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Dossier for Candidate Low-Priority Substance D-gluco-Heptonic
acid, sodium salt (1:1), (2.xi.)- (CASRN 31138-65-5)
(Sodium Glucoheptonate)
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 1
2. Background on Sodium Glucoheptonate 3
3. Physical-Chemical Properties 4
3.1 References 5
4. Relevant Assessment History 6
5. Conditions of Use 7
6. Hazard Characterization 13
6.1 Human Health Hazard 16
6.1.1 Absorption, Distribution, Metabolism, and Excretion 18
6.1.2 Acute Toxicity 19
6.1.3 Repeated Dose Toxicity 19
6.1.4 Reproductive and Developmental Toxicity 19
6.1.5 Genotoxicity 20
6.1.6 Carcinogenicity 20
6.1.7 Neurotoxicity 20
6.1.8 Skin Sensitization 21
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 22
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
7.4.3 Exposures to Children 25
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 Sodium Glucoheptonate IV
A.3 References XII
Appendix B: Hazard Characterization XVI
Appendix C: Literature Search Outcomes XVI
C.1 Literature Search Review XVI
C.1.1 Search for Analog Data XVI
C.1.2 Search terms and results XVII
C.2 Excluded Studies and Rationale XIX
C.2.1 Human Health Hazard Excluded References XIX
C.2.2 Environmental Hazard XXIII
C.2.3 Fate XXV
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Tables
Table 1: Sodium Glucoheptonate at a Glance 3
Table 2: Physical-Chemical Properties for Sodium Glucoheptonate 4
Table 3: Conditions of Use for Sodium Glucoheptonate 8
Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects 13
Table 5:1 Sodium Glucoheptonate and Analog Structures 17
Table A.1:1986-2015 National Production Volume Data for Sodium Glucoheptonate (Non-Confidential I
Production Volume in Pounds)
Table A.2: Sources Searched for Uses of Sodium Glucoheptonate II
Table A.3: Uses of Sodium Glucoheptonate IV
Table B.1: Human Health Hazard XVI
Table B.2: Environmental Hazard XXVI
Table B.3: Fate XXVII
Table C.1: Search Terms Used in Peer-Reviewed Databases XVII
Table C.2: Search Terms Used in Grey Literature and Additional Sources XVIII
Table C.3: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard XIX
Table C.4: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Human XIX
Health Hazard
Table C.5: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXI
Human Health Hazard - Animal
Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXII
Human Health Hazard - In Vitro
Table C.7: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard XXIII
Table C.8: Screening Questions and Off-Topic References Excluded at Full-Text Screening for XXIII
Environmental Hazard
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Table C.9: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXIV
Environmental Hazard
Table C.10: Off-Topic References Excluded at Initial Screening for Fate XXV
Table C.11: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Fate XXV
Table C.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for XXV
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-
gluco-Heptonic acid, sodium salt (1:1), (2.xi.)-, referenced as sodium glucoheptonate 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 Sodium Glucoheptonate
Table 1 below provides the CAS number, synonyms, and other information on sodium
glucoheptonate.
Table 1: Sodium Glucoheptonate at a Glance
Chemical
Name
Sodium Glucoheptonate (D-gluco-Heptonic acid, sodium salt (1:1), (2.xi.)-)
CASRN
31138-65-5
Synonyms
alpha-D-Glucoheptonic acid sodium salt; D-Gluco-heptonic acid, monosodium salt; D-glycero-D-gulo-
Heptonic acid sodium salt; D-glycero-D-gulo-Heptonic acid, monosodium salt; Gluceptate Sodium;
Glucoheptonic Acid Sodium Salt; Glucosecarboxylic Acid Sodium Salt; Glucosecarboxylic acid
sodium salt hydrate; Glucosemonocarboxylicacid; MolPort-006-120-012; Monosodium D-glycero-D-
gulo-heptonate; potassium (2R,3R,4S,5R,6R)-2,3,4,5,6,7-hexahydroxyheptanoate; sodium
(2R,3R,4S,5R,6R)-2,3,4,5,6,7-hexahydroxyheptanoate; sodium (2R,3R,4S,5R,6R)-2,3,4,5,6,7-
hexakis(oxidanyl)heptanoate; Sodium Alpha-Glucoheptonate; Sodium D-glycero-D-gulo-heptonate;
sodium glucopentonate; Monosodium D-glucoheptonate; Sodium glucoheptonate dihydrate
Trade Name(s)
SEQLENE 540; SEQLENE ES-50; H-Quest L-50 LA; Milco 150
Molecular
Formula
C7Hi3Na08
Representative
Structure
% oH 0
H JL Na +
1 C. ; 0
H'6 H-8 ®-«
Sodium glucoheptonate belongs to the hydroxycarboxylic acid salt family. The chemical structure of
sodium glucoheptonate consists of a seven-carbon chain with 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, by binding to positively charged metal ions in
solution and thereby prevent these ions from forming insoluble precipitates with other ions that may
be present. Sodium glucoheptonate functions as a chelating agent over a wide pH range due to its
efficiency in forming stable chelates with divalent and trivalent metal ions such as calcium,
magnesium, iron, aluminum, and other metals, thereby reducing the adverse effects these metals can
have on systems. These properties contribute to the use of sodium glucoheptonate as a high
performing chelating 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 sodium glucoheptonate. 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 Sodium Glucoheptonate
Source/Model
Data Type
Endpoint
Endpoint Value
Notes
Sigma-Aldrich 2019
Experimental
State at room temperature
Solid
ECHA 2018
Experimental
Molecular weight
248 g/mol
EPISuite v.4.113
Calculated
Molecular weight
248.17 g/mol
ECHA 2018
Experimental
Molar volume
220 cm3/mol
ECHA 2018
Experimental
Water solubility
12.63x105 to 13.87x105 mg/L at 20°C and
pH 9.7 (55.8 to 58.1% w/w)
EPISuite v.4.11
Estimated
Water solubility
1.0x106 mg/L
Kow method
ECHA 2018
Experimental
Water solubility
5.09 mol/L
EPISuite v.4.11
Estimated
Log Kow
-6.44
EPISuite v.4.11
Estimated
Log Koa
5.59
EPISuite v.4.11
Estimated
Log Koc
1.0(MCI); -4.23 (Kow)
EPISuite v.4.11
Estimated
Vapor pressure
1.20x10"19 mm Hg
EPISuite v.4.11
Estimated
Henry's Law
2.31x10-14atm-m3/mol
Bond method
EPISuite v.4.11
Estimated
Volatilization
1.66x109 days (river)
1.82x1010 days (lake)
EPISuite v.4.11
Estimated
Photolysis (indirect)
2.64h min (T1/2)
OH rate constant 4.85E-11 cm3/molecules-
sec (12 hour day; 1.5E6 OH/cm3)
EPISuite v.4.11
Estimated
Hydrolysis
Rate constants cannot be estimated
No hydrolysable 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 equation
3 EPI Suite Physical Property Inputs -Water solubility= 1263000 mg/L, SMILES: [0-]C(=0)C(0)C(0)C(0)C(0)C(0)C0.[Na+]
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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 state, sodium glucoheptonate is a solid
at ambient temperatures (Sigma-Aldrich, 2019). In the solid form, sodium glucoheptonate has the
potential for exposure via direct dermal exposure, through ingestion or through inhalation of dust
particles if they are generated. Since it is a salt, sodium glucoheptonate is expected to be non-volatile
at ambient temperatures (US EPA, 2019). Based on measured solubility data (ECHA, 2018), sodium
glucoheptonate is considered water soluble, indicating the potential for this substance to dissolve in
water and form an aqueous solution. The estimated Henry's Law constant (US EPA, 2019) for
sodium glucoheptonate indicates volatilization from water and aqueous solutions is not expected to
occur, and therefore exposure via inhalation of vapors under ambient conditions is expected to be
minimal. Water soluble substances have an increased potential for absorption through the lungs;
therefore, if exposed to the chemical in dust form, absorption through the lungs is likely. Oral
exposure to this chemical could result in absorption through the gastrointestinal tract based on
experimental evidence in closely-related analogs (discussed in Section 6.1.1). However, based on its
estimated log K0W(US EPA, 2019), sodium glucoheptonate is unlikely to sequester in fatty tissues
(also discussed in Section 6.3.2). The estimated log Koc (US EPA, 2019) indicates this substance is
highly mobile in soils, increasing its potential for leaching into, and transport in, groundwater,
including well water. Sodium glucoheptonate is expected to have low persistence (US EPA, 2019).
Experimental biodegradation data for sodium glucoheptonate are not available; however, the
measured biodegradation data for, sodium gluconate, a closely-related analog, indicate it can be
considered readily biodegradable, and ultimately degradable anaerobically (OECD SIDS, 2004,
2072857), meaning that if it were to enter groundwater, it is likely to be broken down into carbon
dioxide and water.
3.1 References
European Chemicals Agency (ECHA). (2018). Sodium glucoheptonate. Retrieved from
https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/8874
Sigma-Aldrich. (2019). Sodium glucoheptonate. Retrieved from.
https://www.sigmaaldrich.com/catalog/buildingblock/product/chemimpexinternationalinc/ch6
hi le4f2d5?lang=en®ion=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/production/files/2015-05/documents/05.pdf
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4. Relevant Assessment History
EPA assessed the toxicological profile of sodium glucoheptonate and added the chemical to the Safer
Choice Program's Safer Chemical Ingredients List (SCIL) in September 2012 under the functional
classes of chelating agents. The SCIL5 is a continuously updated list of chemicals that meet low-
concern Safer Choice criteria.6
In 2011, EPA included sodium glucoheptonate in a test rule under TSCA section 4(a)(1)(B), based on
the potential for exposures of workers and consumers to these chemicals, that required manufacturers
and processors of this and other high production volume (HPV) chemical substances to develop
screening-level health, environmental, and fate data.7 HPV chemicals are chemicals produced or
imported in the United States in quantities of 1 million pounds or more per year. Relevant data
submitted to the agency under this test rule has been incorporated in the Agency's screening review.
EPA also reviewed international assessments of sodium glucoheptonate. EPA identified assessments
by Canada's and Germany's government agencies.
The Canadian Government, through an assessment of toxicity and exposure as part of its
categorization of the Domestic Substance List, found that sodium glucoheptonate did not meet its
criteria for further attention.8
The German Environment Agency (UBA) designated sodium glucoheptonate as "low hazard to
waters" in August 2017 based on an assessment of ecotoxicity and environmental fate.9
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://www.federalregister.gov/docimients/2011/10/21/2011-26894/certain-high-prodiiction-volimie-cheniicals-test-iiile-
and-significant-new-iise-riile-foiirth-groiip-of
8 https://canadachemicals.oecd. org/CliemicalDetails.aspx?ChemicalID=D7922D37-AlB84327-9E5847D212E52C0B
9 https://webrigoletto.iiba.de/rigoletto/piiblic/searchDetail.do7kenniininieF7009
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5. Conditions of Use
EPA assembled information on conditions of use for sodium glucoheptonate. 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. One source of information that EPA used to
understand 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, sodium glucoheptonate is manufactured domestically and imported. Based on
CDR reporting, it is used in processing (incorporation into formulation, mixture or reaction) for use as
a raw material in internal blending of construction materials; soap, cleaning compound, and toilet
preparation manufacturing; plating agents and surface treating agents. Additionally, the commercial
use of sodium glucoheptonate for cleaning and furnishing care products was identified. Based on the
known manufacturing, processing, and uses of this chemical substance, EPA assumes distribution in
commerce. According to CDR, sodium glucoheptonate was recycled by one facility. No information
on disposal is found in CDR or through EPA's Toxics Release Inventory (TRI) Program1" since
sodium glucoheptonate 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 occupational11 and consumer uses. This research improved the Agency's
understanding of the conditions of use for sodium glucoheptonate. Although EPA identified uses of
sodium glucoheptonate 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 sodium glucoheptonate 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).
10 https://www.epa.gov/toxics-release-inventorv-tri-program
11 Occupational uses include industrial and/or commercial uses
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Table 3: Conditions of Use for Sodium Glucoheptonate
Life Cycle Stage
Category
Subcategory of Use
Source
Manufacturing
Domestic manufacture
Domestic manufacture
EPA (2017b)
Import
Import
EPA (2017b)
Processing
Processing- incorporation
into formulation, mixture or
reaction
Plating agents and surface
treating agents - resale of
chemicals
EPA (2017b)
Construction - used as a raw
material in internal blending of
construction materials
Solids separation agents - All
other chemical product and
preparation manufacturing
Plating agents and surface
treating agents -
miscellaneous manufacturing
Processing aids, not
otherwise listed - soap,
cleaning compound, and toilet
preparation manufacturing
Ion exchange agents -
Nonmetallic mineral product
manufacturing (includes clay,
glass, cement, concrete, lime,
gypsum, and other
nonmetallic mineral product
manufacturing, Soap,
cleaning compound, and toilet
preparation manufacturing,
Pesticide,12 fertilizer, and
other agricultural chemical
manufacturing, Oil and gas
drilling, extraction, and
12 EPA's 2016 CDR reports use of sodium glucoheptonate as an ion exchange agent during the processing phase (incorporation into formulation, mixture, or reaction product) of
manufacturing. Sodium glucoheptonate is not registered with the California Department of Pesticide Regulation or the National Pesticide Information Retrieval System.
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Table 3: Conditions of Use for Sodium Glucoheptonate
Life Cycle Stage
Category
Subcategory of Use
Source
support activities
Processing repackaging
Solids separation agents - All
other chemical product and
preparation manufacturing
Primary metal manufacturing
Manufacture of metal
products, treatment and
coating of metals
CPCat (2019); ECHA (2018b)
Plastics product
manufacturing
Manufacture of plastics
products, including
compounding and conversion
ECHA (2018b)
Furniture and related
Manufacture of furniture
ECHA (2018b)
product manufacturing
Rubber product
manufacturing
Manufacture of rubber
products
ECHA (2018b); Synapse Information Resources (n.d.)
