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Dossier for Candidate Low-Priority Substance D-Gluconic Acid,
potassium salt (1:1)
(CASRN 299-27-4)
(Potassium Gluconate)
For Release at Proposal
August 9, 2019
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue
Washington, DC 20460
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Contents
1. Introduction 3
2. Background on Potassium Gluconate 5
3. Physical-Chemical Properties 6
3.1 References 8
4. Relevant Assessment History 9
5. Conditions of Use 10
6. Hazard Characterization 12
6.1 Human Health Hazard 15
6.1.1 Absorption, Distribution, Metabolism, and Excretion 17
6.1.2 Acute Toxicity 18
6.1.3 Repeated Dose Toxicity 18
6.1.4 Reproductive and Developmental Toxicity 19
6.1.5 Genotoxicity 19
6.1.6 Carcinogenicity 20
6.1.7 Neurotoxicity 20
6.1.8 Skin Sensitization 20
6.1.9 Skin Irritation 21
6.1.10 Eye Irritation 21
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations 21
6.2 Environmental Hazard 21
6.2.1 Acute Aquatic Toxicity 21
6.2.2 Chronic Aquatic Toxicity 22
6.3 Persistence and Bioaccumulation Potential 22
6.3.1 Persistence 22
6.3.2 Bioaccumulation Potential 22
7. Exposure Characterization 23
7.1 Production Volume Information 23
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7.2 Exposures to the Environment 23
7.3 Exposures to the General Population 24
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations 24
7.4.1 Exposures to Workers 24
7.4.2 Exposures to Consumers 24
8. Summary of Findings 26
8.1. Hazard and Exposure Potential of the Chemical Substance 26
8.2. Persistence and Bioaccumulation 27
8.3. Potentially Exposed or Susceptible Subpopulations 27
8.4. Storage Near Significant Sources of Drinking Water 28
8.5. Conditions of Use or Significant Changes in Conditions of Use of the Chemical Substance 29
8.6. The Volume or Significant Changes in Volume of the Chemical Substance Manufactured or Processed.... 30
8.7. Other Considerations 30
9. Proposed Designation 31
Appendix A: Conditions of Use Characterization i
A.1. CDR Manufacturers and Production Volume i
A.2. Uses II
A.2.1 Methods for Uses II
A.2.2 Uses of Potassium gluconate IV
A.3 References X
Appendix B: Hazard Characterization XIII
B.1 References XXX
Appendix C: Literature Search Outcomes XXXIII
C.1 Literature Search and Review XXXIII
C.1.1 Search for Analog Data XXXIII
C.1.2 Search Terms and Results XXXIV
C.2 Excluded Studies and Rationale XLIII
C.2.1 Human Health Hazard Excluded References XLIII
C.2.2 Environmental Hazard Llll
C.2.3 Fate LIX
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Tables
Table 1: Potassium Gluconate at a Glance 5
Table 2: Physical-Chemical Properties for Potassium Gluconate 6
Table 3: Conditions of Use for Potassium Gluconate 11
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects 12
Table 5: Potassium Gluconate and Analog Structures 16
Table A.1:1986-2015 National Production Volume Data for Potassium Gluconate (Non-Confidential i
Production Volume in Pounds)
Table A.2: Sources Searched for Uses of Potassium Gluconate II
Table A.3: Uses of Potassium Gluconate IV
Table B.1: Human Health Hazard XIII
Table B.2: Environmental Hazard XXVI
Table B.3: Fate XXVII
Table C.1: Sources Used for Analog Search XXXIV
Table C.2: Search Terms Used in Peer-Reviewed Databases XXXIV
Table C.3: Search Terms Used in Grey Literature and Additional Sources XLII
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard XLIII
Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human XLVII
Health Hazard
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for L
Human Health Hazard - Animal
Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Lll
Human Health Hazard - In Vitro
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard Llll
Table C.9: Screening Questions and Off-Topic References Excluded at Full-Text Screening for LVII
Environmental Hazard
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Table C.10: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for LVIII
Environmental Hazard
Table C.11: Off-Topic References Excluded at Initial Screening for Fate LIX
Table C.12: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate LXXI
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for LXXI
Fate
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1. Introduction
In the Lautenberg amendments to the Toxic Substances Control Act (TSCA) (section 6(b)(1)(B)) and
implementing regulations (40 CFR 702.3), a low-priority substance is described as a chemical
substance that the Administrator concludes does not meet the statutory criteria for designation as a
high-priority substance, based on information sufficient to establish that conclusion, without
consideration of costs or other non-risk factors. A high-priority substance is defined as a chemical
substance that the Administrator concludes, without consideration of costs or other non-risk factors,
may present an unreasonable risk of injury to health or the environment because of a potential hazard
and a potential route of exposure under the conditions of use, including an unreasonable risk to
potentially exposed or susceptible subpopulations identified as relevant by the Administrator. D-
Gluconic Acid, potassium salt (1:1), referenced as potassium gluconate for the remainder of this
document, is one of the 40 chemical substances initiated for prioritization as referenced in a March
21, 2019 notice (84 FR 10491).1
Before determining low or high prioritization status, under EPA's regulations at 40 CFR 702.92 and
pursuant to section 6(b)(1)(A) of the statute, EPA will generally use reasonably available information
to screen the candidate chemical substance under its conditions of use against the following criteria
and considerations:
• the hazard and exposure potential of the chemical substance;
• persistence and bioaccumulation;
• potentially exposed or susceptible subpopulations;
• storage near significant sources of drinking water;
• conditions of use or significant changes in the conditions of use of the chemical substance;
• the chemical substance's production volume or significant changes in production volume; and
• other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority.
Designation of a low-priority substance indicates that the chemical substance does not meet the
statutory criteria for a high-priority substance and that a risk evaluation is not warranted at the time.
This risk-based, screening-level review is organized as follows:
• Section 1 (Introduction): This section explains the requirements of the Lautenberg
amendments to the Toxic Substances Control Act (TSCA) and implementing regulations -
including the criteria and considerations ~ pertinent to prioritization and designation of low-
priority substances.
1 https://www.federalregister.gov/docimients/2019/03/21/2019-054Q4/initiation-of-prioritization-under-tlie-toxic-substances-
control-act-tsca
2 Hie prioritization process is explained in the Procedures for Prioritization of Chemicals for Risk Evaluation Under the
Toxic Substances Control Act (82 ER 33753).
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• Section 2 (Background on the Proposed Low-Priority Substance): This section includes
information on attributes of the chemical substance, including its structure, and relates them
to its functionality.
• Section 3 (Physical-Chemical Properties): This section includes a description of the physical-
chemical properties of the chemical substance and explains how these properties lead to the
chemical's fate, transport, and exposure potential.
• Section 4 (Relevant Assessment History): This section includes an overview of the outcomes
of other governing entities" assessments of the chemical substance.
• Section 5 (Conditions of Use): This section presents the chemical substance's known,
intended, and reasonably foreseen conditions of use under TSCA.
• Section 6 (Hazard Characterization): This section summarizes the reasonably available
hazard information and benchmarks the information against low-concern thresholds.
• Section 7 (Exposure Characterization): This section includes a qualitative summary of
potential exposures to the chemical substance.
• Section 8 (Summary of Findings): In this section, EPA presents information pertinent to
prioritization against each of the seven statutory and regulatory criteria and considerations,
and proposes a conclusion based on that evidence.
• Section 9 (ProposedDesignation): In this section, EPA presents the proposed designation for
this chemical substance.
• Appendix A (Conditions of Use Characterization): This appendix contains a comprehensive
list of TSCA and non-TSCA uses for the chemical substance from publicly available
databases.
• Appendix B (Hazard Characterization): This appendix contains information on each of the
studies used to support the hazard evaluation of the chemical substance.
• Appendix C (Literature Search Outcomes): This appendix includes literature search outcomes
and rationales for studies that were identified in initial literature screening but were found to
be off-topic or unacceptable for use in the screening-level review.
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2. Background on Potassium Gluconate
Table 1 below provides the CAS number, synonyms, and other information on potassium gluconate.
Table 1: Potassium Gluconate at a Glance
Chemical Name
Potassium Gluconate
CASRN
299-27-4
Synonyms
Potassium D-gluconate; D-Giuconic acid, monopotassium salt; Gluconic acid
potassium salt; Gluconic acid, monopotassium salt
Trade Name(s)
Potassuril; Kaon elixir; Katorin; Potalium; Potasoral; Sirokal; Kaon; Kalium-beta;
Glucosan K; Tumil-K
Molecular Formula
CbHuKO?
Representative
Structure
Ho rH
° J °H
Source(s):
Kim etal. (2016)
Potassium gluconate is a water-soluble organic potassium salt of gluconic acid. Gluconate salts are
oxidation products of glucose and occur widely in nature. Potassium gluconate belongs to the
hydroxycarboxylic acid salt family. The chemical structure of potassium gluconate consists of a six-
carbon chain with five hydroxyl (-OH) groups terminating in a carboxylic acid group. The close
proximity of the oxygen atoms within the chemical structure lends to its function as a highly efficient
chelating agent. Chelating agents bind to positively charged metal ions in solution and prevent them
from forming insoluble precipitates with other ions that may be present. Potassium gluconate
functions as a chelating agent over a wide pH range. It is efficient in forming stable chelates with
divalent and trivalent metal ions such as calcium, copper, iron, aluminum, and other metals and can
reduce the adverse effects these metals can have on systems. Potassium gluconate is used as a
sequestrant and skin conditioning agent in a variety of applications and product sectors. Section 5
includes conditions of use for this chemical.
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3. Physical-Chemical Properties
Table 2 lists physical-chemical properties for potassium gluconate. A chemical's physical-chemical properties provide a basis for understanding a
chemical's behavior, including in the environment and in living organisms. These endpoints provide information generally needed to assess
potential environmental release, exposure, and partitioning as well as insight into the potential for adverse toxicological effects.
Table 2: Physical-Chemical Properties for Potassium Gluconate
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
Sigma-Aldrich 2019
Experimental
Physical state at
room temp
(based on melting
point)
Solid (183°C)
OECD SIDS initial
assessment report, Gluconic
acid and its derivatives
(OECD SIDS 2004)
Experimental
Molecular weight
234 g/mol
EPISuite v.4.113
Calculated
Molecular weight
234.25 g/mol
OECD SIDS 2004
Experimental
Molar volume
190.5 cm3/mol
OECD SIDS 2004
Experimental
Water solubility
450000 mg/L at
20°C;
1000000 mg/L at
25°C
EPISuite v.4.11
Estimated
Water solubility
1.0x106 mg/L
OECD SIDS 2004
Experimental
Water solubility
1.92 mol/L
EPISuite v.4.11
Estimated
Log Kow
<-2
EPISuite v.4.11
Estimated
Log Koa
Not calculated
EPISuite v.4.11
Estimated
Log Koc
1 (MCI); 3.98 (Kow)
EPISuite v.4.11
Estimated
Vapor pressure
<1E-8 mm Hg
EPISuite v.4.11
Estimated
Henry's Law
<1E-8 atm-m3/mol
3 EPI Suite Physical Property Inputs - Water solubility= 450000 mg/L, SMILES: 0CC(0)C(0)C(0)C(0)C(=0)(0K))
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Table 2: Physical-Chemical Properties for Potassium Gluconate
Source/
Model
Data Type
Endpoint
Endpoint value
Notes
EPISuite v.4.11
Estimated
Volatilization
7.54x1014days (river)
8.23x1019 days (lake)
EPISuite v.4.11
Estimated
Photolysis
(Indirect)
3.37 hours (T1/2)
OH rate constant 3.81 E-11 cm3/molecules-second (12 hour day; 1.5E6
OH/cm3)
EPISuite v.4.11
Estimated
Hydrolysis
Rate constants
cannot be estimated
No hydrolyzable functional groups
EPISuite v.4.11
Estimated
Biodegradation
potential
Ready prediction: yes
EPISuite v.4.11
Estimated
BAF
0.89
EPISuite v.4.11
Estimated
BCF
3.16
Based on regression
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EPA's Sustainable Futures/P2 Framework Manual4 was used to interpret the physical-chemical
properties provided in Table 2. Based on its reported physical form and measured melting point,
potassium gluconate is a solid under ambient conditions (Sigma-Aldrich, 2019). In the solid form,
potassium gluconate has the potential for exposure via direct dermal contact with the substance,
through ingestion, and through inhalation of dust particles if they are generated. Because it is a salt,
potassium gluconate is expected to be a non-volatile substance. Based on measured solubility data,
potassium gluconate is considered water soluble, indicating the potential for this substance to dissolve
in water and form an aqueous solution (OECD SIDS, 2004). The estimated Henry's Law constant
(U.S. EPA, 2019) indicates volatilization from water and aqueous solutions is not expected to occur.
Therefore, exposure to vapors under ambient conditions via inhalation is expected to be minimal.
Water soluble substances also have an increased potential for absorption through the lungs; therefore,
if exposed to the chemical in dust, absorption through the lungs is likely. Oral exposure to this
chemical could result in absorption through the gastrointestinal tract based on experimental evidence
(discussed in Section 6.1.1). However, based on its estimated log Kow, potassium gluconate is
unlikely to cross lipid membranes and sequester in fatty tissues, as confirmed by its estimated
bioconcentration factor (BCF) and bioaccumulation factor (BAF) (U.S. EPA, 2019). The estimated
log Koc indicates this substance is highly mobile in soils, increasing its potential for leaching into, and
transport in, groundwater, including well water. Potassium gluconate is expected to have low
persistence. Experimental data indicate it is readily biodegradable in aerobic conditions, meaning that
if it were to enter groundwater, it is likely to be broken down into carbon dioxide and water.
3.1 References
OECD. (2004). OECD SIDS initial assessment report: gluconic acid and its derivatives.
Sigma-Aldrich. (2019). Potassium gluconate. Retrieved from
https://www.sigmaaldrich.com/catalog/substance/potassiumgluconate2342529927411?lang=en®io
n=US
U.S. EPA. (2019). Estimation Programs Interface Suite, v 4.11. United States Environmental
Protection Agency, Washington, DC, USA
4 https://www.epa.gov/sites/prodiKtion/files/2015-05/documents/Q5.pdf
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4. Relevant Assessment History
EPA assessed the toxicological profile of potassium gluconate and added the chemical to the Safer
Choice Program's Safer Chemical Ingredients List (SCIL) in September 2016 under the functional
class of skin conditioning agents. The SCIL5 is a continuously updated list of chemicals that meet
low-concern Safer Choice criteria.6
EPA also reviewed international assessments of potassium gluconate. EPA identified assessments by
the Organisation for Economic Co-operation and Development (OECD) and Australia's, Canada's
and Germany's government agencies.
The OECD Screening Information Datasets (SIDS) Initial Assessment Meeting (SIAM) discussed the
SIDS Initial Assessment Report (SIAR) on gluconic acid and its derivatives, including potassium
gluconate, in April 2004. The SIAM determined this chemical to be "low priority for further work"
for human health and the environment.7
The Australian Government's Department of Health National Industrial Chemicals Notification and
Assessment Scheme (NICNAS) determined potassium gluconate to not pose an unreasonable risk to
the health of workers and public health on the basis of the Tier I Inventory Multi-tiered Assessment
and Prioritisation (IMAP) assessment.8
The Canadian Government, through an assessment of toxicity and exposure as part of its
categorization of the Domestic Substance List, found that potassium gluconate did not meet its
criteria for further attention.9
The German Environment Agency (UBA) designated potassium gluconate as "low hazard to waters"
in August 2017 based on an assessment of ecotoxicity and environmental fate.1"
5 https://www.epa.gov/saferchoice/safer-iiigredients
0 https://www.epa.gov/sites/prodiiction/files/2013-12/dociiiiieiits/dfe master criteria safer ingredients v2 l.pdf
7 https://hpvchemicals.oecd.org/UI/handler.axd?id=b94cc5f7-de5c-4417-b6c2-fleb4ffcdb72
8 https://www.nicnas.gov.aii/cheniical-inforniation/iniap-assessnients/iniap-assessnients/liiinian-healtli-assessnients
9 https://canadachemicals.oecd.org/CliemicalDetails.aspx?ChemicalID=B7F4FF7F-7BB4^1D6A-BD18-614AD311A2E6
10 https://webrigoletto.uba.de/rigoletto/piiblic/searcliDetail.do?keniiiininier=2207
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5. Conditions of Use
Per TSCA section 3(4), the term "conditions of use" means the circumstances, as determined by the
Administrator, under which a chemical substance is intended, known, or reasonably foreseen to be
manufactured, processed, distributed in commerce, used, or disposed of. EPA assembled information
on all uses of potassium gluconate (Appendix A) to inform which uses would be determined
conditions of use.11 One source of information that EPA used to help determine conditions of use is
2016 Chemical Data Reporting (CDR). The CDR rule (previously known as the Inventory Update
Rule, or IUR), under TSCA section 8, requires manufacturers (including importers) to report
information on the chemical substances they produce domestically or import into the U.S., generally
above a reporting threshold of 25,000 lb. per site per year. CDR includes information on the
manufacturing, processing, and use of chemical substances with information dating to the mid-1980s.
CDR may not provide information on other life-cycle phases such as chemical substance's end-of-life
after use in products (i.e., disposal).
According to CDR, potassium gluconate is manufactured domestically and imported. It is used in the
processing (incorporation into article, and incorporation into formulation, mixture, or product) of
metal surface cleaners and in various industrial and consumer products (U.S. EPA 2017b). Based on
the known manufacturing, processing, and uses of this chemical, EPA assumes distribution in
commerce. In the CDR, one facility reported that potassium gluconate was recycled (e.g., recycled,
remanufactured, reprocessed, or reused). One facility withheld recycling information and one facility
reported recycling information as confidential business information (CBI). No information on
disposal is found through EPA's Toxics Release Inventory (TRI) Program12 since potassium
gluconate is not a TRI-reportable chemical. Although reasonably available information did not
specify additional types of disposal, for purposes of this proposed prioritization designation, EPA
assumed end-of-life pathways that include releases to air, wastewater, surface water, and land via
solid and liquid waste based on the conditions of use (e.g., incineration, landfill).
To supplement CDR, EPA conducted research through the publicly available databases listed in
Appendix A (Table A.2) and performed additional internet searches to clarify conditions of use or
find additional occupational13 and consumer uses. This research improved the Agency's
understanding of the conditions of use for potassium gluconate. Although EPA identified uses of
potassium gluconate in personal care products, this screening review covers TSCA conditions of use
for the chemical substance and personal care products are not considered further in EPA's
assessment. Exclusions to TSCA's regulatory scope regarding "chemical substance" can be found at
TSCA section 3(2). Table 3 lists the conditions of use for potassium gluconate considered for
chemical substance prioritization, per TSCA section 3(4). Table 3 reflects the TSCA uses determined
as conditions of use listed in Table A.3 (Appendix A).
11 Hie prioritization process, including the definition of conditions of me, is explained in the Procedures for Prioritization
of Chemicals for Risk Evaluation Under the Toxic Substances Control Act (82 ER 33753).
12 https://www.epa.gov/toxics-release-inventorv-tri-program
13 Occupational uses include industrial and/or commercial uses
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Table 3: Conditions of Use for Potassium Gluconate
Life Cycle Stage
Category
Subcategory of Use
Source
Manufacturing
Domestic manufacture
Domestic manufacture
EPA (2017b)
Import
Import14
Processing
Processing- incorporation into
formulation, mixture or reaction
Metal surface cleaner - all other
chemical product and
preparation manufacturing
EPA (2017b)
Recycling
Recycling
EPA (2017b)15
Distribution
Distribution
Distribution
EPA (2017b)
Unknown
Cleaning and furnishing care
products
Finish Remover, high alkalinity
bottle cleanser
NLM (2018)
Cement, electroplating
Construction
Synapse Information
Resources (n.d.), NLM
(2018b)
Fabric, textile, and leather
products not covered
elsewhere
Tanning, textile auxiliaries,
textile bleach stabilizing, paper
auxiliaries
Synapse Information
Resources (n.d.), NLM
(2018)
Industrial
Cleaning and furnishing care
products
Jet engine cleaning compound,
metal surface cleaner
Dionisio (2015), EPA
(2017b)
Consumer
Cleaning and furnishing care
products
Glass and surface cleaner
DeLima Associates
(2013), Amazon.com
(2018)
Disposal
Releases to air, wastewater,
solid and liquid wastes
Though not explicitly
identified, releases
from disposal are
assumed to be
reasonably foreseen16
14 No non-CBI on import was reported.
15 In the 2016 CDR, one facility, Henkel Warren, reported that potassium gluconate was recycled (e.g., recycled,
remanufactured, reprocessed, or reused). One facility withheld recycling information and one facility reported recycling
information as CBI (EPA 2017b).
10 See Section 5 for a discussion on why releases are assumed to be reasonably foreseen for purposes of this proposed
prioritization designation.
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6. Hazard Characterization
EPA reviewed peer-reviewed literature and other data sources to identify reasonably available
information. The literature review approach17 is tailored to capture the reasonably available
information associated with low-hazard chemicals. EPA also used this process to verify the
reasonably available information for reliability, completeness, and consistency. EPA reviewed the
reasonably available information to identify relevant, quality studies to evaluate the hazard potential
for potassium gluconate against the endpoints listed below. EPA's New Chemicals Program has used
these endpoints for decades to evaluate chemical substances under TSCA18 and EPA toxicologists
rely on these endpoints as key indicators of potential human health and environmental effects. These
endpoints also align with internationally accepted hazard characterization criteria, such as the
Globally Harmonized System of Classification and Labelling of Chemicals19 as noted above in
Section 4 and form the basis of the comparative hazard assessment of chemicals.
Human health endpoints evaluated: Acute mammalian toxicity, repeated dose toxicity,
carcinogenicity, mutagenicity/genotoxicity, reproductive and developmental toxicity, neurotoxicity,
skin sensitization, and eye and skin irritation.
Environmental fate and effects endpoints evaluated: Aquatic toxicity, environmental persistence,
and bioconcentration and bioaccumulation.
The low-concern criteria used to evaluate both human health and environmental fate and effects are
included in Table 4 below.
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Human Health
Acute Mammalian
Toxicity20
Very High
High
Moderate
Low
Oral LDso (mg/kg)
<50
>50 - 300
> 300 - 2000
> 2000
Dermal LD50 (mg/kg)
<200
>200- 1000
> 1000- 2000
> 2000
Inhalation LC50
(vapor/gas) (mg/L)
<2
>2-10
>10-20
>20
Inhalation LC50
(dust/mist/fume)
(mg/L)
<0.5
>0.5-1.0
>1.0-5
>5
17 Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances Under
TSCA", also released at proposal.
18 https://www.epa. gov/sustainable-futures/sustainable-futures-p2-framework-manual
19 https://www.unece.org/fileadmiri/DAM/trans/danger/publi/ghs/ghs rev07/English/ST SG AC10 30 Rev7e.pdf
20 Values derived from GHS criteria (Chapter 3.1: Acute Toxicity'. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Repeated Dose
Toxicity (90-day
study)21
High
Moderate
Low
Oral (mg/kg-bw/day)
<10
10-100
> 100
Dermal (mg/kg-
bw/day)
<20
20 - 200
>200
Inhalation
(vapor/gas)
(mg/L/6h/day)
<0.2
0.2-1.0
> 1.0
Inhalation
(dust/mist/fume)
(mg/L/6h/day)
<0.02
0.02-0.2
>0.2
Reproductive
Toxicity22
High
Moderate
Low
Oral (mg/kg/day)
<50
50 - 250
>250
Dermal (mg/kg/day)
<100
100-500
>500
Inhalation (vapor,
gas, mg/L/day)
< 1
1-2.5
>2.5
Inhalation
(dust/mist/fume,
mg/L/day)
<0.1
0.1-0.5
>0.5
Developmental
Toxicity22
High
Moderate
Low
Oral (mg/kg/day)
<50
50 - 250
>250
Dermal (mg/kg/day)
<100
100-500
>500
Inhalation (vapor,
gas, mg/L/day)
< 1
1-2.5
>2.5
Inhalation
(dust/mist/fume,
mg/L/day)
<0.1
0.1-0.5
>0.5
Mutagenicity/
Genotoxicity23
Very High
High
Moderate
Low
Germ cell
mutagenicity
GHS Category 1A
or 1B: Substances
known to induce
heritable mutations
or to be regarded
as if they induce
heritable mutations
in the germ cells of
humans.
GHS Category 2:
Substances which
cause concern for
humans owing to the
possibility that they
may induce heritable
mutations in the germ
cells of humans.
Evidence of
mutagenicity support by
positive results in vitro
OR in vivo somatic cells
of humans or animals
Negative for
chromosomal
aberrations and gene
mutations, or no
structural alerts.
21 Values from GHS criteria for Specific Target Organ Toxicity Repeated Exposure (Chapter 3.9: Specific Target Organ
Toxicity' Repeated Exposure. 2009, United Nations).
22 Values derived from the U.S. EPA's Office of Pollution Prevention & Toxics criteria for HPV chemical categorizations
(Methodology> for Risk-Based Prioritization Under ChM tP), and the EU REACH criteria for Annex IV (2007).
23 From GHS criteria (Chapter 3.5: Germ Cells Mutagenicity. 2009, United Nations) and supplemented with considerations
for mutagenicity and genotoxicity in cells other than germs cells.
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Mutagenicity and
genotoxicity in
somatic cells
OR
Evidence of
mutagenicity
supported by positive
results in in vitro AND
in vivo somatic cells
and/or germ cells of
humans or animals.
Carcinogenicity24
Very High
High
Moderate
Low
Known or
presumed human
carcinogen (GHS
Category 1A and
1B)
Suspected human
carcinogen (GHS
Category 2)
Limited or marginal
evidence of
carcinogenicity in
animals (and
inadequate25 evidence
in humans)
Negative studies or
robust mechanism-
based structure
activity relationship
(SAR)
Neurotoxicity
(90-day study)21
High
Moderate
Low
Oral (mg/kg-bw/day)
<10
10-100
> 100
Dermal (mg/kg-
bw/day)
<20
20 - 200
>200
Inhalation
(vapor/gas)
(mg/L/6h/day)
<0.2
CD
CM
CD
> 1.0
Inhalation
(dust/mist/fume)
(mg/L/6h/day)
<0.02
0.02-0.2
>0.2
Sensitization26
High
Moderate
Low
Skin sensitization
High frequency of
sensitization in
humans and/or high
potency in animals
(GHS Category 1A)
Low to moderate
frequency of
sensitization in human
and/or low to moderate
potency in animals
(GHS Category 1B)
Adequate data
available and not
GHS Category 1Aor
1B
Respiratory
sensitization
Occurrence in
humans or evidence
of sensitization in
humans based on
animal or other tests
(equivalent to GHS
Category 1A or 1B)
Limited evidence
including the presence
of structural alerts
Adequate data
available indicating
lack of respiratory
sensitization
24 Criteria mirror classification approach used by the IARC (Preamble to the L4RC Monographs: B. Scientific Review and
Evaluation: 6. Evaluation and rationale. 2019J and incorporate GHS classification scheme (Chapter 3.6: Carcinogenicity.
2009, United Nations).
25 EPA's approach to determining the adequacy of information is discussed in the document "Approach Document for
Screening Hazard Information for Low-Priority Substances Under TSCA", also released at proposal.
20 Incorporates GHS criteria (Chapter 3.4: Respiratory or Skin Sensitization. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
Irritation/
Corrosivity27
Very High
High
Moderate
Low
Eye irritation/
corrosivity
Irritation persists
for >21 days or
corrosive
Clearing in 8-21
days, severely
irritating
Clearing in 7 days or
less, moderately
irritating
Clearing in less than
24 hours, mildly
irritating
Skin irritation/
corrosivity
Corrosive
Severe irritation at 72
hours
Moderate irritation at 72
hours
Mild or slight irritation
at 72 hours
Environmental Fate and Effects
Acute Aquatic
Toxicity Value
(L/E/IC50)28
Chronic Aquatic
Toxicity Value
(L/E/IC50)28
Persistence (Measured in terms of level of
biodegradation)29
Bioaccumulation
Potential30
May be low concern
if <10 ppm...
...and <1 ppm...
...and the chemical meets the 10-day window as
measured in a ready biodegradation test...
Low concern if >10
ppm and <100
ppm...
...and >1 ppm and
<10 ppm...
...and the chemical reaches the pass level within
28 days as measured in a ready biodegradation
test
...and BCF/BAF <
1000.
Low concern if >100
ppm...
...and > 10 ppm...
... and the chemical has a half-life < 60 days...
6.1 Human Health Hazard
Below is a summary of the reasonably available information that EPA included in the hazard
evaluation of potassium gluconate. In many cases, EPA used analogous chemicals to make findings
for a given endpoint. Where this is case, use of the analog is explained at first mention. If the
chemical studied is not named, the study is for potassium gluconate. Appendix B contains more
information on each study used to assess hazards.
Potassium gluconate is the potassium salt of D-gluconic acid. D-gluconic acid is a 6-carbon aldonic
acid (oxidized sugar) derived from glucose. EPA used best professional judgement to select analogs
for potassium gluconate based on similarity in structure, physical-chemical properties, and
functionality, with the assumption that these chemicals will have similar environmental transport and
persistence characteristics, and bioavailability and toxicity profiles. All analogs are aldonic acids
containing 5-7 carbon atoms, or their corresponding salts or esters. Sodium glucoheptonate is used as
an analog and has a chain length of 7 carbons. Analogs also include the free acid D-gluconic acid and
two additional salts. Like the potassium salt, the calcium and sodium salts are expected to readily
dissociate under environmentally and biologically relevant conditions to release gluconic acid and/or
27 Criteria derived from the Office of Pesticide Programs Acute Toxicity Categories (U.S. EPA. Label Review Manual.
2010).
28 Derived from GHS criteria (Chapter 4.1: Hazards to the Aquatic Environment. 2009, United Nations), EPA OPPT New
Chemicals Program (Pollution Prevention (P2) Framework, 2005) and OPPT's criteria for HPV chemical categorization
(Methodology> for Risk Based Prioritization Under C1l4MP. 2009).
29 Derived from OPPT's New Chemicals Program and DIE Master Criteria and reflects OPPT policy on PBTs (Design for
the Environment Program Master Criteria for Safer Chemicals, 2010).
30 Derived from OPPT's New Chemicals Program and Arnot & Gobas (2006) [Arnote, J.A. and F.A. Gobas, A review of
bioconcentration factor (BCF) and bioaccimndation factor (B*4F) assessments for organic chemicals in aquatic organisms.
Environmental Reviews, 2006. 14: p. 257-297.]
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gluconate anion, depending on the ambient pH. As a result, the environmental and health effects of
these compounds are expected to be very similar to potassium gluconate. In addition, glucono-delta-
lactone is a cyclic ester (lactone) of D-gluconic acid. The lactone and acid are interconverted to each
other and exist in equilibrium in aqueous solution. Based on these factors, the environmental and
toxicological effects of glucono-delta-lactone and D-gluconic acid are expected to be very similar to
each other and to potassium gluconate.
Table 5: Potassium Gluconate and Analog Structures
CASRN
Name
Structure
299-27-4
Potassium gluconate
31138-65-5
Sodium
glucoheptonate
O OH OH
Na
OH
OH OH OH
527-07-1
Sodium gluconate
OH OH O
OH OH
"O" Na*
526-95-4
D-Gluconic acid
OH OH
HO
OH
OH OH 0
299-28-5
Calcium gluconate
OH OH
OH OH O
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Table 5: Potassium Gluconate and Analog Structures
CASRN
Name
Structure
90-80-2
Glucono-delta-lactone
OH
HOIU'Y
HO ^OH
6.1.1 Absorption, Distribution, Metabolism, and Excretion
Absorption
Potassium gluconate has limited potential for inhalation exposure from volatilization under
environmental conditions and if incorporated in a water or aqueous solution (based on its solid state
and low Henry's Law constant, discussed in Section 3). If potassium gluconate is present as a dust
and inhaled, absorption from the lungs is likely based on its water solubility (Section 3).
The potential for dermal absorption of potassium gluconate is predicted to be low when in the neat
form and in a water-based product formulation based on its log Kow (Section 3).
An oral gavage study on rats exposed to analogs provided evidence that potassium gluconate is likely
to be rapidly absorbed through the intestine. When rats were dosed with U-14C labeled glucono-delta-
lactone or sodium gluconate via oral gavage, the chemical was present in blood and the intestine
within 5 hours of exposure (discussed further in Excretion) (ECHA. 1979a. b). Based on these data,
potassium gluconate is expected to be absorbed through the intestine.
Distribution
Potassium gluconate is water soluble (Section 3) and is likely to be distributed mainly in aqueous
compartments in an organism. This prediction is supported by experimental evidence. Following an
oral gavage dose of U-14C labeled glucono-delta-lactone or sodium gluconate in rats, radioactivity
was measured in blood, feces, and the intestine within 5 hours of exposure, indicating rapid
absorption and distribution (discussed further in Excretion) (ECHA. 1979a. b).
Metabolism
Gluconate is a metabolite of glucose oxidation. Because quality experimental data31 on potassium
gluconate metabolite formation were limited, the Quantitative Structure-Activity Relationship
(QSAR) toolbox32 was used to run the rat liver S9 metabolism simulator, the skin metabolism
simulator, and the in vivo rat metabolism simulator. The QSAR toolbox was used to identify putative
31 Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances under
TSCA", also released at proposal.
