ground-water-
and-drinking-water/table-regulated-
drinking-water-contaminants
Office of Water: EPA Clean Water Act
Manual
0
1008
US EPA Resources
https://www.waterqualitydata.us/portal
/
Office of Water: STORET and WQX
Manual
1
1155
US EPA Resources
https://www.epa.gov/assessing-and-
managing-chemicals-under-
tsca/persistent-bioaccumulative-and-
toxic-pbt-chemicals-under
TSCA PBT Use Documents
Manual
0
2150
Other US Agency
Resources
cdc.gov
Centers for Disease Control (includes
NIOSH and ATSDR)
Automated
63
2511
Other US Agency
Resources
energy.gov
Department of Energy
Automated
108
2300
Other US Agency
Resources
fda.gov
US Food and Drug Administration
Automated
14
2050
Other US Agency
Resources
niehs.nih.gov
NIH National Institute of Environmental
Health and Safety
Automated
17
2400
Other US Agency
Resources
osha.gov
OSHA Occupational Safety and Health
Administration
Automated
6
Page 26 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search Result
Counts2
2521
Other US Agency
Resources
pnnl.gov
Pacific Northwest National Laboratory
Automated
11
2509
Other US Agency
Resources
usgs.gov
US Geological Survey
Automated
63
2027
Other US Agency
Resources
https://ntp.niehs.nih.gov/pubhealth/roc
/index-l.html#C
NIH Report on Carcinogens
Manual
0
2414
Other US Agency
Resources
https://www.osha.gov/opengov/healths
amples.html
OSHA Chemical Exposure Health Data
Manual (inclusive of
all results; not
limited to first 100)
1
2123
Other US Agency
Resources
https://www2a.cdc.gov/hhe/search.asp
CDC NIOSH Health Hazard Evaluations
Manual and
Automated
(inclusive of all
results; not limited
to first 100)
0
2104
Other US Agency
Resources
www.atsdr.cdc.gov/hac/pha/
CDC ATSDR Health Hazard Consultations
Manual and
Automated
(inclusive of all
results; not limited
to first 100)
51
3160
Other Resources
oecd.org
The Organisation for Economic Co-
operation and Development (OECD)
Automated
21
5000
Other Resources
sustainableproduction.org
Lowell Center for Sustainable
Production
Automated
2
5020
Other Resources
lnfohouse.p2ric.org
Pollution Prevention Infohouse
Automated
50
3600
Other Resources
http://www.spin2000.net/spinmyphp/
Substances in Preparations in Nordic
Countries (SPIN) Database
Manual
0
5027
Other Resources
Kirk Othmer Encyclopedia
Book
Manual
0
5028
Other Resources
Ashford's Dictionary of Industrial
Chemicals, 2001
Book
Manual
0
5029
Other Resources
Hawley's Chemical Dictionary, 2016
Book
Manual
1
3425
International
Resources
carexcanada.ca
Carex Canada
Automated
0
Page 27 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search Result
Counts2
3520
International
Resources
env.go.jp
Government of Japan: Ministry of the
Environment
Automated
8
3050
International
Resources
europa.eu
European Union
Automated
162
3057
International
Resources
https://echa.europa.eu/information-on-
chemicals/registered-substances
ECHA
Manual
0
3100
International
Resources
iarc.fr
International Agency for Research on
Cancer
Automated
52
3350
International
Resources
nicnas.gov.au
Australian Government: Department of
Health, National Industrial Chemicals;
NICNAS
Automated
2
3250
International
Resources
who.int
World Health Organization
Automated
36
3421
International
Resources
https://www.canada.ca/en/health-
canada/services/chemical-
substances/fact-sheets/chemicals-
glance.html#interest
Canada Chemicals Portal
Manual
1
3450
International
Resources
http://limitvalue.ifa.dguv.de/
GESTIS Database
Manual
10
Total Unique (Duplicates Removed)
1064
^'Source ID" refers to an internal ID assigned to each source for trac
-------
Table B-3. Gray Literature Search Strings
Chemical
Manual Search Terms
Google Search Terms (up to 128
characters)
Hexachlorobutadiene (HCBD)
Search database by CAS or
chemical name, or select
from a list on the website
"87-68-3" OR "Hexachlorobutadiene" OR
"HCBD" OR "Perchlorobutadiene" OR
"Hexachloro-l,3-butadiene"
Table B-4. Detailed Results from Public Comments Backwards Search for HCBD
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Christina Franz, Senior
Director, Regulatory & Technical Affairs,
American Chemistry Council (ACC)
American Chemistry
Council (ACC)
EPA-HQ-OPPT-
2016-0738-0007
10
Comment submitted by Sarah E. Amick, Vice
President EHS&S and Senior Counsel, Rubber
Manufacturers Association (RMA)
Rubber Manufacturers
Association (RMA)
EPA-HQ-OPPT-
2016-0738-0003
0
Comment submitted by Veena Singla, PhD,
Associate Director, Science and Policy,
Program on Reproductive Health and the
Environment, University of California, San
Francisco (UCSF) et al.
UCSF Program on
Reproductive Health and
the Environment,
academics, scientists and
clinicians
EPA-HQ-OPPT-
2016-0738-0008
45
Comment submitted by Robert Stockman,
Senior Attorney on behalf of Environmental
Defense Fund (EDF)
Environmental Defense
Fund (EDF)
EPA-HQ-OPPT-
2016-0738-0011
8
Comment submitted by Jyotsna S. Jagai, PhD,
Research Assistant Professor, University of
Illinois, Chicago Chair, Environment Section,
American Public Health Association
EPA-HQ-OPPT-
2016-0738-0016
6
Comment submitted by Elizabeth Hitchcock,
Acting Director, Safer Chemicals Healthy
Families (SCHF) et al.
Safer Chemicals Healthy
Families (SCHF), Alaska
Community Action on
Toxics, Center for
Environmental Health,
Earthjustice,
Environmental Health
Strategy Center, Natural
Resources Defense
Council, Toxic-Free Future
EPA-HQ-OPPT-
2016-0738-0012
27
Comment submitted by Ken Zarker, Section
Manager, Hazardous Waste and Toxics
Reduction Program, Washington State
Department of Ecology
Washington State
Department of Ecology
EPA-HQ-OPPT-
2016-0738-0009
114
Comment submitted by Dianne C. Barton,
Chair, National Tribal Toxics Council (NTTC)
National Tribal Toxics
Council (NTTC)
EPA-HQ-OPPT-
2016-0738-0013
18
TOTAL
8
228
Total Unique (Duplicates Removed)
218
Page 29 of 94
-------
B.1.3. Supplemental Search Strategy
Backward Search
To both supplement and test the database and gray literature searches, backward searches of
frequently used sources were conducted. These sources consist of previous risk assessments,
systematic reviews, and other assessments, generally conducted by EPA or other government
agencies of the chemicals of interest and presented in Table B-6. The references that are cited
within sections deemed relevant to this assessment were gathered into Endnote libraries for
title abstract review.
Google Scholar Search
To further supplement and test the database searches, a Google Scholar search was conducted
for each of the five PBT chemicals. The top 100 results returned by Google Scholar for each
chemical were exported into Endnote libraries. These results were compared to the references
identified in the database, backward, and gray literature searches to identify references not
found by the previous searches. While Google Scholar results are expected to be primarily peer-
reviewed rather than gray literature, the results were still compared to all searches.
B.1.4. Literature Search Results
The literature searches were conducted, and for PubMed, Web of Science, ToxLine, Backwards
searches, and Google Scholar searches, the results were imported into one Endnote library per
chemical. After the results were combined, duplicates were removed and TSCATS/NIH Reporter
data, a subset of ToxLine, were moved into a separate folder. The resulting counts are
presented in Table B-5. Detailed results for the HCBD backwards search are presented in
Table B-6.
Table B-5. Count of Peer-reviewed Literature Search Results by Search Type for HCBD
Chemical
PubMed
WoS
ToxLine
TSCATS/ NIH
Reporter
Backwards
Google
Scholar
HCBD
246
189
511
94
53
17
Table B-6. Detailed Results of Backwards Search of Frequently Used Sources for HCBD
HERO ID
Document title
Reference count
1464554
PRIORITY SUBSTANCES LIST ASSESSMENT REPORT
Canadian Environmental
Protection Act, 1999
Hexachlorobutadiene
54
4182482
Euro Chlor Risk Assessment for the Marine Environment
OSPARCOM Region - North Sea
19
TOTAL
73
Total Unique (Duplicates Removed)
65
EndNote Library: Total Unique (Duplicates Removed)
53
Page 30 of 94
-------
B.2 Literature Screening Strategy
B.2.1. Development of the Literature Screening Approach
The steps involved in developing the title abstract screening approach are:
1. Define inclusion/exclusion criteria.
2. Conduct the pilot using 10 randomly selected studies for each chemical from both the
peer-reviewed and gray literature that are screened by EPA experts.
3. Use the results of the pilot to refine inclusion/exclusion criteria.
4. Use the refined pilot to train screeners in applying the tags.
The overall workflow of the systematic review process including the literature screening is
presented in Appendix F.
In these assessments, the results of the title/abstract literature screening will be used to
develop the PECO statement. The PECO statement is included in Appendix 0. Four tags were
used at the title-abstract phase: Peer On Topic, Peer Off Topic, Gray On Topic, and Gray Off
Topic and recorded on the HERO project pages. Title abstract screening was conducted in
DRAGON4. A screenshot of the DRAGON form and all DRAGON tags is presented in Appendix H.
The inclusion/exclusion criteria for title/abstract and full text screening are included in
Appendix G. During full text screening, studies were also screened for "Red Flag Criteria," which
represent the "Unacceptable" criteria from the Data Evaluation criteria (U.S. EPA. 2018).
B.2.2. Literature Screening Pilot
A pilot with 100 results representative of the five chemicals and the peer, backwards, and gray
literature search results was developed by EPA. Two exposure experts scored the pilot, and met
with EPA to refine the criteria and application of the criteria.
Before screening, all screeners were required to meet a 90% accuracy in tagging the pilot
screening studies. Screeners who met this level of proficiency were able to begin title abstract
screening. Screeners who do not meet this level of proficiency, continued to train, using the
studies screened by screeners who had passed the pilot as additional training studies.
Documentation of all pilot tagging results was maintained in Excel spreadsheets for both the
peer-reviewed and gray literature.
B.2.3. Literature Screening
Title abstract screening of the peer-reviewed and gray literature occurred in DRAGON, an
online tool for systematic review. Results of the HCBD search were manually screened with one
screener who has been trained via the pilot process. Additionally, a subject matter expert
4 DRAGON is an online tool for systematic review developed by ICF that stores qualitative and quantitative data
from literature to help scientists implement the elements of systematic review, including problem formulation,
literature screening, risk of bias evaluation, and data integration.
Page 31 of 94
-------
reviewed 10% of the references deemed to be On Topic and Off Topic as a quality assurance
check to ensure that they have been categorized appropriately.
For gray literature, title/abstract and full text screening was done simultaneously, and tags for
screening are included in Appendix H. For peer-reviewed literature, title/abstract and full text
screening were done separately, and tags for each stage are included in Appendix H.2.
B.3 PECO Statement
PECO statements were written after full-text screening and informed how articles were
identified for inclusion in the exposure characterization.
Chemical
HCBD
PECO Element
Evidence
Population
Human: Women of child-bearing age (WOCBA) with occupational exposure; WOCBA,
children, infants living at or near hazardous waste, industrial or chemical waste disposal
sites, or who consume contaminated fish. WOCBA and children who use consumer
products containing HCBD. No chemical-specific exclusions are suggested at present.
Ecological: Aauatic organisms (edible and nonedible fish, aauatic invertebrates
(daphnia), amphibians); terrestrial organisms (plants, soil invertebrates (worms), birds,
mammals). No chemical specific exclusions are suggested at present.
Exposure
Expected Exposure Sources, Pathways, Routes
Source Hazardous waste sites, contaminated industrial sites, waste management sites,
and associated releases from such sites to air, water, or wastes (wastewater/liquid
wastes, solid wastes). Contact with consumer products containing HCBD. Consumption
of contaminated fish and shellfish products.
Pathwav: Inhalation of vapors in indoor and outdoor air; contact with consumer
products; ingestion of contaminated soil, water, fish, shellfish; waste streams (landfills,
biosolids); outdoor air (fugitive/stack emissions); soil/sediment contact.
Routes: Inhalation (outdoor and indoor air and dust); oral (dietarv ingestion of
breastmilk, food, incidental ingestion of contaminated soil and dust); mouthing of
consumer articles; hand-to-mouth contact.
Comparator
(Scenario)
Human: Populations in alternative geographic regions and differing age groups.
Populations at different distances from industrial and recycling sites. Populations
occupationally exposed. Populations with alternative diets.
Ecological: Receptors in alternative geographical locations. Receptors with differing
levels of proximity to sources and releases.
Outcomes for
Exposure
Concentration or
Dose
Human: Acute, subchronic. and/or chronic external dose estimates (mg/kg/dav); acute,
subchronic, and/or chronic internal dose based on biomonitoring and reverse
dosimetry (mg/kg/day); acute, subchronic, and/or chronic air, soil, dust, water and
biomonitoring concentration estimates (mg/m3 or mg/L).
Ecological: A wide range of ecological receptors will be considered using surface water,
sediment, soil, and air concentrations. Targeted use of wildlife biomonitoring data will
also be explored.
Page 32 of 94
-------
B.4 PRISMA Diagram
The PRISMA Diagram for HCBD, including literature counts from search, screening and included
phases from all sources, is presented in Figure B-2. A subset of studies that passed the
screening phase were not extracted or evaluated due to the ready availability of the full text
and supplemental information. Due to time constraints, studies that did not include data in text
or tables, and studies that had fewer than 10 observations were not extracted or evaluated.
HCBD
Data sources identified
through open literature,
backward searching, and
public comments n = 1,222
Data sources identified
through gray literature
n = 1,064
~W~
On-topic after title-
abstract screen n= 541
T
Data sources identified
through open lit from
similar chemicals n = n/a
On-topic after full-text
screen n= 165
On-topic after combined
title-abstract—full-text
screen n= 272
On-topic after machine
learning n= n/a
On-topic after full-text
screen n= n/a
Total On-topic
Core n= 396
Total On-topic
Supplemental n= 201
Total on
topic
= 437
Total
Searched ¦
2,286
Did not meet
evaluation
criteria screen
n = 119
Not on Topic-
Did not meet
full text tag
criteria
n = 1,849
Total Studies that were able to
be extracted n= 64
Total
included
= 58
Total Studies that were
extracted and passed
evaluation criteria n= 58
Excluded-
Were not able
to be
extracted n
=177
Excluded - Did
not meet full
evaluation
criteria n = 6
Figure B-2. PRISMA Diagram for HCBD
B.5 Data Evaluation Criteria
Core exposure data includes the following exposure data types:
- Environmental monitoring
- Biomonitoring
- Database Sources
- Completed Assessments
- Modeling
Page 33 of 94
-------
Assessors evaluated the extracted core exposure data for evaluation criteria specific to the data
type. The data evaluation criteria are included in (U.S. EPA. 2018).
B.6 Data Extraction Fields
Core exposure data, including monitoring data and modeled estimates of concentration or
dose, was extracted in DRAGON. The data extraction fields are included in Appendix I.
Page 34 of 94
-------
Appendix C. Supplemental Document for Phenol, isopropylated, phosphate (3:1)
(ITPP)
C.l Literature Search Strategy
This document describes the literature search strategy to support the exposure assessments for
five persistent, bioaccumulative, and toxic (PBT) chemicals. The intent of the search is to assess
the likely exposure of the general population, consumers, occupational populations, potentially
exposed or susceptible subpopulations, and the environment to the conditions of use of PBT
chemicals based on the criteria outlined in the Toxic Substances Control Act (TSCA) section 6(h)
(OLRC, 2016). The conditions of use are defined as the circumstances under which a chemical
substance is intended, known or reasonably foreseen to be manufactured, processed,
distributed in commerce, used or disposed of.
Data sources in the peer-reviewed (open) and gray literature were considered as shown in
Figure C-l. In addition to the primary searches of the peer-reviewed literature in Web of
Science, PubMed, and Toxline, there were additional supplemental searches that were used to
complement and/or evaluate the primary peer-reviewed search strategy. These were:
backward searches of frequently used sources5, a Google Scholar search of the top 100 results
by chemical, and public comments and associated references cited in those comments
submitted to the dockets by mid-January 2018.
An additional search of the gray literature was conducted as described in the Gray Literature
Search Strategy section and was based off the protocol developed for the Systematic Review of
the "First 10" chemicals under TSCA.