Textiles, apparel, and
leather manufacturing
Manufacture of textiles,
leather and fur
CPCat (2019); ECHA (2018b)
All other chemical product
and preparation
manufacturing
Printing and reproduction of
recorded media
All other chemical product and preparation
manufacturing
Electrical and electronic
products
Manufacture of computer,
electronic and optical
products, electrical equipment
ECHA (2018b); ECHA (2018c); Synapse Information
Resources (n.d.)
Recycling
Recycling
EPA (2017b)13
Distribution
Distribution
Distribution
EPA (2017b)
Agriculture, forestry, fishing
and hunting14
Chelating agent
CPCat (2019), ECHA (2018b)
13 According to CDR reports, at least one manufacturer recycles the chemical substance. No other information on recycling was identified.
14 Assumed to be a mix of TSCA and non-TSCA products. It is expected that more specifically defined uses in the table are representative of the uses that fall into this category.
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Table 3: Conditions of Use for Sodium Glucoheptonate
Life Cycle Stage
Category
Subcategory of Use
Source
Mining (except oil and gas)
and support activities
Mining
ECHA (2018b)
Industrial/Commercial uses
Oil and Gas Exploration
Oil and gas drilling, extraction,
and support activities;
extraction agents
EPA (2017b); ECHA (2018c); ECHA (2018b)
Odor Agents
Air care products
ECHA (2018c); ECHA (2018b)
Laundry and dishwashing
care products
Laundry booster
Alco-Chem Inc. (2015b); Alco-Chem Inc. (2015a)
Agricultural products (non-
pesticidal)
Plant protection products
ECHA (2018c); ECHA (2018b)
Adsorbents
Chelating agent
ECHA (2018c); ECHA (2018b)
Anti-freeze and de-icing
products
Anti-freeze and de-icing
products
ECHA (2018c); ECHA (2018b)
Explosive materials
Explosives
ECHA (2018c); ECHA (2018b)
Fuels and related products
Fuels, Heat transfer fluids,
Hydraulic fluids
ECHA (2018c); ECHA (2018b)
Other
Laboratory chemicals,
intermediates
ECHA (2018c); ECHA (2018b)
Industrial/commercial/consumer uses
Fabric, textile, and leather
products not covered
elsewhere
Leather treatment products
ECHA (2018a); ECHA (2018c); ECHA (2018b)
Cleaning and furnishing care
products
Degreaser, Polishes and wax
blends15
EPA (2017b); CPCat (2019); ECHA (2018a); ECHA
(2018c); ECHA (2018b)
Laundry and dishwashing
care products
Cleaning/washing agents for
dish washing machines
CPCat (2019)
15 One manufacturer reported 100% commercial use for cleaning and furnishing care products to the 2016 CDR (EPA (2017b)). While specific products are not identified on the
CDR, other sources seem to suggest me in degreasers, polishes, and wax blends.
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Table 3: Conditions of Use for Sodium Glucoheptonate
Life Cycle Stage
Category
Subcategory of Use
Source
Paints and coatings
Coatings and paints, thinners,
paint removers,
ECHA (2018a); ECHA (2018c); ECHA (2018b);
Synapse Information Resources (n.d.)
Adhesives and sealants
Chelating agent
ECHA (2018)
Lubricants and greases
Lubricants, greases, release
products
ECHA (2018a); ECHA (2018c); ECHA (2018b)
Lawn and garden products
Fertilizers
ECHA (2018a): ECHA (2018b): ECHA (2018c)
Odor Agents
Fragrances
ECHA (2018); CPCat (2019)
Other
Fluid property modulator,
Food-contact
paper/paperboard
manufacturing, Electricity,
steam, gas, water supply and
sewage treatment
CPCat (2019), Synapse Information Resources (n.d.);
ECHA (2018a); ECHA (2018c); ECHA (2018b)
Ink, toner, and colorant
products
Ink and toners
ECHA (2018a); ECHA (2018c); ECHA (2018b)
Photographic supplies, film,
and photo chemicals
Photo-chemicals
ECHA (2018a); ECHA (2018c); ECHA (2018b)
Commercial/consumer uses
Plating agents and surface
treating agents
C909 the product is used as a
cleaner in plating processes.
The processes are diverse,
examples of final uses are:
automotive, machinery,
basically all applications of
plating
EPA (2017b)
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Table 3: Conditions of Use for Sodium Glucoheptonate
Life Cycle Stage
Category
Subcategory of Use
Source
Other metal products
Metal products not covered
elsewhere
Arts, crafts, and hobby
materials
Finger paints
ECHA (2018a); ECHA (2018b); ECHA (2018c)
Consumer
Laundry and dishwashing
products
Color-safe bleach, stain
remover
DeLima Associates (2017); Walmart (2018)
Automotive care products
Automotive wheel and tire
cleaner
DeLima Associates (2012)
Disposal
Releases to air, wastewater,
solid and liquid wastes
Though not explicitly identified, releases from disposal
are assumed to be reasonably foreseen16
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 primary literature and other data sources to identify reasonably available information.
This 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 sodium glucoheptonate 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 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
Repeated Dose
Toxicity (90-day
study)21
High
Moderate
Low
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 AC 10 30 Rev7e.pdf
20 Values derived from GHS criteria (Chapter 3.1: Acute Toxicity'. 2009, United Nations).
21 Values from GHS criteria for Specific Target Organ Toxicity Repeated Exposure (Chapter 3.9: Specific Target Organ
Toxicity> Repeated Exposure. 2009, United Nations).
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Table 4: Low-Concern Criteria for Human Health and Environmental Fate and Effects
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
Toxicity26
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.
Mutagenicity and
genotoxicity in
somatic cells
OR
Evidence of
mutagenicity
11 Values derived from the U.S. EPA's Office of Pollution Prevention & Toxics criteria for HPV chemical categorizations
(Methodology for Risk-Based Prioritization Under ChMtP), 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
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)215
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/ICso)28
Chronic Aquatic
Toxicity Value
(L/E/ICso)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 sodium glucoheptonate. In many cases, EPA used analogous chemicals to make
findings for a given endpoint. Where this is the case, use of the analog is explained. If the chemical
studied is not named, the study is for sodium glucoheptonate. Appendix B contains more information
on each study.
Sodium glucoheptonate is the sodium salt of glucoheptanoic acid, which is a 7-carbon aldonic acid
(oxidized sugar) derived from glucoheptose. EPA used best professional judgement to select analogs
for sodium glucoheptonate based on similarity in structure and functionality, with the assumption that
these chemicals will have similar environmental transport and persistence characteristics, and
bioavailability and toxicity profiles. All of the analogs presented in Table 4 are either salts or esters of
aldonic acids containing 5-7 carbon atoms. D-gluconic acid, an aldonic acid containing 6 carbon
atoms, some of its corresponding salts, and one ester derivative. The sodium, potassium and calcium
salts of D-gluconic acid are expected to readily dissociate under environmentally and biologically
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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relevant conditions to release gluconic acid and/or 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
those of sodium glucoheptonate. In addition, glucono-delta-lactone is an analog for the target
compound. 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 sodium glucoheptonate.
Table 5: Sodium Glucoheptonate and Analog Structures
CASRN
Name
Structure
31138-65-5
Sodium glucoheptonate
OH
OH
OH
0'
OH
OH
OH
526-95-4
D-Gluconic acid
OH
OH
OH
HO
OH
OH
527-07-1
Sodium gluconate
OH
OH
HO.
O
OH
OH
299-28-5
Calcium gluconate
90-80-2
Glucono-delta-lactone
OH
OH
HO
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6.1.1 Absorption, Distribution, Metabolism, and Excretion
Absorption
Sodium glucoheptonate has limited potential for inhalation exposure under environmental conditions
and if incorporated in a water or aqueous solution (based on its solid state and low Henry's Law
constant, Section 3). If sodium glucoheptonate is present as dust and inhaled, absorption from the
lungs is likely based on its high water solubility (Section 3).
The potential for dermal absorption of sodium glucoheptonate is predicted to be low when in the neat
form and in a water-based product formulation based on its low log Kow (Section 3).
An oral gavage study on rats in closely-related analogs provided evidence that sodium glucoheptonate
is likely to be absorbed through the intestine. Rats dosed with U-14C labeled glucono-delta-lactone or
sodium gluconate via oral gavage displayed evidence of distribution into blood and the intestine
within 5 hours of exposure (discussed further below in Excretion), indicating the chemical is rapidly
absorbed through the gastrointestinal tract (ECHA. 1979a. b). Based on these data, sodium
glucoheptonate is expected to be absorbed through the intestine following an oral exposure.
Distribution
Sodium glucoheptonate is considered 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 occurred (discussed further in Excretion) (ECHA. 1979a. b).
Metabolism
Because quality experimental data31 on sodium glucoheptonate 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 sodium glucoheptonate metabolites. Sodium
glucoheptonate is expected to be metabolized by oxidation in the liver to sodium hydroxide and
sugar, sugar acids, and a sugar alcohol, and metabolized to a number of highly oxidized metabolites
in the skin. In vivo metabolites are expected to include some carbohydrate acids, and derivatives of
tetrahydro-furan-2-carbaldehyde and tetrahydro-2-fiirancarboxylic acid.
Excretion
To assess sodium glucoheptonate"s excretion pathways, EPA used experimental data from analogs.
An oral study in rats dosed with glucono-delta-lactone found 25% was exhaled as carbon dioxide,
23% remained in the whole body (excluding the gastrointestinal tract), 29.5% in the intestine and
feces, and 7% in urine (ECHA. 1979a. b). For animals orally dosed with sodium gluconate, 12.1,
31 Discussed in the document "Approach Document for Screening Hazard Information for Low-Priority Substances under
TSCA."
32 https://www.oecd.org/chemicalsafetv/risk-assessment/oecd-qsar-toolbox.htm
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19.7, 44.9, and 5% was recovered from exhaled carbon dioxide, whole body (excluding
gastrointestinal tract), intestine and feces, and in urine, respectively (ECHA. 1979a. b).
In a human study, approximately 7.7% to 15% of an administered oral dose of glucono-delta-lactone
was reported in urine following exposure (JECFA. 1986). In another human study, there was no
recovery in the urine following a single oral dose of glucono-delta-lactone (JECFA. 1986).
Based on these data, it is expected that sodium glucoheptonate will be primarily excreted through
feces and exhaled breath.
6.1.2 Acute Toxicity
EPA assessed the mammalian toxicity potential from acute exposure to sodium glucoheptonate using
experimental data. An OECD Guideline 425 study exposed rats via oral gavage to sodium
glucoheptonate and indicated no mortality in rats at the highest dose tested, 2000 mg/kg (ECHA.
2013b; Harlan Laboratories. 2013a). An OECD Guideline 402 study for acute dermal exposure to rats
also indicated no mortality at the highest dose tested, 2000 mg/kg (ECHA. 2013a). These studies
indicated low concern for acute toxicity with expected LD50S above the low-concern threshold of
2000 mg/kg for dermal and oral exposures.
6.1.3 Repeated Dose Toxicity
EPA assessed the potential for mammalian toxicity from repeated exposure using experimental data.
An OECD Guideline 422 (combined repeated dose toxicity study and reproduction/developmental
toxicity screening test) oral gavage study exposed rats to sodium glucoheptonate beginning two
weeks prior to mating and continued the exposure through gestation to lactation day 5 (for females),
for a total of 8 weeks (ECHA. 2013e). The no observed adverse effect level (NOAEL) was
determined to be 1000 mg/kg-day. The NOAEL identified in this study indicated low concern for
toxicity resulting from sub-chronic exposure by far exceeding the low-concern threshold of 100
mg/kg-day for a 90-day exposure (the threshold is 200 mg/kg-day for a 45-day exposure).
6.1.4 Reproductive and Developmental Toxicity
In the previously mentioned OECD Guideline 422 oral gavage study on rats (Section 6.1.3), no
adverse reproductive effects were noted at the highest dose, 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 (ECHA. 2013e).
EPA further examined the potential for developmental toxicity using data from an analog, glucono-
delta-lactone. Oral gavage studies on several species, including mice (JECFA. 1986; ECHA. 1973b;
Inc. 1973). hamsters (JECFA. 1986; ECHA. 1979a; Inc. 1973). rabbits (JECFA. 1986; ECHA. 1973c;
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 ranged from 560 to 780 mg/kg-day.
These results, taken with the low-concern criteria oral threshold of 250 mg/kg-day, indicate low
concern for reproductive and developmental toxicity.
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6.1.5 Genotoxicity
EPA assessed the potential for genotoxicity using an OECD Guideline 474 in vivo DNA damage
study (Harlan Laboratories. 2013c). Mice exposed to sodium glucoheptonate by intraperitoneal
injection resulted in no reported increases in DNA damage and repair effects. EPA also considered
several in vitro and in vivo gene mutation and chromosomal aberration studies on closely-related
analogs. All studies resulted in negative findings, providing further evidence these results indicate
low concern for genotoxicity from sodium glucoheptonate.
6.1.6 Carcinogenicity
Because quality experimental data on sodium glucoheptonate were limited, EPA relied on publicly
available quantitative structure activity relationship (QSAR) models and structural alerts (SA) to
assess the carcinogenic potential for sodium glucoheptonate. 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. Sodium glucoheptonate is not an
electrophile. ISS profiler, a QSAR model,34 identified an aldehyde metabolite alert; however, this
aldehyde metabolite is formed in the first oxidation transformation during metabolism and will
rapidly be transformed to the corresponding carboxylic acid. Further, the Virtual models for property
Evaluation of chemicals within a Global Architecture (VEGA) models"35 results indicate sodium
glucoheptonate has low potential to be carcinogenic or mutagenic.