32 https://www.oecd.org/chemicalsafetv/risk-assessment/oecd-qsar-toolbox.htm
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potassium gluconate metabolites. The predicted metabolites included various molecules involved in
glucose metabolism and other carbon containing sugars including, but not limited to, D-gluconic acid,
D-galactaric acid, 2,3-diketogulonic acid, D-xylo-5-hexulosonic acid, and glucono-delta-lactone.
Each simulator also identified potassium hydroxide as a putative metabolite.
Excretion
To assess potassium gluconate's excretion pathways, EPA used experimental data from analogs. Rats
dosed with glucono-delta-lactone by oral gavage excreted 25% in the form of exhaled as carbon
dioxide, 23% remained the whole body (excluding the gastrointestinal tract), 29.5% was excreted
through the intestine and feces, and 7% was excreted in urine (ECHA. 1979a. b). Rats exposed to
sodium gluconate by oral gavage excreted 12.1% in the form of exhaled carbon dioxide, 19.7%
remained in the whole body (excluding the gastrointestinal tract), 44.9% was excreted through the
intestine and feces, and 5% was excreted in urine (ECHA. 1979a. b). Based on the data, it is expected
that potassium gluconate will be primarily excreted through feces and exhaled breath.
6.1.2 Acute Toxicity
To evaluate the potential for mammalian toxicity from acute exposures, EPA used an oral gavage
study with rats exposed to potassium gluconate (OECD. 2004). The authors reported an LD50 of 6060
mg/kg, with the 95% confidence interval ranging between 5,640 and 6,510 mg/kg. EPA also
performed read-across from D-gluconic acid to assess acute toxicity from other exposure routes. Rats
exposed dermally to D-gluconic acid indicated no mortality in either sex at the highest tested dose of
2000 mg/kg (ECHA. 2009a). These studies indicate low concern for mammalian toxicity from acute
exposures with LD50S above the low-concern criteria threshold of 2000 mg/kg.
6.1.3 Repeated Dose Toxicity
EPA assessed the potential mammalian toxicity from repeated exposures using read-across from
glucono-delta-lactone and sodium gluconate.
An OECD Guideline 408 study exposed rats to glucono-delta-lactone by oral gavage for six months
(ECHA. 1978a. b). A lowest observed adverse effect level (LOAEL) of 250 mg/kg-day was reported
based on hypertrophy of stratified squamous epithelium in stomach. The authors noted that the
specific area affected was the limiting ridge of the forestomach, which is unique to the rodent. EPA
does not consider the effects observed in this study to be relevant to humans.
A 29-month study on rats exposed to glucono-delta-lactone in their diet identified a repeated dose no
observed adverse effect level (NOAEL) of 340 mg/kg-day (JECFA. 1986).
A 28-day study on rats exposed to sodium gluconate by oral gavage identified a NOAEL of 500
mg/kg-day, with a LOAEL of 1000 mg/kg-day based on increased relative kidney weight (OECD.
2004; JECFA. 1999).
A 28-day study on rats exposed to sodium gluconate in their diet noted effects on feed efficiency,
water intake, urinary changes, and prothrombin times; however, these effects were not considered
adverse effects by the study authors because they were neither significantly different from the effects
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observed in control animals dosed with sodium nor displayed dose-dependent responses. The authors
also noted increased relative kidney weights in males at the highest dose and in females only at
second highest dose; however, these effects were not considered adverse given the lack of a dose-
response relationship. EPA determined the NOAEL to be 4100 mg/kg-day (OECD. 2004; JECFA.
1999).
A 28-day study on dogs exposed to sodium gluconate in their diet identified a NOAEL of 500 mg/kg-
day with a LOAEL of 1000 mg/kg-day based on diarrhea and vomiting (OECD. 2004).
All available study results indicate low concern for toxicity from repeated exposures because the
NOAELs and LOAELs far exceed the low-concern criteria threshold of 100 mg/kg-day for a 90-day
repeated dose study (or extrapolated to 300 mg/kg-day for a ~30-day repeated dose study).
6.1.4 Reproductive and Developmental Toxicity
EPA assessed the potential for reproductive and developmental mammalian toxicity for potassium
gluconate using read-across from sodium glucoheptonate. An OECD Guideline 422 oral gavage study
exposed female rats to sodium glucoheptonate beginning two weeks prior to mating and continued the
exposure through gestation to lactation day 5 (Harlan Laboratories. 2013). No adverse reproductive
effects were noted at the highest dose (1000 mg/kg-day), resulting in a NOAEL of 1000 mg/kg-day.
The study also examined a subset of developmental endpoints, such as litter parameters and
assessment of surface righting reflexes. No adverse effects were noted for these developmental
endpoints.
EPA further examined the potential for developmental toxicity using data from another analog,
glucono-delta-lactone. Oral gavage studies on several species, including mice (JECFA. 1986; ECHA.
1973b; Inc. 1973). hamsters (JECFA. 1986; ECHA. 1973c; Inc. 1973). rabbits (JECFA. 1986; ECHA.
1973d; Inc. 1973). and rats (JECFA. 1986; ECHA. 1973a; Inc. 1973). indicated no adverse effects at
the highest dose tested in each study. For these studies, the NOAELs range from 560 to 780 mg/kg-
day.
The results from the reproductive and developmental studies, taken with the low-concern criteria oral
threshold of 250 mg/kg-day, indicate low concern for reproductive and developmental toxicity.
6.1.5 Genotoxicity
EPA assessed the potential for genotoxic carcinogenicity using gene mutation studies from analogs,
D-gluconic acid (ECHA. 2015a. b, c), glucono-delta-lactone (NTP. 2018; OECD. 2004; Litton
Bionetics. 1974). calcium gluconate (OECD. 2004; Litton Bionetics. 1975a). and sodium gluconate
(OECD. 2004; Litton Bionetics. 1975b). which were all negative. Chromosomal aberration studies
were also all negative for D-gluconic acid (ECHA. 2015d). glucono-delta-lactone (OECD. 2004). and
sodium gluconate (OECD. 2004). These negative results for the potential to cause gene mutations and
chromosomal aberrations indicate low concern for genotoxicity.
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6.1.6 Carcinogenicity
Because quality experimental data on potassium gluconate were limited, EPA relied on publicly
available quantitative structure activity relationship (QSAR) models and structural alerts (SA) to
assess carcinogenic potential for potassium gluconate, discussed further below. Potassium gluconate
will dissociate into gluconate and potassium salt under physiological conditions. To more accurately
assess the carcinogenic potential, EPA focused on the gluconate form of the molecule. Structural
alerts represent molecular functional groups or substructures that are known to be linked to the
carcinogenic activity of chemicals. The most common structural alerts are those for electrophiles
(either direct acting or following activation). Modulating factors that will impact the carcinogenic
potential of a given electrophile will include its relative hardness or softness, its molecular flexibility
or rigidity, and the balance between its reactivity and stability.33 For this chemical, there is an absence
of the types of reactive structural features that are present in genotoxic carcinogens. Gluconic acid
and gluconate are not electrophiles. ISS profiler, a QSAR model,34 identified aldehyde and dibutyl
diesters as potential metabolite alerts; however, these metabolites will be excreted. Further, the
Virtual models for property Evaluation of chemicals within a Global Architecture (VEGA) models"35
results indicate potassium gluconate has low potential to be carcinogenic or mutagenic.
Gluconic acid is a multi-hydroxy acid that is likely to be metabolized through oxidation.
Potassium gluconate's metabolism, lack of structural alerts, and experimental genotoxicity studies
indicate that this chemical is unlikely to be carcinogenic or mutagenic.
6.1.7 Neurotoxicity
EPA assessed the potential for neurotoxicity using read-across from calcium gluconate. One study
exposed male rats to calcium gluconate daily in drinking water for 30 days (Godinho et al.. 2014).
This study tested motor coordination, exploration, spontaneous locomotor activity and post-sacrifice
brain and body weight. No adverse effects were observed. Another study exposed male rats to
calcium gluconate in drinking water for three days (Godinho et al.. 2002). This study tested the rats
based on open-field, social interactions, hole-board, and elevated plus-maze tests. Post-sacrifice,
blood and brain calcium levels were measured. An increase in motor and exploratory behavior was
reported; however, these were not considered adverse effects. These results indicate potassium
gluconate is of low concern for neurotoxicity.
6.1.8 Skin Sensitization
EPA assessed the potential for potassium gluconate to cause skin sensitization based on read-across
from D-gluconic acid. An OECD Guideline 429 study in mice exposed to D-gluonic acid was
negative for dermal sensitization (ECHA. 2009d). The same guideline study was performed in mice
33 "Fundamental and Guiding Principles for (Q)SAR Analysis of Chemical Carcinogens with Mechanistic Considerations:
Series on Testing and Assessment, No. 229." 2015. Environment Directorate, Joint Meeting of the Chemicals Committee
and the Working Party on Chemicals, Pesticides and Biotechnology.
34 Carcinogenicity alerts by ISS 2.4 profiler as encoded in the QSAR Toolbox 4.3 (qsartoolbox.org). A summary of the
results from these models is provided in Appendix B.
35 There are four carcinogenicity models housed within the VEGA 1.1.4 software tool available from
https://www.vegaliub.eu. A summary of the results from these models is provided in Appendix B.
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exposed to sodium glucoheptonate and also resulted in negative findings for skin sensitization
(ECHA. 2013). These negative results indicate low concern for skin sensitization for potassium
gluconate.
6.1.9 Skin Irritation
EPA assessed dermal irritation effects using read-across from D-gluconic acid. Two dermal studies in
rabbits demonstrated D-gluconic acid was negative for dermal irritation (ECHA. 2009c):(QECD.
2004). Using read-across from analogs, the negative results indicate low concern for skin irritation
from potassium gluconate.
6.1.10 Eye Irritation
To assess potential for eye irritation, EPA used read-across from glucono-delta-lactone and D-
gluconic acid. An in vitro bovine corneal opacity and permeability assay found glucono-delta-lactone
to be a severe irritant (Gautheron et al.. 1994). D-gluconic acid had moderate results for eye irritation
using in vivo studies. One study in rabbits indicated D-gluconic acid was mildly irritating to the eyes
with all effects fully reversible in 72 hours (OECD. 2004). while another study in rabbits concluded
D-gluconic acid was irritating with most effects reversed by the study's end at 72 hours (ECHA.
2009b). Slight chemosis and conjunctival redness remained in one test animal at 72 hours. While the
in vitro study provided evidence of irritation, EPA weighed the outcome of the in vivo effects to
determine that the reversible results indicated moderate concern for eye irritation from potassium
gluconate.
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations
The above information supports a low human health hazard finding for potassium gluconate based on
low-concern criteria. This finding includes considerations such as the potential for developmental
toxicity, reproductive toxicity, and acute or repeated dose toxicity that may impact potentially
exposed or susceptible subpopulations. Based on the hazard information discussed in Section 6, EPA
did not identify populations with greater susceptibility to potassium gluconate.
6.2 Environmental Hazard
EPA assessed environmental hazard for potassium gluconate based on available acute toxicity
experimental data from its analog, sodium gluconate, and estimated chronic toxicity values using the
Ecological Structure Active Relationships (ECOSAR) Predictive Model.36 Appendix B contains a
summary of all available environmental hazard data.
6.2.1 Acute Aquatic Toxicity
EPA assessed environmental hazard from acute exposures to potassium gluconate using read-across
from sodium gluconate. No adverse effects were observed in aquatic invertebrates and aquatic
vertebrates exposed to sodium gluconate at the highest doses tested (100 mg/L and 1000 mg/L,
30 https://www.epa.gov/tsca-screemng4ools/ecological-structure-activitv-relationships-ecosar-predictive-model
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respectively), resulting in no effects expected at concentrations less than 100 mg/L for aquatic
vertebrates (OECD. 2004; ECHA. 2002) and 1000 mg/L for invertebrates (OECD. 2004; ECHA.
2001a). Two studies evaluated the effects of acute exposures of sodium gluconate to algae. S.
siibspicatus exposed to sodium gluconate resulted in 70% biomass inhibition at 100 mg/L (ECHA.
2001b). while S.capricormitiim exposed to sodium gluconate resulted in a no observed effect
concentration (NOEC) of 560 mg/L based on growth rate (OECD. 2004). These aquatic toxicity
studies indicate low concern for acute aquatic exposure by exceeding the low-concern threshold of 10
mg/L and demonstrating greater than 60% biodegradation within 28 days.
6.2.2 Chronic Aquatic Toxicity
Toxicity from chronic exposures were estimated by ECOSAR using the neutral organics chemical
class to occur at 300,000 mg/L for aquatic vertebrates, 69,000 mg/L for aquatic invertebrates, and
38,000 mg/L for algae. The toxicity values indicate potassium gluconate is expected to have low
environmental hazard for aquatic vertebrate, aquatic invertebrates and algae, based on the low-
concern criteria chronic aquatic toxicity threshold of 10 mg/L.
6.3 Persistence and Bioaccumulation Potential
6.3.1 Persistence
EPA assessed environmental persistence for potassium gluconate using read-across from sodium
gluconate. An experimental OECD Guideline 30ID biodegradation study demonstrated sodium
gluconate biodegraded by greater than 60 percent in 10 days, confirming it is readily biodegradable in
a sludge inoculum (OECD. 2004). Further, using read-across from sodium gluconate, potassium
gluconate will anaerobically biodegrade completely after 35 days (OECD. 2004). No degradation
products of concern were identified for this chemical substance. The available aerobic biodegradation
results meet the low-concern threshold and indicate potassium gluconate has low persistence.
6.3.2 Bioaccumulation Potential
Based on the estimated bioaccumulation factor (BAF) value of 0.89 using the Estimation Programs
Interface (EPI) Suite models,37 potassium gluconate has low potential for bioaccumulation in the
environment based on the low-concern threshold of less than 1000.
37 https://www.epa.gov/tsca-screemiig-tools/epi-suitetm-estimation-program-iiiterface
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7. Exposure Characterization
EPA considered reasonably available information on exposure for potassium gluconate. In general,
there is limited information on exposure for low-hazard chemicals. EPA determined the CDR
database and certain other sources of potassium gluconate use information are sources of information
relevant to potassium gluconate's exposure potential. Of these sources, EPA determined that the CDR
database contained the primary source of information on the conditions of use for this exposure
characterization. EPA also consulted sources of use information from other databases and public
sources (listed in Table A.2). EPA used these sources only where they augmented information from
the CDR database to inform intended, known, or reasonably foreseen uses (Section 5).
As shown in Tables 3 and A.3, potassium gluconate is used as a processing aid for metal surface
cleaners, as well as in industrial and consumer uses, such as cleaning and furnishing care. The
chemical substance also has non-TSCA uses, which are beyond the scope of this assessment because
of the exclusions under TSCA section 3(2). (See Table A.3)
Under the conditions of use identified in Table 3, EPA assessed the potential exposure to the
following categories: the environment, the general population, and potentially exposed or susceptible
subpopulations including workers and consumers.
7.1 Production Volume Information
Production volume information for potassium gluconate is based on an analysis of CDR data reported
from 1986 to 2015.38 The CDR database indicates that, for reporting year 2015, three companies
manufactured or imported potassium gluconate at three sites. In reporting years 1986, 1994, 1998,
and 2002, aggregate production volume for potassium gluconate appears to have peaked between
500,000 lbs. and 1,000,000 lbs. Since then, the production volume has remained below 500,000 lbs
and in the most recent years reported, 2011-2015, has remained stable at 100,000 lbs. to 500,000 lbs.
7.2 Exposures to the Environment
EPA expects most exposures to the environment to occur during the manufacturing and processing of
potassium gluconate. Exposure is also possible from other uses, such as distribution, industrial and
consumer use, and disposal. These activities could result in releases of potassium gluconate to media
including surface water, landfills, and air.
EPA expects high levels of removal of potassium gluconate during wastewater treatment (either
directly from the facility or indirectly via discharge to a municipal treatment facility or Publicly
Owned Treatment Works (POTW)). Further, potassium gluconate has low persistence (aerobically
and anaerobically) and has the potential to be broken down in the environment to carbon dioxide and
38 Hie CDR requires manufacturers (including importers) to report information on the chemical substances they produce
domestically or import into the U.S. generally above 25,000 lb. per site.
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water. Therefore, any release of the chemical is expected to break down, reducing exposure to aquatic
organisms in the water column, benthic organisms, and groundwater sources of drinking water,
including well water.
If disposed of in a landfill, potassium gluconate is expected to degrade under aerobic and anaerobic
conditions (aerobic and anaerobic biodegradation are discussed in Section 6.3.1).
If incineration releases during manufacturing and processing occur, EPA expects significant
degradation of potassium gluconate to the point that it will not be present in the air.
7.3 Exposures to the General Population
EPA expects the general population is unlikely to be exposed to potassium gluconate from the
environmental releases described above. The general population is unlikely to be exposed to
potassium gluconate via inhalation of ambient air because potassium gluconate is a solid, has a low
vapor pressure, and will break down if incinerated. Potassium gluconate is also unlikely to be present
in surface water because it will degrade (aerobically and anaerobically, discussed in Section 6.3.1),
reducing the potential for the general population to be exposed by oral ingestion or dermal exposure.
Given the low bioconcentration and bioaccumulation potential of potassium gluconate, oral exposure
to potassium gluconate via fish ingestion is unlikely.
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations
EPA identified workers as a potentially exposed or susceptible subpopulation based on greater
exposure to potassium gluconate than the general population during manufacturing, processing,
distribution, use, and disposal. EPA also identified consumers as a population that may experience
greater exposure to potassium gluconate than the general population through the use of cleaning and
furnishing care products. EPA did not identify populations with greater susceptibility to potassium
gluconate.
7.4.1 Exposures to Workers
Based on its reported physical form and measured melting point, potassium gluconate is a solid under
ambient conditions. Based on potassium gluconate's conditions of use (Table 3), workers may be
exposed to solids through direct dermal contact with the substance and inhalation of dust if it is
generated. Potassium gluconate is a salt and therefore not expected to be a volatile substance,
meaning workers are unlikely to be exposed through inhalation of vapors. Workers may be exposed
to potassium gluconate in manufacturing, processing, distribution, use, and disposal.
7.4.2 Exposures to Consumers
Consumers could be exposed to potassium gluconate through the use of cleaning and furnishing care
products. For these uses, if dermal contact does occur, potassium gluconate is expected to be
minimally absorbed through the skin. If the chemical is in an aerosol product and inhalation exposure
occurs, potassium gluconate's absorption from the lungs is likely. EPA does not include intentional
misuse, such as people drinking products containing this chemical, as part of the known, intended or
reasonably foreseen conditions of use that could lead to an exposure (82 FR 33726). Thus, oral
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exposures will be incidental (meaning inadvertent and low in volume). Potassium gluconate is
expected to be metabolized and excreted, further reducing the duration of exposure.
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8. Summary of Findings
EPA has used reasonably available information on the following statutory and regulatory criteria and
considerations to screen potassium gluconate against each of the priority designation considerations
in 40 CFR 702.9(a) and discussed individually in this section, under its conditions of use:
• the hazard and exposure potential of the chemical substance (See Sections 6 and 7);
• persistence and bioaccumulation (See Section 6.3);
• potentially exposed or susceptible subpopulations (See Section 7.4);
• storage near significant sources of drinking water (See Section 8.4);
• conditions of use or significant changes in the conditions of use of the chemical substance
(See Section 5);
• the chemical substance's production volume or significant changes in production volume
(See Section 7.1); and
• other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority.
EPA conducted a risk-based, screening-level review based on the criteria and other considerations
above and other relevant information described in 40 CFR 702.9(c) to inform the determination of
whether the chemical substance meets the standard of a high-priority substance. High-priority
substance means a chemical substance that EPA determines, without consideration of costs or other
non-risk factors, may present an unreasonable risk of injury to health or the environment because of a
potential hazard and a potential route of exposure under the conditions of use, including an
unreasonable risk to potentially exposed or susceptible subpopulations identified as relevant by EPA
(40 CFR 702.3). This section explains the basis for the proposed designation and how EPA applied
statutory and regulatory requirements, addressed issues, and reached conclusions.
8.1. Hazard and Exposure Potential of the Chemical Substance
Approach: EPA evaluated the hazard and exposure potential of potassium gluconate. EPA used this
information to inform its proposed determination of whether potassium gluconate would meet the
statutory criteria and considerations for proposed designation as a low-priority substance.
• Hazard potential:
For potassium gluconate's hazard potential, EPA gathered information for a broad set of human
health and environmental hazard endpoints described in detail in Section 6 of this document. EPA
benchmarked this information against the low-concern thresholds. EPA found that potassium
gluconate is of low concern for human health and environmental hazard across the range of endpoints
in the low-concern criteria except for eye irritation (see the discussion below).
• Exposure potential:
To understand exposure potential, EPA gathered information on physical-chemical properties,
production volumes, and the types of exposures likely to be faced by workers, the general population,
children, and consumers (discussed in Sections 3 and 7). EPA also gathered information on
environmental releases. EPA identified workers, the general population, consumers, and the
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environment as most likely to experience exposures. EPA determined that while the general
population, consumers, and workers may be exposed to potassium gluconate, exposure by dermal,
inhalation, and ingestion pathways are limited by potassium gluconate's physical-chemical properties.
If potassium gluconate is released into the environment, its exposure potential will be reduced
through biodegradation under aerobic and anaerobic conditions.
Rationale: EPA found that potassium gluconate is moderately irritating to eyes. Although read-across
from some studies indicated that potassium gluconate may cause eye irritation, the effects are
reversible, reducing concern for longer-term. Workers could be exposed during processing,
manufacturing, distribution, use, and disposal, splashing of solutions, or hand-to-face and eye contact.
Other uses covered under TSCA, especially consumer uses in cleaning and furnishing care products
and laundry, would be unlikely to result in more than incidental eye exposure. Eye irritation resulting
from exposure in an occupational and consumer setting is mitigated by the reversible nature of the
effect and addressed by rinsing with water.
Proposed conclusion: Based on an initial analysis of reasonably available hazard and exposure
information, EPA proposes to conclude that the risk-based, screening-level review under 40 CFR
702.9(a)(1) does not support a finding that potassium gluconate meets the standard for a high-priority
substance. The reasonably available hazard and exposure information described above provides
sufficient information to support this proposed finding.
8.2. Persistence and Bioaccumulation
Approach: EPA has evaluated both the persistence and bioaccumulation potential of potassium
gluconate based on a set of EPA and internationally accepted measurement tools and thresholds that
are sound indicators of persistence and bioaccumulation potential (described in Section 6). These
endpoints are key components in evaluating a chemical's persistence and bioaccumulation potential.
Rationale: EPA review of estimated data indicates potassium gluconate is readily biodegradable
under aerobic and anaerobic conditions, with greater than 60 percent biodegradation within 10 days.
Ultimate biodegradable is expected under anaerobic conditions based on an analog (Section 6.3.1).
EPA's EPI Suite models indicate a low potential for bioaccumulation (Section 6.3.2).
Proposed conclusion: Based on an initial screen of reasonably available information on persistence
and bioaccumulation, EPA proposes to conclude that the screening-level review under 40 CFR
702.9(a)(2) does not support a finding that potassium gluconate meets the standard for a high-priority
substance. The reasonably available persistence and bioaccumulation information described above
provides sufficient information to support this proposed finding.
8.3. Potentially Exposed or Susceptible Subpopulations
Approach: TSCA Section 3(12) states that the "term 'potentially exposed or susceptible
subpopulation' means a group of individuals within the general population identified by the
Administrator who, due to either greater susceptibility or greater exposure, may be at greater risk than
the general population of adverse health effects from exposure to a chemical substance or mixture,
such as infants, children, pregnant women, workers, or the elderly." EPA identified workers engaged
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in the manufacturing, processing, distribution, use and disposal of potassium gluconate as a
potentially exposed or susceptible subpopulation (described in more detail in Section 7). Consumers
are also a potentially exposed subpopulation because of their use of cleaning and furnishing care
products.
Rationale: EPA did not identify hazard effects for this chemical that would make any population
susceptible. EPA expects workers and consumers to have a higher exposure to potassium gluconate
than the general population. Because of the chemical's low-concern hazard properties and
reversibility of effects, this exposure does not pose a significant increase in risk for workers or
consumers.
Proposed conclusion: Based on the Agency's understanding of the conditions of use and expected
users such as potentially exposed or susceptible subpopulations, EPA proposes to conclude that the
screening-level review under 40 CFR 702.9(a)(3) does not support a finding that potassium gluconate
meets the standard for a high-priority substance. While the conditions of use will result in an
increase in exposures to certain populations, the consistently low-hazard profile and reversible
effects of potassium gluconate provides sufficient evidence to support a finding of low concern.
The reasonably available information on conditions of use, hazard, and exposure described above
provides sufficient information to support this proposed finding.
8.4. Storage Near Significant Sources of Drinking Water
Approach: In Sections 6 and 7, EPA explains its evaluation of the elements of risk relevant to the
storage of potassium gluconate near significant sources of drinking water. For this criterion, EPA
focused primarily on the chemical substance's potential human health hazards, including to
potentially exposed or susceptible subpopulations, and environmental fate properties, and explored a
scenario of a release to a drinking water source. EPA also investigated whether the chemical was
monitored for and detected in a range of environmental media. The requirement to consider storage
near significant sources of drinking water is unique to prioritization under TSCA Section 6(b)(1)(A)
and 40 CFR 702.9(a)(4).
Rationale: In terms of health hazards, potassium gluconate is expected to present low concern to the
general population, including potentially exposed or susceptible subpopulations, across a spectrum of
health endpoints.
In the event of an accidental release into a surface drinking water source, potassium gluconate is
expected to be water soluble (see Section 3) and has low persistence (see Section 6) in the drinking
water supply. In the event of an accidental release to land, the estimated log Koc indicates this
substance is highly mobile in soils, increasing its potential for leaching into groundwater, including
well water. Fate and transport evaluation indicated potassium gluconate is unlikely to partition into
sediment, predicted to biodegrade under aerobic and anaerobic conditions, (see Section 3) and
unlikely to bioaccumulate (see Section 6), minimizing the likelihood that the chemical would be
present in sediment or groundwater to pose a longer-term drinking water contamination threat.
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A sudden release of large quantities of the chemical near a drinking water source could have
immediate effects on the usability of a surface drinking water source. If such a release were to occur,
two primary factors would operate together to reduce concern. First, the chemical would be expected
to present low concern to the general population, including susceptible subpopulations, across a
spectrum of health endpoints (see Section 6). Second, potassium gluconate would degrade in aerobic
and anaerobic environments (see Section 6). Together, these factors mean that any exposures to this
chemical through drinking water sources would be short-lived, and that if ingestion were to take
place, concern for adverse health effects would be low.
EPA also explored whether the chemical had been identified as a concern under U.S. environmental
statutes in the past. EPA searched lists of chemicals and confirmed that potassium gluconate does not
appear on these lists. The lists reviewed include EPA's List of Lists
(https://www.epa.gov/sites/production/files/2015-03/documents/list of lists.pdf). EPA also searched
the lists of chemicals included in the National Primary Drinking Water Regulations and the
Unregulated Contaminant Monitoring Rule (UCMR) under the Safe Drinking Water Act (SDWA).
Proposed conclusion: Based on a qualitative review of a potential release near a significant source of
drinking water, EPA proposes to conclude that the screening-level review under 40 CFR 702.9(a)(4)
does not support a finding that potassium gluconate meets the standard for a high-priority substance.
The reasonably available information on storage near significant sources of drinking water described
above provides sufficient information to support these proposed findings.
8.5. Conditions of Use or Significant Changes in Conditions of Use of the
Chemical Substance
Approach: EPA evaluated the conditions of use for potassium gluconate and related potential
exposures and hazards.
Rationale: EPA evaluated the conditions of use of potassium gluconate (see Section 5 and Appendix
A) and found it to have a broad range of conditions of use.
EPA expects that even if the conditions of use were to expand beyond activities that are known,
intended, or reasonably foreseen, the exposure outcome of the screening review would likely not
change and would not alter the Agency's conclusion of low concern. EPA bases this expectation on
potassium gluconate's consistently low-concern hazard characteristics across the spectrum of hazard
endpoints and regardless of a change in the nature or extent of its use and resultant increased
exposures.
Proposed conclusion: EPA's qualitative evaluation of potential risk does not support a finding that
potassium gluconate meets the standard for a high-priority substance, based on its low-hazard profile
under the current conditions of use. EPA proposes to find that even if conditions of use broaden,
resulting in an increase in the frequency or amount of exposures, the analysis conducted to support
the screening-level review under 40 CFR 702.9(a)(5) would not change significantly. In particular,
the analysis of concern for hazard, which forms an important basis for EPA's findings, would not be
impacted by a change in conditions of use. Therefore, such changes would not support a finding that
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potassium gluconate meets the standard for a high-priority substance. The reasonably available
information on conditions of use, or significant changes in conditions of use, described above
provides sufficient information to support this proposed finding.
8.6. The Volume or Significant Changes in Volume of the Chemical
Substance Manufactured or Processed
Approach: EPA evaluated the current production volumes of potassium gluconate (See Section 7.1)
and related potential exposures (Sections 7.2 and 7.4).
Rationale: EPA used reasonably available information on production volume (see Appendix A) in
considering potential risk. It is possible that designation of potassium gluconate as a low-priority
substance could result in increased use and higher production volumes. EPA expects, however, that
any changes in potassium gluconate's production volume would not alter the Agency's assessment of
low concern given the chemical's low-hazard profile of the chemical. EPA bases this expectation on
potassium gluconate's consistently low-concern hazard characteristics across the spectrum of hazard
endpoints. This expectation would apply, even with a significant change in the volume of the
chemical substance manufactured or processed and resultant increased exposures.
Proposed conclusion: Based on this screening criteria under 40 CFR 702.9(a)(g), EPA proposes to
find that even if production volumes increase, resulting in an increase in the frequency or level of
exposure, potassium gluconate does not meet the standard for a high-priority substance. The
reasonably available information on production volume, or significant changes in production volume
described above provides sufficient information to support this proposed finding.
8.7. Other Considerations
EPA did not identify other considerations for the screening review to support the proposed
designation of potassium gluconate as a low-priority substance.
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9. Proposed Designation
Based on a risk-based, screening-level review of the chemical substance and, when applicable,
relevant information received from the public and other information as appropriate and consistent
with TSCA section 26(h) and (i), EPA is proposing to designate potassium gluconate as a low-priority
substance as it does not meet the statutory criteria for a high-priority substance.
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Appendix A: Conditions of Use Characterization
EPA gathered information on and related to conditions of use including uses of the chemical,
products in which the chemical is used, types of users, and status (e.g., known, regulated).
A.1. CDR Manufacturers and Production Volume
The Chemical Data Reporting (CDR) rule (previously known as the Inventory Update Rule, or IUR),
under TSCA section 8, requires manufacturers (including importers) to report information on the
chemicals they produce domestically or import into the U.S., generally above a reporting threshold of
25,000 lb. per site per year.
According to the 2016 Chemical Data Reporting (CDR) database, three companies manufactured or
imported potassium gluconate at three sites for reporting year 2015. Table A.l presents the historic
production volume of potassium gluconate from the CDR from 1986 to 2015. In reporting years
1986, 1994, 1998, and 2002, aggregate production volume for potassium gluconate appears to have
peaked between 500,000 lbs. and 1,000,000 lbs. Since then, the production volume has remained
below 500,000 lbs and in the most recent years reported, 2011-2015, has remained stable at 100,000
lbs. to 500,000 lbs.
Table A.1:1986-2015 National Production Volume Data for Potassium Gluconate (Non-Confidential Production
Volume in Pounds)
1986
1990
1994
1998
2002
2006
2011
2012
2013
2014
2015
10 K —
500 K
> 500 K
-1 M
10 K —
500 K
10 K —
500 K
10 K —
500 K
Unknown1
25K-
<100K
100K-
<500 K
100K-
<500 K
100K-
<500 K
100K-
<500 K
Note(s):
K = Thousand; M = Million; NDR = No data reported, Sherlock (2019)
1. The CAS RN 299-27-4 could not be found in the 2006 IUR. It is possible that no single entity triggered the reporting
threshold in this year.
Source(s):
EPA (2018a; 2017b; 2006; 2002)
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A.2. Uses
A.2.1 Methods for Uses
Section A.2.2 provides a list of known uses of potassium gluconate, organized by category of use. To
compile the uses, EPA searched publicly available databases listed in Table A.2 conducted additional
internet searches to clarify uses. Search terms differed among databases because of different search
term requirements for each database (i.e., some databases search by CASRN while others search by
chemical name).
Table A.2: Sources Searched for Uses of Potassium Gluconate
Title
Author and Year
Search Term(s)
Found Use Information? 1
Sources searched for all use reports I
California Links to
Pesticides Data
California Dept of Pesticide
Regulation (2013)
299-27-4
No
Canada Chemicals
Government of Canada
(2018)
Management Plan
Potassium gluconate
No
information sheets
Chemical and Product
Categories (CPCat)
CPCat (2019)
299-27-4
Yes
ChemView2
EPA (2018a)
299-27-4
Yes
Children's Safe Product
Act Reported Data
Washington State Dept. of
Ecology (2018)
299-27-4
No
Consumer Product
Information Database
DeLima Associates (2018)
299-27-4
Yes
(CPID)
N/A, There is no
Danish surveys on
search but report titles
chemicals in consumer
Danish EPA (2018)
were checked for
No
products
possible information on
the chemical
Datamyne
Descartes Datamyne
(2018)
299-27-4
No
DrugBank
DrugBank (2018)
Potassium gluconate
Yes
European Chemicals
Agency (ECHA)
ECHA (2018)
299-27-4
No
Registration Dossier
eChemPortal2
OECD (2018)
299-27-4
Yes
Envirofacts2
EPA (2018b)
299-27-4
No
Functional Use Database
(FUse)
EPA (2017a)
299-27-4
Yes
Kirk-Othmer Encyclopedia
of Chemical Technology
Kirk-Othmer (2006)
Potassium gluconate
No
Non-Confidential 2016
Chemical Data Reporting
EPA (2017b)
299-27-4
Yes
(CDR)
PubChem Compound
Kimetal. (2016)
299-27-4
Yes
II
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Table A.2: Sources Searched for Uses of Potassium Gluconate
Title
Author and Year
Search Term(s)
Found Use Information? 1
Safer Chemical Ingredients
List (SCIL)
EPA (2018d)
299-27-4
Yes
Synapse Information
Resources2
Synapse Information
Resources (n.d.)