The results of the literature searches were compiled into Endnote libraries (database searches)
and Excel spreadsheets (gray literature).
C.l.l. Database (Peer-reviewed) Search Strategies
The literature searches for the five PBT chemicals were designed to be as broad as possible,
searching only for the chemical name and synonyms, but not including any limiters such as
terms describing expected uses or dates. For ITPP, no chemical category name was included in
the search, but a series of similar chemicals were searched for potential information.
The search strategies for ITPP are presented in Table C-l and Table C-2.
5 Frequently used sources are sources expected to be of high quality, such as assessments conducted by other
government agencies.
Page 35 of 94
-------
Peer Reviewed
Database Search
• Search peer
reviewed databases:
WoS, PubMed,
Toxlne (except
TSCATS) and
comipile in Endnote
at
Backwards Search
• Conduct
backward
searches from
frequently used
sources and
com pile in
Endnote libraries
i
Generate Master Libraries
• Remove duplicates
Google Scholar Search (100 hits/chem)
Rem ove du plicates ca pt u re d previously
• Evaluate search strategy
ir
Supplemental Public Comments Search
Search docket for public comments and
references cited therein
Add to HERO by docket #
\7
Gray Literature Search
Step 1: Conduct automated
search of approved websites
Step2: Conduct manual
search of approved websites
(except TSCATS)
Step 3: Compile results in
Excel spreadsheets with mini-
citations
Step 4: Remove dupficates
from gray results
Step 5: Develop full citations
for "on topics"
< 7
Submit Citations to HERO for HEROIDs & Addition to SR Database
Figure C-l. Literature Search Strategy Workflow
Table C-l. ITPP Open Literature Search Strategy
Date of Searc
r December 15, 2017
Database
Search Strategy
PubMed
("isopropylated phenyl phosphates"[tiab] OR OS-70[tiab])
AND (English[lang])
Web of
Science
("Duran MP280(sup R)" OR "fenol, isopropilado, fosfato (3:1)" OR "Isopropylated phenol
phosphate (3:1)" OR "Isopropylated phenol, phosphate" OR "Phenol Isopropylated phosphate"
OR "Phenol isopropyle, phosphate (3:1)" OR "Phenol, isopropylated, phosphate (3:1)" OR
"PHENOL, ISOPROPYLATED, PHOSPHATE" OR "Phenol, isopropyliert, Phosphate (3:1)" OR
"Triphenyl phosphates isopropylated" OR 68937-41-7 OR Durad-100 OR "isopropylated phenyl
phosphates" OR OS-70)
AND English
Toxline
68937-41-7
Include Synonyms
Exclude PubMed
Records from TSCATS and NIH Reporter Database removed in EndNote
Page 36 of 94
-------
Table C-2. PIPS Supplemental Literature Search Strategy
Date of Searc
r April 5, 2018
Database
Search Strategy
PubMed
("115-86-6"[rn] OR "Phenyl phosphate"[tiab] OR "Triphenyl phosphate"[tiab] OR "Triphenyl
phosphate"[nm] OR "Triphenylphosphate"[tiab])
AND (English[lang])
Web of Science
("(l-Methylethyl)phenol phosphate (3:1)" OR "101299-37-0" OR "115-86-6" OR "2-(l-
Methylethyl)phenyl diphenyl phosphate" OR "2502-15-0" OR "26967-76-0" OR "28108-99-8" OR
"28109-00-4" OR "2-lsopropylphenyl diphenyl phosphate" OR "3,4-Di(propan-2-yl)phenyl diphenyl
phosphate" OR "3,4-Diisopropylphenyl diphenyl phosphate" OR "4-isopropylphenyl diphenyl
phosphate" OR "55864-04-5" OR "64532-94-1" OR "66797-44-2" OR "68155-51-1" OR "69500-29-4"
OR "72668-27-0" OR "96300-97-9" OR "Bis(2-isopropylphenyl) phenyl phosphate" OR
"Bis(isopropylphenyl) phenyl phosphate" OR "Bis(isopropylphenyl)phenylphosphat" OR "Bis(o-
isopropylphenyl) phenyl phosphate" OR "Celluflex TPP" OR "Dl(2-
ISOPROPYLPHENYL)PHENYLPHOSPHATE" OR "Di(isopropylphenyl) phenyl phosphate" OR "Di-
isopropyltriphenyl phosphate" OR "Diphenyl (2-propan-2-ylphenyl) phosphate" OR "Diphenyl 2-
(propan-2-yl)phenyl phosphate" OR "Diphenyl 4-(propan-2-yl)phenyl phosphate" OR "Diphenyl o-
isopropylphenylphenyl phosphate" OR "Diphenyl p-isopropylphenyl phosphate" OR "Disflamoll TP"
OR "fosfato de fenilo y bis(isopropilfenilo)" OR "fosfato de trifenilo" OR "Isopropyl phenyl diphenyl
phosphate" OR "Isopropylphenyl diphenyl phosphate" OR "Kronitex 100" OR "Kronitex 200" OR "o-
Isopropylphenyl diphenyl phosphate mixt. with triphenyl phosphate" OR "o-lsopropylphenyl diphenyl
phosphate" OR "p-Cumenyl phenyl phosphate (7CI)" OR "p-Cumenyl phosphate ((C9H110)3P0)" OR
"Phenol, (1-methylethyl)-, phosphate (3:1" OR "Phenol, (1-methylethyl)-, phosphate (3:1)" OR
"Phenol, 3-(l-methylethyl)-, phosphate (3:1)" OR "Phenol, 4-(l-methylethyl)-, phosphate (3:1)" OR
"Phenyl bis[2-(propan-2-yl)phenyl] phosphate" OR "Phenyl di(isopropylphenyl) phosphate" OR
"Phenyl phosphate ((PhO)3PO)" OR "Phenyl phosphate" OR "Phoscon FR 903N" OR "Phosflex 31P" OR
"Phosflex 41P" OR "Phosflex TPP" OR "phosphate de bis(isopropylphenyle) et de phenyle" OR
"Phosphate de triphenyle" OR "Phosphate, tris(isopropylphenyl)" OR "Phosphoric acid, (1-
methylethyl)phenyl diphenyl ester (9CI)" OR "Phosphoric acid, (l-methylethyl)phenyl diphenyl ester"
OR "Phosphoric acid, 2-(l-methylethyl)phenyl diphenyl ester" OR "Phosphoric acid, 2-(l-
methylethyl)phenyl diphenyl ester, mixt. with triphenyl phosphate" OR "Phosphoric acid, 3,4-bis(l-
methylethyl)phenyl diphenyl ester" OR "Phosphoric acid, 4-(l-methylethyl)phenyl diphenyl ester" OR
"Phosphoric acid, bis((l-methylethyl)phenyl) phenyl ester (9CI)" OR "Phosphoric acid, bis((l-
methylethyl)phenyl) phenyl ester" OR "Phosphoric acid, bis(2-(l-methylethyl)phenyl) phenyl ester"
OR "Phosphoric acid, bis[2-(l-methylethyl)phenyl] phenyl ester" OR "Phosphoric acid, bis[2-(l-
methylethyl)phenyl] phenyl ester" OR "Phosphoric acid, triphenyl ester" OR "p-lsopropylphenyl
diphenyl phosphate" OR "Reofos 95" OR "ReofosTPP" OR "Sumilizer TPP" OR "TP (VAN)" OR
"Tri(isopropylphenyl) phosphate" OR "Trifenylfosfat" OR "Triphenoxyphosphine oxide" OR "Triphenyl
phosphate" OR "Triphenylphosphat" OR "Triphenylphosphate" OR "Tris(3-isopropylphenyl)
phosphate" OR "Tris(4-isopropylphenyl) phosphate" OR "Tris(isopropylphenyl) phosphate" OR
"Tris(isopropylphenyl)phosphate" OR "Tris(isopropylphenyl)phosphates" OR "Tris(p-isopropylphenyl)
phosphate" OR "Tris(p-isopropylphenyl)phosphate" OR "Tris[4-(propan-2-yl)phenyl] phosphate" OR
"Wako TPP")
AND English
Toxline
("101299-37-0" OR "115-86-6" OR "2502-15-0" OR "26967-76-0" OR "28108-99-8" OR "28109-00-4"
OR "55864-04-5" OR "64532-94-1" OR "66797-44-2" OR "68155-51-1" OR "69500-29-4" OR "72668-
27-0" OR "96300-97-9")
Include Synonyms
Exclude PubMed Records
Page 37 of 94
-------
C.1.2. Gray Literature Search Strategies
The five PBT chemicals searched were targeted to relevant sources and the approach was
adapted from the first 10 chemicals to optimize efficiency by eliminating redundancy. Gray
literature screening criteria excluded peer-reviewed journal articles that were expected to be
caught in the database searches. Mini citations, containing author, title, year, were generated
as a preliminary step to aid in identification and removal of duplicate records prior to tagging.
Automated searches via the Google search API were employed where possible in favor of
manual search sources. A summary of sources and search result counts after the removal of
duplicates is presented in Table C-3. All results were reviewed from each source. The search
strings used for manual and automated searches are found in Table C-4.
EPA is aware of information submitted by companies as part of TSCA requirements under
sections 4, 8(d), 8(e) or as part of an FYI ("TSCATS Submissions data"). This information was not
considered as part of the literature search and screening strategy. EPA plans to consider this
information in the future.
Public comments submitted to the Docket (by Docket Number) were captured and HERO
records were created including the title, author and docket number. The results were then
compared to those of other searches to determine whether references cited in those public
comments were already identified by other searches or need to be included. PDFs of the
individual comments were not captured; instead a special "Public Comment" tag in HERO which
specifies the corresponding round of public comments was used. Detailed results of the Public
Comments submitted with the number of cited references for ITPP is shown in Table C-5.
Page 38 of 94
-------
Table C-3. Summary of Gray Literature Sources and Search Results for Automated and Manual Searches for ITPP
Source
ID1
Source Category
Website
Description
Search type
Search
Result
Counts2
6000
US States
Government
Resources
States website custom search engine, see
Summary of State Sources tab
Custom search engine using States
sites
Automated
6
1000
US EPA Resources
epa.gov
US Environmental Protection Agency
Automated
39
1150
US EPA Resources
http://aqsdrl.epa.gov/aqsweb/aqstmp/aird
ata/download_files.html#Annual
Office of Air: AQS
Manual
0
1101
US EPA Resources
https://chemview.epa.gov/chemview
ChemView (CDR/IUR)
Manual
6
1083
US EPA Resources
https://actor.epa.gov/cpcat/faces/search.xht
ml
CPDat
Manual
1
1154
US EPA Resources
https://comptox.epa.gov/dashboard/
Chemistry Dashboard
Manual
1
1148
US EPA Resources
https://iaspub.epa.gov/oppthpv/existchem_
hpv_prioritizations. report
EPA HPVIS
Manual
0
1001
US EPA Resources
https://www.epa.gov/ground-water-and-
drinking-water/table-regulated-drinking-
water-contaminants
Office of Water: EPA Clean Water Act
Manual
0
1008
US EPA Resources
https://www.waterqualitydata.us/portal/
Office of Water: STORET and WQX
Manual
0
1155
US EPA Resources
https://www.epa.gov/assessing-and-
managing-chemicals-under-tsca/persistent-
bioaccumulative-and-toxic-pbt-chemicals-
under
TSCA PBT Use Documents
Manual
1
2150
Other US Agency
Resources
cdc.gov
Centers for Disease Control (includes
NIOSH and ATSDR)
Automated
2
2511
Other US Agency
Resources
energy.gov
Department of Energy
Automated
0
2300
Other US Agency
Resources
fda.gov
US Food and Drug Administration
Automated
0
Page 39 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search
Result
Counts2
2050
Other US Agency
Resources
niehs.nih.gov
NIH National Institute of
Environmental Health and Safety
Automated
20
2400
Other US Agency
Resources
osha.gov
OSHA Occupational Safety and Health
Administration
Automated
1
2521
Other US Agency
Resources
pnnl.gov
Pacific Northwest National Laboratory
Automated
0
2509
Other US Agency
Resources
usgs.gov
US Geological Survey
Automated
3
2027
Other US Agency
Resources
https://ntp.niehs.nih.gov/pubhealth/roc/ind
ex-l.html#C
NIH Report on Carcinogens
Manual
0
2414
Other US Agency
Resources
https://www.osha.gov/opengov/healthsamp
les.html
OSHA Chemical Exposure Health Data
Manual
(inclusive of
all results;
not limited
to first 100)
0
2123
Other US Agency
Resources
https://www2a.cdc.gov/hhe/search.asp
CDC NIOSH Health Hazard Evaluations
Manual and
Automated
(inclusive of
all results;
not limited
to first 100)
0
2104
Other US Agency
Resources
www.atsdr.cdc.gov/hac/pha/
CDC ATSDR Health Hazard
Consultations
Manual and
Automated
(inclusive of
all results;
not limited
to first 100)
0
3160
Other Resources
oecd.org
The Organisation for Economic Co-
operation and Development (OECD)
Automated
3
5000
Other Resources
sustainableproduction.org
Lowell Center for Sustainable
Production
Automated
0
5020
Other Resources
lnfohouse.p2ric.org
Pollution Prevention Infohouse
Automated
0
Page 40 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search
Result
Counts2
3600
Other Resources
http://www.spin2000.net/spinmyphp/
Substances in Preparations in Nordic
Countries (SPIN) Database
Manual
1
5027
Other Resources
Kirk Othmer Encyclopedia
Book
Manual
1
5028
Other Resources
Ashford's Dictionary of Industrial Chemicals,
2001
Book
Manual
0
5029
Other Resources
Hawley's Chemical Dictionary, 2016
Book
Manual
0
3425
International
Resources
carexcanada.ca
Carex Canada
Automated
0
3520
International
Resources
env.go.jp
Government of Japan: Ministry of the
Environment
Automated
0
3050
International
Resources
europa.eu
European Union
Automated
32
3057
International
Resources
https://echa.europa.eu/information-on-
chemicals/registered-substances
ECHA
Manual
1
3100
International
Resources
iarc.fr
International Agency for Research on
Cancer
Automated
0
3350
International
Resources
nicnas.gov.au
Australian Government: Department
of Health, National Industrial
Chemicals; NICNAS
Automated
3
3250
International
Resources
who.int
World Health Organization
Automated
0
3421
International
Resources
https://www.canada.ca/en/health-
canada/services/chemical-substances/fact-
sheets/chemicals-glance.html#interest
Canada Chemicals Portal
Manual
0
3450
International
Resources
http://limitvalue.ifa.dguv.de/
GESTIS Database
Manual
0
Total Unique (Duplicates Removed)
121
^'Source ID" refers to an internal ID assigned to each source for tracking purposes.
2 Search result counts represent totals after removal of duplicate records.
Page 41 of 94
-------
Table C-4. Gray Literature Search Strings
Chemical
Manual Search Terms
Google Search Terms (up to 128 characters)
Phenol, isopropylated, phosphate (3:1)
Search database by CAS or chemical
name, or select from a list on the
website
"68937-41-7" OR "Phenol, isopropylated, phosphate
(3:1)" OR "isopropylated triphenyl phosphate"
Table C-5. Detailed Results of Public Comments Backwards Search for ITPP
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Derek D. Swick, PhD, Manager, Regulatory and
Scientific Affairs, American Petroleum Institute (API)
American Petroleum Institute
(API)
EPA-HQ-OPPT-2016-0730-
0008
1
Comment submitted by Christina Franz, Senior Director, Regulatory &
Technical Affairs, American Chemistry Council (ACC)
American Chemistry Council
(ACC)
EPA-HQ-OPPT-2016-0730-
0010
11
Comment submitted by David H. Quigley, Akin Gump, Strauss Hauer &
Feld LLP
Akin Gump, Strauss Hauer & Feld
LLP
EPA-HQ-OPPT-2016-0730-
0007
0
Comment submitted by Rick Brown, PhD, Global Product Stewardship
Manager, ExxonMobil Fuels & Lubricants Company
ExxonMobil Fuels & Lubricants
Company
EPA-HQ-OPPT-2016-0730-
0009
1
Comment submitted by David H. Quigley, Akin Gump, Strauss Hauer &
Feld LLP
Akin Gump, Strauss Hauer & Feld
LLP
EPA-HQ-OPPT-2016-0730-
0006
0
Comment submitted by Ryan J. Carra, Beveridge & Diamond PC
Beveridge & Diamond PC
EPA-HQ-OPPT-2016-0730-
0002
3
Anonymous public comment
Anonymous
EPA-HQ-OPPT-2016-0730-
0004
0
Comment submitted by Veena Singla, PhD, Associate Director, Science
and Policy, Program on Reproductive Health and the Environment,
University of California, San Francisco (UCSF) et al.