Sodium glucoheptonate is a multi-hydroxy acid that is likely to be metabolized through oxidation.
Sodium glucoheptonate and its metabolites are expected to be rapidly excreted from the body
(discussed in Section 6.1.1). Therefore, it is anticipated that this chemical will not remain in the body
for a long period of time, reducing concern for carcinogenicity.
Sodium glucoheptonate"s metabolism, a lack of structural alerts, and experimental genotoxicity
studies indicates that this chemical is unlikely to be carcinogenic or mutagenic.
6.1.7 Neurotoxicity
EPA assessed the potential for neurotoxicity from exposure to sodium glucoheptonate on a subset of
the exposed rats from the OECD Guideline 422 described in Section 6.1.3 were used for the
neurotoxicity assessments. No adverse neurological effects on behavior (motor activity, grip strength,
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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sensory reactivity) or histology (brain, spinal cord and sciatic nerve) were observed at the highest
dose tested, 1000 mg/kg-day (ECHA. 2013c. d). The results from this study indicate low concern for
neurotoxicity by exceeding the 100 mg/kg-day threshold.
6.1.8 Skin Sensitization
EPA assessed the potential for sodium glucoheptonate to cause skin sensitization using an OECD
Guideline 429 study in mice (ECHA. 2013i). Sodium glucoheptonate was negative for dermal
sensitization. This negative result indicated low concern to skin sensitization for sodium
glucoheptonate.
6.1.9 Skin Irritation
EPA assessed the potential for sodium glucoheptonate to cause dermal irritation effects using a study
on EPISKINTM tissues (ECHA. 2013h). This study identified sodium glucoheptonate as non-
irritating. EPA also reviewed in vivo data on D-gluconic acid. D-gluconic acid was non-irritating in
two rabbit studies (ECHA. 2009b; OECD. 2004). These results indicated low concern for skin
irritation from sodium glucoheptonate.
6.1.10 Eye Irritation
To assess potential for eye irritation, EPA used read-across from sodium glucoheptonate"s analogs,
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. 2009a). 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 sodium glucoheptonate.
6.1.11 Hazards to Potentially Exposed or Susceptible Subpopulations
The above information supports a low human health hazard finding for sodium glucoheptonate based
on low-concern criteria. This finding includes considerations such as the potential for developmental
toxicity, reproductive toxicity, and acute and 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 sodium glucoheptonate.
6.2 Environmental Hazard
EPA assessed environmental hazard for sodium glucoheptonate based on available acute toxicity
experimental data and estimated chronic toxicity values using the Ecological Structure Active
Relationships (ECOSAR) Predictive Model.36 Appendix B contains a summary of the reasonably
available environmental hazard data.
36 https://www.epa. gov/tsca-screemng-tools/ecological-striicture-activitv-relationships-ecosar-predictive-model
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6.2.1 Acute Aquatic Toxicity
EPA assessed ecological hazard from acute exposures to sodium glucoheptonate. No adverse effects
were observed in aquatic invertebrates and aquatic vertebrates exposed to sodium glucoheptonate at
the highest doses tested (100 mg/L), resulting in no effects expected at concentrations less than 100
mg/L for aquatic vertebrates (Harlan Laboratories. 2015b; ECHA. 2013g) and 100 mg/L for
invertebrates (Harlan Laboratories. 2015a; ECHA. 2013f). Algae exposed to sodium glucoheptonate
resulted in an acute EC50 of 790 mg/L based on growth rate and 190 mg/L based on biomass (ECHA.
2013j; Harlan Laboratories. 2013b). These aquatic toxicity studies indicate low concern for acute
aquatic exposure by exceeding the low-concern threshold of 100 mg/L.
6.2.2 Chronic Aquatic Toxicity
Chronic toxicity values estimated using ECOSAR for aquatic vertebrates, aquatic invertebrates, and
algae are 860,000 mg/L, 175,000 mg/L, and 83,000 mg/L, respectively. These toxicity values
indicated that sodium glucoheptonate is expected to have low environmental hazard 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 the environmental persistence for sodium glucoheptonate. An experimental OECD
Guideline 30IF biodegradation study demonstrated this substance biodegraded under aerobic
conditions by greater than 60 percent in 10 days, confirming it is readily biodegradable in a sewage
sludge inoculum (ECHA. 2012). Based on read-across from sodium gluconate, sodium
glucoheptonate is expected to anaerobically biodegrade completely (OECD. 2004). No degradation
products of concern were identified for sodium glucoheptonate. Given the low aquatic toxicity
concern for this chemical, meeting the low-concern criteria means that the chemical did not produce
degradation products of concern and has a half-life less than 60 days. Further, using read-across from
sodium gluconate, sodium glucoheptonate is expected to anaerobically biodegrade completely after
35 days (OECD. 2004). The available biodegradation results meet the low-concern threshold and
indicate this chemical will have low potential for persistence.
6.3.2 Bioaccumulation Potential
Based on the estimated bioaccumulation factor (BAF) value of 3.16 using the Estimation Programs
Interface (EPI) Suite models,37 sodium glucoheptonate 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 sodium glucoheptonate. In general,
there is limited information on exposure for low-hazard chemicals. EPA determined the CDR
database and certain other sources of sodium glucoheptonate use information are sources of
information relevant to sodium glucoheptonate "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, sodium glucoheptonate is used in processing (incorporation into
formulation, mixture or reaction) for use as a raw material in internal blending of construction
materials; detergents, cleaning compounds, and toilet preparation manufacturing; plating agents and
surface treating agents. Non-TSCA uses 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, consumers, and children.
7.1 Production Volume Information
Production volume information for sodium glucoheptonate is based on an analysis of CDR data
reported from 1986 to 20 1 5.38 The CDR database indicates that, for reporting year 2015, six
companies manufactured or imported sodium glucoheptonate at six sites. For all reporting years
aggregate production volume for sodium glucoheptonate was between 1,000,000 and 10,000,000 lbs.
The exact amount is available for one year, 2011, in which 9,880,022 lbs. of sodium glucoheptonate
was produced or imported. In general, since 1986, production volume has remained relatively stable.
7.2 Exposures to the Environment
EPA expects most exposures to the environment to occur during the manufacturing, processing, and
industrial, consumer, and commercial uses of sodium glucoheptonate. Exposure is also possible from
other uses, such as distribution and disposal. These activities could result in releases of sodium
glucoheptonate to media including surface water, landfills, and air.
EPA expects high levels of removal of sodium glucoheptonate during wastewater treatment (either
directly from the facility or indirectly via discharge to a municipal treatment facility or Publicly
Owned Treatment Works (POTW)). Further, sodium glucoheptonate is expected to have low
persistence (aerobic and anaerobic biodegradation are discussed in Section 6.3.1) and has the
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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potential to be broken down in the environment to carbon dioxide and water. Therefore, any release
of the chemical to surface water 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, this chemical 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 sodium glucoheptonate to the point that it will not be present in air.
7.3 Exposures to the General Population
EPA expects the general population is unlikely to be exposed to sodium glucoheptonate from the
environmental releases described above. The general population is unlikely to be exposed to sodium
glucoheptonate via inhalation of ambient air because sodium glucoheptonate is a solid, has a low
vapor pressure, and will break down if incinerated. Sodium glucoheptonate is also unlikely to be
present in surface water because it will degrade (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 sodium glucoheptonate, oral exposure to sodium
glucoheptonate via fish ingestion is unlikely.
7.4 Exposures to Potentially Exposed or Susceptible Subpopulations
EPA identified workers, consumers, and children as potentially exposed or susceptible
subpopulations. EPA identified workers based on greater exposure to sodium glucoheptonate than the
general population during manufacturing and processing. EPA identified children (including any
adults working closely with children) as a population that may experience greater exposure to sodium
glucoheptonate than the general population during use of arts and crafts products. EPA also identified
consumers as a population that may experience greater exposure to sodium glucoheptonate than the
general population through use of cleaning products or arts and craft products, for example. EPA did
not identify populations with greater susceptibility to sodium glucoheptonate.
7.4.1 Exposures to Workers
Based on its reported physical form and measured melting point, sodium glucoheptonate is a solid
under ambient conditions. Based on sodium glucoheptonate"s conditions of use (Table 3), workers
may be exposed to solids via ingestion or inhalation of dust if generated. Sodium glucoheptonate 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 sodium glucoheptonate in manufacturing,
processing, distribution, use and disposal.
7.4.2 Exposures to Consumers
Consumers could be exposed to sodium glucoheptonate through the use of arts, crafts, and hobby
materials (e.g., finger paints), laundry and dishwashing products, automotive care products, or other
uses as specified in Table 3. For all these uses, if dermal contact does occur, sodium glucoheptonate
is expected to be minimally absorbed through the skin (see Section 6.1.1). If the chemical is in an
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aerosol product and inhalation exposure occurs, sodium glucoheptonatc's absorption from the lungs is
likely based on its high level of water solubility (Section 6.1.1). Consumer exposure is likely through
inhalation or incidental ingestion of dust if using consumer products in a powdered form, such as
powdered laundry and dishwashing products and automotive care products. 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 exposures will be incidental (meaning inadvertent and low in volume). Sodium
glucoheptonate is expected to be rapidly metabolized and excreted, further reducing the duration of
exposure.
7.4.3 Exposures to Children
Children may have dermal contact with sodium glucoheptonate through use of arts and crafts
products, such as finger paints. Given the molecular weight, water solubility, and partitioning
coefficients in Section 3, this chemical is expected to be poorly absorbed through the skin. Based on
its Henry's Law constant (Section 3), sodium glucoheptonate is not expected to be volatile from these
liquid products, reducing the potential for inhalation exposures to children. If arts and crafts products
are in a powdered form, inhalation of dust is likely. Children may also rub their eyes or incidentally
ingest the product. Sodium glucoheptonate is expected to be rapidly metabolized and excreted
(Section 6.1.1), 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 sodium glucoheptonate 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 sodium glucoheptonate. EPA used
this information to inform its proposed determination of whether sodium glucoheptonate would meet
the statutory criteria and considerations for proposed designation as a low-priority substance.
• Hazard potential:
For sodium glucoheptonate's hazard potential, EPA gathered information for a broad set of human
health and environmental endpoints described in detail in Section 6 of this document. EPA
benchmarked this information against the low-concern thresholds explained in Section 6. EPA found
that sodium glucoheptonate is of low concern for human health and environmental hazard across the
range of endpoints in these low-concern criteria.
• 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,
consumers, and children (discussed in Sections 3 and 7). EPA also gathered information on
environmental releases. EPA identified workers, the general population, consumers, children, and the
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environment as most likely to experience exposures. EPA determined that while the general
population, consumers, children and workers may be exposed to sodium glucoheptonate, exposure by
dermal, inhalation, and ingestion pathways are limited by sodium glucoheptonate "s physical-chemical
properties. If sodium glucoheptonate is released into the environment, its exposure potential will be
reduced through biodegradation under aerobic and anaerobic conditions.
Rationale: Although sodium glucoheptonate may cause moderate eye irritation, the effects are
expected to be reversible, reducing concern for longer-term or chronic effects. 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 and dishwashing products, 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 sodium glucoheptonate 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 sodium
glucoheptonate 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 experimental data indicates sodium glucoheptonate is readily
biodegradable under aerobic conditions, with greater than 60 percent biodegradation expected within
10 days, and expected to be biodegradable under anaerobic conditions based on a closely-related
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 sodium glucoheptonate meets the 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
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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
in the manufacturing, processing, distribution and use, and disposal of sodium glucoheptonate as a
potentially exposed or susceptible subpopulation (described in more detail in Section 7). EPA also
identified children (and any adults working closely with children) as a population that may experience
greater exposure to sodium glucoheptonate than the general population during use of arts and crafts
products. Consumers are also a potentially exposed subpopulation because of their use of products
such as arts, crafts, and hobby materials, laundry and dishwashing products, and automotive care
products.
Rationale: EPA did not identify hazard effects for this chemical that would make any population
susceptible. EPA expects workers, consumers, and children to have a higher exposure to sodium
glucoheptonate than the general population. Higher exposure to children could result from use of
finger paints containing sodium glucoheptonate, which might lead to inadvertent eye contact. Because
of the chemical's low-concern hazard properties and reversibility of the effects, this exposure does
not pose a significant increase in risk for children, consumers, or workers.
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 sodium
glucoheptonate 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 of sodium
glucoheptonate 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 sodium glucoheptonate 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, sodium glucoheptonate is expected to present low concern to
the general population, including susceptible subpopulations, across a spectrum of health endpoints.
In the event of an accidental release into a surface drinking water source, though sodium
glucoheptonate is water soluble (see Section 3), it is not expected to persist (see Section 6.3.1) in the
drinking water supply. In the event of an accidental release to land, its biodegradability (aerobically
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and anaerobically, section 6.3.1) reduces its potential for leaching into groundwater, including well
water. Fate and transport evaluation indicated sodium glucoheptonate 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.
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, sodium glucoheptonate 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 sodium glucoheptonate 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 sodium glucoheptonate 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 sodium glucoheptonate and related potential
exposures and hazards.
Rationale: EPA assessed the conditions of use of sodium glucoheptonate (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 sodium glucoheptonate"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
sodium glucoheptonate meets the high-priority substance based on its low-hazard profile under the
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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 condition of use. Therefore, such changes would not support a finding that sodium
glucoheptonate 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 sodium glucoheptonate (Section 7.1)
and related potential exposures (Sections 7.2 through 7.4).