Potassium gluconate
Yes
Resource Conservation
and Recovery Act (RCRA)
EPA (2018c)
Potassium gluconate
No
Scorecard: The Pollution
Information Site
GoodGuide (2011)
299-27-4
No
Skin Deep Cosmetics
Database
EWG2018
299-27-4
Yes
Toxics Release Inventory
(TRI)
EPA (2018e)
299-27-4
No
TOXNET2
NLM (2018a)
299-27-4
Yes
Ullmann's Encyclopedia of
Industrial Chemistry
Ullmann's (2000)
Potassium gluconate
Yes
Additional Sources Identified from Reasonably Available Information |
Amazon.com
Amazon.com (2018)
Incidentally identified
while researching
details of this
chemical's uses and
products.
Yes
Henkel Corporation
Henkel (2001)
Neogen Corporation
Neogen Corporation
(2016)
State Agency for Nature,
Environment and
Consumer Protection
LANUV (2018)
Note(s):
1. If use information was found in the resource, it will appear in Table A.3 unless otherwise noted.
2. This source is a group of databases; thus the exact resource(s) it led to will be cited instead of the database as whole.
The U.S. Patent and Trademark Office has an online database that shows 1,474 patents referencing
"potassium gluconate" (USPTO 2018). Although patents could be useful in determining reasonably
foreseeable uses, it is difficult to confirm whether any of the patented technologies are currently in
use. Uses inferred from patents containing potassium gluconate were not included in Table A.3. Note
that the uses in Table A. 3 that are covered under TSCA are included in Section 5, Table 3 of this
document.
Ill
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A.2.2 Uses of Potassium gluconate
Table A.3: Uses of Potassium Gluconate
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Cleaning Products
Haz-Map identifies use of potassium gluconate as a chelating agent in cleaning products (NLM 2018b).
NLM (2018b)
Finish remover
Unknown
Haz-Map identifies use of potassium gluconate in finish removers. No further information about this
use could be found and it is unknown whether this is an ongoing use in the United States.
The expected users are unknown, due to the limited availability of information.
DeLima Associates (2013); Amazon.com (2018)
Glass and surface cleaner
Consumer
CPID listed one glass and surface care product containing potassium gluconate, with a caveat that it
is an old product. The product is still available for purchase online but it is unknown whether it still
contains the chemical.
CPID generally includes consumer products, therefore the expected users are consumer.
NLM (2018b)
High alkalinity bottle cleanser
Unknown
Haz-Map identifies use of potassium gluconate in high alkalinity bottle cleanser. No further information
about this use could be found and it is unknown whether this is an ongoing use in the United States.
The expected users are unknown, due to the limited availability of information.
Henkel (2001); CPCat(2019); EPA (2017b)
Jet engine cleaning compound
Industrial
CPCat identified the product "4008-4" by Turco Products as containing potassium gluconate based on
an SDS from 1991. A Google search returned a data sheet for the product, identifying it as a jet
engine cleaner produced by Henkel. Henkel reported domestic manufacture of potassium gluconate
for consumer/commercial use in the 2016 CDR, but the use categories were withheld.
Expected users are assumed to be industrial.
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Table A.3: Uses of Potassium Gluconate
Use
Expected Users
Description of Use and References
EPA (2017b); NLM (2018b)
Metal surface cleaner
Industrial
CDR reported use of potassium gluconate for industrial processing (incorporation into formulation,
mixture, or reaction product) as a metal surface cleaner, at concentrations of at least one percent but
less than 30 percent by weight. Haz-Map identifies use of potassium gluconate in industrial cleaning.
Expected users are industrial based on CDR's Industrial Processing and Use report.
TSCA Conditions of Use: Textiles
NLM (2018b)
Tanning
Unknown
Haz-Map identifies use of potassium gluconate in tanning and textile industries. No further information
about this use could be found and it is unknown whether this is an ongoing use in the United States.
The expected users are unknown, due to the limited availability of information.
Synapse Information Resources (n.d.)
Textile auxiliaries
Unknown
Synapse Information Resources identifies use of potassium gluconate in paper and textile auxiliaries.
No further information about this use could be found and it is unknown whether this is an ongoing use
in the United States.
The expected users are unknown, due to the limited availability of information.
NLM (2018b)
Textile bleach stabilizing
Unknown
Haz-Map identifies use of potassium gluconate in textile bleach stabilizing. No further information
about this use could be found and it is unknown whether this is an ongoing use in the United States.
The expected users are unknown, due to the limited availability of information.
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Table A.3: Uses of Potassium Gluconate
Use
Expected Users
Description of Use and References |
Other TSCA Uses
NLM (2018b)
Aluminum processing
Industrial
Haz-Map identifies use of potassium gluconate in aluminum processing. No further information about
this use could be found and it is unknown whether this is an ongoing use in the United States.
Haz-Map does not specify users; however, we assume aluminum processors to be industrial users.
NLM (2018b)
Cement
Unknown
Haz-Map identifies use of potassium gluconate as a chelating agent in cement set retarding. No
further information about this use could be found and it is unknown whether this is an ongoing use in
the United States.
The expected users are unknown, due to the limited availability of information.
Synapse Information Resources (n.d.)
Electroplating
Unknown
Synapse Information Resources identifies use of potassium gluconate in electroplating. No further
information about this use could be found and it is unknown whether this is an ongoing use in the
United States.
The expected users are unknown, due to the limited availability of information.
Synapse Information Resources (n.d.)
Paper auxiliaries
Unknown
Synapse Information Resources identifies use of potassium gluconate in paper and textile auxiliaries.
No further information about this use could be found and it is unknown whether this is an ongoing use
in the United States.
The expected users are unknown, due to the limited availability of information.
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Table A.3: Uses of Potassium Gluconate
Use
Expected Users
Description of Use and References |
Non-TSCA Uses
EWG (2018)
Anti-wrinkle eye cream
Consumer
EWG's SkinDeep database lists this use with the caveat that it is an old product listing. It is possible
the product is no longer for sale and/or no longer contains potassium gluconate.
EWG generally includes consumer products, therefore the expected users are consumer.
EWG (2018)
Conditioner
Consumer
EWG's SkinDeep database lists this use with the caveat that it is an old product listing. It is possible
the product is no longer for sale and/or no longer contains potassium gluconate.
EWG generally includes consumer products, therefore the expected users are consumer.
CPCat (2019); DrugBank (2018); Synapse Information Resources (n.d.); NLM (2018b)
Dietary supplement
Unknown, consumer
DrugBank identifies use of potassium gluconate as a dietary supplement to prevent or treat potassium
deficiency. Synapse Information Resources reports use of potassium gluconate in dietetic foods. Haz-
Map identifies use of potassium gluconate in injection solutions.
The expected users are unknown due to the limited availability of information, however the users of
over-the-counter potassium gluconate tablets are likely to be consumers.
EWG (2018)
Firming serum
Consumer
EWG's SkinDeep database lists this use with the caveat that it is an old product listing. It is possible
the product is no longer for sale and/or no longer contains potassium gluconate.
EWG generally includes consumer products, therefore the expected users are consumer.
VII
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Table A.3: Uses of Potassium Gluconate
Use
Expected Users
Description of Use and References
CPCat (2019); LANUV (2018); OECD (2004); FDA (2018); Synapse Information Resources (n.d.);
Ullmann's (2016)
Food additive
Unknown
The FDA lists potassium gluconate as a nutrient supplement and sequestrant in its Substances
Added to Food inventory. Synapse Information Resources reports use of potassium gluconate in
beverages and as a sequestrant in foods. LANUV identifies use of potassium gluconate as an
antioxidant and preservative in food, as well as an emulsifying salt in the manufacture of cheese, in
Germany. OECD also identifies use of potassium gluconate in artificial sweeteners, and Ullmann's
identifies use in food additives.
The expected users are unknown, due to the limited availability of information.
CPCat (2019); National Pesticide Information Retrieval System (2016)
Pesticide inert
Unknown
EPA's InertFinder and CPCat list potassium gluconate as a pesticide inert approved for nonfood use.
The National Pesticide Information Retrieval System and California Department of Pesticide
Regulation indicate that the substance is not currently used in pesticides in the United States and
California, respectively.
The expected users are unknown, due to the limited availability of information.
EWG (2018)
Moisturizer
Consumer
EWG's SkinDeep database lists this use with the caveat that it is an old product listing. It is possible
the product is no longer for sale and/or no longer contains potassium gluconate.
EWG generally includes consumer products, therefore the expected users are consumer.
EWG (2018)
Shampoo
Consumer
EWG's SkinDeep database lists this use with the caveat that it is an old product listing. It is possible
the product is no longer for sale and/or no longer contains potassium gluconate.
EWG generally includes consumer products, therefore the expected users are consumer
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Table A.3: Uses of Potassium Gluconate
Use
Expected Users
Description of Use and References
CPCat (2019); Neogen Corporation (2016)
Veterinary drug
Consumer, commercial
Similar to its use in pharmaceuticals, potassium gluconate can be used as a dietary supplement to
treat potassium deficiency in dogs and cats.
Neogen states that federal law allows only licensed veterinarians to use or order use of this drug,
however this drug is also available for retail sale.
Children's Products
CDR did not report any use of potassium gluconate in children's products.
Recycling and Disposal
In the 2016 CDR, one facility, Henkel Warren, reported that potassium gluconate was recycled (e.g., recycled, remanufactured, reprocessed, or reused). One facility
withheld recycling information and one facility reported recycling information as CBI (EPA 2017b).
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A.3 References
Amazon.com. (2018). Simple Green 3.11E+12 Glass and Surface Cleaner, 32 oz, Clear. Retrieved from
https://www.amazon.com/Simple-Green-Naturals-Glass-Surface/dp/B001CWIU7K
California Dept of Pesticide Regulation. (2013). DPR Databases. Retrieved from
https://www.cdpr.ca.gov/dprdatabase .htm
Danish EPA. (2018). Danish surveys on chemicals in consumer products. Retrieved from
https://cng.mst.dk/chcmicals/chcmicals-in-products/consumcrs-consumcr-products/danish-
survevs-on-consumer-products/
DeLima Associates. (2013). Simple Green Naturals Glass & Surface Care Pump Spray, Rosemary Mint-
Old Product. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/1/1283 l/standard/span%20stvle=%22color:#
a9a9a9;%22%3ESimple%20Green%20Naturals%20Glass%20&%20
DeLima Associates. (2018). Potassium Gluconate. Retrieved from
https://www.whatsinproducts.eom/chemicals/view/l/4653/000299-27-4/Potassium%20Gluconate
Descartes Datamyne. (2018). Descartes Datamyne Import-Export Database.
Dionisio, K. L., Frame, A. M., Goldsmith, M.-R., Wambaugh, J. F., Liddell, A., Cathey, T., . . . Judson,
R. S. (2015). Exploring consumer exposure pathways and patterns of use for chemicals in the
environment. Toxicology! Reports, 2, 228-237. doi:http://dx.doi.org/10.1016/i.toxrep.2014.12.009
DrugBank. (2018). Potassium gluconate. Retrieved from https://www.drugbank.ca/drugs/DB13620
European Chemicals Agency (ECHA). (2018). Potassium gluconate. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/10349
EWG. (2018). SkinDeep - Products containing potassium gluconate. Retrieved from
https://www.ewg.org/skindeep/browse.php?containing=705201&showproducts=l
GoodGuide. (2011). Scorecard: The Pollution Information Site. Retrieved from
http://scorecard.goodguide.com/chemical-profiles/index.tcl
Government of Canada. (2018). Chemical Substances: Services and Information. Retrieved from
https://www.canada.ca/en/health-canada/services/chemical-substances.html
Henkel. (2001). TURCO® 4008 TURCO® 4008-3 & 4008-4. Retrieved from
https://henk0008.home.xs4all.nl/Turco/TURCQ%204008-N.pdf
Kim, S., Thiessen, P. A., Bolton, E. E., Chen, J., Fu, G., Gindulyte, A., . . . Bryant, S. H. (2016).
PubChem Substance and Compound databases. Nucleic Acids Research, -/-/(Database issue),
D 1202-D 1213. doi: 10.1093/nar/gkv951
Kirk-Othmer. (2006). Kirk-Othmer Encyclopedia of Chemical Technology.
X
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Knox, C., Law, V., Jewison, T., Liu, P., Ly, S., Frolkis, A., . . . Wishart, D. S. (2011). DrugBank 3.0: a
comprehensive resource for 'omics' research on drugs. Nucleic Acids Res, J 9( Database issue),
D1035-1041. doi:10.1093/nar/gkql 126
LANUV. (2018). IGS Public Information system for dangerous substances. Retrieved from
https://igsvtu.lanuv.nrw.de/igs70s/oberfl/sliste/formHtml/AUSGABE.app7INnM&P PROFIL=
Public&DATENPROFIL=Public&DATEI=igs ausgabe2.vm&AUSGABE NEU=1&USER ID=
3 825 &STOFF= 1 &PROFIL CHANGE=1&T KAPITELNR= 1 &T KAP=1&P RESET SUCHE
=1&T Time=1528923450&T TREFFER=1
National Pesticide Information Retrieval System. (2016). Active Ingredient Information, from Purdue
University http://ppis.ceris.purdue.edu/Default.aspx
Neogen Corporation. (2016). RenaKare™ (Potassium Gluconate Powder). Retrieved from
http://animalsafetv.neogen.com/pdf/msds/general/sds/united states/sds renakarepowder unitedst
ates-english.pdf
Organisation for Economic Cooperation and Development (OECD). (2004). Gluconic Acid and its
Derivatives. Retrieved from http://www.inchem.org/documents/sids/sids/gluconates.pdf
Organisation for Economic Cooperation and Development (OECD). (2018). eChemPortal: Global Portal
to Information on Chemical Substances. Retrieved from
https://www.echemportal.org/echemportal/index.action
Sherlock, Scott (2019). Email to Lynne Blake-Hedges. Public Production Volume References - CASRNs
299-27-4 and 90-80-2. June 18.
Synapse Information Resources, (n.d.). Synapse Information Resources. Retrieved from: Excel file.
U.S. Environmental Protection Agency (EPA). (2002). 1986-2002 Historical IUR Data. Retrieved from
Excel File
U.S. Environmental Protection Agency (EPA). (2006). 2006 IUR Public Database.
U.S. Environmental Protection Agency (EPA). (2017a). Functional Use Database (FUse). Retrieved
from: https://catalog.data.gov/dataset/functional-use-database-fuse
U.S. Environmental Protection Agency (EPA). (2017b). Non-Confidential 2016 Chemical Data Reporting
(CDR). Retrieved from https://www.epa.gov/chemical-data-reporting
U.S. Environmental Protection Agency (EPA). (2018a). ChemView. Retrieved from
https://chemview.epa.gov/chemview
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from https://www3.epa.gov/enviro/facts/multisvstem.html
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Biennial RCRA Hazardous Waste Report). Retrieved from
https://iaspub.epa.gov/enviro/brs codes v2.waste lookup
XI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
U.S. Environmental Protection Agency (EPA). (2018d). Safer Chemical Ingredients List. Retrieved from
https://www.epa.gov/saferchoice/safer-ingredients
U.S. Environmental Protection Agency (EPA). (2018e). TRI-Listed Chemicals. Retrieved from
https://www.epa.gov/toxics-release-inventorv-tri-program/tri-listed-chemicals
U.S. Food and Drug Administration (FDA). (2018). Substances Added to Food. Retrieved from
https://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=FoodSubstances&id=POTASSIUMG
LUCONATE
U.S. National Library of Medicine (NLM). (2018a). ChemlDplus, a TOXNET Database. Retrieved from
https://chem.nlm.nih.gov/chemidplus/
U.S. National Library of Medicine (NLM). (2018b). Haz-Map®: Information on Hazardous Chemicals
and Occupational Diseases. Retrieved from https://hazmap.nlm.nih.gov/categorv-
details?table=copvtblagents&id=19088
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Parser?Sectl=PT02&Sect2=HIT0FF&p=l&u=%2Fnetahtml%2FPT0%2Fsearch-
bool.html&r=0&f=S&l=5 O&TERM 1 =potassium+gluconate&FIELD 1=&co 1 =AND&TERM2=&
FIELD2=&d=PTXT
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https://onlinelibrarv.wilev.com/doi/10.1002/143560Q7.al 1 561.pub2
Washington State Dept. of Ecology. (2018). Children's Safe Product Act Reported Data. Retrieved from
https ://fortress. wa. gov/ecv/cspareporting/
XII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Appendix B: Hazard Characterization
Table B.1: Human Health Hazard
ADME
Source
Exposure
Route
Species & strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
4940231,
4940243
Oral (gavage)
Wistar rats
Single dose
Dose: 0 and 4000
mg/kg
Replicates: 4-14
male rats
Enzyme levels of glucose-6-
phosphate and 6-
phosphogluconate were 163 and
27 |jmol/kg 5 hours following
treatment and were similar to
levels in the control animals
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• OECD Guideline 417
• GLP compliance not reported
4947912
Oral
Humans
Single dose,
urine
collected 7
hours post
exposure
Dose: 84 or 167
mg/kg
Replicates: 3
healthy males
The recovered GDL in urine was
0 and 7.7-15% of the original
dose at 84 and 167 mg/kg,
respectively
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• Pre-dates GLP compliance
4940243
Oral (gavage)
Wistar rats
Single dose
Dose: 800 mg/kg
mg/kg
Replicates: 9-10
fasted male rats
The radioactivity of D-glucono-
delta-lactone was reported to be
25.0 (whole body), 23.1
(intestines and feces), 29.5
(urine), and 7.0% (exhaled
carbon dioxide)
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• OECD Guideline 417
• GLP compliance not reported
4940231,
4940243
Oral (gavage)
Wistar rats
Single dose
Dose: 800 mg/kg
mg/kg
Replicates: 9-23
fasted male rats
After 5 hours, radioactivity was
reported to be 12.1% (exhaled
carbon dioxide) 19.7% (whole
body), 44.9% (intestine and
feces) and 5.0% (urine)
• Test substance reported as CASRN 527-
07-1
• Purity not reported
• OECD Guideline 417
• GLP compliance not reported
4941343
Oral (gavage)
Sprague-Dawley
rats
Single dose
Dose: 30 mg/kg
Replicates: 7 male
rats
Total amount of radiolabeled
calcium excreted in urine was
1.241 ±0.473%. The highest
concentration of radioactivity
was found in bone as 98.7 ±
1.6%
• Test substance reported as CASRN 299-
28-5 (radiolabeled)
• Purity not reported
• GLP compliance not reported
XIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
4946680
Nasogastric
tube
Humans
Single dose
Dose: 20 mL of
10% calcium
gluconate
Replicates: 15
fasting males
Acid secretion post dosing was
greater than levels prior to
testing. Serum gastrin levels
also increased 30min after
dosing
• Test substance reported as CASRN 299-
28-5
• Purity not reported
• Pre-dates GLP compliance
Acute Mammalian Toxicity
Source
Exposure
Route
Species & strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
2072857
Oral (gavage)
Wister rats
Single
exposure,
14-day
observation
Doses: 3,000,
3,600, 4,320,5,190
and 6,210 mg/kg
Replicates: 5 per
sex per dose
LDso: 6060 mg/kg (95%
confidence interval: 5,640 and
6,510 mg/kg)
Methods:
• Test substance reported as CASRN 299-
27-4
• Purity not specified
• GLP compliance not reported
Results:
• 5190 mg/kg: Mortality in 1 male and 1
female
• 6,210 mg/kg: Mortality in 4 males and 3
females
2072857
Dermal
Sprague-Dawley
rats
24 hours,
observed for
14 days
Dose: 2000 mg/kg
Replicates: 5 per
sex
LDso > 2000 mg/kg
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity: 54.4%
• OECD Guideline 402
• GLP compliant
Repeated Dose Toxicity
Source
Exposure
Route
Species & strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
4947904,
2072857
Oral (gavage)
Sprague-Dawley
rats
28 days
Doses: 0, 500,
1000, or 2000
mg/kg-day
Replicates: 12 per
sex per dose
NOAEL: 500 mg/kg-day
LOAEL: 1000 mg/kg-day based
on increased relative kidney
weight
Methods:
• Test substance reported as CASRN 527-
07-1
• Purity not reported
• GLP not reported
Results:
XIV
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
• Urinalysis showed increased sodium
excretion at 2000mg/kg-day (both sexes)
• Increased relative kidney weight was
observed in males > 1000 mg/kg-day
• Increased absolute adrenal weight was
seen in males at 1000 mg/kg-day but not
2000mg/kg-day
• Increased thickening of the limiting ridge
of the stomach was observed in 5/12
males at 2000 mg/kg-day.
o Study authors considered
lesions to not to be
toxicologically significant for
humans because the limiting
ridge is tissue specific to rodents
4947904,
2072857
Oral
Sprague-Dawley
rats
28 days
Doses: 0,1.25,2.5,
or 5%
(corresponding to 0,
1000,2000 and
4100 (M) or 4400
(F) mg/kg-day)
Replicates: 10 per
sex per dose
NOAEL: 4100 mg/kg-day
Methods:
• Test substance reported as CASRN 527-
07-1
• Purity not reported
• GLP not reported
Results:
• A transient decrease in feed efficiency
(males 4100 mg/kg-day) was observed at
week 4 but was not different overall, so it
was not considered an adverse effect
• Water intake increased (26%) in 4100
mg/kg-day males, but not females. This
was not considered an adverse effect
• Decreased prothrombin times were
observed in males at 2000 and 4100
mg/kg-day. The study authors did not
consider this an adverse effect
• Urinary changes were observed in both
treated and control groups and was
attributed to sodium. Increased urinary
ketone bodies were observed in 2000
mg/kg/d, but not 4100 mg/kg-day males
XV
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
• Increased relative kidney weights were
observed in males at 4100 mg/kg-day and
in females at 2000 mg/kg-day, but not
4400 mg/kg-day. Given the above effects
and non-dose dependent nature, this was
not considered an adverse effect for this
study
2072857
Oral
Beagle dogs
4 weeks
Doses: 0, 500,
1000, and 2000
mg/kg-day
Replicates: 4 per
sex per dose
NOAEL: 500 mg/kg-day
LOAEL: 1000 mg/kg based on
watery stools and vomiting
Methods:
• Test substance reported as CASRN 527-
07-1
• Purity not reported
• GLP not reported
Results:
• No animals died. Significant increases in
the frequency of vomiting and passage of
loose or watery stools was observed in the
1,000 and 2,000 mg/kg-day groups
4947912
Oral
Rats
29 months
Dose: 340 mg/kg-
day
Replicates: 30 per
sex
NOAEL: 340 mg/kg-day
Methods:
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• Pre-dates GLP compliance
4940241,
Oral (gavage)
JCL: Sprague
6 months
Doses: 0, 250, 500,
NOAEL < 250 mg/kg-day
Methods:
4940253
Dawley rats
1000,2000, and
4000 mg/kg-day
Replicates: 10 per
sex per dose
LOAEL: 250 mg/kg-day based
on hypertrophy of stratified
squamous epithelium in stomach
• Test substance reported as CASRN 90-
80-2
• Purity: 99%
• OECD Guideline 408
• Not GLP compliant
Reproductive Toxicity
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
4864285
Oral (gavage)
Wistar rats
8 weeks
Doses: 0, 30,300,
NOAEL: 1000 mg/kg-day, no
Methods:
• Dosing
and 1000 mg/kg-
adverse reproductive effects
• Test substance reported as CASRN
began 2
day
31138-65-5
weeks
Replicates: 12 per
• Purity: 49.5%
prior to
sex per group
• OECD Guideline 422
mating
• GLP compliant
XVI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
• Dosing
continue
U,
through
gestation
to
lactation
day 5 (for
females)
Developmental Toxicity
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
4947912,
4940251,
4947704
Oral (gavage)
Albino CD-1 mice
GD 6-15
Doses: 0, 6.95,
32.5, 150 and 695
mg/kg-day
Replicates: 21-25
per dose
NOAEL: 695 mg/kg-day
Methods
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• OECD Guideline 414
• Pre-dates GLP
4947912,
4940249,
4947704
Oral (gavage)
Golden outbred
hamsters
GD 6-10
Doses: 0, 5.6, 26,
121, and 560
mg/kg-day
Replicates: 20-25
per dose
NOAEL: 560 mg/kg-day
Methods
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• OECD Guideline 414
• Pre-dates GLP
4947912,
4940230,
4947704
Oral (gavage)
Dutch rabbits
GD 6-18
Doses: 0, 7.8, 32.2,
168 and 780 mg/kg-
day
Replicates: 10-13
per dose
NOAEL: 780 mg/kg-day
Methods
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• OECD Guideline 414
• Pre-dates GLP
4947912,
4940250,
4947704
Oral, (gavage)
Wister rats
GD 6-15
Doses: 0, 5.94,
27.6, 128 and 594
mg/kg-day
NOAEL: 594 mg/kg-day
Methods
• Test substance reported as CASRN 90-
80-2
XVII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
Replicates: 21-25
per dose
• Purity not reported
• GLP not reported
Cancer
Source
Effect
Study Details
OncoLogic
v8.0
OncoLogic currently has no assessment criteria regarding sugar
derivatives.
Structure could not be evaluated by Oncologic.
ISS v2.439
Negative (Estimated)
D-Gluconic Acid is a multi-hydroxy acid which does not contain any
structural features indicative of electrophilic potential.
Methods:
Carcinogenicity alerts (genotoxic and non-genotoxic) by ISS profiler as available
within the OECD Toolbox v4.3
Results:
No alerts were identified for the parent structure (an aldehyde and a butyl diester
alert are flagged for its metabolites)
VEGA
1 1 440
D-Gluconic acid and its salts were processed through all 4 models. ISS
1.0.2 and IRFMN/ISSCAN-GX 1.0.0 predicted the acid to be non-
carcinogenic with moderate reliability.
Methods:
VEGA 1.1.4 contains 4 models for carcinogenicity - CAESAR 2.1.9, ISS 1.0.2,
IRFMN/Antares 1.0.0, IRFMN/ISSCAN-GX 1.0.0
Results:
• CAESAR 2.1.9: Low reliability (D-Gluconic acid lies outside of the
applicability domain (AD) of the model)
• ISS 1.0.2: Moderate reliability (D-Gluconic acid could be outside of the
AD)
• IRFMN/Antares 1.0.0: Low reliability (D-Gluconic acid lies outside of the
AD)
39 Carcinogenicity alerts by ISS profiler comprises 55 structural alerts for genotoxic and non-genotoxic carcinogenicity. Hie alerts have been compiled upon existing knowledge of
the mechanism of action of carcinogenic chemicals that have been published elsewhere (Benigni and Bossa (2011) ChemRev 111: 2507-2536 and Benigni R et al. (2013) Chem
Rev. 113:2940-2957).
40 VEGA 1.1.4 contains 4 different models to facilitate an in silico assessment of carcinogenicity potential. The models are summarized in Golbamaki et al. (2016) J Environ Sci
and Health Part C http://dx.doi.org/10.1080/10590501.2Q16.1166879 as well as in documentation that is downloadable from within the VEGA tool itself
(https://www. vegahub. eu/).
• CAESAR 2.1.9 is a classification model for carcinogenicity based on a neural network.
• ISS 1.0.2 is a classification model based on the ISS ruleset (as described above for the OECD Toolbox).
• IREMN/Antares 1.0.0 and IREMN/ISSCAN-GX 1.0.0 are classification models based on a set of rules built with SARpy software (part of the same suite of VEGA tools
https://www.vegahub.eu/) extracted from the Antares and ISSCAN-CGX datasets respectively.
XVIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
Overall, D-Gluconic acid and its salts are expected not to be carcinogenic
on the basis of the VEGA predictions.41
• IRFMN/ISSCAN-GX 1.0.0: Moderate reliability (D-Gluconic acid could be
outside of the AD)
Genotoxicity
Source
Test Type &
endpoint
Species & strain
(if available)
Metabolic
activation
Doses and
controls
Results
Study Details
4940235
Gene mutation
(in vitro)
Salmonella
typhi murium
TA1535,1537,
98,100, and 102
With and
Without
Doses: 50,150,
500,1500, and
5000 pg/plate
Negative
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity: 52%
• OECD Guideline 471
• GLP compliant
4940252
Chromosomal
aberrations (in
vitro)
Human
lymphocytes
With and
Without
Doses: 0, 0.16,
0.31,0.625, 1.25,
2.5, and 10 mM
Negative
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity: 52%
• OECD Guideline 473
• GLP compliant
4940247,
4940234
Gene mutation
(in vitro)
Mouse lymphoma
L5178Y cells
With and
Without
Doses: 1.25, 2.5, 5,
and 10 mM
Negative
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity: 52%
• OECD Guideline 490
• GLP compliant
4940109
Gene mutation
(In vitro)
Salmonella
typhi murium
TA97, 98, 100,
and 1535
With and
without
Doses: 0,100, 333,
1000,3333, and
10000 pg/plate
Negative
Methods:
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• NTP mutagenicity protocol for Ames test
41 Each model is characterized by an applicability domain (AD) that depends on at least 5 components:
• Similar substances with known experimental values within the underlying training set
• Accuracy of prediction for similar substances
• Concordance for similar substances,
• Fragments similarity check on the basis of atom centered fragments,
• Model descriptors range check.
A global AD index considers the other 5 components to provide an overall reliability score - low, moderate or high. EPA has not included low-reliability model results.
XIX
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Table B.1: Human Health Hazard
• GLP compliance not reported
4947757
Gene mutation
Salmonella
With and
Doses: 0.25% and
Negative
Methods:
(In vitro)
typhi murium
TA1535,1537,
1538
without
0.5% test substance
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• GLP compliance not reported
4947757,
Gene mutation
Saccharomyces
With and
Doses: 1.25% and
Negative
Methods:
2072857
(In vitro)
cerevisiae strain
D4
without
2.5% test substance
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• GLP compliance not reported
2072857
Gene mutation
Salmonella
With and
Doses: 0.25% and
Negative
Methods:
(In vitro)
typhi murium
TA1535,1537,
1538
without
0.5% test substance
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• OECD Guideline 471
• Not GLP compliant
Endpoints:
• Cytotoxicity observed at 1 %
2072857
Chromosomal
aberrations (In
vivo)
C57BL mice
With
Single dose study:
Doses: 2000,4000,
and 8000 mg/kg
Replicates: 3 per
group
Repeat dose study:
Doses: 2000 and
4000 mg/kg-day
Replicates: 2-3 per
group
Negative
Methods:
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• GLP compliance not reported
Mortality Results:
• 3/3 died in 8000 mg/kg
4947764,
Gene mutation
Saccharomyces
With and
Doses: 0.75, 1.50,
Negative
Methods:
2072857
(in vitro)
cerevisiae strain
D4
without
and 3.00% of
substance
• Test substance reported as CASRN 299-
28-5
• Purity not reported
• OECD Guideline 471
• GLP not reported
Endpoints:
XX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
• Cytotoxicity observed at 3%
4947764,
Gene mutation
Salmonella
With and
Doses: 1.25, 2.5
Negative
Methods:
2072857
(in vitro)
typhimurium
strains TA1535,
TA1537, and
TA1538
without
and 5.0% of
substance
• Test substance reported as CASRN 299-
28-5
• Purity not reported
• OECD Guideline 471
• GLP not reported
4947765,
Gene mutation
Salmonella
With and
Doses: 0.0006,
Negative
Methods:
2072857
(in vitro)
typhimurium
strains TA1535,
TA1537, and
TA1538
without
0.0012, and
0.0024% substance
• Test substance reported as CASRN 527-
07-1
• Purity not reported
• OECD Guideline 472
• Non-GLP compliant
Results:
• Cytotoxicity was observed at 0.0024%
4947765,
Gene mutation
Saccharomyces
With and
Doses: 1.25%,
Negative
Methods:
2072857
(in vitro)
cerevisiae strain
D4
without
2.5%, and 5%
substance
• Test substance reported as CASRN 527-
07-1
• Purity not reported
• OECD Guideline 472
• Non- GLP compliant
Results:
• Cytotoxicity was observed at 5%.
2072857
Chromosomal
aberrations (In
vivo)
C57BL mice
With
Doses: 0, 2500,
5000, and 1000
mg/kg-day for 1
day, and 1250 and
2500 mg/kg-day for
4 consecutive days.
Negative
Methods:
• Test substance reported as CASRN 527-
07-1
• Purity not reported
• GLP not reported
Results:
• In the single dose groups, all mice in the
5,000 and 10,000 mg/kg groups died. Only
two mice in the 2,500 mg/kg dose could
be evaluated due to technical issues.
Sodium gluconate induced chromosomal
aberrations at a rate of 0.5% which was
comparable to controls.