UCSF Program on Reproductive
Health and the Environment,
academics, scientists and
clinicians
EPA-HQ-OPPT-2016-0730-
0011
45
Comment submitted by Leslie Riegle, Director of Environmental Policy
Aerospace Industries Association (AIA)
Aerospace Industries Association
(AIA)
EPA-HQ-OPPT-2016-0730-
0012
0
Comment submitted by Dianne C. Barton, Chair, National Tribal Toxics
Council (NTTC)
National Tribal Toxics Council
(NTTC)
EPA-HQ-OPPT-2016-0730-
0015
18
Comment submitted by Robert Stockman, Senior Attorney,
Environmental Defense Fund (EDF)
Environmental Defense Fund
(EDF)
EPA-HQ-OPPT-2016-0730-
0014
8
Page 42 of 94
-------
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Levi Howell, Regulatory Affairs Specialist, ICL-IP
ICL-IP America Inc.
EPA-HQ-OPPT-2016-0730-
0
America Inc.
0013
Comment submitted by Jyotsna S. Jagai, Research Assistant Professor,
EPA-HQ-OPPT-2016-0730-
6
University of Illinois, Chicago Chair, Environment Section, American
0019
Public Health Association et al.
Comment submitted by Ken Zarker, Section Manager, Hazardous Waste
Washington State Department of
EPA-HQ-OPPT-2016-0730-
3
and Toxics Reduction Program, Washington State Department of
Ecology
0018
Ecology
Safer Chemicals Healthy Families
EPA-HQ-OPPT-2016-0730-
51
(SCHF), Alaska Community Action
0022
on Toxics, Center for
Comment submitted by Elizabeth Hitchcock, Acting Director, Safer
Environmental Health,
Chemicals Healthy Families (SCHF) et al.
Earthjustice, Environmental
Health Strategy Center, Natural
Resources Defense Council,
Toxic-Free Future
TOTAL
15
147
Total Unique (Duplicates Removed)
135
Page 43 of 94
-------
C.1.3. Supplemental Search Strategy
Backward Search
To both supplement and test the database and gray literature searches, backward searches of
frequently used sources were conducted. These sources consist of previous risk assessments,
systematic reviews, and other assessments, generally conducted by EPA or other government
agencies of the chemicals of interest and presented in Table C-7. The references that are cited
within sections deemed relevant to this assessment were gathered into Endnote libraries for
title abstract review.
Google Scholar Search
To further supplement and test the database searches, a Google Scholar search was conducted
for each of the five PBT chemicals. The top 100 results returned by Google Scholar for each
chemical were exported into Endnote libraries. These results were compared to the references
identified in the database, backward, and gray literature searches to identify references not
found by the previous searches. While Google Scholar results are expected to be primarily peer-
reviewed rather than gray literature, the results were still compared to all searches.
C.1.4. Literature Search Results
The literature searches were conducted, and for PubMed, Web of Science, ToxLine, Backwards
searches, and Google Scholar searches, the results were imported into one Endnote library per
chemical. After the results were combined, duplicates were removed and TSCATS/NIH Reporter
data, a subset of ToxLine, were moved into a separate folder. The resulting counts are
presented in Table C-6. Detailed results for the ITPP backwards search are presented in
Table C-7.
Table C-6. Count of Peer-reviewed Literature Search Results by Search Type for ITPP
Chemical
PubMed
WoS
ToxLine
TSCATS/ NIH
Reporter
Backwards
Google
Scholar
ITPP
4
43
1
27
129
100
Table C-7. Detailed Results of Backwards Search of Frequently Used Sources for ITPP
HEROID
Document title
Reference
Count
4182594
Environmental risk evaluation report:
Isopropylated triphenyl phosphate
23
4182605
Indoor emissions and fate of flame retardants: A modelling approach
106
TOTAL
129
Total Unique (Duplicates Removed)
129
EndNote Library: Total Unique (Duplicates Removed)
129
Page 44 of 94
-------
C.2 Literature Screening Strategy
C.2.1. Development of the Literature Screening Approach
The steps involved in developing the title abstract screening approach are:
1. Define inclusion/exclusion criteria.
2. Conduct the pilot using 10 randomly selected studies for each chemical from both the
peer-reviewed and gray literature that are screened by EPA experts.
3. Use the results of the pilot to refine inclusion/exclusion criteria.
4. Use the refined pilot to train screeners in applying the tags.
The overall workflow of the systematic review process including the literature screening is
presented in Appendix F.
In these assessments, the results of the title/abstract literature screening will be used to
develop the PECO statement. The PECO statement is included in Appendix 0. Four tags were
used at the title-abstract phase: Peer On Topic, Peer Off Topic, Gray On Topic, and Gray Off
Topic and recorded on the HERO project pages. Title abstract screening was conducted in
DRAGON6. A screenshot of the DRAGON form and all DRAGON tags is presented in Appendix H.
The inclusion/exclusion criteria for title/abstract and full text screening are included in
Appendix G. During full text screening, studies were also screened for "Red Flag Criteria," which
represent the "Unacceptable" criteria from the Data Evaluation criteria (U.S. EPA. 2018).
C.2.2. Literature Screening Pilot
A pilot with 100 results representative of the five chemicals and the peer, backwards, and gray
literature search results was developed by EPA. Two exposure experts scored the pilot, and met
with EPA to refine the criteria and application of the criteria.
Before screening, all screeners were required to meet a 90% accuracy in tagging the pilot
screening studies. Screeners who met this level of proficiency were able to begin title abstract
screening. Screeners who do not meet this level of proficiency, continued to train, using the
studies screened by screeners who had passed the pilot as additional training studies.
Documentation of all pilot tagging results was maintained in Excel spreadsheets for both the
peer-reviewed and gray literature.
C.2.3. Literature Screening
Title abstract screening of the peer-reviewed and gray literature occurred in DRAGON, an
online tool for systematic review. Results of the ITPP search were manually screened with one
screener who has been trained via the pilot process. Additionally, a subject matter expert
6 DRAGON is an online tool for systematic review developed by ICF that stores qualitative and quantitative data
from literature to help scientists implement the elements of systematic review, including problem formulation,
literature screening, risk of bias evaluation, and data integration.
Page 45 of 94
-------
reviewed 10% of the references deemed to be On Topic and Off Topic as a quality assurance
check to ensure that they have been categorized appropriately.
For gray literature, title/abstract and full text screening was done simultaneously, and tags for
screening are included in Appendix H. For peer-reviewed literature, title/abstract and full text
screening were done separately, and tags for each stage are included in Appendix H.2.
C.2.4. Prioritization
The database search strategy for ITPP returned approximately 50 results. The supplemental
search for related chemicals returned approximately 1,600 results. Few of the results added by
the related chemicals search are likely to be relevant to an exposure assessment of ITPP;
therefore, the results from title abstract screening of the ITPP search results were used to
prioritize the related chemicals search results using text analytics in DoCTER.
For prioritization, multiple text analytic algorithms can be used to find studies with titles and
abstracts similar to seed studies previously identified as On Topic by EPA experts. DoCTER
employs two main metrics, ensemble clustering and machine learning, including active machine
learning. Supervised clustering using an ensemble approach uses multiple algorithms in
Varghese et ai, (2017) to prioritize references for review. The prioritization strategy is shown in
Figure C-2 and presented in Varghese et al. (2017). These algorithms create a user-defined
number of clusters based on similarities in the text of the title and abstract, and each algorithm
is broadly-accepted in the text analytics scientific field, as described in Varghese et ai, (2017).
The clusters are populated by the algorithms that first convert the text in each title and abstract
into a numerical matrix (using binary or 0s and Is to represent the text) and then identifies
similarities or similar numerical strings between each matrix representation of a title and
abstract. Based on the similarities, the reference is assigned to a cluster. In the example, each
of the algorithms was used to bin the studies into 10, 20, or 30 clusters, for a total of six
different cluster analyses (six large circles in the figure). A random sample of studies identified
as relevant serve as "tracer" or "seed" studies (pink circles in the figure). The tracer method
involves following these relevant studies and determining the clusters the majority occur in;
these clusters are then deemed more likely to contain other (as-yet unidentified) relevant
studies. Off topic references, or negative seeds, can be used to estimate performance of the
tool using the metric of precision, but are not required for clustering.
To identify these high-priority clusters, the clusters containing a given fraction (75% in the
example) of the relevant tracer studies are identified for each of the six analyses and termed
"high concentration of tracer" clusters. All non-tracer studies in those high-concentration
clusters can then be marked as "high priority" for further screening. This ensemble method is
used to increase confidence in the selection of prioritized studies by mitigating uncertainty
from each individual analysis. Additionally, studies in the "low priority" clusters can be further
analyzed using machine learning algorithms that also use the "tracer" studies in conjunction
with Off Topic references, or negative seeds, and assign a probability score to each of the
remaining studies as likely to be On Topic.
Page 46 of 94
-------
NMF
Algorithm
10 20 30
clusters clusters clusters
Figure C-2. Ensemble text analytics method for prioritizing studies for screening
Any reference that was flagged as high priority by DoCTER was loaded into DRAGON for title
abstract screening.
O Algorithm/number of
clusters combination
0 Cluster identified by
algorithm
# Tracer study (identified
as relevant during
Round 1 screening)
+ Studies to be
prioritized
Q Prioritized clusters for
each analysis (have up
to 75% of tracers)
K-Means
Algorithm
AmmQo®
ccoeo
ocooc
oot/
l©©oeol
eoooe
eooeo
Page 47 of 94
-------
C.3 PECO Statement
Chemical
PIP3
PECO
Element
Evidence
Population
Human: Workers and occupational non-users (e.g., fire fighters); general population; consumers
and bystanders in residential settings; near-facility populations (includes industrial and
commercial facilities manufacturing, processing, or using PIP3); populations exposed from
transfer from workplaces through take home exposures; populations in co-located residences or
businesses; populations with subsistence diets; children; infants; pregnant women; lactating
women; women of childbearing age; susceptible populations (life stages, preexisting conditions,
genetic factors). No chemical-specific exclusions are suggested at present.
Ecological: Aquatic organisms (edible and nonedible fish, aquatic invertebrates (daphnia),
amphibians); terrestrial organisms (plants, soil invertebrates (worms), birds, mammals). No
chemical specific exclusions are suggested at present.
Exposure
Expected Exposure Sources, Pathways, Routes
Source: Industrial activities (manufacturing, processing, recycling, treatment, disposal of
products); commercial and consumer uses of consumer products containing PIP3 and associated
releases to air, water, or wastes (wastewater/liquid wastes, solid wastes); indoor
sources/materials that cover a large surface area, are abraded during use, or have high potential
for direct contact.
Pathway: Waste streams (e.g., landfills, biosolids); outdoor air (fugitive/stack emissions);
drinking water; surface water/groundwater (transfer from outdoor air/soil); indoor air (transfer
from outdoor air); soil/sediment; dust; contact with products; liquid contact; vapor intrusion;
food (breastmilk, fish, meat, eggs, dairy); media-specific background and source attribution to
be considered.
Routes: Inhalation (indoor air, smoke from burning buildings or PVC products); oral (dietary
ingestion of food or breastmilk, incidental ingestion of contaminated soil and dust, hand-to-
mouth contact, ingestion of drinking water, ingestion of suspended particles, mouthing of
consumer articles); dermal (contact with dust, soil, consumer products containing PIP3 or other
secondary vectors)
Comparator
(Scenario)
Human: Consider media-specific background exposure scenarios and use/source specific
exposure scenarios as well as which receptors are and are not reasonably exposed across the
projected exposure scenarios.
Ecological: Consider media-specific background exposure scenarios and use/source specific
exposure scenarios as well as which receptors are and are not reasonably exposed across the
projected exposure scenarios.
Outcomes for
Exposure
Concentration
or Dose
Human: Acute, subchronic, and/or chronic external dose estimates (mg/kg/day); acute,
subchronic, and/or chronic internal dose based on biomonitoring and reverse dosimetry
(mg/kg/day); acute, subchronic, and/or chronic air, soil, dust, and water concentration
estimates (mg/m3 or mg/L).
Ecological: A wide range of ecological receptors will be considered using surface water,
sediment, soil, and air concentrations. Targeted use of wildlife biomonitoring data will also be
explored.
Page 48 of 94
-------
C.4 PRISMA Diagram
The PRISMA Diagram for ITPP, including literature counts from search, screening and included
phases from all sources, is presented in Figure C-3. A subset of studies that passed the
screening phase were not extracted or evaluated due to the ready availability of the full text
and supplemental information. Due to time constraints, studies that did not include data in text
or tables, and studies that had fewer than 10 observations were not extracted or evaluated.
IPTPP
Data sources identified
through open literature,
backward searching, and
public comments n = 450
Data sources identified
through gray literature
n = 121
*
On-topic after title-
abstract screen n= 267
On-topic after full-text
screen n= 111
On-topic after combined
title-abstract—full-text
screen n= 16
Data sources identified
through open lit from
similar chemicals
n = 1,591
On-topic after machine
learning n= 38
On-topic after full-text
screen n= 35
Total On-topic
Core n= 98
Total On-topic
Supplemental n= 103
Total on
topic
= 162
Total
Searched =
2,162
Did not meet
evaluation
criteria screen
n = 35
Not on Topic-
Did not meet
full text tag
criteria
n = 2,000
Total Studies that were able to
be extracted n= 33
Total Studies that were
extracted and passed
evaluation criteria n= 31
Total
included
= 31
Figure C-3. PRISMA Diagram for ITPP
C.5 Data Evaluation Criteria
Core exposure data includes the following exposure data types:
- Environmental monitoring
- Biomonitoring
- Database Sources
- Completed Assessments
- Modeling
Page 49 of 94
Excluded -
Were not able
to be
extracted n =
48
Excluded - Did
not meet full
evaluation
criteria n = 2
-------
Assessors evaluated the extracted core exposure data for evaluation criteria specific to the data
type. The data evaluation criteria are included in (U.S. EPA. 2018).
C.6 Data Extraction Fields
Core exposure data, including monitoring data and modeled estimates of concentration or
dose, was extracted in DRAGON. The data extraction fields are included in Appendix I.
Page 50 of 94
-------
Appendix D. Supplemental Document for 2,4,6-Tris(tert-butyl) phenol (HBP)
D.l Literature Search Strategy
This document describes the literature search strategy to support the exposure assessments for
five persistent, bioaccumulative, and toxic (PBT) chemicals. The intent of the search is to assess
the likely exposure of the general population, consumers, occupational populations, potentially
exposed or susceptible subpopulations, and the environment to the conditions of use of PBT
chemicals based on the criteria outlined in the Toxic Substances Control Act (TSCA) section 6(h)
(OLRC. 2016).The conditions of use are defined as the circumstances under which a chemical
substance is intended, known or reasonably foreseen to be manufactured, processed,
distributed in commerce, used or disposed of.
Data sources in the peer-reviewed (open) and gray literature were considered as shown in
Error! Reference source not found.. In addition to the primary searches of the peer-reviewed
literature in Web of Science, PubMed, and Toxline, there were additional supplemental
searches that were used to complement and/or evaluate the primary peer-reviewed search
strategy. These were: backward searches of frequently used sources7, a Google Scholar search
of the top 100 results by chemical, and public comments and associated references cited in
those comments submitted to the dockets by mid-January 2018.
An additional search of the gray literature was conducted as described in the Gray Literature
Search Strategy section and was based off the protocol developed for the Systematic Review of
the "First 10" chemicals under TSCA.
Peer Reviewed
Database Search
Search peer
reviewed databases:
WoS, PubMed,
Toxine (except
TSCATS) and
compile in Endnote
libraries
I
Backwards Search
¦ Conduct
backward
searchesfrom
frequently used
sources and
compile in
Endnote libraries
X
Supplemental Public Comments Search
Search docket for public comments and
references cited therein
• Add to HERO docket #
Generate Master Libraries
• Remove duplicates
Google Scholar Search (100 hits/chem)
Remove duplicates captured previously
Evaluate search strategy
Gray Literature Search
Step 1: Conduct automated
search of approved websites
Step 2: Conduct manual
search of approved websites
(except TSCATS)
Step 3: Compile results in
Excel spreadsheets with mini-
citations
Step 4: Remove duplicates
from gray results
Step 5: Developfull citations
for "on topics"
< 7
Submit Citations to HERO for HEROIDs & Addition to SR Database
Figure D-l. Literature Search Strategy Workflow
7 Frequently used sources are sources expected to be of high quality, such as assessments conducted by other
government agencies.