Rationale: EPA used reasonably available information on production volume (see Appendix A) in
considering potential risk. It is possible that designation of sodium glucoheptonate as a low-priority
substance could result in increased use and higher production volumes. EPA expects, however, that
any changes in sodium glucoheptonate's production volume would not alter the Agency's assessment
of low concern given the chemical's low-hazard profile. EPA bases this expectation on sodium
glucoheptonate'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)(6), EPA proposes to
find that even if production volumes increase, resulting in an increase in the frequency or level of
exposure, sodium glucoheptonate 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 sodium glucoheptonate 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 sodium glucoheptonate 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), 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. According to the 2016 CDR database, six companies manufactured or
imported sodium glucoheptonate for reporting year 2015. Individual production volumes were
withheld, but may be available in later releases of the 2016 CDR.
Table presents the historic production volume of sodium glucoheptonate from the CDR from 1986-
2015. For all reporting years aggregate production volume for sodium glucoheptonate was between
1,000,000 and 10,000,000 lbs. The exact amount is available for one year, 2011, in which 9,880,022
lbs. of sodium glucoheptonate was produced or imported.
Table A.1:
1986-2015 National Production Volume Data for Sodium Glucoheptonate (Non-Confidential
Production Volume in Pounds)
1986
1990
1994
1998
2002
2006
2011
2012
2013
2014
2015
1 M -10
1 M -10
1 M-
1 M-
1 M-
1 M-
9,880,022
1 M-
1 M-
1 M-
1 M-
M
M
10 M
10 M
10 M
10 M
10 M
10 M
10 M
10 M
Source(s):
EPA (2018a; 2017b; 2006; 2002)
Note(s):
K = Thousand; M = Milli
ion; NDR =
No data reported
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A.2 Uses
A.2.1 Methods for Uses
Section A.2 provides a list of known uses of sodium glucoheptonate, organized by category of use. To
compile the uses, EPA searched publicly available databases listed in Table A.2 and conducted
additional Google 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 Sodium Glucoheptonate
Title
Author and Year
Search Term(s)
Found Use
Information?1
Sources search for all use reports
California Links to
Pesticides Data
California Dept of Pesticide
Regulation (2013)
31138-65-5
No
Canada Chemicals
Management Plan
information sheets
Government of Canada (2018)
D-gluco-Heptonic acid;
Sodium glucoheptonate
No
Chemical and Product
Categories (CPCat)
Dionisioet al. (2015)
31138-65-5
Yes
ChemView2
EPA (2018a)
31138-65-5
Yes
Children's Safe Product Act
Reported Data
Washington State Dept. of
Ecology (2018)
31138-65-5
No
Consumer Product
Information Database
(CPID)
DeLima Associates (2018)
31138-65-5
Yes
Danish surveys on
chemicals in consumer
products
Danish EPA (2018)
N/A, There is no search, but
report titles were checked for
possible information on the
chemical
No
Datamyne
Descartes Datamyne (2018)
Sodium glucoheptonate
Yes
DrugBank
DrugBank 2018
31138-65-5; Sodium
glucoheptonate
No
European Chemicals
Agency (ECHA)
Registration Dossier
ECHA (2018b)
31138-65-5
Yes
eChemPortal2
OECD (2018)
31138-65-5
Yes
Envirofacts2
EPA (2018b)
31138-65-5
No
Functional Use Database
(FUse)
EPA (2017a)
31138-65-5
Yes
Kirk-Othmer Encyclopedia
of Chemical Technology
Kirk-Othmer (2006)
31138-65-5; Sodium
glucoheptonate
No
Non-Confidential 2016
Chemical Data Reporting
(CDR)
EPA (2017b)
31138-65-5
Yes
PubChem Compound
Kimetal. (2016)
31138-65-5
Yes
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Table A.2: Sources Searched for Uses of Sodium Glucoheptonate
Title
Author and Year
Search Term(s)
Found Use
Information?1
Safer Chemical Ingredients
List (SCIL)
EPA (2018d)
31138-65-5
Yes
Synapse Information
Resources2
Synapse Information
Resources (n.d.)
31138-65-5
Yes
Resource Conservation
and Recovery Act (RCRA)
EPA (2018c)
Sodium glucoheptonate; D-
gluco-Heptonic
No
Scorecard: The Pollution
Information Site
GoodGuide (2011)
31138-65-5
No
Skin Deep Cosmetics
Database
EWG (2018)
31138-65-5; Sodium
glucoheptonate; Sodium
gluceptate
No
Toxics Release Inventory
(TRI)
EPA (2018e)
31138-65-5
No
TOXNET2
NLM (2018)
31138-65-5
No
Ullmann's Encyclopedia of
Industrial Chemistry
Ullmann's (2000)
Sodium glucoheptonate
No
Additional sources identified from reasonably available information
Alco-Chem Inc.
Alco-Chem Inc. (2015a)
Identified while reviewing
details of this chemical's
uses and products.
Yes
Harcros Chemicals Inc.
Harcros Chemicals Inc. (2014)
TCI America
TCI America (2014)
Walmart
Walmart (2018)
Note(s):
1. If use information was found in the resource, it will appear in Error! Reference source not found, 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 398 patents referencing
"sodium glucohcptonate" (USPTO 2018). Although patents could be useful in determining
reasonably foreseen uses, it is difficult to confirm whether any of the patented technologies are
currently in use. Uses inferred from patents containing sodium glucoheptonate 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.
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A.2.2 Uses of Sodium Glucoheptonate
Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Cleaning Products
ECHA (2018d); ECHA (2018c)
Air care products
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in air care products. ECHA does not expand on this use, however
this category generally includes products such as air fresheners, candles, and
scented gels. No further information about this use could be found, and it is
unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
DeLima Associates (2012)
Automotive wheel and tire cleaner
Consumer
CPID lists one automotive cleaner containing sodium glucoheptonate.
CPID generally includes products for consumer use; therefore, the expected user is
a consumer.
EPA (2017b); Harcros Chemicals Inc. (2014); Synapse Information Resources
(n.d.)
Cleaning and furnishing care products
Commercial
CDR reports use of liquid sodium glucoheptonate in commercial cleaning and
furnishing care products, with a concentration of 30-60 percent by weight. Synapse
Information Resources identifies use of sodium glucoheptonate in dairy cleaners
and bottle cleaners.
Expected users are commercial based on CDR's user classification.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
Dionisioet al. (2015)
Cleaning/washing agents for dish washing machines
Consumer,
commercial,
industrial
CPCat identifies use of sodium glucoheptonate in cleaning/washing agents in
Nordic countries. This use could not be confirmed by the SPIN databases. No
further information about this use could be found and it is unknown whether this is
an ongoing use in the United States.
Expected users are consumer, commercial, and industrial.
ECHA (2018a); ECHA (2018d); ECHA (2018c); Synapse Information Resources
(n.d.)
Coatings and paints, thinners, paint removers
Consumer,
commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate in coatings,
paints, thinners, and paint removers. Synapse Information Resources identifies use
of sodium glucoheptonate in paint stripping. No further information about this use
could be found and it is unknown whether this is an ongoing use in the United
States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
Dionisioet al. (2015)
Degreaser
Consumer,
commercial,
industrial
CPCat identifies use of sodium glucoheptonate in cold degreasing, de-waxing, and
de-polishing in Nordic countries. This use could not be confirmed by the
Substances in Preparations in Nordic Countries (SPIN) databases. No further
information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are consumer, commercial, and industrial.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
Alco-Chem Inc. (2015b); Alco-Chem Inc. (2015a)
Laundry booster
Commercial,
industrial
An SDS from Alco-Chem identifies the product Liquid Laundry Break containing <5
percent sodium glucoheptonate. According to the manufacturer, the product is a
heavy-duty alkaline builder that improves detergent performance by emulsifying
soils.
Expected user is not identified in the source but is likely commercial and industrial
based on the fact that the product is sold in five and fifteen-gallon pails.
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Polishes and wax blends
Consumer,
commercial,
industrial
The ECHA registration dossier reports use of sodium glucoheptonate in polishes
and wax blends. No further information about this use could be found and it is
unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
DeLima Associates (2017); Walmart (2018)
Stain remover
Consumer
CPID lists one stain remover containing sodium glucoheptonate. This product is
currently for sale.
CPID generally includes products for consumer use; therefore, the expected user is
a consumer.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Manufacturing
EPA (2017b); ECHA (2018c); TCI America (2014)
Chemical manufacturing
Industrial
CDR reports use of sodium glucoheptonate as a solid's separation agent during the
repackaging and processing (incorporation into formulation, mixture, or reaction
product) phases of all other chemical product and preparation manufacturing. TCI
identifies use of sodium glucoheptonate in lab chemicals. The ECHA registration
dossier identifies use of sodium glucoheptonate as a chelating agent in the
manufacture of fine chemicals and bulk, large-scale chemicals including petroleum
products.
Expected users are industrial based on CDR's industrial processing and use report
and reporting under ECHA's uses at industrial sites.
Dionisioet al. (2015)
Fluid property modulator
Consumer,
commercial,
industrial
CPCat identifies use of sodium glucoheptonate as a complexing, sequestering,
surface treatment, and chelating agent in Nordic countries. Use could not be
confirmed by SPIN databases.
Expected users are consumer, commercial, and industrial.
ECHA (2018c); ECHA (2018d); Synapse Information Resources (n.d.)
Manufacture of computer, electronic and optical products,
electrical equipment
Commercial,
industrial
The ECHA registration dossier reports use of sodium glucoheptonate as a
chelating agent in manufacturing of computer, electronic and optical products and
electrical equipment and as a component of semiconductors. Synapse Information
Resources identifies use of sodium glucoheptonate in aluminum etching.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018c)
Manufacture of furniture
Industrial
The ECHA registration dossier reports use of sodium glucoheptonate as a
chelating agent in the manufacture of furniture. No further information about this
use could be found and it is unknown whether this is an ongoing use in the United
States.
Expected users are industrial based on reporting under ECHA's uses at industrial
sites.
Dionisio et al. (2015); ECHA (2018c)
Manufacture of metal products
Industrial
CPCat reports use of sodium glucoheptonate in the manufacture of fabricated
metal products (except machinery) in Nordic countries. Use could not be confirmed
by SPIN databases. The ECHA registration dossier identifies use of sodium
glucoheptonate in the manufacture of basic metals, including alloys. No further
information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are industrial based on CPCat's class of chemical category and
reporting under ECHA's uses at industrial sites.
ECHA (2018c)
Manufacture of plastics products, including compounding and
conversion
Industrial
The ECHA registration dossier reports use of sodium glucoheptonate as a
chelating agent in plastic products manufacturing. No further information about this
use could be found and it is unknown whether this is an ongoing use in the United
States.
Expected users are industrial based on reporting under ECHA's uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018c); Synapse Information Resources (n.d.)
Manufacture of rubber products
Industrial
Synapse Information Resources identifies use of sodium glucoheptonate as a latex
stabilizer. The ECHA registration dossier reports use of sodium glucoheptonate in
rubber product manufacturing. No further information about this use could be found
and it is unknown whether this is an ongoing use in the United States.
Expected users are industrial based on reporting under ECHA's uses at industrial
sites.
Dionisio et al. (2015); ECHA (2018c)
Manufacture of textiles, leather and fur
Industrial
CPCat identifies use of sodium glucoheptonate in Nordic textile manufacturing;
however, use could not be confirmed by SPIN databases. The ECHA registration
dossier reports use of sodium glucoheptonate as a chelating agent in the
manufacture of textiles, leather, and fur. No further information about this use could
be found and it is unknown whether this is an ongoing use in the United States.
Expected users are industrial based on reporting under ECHA's uses at industrial
sites.
ECHA (2018c)
Manufacture of wood and wood products
Industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in the manufacture of wood and wood products. No further
information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are industrial based on reporting under ECHA's uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018c)
Manufacturing (general)
Industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in general manufacturing (machinery, equipment, etc.). No further
information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are industrial based on reporting under ECHA's uses at industrial
sites.
Nonmetallic mineral product manufacturing (includes clay,
glass, cement, concrete, lime, gypsum, and other nonmetallic
mineral product manufacturing)
Industrial
EPA (2017b)
CDR reports use of sodium glucoheptonate as an ion exchange agent during the
processing phase (incorporation into formulation, mixture, or reaction product) of
manufacturing.
Expected users are industrial based on CDR's industrial processing and use report.
EPA (2017b)
Plating agents and surface treating agents
Consumer,
commercial,
industrial
CDR reports use of sodium glucoheptonate as an industrial plating/surface treating
agent in the processing phase (incorporation into formulation, mixture, or reaction
product) of resale of chemicals and miscellaneous manufacturing. CDR also
identifies use of sodium glucoheptonate as a cleaner in multiple consumer and
commercial plating processes, including automotive and machinery applications.
Cleaners in plating processes contain 30-60 percent sodium glucoheptonate by
weight, according to CDR.
Expected users are consumer, commercial, and industrial.
EPA (2017b)
Soap, cleaning compound, and toilet preparation
manufacturing
Industrial
CDR reports use of sodium glucoheptonate as an ion exchange agent and
processing aid during the processing phase (incorporation into formulation,
mixture, or reaction product) of manufacturing.
Expected users are industrial based on CDR's industrial processing and use report.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
Dionisio et al. (2015); Synapse Information Resources (n.d.)
Treatment and coating of metals
Industrial
CPCat identifies use of sodium glucoheptonate in treatment and coating of metals,
metals workshops, and metal machining in Nordic Countries. Use could not be
confirmed by SPIN databases. Synapse Information Resources identifies use of
sodium glucoheptonate in metal cleaning.
Expected users are industrial based on CPCat's class of chemical category.
TSCA Conditions of Use: Food, Agriculture, and Horticulture
ECHA (2018c)
Agriculture, forestry, and fishing1
Industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in agriculture, forestry, and fishing. No further information about
this use could be found and it is unknown whether this is an ongoing use in the
United States.