XXI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table B.1: Human Health Hazard
• In the 1250 mg/kg-day and 2500 mg/kg-
day animals, one mouse in each treatment
group died. Chromosomal aberrations in
surviving animals were similar to the
negative controls. The test substance was
considered non-genotoxic
Sensitization
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses and
replicate number
Effect
Study Details
4940232
Dermal
CBA/CaOlaHsd
mice
5 days
Doses: 25 pL of 25,
50, and 100%
concentration in
dimethyl formamide
Replicates: 4 per
dose
Negative
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity: 54.4%
• OECD Guideline 422
• GLP compliant
4864280
Dermal
CBA mice
3 day
Doses: 25 pL of
25%, 50%, and
100% substance
Not sensitizing
Methods:
• Test substance reported as CASRN
31138-65-5
Replicates: 4 per
group
• Purity not reported
• OECD Guideline 429
• GLP compliant
Results:
Stimulation index was 0.93, 0.86, and 0.61 at
25%, 50% or 100% substance, respectively
Irritation
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses
Effect
Study Details
4940239
Dermal
New Zealand
Exposures
Dose: 0.5 mL
Negative
Methods:
White rabbits
after 3
minutes, 1
hour, and 4
hour;
observed for
72 hours
undiluted test
substance
Replicates: 3
rabbits
• 2/3 rabbits
were exposed
for 4 hours
(single dose)
• Test substance reported as CASRN 526-
95-4
• Purity reported as 54.4%
• Based on EU Method B.4
• GLP compliant
XXII
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Table B.1: Human Health Hazard
• 1/3 rabbits
were exposed
after 3
minutes, 1
hour, and 4
hours (three
doses)
2072857
Dermal
Albino rabbits
4 hour
exposure
observed for
72 hours
Dose: 0.5 mL
undiluted test
substance
Replicates: 12
rabbits
Negative
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity not reported
• Test method: 'Directive 79/831/EEC, B.4.
• GLP compliance not reported
Endpoints:
• Erythema was observed in 3/6 animals 1
hour post exposure and in 1/6 animals
through 48 hours post exposure
4940242
Ocular
New Zealand
White rabbits
Single
exposure
observed for
72 hour
Dose: 0.1 mLtest
material
Replicates: 3
rabbits
Positive
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity 54.4%
• OECD Guideline 405
• GLP compliance not reported
Endpoints:
• At 1 hour, chemosis and conjunctival
redness were mild-moderate or moderate
to severe in all animals. 2 animals
exhibited lacrimation, iris lesions, and 1
animal had corneal lesion
• At 24 hours, one animal had severe
chemosis, lacrimation and conjunctival
redness with lesions of iris and cornea
whereas the other 2 animals had slight to
minimal effects
XXIII
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Table B.1: Human Health Hazard
• At 48 hours, 1 animal had chemosis,
lacrimation, conjunctival redness, iris
lesions, and corneal lesions
• At 72 hours, slight chemosis and
conjunctival redness persisted in one
animal
• All effects were fully reversible
• D-gluconic acid was considered mildly
irritating
2072857
Ocular
New Zealand
White albino
rabbits
Single
exposure,
observed for
up to 7 days
Dose: 0.1 mLof
50% test substance
Replicates: 9
rabbits
Negative
Methods:
• Test substance reported as CASRN 526-
95-4
• Purity not reported
• Test method: Draize Test
• GLP compliance not reported
Endpoints:
• Some redness and chemosis of the
conjunctivae, irritation of the iris and
discharge were observed 1 hour post
exposure
• Conjunctivae redness and chemosis were
also observed at 24 and 48 hours post
exposure
• All effects were reversed by 72 hours
• D-gluconic acid was considered non-
irritating
2077994
Ocular
Bovine
4 hours
Dose: 0.75 mL of
20% suspension of
test material
Replicates: 6
Severely irritating
Methods:
• Test substance reported as CASRN 90-
80-2
• Purity not reported
• According to bovine corneal opacity and
permeability assay based on the method
of muir (1984)
• GLP not reported
Endpoints:
XXIV
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Table B.1: Human Health Hazard
• Corneal opacity scores were evaluated
before and after treatment. Classification
of this test material is a severe irritant
Neurotoxicity
Source
Exposure
Route
Species & Strain
(if available)
Duration
Doses
Effect
Study Details
2540871
Oral (drinking
water)
Wistar rats
30 days
Doses: 0 or 1% of
substance
Replicates: 10
males per group
Negative
Methods:
• Test substance reported as CASRN 299-
28-5
• Purity not reported
• GLP not reported
4941088
Oral (drinking
water)
Wistar rats
3 days
Doses: 0 or 1% of
substance
Replicates: 50
males per group
Negative
Methods:
• Test substance reported as CASRN 299-
28-5
• Purity not reported
• GLP not reported
XXV
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Table B.2: Environmental Hazard
Aquatic Toxicity: Experimental
Source
Species &
strain (if
available)
Duration
Doses and replicate
number
Effect
Study Details
4940263, 2072857
Oryzias
latipes
96 hours
Dose: 100 mg/L
(nominal)
LCso > 100 mg/L
Methods:
• Test substance reported as CAS RN 527-07-1
• Purity: 99.6%
• OECD Guideline 203
• GLP compliant
Results:
• No deaths, no behavioral abnormalities, no symptoms of toxicity
observed
4940259, 2072857
Daphnia
magna
48 hours
Dose: 1000 mg/L
(nominal)
EC50 >1000 mg/L
Methods:
• Test substance reported as CAS RN 527-07-1
• Purity: 99-101%
• OECD Guideline 202
• GLP compliant
Results:
• No immobility or mortality in test vessels
2072857
Daphnia
magna
48 hours
Dose: 1000 mg/L
(nominal)
EC50 > 1000 mg/L
Methods:
• Test substance reported as CAS RN 527-07-1
• Purity: 99.6%
• OECD Guideline 202
• GLP compliant
Results:
• No immobility or mortality
4940257
Scenedesmus
subspicatus
72 hours
Doses: 100 mg/L
(nominal)
ECo < 100 mg/L
Methods:
• Test substance reported as CAS RN 527-07-1
• Purity: 99-101%
• OECD Guideline 201
• GLP compliant
Results:
• 70% inhibition at 100 mg/L (nominal, biomass) and 42% inhibition
at 100 mg/L (nominal, growth rate)
XXVI
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2072857
Selenastrum
capricornutum
72 hours
Doses: 0,100,180,
320, 560, 1000 mg/L
(nominal)
EC50 > 1000 mg/L
Methods:
• Test substance reported as CAS RN 527-07-1
• Purity: 99.6%
• OECD Guideline 201
• GLP compliant
Results:
• NOEC: 560 mg/L (nominal, growth rate)
Aquatic Toxicity: Estimated
Model
Endpoint
Species
Predicted Effect
Level
Notes
ECOSAR
Acute
Algae
320,000 mg/L
Input SMILES: 0=C(0)C(0)C(0)C(0)C(0)C0. Experimental input values: Water Solubility =
316000 mg/L; MP = 131 C.
ECOSAR
Acute
Invertebrate
1,900,000 mg/L
Input SMILES: 0=C(0)C(0)C(0)C(0)C(0)C0. Experimental input values: Water Solubility =
316000 mg/L; MP = 131 C.
ECOSAR
Acute
Vertebrate
4,800,000 mg/L
Input SMILES: 0=C(0)C(0)C(0)C(0)C(0)C0. Experimental input values: Water Solubility =
316000 mg/L; MP = 131 C.
ECOSAR
Chronic
Algae
38,000 mg/L
Input SMILES: 0=C(0)C(0)C(0)C(0)C(0)C0. Experimental input values: Water Solubility =
316000 mg/L; MP = 131 C.
ECOSAR
Chronic
Invertebrate
69,000 mg/L
Input SMILES: 0=C(0)C(0)C(0)C(0)C(0)C0. Experimental input values: Water Solubility =
316000 mg/L; MP = 131 C.
ECOSAR
Chronic
Vertebrate
300, 000 mg/L
Input SMILES: 0=C(0)C(0)C(0)C(0)C(0)C0. Experimental input values: Water Solubility =
316000 mg/L; MP = 131 C.
Table B.3: Fate
Environmental Fate: Experimental
Source
Endpoint
Duration
Doses and
number of
replicates
Results
Study Details
2072857
ThOD
28 day
Dose: 3 mg/L
Readily biodegradable,
10-day window met
Methods:
• Test substance reported as CASRN 527-07-1.
• Purity: 99-101%
• Test method: Directive 92/69/EEC, C.4-E and OECD Guideline
301D (Closed bottle test)
• GLP compliant
Results:
• Degradation kinetics: 3 days (61.13%); 7 days (74.35%); 14 days,
(66.09%), 21 days (71.94%), 28 days, (88.88%)
XXVII
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Table B.3: Fate
2072857
Anaerobic
mineralization
35 days
Dose: 303
mg/L
100% degradation after
35 days (based on net-
mass carbon)
Methods:
• Test substance reported as CASRN 527-07-1
• Purity not reported
• Test method: DIN EN ISO 11734
• GLP compliant
Results:
• Degradation kinetics: 1 days (8%); 8 days (51%); 15 days (57%), 22
days (61%), 35 days (100%), when accounting for biogas production
and dissolved inorganic carbon (DIC)
2072857
Other: Absorption
mechanisms
(sorption to gibbsite
mineral)
NA
Doses: 1 and
100 mmol/L
Results indicate that
electrostatic interaction is
the primary mechanism
at low pH, hydrophilic
interactions at
intermediate pH and
inner sphere complex
formation at high pH.
Methods:
• Test substance CASRN 527-07-1
• Purity not reported
• Method: Batch sorption experiment
Notes:
• Sorption kinetics best described as two-site Langmuir isotherm
based on experimental equilibration
o Sorption constants: Kf = 9.33±0.78. 7.48±0.77,1.2±0.25,
and 2.91 ±0.36 mmol-L/Kg atpH 4, 7, 9, and 12,
respectively;
o Distribution constant Kd = 41.8 L/Kg at pH 13.3;
• Gibbsite properties:
• Purity: 99.4%, Density: 2.4 g/cm3
2072857
ThOD
28 day
Dose: 3 mg/L
Readily biodegradable,
10-day window met
Methods:
• Test substance reported as CASRN 527-07-1
• Purity: 99-101%
• Test method: Directive 92/69/EEC, C.4-E and OECD Guideline
301D (Closed bottle test)
• GLP compliant
Results:
• Degradation kinetics: 3 days (61.13%); 7 days (74.35%); 14 days,
(66.09%), 21 days (71.94%), 28 days, (88.88%)
Experimental Fate: Modelled
Model
Data Type
Endpoint
Predicted
Endpoint
Notes
EPISuite
v.4.11
Estimated
BAF
0.89
XXVIII
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Table B.3: Fate
EPISuite
v.4.11
Estimated
BCF
3.16
(regression on
eq)
EPI Suite
Reference
EPI Suite (Physical Property Inputs - WS = 450000 mg/L), SMILES:
0CC(0)C(0)C(0)C(0)C(=0)(0K)
XXIX
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B.1 References
ECHA (European Chemicals Agency). (1973a). D-glucono-l,5-lactone: developmental
toxicity/teratogenicity: in vitro: 001 key | experimental result. Helsinki, Finland.
https://ccha.curopa.cu/rcgistration-dossicr/-/registered-
dossier/ 1952/7/9/3/'MocumcntUUID=5437f5a7-dcSc-4f57-96cf-4a 1 a5dd50ffc
ECHA (European Chemicals Agency). (1973b). D-glucono-1,5-lactone: developmental
toxicity/teratogenicity: in vitro: 002 key | experimental result, https://echa.europa.eu/registration-
dossier/-/registered-dossier/1952/7/9/3/?documentUUID=fe2a970c-123e-40cc-80ef-
cb310cc210ab
ECHA (European Chemicals Agency). (1973c). D-glucono-1,5-lactone: developmental
toxicity/teratogenicity: in vitro: 003 supporting | experimental result.
https://ccha.curopa.cu/rcgistration-dossicr/-/registered-
dossier/ 1952/7/9/3/?documentUUID=ce9e8 820-3 6a6-4e4 8-b021-257 Ib4d83 5 09
ECHA (European Chemicals Agency). (1973d). D-glucono-1,5-lactone: Developmental
toxicity/teratogenicity: In vitro: 004 supporting | experimental result. Helsinki, Finland.
https://ccha.curopa.cu/rcgistration-dossicr/-/registered-
dossier/ 1952/7/9/3/'MocumcntUUID=7f2cdd3d-df71 -443 f-a 121 -585e86195729
ECHA (European Chemicals Agency). (1978a). D-gluconic acid: repeated dose toxicity: oral: 001 key |
read-across (structural analogue/surrogate), https://ccha.curopa.cu/rcgistration-dossicr/-
/registered-dossier/1957/7/6/2/?documentUUID=f0ff9c7c-8a02-4723-aacl-45f06e439682
ECHA (European Chemicals Agency). (1978b). D-glucono-1,5-lactone: repeated dose toxicity: oral: 001
key | experimental result. Helsinki, Finland, https://ccha.curopa.cu/rcgistration-dossicr/-
/registered-dossier/1952/7/6/2/?documentUUID=93daf682-ff67-4025-aacc-2ae69acd2f0b
ECHA (European Chemicals Agency). (1979a). D-glucono-l,5-lactone: basic toxicokinetics.
https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/1952/7/2/2
ECHA (European Chemicals Agency). (1979b). Potassium gluconate: basic toxicokinetics.
https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/10349/7/2/2
ECHA (European Chemicals Agency). (2001a). Potassium gluconate: short-term toxicity to aquatic
invertebrates. https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/l 0349/6/2/4
ECHA (European Chemicals Agency). (2001b). Potassium gluconate: toxicity to aquatic algae and
cyanobacteria. https://echa.europa.eu/registration-dossier/-/registered-dossier/10349/6/2/6
ECHA (European Chemicals Agency). (2002). Potassium gluconate: short-term toxicity to fish.
https://echa.europa.eu/registration-dossier/-/registered-dossier/10349/6/2/2
ECHA (European Chemicals Agency). (2009a). D-gluconic acid: acute toxicity: dermal. Helsinki,
Finland. https://echa.europa.eu/registration-dossier/-/registered-dossier/1957/7/3/4
XXX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
ECHA (European Chemicals Agency). (2009b). D-gluconic acid: eye irritation: 001 Key | experimental
result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/1957/7/4/3/?documentUUID=54973aef-65d5-4a45-baal-686b9d404172
ECHA (European Chemicals Agency). (2009c). D-gluconic acid: skin irritation/corrosion.
https://ccha.curopa.cu/registration-dossier/-/registered-
dossier/1957/7/4/2/'MocumcntUUID=7c5421ffl-0cb7-477S-bdSb-23cdclc62d24
ECHA (European Chemicals Agency). (2009d). D-gluconic acid: skin sensitisation: in vivo (LLNA).
Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-dossier/1957/7/5/2
ECHA (European Chemicals Agency). (2013). Sodium glucoheptonate: skin sensitisation: in vivo
(LLNA). https://echa.europa.eu/registration-dossier/-/registered-dossier/8874/7/5/2
ECHA (European Chemicals Agency). (2015a). D-gluconic acid: genetic toxicity: in vitro: 001 key |
experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/1957/7/7/2/?documentUUID=6f375db7-807a-4898-b654-5569828e5ee4
ECHA (European Chemicals Agency). (2015b). D-gluconic acid: genetic toxicity: in vitro: 003 key |
experimental result. Helsinki, Finland. https://echa.europa.eu/registration-dossier/-/registered-
dossier/1957/7/7/2/?documentUUID=dl628eb2-7b0e-475e-ad72-f88cl013e568
ECHA (European Chemicals Agency). (2015c). D-glucono-1,5-lactone: genetic toxicity: in vitro: 006 key
| experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/1952/7/7/2/?documentUUID=bdc6a902-15a0-471c-b347-87df4bed48a3
ECHA (European Chemicals Agency). (2015d). D-glucono-1,5-lactone: genetic toxicity: in vitro: 010
supporting | experimental result. https://echa.europa.eu/registration-dossier/-/registered-
dossier/1952/7/7/2/?documentUUID=d2f3b96e-f5bl-4338-af8c-c5ab4161aca2
Gautheron. P; Giroux. J; Cottin. M; Audegond. L; Morilla. A; Mayordomo-Blanco. L; Tortaiada. A;
Havnes. G; Vericat. JA; Pirovano. R; Gillio. TE; Hagemann. C; Vanparvs. P; Deknudt. G; Jacobs.
G: Prinsen. M; Kalweit. S: Spielmann. H. (1994). Interlaboratory assessment of the bovine
corneal opacity and permeability (BCOP) assay. Toxicol In Vitro 8: 381-392.
Godinho. AF; Stanzani. SL; Ferreira. FC; Braga. TC; Silva. MC; Chaguri. JL; Dias-Junior. CA. (2014).
"Permethrin chronic exposure alters motor coordination in rats: effect of calcium
supplementation and amlodipine". Environ Toxicol Pharmacol 37: 878-884.
http://dx.doi.Org/10.1016/i.etap.2014.02.017
Godinho. AF; Trombini. TV; Oliveira. EC. (2002). Effects of elevated calcium on motor and exploratory
activities of rats. Braz J Med Biol Res 35: 451-457. http://dx.doi.org/10.1590/S010Q-
879X2002000400007
Harlan Laboratories. (2013). Chemical test rule data: sodium glucoheptonate (EC250-480-2): oral
(gavage) combined repeat dose toxicity study with reproduction/developmental toxicity screening
test in the rat (OECD 422). Harcros Chemicals Inc.
https://chemview.epa.gov/chemview/chemical data.do?sourceId=2&templateType=Endpoint&che
micalDataId=31688321&chemicalId=80358&modalVaeKev=0-0-2-l
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JECFA, JFWECoFA. (1986). Glucono delta-lactone. In Food additives and contaminants: WHO food
additives series 21. Joint FAO/WHO Expert Committee on Food Additives (JECFA).
http://www.inchem.org/documents/iecfa/iecmono/v21 i e 14 .htm
JECFA, JFWECoFA. (1999). Safety evaluation of certain food additives: WHO food additives series 42.
Glucono-delta-lactone and the calcium, magnesium, potassium, and sodium salts of gluconic acid
(pp. 203-212). Geneva, Switzerland: Joint FAO/WHO Expert Committee on Food Additives
(JECFA). http://www.inchem.org/documents/iecfa/iecmono/v042ie 12.htm
Litton Bionetics. (1974). Mutagenic evaluation of compound FDA 71-72, glucono-delta-lactone.
(FDABF-GRAS-282). Washington, DC: U.S. Food and Drug Administration.
Litton Bionetics. (1975a). Mutagenic evaluation of compound FDA 73-5, calcium gluconate. (FDABF-
GRAS - 328). Washington, DC: U.S. Food and Drug Administration.
Litton Bionetics. I. nc. (1975b). Mutagenic evaluation of compounds FDA 75-5, 000527-07-1, sodium
gluconate, FCC, fine granular. Litton Bionetics, Inc.
Liu. D: Yu. Y. un; Zhang. J. ie: Liu. X; Wang. M; Hemar. Y; Regenstein. J. oeM; Zhou. P. (2017).
Biochemical and physico-chemical changes of skim milk during acidification with glucono-delta-
lactone and hydrogen chloride. Food Hydrocolloids 66: 99-109.
http://dx.doi.Org/10.1016/i.foodhvd.2016.12.030
NTP (National Toxicology Program). (2018). G06 - Ames summary data: gluono delta lactone.
https://manticore.niehs.nih.gov/cebssearch/studv/002-02207-0001-000Q-4
OECD (Organisation for Economic Co-operation and Development). (2004). Gluconic acid and its
derivatives. Belgium; Japan: UNEP Publications.
https://hpvchemicals.oecd.org/UI/handler.axd?id=b94cc5f7-de5c-4417-b6c2-fleb4ffcdb72
Zhang. YH; Wang. XG: Tian. PF; Zhang. JF; Hu. ZL; Xu. B; Ye. CJ: Ni. LF; Han. CM. (2018). [Analysis
on effects of modified dosage of calcium gluconate on patients with hydrofluoric acid burns not
in hands or feet]. Zhonghua Shao Shang Za Zhi 34: 277-282.
http://dx.doi.Org/10.3760/cma.i.issn.1009-2587.2018.05.005
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Appendix C: Literature Search Outcomes
C.1 Literature Search and Review
This section briefly describes the literature search and review process, search terms, and search outcomes
for the hazard and fate screening of potassium gluconate. Search outcomes and reference details are
provided on the candidate's HERO42 project page.
EPA created a fit-for-purpose process to transparently document the literature search and review43 of
available hazard and fate information for low-priority substance (LPS) candidates. References from peer-
reviewed primary sources, grey sources,44 and other sources were identified, screened at the title/abstract
and full-text level, and evaluated for data quality based on discipline-specific criteria. An overview of the
literature search and review process is illustrated in Figure CI.
Figure C.l: Overview of the Literature Search and Review Process
LU
References available at
title/abstract screening
References available at data quality evaluation
References included in LPS screening reviews
References available at full text screening
References excluded at
full text screening
References excluded at
data quality evaluation
References excluded at
title/abstract screening
References available
from grey literature
and other sources
References available
from primary peer-
reviewed sources
C.1.1 Search for Analog Data
To supplement the information on the candidate chemical, potassium gluconate, the following LPS
candidates were used as analogs for read-across: sodium glucoheptonate (CASRN 31138-65-5), D-
gluconic acid (CASRN 526-95-4), calcium gluconate (CASRN 299-28-5), glucono-delta-lactone
41 Hie HERO low-priority substance candidate project pages are accessible to the public at https;//hero. epa.gov/hero/.
43 Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances Under
TSCA", also released at proposal.
44 Grey literature and additional sources are the broad category of studies not found in standard, peer-reviewed literature database
searches. This includes U.S. and international government agency websites, non-government organization (NGO) websites, and
data sources that are difficult to find, or are not included, in the peer-reviewed databases, such as white papers, conference
proceedings, technical reports, reference books, dissertations, and information on various stakeholder websites.
XXXIII
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(CASRN 90-80-2), and sodium gluconate (CASRN 527-07-1). D-arabinonic acid (CASRN 488-30-2) was
also considered as an analog but not used for designation. For more details and justification on analogs,
see section 6.1.1. Analogs were used to fill data gaps on endpoints for which potassium gluconate lacked
quality data, such as repeat dose and developmental toxicity, and to add to the weight of the scientific
evidence. Analog references were searched, screened, and evaluated using the same process as references
on potassium gluconate described above.43 Potassium gluconate and the five analogs mentioned above fall
under the gluconates cluster in HERO.
Table C.1: Sources Used for Analog Search
Resource
URL
ATSDR
http://www.atsdr.cdc.gov/toxprofiies/index.asp
ChemID (EPA - HPVIS via
ChemID)
http://chem.sis.nlm.nih.gov/chemidplus/
CIR
http://www.cir-safety.org/ingredients
ECHA
http://echa.europa.eu/web/guest/information-on-chemicais/registered-substances
ECOTOX
https://cfpub.epa.gov/ecotox/quick_query.htm
EPA - ChemView (incl. TSCATS,
RBP/HC, and HPV/HPVIS)
https://chemview.epa.gov/chemview
European Food Safety Authority
(EFSA)
http://www.efsa.europa.eu/
FDA
https://www.fda.gov/defauit.htm
HERA
http://www.heraproject.com/RiskAssessment.cfm
NICNAS
http://www.nicnas.gov.au/
NITE (J-CHECK)
http://www.safe.nite.go.jp/jchec k/search.action?request_locale=en
NTP
https://ntpsearch.niehs.nih.gov/home
OECD/SIDS
https://hpvchemicals.oecd.org/UI/Search.aspx;
http://webnet.oecd.org/hpv/ui/SponsoredChemicais.aspx
C.1.2 Search Terms and Results
EPA began the literature review process for the hazard screening of potassium gluconate by developing
search terms. To gather publicly available information, specific search terms were applied for each
discipline and across databases and grey literature sources. Table C.2 lists the search terms used in the
database search of peer-reviewed literature for the gluconates cluster including potassium gluconate. For
grey literature and other secondary sources, Table C.3 lists the search terms used for the gluconates
cluster.
Table C.2: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms45
Human Health
PubMed
((527-07-1 [rn] OR 299-27-4[rn] OR 526-95-4[rn] OR 90-80-2[rn] OR 299-28-
5[rn]) AND (("Gluconates/toxicity"[mh] OR "Gluconates/adverse effects"[mh]
OR "Gluconates/poisoning"[mh] OR "Gluconates/pharmacokinetics"[mh])
OR ("Gluconates"[mh] AND ("environmental exposure"[mh] OR ci[sh])) OR
("Gluconates"[mh] AND toxicokinetics[mh:noexp]) OR
45 Additional language or syntax such as [tw], [rn], [org], and [nm] were added to search terms. These are unique to individual
databases and must be applied to search terms so that the query can run properly.
