TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0381

Number: P-18-0381

TSCA Section 5(a)(3) Determination: The chemical substance is not likely to present an
unreasonable risk (5(a)(3)(C))

Chemical Name:

Specific: Indium manganese yttrium oxide; CASRN: 1239902-45-4

Conditions of Use (intended, known, or reasonably foreseen)1:

Intended conditions of use (generic): Manufacture for use in exterior paints and plastics,

consistent with the manufacturing, processing, use, distribution, and disposal information
described in the PMN.

Known conditions of use: Applying such factors as described in footnote 1, EPA evaluated
whether there are known conditions of use and found, based on information in a prior
TSCA submission, that the new chemical substance is known to be used in a manner
nearly identical to some of the intended conditions of use, though the PMN describes
additional conditions of use.

Reasonably foreseen conditions of use: Applying such factors as described in footnote 1, EPA
has identified use of the new chemical substance in spray applications for industrial or
consumer use as reasonably foreseen based on the submitter's history of manufacturing
similar, sprayable products for industrial and consumer use.

Summary: The chemical substance is not likely to present an unreasonable risk of injury to
health or the environment, without consideration of costs or other nonrisk factors, including an
unreasonable risk to a potentially exposed or susceptible subpopulation identified as relevant by
the Administrator under the conditions of use, based on the risk assessment presented below and
the terms of the proposed Significant New Use Rule (SNUR) signed by EPA. Although EPA

1	Under TSCA § 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." In general, EPA considers the intended conditions of use of a new
chemical substance to be those identified in the section 5(a) notification. Known conditions of use include activities
within the United States that result from manufacture that is exempt from PMN submission requirements.

Reasonably foreseen conditions of use are future circumstances, distinct from known or intended conditions of use,
under which the Administrator expects the chemical substance to be manufactured, processed, distributed, used, or
disposed of. The identification of "reasonably foreseen" conditions of use will necessarily be a case-by-case
determination and will be highly fact-specific. Reasonably foreseen conditions of use will not be based on
hypothetical or conjecture. EPA's identification of conditions of use includes the expectation of compliance with
federal and state laws, such as worker protection standards or disposal restrictions, unless case-specific facts indicate
otherwise. Accordingly, EPA will apply its professional judgment, experience, and discretion when considering such
factors as evidence of current use of the new chemical substance outside the United States, evidence that the PMN
substance is sufficiently likely to be used for the same purposes as existing chemical substances that are structurally
analogous to the new chemical substance, and conditions of use identified in an initial PMN submission that the
submitter omits in a revised PMN. The sources EPA uses to identify reasonably foreseen conditions of use include
searches of internal confidential EPA PMN databases (containing use information on analogue chemicals), other
U.S. government public sources, the National Library of Medicine's Hazardous Substances Data Bank (HSDB), the
Chemical Abstract Service STN Platform, REACH Dossiers, technical encyclopedias (e.g., Kirk-Othmer and
Ullmann), and Internet searches.

2	Reasonably foreseen conditions of use subject to a proposed SNUR are not likely to present an unreasonable risk
of injury to health or the environment. Based on EPA's experience, it is the Agency's judgment that a new use

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0381

estimated that the new chemical substance could be very persistent, the substance does not
bioaccumulate by lipophilic partitioning and there is low concern that it will accumulate in some
organisms; thus, repeated exposures are not expected to cause food-chain effects via
accumulation in exposed organisms. Based on EPA's TSCA New Chemicals Program Chemical

"3

Category for Respirable, Poorly Soluble Particulates, estimated physical/chemical properties,
available data on the new chemical substance, and test data on analogous chemical substances,
EPA estimates that the chemical substance has low environmental hazard and potential for the
following human health hazard: specific target organ toxicity. The PMN describes conditions of
use that mitigate the human health risks. Therefore, EPA concludes that the new chemical is not
likely to present unreasonable risk to human health or the environment under the intended
conditions of use.

As set forth below, the information available to EPA is sufficient to permit the Agency to
conduct a reasoned evaluation of the health and environmental effects of the chemical substance
under the conditions of use that are not subject to the proposed SNUR, in order to determine that
the chemical substance is not likely to present an unreasonable risk under those conditions of
use. As such, EPA does not need to impose testing requirements to conduct this evaluation.
Whether testing is needed to evaluate the effects of the intended, known, or reasonably foreseen
conditions of use of a chemical substance subject to a PMN is determined on a case-by-case
basis. To the extent that testing may be necessary to conduct a reasoned evaluation of the health
or environmental effects of the reasonably foreseen conditions of use that are subject to the
proposed SNUR, EPA will make the appropriate determination if a SNUN is submitted
following finalization of the SNUR.