Expected users are industrial based on CPCat's class of chemical category.
Dionisio et al. (2015)
Crop and animal production, hunting and related service
activities1
Industrial
CPCat reports use of sodium glucoheptonate in crop and animal production,
hunting, and related service activities in Nordic countries, however this use could
not be verified by SPIN databased. No further information about this use could be
found and it is unknown whether this is an ongoing use in the United States.
Expected users are industrial based on CPCat's class of chemical category.
ECHA (2018a); ECHA (2018c); ECHA (2018d)
Fertilizers
Consumer,
Commercial,
Industrial
The ECHA registration dossier reports use of sodium glucoheptonate in fertilizers.
No further information about this use could be found and it is unknown whether this
is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
Synapse Information Resources (n.d.)
Food-contact paper/paperboard manufacturing
Consumer,
commercial,
industrial
Synapse identifies use of sodium glucoheptonate in the manufacture of food-
contact paper/paperboard. No further information about this use could be found,
and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial.
EPA (2017b)
Pesticide, fertilizer, and other agricultural chemical
manufacturing
Industrial
EPA's 2016 CDR reports use of sodium glucoheptonate as an ion exchange agent
during the processing phase (incorporation into formulation, mixture, or reaction
product) of manufacturing. Sodium glucoheptonate is not registered with the
California Department of Pesticide Regulation or the National Pesticide Information
Retrieval System.
Expected users are industrial based on CDR's industrial processing and use report.
ECHA (2018d); ECHA (2018c)
Plant protection products
Commercial,
industrial
The ECHA registration dossier reports use of sodium glucoheptonate as a
chelating agent in plant protection products. No further information about this use
could be found and it is unknown whether this is an ongoing use in the United
States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
TSCA Conditions of Use: Media and Printing
Finger paints
Consumer,
commercial
ECHA (2018a); ECHA (2018d); ECHA (2018c)
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in finger paints. No further information about this use could be
found and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses and uses by professional workers. ECHA also
indicated industrial use; however, this is likely referring to its manufacture for this
use as finger paints are not likely used industrially.
Fragrances2
Consumer,
commercial,
Industrial
ECHA (2018a); ECHA (2018d); ECHA (2018c)
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in fragrances. No relevant products containing sodium
glucoheptonate could be found and it is unknown whether this is an ongoing use in
the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
Ink and toners
Consumer,
commercial,
industrial
ECHA (2018a); ECHA (2018d); ECHA (2018c)
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in ink and toners. No further information about this use could be
found and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Photo-chemicals
Consumer,
commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in photo-chemicals. No further information about this use could be
found and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
ECHA (2018c)
Printing and reproduction of recorded media
Industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in printing and reproduction of recorded media. No further
information about this use could be found and it is unknown whether this is an
ongoing use in the United States.
Expected users are industrial based on reporting under ECHA's uses at industrial
sites.
TSCA Conditions of Use: Miscellaneous
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Adhesives, sealants
Consumer,
commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in adhesives, sealants. No further information about this use could
be found, and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018d); ECHA (2018c)
Adsorbents
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in adsorbents. No further information about this use could be
found, and it is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
ECHA (2018d); ECHA (2018c)
Anti-freeze and de-icing products
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in anti-freeze and de-icing products. No further information about
this use could be found, and it is unknown whether this is an ongoing use in the
United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
EPA (2017b); ECHA (2018c); Harcros Chemicals Inc. (2014)
Construction
Industrial
CDR reported use of sodium glucoheptonate as a raw material in internal blending
of construction materials.
Expected users are industrial based on identification in CDR's industrial processing
and use report.
Dionisio et al. (2015); ECHA (2018a); ECHA (2018d); ECHA (2018c)
Electricity, steam, gas, water supply and sewage treatment
Consumer,
Commercial,
industrial
CPCat identifies use of sodium glucoheptonate as an ion exchange agent in
industrial water treatment. The ECHA registration dossier lists sodium
glucoheptonate as an ingredient in consumer, commercial and industrial water
treatment chemicals.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018d); ECHA (2018c)
Explosives
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in explosives. No further information about this use could be found,
and it is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
ECHA (2018d); ECHA (2018c)
Extraction agents
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in extraction agents. No further information about this use could be
found, and it is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
ECHA (2018d); ECHA (2018c)
Fuels
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in fuels. No further information about this use could be found, and it
is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
ECHA (2018d); ECHA (2018c)
Heat transfer fluids
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in heat transfer fluids. No further information about this use could
be found, and it is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018d); ECHA (2018c)
Hydraulic fluids
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in hydraulic fluids. No further information about this use could be
found, and it is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
ECHA (2018d); ECHA (2018c)
Intermediate
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in intermediates. No further information about this use could be
found, and it is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
ECHA (2018d); ECHA (2018c)
Laboratory chemicals
Commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in lab chemicals. No further information about this use could be
found, and it is unknown whether this is an ongoing use in the United States.
Expected users are commercial and industrial based on reporting under ECHA's
uses by professional workers and uses at industrial sites.
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Leather treatment products
Consumer,
commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in leather treatment products. No further information about this use
could be found, and it is unknown whether this is an ongoing use in the United
States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Lubricants, greases, release products
Consumer,
commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in lubricants, greases, and release products. No further information
about this use could be found, and it is unknown whether this is an ongoing use in
the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
ECHA (2018c)
Mining
Industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in mining activities. No further information about this use could be
found, and it is unknown whether this is an ongoing use in the United States.
Expected users are industrial based on identification under ECHA's uses at
industrial sites.
ECHA (2018c)
Offshore industries
Industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in offshore industries. No further information about this use could
be found, and it is unknown whether this is an ongoing use in the United States.
Expected users are industrial based on identification under ECHA's uses at
industrial sites.
EPA (2017b)
Oil and gas exploration, drilling, extraction, and support
activities
Commercial,
industrial
CDR reported use of Sodium Glucoheptonate in commercial and industrial oil and
gas exploration and as an ion exchange agent in industrial oil and gas drilling,
extraction and support activities.
Expected users are commercial based on CDR's user classification, and industrial
based on identification in CDR's industrial processing and use report.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
EPA (2017b)
Other metal products
Consumer,
commercial
CDR reports use of sodium glucoheptonate in metal products not covered
elsewhere. These products contain less than one percent sodium glucoheptonate
by weight, according to CDR.
Expected users are consumer and commercial based on CDR's user classification.
ECHA (2018a); ECHA (2018d); ECHA (2018c); Synapse Information Resources
(n.d.)
Paper and board treatment products
Consumer,
commercial,
industrial
Synapse Information Resources identifies use of sodium glucoheptonate in kier
boiling (used to bleach or scour cotton or process paper pulp) and caustic boiloff
(possibly referring to boil-out which is the removal of excess fibers and minerals in
paper treatment). The ECHA registration dossier reports use of sodium
glucoheptonate in paper and board treatment products as well as the manufacture
of pulp, paper, and paper products. No further information about this use could be
found and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Products such as pH-regulators, flocculants, precipitants,
neutralization agents
Consumer,
commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in products such as pH-regulators, etc. No further information
about this use could be found, and it is unknown whether this is an ongoing use in
the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
Non-TSCA Uses
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Biocidal products (e.g. disinfectants, pest control)
Consumer,
commercial,
industrial
The ECHA registration dossier reports use of sodium glucoheptonate in biocidal
products. No further information about this use could be found and it is unknown
whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
FDA (2018); Dionisio etal. (2015); ECHA (2018c); Synapse Information Resources
(n.d.)
Boiler water additive
Consumer,
commercial,
industrial
Sodium Glucoheptonate is listed as a boiler water additive on the U.S. FDA's Food
Additive Status List. It is currently regulated by the FAA as a boiler compound with
less than 1 ppm of cyanide. Additionally, the ECHA registration dossier identifies
use of sodium glucoheptonate as a chelating agent in the manufacture of food and
in consumer and commercial water softeners.
Expected users are based on identification under ECHA's consumer uses, uses by
professional workers, and uses at industrial sites.
ECHA (2018a); ECHA (2018d); ECHA (2018c); Synapse Information Resources
(n.d.)
Cosmetics, personal care products
Consumer,
commercial,
industrial
Synapse Information Resources identifies use of sodium glucoheptonate as a
chelating agent in cosmetics. The ECHA registration dossier reports use of sodium
glucoheptonate as a chelating agent in cosmetics and other personal care
products. No personal care products containing sodium glucoheptonate could be
found and it is unknown whether this is an ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use
Expected Users
Description of Use and References
Synapse Information Resources (n.d.)
Food additive
Unknown
Synapse Information Resources identifies use of sodium glucoheptonate as a
sequestrant. 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.
ECHA (2018a); ECHA (2018d); ECHA (2018c)
Perfumes
Consumer,
commercial,
industrial
The ECHA registration dossier identifies use of sodium glucoheptonate as a
chelating agent in perfumes. No relevant products containing sodium
glucoheptonate could be found and it is unknown whether this is an ongoing use in
the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
ECHA (2018a); ECHA (2018d); ECHA (2018c); Synapse Information Resources
(n.d.)
Pharmaceuticals
Consumer,
commercial,
industrial
Synapse Information Resources identifies use of sodium glucoheptonate in
intravenous pharmaceuticals, and the ECHA registration dossier reports use of
sodium glucoheptonate in pharmaceuticals and health services. No further
information could be found in DrugBank, and it is unknown whether this is an
ongoing use in the United States.
Expected users are consumer, commercial, and industrial based on reporting
under ECHA's consumer uses, uses by professional workers, and uses at industrial
sites.
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Table A.3: Uses of Sodium Glucoheptonate
Use | Expected Users | Description of Use and References
Children's Products
CDR and other databases did not specifically indicate uses in children's products; however, use in finger paints was identified in European countries (see above).
Recycling and Disposal
In the 2016 CDR, one facility, Milport Enterprises Inc., reported recycling (e.g., recycled, remanufactured, reprocessed, or reused) sodium glucoheptonate. Four facilities
reported not recycling sodium glucoheptonate, and one facility withheld recycling information (EPA 2017b).
Note(s):
1. Assumed to be a mix ofTSCAand non-TSCA products. It is expected that more specifically-defined uses in the table are representative of the uses that fall into this category.
2. Potentially a non-TSCA use as category may contain both TSCA and non-TSCA uses, however, because information is insufficient to determine, it is assumed to be covered by TSCA.
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A.3 References
Alco-Chem Inc. (2015a). Liquid Laundry Break. Retrieved from https://www.alco-chem.com/liquid-
laundrv-break.html
Alco-Chem Inc. (2015b). Safety Data Sheet: Liquid Laundry Break. Retrieved from http://catalog.alco-
chem.com/sds/Alco275 .pdf
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://eng.mst.dk/chemicals/chemicals-in-products/consumers-consumer-products/danish-
survevs-on-consumer-products/
DeLima Associates. (2012). Eagle One EnviroShine All Wheel & Tire Cleaner. Retrieved from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/12283/standard/Eagle%20Qne%20EnviroS
hine%20All%20Wheel%20&%20Tire%20Cleaner/22-001 -048
DeLima Associates. (2017). Carbona Stain Devils No.9, Rust & Perspiration-02/27/2017. Retrieved
from
https://www.whatsinproducts.com/tvpes/tvpe detail/l/19472/standard/p%20class=%22pl%22%3
ECarbona%20Stain%20Devils%20No.9.%20Rust%20&%20Perspiration-02/27/2017/p%3E/04-
030-012
DeLima Associates. (2018). Consumer Product Information Database. Retrieved from
https ://www.whatsinproducts .com/
Descartes Datamyne. (2018). Sodium glucoheptonate exports 2011-2018.
https://www.descartes.com/datamvne
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). DrugBank Database. Retrieved from https://www.drugbank.ca/
European Chemicals Agency (ECHA). (2018a). Consumer Uses. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/8874/3/l/6
European Chemicals Agency (ECHA). (2018b). Sodium glucoheptonate. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/8874
European Chemicals Agency (ECHA). (2018c). Uses at industrial sites. Retrieved from
https://echa.europa.eu/registration-dossier/-/registered-dossier/8874/3/l/4
XII
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
European Chemicals Agency (ECHA). (2018d). Uses by professional workers. Retrieved from
https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/SS74/3/l/5
EWG. (2018). Sodium Gluceptate. Retrieved from
https://\\\v\\ .cw g.org/skindccp/bro\\sc.php?containing=723743&sho\\products=l#.W4cot85KiM
8
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
Hallstar. (2018). Search Results. Retrieved from https://www.hallstar.com/?s=SEQLENE+540
Harcros Chemicals Inc. (2014). Safety Data Sheet. Retrieved from:
https://www.chemical.net/content/images/uploaded/sds/Sodium%20Glucoheptonate%2050%20L
A.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.
Milport Enterprises Inc. (2013). Chelating Agents & Polymers. Retrieved from
http ://www. milport. com/chelating.html
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
Synapse Information Resources, (n.d.). Synapse Information Resources. Retrieved from: Excel file.
TCI America. (2014). Safety Data Sheet Sodium Glucoheptonate Dihydrate. Retrieved from
https://www.spectrumchemical.com/MSD S/TCI-G0214 .pdf
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
XIII
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
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
U.S. Environmental Protection Agency (EPA). (2018b). Envirofacts Multisystem Search. Retrieved
from https://www3.epa.gov/enviro/facts/multisvstem.html
U.S. Environmental Protection Agency (EPA). (2018c). Look up table for BR Waste Code (National
Biennial RCRA Hazardous Waste Report). Retrieved from
https://iaspub.epa.gov/enviro/brs codes v2.waste lookup
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). Food Additive Status List. Retrieved from
https://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm091048.
htm#ftnS
U.S. National Library of Medicine (NLM). (2018). TOXNET® (TOXicology DataNETwork).