XXXIV
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
("Gluconates/blood"[mh] OR "Gluconates/cerebrospinal fluid"[mh] OR
"Gluconates/urine"[mh]) OR ("Gluconates"[mh] AND ("endocrine
system"[mh] OR "hormones, hormone substitutes, and hormone
antagonists"[mh] OR "endocrine disruptors"[mh])) OR ("Gluconates"[mh]
AND ("computational biology"[mh] OR "medical informatics"[mh] OR
genomics[mh] OR genome[mh] OR proteomics[mh] OR proteome[mh] OR
metabolomics[mh] OR metabolome[mh] OR genesjmh] OR "gene
expression"[mh] OR phenotype[mh] OR genetics[mh] OR genotype[mh] OR
transcriptome[mh] OR ("systems biology"[mh] AND ("environmental
exposure"[mhj OR "epidemiological monitoring"[mh] OR analysis[sh])) OR
"transcription, genetic "[mh] OR "reverse transcription"[mh] OR
"transcriptional activation"[mh] OR "transcription factors"[mh] OR
("biosynthesis"[sh] AND (RNA[mh] OR DNA[mh])) OR "RNA,
messenger"[mh] OR "RNA, transfer"[mh] OR "peptide biosynthesis"[mh] OR
"protein biosynthesis"[mh] OR "reverse transcriptase polymerase chain
reaction"[mh] OR "base sequence"[mh] OR "trans-activators"[mh] OR "gene
expression profiling"[mh])) OR ("Gluconates/antagonists and inhibitors"[mh])
OR ("Gluconates/metabolism"[mh] AND ("humans"[mh] OR "animals"[mh]))
OR ("Gluconates"[mh] AND cancer[sb]) OR
("Gluconates/pharmacology"[majr])))
(("1,5-D-Gluconolactone"[tw] OR "1,5-Gluconolactone"[tw] OR "2,3,4,5,6-
Pentahydroxyhexanoic acid"[tw] OR "BVD Addicrete"[tw] OR "Biocal"[tw]
OR "CalGlucon"[tw] OR "Calcicol"[tw] OR "Calcium D-Gluconate"[tw] OR
"Calcium Gluconate"[tw] OR "D-(+)-Gluconic acid delta-lactone"[tw] OR "D-
Gluconic acid"[tw] OR "D-Gluconic acid delta-lactone"[tw] OR "D-Gluconic
acid lactone"[tw] OR "D-Gluconic acid-delta-lactone"[tw] OR "D-Gluconic
delta-lactone"[tw] OR "D-Glucono-1,5-lactone"[tw] OR "D-Glucono-delta-
lactone"[tw] OR "D-delta-Gluconolactone"[tw] OR "GLUCONO-delta-
LACTONE"[tw] OR "Glucal"[tw] OR "Gluconic acid"[tw] OR "Gluconic acid
sodium salt"[tw] OR "Gluconic delta-lactone"[tw] OR "Glucono delta
lactone"[tw] OR "Glucono delta-lactone"[tw] OR "Gluconodeltalactone"[tw]
OR "Gluconolactone"[tw] OR "Glycogenic acid"[tw] OR "Glyconic acid"[tw]
OR "Kalium-beta"[tw] OR "Maltonic acid"[tw] OR "Monopotassium D-
Gluconate"[tw] OR "Monosodium D-Gluconate"[tw] OR "Monosodium
Gluconate"[tw] OR "Pentahydroxycaproic acid"[tw] OR "Potassium D-
Gluconate"[tw] OR "Potassium Gluconate"[tw] OR "Sodium 2,3,4,5,6-
pentahydroxy-1-hexanoate"[tw] OR "Sodium D-Gluconate"[tw] OR "Sodium
Gluconate"[tw] OR "Sodium Gluconate [USP]"[tw] OR "beta-Glucono-1,5-
lactone"[tw] OR "calcium Gluconate"[tw] OR "delta-D-Gluconolactone"[tw]
OR "delta-Gluconolactone"[tw] OR "sodium Gluconate"[tw] OR "delta-
Gluconolactone"[tw] OR ",delta.-Gluconolactone"[tw] OR "Calcium
hexagluconate"[tw] OR "GLUCONATE CALCIUM"[tw] OR "GLUCONATE
SODIUM"[tw] OR "GLUCONATE, CALCIUM"[tw] OR "GLUCONATE,
SODIUM"[tw] OR "Calcet"[tw] OR "Calciofon"[tw] OR "Calcipur"[tw] OR
"Calcium hexagluconate"[tw] OR "Calglucol"[tw] OR "Clewat GL"[tw] OR
"Delta-D-GLUCONOLACTON"[tw] OR "Deltagluconolactone"[tw] OR
"Dextronic acid"[tw] OR "D-Glucono-1,5-lacton"[tw] OR "D-glucono-1,5-
lactona"[tw] OR "D-Glulonic acid, monosodium salt"[tw] OR "D-Guconic
acid, .delta.-Iactone"[tw] OR "Disparlight DV"[tw] OR "Dragocal"[tw] OR
"Ebucin"[tw] OR "Fujiglucon"[tw] OR "Glonsen"[tw] OR "Glosanto"[tw] OR
XXXV
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
"Glucobiogen"[tw] OR "GLUCONATE SODIUM"[tw] OR "GLUCONATE,
SODIUM"[tw] OR "GLUCONO-1.5-LACTONE, D-"[tw] OR "Gluconsan K"[tw]
OR "Helshas A"[tw] OR "Kalium Gluconate"[tw] OR "Kalpren"[tw] OR "Kaon
elixir"[tw] OR "Katorin"[tw] OR "K-lao"[tw] OR "Novocal"[tw] OR "Pasexon
100T"[tw] OR "PMP Sodium Gluconate"[tw] OR "Potalium"[tw] OR
"Potasoral"[tw] OR "Potassuril"[tw] OR "Resitard P 608A"[tw] OR
"Sirokal"[tw] OR "Sunmorl N 60S"[tw]) NOT medline[sb])
Toxline (527-07-1 [rn] OR 299-27-4[rn] OR 526-95-4[rn] OR 90-80-2[rn] OR 299-28-
5[rn] OR'BVD Addicrete" OR "1,5-D-Gluconolactone" OR "1,5-
Gluconolactone" OR "2,3,4,5,6-Pentahydroxyhexanoic acid" OR "Biocal" OR
"CaiGiucon" OR "Caicicoi" OR "Calcium D-Gluconate" OR "Calcium
Gluconate" OR "Gluconic acid delta-lactone" OR "D-Gluconic acid" OR "D-
Gluconic acid delta-lactone" OR "D-Gluconic acid lactone" OR "D-Gluconic
acid-delta-lactone" OR "D-Gluconic delta-lactone" OR "D-Glucono-1,5-
lactone" OR "D-Glucono-delta-lactone" OR "D-delta-Gluconolactone" OR
"GLUCONO-delta- LACTONE" OR "Glucal" OR "Gluconic acid" OR
"Gluconic acid sodium salt" OR "Gluconic delta-lactone" OR "Glucono delta
lactone" OR "Glucono delta-lactone" OR "Gluconodeltalactone" OR
"Gluconolactone" OR "Glycogenic acid" OR "Glyconic acid" OR "Kalium-
beta" OR "Kaon" OR "Maltonic acid" OR "Monopotassium D-Gluconate" OR
"Monosodium D-Gluconate" OR "Monosodium Gluconate" OR
"Pentahydroxycaproic acid" OR "Potassium D-Gluconate" OR "Potassium
Gluconate" OR "Sodium 2,3,4,5,6-pentahydroxy-1-hexanoate" OR "Sodium
D-Gluconate" OR "Sodium Gluconate" OR "Sodium Gluconate (USP)" OR
"beta-Glucono-1,5-lactone" OR "calcium Gluconate" OR "delta-D-
Gluconolactone" OR "delta-Gluconolactone" OR "sodium Gluconate" OR
"delta-Gluconolactone" OR ".delta.-Gluconolactone" OR "Calcium
hexagluconate" OR "GLUCONATE CALCIUM" OR "GLUCONATE
SODIUM" OR "GLUCONATE, CALCIUM" OR "GLUCONATE, SODIUM" OR
"Calcet") AND (ANEUPL [org] OR BIOSIS [org] OR CIS [org] OR DART
[org] OR EMIC [org] OR EPIDEM [org] OR FEDRIP [org] OR HEEP [org]
OR HMTC [org] OR IPA [org] OR RISKLINE [org] OR MTGABS [org] OR
NIOSH [org] OR NTIS [org] OR PESTAB [org] OR PPBIB [org]) AND NOT
PubMed [org] AND NOT pubdart [org]
"Calciofon" OR "Calcipur" OR "Calglucol" OR "Clewat GL" OR "Delta-D-
GLUCONOLACTON" OR "Deltagluconolactone" OR "Dextronic acid" OR
"D-Glucono-1,5-lacton" OR "D-glucono-1,5-lactona" OR "D-Glulonic acid,
monosodium salt" OR "D-Guconic acid, .delta.-lactone" OR "Disparlight DV"
OR "Dragocal" OR "Ebucin" OR "Fujiglucon" OR "Glonsen" OR "Glosanto"
OR "Glucobiogen" OR "GLUCONO-1,5-LACTONE, D-" OR "Gluconsan K"
OR "Helshas A" OR "Kalium Gluconate" OR "Kalpren" OR "Kaon elixir" OR
"Katorin" OR "K-lao" OR "Novocal" OR "Pasexon 100T" OR "PMP Sodium
Gluconate" OR "Potalium" OR "Potasoral" OR "Potassuril" OR "Resitard P
608A" OR "Sirokal" OR "Sunmorl N 60S"
TSCATS 1 (527-07-1 [rn] OR 299-27-4 [rn] OR 526-95-4 [rn] OR 90-80-2 [rn] OR 299-
28-5 [rn]) AND (TSCATS [org])
WOS TS=("527-07-1" OR "299-27-4" OR "526-95-4" OR "90-80-2" OR "299-28-5"
OR "1,5-D-Gluconolactone" OR "1,5-Gluconolactone" OR "2,3,4,5,6-
Pentahydroxyhexanoic acid" OR "BVD Addicrete" OR "Biocal" OR
"CaiGiucon" OR "Caicicoi" OR "Calcium D-Gluconate" OR "Calcium
Gluconate" OR "D-(+)-Gluconic acid 5-lactone" OR "D-Gluconic acid" OR
XXXVI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
"D-Gluconic acid delta-lactone" OR "D-Gluconic acid lactone" OR "D-
Gluconic acid-delta-lactone" OR "D-Gluconic delta-lactone" OR "D-Glucono-
1,5-lactone" OR "D-Glucono-5-lactone" OR "D-delta-Gluconolactone" OR
"GLUCONO-5- LACTONE" OR "Glucal" OR "Gluconic acid" OR "Gluconic
acid sodium salt" OR "Gluconic delta-lactone" OR "Glucono delta lactone"
OR "Glucono delta-lactone" OR "Gluconodeltalactone" OR "Gluconolactone"
OR "Glycogenic acid" OR "Glyconic acid" OR "Kalium-beta" OR "Maltonic
acid" OR "Monopotassium D-Gluconate" OR "Monosodium D-Gluconate"
OR "Monosodium Gluconate" OR "Pentahydroxycaproic acid" OR
"Potassium D-Gluconate" OR "Potassium Gluconate" OR "Sodium
2,3,4,5,6-pentahydroxy-1-hexanoate" OR "Sodium D-Gluconate" OR
"Sodium Gluconate" OR "Sodium Gluconate [USP]" OR "beta-Glucono-1,5-
lactone" OR "calcium Gluconate" OR "delta-D-Gluconolactone" OR "delta-
Gluconolactone" OR "sodium Gluconate" OR "5-Gluconolactone" OR
".delta.-Gluconolactone" OR "Calcium hexagluconate" OR "GLUCONATE
CALCIUM" OR "GLUCONATE SODIUM" OR "GLUCONATE, CALCIUM"
OR "GLUCONATE, SODIUM" OR "D-glucono-1,5-lactona" OR "GLUCONO-
1,5-LACTONE, D-" OR "K-lao") AND ((WC=("Toxicology" OR
"Endocrinology & Metabolism" OR "Gastroenterology & Hepatology" OR
"Gastroenterology & Hepatology" OR "Hematology" OR "Neurosciences"
OR "Obstetrics & Gynecology" OR "Pharmacology & Pharmacy" OR
"Physiology" OR "Respiratory System" OR "Urology & Nephrology" OR
"Anatomy & Morphology" OR "Andrology" OR "Pathology" OR
"Otorhinolaryngology" OR "Ophthalmology" OR "Pediatrics" OR "Oncology"
OR "Reproductive Biology" OR "Developmental Biology" OR "Biology" OR
"Dermatology" OR "Allergy" OR "Public, Environmental & Occupational
Health") OR SU=("Anatomy & Morphology" OR "Cardiovascular System &
Cardiology" OR "Developmental Biology" OR "Endocrinology & Metabolism"
OR "Gastroenterology & Hepatology" OR "Hematology" OR "Immunology"
OR "Neurosciences & Neurology" OR "Obstetrics & Gynecology" OR
"Oncology" OR "Ophthalmology" OR "Pathology" OR "Pediatrics" OR
"Pharmacology & Pharmacy" OR "Physiology" OR "Public, Environmental &
Occupational Health" OR "Respiratory System" OR "Toxicology" OR
"Urology & Nephrology" OR "Reproductive Biology" OR "Dermatology" OR
"Allergy")) OR (WC="veterinary sciences" AND (TS="rat" OR TS="rats" OR
TS="mouse" OR TS="murine" OR TS="mice" OR TS="guinea" OR
TS="muridae" OR TS=rabbit* OR TS=lagomorph* OR TS=hamster* OR
TS=ferret* OR TS=gerbil* OR TS=rodent* OR TS="dog" OR TS="dogs" OR
TS=beagle* OR TS="canine" OR TS="cats" OR TS="feline" OR TS="pig"
OR TS="pigs" OR TS="swine" OR TS="porcine" OR TS=monkey* OR
TS=macaque* OR TS=baboon* OR TS=marmoset*)) OR (TS=toxic* AND
(TS="rat" OR TS="rats" OR TS="mouse" OR TS="murine" OR TS="mice"
OR TS="guinea" OR TS="muridae" OR TS=rabbit* OR TS=lagomorph* OR
TS=hamster* OR TS=ferret* OR TS=gerbil* OR TS=rodent* OR TS="dog"
OR TS="dogs" OR TS=beagle* OR TS="canine" OR TS="cats" OR
TS="feline" ORTS="pig" ORTS="pigs" ORTS="swine" OR TS="porcine"
OR TS=monkey* OR TS=macaque* OR TS=baboon* OR TS=marmoset*
OR TS="child" OR TS="children" OR TS=adolescen* OR TS=infant* OR
TS="WORKER" ORTS="WORKERS" ORTS="HUMAN" OR TS=patient*
OR TS=mother OR TS=fetal OR TS=fetus OR TS=citizens OR TS=milk OR
TS=formula OR TS=epidemio* OR TS=population* OR TS=exposure* OR
TS=questionnaire OR SO=epidemio*)) OR TI=toxic*)
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-
EXPANDED, IC Timespan=AII years
XXXVII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
TS=("Calcet" OR "Calciofon" OR "Calcipur" OR "Calglucol" OR "Clewat GL"
OR "Delta-D-GLUCONOLACTON" OR "Deltagluconolactone" OR "Dextronic
acid" OR "D-Glucono-1,5-lacton" OR "D-Glulonic acid, monosodium salt"
OR "D-Guconic acid, .delta.-lactone" OR "Disparlight DV" OR "Dragocal"
OR "Ebucin" OR "Fujiglucon" OR "Glonsen" OR "Glosanto" OR
"Glucobiogen" OR "Gluconsan K" OR "Helshas A" OR "Kalium Gluconate"
OR "Kalpren" OR "Kaon elixir" OR "Katorin" OR "Novocal" OR "Pasexon
100T" OR "PMP Sodium Gluconate" OR "Potalium" OR "Potasoral" OR
"Potassuril" OR "Resitard P 608A" OR "Sirokal" OR "Sunmorl N 60S")
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-
EXPANDED, IC Timespan=AII years
Environmental
Hazard
WOS
TS=("527-07-1" OR "299-27-4" OR "526-95-4" OR "90-80-2" OR "299-28-5"
OR "1,5-D-Gluconolactone" OR "1,5-Gluconolactone" OR "2,3,4,5,6-
Pentahydroxyhexanoic acid" OR "BVD Addicrete" OR "Biocal" OR
"CalGlucon" OR "Calcicol" OR "Calcium D-Gluconate" OR "Calcium
Gluconate" OR "D-(+)-Gluconic acid 5-lactone" OR "D-Gluconic acid" OR
"D-Gluconic acid delta-lactone" OR "D-Gluconic acid lactone" OR "D-
Gluconic acid-delta-lactone" OR "D-Gluconic delta-lactone" OR "D-Glucono-
1,5-lactone" OR "D-Glucono-5-lactone" OR "D-delta-Gluconolactone" OR
"GLUCONO-5- LACTONE" OR "Glucal" OR "Gluconic acid" OR "Gluconic
acid sodium salt" OR "Gluconic delta-lactone" OR "Glucono delta lactone"
OR "Glucono delta-lactone" OR "Gluconodeltalactone" OR "Gluconolactone"
OR "Glycogenic acid" OR "Glyconic acid" OR "Kalium-beta" OR "Maltonic
acid" OR "Monopotassium D-Gluconate" OR "Monosodium D-Gluconate"
OR "Monosodium Gluconate" OR "Pentahydroxycaproic acid" OR
"Potassium D-Gluconate" OR "Potassium Gluconate" OR "Sodium
2,3,4,5,6-pentahydroxy-1-hexanoate" OR "Sodium D-Gluconate" OR
"Sodium Gluconate" OR "Sodium Gluconate [USP]" OR "beta-Glucono-1,5-
lactone" OR "calcium Gluconate" OR "delta-D-Gluconolactone" OR "delta-
Gluconolactone" OR "sodium Gluconate" OR "5-Gluconolactone" OR
".delta.-Gluconolactone" OR "Calcium hexagluconate" OR "GLUCONATE
CALCIUM" OR "GLUCONATE SODIUM" OR "GLUCONATE, CALCIUM"
OR "GLUCONATE, SODIUM" OR "D-glucono-1,5-lactona" OR "GLUCONO-
1,5-LACTONE, D-" OR "K-lao") AND ((WC=("Agriculture, Dairy & Animal
Science" OR "Biodiversity Conservation" OR "Biology" OR "Developmental
Biology" OR "Ecology" OR "Entomology" OR "Environmental Sciences" OR
"Environmental Studies" OR "Fisheries" OR "Forestry" OR "Limnology" OR
"Marine & Freshwater Biology" OR "Microbiology" OR "Mycology" OR
"Oceanography" OR "Ornithology" OR "Plant Sciences" OR "Reproductive
Biology" OR "Zoology")) OR (SU=("Agriculture" OR "Biodiversity &
Conservation" OR "Developmental Biology" OR "Entomology" OR
"Environmental Sciences & Ecology" OR "Fisheries" OR "Forestry" OR
"Marine & Freshwater Biology" OR "Microbiology" OR "Mycology" OR "Plant
Sciences" OR "Reproductive Biology" OR "Zoology" OR "Oceanography"))
OR (TI=toxic*) OR (TS=(ecotox* OR environment* OR phytotox* OR pollut*
OR "A. platyrhynchos" OR "agnatha" OR "agnathan" OR "alligator" OR
"alligators" OR "amphibian" OR "amphibians" OR "amphipod" OR
"amphipoda" OR "amphipods" OR "Anas platyrhynchos" OR "annelid" OR
"annelida" OR "annelids" OR "Antilocapridae" OR "apidae" OR
"Aplodontidae" OR "Apoidea" OR "aquatic" OR "archiannelid" OR
"archiannelida" OR "Arvicolinae" OR "aves" OR "avian" OR "avians" OR
"badger" OR "badgers" OR "barnacle" OR "barnacles" OR "bass" OR "bear"
OR "bears" OR "beaver" OR "beavers" OR "bee" OR "bees" OR "bird" OR
"birds" OR "bivalve" OR "bivalves" OR "bleak" OR "bluegill" OR "bluegills"
XXXVIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
OR "bluehead" OR "bobwhite" OR "bobwhites" OR "Bovidae" OR "C. carpio"
OR "caiman" OR "Canidae" OR "carp" OR "Castoridae" OR "catfish" OR
"cephalopod" OR "cephalopoda" OR "cephalopods" OR "Cervidae" OR
"chicken" OR "chickens" OR "chiselmouth" OR "clam" OR "clams" OR
"cockle" OR "cockles" OR "cod" OR "copepod" OR "copepoda" OR
"copepods" OR "coturnix" OR "crab" OR "crabs" OR "crappie" OR
"crappies" OR "crayfish" OR "croaker" OR "crocodile" OR "crocodiles" OR
"crustacea" OR "crustacean" OR "crustaceans" OR "Cyprinus carpio" OR
"D. magna" OR "D. rerio" OR "dace" OR "Danio rerio" OR "daphnia" OR
"Daphnia magna" OR "darter" OR "darters" OR "Dasypodidae" OR
"Dicotylidae" OR "Didelphidae" OR "Dipodidae" OR "dog" OR "dogs" OR
"dogfish" OR "duck" OR "duckling" OR "ducklings" OR "ducks" OR
"earthworm" OR "earthworms" OR "ec50" OR "ec50s" OR "echinoderm" OR
"echinoderms" OR "eel" OR "eels" OR "elasmobranch" OR "Equidae" OR
"Erethizontidae" OR "Felidae" OR "ferret" OR "fish" OR "fisher" OR "fishers"
OR "fishes" OR "flagfish" OR "flatworm" OR "flatworms" OR "flounder" OR
"frog" OR "frogs" OR "galaxias" OR "gallus" OR "gastropod" OR
"gastropoda" OR "gastropods" OR "Geomyidae" OR "goldfish" OR
"gourami" OR "gouramy" OR "Green Algae" OR "grunion" OR "guppies" OR
"guppy" OR "haddock" OR "hagfish" OR "haplodrili" OR "Harvest mice" OR
"Harvest mouse" OR "herring" OR "Heteromyidae" OR "honeybee" OR
"honeybees" OR "hooknose" OR "inanga" OR "killifish" OR "L. idus" OR "L.
macrochirus" OR "lamprey" OR "lampreys" OR "Ic50" OR "Ic50s" OR "leech"
OR "lemming" OR "Lepomis macrochirus" OR "Leporidae" OR "lethal
concentration" OR "Leuciscus idus" OR "lizard" OR "lizards" OR "lobster"
OR "lobsters" OR "macroinvertebrate" OR "macroinvertebrates" OR
"mallard" OR "mallards" OR "marten" OR "medaka" OR "menhaden" OR
"Microtus" OR "milkfish" OR "mink" OR "minnow" OR "minnows" OR
"mollusc" OR "molluscs" OR "mollusk" OR "mollusks" OR "molly" OR
"mrigal" OR "mudfish" OR "mudsucker" OR "mulles" OR "mullet" OR
"mummichog" OR "mummichogs" OR "mussel" OR "mussels" OR
"Mustelidae" OR "Myocastoridae" OR "Mysid shrimp" OR "newt" OR "newts"
OR "northern pike" OR "0. latipes" OR "0. mykiss" OR "Ochotonidae" OR
"octopi" OR "octopus" OR "oligochaeta" OR "oligochaete" OR
"Oncorhynchus mykiss" OR "Onychomys" OR "opossum" OR "Oryzias
latipes" OR "oyster" OR "oysters" OR "P. promelas" OR "P. reticulata" OR
"P. subcapitata" OR "perch" OR "Peromyscus" OR "Pimephales promelas"
OR "pinfish" OR "pinfishes" OR "planaria" OR "planarian" OR "Poecilia
reticulata" OR "polychaeta" OR "polychaete" OR "polychaetes" OR
"Procyonidae" OR "Pseudokirchneriella subcapitata" OR "puffer" OR
"puffers" OR "pumpkinseed" OR "pumpkinseeds" OR "pupfish" OR "quahog"
OR "quahogs" OR "quail" OR "quails" OR "rasbora" OR "rasboras" OR
"Reithrodontomys" OR "reptile" OR "reptiles" OR "rohu" OR "S.
erythrophthalmus" OR "S. quadricauda" OR "S. subspicatus" OR
"salamander" OR "salamanders" OR "salmon" OR "scallop" OR "scallops"
OR "Scardinius erythrophthalmus" OR "Scenedesmus quadricauda" OR
"Scenedesmus subspicatus" OR "Sciuridae" OR "sea anemone" OR "sea
anemones" OR "sea cucumber" OR "sea cucumbers" OR "sea urchin" OR
"sea urchins" OR "seabass" OR "seabream" OR "shark" OR "sharks" OR
"shiner" OR "shiners" OR "shrimp" OR "Sigmodon" OR "Sigmodontinae" OR
"silverside" OR "silversides" OR "skunk" OR "skunks" OR "snake" OR
"snakehead" OR "snakes" OR "songbird" OR "songbirds" OR "Soricidae"
OR "squid" OR "starfish" OR "stickleback" OR "sticklebacks" OR "sting ray"
OR "sting rays" OR "sucker" OR "suckers" OR "Suidae" OR "sunfish" OR
"Talpidae" OR "teleost" OR "teleostei" OR "teleosts" OR "terrapin" OR
XXXIX
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
"terrapins" OR "tilapia" OR "tilapiaz" OR "toad" OR "toadfish" OR
"toadfishes" OR "toads" OR "tortoise" OR "tortoises" OR "trout" OR
"tubificid" OR "tubificidae" OR "tubificids" OR "turkey" OR "turkeys" OR
"turtle" OR "turtles" OR "Ursidae" OR "vole" OR "walleye" OR "walleyes" OR
"water flea" OR "water fleas" OR "waterbird" OR "waterbirds" OR
"waterfowl" OR "waterfowls" OR "weakfish" OR "weasel" OR "whelk" OR
"whelks" OR "wildlife")))
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-
EXPANDED, IC Timespan=AII years
Toxline Same as human health strategy synonyms only
TSCATS 1 Same as human health strategy CASRN only
Proquest TITLE=("Gluconic acid 5-lactone" OR "D-Glucono-5-lactone" OR "glucono-
5-lactone")
TITLE=("1,5-Gluconolactone" OR "Calcicol" OR "Calcium Gluconate" OR
"Calcium D-Gluconate" OR "D-Gluconic acid" OR "D-Gluconic acid delta-
lactone" OR "D-Gluconic acid lactone" OR "D-Gluconic acid-delta-lactone"
OR "D-Gluconic delta-lactone" OR "D-Glucono-1,5-lactone" OR "D-delta-
Gluconolactone" OR "Glucal" OR "Gluconic acid" OR "Gluconic delta-
lactone" OR "Glucono delta lactone" OR "Glucono delta-lactone" OR
"Gluconodeltalactone" OR "Gluconolactone" OR "Glycogenic acid" OR
"Glyconic acid" OR "Monosodium D-Gluconate")
TITLE=("Monosodium Gluconate" OR "Potassium D-Gluconate" OR
"Potassium Gluconate" OR "Sodium D-Gluconate" OR "Sodium Gluconate"
OR "beta-Glucono-1,5-lactone" OR "calcium Gluconate" OR "delta-D-
Gluconolactone" OR "delta-Gluconolactone" OR "sodium Gluconate" OR
"gluconate calcium" OR "gluconate sodium" OR "d-glucono-1,5-lactona" OR
"glucono-1,5-lactone, d-" OR "1,5-D-Gluconolactone" OR
"Deltagluconolactone" OR "Biocal" OR "Kalium Gluconate")
SUBJECT=(" 1,5-Gluconolactone" OR "Calcicol" OR "Calcium Gluconate"
OR "Calcium D-Gluconate" OR "D-Gluconic acid" OR "D-Gluconic acid
delta-lactone" OR "D-Gluconic acid lactone" OR "D-Gluconic acid-delta-
lactone" OR "D-Gluconic delta-lactone" OR "D-Glucono-1,5-lactone" OR "D-
delta-Gluconolactone" OR "Glucal" OR "Gluconic acid" OR "Gluconic delta-
lactone" OR "Glucono delta lactone" OR "Glucono delta-lactone" OR
"Gluconodeltalactone" OR "Gluconolactone" OR "Glycogenic acid" OR
"Glyconic acid" OR "Monosodium D-Gluconate")
SUBJECT=("Monosodium Gluconate" OR "Potassium D-Gluconate" OR
"Potassium Gluconate" OR "Sodium D-Gluconate" OR "Sodium Gluconate"
OR "beta-Glucono-1,5-lactone" OR "calcium Gluconate" OR "delta-D-
Gluconolactone" OR "delta-Gluconolactone" OR "sodium Gluconate" OR
"gluconate calcium" OR "gluconate sodium" OR "d-glucono-1,5-lactona" OR
"glucono-1,5-lactone, d-" OR "1,5-D-Gluconolactone" OR
"Deltagluconolactone" OR "Biocal" OR "Kalium Gluconate")
ABSTRACT=("1,5-Gluconolactone" OR "Calcicol" OR "Calcium Gluconate"
OR "Calcium D-Gluconate" OR "D-Gluconic acid" OR "D-Gluconic acid
delta-lactone" OR "D-Gluconic acid lactone" OR "D-Gluconic acid-delta-
lactone" OR "D-Gluconic delta-lactone" OR "D-Glucono-1,5-lactone" OR "D-
delta-Gluconolactone" OR "Glucal" OR "Gluconic acid" OR "Gluconic delta-
XL
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
lactone" OR "Glucono delta lactone" OR "Glucono delta-lactone" OR
"Gluconodeltalactone" OR "Gluconolactone" OR "Glycogenic acid" OR
"Glyconic acid" OR "Monosodium D-Gluconate")
ABSTRACT=("Monosodium Gluconate" OR "Potassium D-Gluconate" OR
"Potassium Gluconate" OR "Sodium D-Gluconate" OR "Sodium Gluconate"
OR "beta-Glucono-1,5-lactone" OR "calcium Gluconate" OR "delta-D-
Gluconolactone" OR "delta-Gluconolactone" OR "sodium Gluconate" OR
"gluconate calcium" OR "gluconate sodium" OR "d-glucono-1,5-lactona" OR
"glucono-1,5-lactone, d-" OR "1,5-D-Gluconolactone" OR
"Deltagluconolactone" OR "Biocal" OR "Kalium Gluconate")
ABSTRACT=("2,3,4,5,6-Pentahydroxyhexanoic acid" OR "BVD Addicrete"
OR "CalGlucon" OR "Kalium-beta" OR "Maltonic acid" OR "Monopotassium
D-Gluconate" OR "Pentahydroxycaproic acid" OR "Sodium 2,3,4,5,6-
pentahydroxy-1-hexanoate" OR "Calcium hexagluconate" OR "K-lao" OR
"Calcet" OR "Calcipur" OR "D-Glucono-1,5-lacton" OR "Novocal")
SUBJECT=("2,3,4,5,6-Pentahydroxyhexanoic acid" OR "BVD Addicrete" OR
"CalGlucon" OR "Kalium-beta" OR "Maltonic acid" OR "Monopotassium D-
Gluconate" OR "Pentahydroxycaproic acid" OR "Sodium 2,3,4,5,6-
pentahydroxy-1-hexanoate" OR "Calcium hexagluconate" OR "K-lao" OR
"Calcet" OR "Calcipur" OR "D-Glucono-1,5-lacton" OR "Novocal")
TITLE=("2,3,4,5,6-Pentahydroxyhexanoic acid" OR "BVD Addicrete" OR
"CalGlucon" OR "Kalium-beta" OR "Maltonic acid" OR "Monopotassium D-
Gluconate" OR "Pentahydroxycaproic acid" OR "Sodium 2,3,4,5,6-
pentahydroxy-1-hexanoate" OR "Calcium hexagluconate" OR "K-lao" OR
"Calcet" OR "Calcipur" OR "D-Glucono-1,5-lacton" OR "Novocal")
"Calciofon" OR "Calglucol" OR "Clewat GL" OR "Delta-D-
GLUCONOLACTON" OR "Dextronic acid" OR "D-Glulonic acid,
monosodium salt" OR "D-Guconic acid, .delta.-lactone" OR "Disparlight DV"
OR "Dragocal" OR "Ebucin" OR "Fujiglucon" OR "Glonsen" OR "Glosanto"
OR "Glucobiogen" OR "Gluconsan K" OR "Helshas A" OR "Kalpren" OR
"Kaon elixir" OR "Katorin" OR "Pasexon 100T" OR "Potalium" OR
"Potasoral" OR "Potassuril" OR "Resitard P 608A" OR "Sirokal" OR
"Sunmorl N 60S"
Fate
WOS
TS=("527-07-1" OR "299-27-4" OR "526-95-4" OR "90-80-2" OR "299-28-
5" OR "1,5-D-Gluconolactone" OR "1,5-Gluconolactone" OR "2,3,4,5,6-
Pentahydroxyhexanoic acid" OR "BVD Addicrete" OR "Biocal" OR
"CalGlucon" OR "Calcicol" OR "Calcium D-Gluconate" OR "Calcium
Gluconate" OR "D-(+)-Gluconic acid 5-lactone" OR "D-Gluconic acid" OR
"D-Gluconic acid delta-lactone" OR "D-Gluconic acid lactone" OR "D-
Gluconic acid-delta-lactone" OR "D-Gluconic delta-lactone" OR "D-
Glucono-1,5-lactone" OR "D-Glucono-5-lactone" OR "D-delta-
Gluconolactone" OR "GLUCONO-5- LACTONE" OR "Glucal" OR
"Gluconic acid" OR "Gluconic acid sodium salt" OR "Gluconic delta-
lactone" OR "Glucono delta lactone" OR "Glucono delta-lactone" OR
"Gluconodeltalactone" OR "Gluconolactone" OR "Glycogenic acid" OR
"Glyconic acid" OR "Kalium-beta" OR "Maltonic acid" OR "Monopotassium
D-Gluconate" OR "Monosodium D-Gluconate" OR "Monosodium
Gluconate" OR "Pentahydroxycaproic acid" OR "Potassium D-Gluconate"
OR "Potassium Gluconate" OR "Sodium 2,3,4,5,6-pentahydroxy-1-
hexanoate" OR "Sodium D-Gluconate" OR "Sodium Gluconate" OR
"Sodium Gluconate fUSPl" OR "beta-Glucono-1,5-lactone" OR "calcium
XLI
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.2: Search Terms Used in Peer-Reviewed Databases
Gluconate" OR "delta-D-Gluconolactone" OR "delta-Gluconolactone" OR
"sodium Gluconate" OR "5-Gluconolactone" OR ".delta.-Gluconolactone"
OR "Calcium hexagluconate" OR "GLUCONATE CALCIUM" OR
"GLUCONATE SODIUM" OR "GLUCONATE, CALCIUM" OR
"GLUCONATE, SODIUM" OR "D-glucono-1,5-lactona" OR "GLUCONO-
1,5-LACTONE, D-" OR "K-lao") AND TS=(adsorp* OR aerob* OR
anaerob* OR bioaccumulat* OR bioavail* OR bioconcentrat* OR
biodegrad* OR biomoni* OR biotrans* OR degrad* OR dispers* OR fish*
OR hydroly* leach* OR migrat* OR partic* OR partition* OR persisten* OR
photoly* OR volatil* OR abiotic OR absorb OR absorption OR
accumulation-rate OR aerosol OR aerosols OR air OR anoxic OR atm-
m3/mol OR biomagnification OR biosolids OR biota OR breakdown-
product OR breakdown-products OR chelation OR coagulation
complexation OR decay-rate OR diffusion-coefficient OR dissolution OR
dust OR effluent OR environmental-fate OR evaporation-from-water OR
excretion OR flocculation OR flux OR fugacity OR gas-phase-mass-
transfer OR ground-water OR groundwater OR half-life OR henry's-law
OR incinerate OR incineration OR indoor-outdoor-ratio OR influent OR
ingestion OR intake OR kinetics OR liquid-phase-mass-transfer OR mass-
transfer-coefficient OR microcosm OR modified-state-space OR particle-
size OR particulate OR pathway OR pathways OR penetration-factor OR
penetration-ratio OR photostability OR placenta OR plasma OR plume OR
point-source OR point-sources OR pore-water OR pretreatment-program
OR redox OR sediment OR serum OR sewage-treatment OR sludge OR
soil OR subsurface-intrusion OR surface-water-concentration OR time-
weighted-average OR transfer OR transformation OR trophic-
magnification OR vapor OR wait-time OR wastewater-treatment OR
weight-fraction OR wildlife OR BAF OR BCF OR BSAF OR BSAFs OR
KAW OR Kd OR KOA OR KOC OR POTW OR SES OR WWTP OR
((OECD OR OPPTS OR OCSPP) AND (Guideline OR guidelines)))
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH,
CCR-EXPANDED, IC Timespan=AII years
Table C.3: Search Terms Used in Grey Literature and Additional Sources
Chemical
Search terms
Gluconates
cluster (Calcium
gluconate;
Potassium
gluconate;
Sodium
gluconate; D-
gluconic acid;
Sodium
glucoheptonate,
Glucono-delta-
lactone)
Searched as a string or individually depending on resource: 527-07-1 [rn] OR 299-27-4[rn] OR 526-95-4[rn] OR
90-80-2[rn] OR 299-28-5[rn] OR "1,5-D-Gluconolactone" OR "1,5-Gluconolactone" OR "2,3,4,5,6-
Pentahydroxyhexanoic acid" OR "BVD Addicrete" OR "Biocal" OR "CalGlucon" OR "Calcicol" OR "Calcium D-
Gluconate" OR "Calcium Gluconate" OR "D-(+)-Gluconic acid 5-lactone" OR "D-Gluconic acid" OR "D-
Gluconic acid delta-lactone" OR "D-Gluconic acid lactone" OR "D-Gluconic acid-delta-lactone" OR "D-
Gluconic delta-lactone" OR "D-Glucono-1,5-lactone" OR "D-Glucono-5-lactone" OR "D-delta-Gluconolactone"
OR "GLUCONO-5- LACTONE" OR "Glucal" OR "Gluconic acid" OR "Gluconic acid sodium salt" OR "Gluconic
delta-lactone" OR "Glucono delta lactone" OR "Glucono delta-lactone" OR "Gluconodeltalactone" OR
"Gluconolactone" OR "Glycogenic acid" OR "Glyconic acid" OR "KOK" OR "Kalium-beta" OR "Kaon" OR
"Maltonic acid" OR "Monopotassium D-Gluconate" OR "Monosodium D-Gluconate" OR "Monosodium
Gluconate" OR "Pentahydroxycaproic acid" OR "Potassium D-Gluconate" OR "Potassium Gluconate" OR
"Sodium 2,3,4,5,6-pentahydroxy-1-hexanoate" OR "Sodium D-Gluconate" OR "Sodium Gluconate" OR
"Sodium Gluconate [USP]" OR "beta-Glucono-1,5-lactone" OR "calcium Gluconate" OR "delta-D-
Gluconolactone" OR "delta-Gluconolactone" OR "sodium Gluconate" OR "5-Gluconolactone"
Analog
searched
D-arabinonic acid (488-30-2)
XLII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
After the search terms were applied, more than 5, 200 references were returned by all search efforts
across peer-reviewed databases and grey literature sources. The total number of references include
database results, additional strategies, and analog searches. All references from the search efforts were
screened and evaluated through the LPS literature search and review process.43 Of these, 43 references
were included for data evaluation and used to support the designation of potassium gluconate as LPS. The
included hazard and fate references are listed in the bibliography of Appendix B.
C.2 Excluded Studies and Rationale
This section lists the excluded references, by HERO ID, found to be off-topic or unacceptable for use in
the hazard screening of potassium gluconate. The excluded references are organized by discipline (human
health hazard, environmental hazard, and fate), presented along with a rationale based on exclusion
criteria. The criteria43 was used to determine off-topic references in the title/abstract or full-text screening
and to determine unacceptable references in the data quality evaluation are provided in the form of
questions.
C.2.1 Human Health Hazard Excluded References
For the screening review of potassium gluconate, EPA excluded a total of 2163 references when assessing
human health hazard. Off-topic references (e.g., studies that did not contain information relevant to
human health) were excluded at either title/abstract screening (see Table C.4), or full-text screening (see
Table C.5). Unacceptable references (e.g., studies that did not meet data quality metrics) were excluded at
full-text screening (see Tables C.6 and C.7). Off-topic and unacceptable references are displayed next to
the corresponding exclusion criteria.
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
Reference excluded (HERO ID) because the reference did NOT contain information needs46 relevant to human health hazard
4941098
4947559
4945570
4944757
4942343
4946452
4946710
4948770
4947042
4941553
1001515
4947560
4945571
4944758
4942344
4946453
4946711
4948772
4947043
4941555
1022900
4947561
4945616
4944759
4942372
4946454
4946712
4948773
4947046
4941558
1038153
4947562
4945617
4944760
4942373
4946455
4946713
4948774
4947047
4941559
1066651
4947563
4945619
4944761
4942374
4946481
4946714
4948777
4947049
4941562
1089041
4947564
4945622
4944762
4942376
4946482
4946716
4948778
4947050
4941563
1170178
4947569
4945623
4944763
4942379
4946483
4946717
4948779
4947051
4941569
1170332
4947570
4945625
4944764
4942415
4946484
4946718
4948781
4947052
4941572
1170465
4947571
4945627
4944765
4942417
4946485
4946719
4948782
4947054
4941575
1174803
4947572
4945628
4944766
4942420
4946486
4946722
4948783
4947055
4941581
1187359
4947573
4945629
4944767
4942426
4946487
4946723
4948784
4947057
4941590
1194210
4947574
4945632
4944768
4942429
4946488
4946724
4948786
4947059
4941594
1199146
4947575
4945633
4944769
4942435
4946489
4946725
4948787
4947060
4941598
1199417
4947578
4945634
4944770
4942437
4946490
4946726
4948788
4947061
4941599
1203834
4947580
4945636
4944771
4942441
4946492
4946729
4948789
4947062
4941604
1296238
4947581
4945637
4944772
4942442
4946494
4946730
4948790
4947063
4941607
1299143
4947583
4945639
4944774
4942443
4946495
4946731
4948791
4947064
4941612
40 Hie information needs for human health hazard includes a list of study characteristics pertaining to the study population/test
organism, types of exposures and routes, me of controls, type and level of effects. A complete list of the information needs is
provided in Table A1 of the "Approach Document for Screening Hazard Information for Low-Priority Substances Under TSCA".