EPA previously assessed the new chemical substance under the known conditions of use,
assessed the intended conditions of use, and addressed reasonably foreseen conditions of use by
proposing a SNUR. Therefore, EPA determines the new chemical substance is not likely to
present unreasonable risk to human health or the environment.

Fate: Environmental fate is the determination of which environmental compartment(s) a
chemical moves to, the expected residence time in the environmental compartment(s) and
removal and degradation processes. Environmental fate is an important factor in determining
exposure and thus in determining whether a chemical may present an unreasonable risk. EPA

would not commence during the pendency of a proposed SNUR because web posting of a proposed SNUR serves as
the cut-off date for a significant new use. Therefore, manufacturers and processors would not commence a
prohibited new use that would be legally required to cease upon the finalization of the SNUR. Once a SNUR is final
and effective, no manufacturer or processor - including the PMN submitter - may undertake the conditions of use
identified as a significant new use of the PMN substance in the SNUR. EPA must first evaluate the new use in
accordance with the requirements of TSCA Section 5 and (a) either conclude that the new use is not likely to present
an unreasonable risk under the conditions of use; or (b) take appropriate action under section 5(e) or 5(f). If EPA
were not to finalize the proposed SNUR, then that decision would be based on information and data provided to the
Agency during the comment period demonstrating that the reasonably foreseen conditions of use subject to the
proposed SNUR are not likely to present an unreasonable risk. Under either scenario, the reasonably foreseen
condition of use is not likely present an unreasonable risk.

3 TSCA New Chemicals Program (NCP) Chemical Categories, https://www.epa.gov/reviewing-new-chemicals-
under-toxic-substances-control-act-tsca/chemical-categories-used-review-new.

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0381

estimated physical/chemical and fate properties of the new chemical substance using data for
analogues (metal oxides). In wastewater treatment, the new chemical substance is expected to be
removed with an efficiency of 90% due to sorption. Removal of the new chemical substance by
biodegradation is negligible. Sorption of the new chemical substance to sludge is expected to be
strong and to soil and sediment is expected to be very strong. Migration of the new chemical
substance to groundwater is expected to be negligible due to very strong sorption to soil and
sediment. Due to low estimated vapor pressure and Henry's law constant, the new chemical
substance is expected to undergo negligible volatilization to air. Overall, these estimates indicate
that the new chemical substance has low potential to volatilize to air or migrate to groundwater.

Persistence4: Persistence is relevant to whether a new chemical substance is likely to present an
unreasonable risk because chemicals that are not degraded in the environment at rates that
prevent substantial buildup in the environment, and thus increase potential for exposure, may
present a risk if the substance presents a hazard to human health or the environment. EPA
estimated degradation half-lives of the new chemical substance using data for analogues (metal
oxides). EPA estimated that the new chemical substance's aerobic and anaerobic biodegradation
half-lives are > 6 months. These estimates indicate that the new chemical substance may be very
persistent in aerobic environments (e.g., surface water) and anaerobic environments (e.g.,
sediment).

Bioaccumulation5: Bioaccumulation is relevant to whether a new chemical substance is likely to
present an unreasonable risk because substances that bioaccumulate in aquatic and/or terrestrial
species pose the potential for elevated exposures to humans and other organisms via food chains.
EPA estimated the potential for the new chemical substance to bioaccumulate using data for
analogues (metal oxides). EPA estimated that the new chemical substance does not
bioaccumulate by lipophilic partitioning, and there is low concern that it may accumulate in
some organisms. Although EPA estimated that the new chemical substance could be very
persistent, the substance does not bioaccumulate by lipophilic partitioning and there is low
concern that it will accumulate in some organisms; thus, repeated exposures are not expected to
cause food-chain effects via accumulation in exposed organisms.