Retrieved from https://toxnet.nlm.nih.gov/
U.S. Patent and Trademark Office (USPTO). (2018). USPTO Patent Full-Text and Image Database.
Retrieved from http://patft.uspto.gov/netacgi/nph-
Parser?Sectl=PT02&Sect2=HIT0FF&p=l&u=%2Fnetahtml%2FPT0%2Fsearch-
bool.html&r=0&f=S&l=50&TERMl=sodium+glucoheptonate&FIELDl=&col=AND&TERM2
=&FIELD2=&d=PTXT
Ullmann's. (2000). ULLMANN'S Encyclopedia of Industrial Chemistry.
Walmart. (2018). Carbona Stain Devils® Rust And Perspiration Stain Remover, 1.7 Ounces. Retrieved
from https://www.walmart.com/ip/Carbona-Stain-Devils-Rust-And-Perspiration-Stain-Remover-
l-7-Ounces/17283471?wmlspartner=wlpa&selectedSellerId=2419
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https ://fortress. wa. gov/ecv/cspareporting/
XIV
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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
Species &
Duration
Doses and
Effect
Study Details
(HERO
Route
Strain (if
Replicate Number
ID)
available)
4940231,
Oral
Wistar rats
Single dose
Dose: 0 and 4000
Enzyme levels of glucose-6-
• Test substance reported as CASRN 90-80-2
4940243
(gavage)
mg/kg
Replicates: 4-14
male rats
phosphate and 6-
phosphogluconate were 163 and
27 |jmol/kg 5 hours following
treatment and were similar to
levels in the control animals
• Purity not reported
• OECD Guideline 417
• GLP compliance not reported
4947912
Oral
Humans
Single dose,
Dose: 84 or 167
The recovered GDL in urine was
• Test substance reported as CASRN 90-80-2
urine collected
7 hours post
exposure
mg/kg
Replicates: 3
healthy males
0 and 7.7-15% of the original
dose at 84 and 167 mg/kg,
respectively
• Purity not reported
• Pre-dates GLP compliance
4940243
Oral
Wistar rats
Single dose
Dose: 800 mg/kg
The radioactivity of D-glucono-
• Test substance reported as CASRN 90-80-2
(gavage)
mg/kg
Replicates: 9-10
fasted male rats
delta-lactone was reported to be
25.0 (whole body), 23.1
(intestines and feces), 29.5
(urine), and 7.0% (exhaled
carbon dioxide)
• Purity not reported
• OECD Guideline 417
• GLP compliance not reported
4940231,
Oral
Wistar rats
Single dose
Dose: 800 mg/kg
After 5 hours, radioactivity was
• Test substance reported as CASRN 527-07-1
4940243
(gavage)
mg/kg
Replicates: 9-23
fasted male rats
reported to be 12.1% (exhaled
carbon dioxide) 19.7% (whole
body), 44.9% (intestine and
feces) and 5.0% (urine).
• Purity not reported
• OECD Guideline 417
• GLP compliance not reported
4941343
Oral
Sprague-
Single dose
Dose: 30 mg/kg
Total amount of radiolabeled
• Test substance reported as CASRN 299-28-5
(gavage)
Dawley rats
Replicates: 7 male
rats
calcium excreted in urine was
1.241 ±0.473%. The highest
concentration of radioactivity
was found in bone as 98.7 ±
1.6%
(radiolabeled)
• Purity not reported
• GLP compliance not reported
XVI
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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
4851345,
4864278
Oral
gavage
Wistar rat
Single
exposure,
observed for
14 day
Doses and
replicates:
354 mg/kg (175 mg
active/kg), 1 female
1112 mg/kg (550
mg active/kg), 1
female
4042 mg/kg (2000
mg active/kg), 3
females
LD50 > 2000 mg/kg
Methods:
• Test substance reported as CASRN 31138-65-5
• Purity: 49.5%
• OECD Guideline 425
• GLP compliant
4864277
Dermal
Wistar rats
24-hour
exposure,
observed for
14 days
Dose: Single dose
of 4041 mg/kg or
2000 mg active/kg
Replicates: 5 per
sex
LD50 > 2000 mg/kg
Methods:
• Test substance reported as CASRN 31138-65-5
• Purity: 49.5%
• OECD Guideline 402, EU method B.3.
• GLP compliant
Repeated Dose Toxicity
Source
Exposure
Route
Species &
strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
4851346,
4864281,
4864283,
4864285
Oral
(gavage)
Wistar rats
8 weeks
Doses: 0, 30,300,
and 1000 mg/kg-
day
NOAEL: 1000 mg/kg-day
Methods:
• Test substance reported as CASRN 31138-65-5
• Purity: 50.5%
• OECD Guideline 422
XVII
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table B.1:
Human Health Hazard
• Dosing
Replicates: 12 per
• GLP compliant
began 2
sex per group
weeks
prior to
mating
• Dosing
continued,
through
gestation
to
lactation
day 5 (for
females)
Reproductive Toxicity
Source
Exposure
Route
Species &
Strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
4864285
Oral
Wistar rats
8 weeks
Doses: 0,30, 300,
NOAEL: 1000 mg/kg-day
Methods:
(gavage)
• Dosing
began 2
weeks
prior to
mating
• Dosing
continued,
through
gestation
to
lactation
day 5 (for
females)
and 1000 mg/kg-
day
Replicates: 12 per
sex per group
• Test substance reported as CASRN 31138-65-5
• Purity: 50.5%
• OECD Guideline 422
• GLP compliant
Developmental Toxicity
Source
Exposure
Route
Species &
Strain (if
available)
Duration
Doses and
replicate number
Effect
Study Details
XVIII
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
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/d
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 rat
GD 6-15
Doses: 0,5.94,
27.6, 128 and 594
mg/kg-day
Replicates: 21-25
per dose
NOAEL: 594 mg/kg-day
Methods
• Test substance reported as CASRN 90-80-2
• Purity not reported
• GLP not reported
Cancer
Source
Effect
Study Details
OncoLogic v8.0
Structure could not be evaluated by Oncologic.
OncoLogic currently has no assessment criteria regarding sugar derivatives.
ISS v2.439
Negative (Estimated)
Monosodium D-glucoheptonate 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 alert was identified for the initial aldehyde
metabolite that is formed in the first oxidation transformation that occurs during the metabolism of
39 Carcinogenicity alerts by ISS profiler comprises 55 structural alerts for genotoxic and non-genotoxic carcinogenicity. The alerts have been compiled upon existing knowledge of mechanism of
action of carcinogenic chemicals that have been published elsewhere (Benigni and Bossa (2011) ChemRev 111:2507-2536 and Benigni Ret al. (2013) ChemRev. 113:2940-2957).
XIX
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Monosodium D-glucoheptonate). This aldehyde will be rapidly transformed to the corresponding
carboxylic acid.
VEGA 1.1.4«
Monosodium D-glucoheptonate was processed
through all 4 models. ISS 1.0.2and
IRFMN/ISSCAN-GX 1.0.0 predicted it to be
non-carcinogenic with moderate reliability41.
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 (Monosodium D-glucoheptonate lies outside of the applicability
domain (AD) of the model)
• ISS 1.0.2: Moderate reliability (Monosodium D-glucoheptonate could lie outside of the AD)
• IRFMN/Antares 1.0.0:Low reliability (Monosodium D-glucoheptonate lies outside of the AD)
• IRFMN/ISSCAN-GX 1.0.0:Moderate reliability (Monosodium D-glucoheptonate could be outside
of the AD)
Genotoxicity
Source
Test Type &
Endpoint
Species & Strain
(if available)
Metabolic
Activation
Doses and Controls
Results
Study Details
4851347
In vivo
(Mouse, IP
exposure)
DNA Damage
and Repair
Albino CD-1 mice
Yes
Doses: 500, 1000, and
2000 mg/kg
Replicates: 7 male per
group
Negative
Methods:
• Test substance reported as CASRN 31138-65-5
• Purity: 50.5%
• OECD Guideline 474
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 Parte
htto://dx.doi.ora/10.1080/10590501.2016.1166879 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).
• IRFMN/Antares 1.0.0 and IRFMN/ISSCAN-GX1.0.0 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.
41 Each model is characterized by an applicability domain (AD) that depends on at least 5 various 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 takes into account the other 5 components to provide an overall reliability score - low, moderate or high. EPA has not included low-reliability model results
XX
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• GLP compliant
4940235
Gene
Salmonella
With and
Doses: 50,150, 500,1500,
Negative
Methods:
mutation (in
typhimurium
without
and 5000 pg/plate
• Test substance reported as CASRN 526-95-4
vitro)
TA1535, 1537, 98,
100, and 102
• Purity: 52%
• OECD Guideline 471
• GLP compliant
4940252
Chromosomal
Human
With and
Doses: 0, 0.16, 0.31,
Negative
Methods:
aberrations
lymphocytes
without
0.625, 1.25, 2.5, and 10
• Test substance reported as CASRN 526-95-4
(in vitro)
mM
• Purity: 52%
• OECD Guideline 473
• GLP compliant
4940247,
Gene
Mouse lymphoma
With and
Doses: 1.25, 2.5, 5, and 10
Negative
Methods:
4940234
mutation (in
vitro)
L5178Y cells
without
mM
• Test substance reported as CASRN 526-95-4
• Purity: 52%
• OECD Guideline 490
• GLP compliant
4940109
Gene
Salmonella
With and
Doses: 0,100, 333, 1000,
Negative
Methods:
mutation (In
typhimurium TA97,
without
3333, and 10000 pg/plate
• Test substance reported as CASRN 90-80-2
vitro)
98,100, and 1535
• Purity not reported
• NTP mutagenicity protocol for Ames test
• GLP compliance not reported
4947757
Gene
Salmonella
With and
Doses: 0.25% and 0.5%
Negative
Methods:
mutation (In
typhimurium
without
test substance
• Test substance reported as CASRN 90-80-2
vitro)
TA1535, 1537,
1538
• Purity not reported
• GLP compliance not reported
4947757,
Gene
Saccharomyces
With and
Doses: 1.25% and 2.5%
Negative
Methods:
2072857
mutation (In
vitro)
cerevisiae strain
D4
without
test substance
• Test substance reported as CASRN 90-80-2
• Purity not reported
• GLP compliance not reported
2072857
Gene
Salmonella
With and
Doses: 0.25% and 0.5%
Negative
Methods:
mutation (In
typhimurium
without
test substance
• Test substance reported as CASRN 90-80-2
vitro)
TA1535, 1537,
1538
• Purity not reported
• OECD Guideline 471
• Not GLP compliant
Endpoints:
Cytotoxicity observed at 1 %
XXI
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
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,
2072857
Gene
mutation (in
vitro)
Saccharomyces
cerevisiae strain
D4
With and
without
Doses: 0.75, 1.50, and
3.00% of substance
Negative
Methods:
• Test substance reported as CASRN 299-28-5
• Purity not reported
• OECD Guideline 471
• GLP not reported
Endpoints:
Cytotoxicity observed at 3%
4947764,
2072857
Gene
mutation (in
vitro)
Salmonella
typhimurium
strains TA1535,
TA1537, and
TA1538
With and
without
Doses: 1.25, 2.5 and 5.0%
of substance
Negative
Methods:
• Test substance reported as CASRN 299-28-5
• Purity not reported
• OECD Guideline 471
• GLP not reported
4947765,
2072857
Gene
mutation (in
vitro)
Salmonella
typhimurium
strains TA1535,
TA1537, and
TA1538
With and
without
Doses: 0.0006, 0.0012,
and 0.0024% substance
Negative
Methods:
• 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,
2072857
Gene
mutation (in
vitro)
Saccharomyces
cerevisiae strain
D4
With and
without
Doses: 1.25%, 2.5%, and
5% substance
Negative
Methods:
• Test substance reported as CASRN 527-07-1
• Purity not reported
• OECD Guideline 472
• Non-GLP compliant
Results:
Cytotoxicity was observed at 5%.
XXII
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2072857
Chromosomal
aberrations
(In vivo)
C57BL mice
With
Doses: 0, 2500,5000, and
1000 mg/kg-dayfor 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.