Page 51 of 94
-------
The results of the literature searches were compiled into Endnote libraries (database searches)
and Excel spreadsheets (gray literature.)
D.l.l. Database (Peer-reviewed) Search Strategies
The literature searches for the five PBT chemicals were designed to be as broad as possible,
searching only for the chemical name and synonyms, but not including any limiters such as
terms describing expected uses or dates. ForTTBP, no chemical category name was included in
the search, but a series of similar chemicals were searched for potential information. The
search strategies for TTBP are presented in Table D-l and Table D-2.
Table D-l. TTBP Open Literature Search Strategy
Date of Searc
i: December 15, 2017
Database
Search Strategy
PubMed
(2,4,6-tri-tert-butylphenol[nm] OR "2,4,6-Tri-t-butylphenol"[tiab] OR "2,4,6-TRI-TERT.-
BUTYLPHENOL"[tiab] OR "2,4,6-TRI-TERT-BUTYL PHENOL"[tiab] OR "2,4,6-Tri-tert-
butylphenol"[tiab] OR 732-26-3[rn] ORTri-tert-butylphenol[tiab])
AND (English[lang])
Web of
Science
("2,4,6-Tris(l,l-dimethylethyl)phenol" OR "2,4,6-Tris(tert-butyl)phenol" OR "2,4,6-tri-terc-
butilfenol" OR "2,4,6-Tri-tert-butyl-l-hydroxybenzene" OR "Phenol, 2,4,6-tri(l,l-dimethylethyl)-
" OR "Phenol, 2,4,6-tris(l,l-dimethylethyl)-" OR "Phenol, 2,4,6-tri-tert-butyl-" OR "Phenol,
tris(l,l-dimethylethyl)-" OR "Tris(l,l-dimethylethyl)phenol" OR Alkofen-B OR Voidox OR "2,4,6-
Tri-t-butylphenol" OR "2,4,6-TRI-TERT.-BUTYLPHENOL" OR "2,4,6-TRI-TERT-BUTYL PHENOL" OR
"2,4,6-Tri-tert-butylphenol" OR 732-26-3 OR Tri-tert-butylphenol)
AND English
Toxline
732-26-3
Include Synonyms
Exclude PubMed
Records from TSCATS and NIH Reporter Database removed in EndNote
Table D-2. TTBP Supplemental Literature Search Strategy
Date of Searc
r April 5, 2018
Database
Search Strategy
PubMed
("Topanol"[tiab] OR "Tonarol"[tiab] OR "Sustane"[tiab] OR "Phenol, 2,6-bis(l,l-dimethylethyl)-
4-methyl-"[tiab] OR "Phenol, 2,4-bis(l,l-dimethylethyl)-"[tiab] OR "p-Cresol, 2,6-di-tert-butyl-
"[tiab] OR "o-t-Butylphenol"[tiab] OR "lonole"[tiab] OR "lonol"[tiab] OR "Di-tert-
butylphenol"[tiab] OR "Di-tert-butyl-p-cresol"[tiab] OR "Dibunol"[tiab] OR "CAO 3"[tiab] OR
"CAO l"[tiab] OR "Butylhydroxytoluene"[tiab] OR "Butylated hydroxytoluene"[mh] OR
"Butylated hydroxytoluene"[tiab] OR "A0 4"[tiab] OR "Agidol"[tiab] OR "96-76-4"[rn] OR "96-
70-8"[rn] OR "88-18-6"[rn] OR "6-tert-Butyl-2,4-xylenol"[tiab] OR "6-tert-Butyl-2,4-
dimethylphenol"[tiab] OR "4-Methyl-2,6-di-tert-butylphenol"[tiab] OR "4-Methyl-2,6-
ditertbutylphenol"[tiab] OR "4 Methyl 2,6 ditertbutylphenol"[tiab] OR "3,5-Di-tert-butyl-4-
hydroxytoluene"[tiab] OR "2-tert-Butylphenol"[tiab] OR "2-tert-Butylphenol"[nm] OR "2-tert-
Butyl-p-cresol"[tiab] OR "2-tert-Butyl-4-methylphenol"[tiab] OR "2-tert-Butyl-4-
methylphenol"[nm] OR "2-tert-Butyl-4-ethylphenol"[tiab] OR "2-tert-Butyl-4-ethylphenol"[nm]
OR "2-tert-Butyl-4,6-dimethylphenol"[tiab] OR "2-t-Butylphenol"[tiab] OR "2-t-Butyl-4-
methylphenol"[tiab] OR "2409-55-4"[rn] OR "2,6-Di-tert-butylphenol"[tiab] OR "2,6-Di-tert-
Page 52 of 94
-------
Database
Search Strategy
butylphenol"[nm] OR "2,6-Di-tert-butyl-p-cresol"[tiab] OR "2,6-Di-tert-butyl-4-
methylphenol"[tiab] OR "2,6-Di-tert-butyl-4-hydroxytoluene"[tiab] OR "2,6-Di-tert-butyl-4-
ethylphenol"[tiab] OR "2,6-Di-t-butylphenol"[tiab] OR "2,6-Di-t-butyl-p-cresol"[tiab] OR "2,6-Di-
t-butyl-4-methylphenol"[tiab] OR "2,6-Bis(l,l-dimethylethyl)phenol"[tiab] OR "2,6-Bis(l,l-
dimethylethyl)-4-methylphenol"[tiab] OR "2,6 Di-tert-butylphenol"[tiab] OR "2,6 Di tert butyl p
cresol"[tiab] OR "2,6 Di t butyl 4 methylphenol"[tiab] OR "2,4-Di-tert-butylphenol"[tiab] OR
"2,4-Di-tert-butylphenol"[nm] OR "1879-09-0"[rn] OR "128-39-2"[rn] OR "128-37-0"[rn] OR
"2,4-Bis(l,l-dimethylethyl)phenol"[tiab] OR "2,4-DI-TERT-BUTYL PHENOL"[tiab] OR "2,6-bis(l,l-
Dimethylethyl)-4-methyl-phenol"[tiab] OR "2,6-Bis(tert-butyl)-4-methylphenol"[tiab] OR "2,6-
Di(tert-butyl)hydroxytoluene"[tiab] OR "2,6-DI-TERT BUTYL-4-METHYLPHENOL"[tiab] OR "2,6-
DI-TERT.-BUTYLPHENOL"[tiab] OR "2,6-DI-TERT-BUTYL-4-METHYL PHENOL"[tiab] OR "2,6-Di-
tert-butylcresol"[tiab] OR "2,6-tert-Butyl-4-methylphenol"[tiab] OR "Butyl hydroxy
toluene"[tiab] OR "DIBUTYL HYDROXYTOLUENE"[tiab] OR "Dibutylhydroxytoluene"[tiab] OR
"Di-tert-Butyl-4-methylphenol"[tiab] OR "Di-tert-butylcresol"[tiab] OR "DITERTIARY BUTYL P-
CRESOL"[tiab] OR "E321"[tiab] OR "Popol"[tiab])
AND (English[lang])
Web of
Science
("Vulkanox KB" OR "Vianol" OR "Vanlube PCX" OR "Vanlube PC" OR "Toxolan P" OR "Topanol"
OR "Topanol OC" OR "Topanol 0" OR "Tonarol" OR "Tenox BHT" OR "Tenamene 3" OR
"Tenamen 3" OR "Swanox BHT" OR "Sustane" OR "Sustane BHT" OR "Sumilizer BHT" OR
"Stavox" OR "Prodox 340" OR "Prodox 146A-85X" OR "Prodox 146" OR "Phenol, o-tert-butyl-"
OR "Phenol, o-(tert-butyl)-" OR "Phenol, 2-tert-butyl-4-ethyl-" OR "Phenol, 2,6-di-tert-butyl-4-
ethyl-" OR "Phenol, 2,6-di-tert-butyl-4-ethyl- (8CI)" OR "Phenol, 2,6-di-tert-butyl-" OR "Phenol,
2,6-bis(l,l-dimethylethyl)-4-methyl-" OR "Phenol, 2,6-bis(l,l-dimethylethyl)-4-ethyl-" OR
"Phenol, 2,6-bis(l,l-dimethylethyl)-" OR "Phenol, 2,4-di-tert-butyl-" OR "Phenol, 2,4-di(l,l-
dimethylethyl)-" OR "Phenol, 2,4-bis(l,l-dimethylethyl)-" OR "Phenol, 2-(l,l-dimethylethyl)-4-
methyl-" OR "Phenol, 2-(l,l-dimethylethyl)-4-ethyl-" OR "Phenol, 2-(l,l-dimethylethyl)-4,6-
dimethyl-" OR "Phenol, 2-(l,l-dimethylethyl)-" OR "p-Cresol, 2-tert-butyl-" OR "p-Cresol, 2,6-di-
tert-butyl-" OR "Paranox 441" OR "Parabar 441" OR "o-tert-Butylphenol" OR "o-tert-Butyl-p-
cresol" OR "o-t-Butylphenol" OR "o-Di-tert-butyl-p-methylphenol" OR "Nonox TBC" OR "Nocrac
200" OR "Kerabit" OR "Isonox 103" OR "lonole" OR "lonol" OR "lonol 2" OR "Impruvol" OR
"Hitec 4701" OR "Ethyl AN 701" OR "Ethyl 701" OR "Ethanox 701" OR "Di-tert-butyl-p-
methylphenol" OR "Di-tert-butylphenol" OR "Di-tert-butyl-p-cresol" OR "Dibutylated
hydroxytoluene" OR "Dibunol" OR "Deenax" OR "Dalpac" OR "Chemanox 11" OR "Catalin cao-3"
OR "Catalin antioxydant 1" OR "CAO 3" OR "CAO 1" OR "Butylohydroksytoluenu" OR
"Butylhydroxytoluene" OR "Butylated hydroxytoluol" OR "Butylated hydroxytoluene" OR
"BUKS" OR "BHT 264" OR "BHT (food grade)" OR "Benzene, 2-tert-butyl-4-ethyl-l-hydroxy-" OR
"Benzene, l-tert-butyl-2-hydroxy-" OR "AOX 4K" OR "AOX 4" OR "AO 4K" OR "AO 4" OR "AO 29"
OR "Antrancine 8" OR "Antox QT" OR "Antioxidant T 501" OR "Antioxidant No. 33" OR
"Antioxidant MPJ" OR "Antioxidant KB" OR "Antioxidant DBPC" OR "Antioxidant 4K" OR
"Antioxidant 4" OR "Antioxidant 30" OR "Antioxidant 29" OR "Antioxidant 264" OR "Alkofen BP"
OR "Agidol" OR "Advastab 401" OR "96-76-4" OR "96-70-8" OR "88-18-6" OR "6-tert-Butyl-2,4-
xylenol" OR "6-tert-Butyl-2,4-dimethylphenol" OR "6-t-Butyl-2,4-xylenol" OR "6-t-Butyl-2,4-
dimethylphenol" OR "4-Methyl-6-t-butylphenol" OR "4-Methyl-2-tert-butylphenol" OR "4-
Methyl-2-t-butylphenol" OR "4-Methyl-2,6-tert-butylphenol" OR "4-Methyl-2,6-di-tert-
butylphenol" OR "4-Methyl-2,6-ditertbutylphenol" OR "4-Methyl-2,6-di-terc. butylfenol" OR "4-
Methyl-2-(l,l-dimethylethyl)phenol" OR "4-Hydroxy-3,5-di-tert-butyltoluene" OR "4-Ethyl-2-
tert-butylphenol" OR "4-Ethyl-2,6-di-tert-butylphenol" OR "4130-42-1" OR "4 Methyl 2,6
ditertbutylphenol" OR "3,5-Di-tert-butyl-4-hydroxytoluene" OR "2-tert-Butylphenol" OR "2-tert-
Butyl-p-cresol" OR "2-tert-Butyl-4-methylphenol" OR "2-tert-Butyl-4-methyl-l-phenol" OR "2-
tert-Butyl-4-ethylphenol" OR "2-tert-Butyl-4,6-dimethylphenol" OR "2-tert-Butyl-l-
Page 53 of 94
-------
Database
Search Strategy
hydroxybenzene" OR "2-terc.Butyl-p-kresol" OR "2-t-Butylphenol" OR "2-t-Butyl-p-cresol" OR
"2-t-Butyl-4-methylphenol" OR "2-t-Butyl-4-ethylphenol" OR "2409-55-4" OR "2,6-Di-tert-butyl-
p-methylphenol" OR "2,6-Di-tert-butylphenol" OR "2,6-Di-tert-butyl-p-cresol" OR "2,6-Di-tert-
butyl-4-methylphenol" OR "2,6-Di-tert-butyl-4-methylhydroxybenzene" OR "2,6-Di-tert-butyl-4-
hydroxytoluene" OR "2,6-Di-tert-butyl-4-ethylphenol" OR "2,6-Di-tert-butyl-4-cresol" OR "2,6-
Di-tert-butyl-l-hydroxy-4-methylbenzene" OR "2,6-Di-terc.butyl-p-kresol" OR "2,6-Di-t-
butylphenol" OR "2,6-Di-t-butyl-p-cresol" OR "2,6-Di-t-butyl-4-methylphenol" OR "2,6-Bis(tert-
butyl)phenol" OR "2,6-Bis(l,l-dimethylethyl)phenol" OR "2,6-Bis(l,l-dimethylethyl)-4-
methylphenol" OR "2,6-Bis(l,l-dimethylethyl)-4-ethylphenol" OR "2,6 Di-tert-butylphenol" OR
"2,6 Di tert butyl p cresol" OR "2,6 Di t butyl 4 methylphenol" OR "2,4-Xylenol, 6-tert-butyl-" OR
"2,4-Di-tert-butylphenol" OR "2,4-Dimethyl-6-tert-butylphenol" OR "2-(l,l-
Dimethylethyl)phenol" OR "2-(l,l-Dimethylethyl)-4-methylphenol" OR "l-Hydroxy-4-methyl-
2,6-di-tert-butylbenzene" OR "l-Hydroxy-4-ethyl-2,6-di-tert-butylbenzene" OR "l-Hydroxy-2-
tert-butyl-4-methylbenzene" OR "l-Hydroxy-2,4-di-tert-butylbenzene" OR "1879-09-0" OR
"128-39-2" OR "128-37-0" OR "2-(l,l-Dimethylethyl)-4-methyl-phenol" OR "2,4-BIS(TERT-
BUTYL)PHENOL" OR "2,4-di-terc-butilfenol" OR "2,4-Di-tert-butylhydroxybenzene" OR "2,6-
Bis(l,l-dimethylethyl)-4-methylphenol, 9CI" OR "2,6-di-terc-butilfenol" OR "2,6-di-terc-butil-p-
cresol" OR "2,6-DI-TERT.-BUTYL-P-KRESOL" OR "2,6-Di-tert-butyl-4-methyl-l-hydroxybenzene"
OR "2,6-DI-TERT-BUTYL-4-METHYLPHENOL(3,5-DI-TERT-BUTYL-4-HYDROXYTOLUENE)(2,6-DI-
TERT-BUTYL-P-CRESOL)" OR "2,6-Di-tert-butyl-4-methyphenol" OR "2,6-Di-tert-
butylmethylphenol" OR "2,6-Di-tert-butyl-p-cresol, 8CI" OR "2,6-Di-tert-butyl-p-cresole" OR
"2,6-Di-tert-butyl-p-kresol" OR "2-terc-butilfenol" OR "3,5-Di-tert-butyl-p-hydroxytoluene" OR
"4-Methyl-2,6-bis(l,l-dimethylethyl)phenol" OR "Antage BHT" OR "Antioxidant 246" OR "BHT
Swanox" OR "B-NOX BHT-P" OR "BRN 1910383" OR "Catalin CAO 3" OR "DIBUTYL PARACRESOL"
OR "Dibutylcresol" OR "FEMA 2184" OR "lonol K" OR "K-NOX-BHT" OR "Lowinox BHT" OR
"Lubrizol 817" OR "Naugard BHT" OR "Nipanox" OR "Nocrac 2000" OR "Permanax BHT" OR
"PHENOL, 2,6-DI-TERT-BUTYL-4-METHYL" OR "PHENOL, 2,6-DI-TERT-BUTYL-4-METHYL-" OR
"Phenol, bis(l,l-dimethylethyl)methyl-" OR "Ralox BHT" OR "Reaction product from p-cresol
and isobutylene" OR "Selosol H 633" OR "Sumilizer BHT-R" OR "TOLUENE, 3,5-DI-TERTIARY-
BUTYL-4-HYDROXY-" OR "Topanol BHT" OR "Topanol O-FG" OR "Topanol OL" OR "Ultranox 226"
OR "Vanox PC" OR "Yoshinox BHT" OR "2,4-Bis(l,l-dimethylethyl)phenol" OR "2,4-DI-TERT-
BUTYL PHENOL" OR "2,6-bis(l,l-Dimethylethyl)-4-methyl-phenol" OR "2,6-Bis(tert-butyl)-4-
methylphenol" OR "2,6-Di(tert-butyl)hydroxytoluene" OR "2,6-DI-TERT BUTYL-4-
METHYLPHENOL" OR "2,6-DI-TERT.-BUTYLPHENOL" OR "2,6-DI-TERT-BUTYL-4-METHYL
PHENOL" OR "2,6-Di-tert-butylcresol" OR "2,6-tert-Butyl-4-methylphenol" OR "Butyl hydroxy
toluene" OR "DIBUTYL HYDROXYTOLUENE" OR "Dibutylhydroxytoluene" OR "Di-tert-Butyl-4-
methylphenol" OR "Di-tert-butylcresol" OR "DITERTIARY BUTYL P-CRESOL" OR "E321" OR
"PHENOL,2,6-BIS(l,l-DIMETHYL-ETHYL)-4-METHYL" OR "Popol")
AND English
Toxline
("96-76-4" OR "96-70-8" OR "88-18-6" OR "4130-42-1" OR "2409-55-4" OR "1879-09-0" OR
"128-39-2" OR "128-37-0")
Include Synonyms
Exclude PubMed Records
D.1.2. Gray Literature Search Strategies
The five PBT chemicals searched were targeted to relevant sources and the approach was
adapted from the first 10 chemicals to optimize efficiency by eliminating redundancy. Gray
literature screening criteria excluded peer-reviewed journal articles that were expected to be
Page 54 of 94
-------
caught in the database searches. Mini citations, containing author, title, year, were generated
as a preliminary step to aid in identification and removal of duplicate records prior to tagging.