These information needs helped guide the development of questions for title/abstract and full-text screening.
XLIII
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***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
1333838
4947584
4945641
4944775
4942444
4946496
4946732
4948792
4947066
4941625
1344568
4947585
4945642
4944776
4942448
4946497
4946733
4948793
4947067
4941627
1425184
4947586
4945645
4944777
4942449
4946498
4946734
4948794
4947068
4941632
1441798
4947588
4945646
4944779
4942450
4946499
4946735
4948795
4947070
4941633
1457562
4947589
4945647
4944780
4942451
4946500
4946736
4948797
4947071
4941639
1478015
4947590
4945648
4944782
4942452
4946501
4946737
4948798
4947072
4941647
1510657
4947591
4945649
4944783
4942453
4946514
4946738
4948799
4947074
4941649
1576583
4947592
4945650
4944784
4942456
4946515
4946739
4948800
4947075
4941696
1615817
4947593
4945652
4944785
4942459
4946516
4946740
4948801
4947076
4941701
1619316
4947594
4945654
4944786
4942460
4946518
4946741
4948802
4947077
4941703
1686935
4947595
4945655
4944832
4942461
4946519
4946742
4948803
4947078
4941705
1759188
4947596
4945657
4944833
4942504
4946520
4946743
4948804
4947102
4941706
1759826
4947597
4945682
4944834
4942506
4946521
4946744
4948805
4947103
4941782
1759942
4947600
4945684
4944835
4942508
4946522
4946757
4948806
4947524
4941786
1779633
4947602
4945685
4944838
4942509
4946523
4946758
4948808
4947525
4941789
1795253
4947616
4945686
4944840
4942510
4946524
4946759
4948810
4947540
4941790
1796284
4947617
4945687
4944843
4942511
4946525
4946760
4948811
4947541
4941794
1796454
4947618
4945689
4944844
4942514
4946526
4946761
4948812
4947542
4941796
1834323
4947619
4945690
4944845
4942515
4946527
4946762
4948813
4947543
4941800
1838996
4947621
4945692
4944847
4942517
4946528
4946763
4948816
4947545
4941801
1854895
4947623
4945693
4944848
4942519
4946529
4946765
4948817
4947546
4941870
1854935
4947624
4945694
4944849
4942520
4946530
4946766
4948818
4947547
4941876
1855160
4947625
4945695
4944850
4942521
4946531
4946767
4948819
4947548
4941883
1860655
4947626
4945696
4944851
4942522
4946533
4946768
4948820
4947550
4941984
1874618
4947627
4945697
4944852
4942523
4946534
4946769
4948821
4947552
4941985
1925103
4947628
4945698
4944853
4942528
4946535
4946770
4948822
4947553
4941990
1941284
4947629
4945699
4944854
4942529
4946536
4946772
4948823
4947554
4941995
194296
4947631
4945700
4944855
4942531
4946537
4946774
4948824
4947555
4941999
19702
4947632
4945701
4944856
4942533
4946553
4946775
4948825
4947556
4942157
19800
4947633
4945702
4944857
4942535
4946554
4946776
4948826
4947557
4942164
19855
4947634
4945703
4944858
4942536
4946555
4946783
4948827
4947558
4942166
1989183
4947635
4945704
4944859
4942543
4946556
4946784
4948829
4946353
4942173
1989218
4947636
4945705
4944860
4942551
4946558
4946786
4948830
4946354
4942174
1995656
4947638
4945728
4944861
4942575
4946559
4946787
4948831
4946355
4942176
1996971
4947639
4945729
4944862
4942577
4946561
4946788
4948832
4946356
4942177
1997743
4947640
4945730
4944863
4942579
4946562
4946789
4948833
4946358
4942248
1998522
4947641
4945732
4944864
4942583
4946563
4946791
4948836
4946381
4942252
2047443
4947642
4945733
4944865
4942586
4946564
4946792
4948837
4946382
4942258
2055366
4947643
4945735
4944885
4942589
4946567
4946805
4948838
4946383
4942259
2055579
4947644
4945736
4944886
4942591
4946568
4946806
4948839
4946385
4942260
2061011
4947645
4945738
4944887
4942594
4946569
4946809
4948840
4946386
4942262
2065984
4947646
4945739
4944888
4942645
4946570
4946810
4948841
4946388
4942266
2066129
4947647
4945741
4944889
4942649
4946571
4946812
4948842
4946390
4942267
2066780
4947648
4945743
4944891
4942650
4946572
4946814
4948843
4946391
4942268
2067584
4947649
4945744
4944892
4942651
4946573
4946816
4948844
4946394
4942276
2070843
4947652
4945745
4944894
4942652
4946575
4946817
4948845
4946395
4942284
2071429
4947654
4945746
4944896
4942653
4946576
4946818
4948848
4946396
4942308
2072857
4947656
4945747
4944897
4942654
4946587
4946819
4948849
4946397
4942310
XLIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
2073796
4947658
4945749
4944898
4942655
4946588
4946841
4948850
4946398
4942317
2153531
4947659
4945750
4944899
4942659
4946589
4946842
4948851
4946400
4942319
2173478
4947664
4945776
4944900
4942661
4946591
4946845
4948853
4946401
4942330
2239588
4947672
4945777
4944901
4942663
4946592
4946846
4948854
4946402
4942337
2247422
4947673
4945778
4944902
4942665
4946593
4946847
4948856
4946403
4942339
2251366
4947675
4945779
4944903
4942693
4946594
4946848
4948857
4946404
4942342
2283940
4947677
4945780
4944928
4942694
4946595
4946850
4948858
4946405
4941190
2303508
4947679
4945781
4944929
4942703
4946598
4946851
4948859
4946431
4941192
2305122
4947680
4945782
4944930
4942710
4946600
4946852
4948860
4946432
4941200
2534708
4947681
4945784
4944931
4942711
4946601
4946853
4948861
4946433
4941208
2600620
4947682
4945786
4944933
4942759
4946602
4946854
4948862
4946434
4941212
2740828
4947683
4945787
4944934
4942764
4946603
4946855
4948863
4946435
4941216
2777828
4947684
4945788
4944935
4942765
4946606
4946856
4948864
4946436
4941219
2789501
4947685
4945789
4944936
4942766
4946607
4946857
4948866
4946437
4941227
2789962
4947686
4945791
4944937
4942767
4946609
4946860
4948867
4946438
4941240
2791730
4947702
4945792
4944938
4942771
4946610
4946861
4948868
4946440
4941241
2792369
4947703
4945793
4944940
4942818
4946640
4946862
4948869
4946443
4941246
2794737
4947705
4945794
4944941
4942821
4946641
4946863
4948870
4946445
4941260
2797535
4947706
4945814
4944942
4942823
4946642
4946864
4948871
4946446
4941262
2807224
4947707
4945816
4944943
4942826
4946644
4946865
4948872
4946448
4941265
2850509
4947708
4945817
4944944
4942830
4946645
4946866
4948873
4946449
4941271
2862040
4947709
4945818
4944945
4942831
4946646
4946867
4948874
4946451
4941273
2878901
4947710
4945819
4944946
4942832
4946647
4946868
4948875
4941311
4941281
2885345
4947711
4945820
4944990
4942833
4946648
4946869
4948876
4941314
4941286
2949563
4947713
4945821
4944991
4942834
4946649
4946870
4948877
4941317
4941294
3000211
4947715
4945823
4944992
4942835
4946650
4946872
4948879
4941325
4941297
3010958
4947716
4945824
4944994
4942837
4946651
4946874
4948880
4941326
4941298
3036081
4947718
4945826
4944995
4942838
4946652
4946875
4948881
4941329
4941300
3036375
4947736
4945827
4944997
4942873
4946654
4946876
4948882
4941330
4941301
3045285
4947737
4945828
4944998
4942874
4946656
4946877
4948883
4941340
4941305
3055823
4947738
4945829
4945002
4942876
4946657
4946906
4949354
4941306
4945443
3103748
4947739
4945833
4945003
4942877
4946658
4946907
4949487
4943591
4945445
3115256
4947740
4945834
4945004
4942879
4946660
4946909
4949488
4943643
4945446
3147238
4947741
4945835
4945005
4942881
4946661
4946910
4949489
4943648
4945447
3188921
4947743
4945836
4945006
4942882
4946662
4946912
4949490
4943656
4945448
3196035
4947744
4945837
4945007
4942883
4946692
4946914
516548
4943660
4945449
3235430
4947745
4945859
4945008
4942885
4946693
4946915
540101
4943731
4945450
3350277
4947746
4945860
4945009
4942886
4946694
4946918
56529
4943733
4945451
3382476
4947747
4945861
4945010
4942887
4946695
4946919
57347
4943737
4945452
3491920
4947748
4945862
4945012
4942889
4946696
4946931
607379
4943744
4945454
3514544
4947749
4945863
4945013
4942890
4946697
4946932
620381
4943746
4945455
3538354
4947752
4945864
4945015
4942891
4946698
4946933
625668
4943775
4945456
3664515
4947753
4945865
4945016
4942892
4946699
4946934
646810
4943777
4945457
3673078
4947754
4945866
4945019
4942894
4946701
4946935
662010
4943782
4945458
3734303
4947758
4945867
4945021
4942932
4946702
4946936
700296
4943783
4945460
3737219
4947759
4945868
4945022
4942936
4946703
4946937
74679
4943791
4945461
3738347
4947760
4945869
4945023
4942939
4946705
4946939
76919
4943793
4945462
3740044
4947761
4945870
4945024
4942945
4946706
4946940
824640
4943862
4945513
XLV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
3791358
4947763
4945871
4945025
4943111
4946707
4946941
882492
4943867
4945514
3804682
4947766
4945872
4945026
4943115
4946708
4946942
895563
4943868
4945515
3804687
4947767
4945873
4945027
4943117
4945319
4946943
4941397
4943869
4945516
3810075
4947768
4945874
4945028
4943121
4945322
4946944
4941402
4943874
4945517
3817993
4947769
4945875
4945029
4943126
4945323
4946945
4941408
4943879
4945518
3818691
4947770
4945876
4945031
4943152
4945324
4946946
4941413
4943929
4945519
3822728
4947780
4945877
4945032
4943155
4945325
4946948
4941414
4943931
4945520
3877916
4947781
4945878
4945033
4943165
4945327
4946950
4941425
4943946
4945521
3993283
4947782
4945879
4945034
4943169
4945328
4946951
4941429
4943947
4945522
3994810
4947783
4945880
4945035
4943216
4945329
4946952
4941430
4944146
4945523
3996821
4947784
4945881
4945037
4943217
4945330
4946953
4941433
4944149
4945524
3998333
4947785
4945882
4945038
4943221
4945380
4946954
4941434
4944150
4945526
3998349
4947786
4945903
4945040
4943234
4945381
4946956
4941439
4944156
4945527
3998366
4947787
4945905
4945072
4943235
4945382
4946957
4941441
4944157
4945528
3998664
4947788
4945907
4945073
4943267
4945383
4946959
4941442
4944162
4945529
3998780
4947789
4945908
4945078
4943274
4945384
4946961
4941446
4944164
4945530
3999112
4947790
4945910
4945082
4943276
4945386
4946963
4941453
4944464
4945531
3999175
4947791
4945912
4945085
4943279
4945387
4946966
4941454
4944471
4945553
3999274
4947792
4945914
4945087
4943282
4945389
4946985
4941457
4944475
4945555
3999304
4947793
4945915
4945088
4943287
4945390
4946987
4941461
4944476
4945556
3999778
4947794
4945916
4945089
4943295
4945391
4946989
4941464
4944486
4945559
4000762
4947795
4945917
4945090
4943301
4945392
4946991
4941471
4944582
4945560
4001000
4947796
4945919
4945092
4943306
4945393
4946993
4941473
4944584
4945561
4016792
4947797
4945920
4945093
4943332
4945394
4946996
4941474
4944587
4945565
4072289
4947798
4945921
4945094
4943334
4945395
4946997
4941475
4944595
4945566
4078713
4947800
4945923
4945095
4943340
4945396
4946998
4941478
4944599
4945567
4114843
4947801
4945924
4945096
4943345
4945397
4946999
4941480
4944742
4945569
4119345
4947802
4945973
4945097
4943349
4945398
4947000
4941483
4944743
4946225
4119539
4947803
4945974
4945098
4943395
4945399
4947004
4941485
4944747
4946226
4119545
4947805
4945976
4945099
4943399
4945400
4947005
4941488
4944751
4946227
4119546
4947806
4945977
4945100
4943400
4945401
4947006
4941495
4944756
4946228
4119556
4947807
4945979
4945101
4943461
4945403
4947007
4941505
4946278
4946229
4119563
4947808
4945981
4945103
4943471
4945405
4947009
4941510
4946280
4946230
4119567
4947809
4945982
4945104
4943473
4945406
4947010
4941511
4946281
4946231
4119601
4947810
4945983
4945108
4943478
4945407
4947013
4941512
4946282
4946232
4119602
4947811
4945984
4945109
4943537
4945408
4947014
4941513
4946283
4946233
4119603
4947812
4945985
4945125
4943541
4945409
4947015
4941517
4946284
4946235
4119721
4947813
4945986
4945126
4943545
4945410
4947016
4941524
4946285
4946236
4119722
4947814
4945987
4945127
4943548
4945411
4947017
4941533
4946286
4946237
4120082
4947815
4945988
4945129
4943577
4945412
4947020
4941534
4946287
4946238
4120474
4947830
4945989
4945136
4943580
4945413
4947021
4941537
4946336
4946239
4120476
4947831
4945991
4945137
4943581
4945414
4947024
4941542
4946337
4946240
4120490
4947832
4945992
4945138
4943583
4945415
4947026
4941543
4946338
4946241
4120587
4947833
4945993
4945139
4943588
4945416
4947027
4941544
4946339
4946242
4120643
4947834
4945994
4945142
4943589
4945417
4947028
4941546
4946340
4946243
4120652
4947835
4945995
4945144
4943590
4945442
4947029
4941552
4946342
4946265
4120814
4947836
4945996
4945145
4946155
4945273
4850105
4948636
4946343
4946267
4139774
4947837
4946019
4945146
4946156
4945274
4917748
4948637
4946344
4946268
XLVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.4: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
4163187
4947838
4946021
4945147
4946157
4945275
4940942
4948638
4946345
4946270
4168726
4947840
4946022
4945148
4946159
4945276
4940944
4948639
4946346
4946271
4220713
4947841
4946023
4945149
4946160
4945277
4940945
4948641
4946347
4946272
4231040
4947842
4946024
4945150
4946161
4945278
4940947
4948642
4946348
4946273
4232125
4947843
4946026
4945151
4946162
4945280
4940948
4948643
4946350
4946275
4291829
4947844
4946027
4945152
4946163
4945281
4940952
4948644
4946351
4948733
4291993
4947845
4946028
4945153
4946165
4945282
4940954
4948647
4946352
4948734
4292632
4947846
4946030
4945154
4946166
4945283
4940955
4948648
4941123
4948735
4298898
4947856
4946031
4945155
4946167
4945284
4940956
4948649
4941128
4948736
4302320
4947879
4946032
4945157
4946168
4945285
4940957
4948650
4941129
4948738
4314415
4947880
4946034
4945159
4946169
4945287
4940960
4948651
4941132
4948739
4314853
4947881
4946035
4945164
4946170
4945288
4940961
4948652
4941134
4948742
4316393
4947882
4946036
4945189
4946220
4945314
4940962
4948653
4941138
4948748
4318467
4947883
4946037
4945191
4946221
4945316
4940963
4948654
4941139
4948749
4319651
4947884
4946038
4945192
4946223
4945317
4940965
4948655
4941140
4948750
4328331
4947885
4946039
4945194
4946224
4945318
4940967
4948656
4941141
4948751
4328874
4947886
4946040
4945195
4948690
4941347
4940970
4948657
4941155
4948752
4331885
4947887
4946042
4945196
4948691
4941349
4940982
4948659
4941159
4948753
4335224
4947888
4946066
4945197
4948692
4941351
4940988
4948660
4941167
4948754
4367920
4947889
4946067
4945199
4948695
4941365
4940991
4948661
4941174
4948755
4370006
4947890
4946068
4945202
4948696
4941366
4940999
4948662
4941178
4948756
4375986
4947891
4946070
4945203
4948697
4941371
4941003
4948663
4941184
4948757
4386526
4947892
4946071
4945206
4948698
4941376
4941010
4948665
4941186
4948758
4403828
4947893
4946072
4945207
4948699
4941382
4941015
4948666
4948766
4948759
4435320
4947895
4946074
4945208
4948700
4941384
4941020
4948670
4948767
4948760
4476451
4947896
4946075
4945209
4948701
4941385
4941024
4948671
4948769
4948762
4487858
4947897
4946076
4945210
4948703
4941388
4941028
4948672
4941116
4948763
4496995
4947898
4946077
4945211
4948704
4941389
4941029
4948674
4941119
4948764
4543359
4947899
4946078
4945213
4948705
4941395
4941031
4948675
4948720
4948765
4552415
4947900
4946079
4945214
4948706
4948721
4941039
4948676
4948689
4948719
4556226
4947901
4946082
4945215
4948707
4948722
4941049
4948677
4948688
4945272
4559952
4947902
4946083
4945216
4948710
4948724
4941054
4948678
4946099
4945240
4566619
4947903
4946084
4945218
4948711
4948725
4941055
4948680
4946100
4945241
4631617
4947905
4946085
4945219
4948712
4948726
4941057
4948681
4946101
4945242
4650894
4947906
4946086
4945220
4948713
4948727
4941062
4948682
4946102
4945244
4653850
4947907
4946087
4945221
4948714
4948729
4941074
4948683
4946103
4945245
4657003
4947908
4946088
4945231
4948715
4948730
4941078
4948684
4946105
4945246
4665367
4947909
4946089
4945232
4948716
4948731
4941085
4948685
4946106
4945247
4684048
4947910
4946092
4945233
4948717
4948732
4941094
4948686
4946153
4945248
4686505
4947911
4946094
4945234
4948718
4941099
4941097
4948687
4850050
4948635
4730988
4947913
4946095
4945235
4946154
4850046
4948633
4948632
4850039
4948631
4744135
4947914
4946096
4945238
4850044
4837204
4948630
4948625
4837184
4948627
4799476
4947915
4946097
4945239
4836748
4830850
4948624
4823251
4947916
Reference excluded (HERO ID) because the reference primarily contained in silico data
4946274
Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
Question Off-topic if answer is:
References excluded (HERO ID)
XLVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
Does the reference contain
No
1989362
information pertaining to a low-
2207460
priority substance candidate?
2789349
2791674
3086385
3814978
4057262
4120689
4940080
4940983
4941058
4941079
4941188
4942457
4943219
4943543
4944890
4944993
4945140
4945217
4945402
4945459
4945624
4945990
4946069
4946090
4946098
4946349
4946399
4946439
4946444
4946557
4946560
4947799
4947804
4947894
4947526
4947549
4947587
4947620
4947717
4946779
4946605
4946611
4941448
4941472
What type of source is this
Review article or book chapter that
4947756
reference?
contains only citations to primary
4947348
literature sources
4940076
4940077
XLVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
4940079
1336123
What kind of evidence does this
In silico studies that DO NOT
N/A
reference primarily contain?
contain experimental verification
The following question apply to HUMAN evidence only
Does the reference report an
No
2061182
exposure route that is or is
4944778
presumed to be by an inhalation,
4944939
oral, or dermal route?
4945001
4945909
4946517
4946532
4946565
4946604
4946655
4948629
4948634
4948780
4946663
Does the reference report both test
No
4944778
substance exposure(s) AND related
4946604
health outcome(s)?
4942320
4943939
4945243
4945321
If the reference reports an exposure
No
4948629
to a chemical mixture, are
4116098
measures of the test substance or
4944841
related metabolite(s) reported
independently of other chemicals?
Note: If the paper does not pertain
to mixtures, choose "Not
Applicable".
The following question apply to ANIMAL evidence only
Does the reference report an
No
4946655
exposure route that is by inhalation,
988952
oral, or dermal route?
4941309
4941406
4941988
4943652
4945832
4946152
4946704
4946709
4947073
4941708
4946590
XLIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.5: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human Health Hazard
Does the reference report both test
substance-related exposure(s) AND
related health outcome(s)?
No
4945832
1285752
1990523
2126383
Does the reference report the
duration of exposure?
No
4948878
Does the reference report an
exposure to the test substance only
(i.e. no mixtures with the exception
of aqueous solutions and
reasonable impurities and
byproducts)?
No
4946152
4072921
4945922
4948855
Does the paper report a negative
control that is a vehicle control or
no treatment control?
No47
4941309
4946655
The following questions apply to MECHANISTIC/ALTERNATIVE TEST METHODS evidence only
Does the reference report a
negative control that is a vehicle
control or no treatment control?
No
689851
Does the reference report an
exposure to the test substance only
(i.e. no mixtures with the exception
of aqueous solutions and
reasonable impurities and
byproducts)?
No
900745
For genotoxicity studies only: Does
the study use a positive control?
No
N/A.
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - Animal
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance identity
• The test substance identity
cannot be determined from
the information provided
(e.g., nomenclature was
unclear and CASRN or
structure were not reported).
OR
• For mixtures, the components
and ratios were not characterized or
did not include information that could
result in a reasonable approximation
of components.
N/A.
Metric 2:
Negative and vehicle controls
A concurrent negative control group
was not included or reported.
OR
N/A.
47 Except for acute mammalian toxicity and skin and eye irritation studies, where the me of a negative control may not be
required (e.g., OECD 403 Acute Inhalation Toxicity Guidelines).
L
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - Animal
The reported negative control group
was not appropriate (e.g.,
age/weight of animals differed
between control and treated
groups).
Metric 3:
Positive controls
When applicable, an appropriate
concurrent positive control (i.e.,
inducing a positive response) was
not used.
4947904
Metric 4:
Reporting of doses/concentrations
Doses/concentrations were not
reported and could not be calculated
using default or reported estimates
of body weight and diet/water intake
(e.g., default intake values are not
available for pregnant animals).
4940200
4947904
4947912
Metric 5:
Exposure duration
The duration of exposure was not
reported.
OR
The reported exposure duration was
not suited to the study type and/or
outcome(s) of interest (e.g., <28
days for repeat dose).
4947904
Metric 6:
Test animal characteristics
The test animal species was not
reported.
OR
The test animal (species, strain, sex,
life-stage, source) was not
appropriate for the evaluation of the
specific outcome(s) of interest (e.g.,
genetically modified animals, strain
was uniquely susceptible or resistant
to one or more outcome of interest).
4947912
4946441
4940200
Metric 7:
Number of animals per group
The number of animals per study
group was not reported.
OR
The number of animals per study
group was insufficient to
characterize toxicological effects
(e.g., 1-2 animals in each group).
N/A.
Metric 8:
Outcome assessment methodology
The outcome assessment
methodology was not sensitive for
the outcome(s) of interest (e.g.,
evaluation of endpoints outside the
critical window of development, a
systemic toxicity study that
evaluated only grossly observable
4953507
4947912
4940200
4940252
4940248
LI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - Animal
endpoints, such as clinical signs and
mortality, etc.).
Metric 9:
Reporting of data
Data presentation was
inadequate (e.g., the report
does not differentiate among
findings in multiple exposure
groups).
OR
Major inconsistencies were present
in reporting of results.
4946441
4940200
2077994
Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - In Vitro
Data Quality Metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
Test substance identity
The test substance identity or
description cannot be determined
from the information provided (e.g.,
nomenclature was unclear and
CASRN or structure were not
reported).
OR
For mixtures, the components and
ratios were not characterized or did
not include information that could
result in a reasonable approximation
of components.
N/A.
Metric 2:
Negative controls
A concurrent negative control group
was not included or reported.
OR
The reported negative control
group was not appropriate (e.g.,
different cell lines used for
controls and test substance
exposure).
N/A.
Metric 3:
Positive controls
A concurrent positive control or
proficiency group was not used.
N/A.
Metric 4:
Assay type
The assay type was not reported.
OR
The assay type was not appropriate
for the study type or outcome of
interest (e.g., in vitro skin corrosion
protocol used for in vitro skin
irritation assay).
N/A.
Metric 5:
Reporting of concentration
The exposure doses/concentrations
or amounts of test substance were
not reported.
4940248
4940252
4947755
Metric 6:
Exposure duration
No information on exposure
duration(s) was reported.
OR
The exposure duration was not
appropriate for the study type and/or
outcome of interest (e.g., 24 hours
4940248
4940252
Lll
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.7: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - In Vitro
exposure for bacterial reverse
mutation test).
Metric 7:
Metabolic activation
No information on the
characterization and use of a
metabolic activation system was
reported.
OR
The exposure duration was
not appropriate for the study
type and/or outcome of
interest (e.g., 24 hours
exposure for bacterial reverse
mutation test).
4940252
Metric 8:
Test model
The test model was not reported
OR
The test model was not routinely
used for evaluation of the specific
outcome of interest.
4940252
Metric 9:
Outcome assessment methodology
The outcome assessment
methodology was not reported.
OR
The assessment methodology was
not appropriate for the outcome(s) of
interest (e.g., cells were evaluated
for chromosomal aberrations
immediately after exposure to the
test substance instead of after post-
exposure incubation period).
N/A.
C.2.2 Environmental Hazard
For the screening review of LPS candidate potassium gluconate, EPA excluded a total of 1892 references
when assessing environmental hazard. Off-topic environmental hazard references excluded at
title/abstract screening are listed in Table C.8, and those excluded at full-text screening are listed in Table
C.9. References in Table C.10 represent unacceptable studies based on specific data quality metrics for
environmental hazard. Off-topic and unacceptable references are displayed next to the corresponding
exclusion criteria.
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
Reference excluded (HERO ID) because the reference did NOT contain information needs48 relevant to environmental hazard
4947751
4941614
4947806
4942654
4941384
4942713
4267702
4941467
4941052
4941595
19702
4941616
4947807
4942655
4941385
4942714
4302029
4941484
4941053
4941601
19800
4941617
4947808
4942659
4941388
4942754
4327101
4941487
4941056
4941608
19855
4941618
4947809
4942661
4941389
4942758
4366817
4941491
4941058
4942451
48 Hie information needs for environmental hazard includes a list of study characteristics pertaining to the test organism/species,
type and level of effects, and me of controls. A complete list of the information needs is provided in Table A2 of the "Approach
Document for Screening Hazard Information for Low-Priority Substances Under TSCA". These information needs helped guide
the development of questions for title/abstract and full-text screening.