• 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
4864280
Dermal
CBA mice
3 day
Doses: 25 |jL of 25%,
50%, and 100% substance
Replicates: 4 per group
Not
sensitizin
g
Methods:
• Test substance reported as CAS RN 31138-65-5
• 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
XXIII
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
4864279
In vitro skin
EPISKINTM
tissues
15-minute
exposure
followed by 42
hour of post-
exposure
incubation
Dose: 10 pL
Non-
irritating
Methods:
• Test substance identified as CASRN 31138-65-5
• Purity: 99%
• OECD Guideline 439 and EU method B.46
• GLP compliant
4940239
Dermal
New Zealand white
rabbits
Exposures
after 3 minutes,
1 hour, and 4
hours;
observed for
72 hours
Dose: 0.5 mL undiluted test
substance
Replicates: 3 rabbits
2/3 rabbits were exposed
for 4 hours (single dose)
1/3 rabbits were exposed
after 3 minutes, 1 hour, and
4 hours (three doses)
Negative
Methods:
• Test substance reported as CASRN 526-95-4
• Purity reported as 54.4%
• Based on EU Method B.4
• GLP compliant
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 hours
Dose: 0.1 mL test 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
XXIV
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• 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
Single
Dose: 0.1 mL of 50% test
Negative
Methods:
albino rabbits
exposure,
observed for
up to 7 days
substance
Replicates: 9 rabbits
• 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:
• 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
4864283,
Oral (gavage)
Wistar rats
8 weeks
Doses: 0, 30, 300, and
NOAEL:
Methods:
4864285
• Dosing
1000 mg/kg-day
1000
• Test substance reported as CAS RN 31138-65-5
began 2
Replicates: 5 per sex per
mg/kg-
day
• Purity: 49.5%
weeks
group
• OECD Guideline 422
• GLP compliant
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prior to
mating
• Dosing
continued,
through
gestation
to
lactation
day 5 (for
females)
Table B.2: Environmental Hazard
Aquatic Toxicity: Experimental
Source
Species & strain
(if available)
Duration
Doses and
Replicate Number
Effect
Study Details
4851242
Oncorhynchus
mykiss
96 hours
Dose: 100 mg/L
Replicates: 10
LCso> 100
mg/L
Methods:
• Test substance reported as CASRN 31138-65-5
• Purity: 39.94%
• OECD Guideline 203 and U.S. EPA Draft Ecological Effects Test
Guidelines OPPTS 850.1075
• GLP Compliant
4864288
Oncorhynchus
mykiss
96 hours
Doses: 0,100,
180, 320, 560, and
1000 mg/L
LCso> 1000
mg/L
Methods:
• Test substance identified as CASRN 31138-65-5
• Purity: 49.5%
• OECD Guideline 203
• GLP compliant
4851344
Daphnia magna
48 hours
Doses: 0, 0.10,1,
10, and 100 mg/L
Replicates: 4
replicates per dose
ECso > 100
mg/L
Methods:
• Test substance reported as CASRN 31138-65-6
• Purity: 39.94%
• OECD Guideline 202 and the U.S. EPA Draft Ecological Effects
Test Guidelines OPPTS 850.1010
• GLP compliant
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Table B.2: Environmental Hazard
4864287
Daphnia magna
48 hours
Doses: 0,100,
180, 320, 560, and
1000 mg/L
Replicates: 4
replicates per dose
ECso > 1000
mg/L
Methods:
• Test substance reported as CASRN 31138-65-6
• Purity: 49.5%
• OECD Guideline 202
• GLP compliance not reported
4851140, 4897790
Pseudokirchneriella
subcapitata
96 hours
Doses: 0,10,32,
100, 320 and 1000
mg/L
Replicate: 3
replicates per dose
ECso: 790 mg/L
(growth rate)
Methods:
• Test substance reported as CASRN 31138-65-6
• Purity: 49.5%
• OECD Guideline 201
• GLP compliant
Aquatic Toxicity: Estimated
Model
Species
Predicted Effect
Level
Notes
ECOSARv2.0 (Class:
Neutral Organics)
Aquatic
Vertebrates
ChV = 8.6E+5
mg/L
Estimated with the following inputs: SMILES [0-]C(=0)C(0)C(0)C(0)C(0)C(0)C0.[Na+];
MP = 146.5°C (est); WS = 1.0E6 mg/L (est); LogKow = -2.32
ECOSARv2.0 (Class:
Neutral Organics)
Daphnia
magna
ChV = 1.75E+5
mg/L
Estimated with the following inputs: SMILES [0-]C(=0)C(0)C(0)C(0)C(0)C(0)C0.[Na+];
MP = 146.5°C (est); WS = 1.0E6 mg/L (est); LogKow = -2.32
ECOSARv2.0 (Class:
Neutral Organics)
Green
algae
ChV = 8.3E+4
mg/L
Estimated with the following inputs: SMILES [0-]C(=0)C(0)C(0)C(0)C(0)C(0)C0.[Na+];
MP = 146.5°C (est); WS = 1.0E6 mg/L (est); LogKow = -2.32
Table B.3: Fate
Environmental Fate: Experimental
Source
Endpoint
Duration
Doses and number of
replicates
Results
Study Details
4864276
Biodegradation,
O2 consumption
28 day
Dose: 49.5 mg/L
Readily
biodegradable,
10-day window
met
Methods:
• Test substance reported as CASRN 31138-65-5
• Purity: 49.5%
• OECD Guideline 301F
• GLP compliant
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:
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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)
Experimental Fate: Modelled
Model
Data Type
Endpoint
Results
Notes
EPI Suite
v4.11
Estimated
BCF
0.89
EPI Suite
v4.11
Estimated
BAF
3.16
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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://ccha.curopa.cu/rcgistration-
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: 004 supporting | experimental result. Helsinki, Finland.
https://echa.europa.eu/registration-dossier/-/registered-
dossier/1952/7/9/3/?documentUUID=7f2cdd3d-df71-443f-al21-585e86195729
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). (2009a). D-gluconic acid: eye irritation: 001 Key | experimental
result. https://ccha.curopa.cu/rcgistration-dossicr/-/registered-
dossier/ 1957/7/4/3/'MocumcntUUID=54973acf-65d5-4a45-baa 1 -686b9d404172
ECHA (European Chemicals Agency). (2009b). D-gluconic acid: skin irritation/corrosion.
https://ccha.curopa.cu/rcgistration-dossicr/-/registered-
dossier/1957/7/4/2/'MocumcntUUID=7c5421ffl-0cb7-4778-bd8b-23cdclc62d24
ECHA (European Chemicals Agency). (2012). Sodium glucoheptonate: Biodegradation in water:
screening tests. https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/8874/5/3/2
ECHA (European Chemicals Agency). (2013a). Sodium glucoheptonate: acute toxicity: dermal.
https://echa.europa.eu/registration-dossier/-/registered-dossier/8874/7/3/4
ECHA (European Chemicals Agency). (2013b). Sodium glucoheptonate: acute toxicity: oral.
https://echa.europa.eu/registration-dossier/-/registered-dossier/8874/7/3/2
ECHA (European Chemicals Agency). (2013c). Sodium glucoheptonate: developmental
toxicity/teratogenicity: 001 key | experimental result, https://echa.europa.eu/registration-dossier/-
/registered-dossier/8874/7/9/3/?documentUUID=af30alea-cbfe-4b43-b0ad-3d284557ce42
ECHA (European Chemicals Agency). (2013d). Sodium glucoheptonate: in vitro
cytogenicity/chromosome aberration study in mammalian cells: 002 key | experimental result.
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https://echa.europa.eu/registration-dossier/-/registered-
dossier/8874/7/7/2/?documentUUID=195f5a81-la59-4212-bb57-0721d0c08959
ECHA (European Chemicals Agency). (2013e). Sodium glucoheptonate: short-term repeated dose
toxicity: oral 001 key | experimental result, https://ccha.curopa.cu/rcgistration-dossicr/-
/registered-dossier/8874/7/6/2/?documentUUID=b56fe43a-f936-4b2d-b6bd-45488c505bbe
ECHA (European Chemicals Agency). (2013f). Sodium glucoheptonate: Short-term toxicity to aquatic
invertebrates. https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/8874/6/2/4
ECHA (European Chemicals Agency). (2013g). Sodium glucoheptonate: Short-term toxicity to fish.
https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/8874/6/2/2
ECHA (European Chemicals Agency). (2013h). Sodium glucoheptonate: skin irritation/corrosion.
https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/8874/7/4/2
ECHA (European Chemicals Agency). (2013i). Sodium glucoheptonate: skin sensitisation: in vivo
(LLNA). https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-dossicr/8874/7/5/2
ECHA (European Chemicals Agency). (2013j). Sodium glucoheptonate: toxicity to aquatic algae and
cyanobacteria. Helsinki, Finland. https://ccha.curopa.cu/rcgistration-dossicr/-/rcgistcrcd-
dossier/8874/6/2/6
Gautheron. P; Giroux. J; Cottin. M; Audcgond. 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.
Harlan Laboratories. (2013a). Chemical test rule data. Sodium glucoheptonate, acute oral toxicity in the
rate - up-and-down procedure. (Project Number: 41104687). Dalton, GA: Harcros Chemicals Inc.
https://chemview.epa.gov/chemview/chemical data.do?sourceId=2&templateTvpe=Endpoint&che
micalDataId=31658760&chemicalId=80358&modalVaeKev=0-0-2-0
Harlan Laboratories. (2013b). Chemical test rule data: sodium glucoheptonate: algal inhibition test.
Harcros Chemicals Inc.
https://chemview. epa.gov/chemview/chemical data.do?sourceId=2&templateType=Endpoint&che
micalDataId=31713515&chemicalId=80358&modalVaeKev=0-0-0-0
Harlan Laboratories. (2013c). Chemical test rule data: sodium glucoheptonate: micronucleus test in the
mouse. Harcros Chemicals Inc.
https://chemview.epa.gov/chemview/chemical data.do?sourceId=2&templateType=Endpoint&che
micalDataId=31674335&chemicalId=80358&modalVaeKev=0-0-2-2
Harlan Laboratories. (2015a). Chemical test rule data: sodium glucoheptonate CAS No. 31138-65-5:
daphnia sp., 48-hour acute immobilization test. Harcros Chemicals Inc.
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https://chemview.epa.gov/chemview/chemical data.do?sourceId=2&templateTvpe=Endpoint&che
micalDataId=31710114&chemicalId=80358&modalVaeKev=0-0-0-l
Harlan Laboratories. (2015b). Chemical test rule data: sodium glucoheptonate CAS No. 31338-65-5:
acute toxicity to Rainbow Trout. (Harlan Study Number: 41402585). Dalton, GA: Harcros
Chemicals Inc.
https://chemview.epa.gov/chemview/chemical data.do?sourceId=2&templateTvpe=Endpoint&che
micalDataId=31704458&chemicalId=80358&modalVaeKev=0-0-0-l
Inc. FaDRL. (1973). Teratologic evaluation of FDA 71-72 (glucono delta lactone) (pp. 58). Maspeth, NY:
Food and Drug Research Labs Inc.
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
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/v2 liel 4 .htm
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Appendix C: Literature Search Outcomes
C.1 Literature Search Review
This section briefly describes the literature search and review process, search terms, and search outcomes
for the hazard and fate screening of sodium glucoheptonate. 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 C1.
Figure C.l: Overview of the Literature Search and Review Process
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, sodium glucoheptonate, the following LPS
candidates were used as analogs for read-across: D-gluconic acid (CASRN 526-95-4)), sodium gluconate
(CASRN 527-07-1), calcium gluconate (CASRN 299-28-5), and glucono-delta-lactone (CASRN 90-80-
42 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.
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2). For more details and justification on analogs, see section 6.1.1. Analogs were used to fill data gaps on
endpoints for which sodium glucoheptonate lacked quality data, such as developmental toxicity, or to add
to the weight of the scientific evidence. Analog references were searched, screened, and evaluated using
the same process as references on sodium glucoheptonate described above.43
C.1.2 Search terms and results
EPA began the literature review process for the hazard screening of sodium glucoheptonate 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. 1 lists the search terms used in the
database search of peer-reviewed literature for sodium glucoheptonate. For grey literature and other
secondary sources, Table C.2 lists the search terms used for sodium glucoheptonate.
Table C.1: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms45
Human Health
PubMed
31138-65-5[rn] OR "D-Gluco-heptonic acid, monosodium salt, (2.xi)-"[tw] OR "D-gluco-Heptonic
acid, monosodium salt, (2.xi.)-"[tw] OR "D-gluco-Heptonic acid, monosodium salt, (2xi)-"[tw] OR "D-
gluco-Heptonic acid, sodium salt (1:1), (2.xi.)-"[tw] OR "D-gluco-Heptonic acid, sodium salt (1:1),
(2xi)-"[tw] OR "Monosodium D-glucoheptonate"[tw] OR "Sodium glucoheptonate"[tw]
29039-00-7[rn] OR 10094-62-9[rn] OR 100897-12-9[rn] OR "Calcihept"[tw] OR "Calcium bis 2xi -D-
gluco-heptonate"[tw] OR "calcium bis 2£; -D-GLUCO-heptonate"[tw] OR "Calcium gIuceptate"[tw]
OR "Calcium glucoheptonate"[tw] OR "Calcium heptagluconate"[tw] OR "D-gluco-Heptonic acid,
calcium salt"[tw] OR "Glucoheptonic acid, calcium salt"[tw] OR "D-alpha-Glucoheptonic acid,
sodium salt, dihydrate"[tw] OR "D-glycero-D-gulo-Heptonic acid, monosodium salt, dihydrate"[tw]
OR "D-glycero-D-gulo-Heptonic acid, sodium salt, dihydrate"[tw] OR "Gluceptate sodium
dihydrate"[tw] OR "Sodium D-alpha-glucoheptonate dihydrate"[tw] OR "Sodium D-glycero-D-gulo-
heptonate dihydrate"[tw] OR "Ammonium gluceptate"[tw] OR "alpha-glucoheptonic acid "[nm]
Toxline
(31138-65-5 [rn] OR "d-gluco-heptonic acid monosodium salt (2 xi) -" OR "d-gluco-heptonic acid
monosodium salt (2 xi) -" OR "d-gluco-heptonic acid monosodium salt (2xi) -" OR "d-gluco-
heptonic acid sodium salt (1 1) (2 xi) -" OR "d-gluco-heptonic acid sodium salt (1 1) (2xi) -" OR
"monosodium d-glucoheptonate" OR "sodium glucoheptonate") 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])
29039-00-7 [rn] OR 10094-62-9 [rn] OR 100897-12-9 [rn] OR "calcihept" OR "calcium bis 2xi -d-
gluco-heptonate" OR "calcium bis 2£; -d-gluco-heptonate" OR "calcium gluceptate" OR "calcium
glucoheptonate" OR "calcium heptagluconate" OR "d-gluco-heptonic acid calcium salt" OR
"glucoheptonic acid calcium salt" OR "d-alpha-glucoheptonic acid sodium salt dihydrate" OR "d-
glycero-d-gulo-heptonic acid monosodium salt dihydrate" OR "d-glycero-d-gulo-heptonic acid
sodium salt dihydrate" OR "gluceptate sodium dihydrate" OR "sodium d-alpha-glucoheptonate
dihydrate" OR "sodium d-glycero-d-gulo-heptonate dihydrate" OR "ammonium gluceptate") 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]
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.