Automated searches via the Google search API were employed where possible in favor of
manual search sources. A summary of sources and search result counts after the removal of
duplicates is presented in Table D-3. All results were reviewed from each source. The search
strings used for manual and automated searches are found in Table D-4.
EPA is aware of information submitted by companies as part of TSCA requirements under
sections 4, 8(d), 8(e) or as part of an FYI ("TSCATS Submissions data"). This information was not
considered as part of the literature search and screening strategy. EPA plans to consider this
information in the future.
Public comments submitted to the Docket (by Docket Number) were captured and HERO
records were created including the title, author and docket number. The results were then
compared to those of other searches to determine whether references cited in those public
comments were already identified by other searches or need to be included. PDFs of the
individual comments were not captured; instead a special "Public Comment" tag in HERO which
specifies the corresponding round of public comments was used. Detailed results of the Public
Comments submitted with the number of cited references forTris is shown in Table D-5.
Page 55 of 94
-------
Table D-3. Summary of Gray Literature Sources and Search Results for Automated and Manual Searches for TTBP
Source
ID1
Source Category
Website
Description
Search type
Search
Result
Counts2
6000
US States
Government
Resources
States website custom search engine, see Summary
of State Sources tab
Custom search engine using
States sites
Automated
7
1000
US EPA Resources
epa.gov
US Environmental Protection
Agency
Automated
8
1150
US EPA Resources
http://aqsdrl.epa.gov/aqsweb/aqstmp/airdata/do
wnload files.html#Annual
Office of Air: AQS
Manual
0
1101
US EPA Resources
https://chemview.epa.gov/chemview
ChemView (CDR/IUR)
Manual
5
1083
US EPA Resources
https://actor.epa.gov/cpcat/faces/search.xhtml
CPDat
Manual
1
1154
US EPA Resources
https://comptox.epa.gov/dashboard/
Chemistry Dashboard
Manual
1
1148
US EPA Resources
https://iaspub.epa.gov/oppthpv/existchem_hpv_pr
ioritizations.report
EPA HPVIS
Manual
0
1001
US EPA Resources
https://www.epa.gov/ground-water-and-drinking-
water/table-regulated-drinking-water-
contaminants
Office of Water: EPA Clean
Water Act
Manual
0
1008
US EPA Resources
https://www.waterqualitydata.us/portal/
Office of Water: STORET and
WQX
Manual
1
1155
US EPA Resources
https://www.epa.gov/assessing-and-managing-
chemicals-under-tsca/persistent-bioaccumulative-
and-toxic-pbt-chemicals-under
TSCA PBT Use Documents
Manual
1
2150
Other US Agency
Resources
cdc.gov
Centers for Disease Control
(includes NIOSH and ATSDR)
Automated
0
2511
Other US Agency
Resources
energy.gov
Department of Energy
Automated
0
2300
Other US Agency
Resources
fda.gov
US Food and Drug
Administration
Automated
0
2050
Other US Agency
Resources
niehs.nih.gov
NIH National Institute of
Environmental Health and
Safety
Automated
0
2400
Other US Agency
Resources
osha.gov
OSHA Occupational Safety and
Health Administration
Automated
0
Page 56 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search
Result
Counts2
2521
Other US Agency
Resources
pnnl.gov
Pacific Northwest National
Laboratory
Automated
0
2509
Other US Agency
Resources
usgs.gov
US Geological Survey
Automated
5
2027
Other US Agency
Resources
https://ntp.niehs.nih.gov/pubhealth/roc/index-
l.html#C
NIH Report on Carcinogens
Manual
0
2414
Other US Agency
Resources
https://www.osha.gov/opengov/healthsamples.ht
ml
OSHA Chemical Exposure
Health Data
Manual
(inclusive of
all results;
not limited to
first 100)
0
2123
Other US Agency
Resources
https://www2a.cdc.gov/hhe/search.asp
CDC NIOSH Health Hazard
Evaluations
Manual and
Automated
(inclusive of
all results;
not limited to
first 100)
0
2104
Other US Agency
Resources
www.atsdr.cdc.gov/hac/pha/
CDC ATSDR Health Hazard
Consultations
Manual and
Automated
(inclusive of
all results;
not limited to
first 100)
0
3160
Other Resources
oecd.org
The Organisation for Economic
Co-operation and Development
(OECD)
Automated
4
5000
Other Resources
sustainableproduction.org
Lowell Center for Sustainable
Production
Automated
0
5020
Other Resources
lnfohouse.p2ric.org
Pollution Prevention Infohouse
Automated
3
3600
Other Resources
http://www.spin2000.net/spinmyphp/
Substances in Preparations in
Nordic Countries (SPIN)
Database
Manual
1
5027
Other Resources
Kirk Othmer Encyclopedia
Book
Manual
0
5028
Other Resources
Ashford's Dictionary of Industrial Chemicals, 2001
Book
Manual
0
Page 57 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search
Result
Counts2
5029
Other Resources
Hawley's Chemical Dictionary, 2016
Book
Manual
0
3425
International
Resources
carexcanada.ca
Carex Canada
Automated
0
3520
International
Resources
env.go.jp
Government of Japan: Ministry
of the Environment
Automated
17
3050
International
Resources
europa.eu
European Union
Automated
32
3057
International
Resources
https://echa.europa.eu/information-on-
chemicals/registered-substances
ECHA
Manual
1
3100
International
Resources
iarc.fr
International Agency for
Research on Cancer
Automated
0
3350
International
Resources
nicnas.gov.au
Australian Government:
Department of Health, National
Industrial Chemicals; NICNAS
Automated
4
3250
International
Resources
who.int
World Health Organization
Automated
0
3421
International
Resources
https://www.canada.ca/en/health-
canada/services/chemical-substances/fact-
sheets/chemicals-glance.html#interest
Canada Chemicals Portal
Manual
0
3450
International
Resources
http://limitvalue.ifa.dguv.de/
GESTIS Database
Manual
0
Total Unique (Duplicates Removed)
91
^'Source ID" refers to an internal ID assigned to each source for tracking purposes.
2 Search result counts represent totals after removal of duplicate records.
Page 58 of 94
-------
Table D-4. Gray Literature Search Strings
Chemical
Manual Search Terms
Google Search Terms (up to 128
characters)
2,4,6-Tris(tert-butyl) phenol
Search database by CAS or chemical
name, or select from a list on the
website
"732-26-3" OR "2,4,6-Tris(tert-butyl)
phenol" OR "2,4,6-tri-tert-butylphenol"
OR "Tri-tert-butylphenol"
Table D-5. Detailed Results of Public Comments Backwards Search for TTBP
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Christina Franz, Senior
Director, Regulatory & Technical Affairs,
American Chemistry Council (ACC)
American
Chemistry
Council (ACC)
EPA-HQ-OPPT-2016-0734-
0007
10
Comment submitted by Derek D. Swick,
Manager, American Petroleum Institute (API)
American
Petroleum
Institute (API)
EPA-HQ-OPPT-2016-0734-
0006
0
Anonymous public comment
Anonymous
EPA-HQ-OPPT-2016-0734-
0004
0
Comment submitted by Veena Singla, PhD,
Associate Director, Science and Policy, Program
on Reproductive Health and the Environment,
University of California, San Francisco (UCSF) et
al.
UCSF Program
on Reproductive
Health and the
Environment,
academics,
scientists and
clinicians
EPA-HQ-OPPT-2016-0734-
0008
45
Comment submitted by Dianne C. Barton, Chair,
National Tribal Toxics Council (NTTC)
National Tribal
Toxics Council
(NTTC)
EPA-HQ-OPPT-2016-0734-
0014
18
Comment submitted by Elizabeth Hitchcock,
Acting Director, Safer Chemicals Healthy
Families (SCHF) et al.
Safer Chemicals
Healthy Families
(SCHF), Alaska
Community
Action on Toxics,
Center for
Environmental
Health,
Earthjustice,
Environmental
Health Strategy
Center, Natural
Resources
Defense Council,
Toxic-Free
Future
EPA-HQ-OPPT-2016-0734-
0013
21
Comment submitted by Jyotsna S. Jagai,
Research Assistant Professor, University of
Illinois, Chicago Chair, Environment Section,
American Public Health Association et al.
EPA-HQ-OPPT-2016-0734-
0011
6
Page 59 of 94
-------
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Leslie Riegle, Director
of Environmental Policy, Aerospace Industries
Association (AIA)
Aerospace
Industries
Association (AIA)
EPA-HQ-OPPT-2016-0734-
0010
0
Comment submitted by Robert Stockman,
Senior Attorney, Environmental Defense Fund
(EDF)
Environmental
Defense Fund
(EDF)
EPA-HQ-OPPT-2016-0734-
0012
8
Comment submitted by Craig Bernard, PhD,
Vice President, Global Regulatory Affairs, Dorf
Ketal Chemicals
Dorf Ketal
Chemicals
EPA-HQ-OPPT-2016-0734-
0015
0
Comment submitted by Ken Zarker, Section
Manager, Hazardous Waste and Toxics
Reduction Program, Washington State
Department of Ecology
Washington
State
Department of
Ecology
EPA-HQ-OPPT-2016-0734-
0009
3
Comment submitted by Kevin M. Kransler, PhD,
Regulatory Affairs Manager, SI Group
SI Group
EPA-HQ-OPPT-2016-0734-
0020
0
TOTAL
12
111
Total Unique (Duplicates Removed)
101
D.1.3. Supplemental Search Strategy
Backward Search
To both supplement and test the database and gray literature searches, backward searches of
frequently used sources were conducted. These sources consist of previous risk assessments,
systematic reviews, and other assessments, generally conducted by EPA or other government
agencies of the chemicals of interest and presented in Table D-7. The references that are cited
within sections deemed relevant to this assessment were gathered into Endnote libraries for
title abstract review.
Google Scholar Search
To further supplement and test the database searches, a Google Scholar search was conducted
for each of the five PBT chemicals. The top 100 results returned by Google Scholar for each
chemical were exported into Endnote libraries. These results were compared to the references
identified in the database, backward, and gray literature searches to identify references not
found by the previous searches. While Google Scholar results are expected to be primarily peer-
reviewed rather than gray literature, the results were still compared to all searches.
D.1.4. Literature Search Results
The literature searches were conducted, and for PubMed, Web of Science, ToxLine, Backwards
searches, and Google Scholar searches, the results were imported into one Endnote library per
chemical. After the results were combined, duplicates were removed and TSCATS/NIH Reporter
data, a subset of ToxLine, were moved into a separate folder. The resulting counts are
presented Table D-6. Detailed results for the TTBP backwards search are presented in
Table D-7.
Page 60 of 94
-------
Table D-6. Count of Peer-reviewed Literature Search Results by Search Type for TTBP
Chemical
PubMed
WoS
ToxLine
TSCATS/ NIH
Reporter
Backwards
Google
Scholar
246-Tris
24
82
20
5
71
80
Table D-7. Detailed Results of Backwards Search of Frequently Used Sources for TTBP
HEROID
Document title
Reference count
4182671
Canada Screening Assessment
43
4182739
EU Risk Assessment
28
4198468
NICNAS (2013)
1
TOTAL
72
Total Unique (Duplicates Removed)
71
EndNote Library: Total Unique (Duplicates Removed)
71
D.2 Literature Screening Strategy
D.2.1. Development of the Literature Screening Approach
The steps involved in developing the title abstract screening approach are:
1. Define inclusion/exclusion criteria.
2. Conduct the pilot using 10 randomly selected studies for each chemical from both the
peer-reviewed and gray literature that are screened by EPA experts.
3. Use the results of the pilot to refine inclusion/exclusion criteria.
4. Use the refined pilot to train screeners in applying the tags.
In these assessments, the results of the title/abstract literature screening will be used to
develop the PECO statement. The overall workflow of the systematic review process including
the literature screening is presented in Appendix F.
The PECO statement is included in Appendix D.3. Four tags were used at the title-abstract
phase: Peer On Topic, Peer Off Topic, Gray On Topic, and Gray Off Topic and recorded on the
HERO project pages. Title abstract screening was conducted in DRAGON8. A screenshot of the
DRAGON form and all DRAGON tags is presented in Appendix H.
The inclusion/exclusion criteria for title/abstract and full text screening are included in
Appendix G. During full text screening, studies were also screened for "Red Flag Criteria," which
represent the "Unacceptable" criteria from the Data Evaluation criteria (U.S. EPA. 2018).
D.2.2. Literature Screening Pilot
8 DRAGON is an online tool for systematic review developed by ICF that stores qualitative and quantitative data
from literature to help scientists implement the elements of systematic review, including problem formulation,
literature screening, risk of bias evaluation, and data integration.
Page 61 of 94
-------
A pilot with 100 results representative of the five chemicals and the peer, backwards, and gray
literature search results was developed by EPA. Two exposure experts scored the pilot, and met
with EPA to refine the criteria and application of the criteria.
Before screening, all screeners were required to meet a 90% accuracy in tagging the pilot
screening studies. Screeners who met this level of proficiency were able to begin title abstract
screening. Screeners who do not meet this level of proficiency, continued to train, using the
studies screened by screeners who had passed the pilot as additional training studies.
Documentation of all pilot tagging results was maintained in Excel spreadsheets for both the
peer-reviewed and gray literature.
D.2.3. Literature Screening
Title abstract screening of the peer-reviewed and gray literature occurred in DRAGON, an
online tool for systematic review. Results of the TTBP search were manually screened with one
screener who has been trained via the pilot process. Additionally, a subject matter expert
reviewed 10% of the references deemed to be On Topic and Off Topic as a quality assurance
check to ensure that they have been categorized appropriately.
For gray literature, title/abstract and full text screening was done simultaneously, and tags for
screening are included in Appendix H. For peer-reviewed literature, title/abstract and full text
screening were done separately, and tags for each stage are included in Appendix H.2.
D.2.4. Prioritization
The database search strategy for TTBP returned approximately 125 results. The supplemental
search for related chemicals returned approximately 7,800 results. Few of the results added by
the related chemicals search are likely to be relevant to an exposure assessment of TTBP;
therefore, the results from title abstract screening of the TTBP search results were used to
prioritize the related chemicals search results using text analytics in DoCTER.
For prioritization, multiple text analytic algorithms can be used to find studies with titles and
abstracts similar to seed studies previously identified as On Topic by EPA experts. DoCTER
employs two main metrics, ensemble clustering and machine learning, including active machine
learning. Supervised clustering using an ensemble approach uses multiple algorithms in
Varghese et ai, (2017) to prioritize references for review. The prioritization strategy is shown in
Figure D-2 and presented in Varghese et ai, (2017). These algorithms create a user-defined
number of clusters based on similarities in the text of the title and abstract, and each algorithm
is broadly-accepted in the text analytics scientific field, as described in Varghese et ai, (2017).