Human Health Hazard6: Human health hazard is relevant to whether a new chemical substance

4	Persistence: A chemical substance is considered to have limited persistence if it has a half-life in water, soil or
sediment of less than 2 months or there are equivalent or analogous data. A chemical substance is considered to be
persistent if it has a half-life in water, soil or sediments of greater than 2 months but less than or equal to 6 months
or if there are equivalent or analogous data. A chemical substance is considered to be very persistent if it has a half-
life in water, soil or sediments of greater than 6 months or there are equivalent or analogous data. (64 FR 60194;
November 4, 1999)

5	Bioaccumulation: A chemical substance is considered to have a low potential for bioaccumulation if there are
bioconcentration factors (BCF) or bioaccumulation factors (BAF) of less than 1,000 or there are equivalent or
analogous data. A chemical substance is considered to be bioaccumulative if there are BCFs or BAFs of 1,000 or
greater and less than or equal to 5,000 or there are equivalent or analogous data. A chemical substance is considered
to be very bioaccumulative if there are BCFs or BAFs of 5,000 or greater or there are equivalent or analogous data.
(64 FR 60194; November 4 1999)

6	A chemical substance is considered to have low human health hazard if effects are observed in animal studies with
a No Observed Adverse Effect Level (NOAEL) equal to or greater than 1,000 mg/kg/day or if there are equivalent
data on analogous chemical substances; a chemical substance is considered to have moderate human health hazard if

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is likely to present an unreasonable risk because the significance of the risk is dependent upon
both the hazard (or toxicity) of the chemical substance and the extent of exposure to the
substance. EPA estimated the human health hazard for this chemical substance based on its
estimated physical/chemical properties, available data on the new chemical substance and by
comparing it to structurally analogous chemical substances for which there is information on
human health hazards, and other structural information. Absorption of the new chemical
substance is expected to be nil through the skin (based on physical-chemical properties) and poor
through the lungs and GI tract (based on data for an analogue). EPA identified lung effects as a
hazard, if respirable, based on respirable, poorly soluble particulates in EPA's TSCA New
Chemicals Program Chemical Categories document. EPA also identified neurotoxicity as a
hazard based on manganese components of the new chemical substance, if bioavailable. EPA
identified a NOAEC of 4 mg/m3 based on lung effects and a NOAEL of 0.14 mg/kg/day based
on neurological effects, which were protective for all health concerns and were used to derive
exposure route- and population-specific points of departure for quantitative risk assessment.

n

Environmental Hazard : Environmental hazard is relevant to whether a new chemical
substance is likely to present unreasonable risk because the significance of the risk is dependent
upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the
substance. EPA estimated environmental hazard of this new chemical substance using
predictions based on the negligible water solubility of the new chemical substance (insoluble
mixed metal oxides (micron sized)). Acute and chronic toxicity values estimated for fish, aquatic
invertebrates and algae are all no effects at saturation. These toxicity values indicate that the new
chemical substance is expected to have low environmental hazard. Because hazards are not

effects are observed in animal studies with a NOAEL less than 1,000 mg/kg/day or if there are equivalent data on
analogous chemical substances; a chemical substance is considered to have high human health hazard if there is
evidence of adverse effects in humans or conclusive evidence of severe effects in animal studies with a NOAEL of
less than or equal to 10 mg/kg/day or if there are equivalent data on analogous chemical substances. EPA may also
use Benchmark Dose Levels (BMDL) derived from benchmark dose (BMD) modeling as points of departure for
toxic effects. See https://www.epa.gov/bmds/what-benchmark-dose-software-bmds. Using this approach, a BMDL
is associated with a benchmark response, for example a 5 or 10 % incidence of effect. The aforementioned
characterizations of hazard (low, medium, high) would also apply to BMDLs. In the absence of animal data on a
chemical or analogous chemical substance, EPA may use other data or information such as from in vitro assays,
chemical categories (e.g., Organization for Economic Co-operation and Development, 2014 Guidance on Grouping
of Chemicals, Second Edition. ENV/JM/MONO(2014)4. Series on Testing & Assessment No. 194. Environment
Directorate, Organization for Economic Co-operation and Development, Paris, France.

(http://www.oecd.org/officialdocuments/publicdisplavdocumentpdf/?cote=env/im/mono(2014)4&doclanguage=en)).
structure-activity relationships, and/or structural alerts to support characterizing human health hazards.