Llll
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
1997743
4941621
4947810
4942663
4941395
4942773
4375143
4941492
4941060
4942452
2061011
4941622
4947811
4942665
4941397
4942775
4380671
4941500
4941068
4942453
2066780
4941623
4947812
4942693
4941402
4942817
4390129
4941503
4941069
4942456
2070843
4941626
4947813
4942694
4941408
4942819
4392515
4941504
4941076
4942459
2073796
4941628
4947814
4942710
4941413
4942820
4396121
4941507
4941081
4942460
2251366
4941629
4947815
4942711
4941414
4942822
4447128
4941509
4941082
4942461
2305122
4941630
4947830
4942759
4941425
4942825
4472242
4941516
4941089
4942504
2740828
4941635
4947831
4942764
4941429
4942827
4529995
4941521
4941090
4942506
2789501
4941637
4947832
4942765
4941430
4942828
4531080
4941522
4941096
4942508
2792369
4941641
4947833
4942766
4941433
4943335
4593855
4941525
4941108
4942509
2885345
4941642
4947834
4942767
4941434
4943351
4602816
4941526
4941109
4942510
3036081
4941702
4947835
4943126
4941439
4943392
4640938
4941529
4941115
4942511
3036375
4941704
4947836
4943155
4941441
4943393
4683188
4941530
4941124
4942514
3045285
4941712
4947837
4943165
4941442
4943394
4734068
4941536
4941125
4942515
3103748
4941781
4947838
4943169
4941446
4943402
4743036
4941538
4941126
4942517
3147238
4941788
4947840
4943216
4941454
4943403
4848493
4941540
4941135
4942519
3188921
4941792
4947841
4943217
4941457
4943413
4940980
4941545
4941136
4942520
3235430
4941793
4947842
4943221
4941461
4943458
4940981
4941547
4941146
4942521
3491920
4941795
4947843
4943234
4941464
4943464
4940984
4941548
4941149
4942522
3514544
4941798
4947844
4943235
4941471
4943466
4940985
4941554
4941152
4942523
3538354
4941799
4947845
4943267
4941473
4943470
4940989
4941560
4941153
4942528
3664515
4941802
4947846
4943279
4941474
4943475
4940994
4941566
4941154
4942529
3673078
4941868
4947856
4943282
4941475
4943476
4940997
4941567
4941161
4942531
3737219
4941869
4947879
4943295
4941478
4943479
4940998
4941570
4941165
4942533
3738347
4941878
4947880
4943301
4941480
4943526
4941001
4941571
4941172
4942535
3740044
4941879
4947881
4943334
4941485
4943530
4941011
4941574
4941173
4942536
3791358
4941882
4947882
4943345
4941488
4943531
4941012
4941578
4941182
4942543
3804682
4941888
4947883
4943395
4941495
4943533
4941013
4941579
4941183
4942551
3804687
4941980
4947884
4943399
4941505
4943535
4941017
4941580
4941185
4942575
3993283
4941987
4947885
4943400
4941510
4943540
4941022
4941583
4941187
4942577
3994810
4941989
4947886
4943541
4941511
4943543
4941023
4941584
4941195
4942579
3998664
4941991
4947888
4943580
4941512
4943547
4941033
4941585
4941197
4942583
3998780
4942158
4947900
4943581
4941513
4943572
4941036
4941586
4941199
4942586
3999304
4942172
4947901
4943648
4941517
4943574
4941037
4941591
4941206
4942589
4072289
4942249
4947911
4943656
4941524
4943582
4941043
4941592
4941214
4942591
4114843
4942250
57347
4943660
4941533
4943586
4941051
4941593
4941215
4942594
4119345
4942253
620381
4943775
4941534
4943641
4941790
4944160
4941218
4942645
4119539
4942257
824640
4944150
4941537
4943645
4941794
4944167
4941220
4942649
4119545
4942261
2126383
4944162
4941542
4943646
4941796
4944168
4941229
4942650
4119546
4942265
2540871
4944164
4941543
4943647
4941800
4944466
4941230
4942651
4119556
4942278
3086385
4944464
4941544
4943650
4941801
4944467
4941235
4942652
4119563
4942280
4057262
4944471
4941552
4943653
4941870
4944473
4941249
4942653
4119567
4942281
4120689
4944475
4941553
4943658
4941876
4944480
4941254
4941357
4119601
4942305
4941406
4944476
4941555
4943659
4941883
4944481
4941256
4941359
4119602
4942315
4942322
4944486
4941558
4943661
4941984
4944484
4941258
4941361
4119603
4942318
4942457
4944582
4941559
4943747
4941985
4944485
4941259
4941369
4119721
4942321
4942502
4944584
4941562
4943748
4941990
4944585
4941261
4941372
4119722
4942327
4942646
4944587
4941563
4943749
4941995
4944594
4941263
4941378
LIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
4120082
4942328
4946444
4944595
4941569
4943771
4941999
4944596
4941267
4941381
4120474
4942335
4946517
4944747
4941572
4943787
4942157
4944602
4941274
4941394
4120476
4942336
4946663
4945164
4941575
4943789
4942164
4944735
4941276
4941399
4120490
4942340
4947549
4945914
4941581
4943857
4942166
4944749
4941283
4941410
4120587
4942345
4947576
4945996
4941590
4943861
4942173
4944752
4941285
4941427
4120643
4942348
4947601
4946076
4941594
4943866
4942174
4945064
4941288
4941428
4120652
4942371
4947653
4946281
4941598
4943870
4942176
4945066
4941304
4941432
4120814
4942377
4947661
4946397
4941599
4943876
4942177
4945070
4941310
4941436
4220713
4942380
4947799
4946398
4941604
4943877
4942248
4945074
4941312
4941444
4291829
4942387
4947804
4946443
4941607
4943878
4942252
4945077
4941315
4941445
4292632
4942418
4947912
4946489
4941612
4943927
4942258
4945079
4941318
4941447
4314415
4942419
689851
4946519
4941627
4943928
4942259
4945114
4941319
4941455
4314853
4942421
1040854
4946593
4941632
4943933
4942260
4945115
4941324
4941458
4316393
4942423
1047348
4946606
4941633
4943935
4942262
4945117
4941335
4941459
4319651
4942425
1048216
4946644
4941639
4943938
4942266
4945130
4941336
4941462
4331885
4942427
1112254
4946651
4941649
4943940
4942267
4945131
4941350
4941463
4375986
4942433
1115753
4946654
4941696
4943943
4942268
4945158
4941352
4953115
4403828
4942438
1159046
4946658
4941701
4943944
4942276
4945161
4941354
4953507
4435320
4942439
1206893
4946661
4941703
4943945
4942284
4945168
4941355
4955506
4496995
4942440
1336123
4947524
4941705
4943949
4942308
4945172
4941356
4955507
4543359
4942445
1454202
4947540
4941706
4943954
4942310
4947587
4942435
4955508
4552415
4942446
1509898
4947541
4941782
4943963
4942317
4947620
4942437
4955537
4556226
4942447
1613593
4947542
4941786
4944154
4942319
4947622
4942441
594396
4941208
4942455
1617565
4947543
4941789
4944155
4942330
4947688
4942442
922028
4941212
4942458
1631128
4947546
4942426
4947755
4942337
4947704
4942344
4947742
4941216
4942462
1749650
4947547
3460102
4947648
4942339
4947712
4941325
4942592
4941219
4942505
1772048
4947553
3469615
4947649
4942342
4947717
4941326
4942593
4941227
4942507
1850785
4947559
3723672
4947656
4942343
4942587
4941329
4942648
4941240
4942512
1939810
4947563
3735756
4947658
4941371
4942705
4941330
4942656
4941241
4942513
2005861
4947569
3753979
4947672
4941376
4942708
4941340
4942657
4941246
4942516
2035841
4947571
3830637
4947677
4941382
4942712
4941347
4942658
4941260
4942518
2036229
4947572
4066561
4947785
4942374
4947765
4941349
4942662
4941262
4942525
2043990
4947588
4074472
4947788
4942376
4947894
4941351
4942666
4941265
4942526
2050830
4947589
4078548
4947800
4942379
4947904
4941365
4942667
4941271
4942527
2077994
4947593
4078783
4947801
4942417
4952780
4941366
4942697
4941281
4942530
2087723
4947594
4081337
4947802
4942420
4947756
3198770
4947646
4941294
4942532
2219727
4947595
4081374
4947803
4941314
4942578
3187873
4947643
4941297
4942534
2226345
4947597
4166472
4947805
4941311
4942576
2952166
4947642
4941298
4942537
2574699
4947623
4942443
4947757
2862299
4947639
4942429
4942373
4941300
4942541
2587722
4947625
4942444
4947762
2821389
4947638
4942450
4942372
4941301
4942544
2589049
4947634
4942448
4947764
4941317
4942545
4941306
4942550
4947751
4941614
4947806
4942654
4941384
4942713
4267702
4941467
4941052
4941595
19702
4941616
4947807
4942655
4941385
4942714
4302029
4941484
4941053
4941601
19800
4941617
4947808
4942659
4941388
4942754
4327101
4941487
4941056
4941608
19855
4941618
4947809
4942661
4941389
4942758
4366817
4941491
4941058
4942451
1997743
4941621
4947810
4942663
4941395
4942773
4375143
4941492
4941060
4942452
2061011
4941622
4947811
4942665
4941397
4942775
4380671
4941500
4941068
4942453
2066780
4941623
4947812
4942693
4941402
4942817
4390129
4941503
4941069
4942456
LV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
2070843
4941626
4947813
4942694
4941408
4942819
4392515
4941504
4941076
4942459
2073796
4941628
4947814
4942710
4941413
4942820
4396121
4941507
4941081
4942460
2251366
4941629
4947815
4942711
4941414
4942822
4447128
4941509
4941082
4942461
2305122
4941630
4947830
4942759
4941425
4942825
4472242
4941516
4941089
4942504
2740828
4941635
4947831
4942764
4941429
4942827
4529995
4941521
4941090
4942506
2789501
4941637
4947832
4942765
4941430
4942828
4531080
4941522
4941096
4942508
2792369
4941641
4947833
4942766
4941433
4943335
4593855
4941525
4941108
4942509
2885345
4941642
4947834
4942767
4941434
4943351
4602816
4941526
4941109
4942510
3036081
4941702
4947835
4943126
4941439
4943392
4640938
4941529
4941115
4942511
3036375
4941704
4947836
4943155
4941441
4943393
4683188
4941530
4941124
4942514
3045285
4941712
4947837
4943165
4941442
4943394
4734068
4941536
4941125
4942515
3103748
4941781
4947838
4943169
4941446
4943402
4743036
4941538
4941126
4942517
3147238
4941788
4947840
4943216
4941454
4943403
4848493
4941540
4941135
4942519
3188921
4941792
4947841
4943217
4941457
4943413
4940980
4941545
4941136
4942520
3235430
4941793
4947842
4943221
4941461
4943458
4940981
4941547
4941146
4942521
3491920
4941795
4947843
4943234
4941464
4943464
4940984
4941548
4941149
4942522
3514544
4941798
4947844
4943235
4941471
4943466
4940985
4941554
4941152
4942523
3538354
4941799
4947845
4943267
4941473
4943470
4940989
4941560
4941153
4942528
3664515
4941802
4947846
4943279
4941474
4943475
4940994
4941566
4941154
4942529
3673078
4941868
4947856
4943282
4941475
4943476
4940997
4941567
4941161
4942531
3737219
4941869
4947879
4943295
4941478
4943479
4940998
4941570
4941165
4942533
3738347
4941878
4947880
4943301
4941480
4943526
4941001
4941571
4941172
4942535
3740044
4941879
4947881
4943334
4941485
4943530
4941011
4941574
4941173
4942536
3791358
4941882
4947882
4943345
4941488
4943531
4941012
4941578
4941182
4942543
3804682
4941888
4947883
4943395
4941495
4943533
4941013
4941579
4941183
4942551
3804687
4941980
4947884
4943399
4941505
4943535
4941017
4941580
4941185
4942575
3993283
4941987
4947885
4943400
4941510
4943540
4941022
4941583
4941187
4942577
3994810
4941989
4947886
4943541
4941511
4943543
4941023
4941584
4941195
4942579
3998664
4941991
4947888
4943580
4941512
4943547
4941033
4941585
4941197
4942583
3998780
4942158
4947900
4943581
4941513
4943572
4941036
4941586
4941199
4942586
3999304
4942172
4947901
4943648
4941517
4943574
4941037
4941591
4941206
4942589
4072289
4942249
4947911
4943656
4941524
4943582
4941043
4941592
4941214
4942591
4114843
4942250
57347
4943660
4941533
4943586
4941051
4941593
4941215
4942594
4119345
4942253
620381
4943775
4941534
4943641
4941790
4944160
4941218
4942645
4119539
4942257
824640
4944150
4941537
4943645
4941794
4944167
4941220
4942649
4119545
4942261
2126383
4944162
4941542
4943646
4941796
4944168
4941229
4942650
4119546
4942265
2540871
4944164
4941543
4943647
4941800
4944466
4941230
4942651
4119556
4942278
3086385
4944464
4941544
4943650
4941801
4944467
4941235
4942652
4119563
4942280
4057262
4944471
4941552
4943653
4941870
4944473
4941249
4942653
4119567
4942281
4120689
4944475
4941553
4943658
4941876
4944480
4941254
4941357
4119601
4942305
4941406
4944476
4941555
4943659
4941883
4944481
4941256
4941359
4119602
4942315
4942322
4944486
4941558
4943661
4941984
4944484
4941258
4941361
4119603
4942318
4942457
4944582
4941559
4943747
4941985
4944485
4941259
4941369
4119721
4942321
4942502
4944584
4941562
4943748
4941990
4944585
4941261
4941372
4119722
4942327
4942646
4944587
4941563
4943749
4941995
4944594
4941263
4941378
4120082
4942328
4946444
4944595
4941569
4943771
4941999
4944596
4941267
4941381
4120474
4942335
4946517
4944747
4941572
4943787
4942157
4944602
4941274
4941394
4120476
4942336
4946663
4945164
4941575
4943789
4942164
4944735
4941276
4941399
LVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.8: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
4120490
4942340
4947549
4945914
4941581
4943857
4942166
4944749
4941283
4941410
4120587
4942345
4947576
4945996
4941590
4943861
4942173
4944752
4941285
4941427
4120643
4942348
4947601
4946076
4941594
4943866
4942174
4945064
4941288
4941428
4120652
4942371
4947653
4946281
4941598
4943870
4942176
4945066
4941304
4941432
4120814
4942377
4947661
4946397
4941599
4943876
4942177
4945070
4941310
4941436
4220713
4942380
4947799
4946398
4941604
4943877
4942248
4945074
4941312
4941444
4291829
4942387
4947804
4946443
4941607
4943878
4942252
4945077
4941315
4941445
4292632
4942418
4947912
4946489
4941612
4943927
4942258
4945079
4941318
4941447
4314415
4942419
689851
4946519
4941627
4943928
4942259
4945114
4941319
4941455
4314853
4942421
1040854
4946593
4941632
4943933
4942260
4945115
4941324
4941458
4316393
4942423
1047348
4946606
4941633
4943935
4942262
4945117
4941335
4941459
4319651
4942425
1048216
4946644
4941639
4943938
4942266
4945130
4941336
4941462
4331885
4942427
1112254
4946651
4941649
4943940
4942267
4945131
4941350
4941463
4375986
4942433
1115753
4946654
4941696
4943943
4942268
4945158
4941352
4953115
4403828
4942438
1159046
4946658
4941701
4943944
4942276
4945161
4941354
4953507
4435320
4942439
1206893
4946661
4941703
4943945
4942284
4945168
4941355
4955506
4496995
4942440
1336123
4947524
4941705
4943949
4942308
4945172
4941356
4955507
4543359
4942445
1454202
4947540
4941706
4943954
4942310
4947587
4942435
4955508
4552415
4942446
1509898
4947541
4941782
4943963
4942317
4947620
4942437
4955537
4556226
4942447
1613593
4947542
4941786
4944154
4942319
4947622
4942441
594396
4941208
4942455
1617565
4947543
4941789
4944155
4942330
4947688
4942442
922028
4941212
4942458
1631128
4947546
4942426
4947755
4942337
4947704
4942344
4947742
4941216
4942462
1749650
4947547
3460102
4947648
4942339
4947712
4941325
4942592
4941219
4942505
1772048
4947553
3469615
4947649
4942342
4947717
4941326
4942593
4941227
4942507
1850785
4947559
3723672
4947656
4942343
4942587
4941329
4942648
4941240
4942512
1939810
4947563
3735756
4947658
4941371
4942705
4941330
4942656
4941241
4942513
2005861
4947569
3753979
4947672
4941376
4942708
4941340
4942657
4941246
4942516
2035841
4947571
3830637
4947677
4941382
4942712
4941347
4942658
4941260
4942518
2036229
4947572
4066561
4947785
4942374
4947765
4941349
4942662
4941262
4942525
2043990
4947588
4074472
4947788
4942376
4947894
4941351
4942666
4941265
4942526
2050830
4947589
4078548
4947800
4942379
4947904
4941365
4942667
4941271
4942527
2077994
4947593
4078783
4947801
4942417
4952780
4941366
4942697
4941281
4942530
2087723
4947594
4081337
4947802
4942420
4947756
3198770
4947646
4941294
4942532
2219727
4947595
4081374
4947803
4941314
4942578
3187873
4947643
4941297
4942534
2226345
4947597
4166472
4947805
4941311
4942576
2952166
4947642
4941298
4942537
2574699
4947623
4942443
4947757
2862299
4947639
4942429
4942373
4941300
4942541
2587722
4947625
4942444
4947762
2821389
4947638
4942450
4942372
4941301
4942544
2589049
4947634
4942448
4947764
4941317
4942545
4941306
4942550
4941305
Reference excluded (HERO ID) because the reference primarily contained in silico data
N/A.
Table C.9: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Environmental Hazard
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain
information pertaining to a low-
priority substance candidate?
No
1576583
2777828
4940080
4941620
LVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.9: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Environmental Hazard
4944742
4940081
4940082
4944478
What type of source is this
reference?
Review article or book chapter that
contains only citations to primary
literature sources
N/A.
Is quantitative environmental
No
N/A.
hazard data presented?
Is this primarily a
Yes
N/A.
modeling/simulation study?
[Note: select "No" if experimental
verification was included in the
study]
Is environmental hazard data
No
4942584
presented for standard or non-
standard aquatic or terrestrial
species (fish, invertebrates,
microorganisms, non-mammalian
terrestrial species)?
Is exposure measured for the target
Mixture
N/A.
substance or is the test substance
Formulated product
N/A.
a mixture (except for reasonable
impurities, byproducts, and
aqueous solutions) or formulated
product?
Does the reference report a
No
N/A.
duration of exposure?
Does the reference report a
No
4940264
negative control that is a vehicle
control or no treatment control?
Does the reference include
No
5077191
endpoints in the information needs?
Table C.10: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Environmental Hazard
Question
Unacceptable if:
References excluded (HERO ID)
Metric 1:
The test substance identity or
4940261
Test substance identity
description cannot be
determined from the information
provided (e.g., nomenclature
was unclear, CASRN or structure
were not reported, substance
name/ description does not
match CASRN).
OR
For mixtures, the components and
ratios were not characterized or did
not include information that could
result in a reasonable approximation
of components.
4940258
LVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.10: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for
Environmental Hazard
Metric 2:
A concurrent negative control group
4940258
Negative controls
was not included or reported.
4940261
Metric 3:
The experimental system (e.g.,
4940256
Experimental system
static, semi-static, or flow-through
4940258
regime) was not described.
4940261
4942597
Metric 4:
Test concentrations were not
4940256
Reporting of concentrations
reported.
4940258
4940261
4942597
Metric 5:
The duration of exposure was not
N/A.
Exposure duration
reported.
OR
The reported exposure duration was
not suited to the study type and/or
outcome(s) of interest (e.g., study
intended to assess effects on
reproduction did not expose
organisms for an acceptable period
of time prior to mating).
Metric 6:
The test species was not reported.
4940256
Test organism characteristics
OR
4940258
The test species, life stage, or age
4940261
was not appropriate for the
4942597
outcome(s) of interest.
Metric 7:
The outcome assessment
N/A.
Outcome assessment methodology
methodology was not reported.
Metric 8:
Data presentation was
4942597
Reporting of data
inadequate.
4940261
OR
4940258
Major inconsistencies were present
4940256
in reporting of results.
C.2.3 Fate
For the screening review of LPS candidate potassium gluconate, EPA excluded a total of 5045 references
when assessing environmental fate. Off-topic fate references excluded at title/abstract screening are listed
in Table C. 11, and those excluded at full-text screening are listed in Table C. 12. References in Table C. 13
represent unacceptable studies based on specific data quality metrics for fate. Off-topic and unacceptable
references are displayed next to the corresponding exclusion criteria.
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
Reference excluded (HERO ID) because the reference did NOT contain information needs49 relevant to environmental fate
4947698
4948277
4947773
4947149
4944733
4941880
4550270
4941700
4947044
4943779
1016211
4948278
4947775
4947150
4944734
4941881
4560033
4941707
4947079
4943780
49 Hie information needs for fate includes a list of study characteristics pertaining to the associated media and exposure
pathways, associated processes, and use of controls. A complete list of the information needs is provided in Table A3 of the
"Approach Document for Screening Hazard Information for Low-Priority Substances Under TSCA". These information needs
helped guide the development of questions for title/abstract and full-text screening.
LIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
1019493
4948279
4947776
4947151
4944736
4941884
4560428
4941708
4947080
4943781
1029322
4948280
4947777
4947152
4944737
4941885
4561187
4941709
4947081
4943784
1033739
4948281
4947779
4947163
4944738
4941887
4566211
4941710
4947082
4943785
1039487
4948282
4947816
4947165
4944739
4941889
4568392
4941711
4947083
4943786
1040116
4948283
4947817
4947166
4944740
4941977
4568878
4941713
4947084
4943788
1046204
4948284
4947818
4947167
4944741
4941978
4569215
4941714
4947085
4943790
1047517
4948285
4947819
4947168
4944744
4941979
4575011
4941715
4947086
4943792
1050803
4948287
4947820
4947169
4944745
4941981
4575154
4941780
4947087
4943794
1050863
4948288
4947821
4947170
4944746
4941982
4580065
4941783
4947088
4943859
1062433
4948289
4947823
4947171
4944748
4941983
4602820
4941784
4947089
4943860
1071558
4948290
4947824
4947172
4944750
4941986
4604183
4941785
4947090
4943864
1110499
4948291
4947825
4947173
4944753
4941988
4605077
4941787
4947091
4943865
1150251
4948292
4947826
4947174
4944754
4941992
4611583
4941791
4947092
4943871
1155637
4948293
4947827
4947205
4944755
4941993
4635279
4941797
4947093
4943872
1157207
4948295
4947828
4947206
4944781
4941996
4649607
4941871
4947094
4943873
1160131
4948296
4947829
4947207
4944836
4941997
465562
4941872
4947095
4943875
1168172
4948297
4947865
4947208
4944837
4941998
4669682
4941873
4947096
4943880
1172952
4948298
4947866
4947209
4944839
4942000
4690884
4941874
4947097
4943922
1177273
4948299
4947867
4947210
4944842
4942156
4701208
4941875
4947098
4943923
1178025
4948300
4947868
4947211
4944846
4942159
4702596
4941877
4947116
4943924
1181715
4948301
4947869
4947212
4944890
4942161
471016
4941257
4947118
4943925
1184177
4948302
4947870
4947213
4944893
4942162
4721847
4941264
4947119
4943926
1195839
4948303
4947871
4947214
4944904
4942163
4731581
4941266
4947120
4943930
1198396
4948304
4947872
4947215
4944932
4942165
4735898
4941268
4947121
4943932
1203783
4948306
4947873
4947216
4944939
4942167
4738596
4941269
4947123
4943934
1205930
4948307
4947874
4947217
4944989
4942168
4740054
4941270
4947124
4943936
1207770
4948308
4947875
4947218
4944996
4942169
4740811
4941272
4947125
4943937
1231527
4948309
4947876
4947219
4945011
4942170
4745391
4941275
4947126
4943939
1235526
4948310
4947877
4947220
4945017
4942171
4745578
4941277
4947127
4943941
1436203
4948311
4947878
4947230
4945018
4942175
4747789
4941278
4947128
4943942
1457148
4948312
4947919
4947232
4945020
4942178
4752490
4941279
4947129
4943948
1457225
4948313
4947920
4947233
4945030
4942247
4752887
4941280
4947142
4943950
1457818
4948314
4947921
4947235
4945036
4942251
4764276
4941282
4947143
4943951
1457820
4948315
4947922
4947237
4945060
4942279
4772353
4941284
4947144
4943952
1533019
4948316
4947923
4947238
4945063
4942282
4787173
4941287
4947145
4943953
1573231
4948317
4947925
4947239
4945065
4942283
4790967
4941289
4947146
4943955
1577430
4948318
4947926
4947240
4945067
4942304
4801136
4941290
4947147
4943956
1585355
4948319
4947927
4947241
4945068
4942306
4802652
4941291
4947148
4943957
1589711
4948320
4947928
4947242
4945069
4942307
4823262
4941292
4388644
4943958
1655444
4948321
4947929
4947243
4945071
4942309
4825338
4941293
4389070
4943959
1666268
4948322
4947930
4947244
4945075
4942311
4825720
4941295
4389626
4943960
1675258
4948323
4947931
4947245
4945076
4942312
4827713
4941296
4389627
4943961
1689366
4948324
4947932
4947275
4945080
4942313
4828341
4941299
4393002
4943962
1693800
4948325
4947933
4947276
4945081
4942314
4837124
4941302
4393091
4943964
1726534
4948326
4947937
4947277
4945084
4942316
4841066
4941303
4393545
4943965
1734774
4948327
4947938
4947278
4945086
4942320
4860634
4941308
4394660
4943966
1735836
4948328
4947939
4947279
4945091
4942323
4868812
4941309
4395155
4943967
1759021
4948329
4947940
4947280
4945102
4942324
4882501
4941313
4397168
4944145
LX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
1759382
4948330
4947941
4947281
4945105
4942325
4911786
4941320
4397170
4944147
1760075
4948335
4947942
4947282
4945106
4942326
4925504
4941322
4399544
4944148
1760390
4948336
4947943
4947283
4945107
4942329
4940943
4941323
4400383
4944151
1760397
4948337
4947944
4947284
4945113
4942331
4940946
4941327
4402033
4944152
1763482
4948338
4947945
4947285
4945116
4942332
4940949
4941328
4402340
4944153
1765216
4948339
4947946
4947286
4945118
4942333
4940950
4941331
4414610
4944158
1766188
4948340
4947947
4947287
4945119
4942334
4940951
4941332
4421420
4944159
1768182
4948342
4947948
4947288
4945120
4942338
4940953
4941333
4421814
4944161
1800285
4948343
4947949
4947289
4945121
4942341
4940959
4941334
4423753
4944163
1866419
4948344
4947950
4947290
4945122
4942346
4940966
4941337
4424564
4944165
1876441
4948346
4947951
4947291
4945123
4942347
4940969
4941338
4428098
4944166
1928573
4948347
4947952
4947293
4945124
4942349
4940972
4941339
4428556
4944465
1930841
4948348
4947983
4947294
4945128
4942370
4940973
4941341
4429864
4944468
1933097
4948351
4947984
4947295
4945132
4942375
4940974
4941342
4432591
4944469
194067
4948353
4947985
4947297
4945133
4942378
4940975
4941343
4435487
4944470
1952145
4948354
4947986
4947298
4945134
4942381
4940976
4941345
4437429
4944472
1953874
4948355
4947987
4947299
4945135
4942382
4940977
4941348
4443804
4944474
1966495
4948356
4947988
4947300
4945141
4942383
4940978
4941353
4446236
4944477
1989950
4948357
4947989
4947301
4945143
4942384
4940979
4941358
4455300
4944479
1991173
4948358
4947991
4947302
4945156
4942385
4940983
4941360
4455775
4944482
1994721
4948359
4947992
4947303
4945162
4942386
4940986
4941362
4458084
4944483
1999661
4948361
4947993
4947304
4945163
4942388
4940987
4941363
4458232
4944583
2015596
4948362
4947994
4947305
4945165
4942389
4940990
4941364
4461689
4944586
2017597
4948363
4947995
4947306
4945166
4942390
4940992
4941367
4466667
4944588
2021125
4948364
4948004
4947307
4945167
4942414
4940993
4941368
4468382
4944589
2023172
4948365
4948005
4947308
4945193
4942416
4940995
4941373
4469050
4944590
2023413
4948366
4948006
4947309
4945200
4942422
4940996
4941374
4474837
4944591
2036356
4948367
4948007
4947310
4945201
4942424
4941000
4941375
4481056
4944592
2039057
4948368
4948008
4947311
4945204
4942428
4941002
4941377
4487506
4944593
2051784
4948369
4948009
4947312
4945205
4942430
4941004
4941379
4489237
4944597
2055086
4948371
4948010
4947313
4945212
4942431
4941005
4941380
4489772
4944598
2056537
4948372
4948011
4947314
4945236
4942432
4941006
4941383
4490354
4944600
2061182
4948373
4948012
4947315
4945237
4942434
4941007
4941386
4490449
4944601
2061422
4948374
4948013
4947316
4945279
4942436
4941008
4941387
4492191
4944603
2061561
4948375
4948014
4947317
4945286
4942454
4941009
4941390
4496631
4944604
2063060
4948376
4948015
4947318
4945315
4942524
4941016
4941391
4498882
4944731
2113515
4948377
4948016
4947319
4945321
4942538
4941018
4941392
4499501
4374970
2113530
4948378
4948025
4947320
4945326
4942540
4941019
4941393
452687
4375238
2113659
4948379
4948026
4947321
4945379
4942542
4941021
4941396
4531331
4377416
2114236
4948380
4948027
4947322
4945385
4942547
4941025
4941400
4533599
4377635
2303433
4948381
4948028
4947323
4945388
4942548
4941026
4941401
4534977
4377831
2338751
4948382
4948029
4947324
4945404
4942549
4941027
4941403
4537145
4378841
2362114
4948383
4948030
4947325
4945418
4942580
4941030
4941404
4538528
4380919
2375285
4948384
4948032
4947326
4945441
4942581
4941032
4941405
4540422
4382409
2457324
4948385
4948033
4947327
4945444
4942582
4941034
4941407
4548071
4382411
2466449
4948386
4948034
4947329
4945453
4942585
4941035
4941409
4548314
4384048
2521268
4948387
4948035
4947330
4945511
4942588
4941038
4941411
4549483
4947034
2522503
4948388
4948036
4947331
4945512
4942590
4941040
4941412
4947695
4947035
LXI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
2524040
4948389
4948037
4947332
4945525
4942595
4941041
4941415
4947697
4374603
2524248
4948390
4948038
4947333
4945557
4942596
4941042
4941416
4946796
4943347
2536666
4948391
4948039
4947335
4945562
4942597
4941044
4941421
4946797
4943348
2563719
4948392
4948040
4947336
4945564
4942598
4941045
4941422
4946798
4943350
2565690
4948393
4948041
4947337
4945568
4942647
4941046
4941423
4946799
4943396
2592746
4948394
4948042
4947338
4945610
4942660
4941047
4941426
4946800
4943397
2594197
4948395
4948043
4947339
4945626
4942664
4941048
4941431
4946801
4943398
2594309
4948396
4948044
4947340
4945630
4942692
4941050
4941437
4946802
4943404
2595846
4948397
4948045
4947341
4945635
4942695
4941059
4941438
4946803
4943405
2604429
4948399
4948046
4947342
4945640
4942696
4941061
4941440
4946804
4943406
2615236
4948400
4948047
4947344
4945643
4942698
4941063
4941443
4946807
4943407
2647504
4948401
4948048
4947345
4945653
4942699
4941064
4941448
4946811
4943408
2648592
4948402
4948049
4947346
4945683
4942700
4941065
4941449
4946813
4943409
2665770
4948403
4948051
4947347
4945727
4942701
4941066
4941450
4946815
4943410
2673392
4948404
4948052
4947348
4945731
4942702
4941067
4941451
4946820
4943411
2675088
4948405
4948054
4947349
4945734
4942704
4941070
4941452
4946821
4943412
2683055
4948406
4948055
4947350
4945737
4942706
4941071
4941456
4946822
4943414
2693859
4948407
4948056
4947351
4945740
4942707
4941072
4941460
4946824
4943415
2742638
4948408
4948057
4947352
4945742
4942709
4941073
4941465
4946825
4943459
2748861
4948410
4948058
4947353
4945775
4942755
4941075
4941466
4946826
4943460
2750435
4948411
4948059
4947354
4945783
4942760
4941077
4941468
4946827
4943462
2750990
4948412
4948060
4947355
4945822
4942761
4941079
4941469
4946828
4943463
2810934
4948413
4948061
4947356
4945825
4942762
4941080
4941470
4946829
4943465
2833030
4948414
4948062
4947357
4945830
4942763
4941083
4941472
4946830
4943467
2861950
4948415
4948063
4947358
4945832
4942768
4941084
4941476
4946831
4943469
2864545
4948416
4948064
4947359
4945904
4942769
4941087
4941477
4946832
4943472
2864817
4948417
4948065
4947360
4945906
4942770
4941088
4941479
4946833
4943474
2880619
4948418
4948066
4947361
4945922
4942772
4941091
4941481
4946834
4943477
2880620
4948419
4948067
4947362
4945925
4942774
4941092
4941482
4946835
4943480
2880624
4948420
4948068
4947363
4945975
4942824
4941093
4941486
4946836
4943525
2893306
4948423
4948070
4947364
4946069
4942880
4941095
4941489
4946837
4943527
2915743
4948424
4948071
4947365
4946073
4942934
4941100
4941490
4946838
4943528
2982625
4948425
4948072
4947366
4946080
4942935
4941101
4941493
4946839
4943529
2984623
4948426
4948073
4947367
4946158
4942937
4941102
4941494
4946840
4943532
3007069
4948427
4948074
4947368
4946172
4942938
4941103
4941496
4946843
4943534
3015522
4948428
4948075
4947369
4946277
4942940
4941104
4941497
4946844
4943536
3022174
4948429
4948076
4947370
4946279
4942941
4941105
4941498
4946849
4943538
3028004
4948430
4948077
4947371
4946447
4942943
4941107
4941499
4946858
4943539
3039688
4948431
4948078
4947372
4946577
4942944
4941110
4941501
4946859
4943542
3068597
4948433
4948079
4947373
4946578
4942947
4941112
4941502
4946873
4943544
3069497
4948441
4948080
4947374
4946579
4942950
4941113
4941506
4946878
4943546
3088505
4948442
4948081
4947375
4946580
4942951
4941114
4941508
4946879
4943573
3115335
4948443
4948082
4947376
4946581
4942952
4941117
4941514
4946880
4943575
3116865
4948444
4948083
4947377
4946582
4942953
4941118
4941515
4946881
4943576
3120121
4948445
4948084
4947378
4946583
4942954
4941120
4941518
4946882
4943578
3163432
4948446
4948085
4947379
4946584
4942955
4941121
4941519
4946883
4943579
3169252
4948447
4948086
4947380
4946585
4943106
4941122
4941520
4946884
4943584
3173200
4948448
4948087
4947381
4946586
4943110
4941130
4941523
4946885
4943585
LXII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
3212876
4948449
4948088
4947382
4946624
4943113
4941131
4941527
4946886
4943587
3213885
4948450
4948089
4947383
4946625
4943114
4941133
4941528
4946887
4943592
3228265
4948451
4948090
4947384
4946627
4943116
4941142
4941531
4946888
4943593
3268792
4948452
4948092
4947385
4946628
4943119
4941143
4941532
4946889
4943594
3328916
4948463
4948093
4947386
4946629
4943122
4941144
4941535
4946890
4943595
3346350
4948464
4948094
4947387
4946630
4943123
4941145
4941539
4946891
4943640
3374260
4948465
4948095
4947388
4946631
4943125
4941147
4941541
4946892
4943642
3379967
4948466
4948096
4947389
4946632
4943149
4941148
4941549
4946893
4943644
3391658
4948467
4948097
4947390
4946633
4943153
4941150
4941550
4946894
4943649
3398035
4948468
4948098
4947391
4946634
4943154
4941151
4941551
4946895
4943651
3410241
4948469
4948099
4947392
4946635
4943156
4941157
4941556
4946896
4943652
3425319
4948470
4948100
4947393
4946636
4943160
4941158
4941557
4946897
4943654
3430301
4948471
4948101
4947394
4946637
4943161
4941160
4941561
4946898
4943655
3453603
4948472