The clusters are populated by the algorithms that first convert the text in each title and abstract
into a numerical matrix (using binary or 0s and Is to represent the text) and then identifies
similarities or similar numerical strings between each matrix representation of a title and
abstract. Based on the similarities, the reference is assigned to a cluster. In the example, each
of the algorithms was used to bin the studies into 10, 20, or 30 clusters, for a total of six
different cluster analyses (six large circles in the figure). A random sample of studies identified
as relevant serve as "tracer" or "seed" studies (pink circles in the figure). The tracer method
Page 62 of 94
-------
involves following these relevant studies and determining the clusters the majority occur in;
these clusters are then deemed more likely to contain other (as-yet unidentified) relevant
studies. Off topic references, or negative seeds, can be used to estimate performance of the
tool using the metric of precision, but are not required for clustering.
To identify these high-priority clusters, the clusters containing a given fraction (75% in the
example) of the relevant tracer studies are identified for each of the six analyses and termed
"high concentration of tracer" clusters. All non-tracer studies in those high-concentration
clusters can then be marked as "high priority" for further screening. This ensemble method is
used to increase confidence in the selection of prioritized studies by mitigating uncertainty
from each individual analysis. Additionally, studies in the "low priority" clusters can be further
analyzed using machine learning algorithms that also use the "tracer" studies in conjunction
with Off Topic references, or negative seeds, and assign a probability score to each of the
remaining studies as likely to be On Topic.
K-Means
Algorithm
mmGGoei
aeeooo
icoeoo
locooc
loool
O Algorithm/number of
clusters combination
0 Cluster identified by
algorithm
m Tracer study (identified
as relevant during
Round 1 screening)
• Studies to be
prioritized
O Prioritized clusters for
each analysis (have up
to 75% of tracers)
\ » i
NMF
Algorithm
10
clusters
20
clusters
30
clusters
Figure D-2. Ensemble text analytics methods for prioritizing studies for screening
Any reference that was flagged as high priority by DoCTER was loaded into DRAGON for title
abstract screening.
OG0OO
oeec
Page 63 of 94
-------
D.3 PECO Statement
Chemical
2,4,6 TRIS
PECO Element
Evidence
Population
Human: Workers and occupational non-users; general population; consumers and
bystanders in residential settings; near-facility populations (includes industrial and
commercial facilities manufacturing, processing, or using 2,4,6 TRIS); populations
exposed from transfer from workplaces through take home exposures; populations in co-
located residences or businesses; populations with subsistence diets; children; infants;
pregnant women; lactating women; women of childbearing age; susceptible populations
(life stages, preexisting conditions, genetic factors). No chemical-specific exclusions are
suggested at present.
Ecological: Aauatic organisms (edible and nonedible fish, aauatic invertebrates
(daphnia), amphibians); terrestrial organisms (plants, soil invertebrates (worms), birds,
mammals). No chemical specific exclusions are suggested at present.
Exposure
Expected Exposure Sources, Pathways, Routes
Source: Industrial activities (manufacturing, processing, recvcling, treatment, disposal of
products); commercial and consumer uses of consumer products containing 2,4,6 TRIS
and associated releases to air, soil, water, or wastes (wastewater/liquid wastes, solid
wastes); historical use in pesticides and agricultural products
Pathwav: Waste streams (e.g., landfills, biosolids); outdoor air (fugitive/stack emissions);
surface water/groundwater (transfer from outdoor air/soil); indoor air (transfer from
outdoor air); soil/sediment; dust; contact with products; vapor intrusion from moist soil
or aqueous solution; food (breastmilk, fish, meat, eggs, dairy, crops)
Routes: Inhalation (indoor air); oral (dietarv ingestion of food or breastmilk, incidental
ingestion of contaminated soil and dust, hand-to-mouth contact, ingestion of suspended
particles); dermal (contact with dust, soil, consumer products containing 2,4,6 TRIS or
other secondary vectors)
Expected Lesser Exposure Sources, Pathways, Routes
• Source: impuritv in 2,6 di-tert-butvlphenol
• Pathwav: outdoor air; drinking water
• Routes: inhalation of outdoor air; ingestion of drinking water
Comparator
(Scenario)
Human: Consider media-specific background exposure scenarios and use/source specific
exposure scenarios as well as which receptors are and are not reasonably exposed across
the projected exposure scenarios.
Ecological: Consider media-specific background exposure scenarios and use/source
specific exposure scenarios as well as which receptors are and are not reasonably
exposed across the projected exposure scenarios.
Outcomes for
Exposure
Concentration or
Dose
Human: Acute, subchronic, and/or chronic external dose estimates (mg/kg/dav); acute,
subchronic, and/or chronic internal dose based on biomonitoring and reverse dosimetry
(mg/kg/day); acute, subchronic, and/or chronic air, soil, dust, and water concentration
estimates (mg/m3 or mg/L).
Ecological: A wide range of ecological receptors will be considered using surface water,
sediment, soil, and air concentrations. Targeted use of wildlife biomonitoring data will
also be explored.
Page 64 of 94
-------
D.4 PRISMA Diagram
The PRISMA Diagram for TTBP, including literature counts from search, screening and included
phases from all sources, is presented in Figure D-3. A subset of studies that passed the
screening phase were not extracted or evaluated due to the ready availability of the full text
and supplemental information. Due to time constraints, studies that did not include data in text
or tables, and studies that had fewer than 10 observations were not extracted or evaluated.
Data sources identified
through open literature,
backward searching, and
public comments n = 632
Data sources identified
through gray literature
n = 91
~
On-topic after title-
abstract screen n= 389
On-topic after full-text
screen n= 71
On-topic after combined
title-abstract—full-text
screen n= 23
Data sources identified
through open lit from
similar chemicals
n = 7,768
On-topic after machine
learning n= 252
On-topic after full-text
screen n= 42
Total On-topic
Core n= 59
Total On-topic
Supplemental n= 75
Total on
topic
= 136
Total
Searched =
8,491
Did not meet
evaluation
criteria screen
n = 27
Not on Topic -
Did not meet
full text tag
criteria
n = 8,355
Total Studies that were able to
be extracted n= 9
Total Studies that were
extracted and passed
evaluation criteria n= 8
Total
included
= 8
Figure D-3. PRISMA Diagram for TTBP
D.5 Data Evaluation Criteria
Core exposure data includes the following exposure data types:
- Environmental monitoring
- Biomonitoring
- Database Sources
- Completed Assessments
- Modeling
Page 65 of 94
Excluded-
Were not able
to be
extracted n =
29
Excluded - Did
not meet full
evaluation
criteria n = 1
-------
Assessors evaluated the extracted core exposure data for evaluation criteria specific to the data
type. The data evaluation criteria are included in (U.S. EPA. 2018).
D.6 Data Extraction Fields
Core exposure data, including monitoring data and modeled estimates of concentration or
dose, was extracted in DRAGON. The data extraction fields are included in Appendix I.
Page 66 of 94
-------
Appendix E. Supplemental Document for Pentachlorothiophenol (PCTP)
E.l Literature Search Strategy
This document describes the literature search strategy to support the exposure assessments for
five persistent, bioaccumulative, and toxic (PBT) chemicals. The intent of the search is to assess
the likely exposure of the general population, consumers, occupational populations, potentially
exposed or susceptible subpopulations, and the environment to the conditions of use of PBT
chemicals based on the criteria outlined in the Toxic Substances Control Act (TSCA) section 6(h)
(OLRC. 2016).The conditions of use are defined as the circumstances under which a chemical
substance is intended, known or reasonably foreseen to be manufactured, processed,
distributed in commerce, used or disposed of.
Data sources in the peer-reviewed (open) and gray literature were considered as shown in
Figure E-l. In addition to the primary searches of the peer-reviewed literature in Web of
Science, PubMed, and Toxline, there were additional supplemental searches that were used to
complement and/or evaluate the primary peer-reviewed search strategy. These were:
backward searches of frequently used sources9, a Google Scholar search of the top 100 results
by chemical, and public comments and associated references cited in those comments
submitted to the dockets by mid-January 2018.
An additional search of the gray literature was conducted as described in the Gray Literature
Search Strategy section and was based off the protocol developed for the Systematic Review of
the "First 10" chemicals under TSCA.
Peer Reviewed
Database Search
Search peer
reviewed databases:
WoS, PubMed,
Toxine (except
TSCATS) and
compile in Endnote
libraries
I
Backwards Search
¦ Conduct
backward
searchesfrom
frequently used
sources and
compile in
Endnote libraries
X
Supplemental Public Comments Search
Search docket for public comments and
references cited therein
• Add to HERO docket #
Generate Master Libraries
• Remove duplicates
Google Scholar Search (100 hits/chem)
Remove duplicates captured previously
Evaluate search strategy
Gray Literature Search
Step 1: Conduct automated
search of approved websites
Step 2: Conduct manual
search of approved websites
(except TSCATS}
Step 3: Compile results in
Excel spreadsheets with mini-
citations
Step 4: Remove duplicates
from gray results
Step 5: Developfull citations
for "on topics"
< 7
Submit Citations to HERO for HEROIDs & Addition to SR Database
Figure E-l. Literature Search Strategy Workflow
9 Frequently used sources are sources expected to be of high quality, such as assessments conducted by other
government agencies.
Page 67 of 94
-------
The results of the literature searches were compiled into Endnote libraries (database searches)
and Excel spreadsheets (gray literature.)
E.l.l. Database (Peer-reviewed) Search Strategies
The literature searches for the five PBT chemicals were designed to be as broad as possible,
searching only for the chemical name and synonyms, but not including any limiters such as
terms describing expected uses or dates. For PCTP, no chemical category name was included in
the search. The search strategy for PCTP is presented inError! Reference source not found.
Table E-l.
Table E-l. PCTP Open Literature Search Strategy
Date of Searc
i: December 15, 2017
Database
Search Strategy
PubMed
(133-49-3[rn] OR PCTP[tiab] OR Pentachlorobenzenethiol[tiab] OR Pentachlorothiophenol[nm]
OR Pentachlorothiophenol[tiab])
AND (English[lang])
Web of
Science
("2,3,4,5,6-Pentachlorobenzene-l-thiol" OR "Benzenethiol, 2,3,4,5,6-pentachloro-" OR
"Benzenethiol, pentachloro-" OR AI3-23118 OR BRN-1108638 OR Pentachloro-benzenethiol OR
Pentachlorthiofenol OR RPA-6 OR 133-49-3 OR PCTP OR Pentachlorobenzenethiol OR
Pentachlorothiophenol)
AND English
Toxline
133-49-3
Include Synonyms
Exclude PubMed
Records from TSCATS and NIH Reporter Database removed in EndNote
E.1.2. Gray Literature Search Strategies
The five PBT chemicals searched were targeted to relevant sources and the approach was
adapted from the first 10 chemicals to optimize efficiency by eliminating redundancy. Gray
literature screening criteria excluded peer-reviewed journal articles that were expected to be
caught in the database searches. Mini citations, containing author, title, year, were generated
as a preliminary step to aid in identification and removal of duplicate records prior to tagging.
Automated searches via the Google search API were employed where possible in favor of
manual search sources. A summary of sources and search result counts after the removal of
duplicates is presented in Table E-2. All results were reviewed from each source. The search
strings used for manual and automated searches are found in Error! Reference source not
found..
EPA is aware of information submitted by companies as part of TSCA requirements under
sections 4, 8(d), 8(e) or as part of an FYI ("TSCATS Submissions data"). This information was not
considered as part of the literature search and screening strategy. EPA plans to consider this
information in the future.
Page 68 of 94
-------
Public comments submitted to the Docket (by Docket Number) were captured and HERO
records were created including the title, author and docket number. The results were then
compared to those of other searches to determine whether references cited in those public
comments were already identified by other searches or need to be included. PDFs of the
individual comments were not captured; instead a special "Public Comment" tag in HERO which
specifies the corresponding round of public comments was used. Detailed results of the Public
Comments submitted with the number of cited references for PCTP is shown in Table E-4
Page 69 of 94
-------
Table E-2. Summary of Gray Literature Sources and Search Results for Automated and Manual Searches for PCTP
Source
ID1
Source Category
Website
Description
Search type
Search
Resu It
Counts2
6000
US States
Government
Resources
States website custom search engine, see
Summary of State Sources tab
Custom search engine using States sites
Automated
4
1000
US EPA Resources
epa.gov
US Environmental Protection Agency
Automated
46
1150
US EPA Resources
http://aqsdrl.epa.gov/aqsweb/aqstmp/ai
rdata/download_files.html#Annual
Office of Air: AQS
Manual
0
1101
US EPA Resources
https://chemview.epa.gov/chemview
ChemView (CDR/IUR)
Manual
0
1083
US EPA Resources
https://actor.epa.gov/cpcat/faces/search
.xhtml
CPDat
Manual
1
1154
US EPA Resources
https://comptox.epa.gov/dashboard/
Chemistry Dashboard
Manual
1
1148
US EPA Resources
https://iaspub.epa.gov/oppthpv/existche
m_hpv_prioritizations. report
EPA HPVIS
Manual
0
1001
US EPA Resources
https://www.epa.gov/ground-water-and-
drinking-water/table-regulated-drinking-
water-contaminants
Office of Water: EPA Clean Water Act
Manual
0
1008
US EPA Resources
https://www.waterqualitydata.us/portal/
Office of Water: STORET and WQX
Manual
0
1155
US EPA Resources
https://www.epa.gov/assessing-and-
managing-chemicals-under-
tsca/persistent-bioaccumulative-and-
toxic-pbt-chemicals-under
TSCA PBT Use Documents
Manual
1
2150
Other US Agency
Resources
cdc.gov
Centers for Disease Control (includes
NIOSH and ATSDR)
Automated
6
2511
Other US Agency
Resources
energy.gov
Department of Energy
Automated
7
2300
Other US Agency
Resources
fda.gov
US Food and Drug Administration
Automated
1
2050
Other US Agency
Resources
niehs.nih.gov
NIH National Institute of Environmental
Health and Safety
Automated
1
Page 70 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search
Resu It
Counts2
2400
Other US Agency
Resources
osha.gov
OSHA Occupational Safety and Health
Administration
Automated
0
2521
Other US Agency
Resources
pnnl.gov
Pacific Northwest National Laboratory
Automated
0
2509
Other US Agency
Resources
usgs.gov
US Geological Survey
Automated
6
2027
Other US Agency
Resources
https://ntp.niehs.nih.gOv/pubhealth/roc/i
ndex-l.html#C
NIH Report on Carcinogens
Manual
0
2414
Other US Agency
Resources
https://www.osha.gov/opengov/healthsa
mples.html
OSHA Chemical Exposure Health Data
Manual (inclusive of all
results; not limited to
first 100)
0
2123
Other US Agency
Resources
https://www2a.cdc.gov/hhe/search.asp
CDC NIOSH Health Hazard Evaluations
Manual and Automated
(inclusive of all results;
not limited to first 100)
0
2104
Other US Agency
Resources
www.atsdr.cdc.gov/hac/pha/
CDC ATSDR Health Hazard Consultations
Manual and Automated
(inclusive of all results;
not limited to first 100)
0
3160
Other Resources
oecd.org
The Organisation for Economic Co-
operation and Development (OECD)
Automated
2
5000
Other Resources
sustainableproduction.org
Lowell Center for Sustainable Production
Automated
0
5020
Other Resources
lnfohouse.p2ric.org
Pollution Prevention Infohouse
Automated
0
3600
Other Resources
http://www.spin2000.net/spinmyphp/
Substances in Preparations in Nordic
Countries (SPIN) Database
Manual
1
5027
Other Resources
Kirk Othmer Encyclopedia
Book
Manual
0
5028
Other Resources
Ashford's Dictionary of Industrial
Chemicals, 2001
Book
Manual
1
5029
Other Resources
Hawley's Chemical Dictionary, 2016
Book
Manual
0
3425
International
Resources
carexcanada.ca
Carex Canada
Automated
0
Page 71 of 94
-------
Source
ID1
Source Category
Website
Description
Search type
Search
Resu It
Counts2
3520
International
Resources
env.go.jp
Government of Japan: Ministry of the
Environment
Automated
4
3050
International
Resources
europa.eu
European Union
Automated
23
3057
International
Resources
https://echa.europa.eu/information-on-
chemicals/registered-substances
ECHA
Manual
0
3100
International
Resources
iarc.fr
International Agency for Research on
Cancer
Automated
0
3350
International
Resources
nicnas.gov.au
Australian Government: Department of
Health, National Industrial Chemicals;
NICNAS
Automated
0
3250
International
Resources
who.int
World Health Organization
Automated
1
3421
International
Resources
https://www.canada.ca/en/health-
canada/services/chemical-
substances/fact-sheets/chemicals-
glance.html#interest
Canada Chemicals Portal
Manual
0
3450
International
Resources
http://limitvalue.ifa.dguv.de/
GESTIS Database
Manual
0
Total Unique (Duplicates Removed)
106
^'Source ID" refers to an internal ID assigned to each source for tracking purposes.