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Table C.1: Search Terms Used in Peer-Reviewed Databases
Discipline
Database
Search terms45
OR NIOSH [org] OR NTIS [org] OR PESTAB [org] OR PPBIB [org]) AND NOT PubMed [org] AND
NOT pubdart [org]
TSCATS1
31138-65-5 [rn] AND tscats[org]
(29039-00-7 [rn] OR 10094-62-9 [rn]) AND tscats[org]
WOS
TS=("31138-65-5" OR "D-Gluco-heptonic acid, monosodium salt, (2.xi)-" OR "D-gluco-Heptonic
acid, monosodium salt, (2.xi.)-" OR "D-gluco-Heptonic acid, monosodium salt, (2xi)-" OR "D-gluco-
Heptonic acid, sodium salt (1:1), (2.xi.)-" OR "D-gluco-Heptonic acid, sodium salt (1:1), (2xi)-" OR
"Monosodium D-glucoheptonate" OR "Sodium glucoheptonate")
lndexes=SCI-EXPANDED, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED, IC
Timespan=AII years
TS=("29039-00-7" OR "10094-62-9" OR "100897-12-9" OR "Calcihept" OR "Calcium bis 2xi -D-
gluco-heptonate" OR "calcium bis 2£; -D-GLUCO-heptonate" OR "Calcium gluceptate" OR "Calcium
glucoheptonate" OR "Calcium heptagluconate" OR "D-gluco-Heptonic acid, calcium salt" OR
"Glucoheptonic acid, calcium salt" OR "D-alpha-Glucoheptonic acid, sodium salt, dihydrate" OR "D-
glycero-D-gulo-Heptonic acid, monosodium salt, dihydrate" OR "D-glycero-D-gulo-Heptonic acid,
sodium salt, dihydrate" OR "Gluceptate sodium dihydrate" OR "Sodium D-alpha-glucoheptonate
dihydrate" OR "Sodium D-glycero-D-gulo-heptonate dihydrate" OR "Ammonium gluceptate")
Environmental
Hazard
WOS
Same as human health strategy synonyms only
Toxline
Same as human health strategy synonyms only
TSCATS1
Same as human health strategy CASRN only
Proquest
"31138-65-5" OR "D-Gluco-heptonic acid, monosodium salt, (2.xi)-" OR "D-gluco-Heptonic acid,
monosodium salt, (2.xi.)-" OR "D-gluco-Heptonic acid, monosodium salt, (2xi)-" OR "D-gluco-
Heptonic acid, sodium salt (1:1), (2.xi.)-" OR "D-gluco-Heptonic acid, sodium salt (1:1), (2xi)-" OR
"Monosodium D-glucoheptonate" OR "Sodium glucoheptonate"
Fate
WOS
Same as human health strategy synonyms only
Table C.2: Search Terms Used in Grey Literature and Additional Sources
Chemical
Search terms
Sodium
Glucoheptonate
Searched as a string or individually depending on source: "31138-65-5" OR "D-Gluco-heptonic acid,
monosodium salt, (2.xi)-" OR "D-gluco-Heptonic acid, monosodium salt, (2.xi.)-" OR "D-gluco-Heptonic acid,
monosodium salt, (2xi)-" OR "D-gluco-Heptonic acid, sodium salt (1:1), (2.xi.)-" OR "D-gluco-Heptonic acid,
sodium salt (1:1), (2xi)-" OR "Monosodium D-glucoheptonate" OR "Sodium glucoheptonate"
After the search terms were applied, more than 180 references were returned by all search efforts across
peer-reviewed databases and grey literature sources. The total number of references include database
results and additional strategies. All references from the search efforts were screened and evaluated
through the LPS literature search and review process.43 Of these, 19 references were included for data
evaluation and used to support the designation of sodium glucoheptonate as LPS. The included hazard
and fate references are listed in the bibliography of Appendix B.
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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 sodium glucoheptonate. 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 sodium glucoheptonate, EPA excluded a total of 81 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.3), or full-text
screening (see Table C.4). Unacceptable references (e.g., studies that did not meet data quality metrics)
were excluded at full-text screening (see Tables C.5 and C.6). Off-topic and unacceptable references are
displayed next to the corresponding exclusion criteria.
Table C.3: Off-Topic References Excluded at Title/Abstract Screening for Human Health Hazard
1 Reference excluded (HERO ID) because the reference did NOT appear to contain information needs46 relevant to 1
human health hazard
24923
4837160
4837180
4850272
4837145
4837170
4850041
4837155
4837176
4850265
2976788
4837162
4837182
4850278
4837146
4837172
4850100
4837156
4837177
4850268
2989178
4837163
4837183
4850279
4837147
4837173
4850116
4837158
4837178
4850269
3692509
4837164
4837184
4850280
4837150
4837174
4850175
4837159
4837179
4850270
4120475
4837165
4837185
4850281
4837152
4837175
4850185
4837168
4850039
4850283
4123163
4837167
4837203
4850282
4837169
4850040
4850285
4837124
4825460
Reference excluded (HERO ID) because the reference primarily contained in silico data
N/A
Table C.4: 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)
Does the reference contain information pertaining to a
low- priority substance candidate?
No
4850126
What type of source is this reference?
Review article or book
chapter that contains only
citations to primary
literature sources
N/A
What kind of evidence does this reference primarily
contain?
In silico studies that DO
NOT contain experimental
verification
N/A
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.
XIX
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Table C.4: 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)
The following question apply to HUMAN evidence only
Does the reference report an exposure route that is or
is presumed to be by an inhalation, oral, or dermal
route?
No
N/A
Does the reference report both test substance
exposure(s) AND related health outcome(s)?
No
N/A
If the reference reports an exposure to a chemical
mixture, are measures of the test substance or related
metabolite(s) reported independently of other
chemicals?
Note: If the paper does not pertain to mixtures, choose
"Not Applicable".
No
N/A
The following question apply to ANIMAL evidence only
Does the reference report an exposure route that is by
inhalation, oral, or dermal route?
No
4837125
4837151
4837154
4850267
4850273
4850277
4851347
Does the reference report both test substance-related
exposure(s) AND related health outcome(s)?
No
4837154
Does the reference report the duration of exposure?
No
N/A
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
N/A
Does the paper report a negative control that is a
vehicle control or no treatment control?
No47
N/A
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
N/A
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
N/A
For genotoxicity studies only: Does the study use a
positive control?
No
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).
XX
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*** Proposal Draft - Do Not Cite, Quote or Release During the Review ***
Table C.5: 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.
4864284
4864282
Metric 2:
Negative and vehicle
controls
A concurrent negative control group was not included or reported.
OR
The reported negative control group was not appropriate (e.g.,
age/weight of animals differed between control and treated groups).
N/A
Metric 3:
Positive
controls
When applicable, an appropriate concurrent positive control (i.e.,
inducing a positive response) was not used.
N/A
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).
4864282
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).
N/A
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).
4851347
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 endpoints, such as clinical signs and mortality, etc.).
4851346
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.
N/A
XXI
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Table C.6: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Human Health
Hazard - In Vitro
Data Quality
Unacceptable if:
References excluded
Metric
(HERO ID)
Metric 1:
The test substance identity or description cannot be determined from the
N/A
Test substance
information provided (e.g., nomenclature was unclear and CASRN or structure
identity
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:
A concurrent negative control group was not included or reported.
N/A
Negative
OR
controls
The reported negative control group was not appropriate (e.g., different cell
lines used for controls and test substance exposure).
Metric 3:
A concurrent positive control or proficiency group was not used.
N/A
Positive
controls
Metric 4:
The assay type was not reported.
N/A
Assay type
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).
Metric 5:
The exposure doses/concentrations or amounts of test substance were not
N/A
Reporting of
reported.
concentration
Metric 6:
No information on exposure duration(s) was reported.
N/A
Exposure
OR
duration
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).
Metric 7:
No information on the characterization and use of a metabolic activation system
N/A
Metabolic
was reported.
activation
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).
Metric 8:
The test model was not reported
N/A
Test model
OR
The test model was not routinely used for evaluation of the specific outcome of
interest.
Metric 9:
The outcome assessment methodology was not reported.
N/A
Outcome
OR
assessment
The assessment methodology was not appropriate for the outcome(s) of
methodology
interest (e.g., cells were evaluated for chromosomal aberrations immediately
after exposure to the test substance instead of after post-exposure incubation
period).
XXII
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C.2.2 Environmental Hazard
For the screening review of LPS candidate sodium glucoheptonate, EPA excluded a total of 117
references when assessing environmental hazard. Off-topic environmental hazard references excluded at
title/abstract screening are listed in Table C.7, and those excluded at full-text screening are listed in Table
C.8. References in Table C.9 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.7: Off-Topic References Excluded at Title/Abstract Screening for Environmental Hazard
Reference excluded (HERO ID) because the reference did NOT appear to contain information needs48 relevant to
environmental hazard
229154
4850145
4850115
4850099
4850267
4837156
4850169
4850130
4850193
4850138
667743
4850146
4850116
4850100
4850268
4837202
4850174
4850131
4850194
4850139
3491604
4850147
4850117
4850101
4850269
4850085
4850175
4850132
4850199
4850140
3702885
4850148
4850118
4850102
4850270
4850086
4850176
4850133
4850201
4850141
3718142
4850150
4850119
4850104
4850272
4850087
4850177
4850134
4850202
4850142
4123163
4850151
4850121
4850105
4850273
4850088
4850183
4850135
4850203
4850143
4759430
4850152
4850122
4850106
4850277
4850090
4850185
4850136
4850265
4850144
4805432
4850153
4850123
4850107
4850278
4850091
4850189
4850137
4850097
4850283
4825459
4850154
4850124
4850108
4850279
4850092
4850168
4850129
4850098
4850285
4825460
4850159
4850125
4850109
4850280
4850093
4850167
4850128
4850095
4850112
4837125
4850164
4850126
4850110
4850281
4850094
4850111
4850282
4850096
4850114
4837146
4850166
4850127
4837151
4837150
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental hazard data
N/A
Table C.8: 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
N/A
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 hazard data presented?
No
N/A
Is this primarily a modeling/simulation study? [Note: select "No" if experimental verification
was included in the study]
Yes
N/A
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.
XXIII
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Table C.8: Screening Questions and Off-Topic References Excluded at Full-Text Screening for Environmental Hazard
Question
Off-topic if
answer is:
References
excluded
(HERO ID)
Is environmental hazard data presented for standard or non-standard aquatic or terrestrial
species (fish, invertebrates, microorganisms, non-mammalian terrestrial species)?
No
N/A
Is exposure measured for the target substance or is the test substance a mixture (except
for reasonable impurities, byproducts, and aqueous solutions) or formulated product?
Mixture
N/A
Formulated
Product
N/A
Does the reference report a duration of exposure?
No
N/A
Does the reference report a negative control that is a vehicle control or no treatment
control?
No
N/A
Does the reference include endpoints in the information needs?
No
N/A
Table C.9: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Environmental
Hazard
Question
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, 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.
N/A
Metric 2:
Negative controls
A concurrent negative control group was not included or reported.
N/A
Metric 3:
Experimental
system
The experimental system (e.g., static, semi-static, or flow-through regime) was not
described.
N/A
Metric 4:
Reporting of
concentrations
Test concentrations were not reported.
N/A
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., study intended to assess effects on reproduction did not expose
organisms for an acceptable period of time prior to mating).
N/A
Metric 6:
Test organism
characteristics
The test species was not reported.
OR
The test species, life stage, or age was not appropriate for the outcome(s) of
interest.
N/A
Metric 7:
Outcome
assessment
methodology
The outcome assessment methodology was not reported.
N/A
Metric 8:
Reporting of data
Data presentation was inadequate.
OR
Major inconsistencies were present in reporting of results.
4851172
4851343
XXIV
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C.2.3 Fate
For the screening review of LPS candidate sodium glucoheptonate EPA excluded a total of 26 references
when assessing environmental fate. Off-topic fate references excluded at title/abstract screening are listed
in Table C. 10, and those excluded at full-text screening are listed in Table C. 11. References in Table C. 12
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.10: Off-Topic References Excluded at Initial Screening for Fate
I Reference excluded (HERO ID) because the reference did NOT appear to contain information needs49 relevant to I
environmental fate
4123163
4850265
4850281
4837156
4850277
4837146
4850270
4850175
4850280
4825459
4850267
4850282
4837202
4850278
4837150
4850272
4837125
4850269
4825460
4850268
4850283
4850273
4850279
4837151
4850137
4850285
Reference excluded (HERO ID) because the reference did NOT present quantitative environmental fate data
N/A
Table C.11: 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
information pertaining to a low-
priority substance candidate?
No
N/A
What type of source is this
reference?
Review article or book chapter that contains only citations to primary
literature sources
N/A
Is quantitative fate data presented?
No
N/A
Is this primarily a
modeling/simulation study? [Note:
Select "Yes" only if there is no
experimental verification]
Yes
N/A
Table C.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
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:
The study did not include or report crucial control groups that consequently made the study
unusable (e.g., no positive control for a biodegradation study reporting 0% removal).
N/A
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.
XXV
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Table C.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Study
controls
OR
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).
N/A
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.
N/A
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
The test organism is not routinely used and would likely prevent meaningful interpretation of
the study results.
N/A
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.
N/A
Metric 11:
Confounding
variables
There were sources of variability and uncertainty in the measurements and statistical
techniques or between study groups.
N/A
Metric 12:
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
XXVI
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Table C.12: Data Quality Metrics and Unacceptable References Excluded at Data Quality Evaluation for Fate
Verification or
plausibility of
results
XXVII
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