4948102
4947395
4946638
4943162
4941162
4941564
4946899
4943657
3457917
4948473
4948103
4947396
4946664
4943163
4941163
4941565
4946900
4943662
3458439
4948474
4948104
4947397
4946665
4943164
4941164
4941568
4946901
4943727
3459150
4948485
4948105
4947398
4946666
4943166
4941166
4941573
4946902
4943728
3459165
4948486
4948106
4947399
4946667
4943167
4941168
4941576
4946903
4946955
3460447
4948487
4948107
4947400
4946668
4943168
4941169
4941577
4946904
4946958
3468890
4948488
4948108
4947401
4946669
4943170
4941170
4941582
4946905
4946960
3472099
4948489
4948109
4947402
4946670
4943215
4941175
4941587
4946908
4946962
3472209
4948490
4948110
4947403
4946671
4943219
4941176
4941588
4946913
4946964
3487563
4948491
4948111
4947404
4946672
4943222
4941177
4941589
4946916
4946965
3578984
4948492
4948112
4947405
4946673
4943223
4941179
4941596
4946917
4946967
3602591
4948493
4948113
4947406
4946674
4943225
4941181
4941600
4946921
4946968
3651958
4948494
4948114
4947407
4946675
4943226
4941188
4941602
4946922
4946969
3652834
4948495
4948115
4947408
4946676
4943229
4941189
4941605
4946923
4946970
3673708
4948498
4948117
4947409
4946677
4943230
4941191
4941606
4946924
4946971
3695614
4948499
4948118
4947410
4946678
4943231
4941193
4941609
4946925
4946972
3701231
4948500
4948119
4947412
4946679
4943232
4941194
4941610
4946926
4946973
3702762
4948501
4948120
4947413
4946680
4943233
4941196
4941611
4946927
4946974
3721521
4948502
4948121
4947414
4946681
4943236
4941198
4941613
4946928
4946975
3725946
4948503
4948122
4947415
4946682
4943262
4941201
4941615
4946929
4946976
3730534
4948504
4948123
4947416
4946684
4943263
4941202
4941620
4946930
4946977
3732912
4948505
4948124
4947417
4946685
4943264
4941203
4941631
4946938
4946978
3736162
4948506
4948125
4947418
4946686
4943265
4941204
4941634
4946947
4946979
3736910
4948507
4948126
4947419
4946687
4943266
4941209
4941636
4948264
4946980
3760441
4948508
4948127
4947420
4946688
4943268
4941211
4941638
4948265
4946981
3766605
4948509
4948128
4947421
4946689
4943269
4941213
4941640
4948266
4946982
3810924
4948510
4948129
4947422
4946690
4943270
4941223
4941643
4948268
4946983
3814826
4948511
4948130
4947423
4946715
4943272
4941224
4941644
4948269
4946986
3814978
4948512
4948131
4947424
4946720
4943275
4941226
4941645
4948270
4946988
382373
4948513
4948132
4947425
4946721
4943277
4941228
4941646
4948271
4946990
3844770
4948514
4948133
4947426
4946727
4943278
4941231
4941648
4948272
4946995
3845301
4948515
4948134
4947427
4946728
4943280
4941232
4941693
4948273
4947002
3890547
4948516
4948135
4947428
4946745
4943283
4941233
4941694
4948274
4947003
3896824
4948517
4948136
4947429
4946746
4943284
4941234
4941695
4948275
4947008
3997235
4948518
4948137
4947430
4946747
4943285
4941236
4941697
4948276
4947011
LXIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
3999296
4948519
4948138
4947431
4946748
4943289
4941237
4941698
4947699
4947012
4000271
4948520
4948139
4947432
4946749
4943291
4941238
4941699
4947700
4947023
4000746
4948521
4948140
4947433
4946750
4943293
4941239
4943729
4947701
4947025
4000887
4948522
4948141
4947434
4946751
4943298
4941242
4943732
4947771
4947031
4001578
4948523
4948142
4947435
4946752
4943300
4941243
4943734
4947772
4947032
4001654
4948525
4948143
4947436
4946753
4943303
4941244
4943735
4948250
4947606
4002230
4948526
4948144
4947437
4946754
4943304
4941245
4943736
4948251
4947607
4002590
4948527
4948145
4947438
4946755
4943305
4941247
4943738
4948254
4947608
4060629
4948528
4948147
4947439
4946756
4943307
4941248
4943739
4948255
4947609
4072033
4948529
4948148
4947440
4946764
4943331
4941250
4943740
4948256
4947610
4072901
4948530
4948149
4947441
4946771
4943333
4941251
4943741
4948257
4947611
4073919
4948531
4948150
4947442
4946773
4943336
4941252
4943742
4948258
4947612
4074665
4948532
4948151
4947443
4946778
4943337
4941253
4943743
4948259
4947613
4075996
4948533
4948152
4947444
4946780
4943338
4941255
4943745
4948260
4947614
4076964
4948534
4948153
4947445
4946781
4943339
4947036
4943750
4948261
4947615
4077417
4948535
4948154
4947446
4946785
4943341
4947037
4943772
4948262
4947637
4077717
4948536
4948155
4947447
4946790
4943342
4947038
4943773
4948263
4947655
4078894
4948537
4948156
4947448
4946793
4943343
4947039
4943774
4947033
4947694
4078912
4948538
4948157
4947449
4946794
4943344
4947040
4943776
4361132
4947671
4079654
4948541
4948158
4947450
4946795
4943346
4947041
4943778
4364365
4947674
4079719
4948542
4948159
4947451
4301328
4948621
4948208
4947500
4372651
4947676
4079990
4948543
4948160
4947452
4304269
4948622
4948209
4947501
4372807
4947689
4080001
4948544
4948161
4947453
4305966
4948623
4948210
4947502
4373863
4947691
4081443
4948545
4948162
4947454
4306562
4948645
4948211
4947504
4374940
4947692
4081645
4948546
4948163
4947455
4306578
4949331
4948212
4947505
4351902
4947662
4081873
4948547
4948165
4947456
4307324
4949337
4948213
4947506
4352597
4947665
4084810
4948548
4948166
4947457
4316595
4949345
4948214
4947507
4353385
4947666
4097819
4948549
4948167
4947458
4316812
4949346
4948215
4947508
4353505
4947667
4114369
4948550
4948168
4947459
4318136
4949347
4948216
4947509
4353835
4947668
4116098
4948552
4948169
4947460
4318925
4949348
4948217
4947510
4357745
4947669
4117629
4948553
4948170
4947461
4320317
4949349
4948218
4947511
4360490
4947670
4117928
4948554
4948171
4947462
4320976
4949350
4948220
4947512
4948201
4947491
4122451
4948563
4948172
4947463
4321430
4949352
4948221
4947513
4948202
4947492
4124988
4948564
4948173
4947464
4322919
4949353
4948222
4947514
4948203
4947493
4126830
4948565
4948174
4947465
4323216
495092
4948223
4947515
4948204
4947495
4126895
4948566
4948175
4947466
4323406
4955505
4948224
4947516
4948205
4947497
4127815
4948567
4948177
4947467
4324327
507820
4948225
4947517
4948206
4947498
4129992
4948568
4948178
4947468
4325158
522256
4948226
4947518
4948207
4947499
4136697
4948569
4948179
4947469
4326156
537490
4948227
4947519
4294080
4948614
4139892
4948570
4948180
4947470
4326235
548569
4948228
4947520
4296853
4948615
4143804
4948571
4948181
4947471
4327041
575554
4948229
4947521
4297436
4948616
4157071
4948572
4948182
4947472
4328316
591959
4948230
4947522
4297712
4948617
4159679
4948573
4948183
4947473
4328408
598668
4948231
4947523
4298001
4948618
4173188
4948574
4948184
4947474
4332430
602441
4948232
4947526
4298548
4948619
4178444
4948575
4948185
4947475
4336125
606605
4948233
4947527
4299510
4948620
4190733
4948598
4948186
4947476
4336978
611913
4948234
4947528
4948246
4947579
4231047
4948599
4948187
4947477
4337606
613239
4948235
4947529
4948247
4947603
4235097
4948600
4948188
4947478
4339098
615871
4948236
4947530
4948248
4947604
LXIV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
4240014
4948601
4948189
4947479
4339522
617208
4948237
4947531
4948249
4947605
4262024
4948602
4948190
4947480
4339956
629282
4948238
4947532
4347581
891935
4262300
4948603
4948191
4947481
4340116
646765
4948240
4947533
4347659
895847
4262485
4948604
4948192
4947482
4342930
647923
4948241
4947534
4348605
988952
4263158
4948605
4948193
4947483
4345073
658259
4948242
4947535
4349589
4947657
4266177
4948607
4948194
4947484
4345505
740516
4948243
4947537
4948198
4947488
4266761
4948608
4948195
4947485
4345787
749061
4948244
4947538
4948199
4947489
4289653
4948609
4948196
4947486
4345880
863181
4948245
4947539
4948200
4947490
4291783
4948610
4948197
4947487
4292272
4948613
4291880
4948612
4291857
4948611
4947698
4948277
4947773
4947149
4944733
4941880
4550270
4941700
4947044
4943779
1016211
4948278
4947775
4947150
4944734
4941881
4560033
4941707
4947079
4943780
1019493
4948279
4947776
4947151
4944736
4941884
4560428
4941708
4947080
4943781
1029322
4948280
4947777
4947152
4944737
4941885
4561187
4941709
4947081
4943784
1033739
4948281
4947779
4947163
4944738
4941887
4566211
4941710
4947082
4943785
1039487
4948282
4947816
4947165
4944739
4941889
4568392
4941711
4947083
4943786
1040116
4948283
4947817
4947166
4944740
4941977
4568878
4941713
4947084
4943788
1046204
4948284
4947818
4947167
4944741
4941978
4569215
4941714
4947085
4943790
1047517
4948285
4947819
4947168
4944744
4941979
4575011
4941715
4947086
4943792
1050803
4948287
4947820
4947169
4944745
4941981
4575154
4941780
4947087
4943794
1050863
4948288
4947821
4947170
4944746
4941982
4580065
4941783
4947088
4943859
1062433
4948289
4947823
4947171
4944748
4941983
4602820
4941784
4947089
4943860
1071558
4948290
4947824
4947172
4944750
4941986
4604183
4941785
4947090
4943864
1110499
4948291
4947825
4947173
4944753
4941988
4605077
4941787
4947091
4943865
1150251
4948292
4947826
4947174
4944754
4941992
4611583
4941791
4947092
4943871
1155637
4948293
4947827
4947205
4944755
4941993
4635279
4941797
4947093
4943872
1157207
4948295
4947828
4947206
4944781
4941996
4649607
4941871
4947094
4943873
1160131
4948296
4947829
4947207
4944836
4941997
465562
4941872
4947095
4943875
1168172
4948297
4947865
4947208
4944837
4941998
4669682
4941873
4947096
4943880
1172952
4948298
4947866
4947209
4944839
4942000
4690884
4941874
4947097
4943922
1177273
4948299
4947867
4947210
4944842
4942156
4701208
4941875
4947098
4943923
1178025
4948300
4947868
4947211
4944846
4942159
4702596
4941877
4947116
4943924
1181715
4948301
4947869
4947212
4944890
4942161
471016
4941257
4947118
4943925
1184177
4948302
4947870
4947213
4944893
4942162
4721847
4941264
4947119
4943926
1195839
4948303
4947871
4947214
4944904
4942163
4731581
4941266
4947120
4943930
1198396
4948304
4947872
4947215
4944932
4942165
4735898
4941268
4947121
4943932
1203783
4948306
4947873
4947216
4944939
4942167
4738596
4941269
4947123
4943934
1205930
4948307
4947874
4947217
4944989
4942168
4740054
4941270
4947124
4943936
1207770
4948308
4947875
4947218
4944996
4942169
4740811
4941272
4947125
4943937
1231527
4948309
4947876
4947219
4945011
4942170
4745391
4941275
4947126
4943939
1235526
4948310
4947877
4947220
4945017
4942171
4745578
4941277
4947127
4943941
1436203
4948311
4947878
4947230
4945018
4942175
4747789
4941278
4947128
4943942
1457148
4948312
4947919
4947232
4945020
4942178
4752490
4941279
4947129
4943948
1457225
4948313
4947920
4947233
4945030
4942247
4752887
4941280
4947142
4943950
1457818
4948314
4947921
4947235
4945036
4942251
4764276
4941282
4947143
4943951
1457820
4948315
4947922
4947237
4945060
4942279
4772353
4941284
4947144
4943952
1533019
4948316
4947923
4947238
4945063
4942282
4787173
4941287
4947145
4943953
1573231
4948317
4947925
4947239
4945065
4942283
4790967
4941289
4947146
4943955
1577430
4948318
4947926
4947240
4945067
4942304
4801136
4941290
4947147
4943956
LXV
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
1585355
4948319
4947927
4947241
4945068
4942306
4802652
4941291
4947148
4943957
1589711
4948320
4947928
4947242
4945069
4942307
4823262
4941292
4388644
4943958
1655444
4948321
4947929
4947243
4945071
4942309
4825338
4941293
4389070
4943959
1666268
4948322
4947930
4947244
4945075
4942311
4825720
4941295
4389626
4943960
1675258
4948323
4947931
4947245
4945076
4942312
4827713
4941296
4389627
4943961
1689366
4948324
4947932
4947275
4945080
4942313
4828341
4941299
4393002
4943962
1693800
4948325
4947933
4947276
4945081
4942314
4837124
4941302
4393091
4943964
1726534
4948326
4947937
4947277
4945084
4942316
4841066
4941303
4393545
4943965
1734774
4948327
4947938
4947278
4945086
4942320
4860634
4941308
4394660
4943966
1735836
4948328
4947939
4947279
4945091
4942323
4868812
4941309
4395155
4943967
1759021
4948329
4947940
4947280
4945102
4942324
4882501
4941313
4397168
4944145
1759382
4948330
4947941
4947281
4945105
4942325
4911786
4941320
4397170
4944147
1760075
4948335
4947942
4947282
4945106
4942326
4925504
4941322
4399544
4944148
1760390
4948336
4947943
4947283
4945107
4942329
4940943
4941323
4400383
4944151
1760397
4948337
4947944
4947284
4945113
4942331
4940946
4941327
4402033
4944152
1763482
4948338
4947945
4947285
4945116
4942332
4940949
4941328
4402340
4944153
1765216
4948339
4947946
4947286
4945118
4942333
4940950
4941331
4414610
4944158
1766188
4948340
4947947
4947287
4945119
4942334
4940951
4941332
4421420
4944159
1768182
4948342
4947948
4947288
4945120
4942338
4940953
4941333
4421814
4944161
1800285
4948343
4947949
4947289
4945121
4942341
4940959
4941334
4423753
4944163
1866419
4948344
4947950
4947290
4945122
4942346
4940966
4941337
4424564
4944165
1876441
4948346
4947951
4947291
4945123
4942347
4940969
4941338
4428098
4944166
1928573
4948347
4947952
4947293
4945124
4942349
4940972
4941339
4428556
4944465
1930841
4948348
4947983
4947294
4945128
4942370
4940973
4941341
4429864
4944468
1933097
4948351
4947984
4947295
4945132
4942375
4940974
4941342
4432591
4944469
194067
4948353
4947985
4947297
4945133
4942378
4940975
4941343
4435487
4944470
1952145
4948354
4947986
4947298
4945134
4942381
4940976
4941345
4437429
4944472
1953874
4948355
4947987
4947299
4945135
4942382
4940977
4941348
4443804
4944474
1966495
4948356
4947988
4947300
4945141
4942383
4940978
4941353
4446236
4944477
1989950
4948357
4947989
4947301
4945143
4942384
4940979
4941358
4455300
4944479
1991173
4948358
4947991
4947302
4945156
4942385
4940983
4941360
4455775
4944482
1994721
4948359
4947992
4947303
4945162
4942386
4940986
4941362
4458084
4944483
1999661
4948361
4947993
4947304
4945163
4942388
4940987
4941363
4458232
4944583
2015596
4948362
4947994
4947305
4945165
4942389
4940990
4941364
4461689
4944586
2017597
4948363
4947995
4947306
4945166
4942390
4940992
4941367
4466667
4944588
2021125
4948364
4948004
4947307
4945167
4942414
4940993
4941368
4468382
4944589
2023172
4948365
4948005
4947308
4945193
4942416
4940995
4941373
4469050
4944590
2023413
4948366
4948006
4947309
4945200
4942422
4940996
4941374
4474837
4944591
2036356
4948367
4948007
4947310
4945201
4942424
4941000
4941375
4481056
4944592
2039057
4948368
4948008
4947311
4945204
4942428
4941002
4941377
4487506
4944593
2051784
4948369
4948009
4947312
4945205
4942430
4941004
4941379
4489237
4944597
2055086
4948371
4948010
4947313
4945212
4942431
4941005
4941380
4489772
4944598
2056537
4948372
4948011
4947314
4945236
4942432
4941006
4941383
4490354
4944600
2061182
4948373
4948012
4947315
4945237
4942434
4941007
4941386
4490449
4944601
2061422
4948374
4948013
4947316
4945279
4942436
4941008
4941387
4492191
4944603
2061561
4948375
4948014
4947317
4945286
4942454
4941009
4941390
4496631
4944604
2063060
4948376
4948015
4947318
4945315
4942524
4941016
4941391
4498882
4944731
2113515
4948377
4948016
4947319
4945321
4942538
4941018
4941392
4499501
4374970
LXVI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
2113530
4948378
4948025
4947320
4945326
4942540
4941019
4941393
452687
4375238
2113659
4948379
4948026
4947321
4945379
4942542
4941021
4941396
4531331
4377416
2114236
4948380
4948027
4947322
4945385
4942547
4941025
4941400
4533599
4377635
2303433
4948381
4948028
4947323
4945388
4942548
4941026
4941401
4534977
4377831
2338751
4948382
4948029
4947324
4945404
4942549
4941027
4941403
4537145
4378841
2362114
4948383
4948030
4947325
4945418
4942580
4941030
4941404
4538528
4380919
2375285
4948384
4948032
4947326
4945441
4942581
4941032
4941405
4540422
4382409
2457324
4948385
4948033
4947327
4945444
4942582
4941034
4941407
4548071
4382411
2466449
4948386
4948034
4947329
4945453
4942585
4941035
4941409
4548314
4384048
2521268
4948387
4948035
4947330
4945511
4942588
4941038
4941411
4549483
4947034
2522503
4948388
4948036
4947331
4945512
4942590
4941040
4941412
4947695
4947035
2524040
4948389
4948037
4947332
4945525
4942595
4941041
4941415
4947697
4374603
2524248
4948390
4948038
4947333
4945557
4942596
4941042
4941416
4946796
4943347
2536666
4948391
4948039
4947335
4945562
4942597
4941044
4941421
4946797
4943348
2563719
4948392
4948040
4947336
4945564
4942598
4941045
4941422
4946798
4943350
2565690
4948393
4948041
4947337
4945568
4942647
4941046
4941423
4946799
4943396
2592746
4948394
4948042
4947338
4945610
4942660
4941047
4941426
4946800
4943397
2594197
4948395
4948043
4947339
4945626
4942664
4941048
4941431
4946801
4943398
2594309
4948396
4948044
4947340
4945630
4942692
4941050
4941437
4946802
4943404
2595846
4948397
4948045
4947341
4945635
4942695
4941059
4941438
4946803
4943405
2604429
4948399
4948046
4947342
4945640
4942696
4941061
4941440
4946804
4943406
2615236
4948400
4948047
4947344
4945643
4942698
4941063
4941443
4946807
4943407
2647504
4948401
4948048
4947345
4945653
4942699
4941064
4941448
4946811
4943408
2648592
4948402
4948049
4947346
4945683
4942700
4941065
4941449
4946813
4943409
2665770
4948403
4948051
4947347
4945727
4942701
4941066
4941450
4946815
4943410
2673392
4948404
4948052
4947348
4945731
4942702
4941067
4941451
4946820
4943411
2675088
4948405
4948054
4947349
4945734
4942704
4941070
4941452
4946821
4943412
2683055
4948406
4948055
4947350
4945737
4942706
4941071
4941456
4946822
4943414
2693859
4948407
4948056
4947351
4945740
4942707
4941072
4941460
4946824
4943415
2742638
4948408
4948057
4947352
4945742
4942709
4941073
4941465
4946825
4943459
2748861
4948410
4948058
4947353
4945775
4942755
4941075
4941466
4946826
4943460
2750435
4948411
4948059
4947354
4945783
4942760
4941077
4941468
4946827
4943462
2750990
4948412
4948060
4947355
4945822
4942761
4941079
4941469
4946828
4943463
2810934
4948413
4948061
4947356
4945825
4942762
4941080
4941470
4946829
4943465
2833030
4948414
4948062
4947357
4945830
4942763
4941083
4941472
4946830
4943467
2861950
4948415
4948063
4947358
4945832
4942768
4941084
4941476
4946831
4943469
2864545
4948416
4948064
4947359
4945904
4942769
4941087
4941477
4946832
4943472
2864817
4948417
4948065
4947360
4945906
4942770
4941088
4941479
4946833
4943474
2880619
4948418
4948066
4947361
4945922
4942772
4941091
4941481
4946834
4943477
2880620
4948419
4948067
4947362
4945925
4942774
4941092
4941482
4946835
4943480
2880624
4948420
4948068
4947363
4945975
4942824
4941093
4941486
4946836
4943525
2893306
4948423
4948070
4947364
4946069
4942880
4941095
4941489
4946837
4943527
2915743
4948424
4948071
4947365
4946073
4942934
4941100
4941490
4946838
4943528
2982625
4948425
4948072
4947366
4946080
4942935
4941101
4941493
4946839
4943529
2984623
4948426
4948073
4947367
4946158
4942937
4941102
4941494
4946840
4943532
3007069
4948427
4948074
4947368
4946172
4942938
4941103
4941496
4946843
4943534
3015522
4948428
4948075
4947369
4946277
4942940
4941104
4941497
4946844
4943536
3022174
4948429
4948076
4947370
4946279
4942941
4941105
4941498
4946849
4943538
LXVII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
3028004
4948430
4948077
4947371
4946447
4942943
4941107
4941499
4946858
4943539
3039688
4948431
4948078
4947372
4946577
4942944
4941110
4941501
4946859
4943542
3068597
4948433
4948079
4947373
4946578
4942947
4941112
4941502
4946873
4943544
3069497
4948441
4948080
4947374
4946579
4942950
4941113
4941506
4946878
4943546
3088505
4948442
4948081
4947375
4946580
4942951
4941114
4941508
4946879
4943573
3115335
4948443
4948082
4947376
4946581
4942952
4941117
4941514
4946880
4943575
3116865
4948444
4948083
4947377
4946582
4942953
4941118
4941515
4946881
4943576
3120121
4948445
4948084
4947378
4946583
4942954
4941120
4941518
4946882
4943578
3163432
4948446
4948085
4947379
4946584
4942955
4941121
4941519
4946883
4943579
3169252
4948447
4948086
4947380
4946585
4943106
4941122
4941520
4946884
4943584
3173200
4948448
4948087
4947381
4946586
4943110
4941130
4941523
4946885
4943585
3212876
4948449
4948088
4947382
4946624
4943113
4941131
4941527
4946886
4943587
3213885
4948450
4948089
4947383
4946625
4943114
4941133
4941528
4946887
4943592
3228265
4948451
4948090
4947384
4946627
4943116
4941142
4941531
4946888
4943593
3268792
4948452
4948092
4947385
4946628
4943119
4941143
4941532
4946889
4943594
3328916
4948463
4948093
4947386
4946629
4943122
4941144
4941535
4946890
4943595
3346350
4948464
4948094
4947387
4946630
4943123
4941145
4941539
4946891
4943640
3374260
4948465
4948095
4947388
4946631
4943125
4941147
4941541
4946892
4943642
3379967
4948466
4948096
4947389
4946632
4943149
4941148
4941549
4946893
4943644
3391658
4948467
4948097
4947390
4946633
4943153
4941150
4941550
4946894
4943649
3398035
4948468
4948098
4947391
4946634
4943154
4941151
4941551
4946895
4943651
3410241
4948469
4948099
4947392
4946635
4943156
4941157
4941556
4946896
4943652
3425319
4948470
4948100
4947393
4946636
4943160
4941158
4941557
4946897
4943654
3430301
4948471
4948101
4947394
4946637
4943161
4941160
4941561
4946898
4943655
3453603
4948472
4948102
4947395
4946638
4943162
4941162
4941564
4946899
4943657
3457917
4948473
4948103
4947396
4946664
4943163
4941163
4941565
4946900
4943662
3458439
4948474
4948104
4947397
4946665
4943164
4941164
4941568
4946901
4943727
3459150
4948485
4948105
4947398
4946666
4943166
4941166
4941573
4946902
4943728
3459165
4948486
4948106
4947399
4946667
4943167
4941168
4941576
4946903
4946955
3460447
4948487
4948107
4947400
4946668
4943168
4941169
4941577
4946904
4946958
3468890
4948488
4948108
4947401
4946669
4943170
4941170
4941582
4946905
4946960
3472099
4948489
4948109
4947402
4946670
4943215
4941175
4941587
4946908
4946962
3472209
4948490
4948110
4947403
4946671
4943219
4941176
4941588
4946913
4946964
3487563
4948491
4948111
4947404
4946672
4943222
4941177
4941589
4946916
4946965
3578984
4948492
4948112
4947405
4946673
4943223
4941179
4941596
4946917
4946967
3602591
4948493
4948113
4947406
4946674
4943225
4941181
4941600
4946921
4946968
3651958
4948494
4948114
4947407
4946675
4943226
4941188
4941602
4946922
4946969
3652834
4948495
4948115
4947408
4946676
4943229
4941189
4941605
4946923
4946970
3673708
4948498
4948117
4947409
4946677
4943230
4941191
4941606
4946924
4946971
3695614
4948499
4948118
4947410
4946678
4943231
4941193
4941609
4946925
4946972
3701231
4948500
4948119
4947412
4946679
4943232
4941194
4941610
4946926
4946973
3702762
4948501
4948120
4947413
4946680
4943233
4941196
4941611
4946927
4946974
3721521
4948502
4948121
4947414
4946681
4943236
4941198
4941613
4946928
4946975
3725946
4948503
4948122
4947415
4946682
4943262
4941201
4941615
4946929
4946976
3730534
4948504
4948123
4947416
4946684
4943263
4941202
4941620
4946930
4946977
3732912
4948505
4948124
4947417
4946685
4943264
4941203
4941631
4946938
4946978
3736162
4948506
4948125
4947418
4946686
4943265
4941204
4941634
4946947
4946979
3736910
4948507
4948126
4947419
4946687
4943266
4941209
4941636
4948264
4946980
LXVIII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
3760441
4948508
4948127
4947420
4946688
4943268
4941211
4941638
4948265
4946981
3766605
4948509
4948128
4947421
4946689
4943269
4941213
4941640
4948266
4946982
3810924
4948510
4948129
4947422
4946690
4943270
4941223
4941643
4948268
4946983
3814826
4948511
4948130
4947423
4946715
4943272
4941224
4941644
4948269
4946986
3814978
4948512
4948131
4947424
4946720
4943275
4941226
4941645
4948270
4946988
382373
4948513
4948132
4947425
4946721
4943277
4941228
4941646
4948271
4946990
3844770
4948514
4948133
4947426
4946727
4943278
4941231
4941648
4948272
4946995
3845301
4948515
4948134
4947427
4946728
4943280
4941232
4941693
4948273
4947002
3890547
4948516
4948135
4947428
4946745
4943283
4941233
4941694
4948274
4947003
3896824
4948517
4948136
4947429
4946746
4943284
4941234
4941695
4948275
4947008
3997235
4948518
4948137
4947430
4946747
4943285
4941236
4941697
4948276
4947011
3999296
4948519
4948138
4947431
4946748
4943289
4941237
4941698
4947699
4947012
4000271
4948520
4948139
4947432
4946749
4943291
4941238
4941699
4947700
4947023
4000746
4948521
4948140
4947433
4946750
4943293
4941239
4943729
4947701
4947025
4000887
4948522
4948141
4947434
4946751
4943298
4941242
4943732
4947771
4947031
4001578
4948523
4948142
4947435
4946752
4943300
4941243
4943734
4947772
4947032
4001654
4948525
4948143
4947436
4946753
4943303
4941244
4943735
4948250
4947606
4002230
4948526
4948144
4947437
4946754
4943304
4941245
4943736
4948251
4947607
4002590
4948527
4948145
4947438
4946755
4943305
4941247
4943738
4948254
4947608
4060629
4948528
4948147
4947439
4946756
4943307
4941248
4943739
4948255
4947609
4072033
4948529
4948148
4947440
4946764
4943331
4941250
4943740
4948256
4947610
4072901
4948530
4948149
4947441
4946771
4943333
4941251
4943741
4948257
4947611
4073919
4948531
4948150
4947442
4946773
4943336
4941252
4943742
4948258
4947612
4074665
4948532
4948151
4947443
4946778
4943337
4941253
4943743
4948259
4947613
4075996
4948533
4948152
4947444
4946780
4943338
4941255
4943745
4948260
4947614
4076964
4948534
4948153
4947445
4946781
4943339
4947036
4943750
4948261
4947615
4077417
4948535
4948154
4947446
4946785
4943341
4947037
4943772
4948262
4947637
4077717
4948536
4948155
4947447
4946790
4943342
4947038
4943773
4948263
4947655
4078894
4948537
4948156
4947448
4946793
4943343
4947039
4943774
4947033
4947694
4078912
4948538
4948157
4947449
4946794
4943344
4947040
4943776
4361132
4947671
4079654
4948541
4948158
4947450
4946795
4943346
4947041
4943778
4364365
4947674
4079719
4948542
4948159
4947451
4301328
4948621
4948208
4947500
4372651
4947676
4079990
4948543
4948160
4947452
4304269
4948622
4948209
4947501
4372807
4947689
4080001
4948544
4948161
4947453
4305966
4948623
4948210
4947502
4373863
4947691
4081443
4948545
4948162
4947454
4306562
4948645
4948211
4947504
4374940
4947692
4081645
4948546
4948163
4947455
4306578
4949331
4948212
4947505
4351902
4947662
4081873
4948547
4948165
4947456
4307324
4949337
4948213
4947506
4352597
4947665
4084810
4948548
4948166
4947457
4316595
4949345
4948214
4947507
4353385
4947666
4097819
4948549
4948167
4947458
4316812
4949346
4948215
4947508
4353505
4947667
4114369
4948550
4948168
4947459
4318136
4949347
4948216
4947509
4353835
4947668
4116098
4948552
4948169
4947460
4318925
4949348
4948217
4947510
4357745
4947669
4117629
4948553
4948170
4947461
4320317
4949349
4948218
4947511
4360490
4947670
4117928
4948554
4948171
4947462
4320976
4949350
4948220
4947512
4948201
4947491
4122451
4948563
4948172
4947463
4321430
4949352
4948221
4947513
4948202
4947492
4124988
4948564
4948173
4947464
4322919
4949353
4948222
4947514
4948203
4947493
4126830
4948565
4948174
4947465
4323216
495092
4948223
4947515
4948204
4947495
4126895
4948566
4948175
4947466
4323406
4955505
4948224
4947516
4948205
4947497
4127815
4948567
4948177
4947467
4324327
507820
4948225
4947517
4948206
4947498
LXIX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.11: Off-Topic References Excluded at Initial Screening for Fate
4129992
4948568
4948178
4947468
4325158
522256
4948226
4947518
4948207
4947499
4136697
4948569
4948179
4947469
4326156
537490
4948227
4947519
4294080
4948614
4139892
4948570
4948180
4947470
4326235
548569
4948228
4947520
4296853
4948615
4143804
4948571
4948181
4947471
4327041
575554
4948229
4947521
4297436
4948616
4157071
4948572
4948182
4947472
4328316
591959
4948230
4947522
4297712
4948617
4159679
4948573
4948183
4947473
4328408
598668
4948231
4947523
4298001
4948618
4173188
4948574
4948184
4947474
4332430
602441
4948232
4947526
4298548
4948619
4178444
4948575
4948185
4947475
4336125
606605
4948233
4947527
4299510
4948620
4190733
4948598
4948186
4947476
4336978
611913
4948234
4947528
4948246
4947579
4231047
4948599
4948187
4947477
4337606
613239
4948235
4947529
4948247
4947603
4235097
4948600
4948188
4947478
4339098
615871
4948236
4947530
4948248
4947604
4240014
4948601
4948189
4947479
4339522
617208
4948237
4947531
4948249
4947605
4262024
4948602
4948190
4947480
4339956
629282
4948238
4947532
4347581
891935
4262300
4948603
4948191
4947481
4340116
646765
4948240
4947533
4347659
895847
4262485
4948604
4948192
4947482
4342930
647923
4948241
4947534
4348605
988952
4263158
4948605
4948193
4947483
4345073
658259
4948242
4947535
4349589
4947657
4266177
4948607
4948194
4947484
4345505
740516
4948243
4947537
4948198
4947488
4266761
4948608
4948195
4947485
4345787
749061
4948244
4947538
4948199
4947489
4289653
4948609
4948196
4947486
4345880
863181
4948245
4947539
4948200
4947490
4291783
4948610
4948197
4947487
4292272
4948613
4291880
4948612
4291857
4948611
Reference excluded (HERO ID) because the reference primarily contained in silico data
N/A.
LXX
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.12: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate
Question
Off-topic if answer is:
References excluded (HERO ID)
Does the reference contain
No
2072857
information pertaining to a low-
2087723
priority substance candidate?
2952166
4940068
4940982
4941471
4941530
4942773
4942837
4943107
4943577
4943581
4943928
4944476
4944582
4947122
4948176
What type of source is this
Review article or book chapter that
N/A.
reference?
contains only citations to primary
literature sources
Is quantitative fate data presented?
No
4943165
Is this primarily a
Yes
N/A.
modeling/simulation study? [Note:
Select "Yes" only if there is no
experimental verification]
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Data quality metric
Unacceptable if:
References excluded (HERO ID)
Metric 1:
The test substance identity or
N/A.
Test substance identity
description cannot be determined
from the information provided (e.g.,
nomenclature was unclear and
CASRN or structure were not
reported).
OR
For mixtures, the components and
ratios were not characterized or did
not include information that could
result in a reasonable approximation
of components.
Metric 2:
The study did not include or report
4940081
Study controls
crucial control groups that
4940201
consequently made the study
unusable (e.g., no positive control
for a biodegradation study reporting
0% removal).
OR
LXXI
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
The vehicle used in the study was
likely to unduly influence the study
results.
Metric 3:
Test substance stability
There were problems with test
substance stability, homogeneity, or
preparation that had an impact on
concentration or dose estimates and
interfered with interpretation of study
results.
N/A.
Metric 4:
Test method suitability
The test method was not reported
or not suitable for the test
substance.
OR
The test concentrations were not
reported.
OR
The reported test concentrations
were not measured and the nominal
concentrations reported greatly
exceeded the substances water
solubility, which would greatly inhibit
meaningful interpretation of the
outcomes.
N/A.
Metric 5:
Testing conditions
Testing conditions were not reported
and the omission would likely have a
substantial impact on study results.
OR
Testing conditions were not
appropriate for the method (e.g., a
biodegradation study at
temperatures that inhibit the
microorganisms).
4940201
Metric 6:
System type and design-
partitioning
Equilibrium was not established or
reported, preventing meaningful
interpretation of study results.
OR
The system type and design (e.g.
static, semi-static, and flow-through;
sealed, open) were not capable of
appropriately maintaining substance
concentrations, preventing
meaningful interpretation of study
results.
4940201
Metric 7:
Test organism-degradation
The test organism, species, or
inoculum source were not reported,
preventing meaningful interpretation
of the study results.
N/A.
Metric 8:
Test organism-partitioning
The test organism information was
not reported.
OR
N/A.
LXXII
-------
***Proposal Draft - Do Not Cite, Quote or Release During the Review***
Table C.13: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
The test organism is not routinely
used and would likely prevent
meaningful interpretation of the
study results.
Metric 9:
Outcome assessment methodology
The assessment methodology did
not address or report the outcome(s)
of interest.
N/A.
Metric 10:
Data reporting
Insufficient data were reported to
evaluate the outcome of interest or
to reasonably infer an outcome of
interest.
OR
The analytical method used was not
suitable for detection or
quantification of the test substance.
OR
Data indicate that disappearance or
transformation of the parent
compound was likely due to some
other process.
4940201
4940081
Metric 11:
Confounding variables
There were sources of variability
and uncertainty in the
measurements and statistical
techniques or between study
groups.
4940201
Metric 12:
Verification or plausibility of results
Reported value was completely
inconsistent with reference
substance data, related physical
chemical properties, or otherwise
implausible, indicating that a serious
study deficiency exists (identified or
not).
N/A.
LXXIII
------- |