2 Search result counts represent totals after removal of duplicate records.
Table E-3. Gray Literature Search Strings
Chemical
Manual Search Terms
Google Search Terms (up to 128 characters)
Pentachlorothiophenol (PCTP)
Search database by CAS or chemical
name, or select from a list on the website
"133-49-3" OR "Pentachlorothiophenol" OR "PCTP"
Page 72 of 94
-------
Table E-4. Detailed Results from Public Comments Backwards Search for PCTP
Public Comment Title
Publisher
Comment ID
References
Cited Count
Comment submitted by Christina Franz, Senior
Director, Regulatory & Technical Affairs,
American Chemistry Council (ACC)
American
Chemistry
Council (ACC)
EPA-HQ-OPPT-2016-0739-
0006
10
Comment submitted by Sarah E. Amick, Vice
President EHS&S and Senior Counsel, Rubber
Manufacturers Association (RMA)
Rubber
Manufacturers
Association
(RMA)
EPA-HQ-OPPT-2016-0739-
0002
0
Comment submitted by Veena Singla, PhD,
Associate Director, Science and Policy, Program
on Reproductive Health and the Environment,
University of California, San Francisco (UCSF) et
al.
UCSF Program
on Reproductive
Health and the
Environment,
academics,
scientists and
clinicians
EPA-HQ-OPPT-2016-0739-
0007
45
Comment submitted by Jyotsna S. Jagai, PhD,
Research Assistant Professor, University of
Illinois, Chicago Chair, Environment Section,
American Public Health Association
EPA-HQ-OPPT-2016-0739-
0013
6
Comment submitted by Robert Stockman,
Senior Attorney on behalf of Environmental
Defense Fund (EDF)
Environmental
Defense Fund
(EDF)
EPA-HQ-OPPT-2016-0739-
0009
8
Comment submitted by Elizabeth Hitchcock,
Acting Director, Safer Chemicals Healthy
Families (SCHF) et al.
Safer Chemicals
Healthy Families
(SCHF), Alaska
Community
Action on Toxics,
Center for
Environmental
Health,
Earthjustice,
Environmental
Health Strategy
Center, Natural
Resources
Defense Council,
Toxic-Free
Future
EPA-HQ-OPPT-2016-0739-
0010
19
Comment submitted by Dianne C. Barton, Chair,
National Tribal Toxics Council (NTTC)
National Tribal
Toxics Council
(NTTC)
EPA-HQ-OPPT-2016-0739-
0011
18
Comment submitted by Dr. Alan Hocknell,
Senior Vice President, Research &
Development, Callaway Golf Company
Callaway Golf
Company
EPA-HQ-OPPT-2016-0739-
0015
0
TOTAL
8
106
Total Unique (Duplicates Removed)
97
Page 73 of 94
-------
E.1.3. Supplemental Search Strategy
Backward Search
To both supplement and test the database and gray literature searches, backward searches of
frequently used sources were conducted. Candidate sources consist of previous risk assessments,
systematic reviews, and other assessments, generally conducted by EPA or other government
agencies of the chemicals of interest, although no frequently used sources were identified for
PCTP.
Google Scholar Search
To further supplement and test the database searches, a Google Scholar search was conducted for
each of the five PBT chemicals. The top 100 results returned by Google Scholar for each chemical
were exported into Endnote libraries. These results were compared to the references identified in
the database, backward, and gray literature searches to identify references not found by the
previous searches. While Google Scholar results are expected to be primarily peer-reviewed rather
than gray literature, the results were still compared to all searches.
E.1.4. Literature Search Results
The literature searches were conducted, and for PubMed, Web of Science, ToxLine, Backwards
searches, and Google Scholar searches, the results were imported into one Endnote library per
chemical. After the results were combined, duplicates were removed and TSCATS/NIH Reporter
data, a subset of ToxLine, were moved into a separate folder. The resulting counts are presented
inError! Reference source not found. Table E-5. Backwards searching was not conducted for PCTP.
Table E-5. Count of Peer-reviewed Literature Search Results by Search Type for PCTP
Chemical
PubMed
WoS
ToxLine
TSCATS/ NIH
Reporter
Backwards
Google
Scholar
PCTP
92
47
24
0
0
81
E.2 Literature Screening Strategy
E.2.1. Development of the Literature Screening Approach
The steps involved in developing the title abstract screening approach are:
1. Define inclusion/exclusion criteria.
2. Conduct the pilot using 10 randomly selected studies for each chemical from both the
peer-reviewed and gray literature that are screened by EPA experts.
3. Use the results of the pilot to refine inclusion/exclusion criteria.
4. Use the refined pilot to train screeners in applying the tags.
The overall workflow of the systematic review process including the literature screening is
presented in Appendix F.
Page 74 of 94
-------
In these assessments, the results of the title/abstract literature screening will be used to develop
the PECO statement. The PECO statement is included in Appendix E.3. Four tags were used at the
title-abstract phase: Peer On Topic, Peer Off Topic, Gray On Topic, and Gray Off Topic and
recorded on the HERO project pages. Title abstract screening was conducted in DRAGON10. A
screenshot of the DRAGON form and all DRAGON tags is presented in Appendix H.
The inclusion/exclusion criteria for title/abstract and full text screening are included in g. During
full text screening, studies were also screened for "Red Flag Criteria," which represent the
"Unacceptable" criteria from the Data Evaluation criteria (U.S. EPA. 2018).
E.2.2. Literature Screening Pilot
A pilot with 100 results representative of the five chemicals and the peer, backwards, and gray
literature search results was developed by EPA. Two exposure experts scored the pilot, and met
with EPA to refine the criteria and application of the criteria.
Before screening, all screeners were required to meet a 90% accuracy in tagging the pilot
screening studies. Screeners who met this level of proficiency were able to begin title abstract
screening. Screeners who do not meet this level of proficiency, continued to train, using the
studies screened by screeners who had passed the pilot as additional training studies.
Documentation of all pilot tagging results was maintained in Excel spreadsheets for both the peer-
reviewed and gray literature.
E.2.3. Literature Screening
Title abstract screening of the peer-reviewed and gray literature occurred in DRAGON, an online
tool for systematic review. Results of the PCTP search were manually screened with one screener
who has been trained via the pilot process. Additionally, a subject matter expert reviewed 10% of
the references deemed to be On Topic and Off Topic as a quality assurance check to ensure that
they have been categorized appropriately.
For gray literature, title/abstract and full text screening was done simultaneously, and tags for
screening are included in Appendix G For peer-reviewed literature, title/abstract and full text
screening were done separately, and tags for each stage are included in Appendix H.2.
10 DRAGON is an online tool for systematic review developed by ICF that stores qualitative and quantitative data from
literature to help scientists implement the elements of systematic review, including problem formulation, literature
screening, risk of bias evaluation, and data integration.
Page 75 of 94
-------
E.3 PECO Statement
Chemical
PCTP
PECO Element
Evidence
Population
Human: Workers and occupational non-users; general population; consumers and
bystanders in residential settings; near-facility populations (includes industrial and
commercial facilities manufacturing, processing, or using PCTP); populations living at or near
hazardous waste, industrial or chemical waste disposal sites; populations with subsistence
diets; children; infants; pregnant women; lactating women; women of childbearing age;
susceptible populations (life stages, preexisting conditions, genetic factors). No chemical-
specific exclusions are suggested at present.
Ecological: Aauatic organisms (edible and nonedible fish, aauatic invertebrates (daphnia),
amphibians); terrestrial organisms (plants, soil invertebrates (worms), birds, mammals). No
chemical specific exclusions are suggested at present.
Exposure
Expected Exposure Sources, Pathways, Routes
Source: Industrial activities (manufacturing, processing, recvcling, treatment, disposal of
products); commercial and consumer uses of consumer products containing PCTP and
associated releases to air, water, or wastes (wastewater/liquid wastes, solid wastes); use as a
soil fungicide, herbicide, and slime prevention in industrial waters; metabolite of
hexachlorobenzene; metabolite and degradation product of pentachloronitrobenzene
Pathwav: Waste streams (e.g., landfills, biosolids); outdoor air (fugitive/stack emissions);
drinking water; surface water/groundwater (transfer from outdoor air/soil); indoor air
(transfer from outdoor air); soil/sediment; dust; contact with products; liquid contact; vapor
intrusion; food (breastmilk, fish, meat, eggs, dairy); media-specific background and source
attribution to be considered.
Routes: Inhalation (indoor and ambient air); oral (dietarv ingestion of food or breastmilk,
incidental ingestion of contaminated soil and dust, hand-to-mouth contact, ingestion of
drinking water, ingestion of suspended particles, mouthing of consumer articles); dermal
(contact with dust, soil, consumer products containing PCTP or other secondary vectors)
Comparator
(Scenario)
Human: Consider media-specific background exposure scenarios and use/source specific
exposure scenarios as well as which receptors are and are not reasonably exposed across the
projected exposure scenarios.
Ecological: Consider media-specific background exposure scenarios and use/source specific
exposure scenarios as well as which receptors are and are not reasonably exposed across the
projected exposure scenarios.
Outcomes for
Exposure
Concentration
or Dose
Human: Acute, subchronic, and/or chronic external dose estimates (mg/kg/dav); acute,
subchronic, and/or chronic internal dose based on biomonitoring and reverse dosimetry
(mg/kg/day); acute, subchronic, and/or chronic air, soil, dust, and water concentration
estimates (mg/m3 or mg/L).
Ecological: A wide range of ecological receptors will be considered using surface water,
sediment, soil, and air concentrations. Targeted use of wildlife biomonitoring data will also
be explored.
Page 76 of 94
-------
E.4 PRISMA Diagram
The PRISMA Diagram for PCTP, including literature counts from search, screening and included
phases from all sources, is presented inError! Reference source not found. Figure E-2. A subset of
studies that passed the screening phase were not extracted or evaluated due to the ready
availability of the full text and supplemental information. Due to time constraints, studies that did
not include data in text or tables, and studies that had fewer than 10 observations were not
extracted or evaluated.
PCTP
Data sources identified
through open literature,
backward searching, and
public comments n = 334
Data sources identified
through gray literature
n = 106
I
Data sources identified
through open lit from
similar chemicals n = n/a
Total
Searched =
440
On-topic after title-
abstract screen n= 99
On-topic after full-text
screen n= 13
On-topic after combined
title-abstract—full-text
screen n= 20
On-topic after machine
learning n= n/a
On-topic after full-text
screen n= n/a
Total On-topic
Core n= 22
Total On-topic
Supplemental n= 23
Total on
topic
= 33
Total Studies that were able to
be extracted n= 3
Total Studies that were
extracted and passed
evaluation criteria n= 0
Total
included
= 0
Did not meet
evaluation
criteria screen
n = 3
Not on Topic-
Did not meet
full text tag
criteria
n = 407
Excluded -
Were not able
to be
extracted n = 9
Excluded - Did
not meet full
evaluation
criteria n = 3
Figure E-2. PRISMA Diagram for PCTP
E.5 Data Evaluation Criteria
Core exposure data includes the following exposure data types:
- Environmental monitoring
- Biomonitoring
- Database Sources
Page 77 of 94
-------
- Completed Assessments
- Modeling
Assessors evaluated the extracted core exposure data for evaluation criteria specific to the data
type. The data evaluation criteria are included in (U.S. EPA. 2018).
E.6 Data Extraction Fields
Core exposure data, including monitoring data and modeled estimates of concentration or dose,
was extracted in DRAGON. The data extraction fields are included in Appendix I.
Page 78 of 94
-------
Appendix F. Overall Workflow for Systematic Review
SR Database with HEROIDs, Titles, Abstracts for Peer & Gray Literature Delivered by Literature Search
Title-Abstract Screening
Development Phase
Full Text Screening Development
Phase
Data Extraction Development
Phase
Data Evaluation Development
Phase
Conducted in Excel
On Topics pass to
Full Text Screening
Full Text & Ref Flag screening
On Topics pass to
Extraction
10% QA
ii
Review
i
¦
10% QA
M
Review
Data Extraction (Peer & Gray)
Extracted studies
pass to evaluation
10% QA
Review
Data Evaluation (Peer& Gray)
Studies of
acceptable quality
pass to integration
Data Integration
(Peer & Gray)
m
10% OA
H
Review
DecaBDE Prioritization
Use text analytics
(ensemble
clustering+
machine learning)
to prioritize results
for manual review
This phase ONLY applies to DecaBDE + PBDE
database search results NOT caught in DecaBDE
database search.
Closely Related Chemical Prioritization
Use text analytics
(ensemble
clustering+
machine learning)
to prioritize results
for manual review
This phase ONLY applies to Tris, PIP, and PCTP
Conducted in ICF's DoCTER
I
Conducted in ICF's DRAGON
Page 79 of 94
-------
Appendix G. Inclusion and Exclusion Criteria for Title/Abstract and Full Text Screening
For title/abstract screening, references were classified as either On Topic or Off Topic with regards to the criteria presented in
Table G-l. Although multiple tags were not introduced at this stage, the inclusion and exclusion criteria were organized around subject
matter areas for purposed of presentation. Full text PDFs will be sought for references that are determined to be On Topic at the
title/abstract stage via HERO's "Fetch" feature, Endnote "Find Full Text", and Reprintz. Only references determined to be On Topic with
a full text PDF available will be considered for full text screening.
Table G-l. Inclusion/Exclusion Criteria for PBT 5
Tier 2 Screening
Category
Exposure
Category
Inclusion Criteria
Exclusion Criteria
Example Keywords
Core
Ecological
Exposure
Covers ecological exposure, including exposure
to aquatic and terrestrial flora and fauna and
media where these organisms live (water, soil,
sediment)
Toxicity studies that describe
hazards to ecological organisms.
Concentration with associated units,
e.g., mg/m3, mg/g, etc., mammal,
avian, fish, aquatic
Covers is measurements were taken, even if
data not reported
Covers any supplemental data on exposure
sources, pathways, routes, or populations that
could be used to construct an ecological
exposure scenario (uses, releases, outdoor
fate).
Core
General
Population
Exposure
Covers exposure to the general population due
to concentrations in outdoor and indoor
environmental media.
Method validation studies
involving exposures to laboratory-
produced chemical or chemical
mixture in a lab setting, rather
than environmentally-derived
samples
general population exposure/dose
with associated units, e.g., mg/kg,
m/kg/day, etc., blood, urine, tissue,
releases, background levels,
ambient/outdoor air, deposition,
surface water, drinking water, ground
water, soil, dust, sediment, sludge,
disposal, life cycle
Covers exposure to the general population due
to concentrations in other edible species and
food through dietary uptake.
Toxicity studies that describe
hazards to animals (usually
terrestrial mammals) used to
assess toxicity to humans
Page 80 of 94
-------
Tier 2 Screening
Category
Exposure
Category
Inclusion Criteria
Exclusion Criteria
Example Keywords
Covers estimated doses to humans through
biomonitoring and/or PBPK or quasi-PBPK
modeling, Toxicokinetics studies using
environmentally relevant exposures.
Toxicokinetic studies that describe
ADME using spiked doses
Covers any supplemental data on exposure
sources, pathways, routes, or populations that
could be used to construct a general
population exposure scenario (uses, releases,
outdoor fate).
Covers exposure to consumers who use a
product or article containing the chemical
Method validation studies
involving exposures to laboratory-
produced chemical, rather than
environmentally-derived samples
consumer product exposure/dose
with associated units, e.g., mg/kg,
m/kg/day, etc., indoor/residential,
product, article, aerosol, dust, indoor
air, hand-to-mouth, surface, shower,
dermal loading, blood, urine, tissue
Core
Consumer
Covers exposure to consumers who are close
proximity of a product or article present in
their living space
Unverifiable or anecdotal reports
of consumer use. For example,
secondary sources that do not cite
a source.
Exposure
Covers any supplemental data on exposure
sources, pathways, routes, or populations that
could be used to construct a consumer
exposure scenario (uses, consumer surveys on
use patterns, releases/emissions from
experimental data, indoor fate).
Toxicity studies that describe
hazards to animals (usually
terrestrial mammals) used to
assess toxicity to humans
Toxicokinetic studies that describe
ADME using spiked doses
Core
Potentially
exposed and
susceptible
subpopulations
Covers exposure for a potentially exposed and
susceptible subpopulation exposed at a higher
level than the general population [Include
above]
susceptible/sensitive subpopulation,
infants, children, pregnancy, senior,
aged, elderly, older women, men,
gender, immunocompromised,
diseased population, preexisting
Page 81 of 94
-------
Tier 2 Screening
Category
Exposure
Category
Inclusion Criteria
Exclusion Criteria
Example Keywords
disease, genetics, socioeconomic
status, race
highly-exposed sub population, near-
facility population, higher-than-
average exposure, above background,
populations near manufacturing
facilities
Supplemental -
Engineering
Process
Information
Studies pertaining to chemical processes
containing information on life cycle,
production volume (including HPV status),
descriptions of processes, and manufacturing
sites
Life cycle, production volume, use
volume, import, process description,
process flow diagram, product
concentration, sites, manufacture,
process, release, emission, industry,
facility
Supplemental -
Engineering
Occupational
exposure
Occupational exposure studies that contain or
may contain information on breathing zone
(personal sample) measurements of
occupational exposures to the chemical(s) of
interest, measured as time-weighted averages
(TWAs), dermal exposure estimates (skin
loading), and/or biological monitoring as part
of occupational surveillance.
Mentions toxicity-based exposure
regulatory limits only but does not
contain exposure
values/estimates;
Worker, worker activities, worker
exposure, occupational exposure,
inhalation, dermal, personal sample,
time-weighted average, breathing
zone, PPE, personal protective
equipment, engineering controls,
exposure reduction, ventilation
Covers any supplemental data on exposure
sources, pathways, routes, or populations that
could be used to construct an occupational
exposure scenario (uses, occupational surveys,
process description, process-flow diagram,
emissions, indoor fate). See below
Toxicity studies that describe
hazards to animals (usually
terrestrial mammals) used to
assess toxicity to humans
Description of worker activities with exposure
potential during the manufacture, processing,
or use of the chemical(s) of interest in each
industrial/commercial life cycle stage.
Toxicokinetic studies that describe
ADME using spiked doses
Page 82 of 94
-------
Tier 2 Screening
Category
Exposure
Category
Inclusion Criteria
Exclusion Criteria
Example Keywords
Physical form of the chemical(s) of interest for
each exposure activity (e.g., liquid, vapor, mist)
and activity.
For solids, bulk and dust particle size
characterization data.
Information on short-term exposures, or peak
exposures in each occupational life cycle stage
(or in a workplace scenario like an
occupational life cycle stage).
Supplemental -
Engineering
Occupational
Exposure
Modeling
Worker exposure duration for specific tasks
(hr/day)
Exposure frequency for specific tasks (days/yr).
Number of workers who potentially handle or
have exposure to the chemical(s) of interest in
each occupational life cycle stage.
Personal protective equipment (PPE) types
employed by the industries within scope.
Engineering controls employed to reduce
occupational exposures in each occupational
life cycle stage (or in a workplace scenario
similar to the life cycle stage of interest), and
associated data or estimates of exposure
reductions.
Supplemental -
Engineering
Environmental
Releases
Studies pertaining to releases from industrial
facilities that manufacture, process, use, or
dispose the chemical substance across the life-
cycle of the chemical.
Release, emission, release rate,
release frequency, point source, area
source,, landfill, incineration, POTW,
WWTP, on-site treatment, sewage or
Page 83 of 94
-------
Tier 2 Screening
Category
Exposure
Category
Inclusion Criteria
Exclusion Criteria
Example Keywords
The total annual U.S. volume (Ib/yr) or kg/yr)
of the chemical(s) of interest manufactured,
imported, processed, and used
The share of total annual manufacturing and
import volume that is processed or used in
each life cycle step.
Description of processes, equipment, unit
operations, and material flows and frequencies
of the chemical(s) of interest during each
industrial/ commercial life cycle step.
Number of sites that manufacture, process, or
use the chemical(s) of interest for each
industrial/ commercial life cycle step and site
locations.
Description of sources of potential
environmental releases, including cleaning of
residues from process equipment and
transport containers, involved during the
manufacture, processing, or use of the
chemical(s) of interest in each life cycle stage.
Estimated mass of the chemical(s) of interest
released from industrial and commercial sites
to each environmental medium (air, water,
land) and treatment and disposal methods
(POTW, incineration, landfill), including
releases per site and aggregated over all sites
(annual release rates, daily release rates)
Release or emission factors, loss fractions.
wastewater treatment, disposal,
pretreatment program, recycling,
sludge, effluent, process diagram,
process flow, loss fraction, emission
rate, flux
Page 84 of 94
-------
Tier 2 Screening
Category
Exposure
Category
Inclusion Criteria
Exclusion Criteria
Example Keywords
Number of release days per year for industrial
process of interest.
Waste treatment methods and pollution
control devices employed by the industries
within scope and associated data on
release/emission reductions.
Any fate information that could be used to
inform an exposure scenario. Studies that
characterize transport and transformation in
the environment or through organisms,
including if the chemical of interest is a
metabolite
Secondary physical-chemical
property information for chemical
substances
KOA, KOW, KAW, KOC, Kd,
partitioning coefficient, fugacity, flux,
groundwater, migration, sediment,
leach, soil, sorb, sorption, adsorption,
dust, particles, aerosol, volatility,
solubility;
Supplemental -
Fate
Fate & Transport
Primary physical-chemical property
information for chemical substances
Studies that are solely for the
purpose of quantifying a fate
parameter above, but are
laboratory experiments using
laboratory-derived chemicals or
laboratory simulations, and do not
put the results in context of
environmentally relevant
conditions
Persistence, half-life, hydrolysis,
photolysis, photostability,
biodegradation, aerobic, anaerobic,
metabolism, reduction, degradation,
transformation;
Any fate information that could be used to
inform an exposure scenario.
Laboratory experiments using
environmental sample under non-
natural conditions or added
substrates, not naturally occurring
in environment
BCF, BAF, BSAF, trophic magnification,
biomagnification, bioaccumulation,
bioconcentration, biota sediment
accumulation factor, biotransfer
Studies that characterize transport and
transformation in the environment or through
organisms.
Test systems, laboratory
experiments, or demonstrations
where conditions are clearly not
Page 85 of 94
-------
Tier 2 Screening
Category
Exposure
Category
Inclusion Criteria
Exclusion Criteria
Example Keywords
The types of data for how chemicals are
transported or transformed in and through
environmental media are listed below: abiotic
reduction rates or half-lives, abiotic
dehalogentation, aerobic biodegradation or
half-lives, anaerobic biodegradation rates or
half-lives, direct and indirect aqueous
photolysis, direct and indirect atmospheric
photolysis or half-lives, bioconcentration
factors and bioaccumulation factors, hydrolysis
rates, or half-lives, volatilization rates, sorption
rates to organic matter in outdoor
environments, diffusion and sorption rates and
sink information in indoor environments
(material-air partition coefficient, diffusion-
coefficient, mass-transfer), source degradation
through abrasion, direct-transfer of dust to
surfaces, abiotic transformation, aerobic
biotransformation, atmospheric deposition,
atmospheric flux, biomagnification and trophic
magnification, coagulation, desorption,
suspension and resuspensions, incineration
removal information, and wastewater
treatment removal information.
relevant to naturally-occurring
conditions
Physical Chemical Properties
Supplemental -
Other
Use
Contains information related to uses described
in EPA's "Preliminary information on Use"
Documents. Screeners should read these
documents prior to screening.
Contains information about potential use
scenarios, even if not chemical specific.
Anecdotal information (without a
reference) about a chemical's use
across its lifecycle.
Supplemental -
Other
Pathways and
Settings
Contains exposure scenarios information or
pathways of Emission to receptor.
Page 86 of 94
-------
Appendix H. DRAGON Form and Screening Tags
H.l DRAGON Screening Form
The user interface for the screening forms in DRAGON is presented in Figure H-l.
T^DAnnM OPPT PBT5 - DecaBDE
UKMV7UM assksnment
'ICF
Full Text Screening: Screener
1
DEVON MORGAN LOG OUT
\
TASKS INSTRUCTIONS
< PREV NEXT >
Task Status: Assigned
Polybrominated diphenyl ethers (PBDEs) in soils along a rural-urban-
rural transect: sources, concentration gradients, and profiles
HIGHLIGHTS
This study reports concentrations of PBDEs in surface soil samples collected
along a 140 km transect across Kuwait to assess the role of urban centers as
sources of persistent organic pollutants to the surrounding environment. The
SPBDE concentrations varied by a factor of -250 and ranged from 289 to
80.078 pgg (-l)d.w. The concentrations of PBDEs in Kuwait City were
significantly higher (p<0.01) than those collected from sites outside the city
supporting the hypothesis that urban centers are sources of PBDEs The
congener profiles were dominated by BDE-209, accounting for 93% of the
PBDEs in the soil samples The concentrations of all congeners (except BDE-
209) were highly correlated with percent organic carbon (%OC) (p>0.05)
when the data from Kuwait City was omitted from the analysis. These findings
suggest that soil concentrations outside the urban centers were close to
equilibrium with the atmosphere.
DRAGON Study Name: Gevao et al. 2011
Authors: Gevao. B. Ghadban, A. N. Uddin, S. Jaward, F. M. Bahloul, M. Zafar, J.
Journal: Environmental Pollution
Reference: Gevao. B. Ghadban. A. N. Uddin. S. Jaward. F. M. Bahloul. M. Zafar. J. (2011).
Polybrominated diphenyl ethers (PBDEs) in soils along a rural-urban-rural transect sources,
concentration gradients, and profiles. Environmental Pollution 159(12): 3666-3672.
DRAGON Id: 1059814
Herold: 1059814
Taskld: 1108493
Categories
DESCRIPTIONS
Full Text
Chemical Specific
Closely related
chemical to PBT5
Different PBT5
HCBD
PIP
PCTP
Tris
General environmental
chemical not related to
PBT5
For PBT Chemical of
interest
Core
Environmental
Title/Abstract (DragonScreen)
Exposure PECO
Chemical-specific
TiAbs On Topic
Peer Title/Abstract (DragonScreen)
Chemical specific
Exposure PECO
TiAbs On
U
~
~ ~
~
~
~
~
~
~
~
~ .
Study navigation
Study details
Full text tagging
Tags selected
during Ti/Abs
Figure H-l. DRAGON Full Text Screening User Interface
Page 87 of 94
-------
H.2 Peer-Reviewed and Gray Literature Tagging Structures in DRAGON
The title/abstract screening and full text screening occurred separately for peer-reviewed
literature. The title/abstract screening and full text screening occurred simultaneously for gray
literature. The full text screening tagging structure for screeners in DRAGON is displayed in
Figure H-2 .
Peer Reviewed Literature Gray Literature
Categories
Fta PSTCNHttctfof
" -
tmm efcemst#
' ¦. I"- i'i *
omvm
Me
Figure H-2. Full Text Tagging Structure in DRAGON
Page 88 of 94
-------
H.3 DRAGON Extraction Form
The user interface for the data extraction forms in DRAGON is presented in Figure H-3.
OPPT PBT5 - DecaBDE
DRAGON
Jc 1
'ICF I
Da&a Extraclion Pitot Exlractor
0CV9MM0AQAN lOGOCTT
T«h l/S TASKS l^rfSTRUCTVOWS
i PflEV MEXT> J3J
Study navigation
fttl* feCincU^^ cf P«D€i.4™JPCB4
flUlSlKUt AMign«d
SlmSy m»Jt
WanrwwJ »
by MOM irrtSa«*f!|
Pu*T«xt
Chftrtitftl SfM^Ac
s
Tags selected during
Dw* Ml »«t Urging nquim QA?
; ' ! . . - •• -
Cora
'
1
Full Text screen
MAfUDflig
C&r«*ftir*e«tt4
Piirrary
Qufrota&v*
r* ApplKJfc** firvl *T*i D*f» Sew -
uuU* tor Mtraeuon?
Ar.-frr.iahU-
1® IHKCI ilw i
Figure H-3. Data Extraction Form Structure in DRAGON
Page 89 of 94
-------
H.4 DRAGON Evaluation Form
The user interface for the data extraction forms in DRAGON is presented in Figure H-4.
Figure H-4. Data Evaluation Form Structure in DRAGON
Page 90 of 94
-------
Appendix I. Data Extraction Fields
Field Name
Descriptor
Study quality Criteria Met?
Yes/No
Are raw data provided in
supporting material?
Yes/No
Study Populations
Population
Homes in Wisconsin, Hispanic Mothers, West Virginia Miners, Coho
Salmon from Great Lakes, Degreasing products,...etc.
Country
USA
Locations Details
Madison, Wl
Location Type
For monitoring studies: Rural, Urban, Near Facility, Remote, Mixed
For Biomonitoring: Occupational Exposure, Studies: Occupational
For... etc.
Description
Description
Medium
Matrix
Air, water, sediment, soil, blood, urine, fish tissue,...etc.
Matrix Type
Environmental sample (monitoring) | Biological sample
(biomonitoring) | Consumer Product
Number of Samples
#
Sampling year (Dates of
collection)
01/1996-06/1998
Sampling Notes (expand)
Description
Chemistry
Chemical Name
HCBD, Deca, PIP, TRIS, PCTP
CAS number (if study provided)
#
Mean
#
Reported Mean?
Study Reported | ICF Calculated
Median
#
Reported Median?
Study Reported | ICF Calculated
Page 91 of 94
-------
Central Tendency Unit
e.g. ng/g or ng/m3...etc.
Central Tendency Notes
Description
Min
#
Max
#
Total observations reported
#
Number of non-detects
reported
#
Is the analytical method
described or referenced?
Yes|No
Analytical Method name
OCs by GC-ECD or VOCs by GC-MS...etc.
Analytical method description
(Combine extraction,
Instrument, Type)
EPA Method 6000, FDA Fish Tissue method, Accelerated solvent
extraction and analysis via LC-MSMS...etc.
Detection Limit
#
Detection Limit Unit
ug/g
Detection Limit Type
Method detection limit | Method reporting limit | Instrument detection
1 imit | Instrument reporting limit
Method Reporting notes
Authors also reported method detection limit of 0.005 ng/g
Modeled Media Concentrations
Matrix
Air, water, sediment, soil, blood, urine, fish,...etc.
MatrixType
Environmental sample (monitoring) | Biological sample
(biomonitoring) | Consumer Product
Modeling Notes
Description
Chemistry
Chemical Name
HCBD, Deca, PIP, TRIS, PCTP
CAS number (if provided)
#
Model Estimate
Estimate Name
50th Percentile, 95th Percentile, High estimate
Estimate
#
Estimate Unit
Hg/g
Estimate Notes
Description
Page 92 of 94
-------
Modeled Dose
Receptor Name
3-year old children, adults...etc.
Receptor Type
Species (e.g., Human)
Receptor notes
Description
Chemistry
Chemical Name
HCBD, Deca, PIP, TRIS, PCTP
CAS number (if provided)
#
Chemical Notes
Description (e.g., Bioavailable concentration)
Dose Estimate
Dose Name
Inhalation (air), inhalation (particulate), food ingestion, total
exposure,...etc
Dose Estimate
#
Dose Unit
(Hg/kg)/day
Dose Notes
Description
Overall Study
Overall Notes
Description (e.g., Raw data provided in Table 3, could calculate mean
and median.)
Does full text tagging require
OA?
Yes|No
Follow up flag
Description
Page 93 of 94
-------
Appendix J. References
Howard. BE; Phillips, J; Miliar, K; Tartdon, A; Mav, D; Shah, MR; Holmgren, S; Reich, KE; Walker.
V; Rooney, AA; Macleod, M; Shah. RR; Thayer, K, (2016). SWIFT-Review: a text-mining
workbench for systematic review. Systematic Reviews. 5: 87.
http://dx.doi.org/10.1186/sl3643-016-Q263-z.
OLRC (Office of the Law Revision Counsel). (2016). Toxic substances control. Prioritization, risk
evaluation, and regulation of chemical substances and mixtures. (15 USC Ch. 53 2605).
http://uscode,house,gov/view,xhtml?path=/prelim%40titlel5/chapter53&edition=preli
m.
U.S. EPA (U.S. Environmental Protection Agency). (2018). Application of systematic review in
TSCA risk evaluations. (740-P1-8001). Washington, D.C.: U.S. Environmental Protection
Agency, Office of Chemical Safety and Pollution Prevention.
https://www.epa.gov/sites/production/files/2018-
06/documents/final application of sr in tsca 05-31-18.pdf.
Varghese, A: Cawley, M: Hong. T, (2017). Supervised clustering for automated document
classification and prioritization: A case study using toxicological abstracts. Environ Syst
Decis. http://dx.doi.org/10.1007/slQ669-017-9670-5.
Page 94 of 94
------- |