7 A chemical substance is considered to have low ecotoxicity hazard if the Fish, Daphnid and Algae LC50 values are
greater than 100 mg/L, or if the Fish and Daphnid chronic values (ChVs) are greater than 10.0 mg/L, or there are not
effects at saturation (occurs when water solubility of a chemical substance is lower than an effect concentration), or
the log Kow value exceeds QSAR cut-offs. A chemical substance is considered to have moderate ecotoxicity hazard
if the lowest of the Fish, Daphnid or Algae LC50s is greater than 1 mg/L and less than 100 mg/L, or where the Fish
or Daphnid ChVs are greater than 0.1 mg/L and less than 10.0 mg/L. A chemical substance is considered to have
high ecotoxicity hazard, or if either the Fish, Daphnid or Algae LC50s are less than 1 mg/L, or any Fish or Daphnid
ChVs is less than 0.1 mg/L (Sustainable Futures https://www.epa.gov/sustainable-futures/sustainable-futures-p2-
framework-manual).

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0381

expected up to the water solubility limit, acute and chronic concentrations of concern are not
identified.

Exposure: The exposure to a new chemical substance is potentially relevant to whether a new
chemical substance is likely to present unreasonable risks because the significance of the risk is
dependent upon both the hazard (or toxicity) of the chemical substance and the extent of
exposure to the substance.

EPA estimates occupational exposure and environmental release of the new chemical substance
under the intended conditions of use described in the PMN using ChemSTEER (Chemical
Screening Tool for Exposures and Environmental Releases; https://www.epa.gov/tsca-screening-
tools/chemsteer-chemical-screening-tool-exposures-and-environmental-releases). EPA uses
EFAST (the Exposure and Fate Assessment Screening Tool; https://www.epa.gov/tsca-
screening-tools/e-fast-exposure-and-fate-assessment-screening-tool-version-2014) to estimate
general population, consumer, and environmental exposures.

EPA considers workers to be a potentially exposed or susceptible subpopulation (PESS) on the
basis of greater exposure potential compared to the general population. EPA also considers PESS
in conducting general population drinking water exposures by evaluating risks associated with
water intake rates for multiple age groups, ranging from infants to adults. EPA considers
consumers of specific products to be a potentially exposed or susceptible subpopulation on the
basis of greater exposure potential compared to the general population who do not use specific
products.

For this new chemical assessment, EPA assessed worker exposures via the dermal and inhalation
routes. Releases to water, air, and landfill were estimated. General population exposures were
assessed via the oral route (drinking water). Exposures to the general population via fish
ingestion, groundwater ingestion (landfill leaching), and stack and fugitive air inhalation were
not assessed as these exposures were expected to be negligible (below modeling thresholds).
Exposures to consumers were assessed via the dermal route under the intended conditions of use
and via the inhalation route under the reasonably foreseen conditions of use.

Risk Characterization: EPA applies a margin of exposure approach to calculate potential
human health risks of new chemicals. A benchmark (acceptable) margin of exposure is derived
by applying uncertainty factors for the following types of extrapolations: intra-species
extrapolation (UFH = 10 to account for variation in sensitivity among the human population),
inter-species extrapolation (UFa = 10 to account for extrapolating from experimental animals to
humans) and LOAEL-to-NOAEL extrapolation (UFL = 10 to account for using a LOAEL when
a NOAEL is not available). Hence, in the New Chemicals Program, a benchmark MOE is
typically 100 and 1,000 when NOAELs and LOAELs, respectively, are used to identify hazard.
When allometric scaling or pharmacokinetic modeling is used to derive an effect level, the UFh
may be reduced to 3, for a benchmark MOE of 30. The benchmark MOE is used to compare to
the MOE calculated by comparing the toxicity NOAEL or LOAEL to the estimated exposure
concentrations. When the calculated MOE is equal to or exceeds the benchmark MOE, the new
chemical substance is not likely to present an unreasonable risk. EPA assesses risks to workers
considering engineering controls described in the PMN but in the absence of personal protective

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equipment (PPE) such as gloves and respirators. If risks are preliminarily identified, EPA then
considers whether the risks would be mitigated by the use of PPE (e.g., impervious gloves,
respirator).

Risks to human health for the new chemical substance were evaluated using the route-specific
effect levels (i.e. NOAEL, NOAEC) described above. Risks to workers were not evaluated for
neurotoxicity via dermal exposure since absorption is expected to be nil through the skin. Risks
were identified for workers for lung effects via inhalation exposure (particulate) based on
quantitative hazard data for an analogue (MOE = 4; benchmark MOE = 100, fold factor = 22).
Risks will be mitigated if exposures are controlled by the use of appropriate PPE, including
impervious gloves and a respirator with assigned protection factor of at least 50. EPA expects
that employers will require and workers will use appropriate PPE (i.e., impervious gloves,
respirator), consistent with the Safety Data Sheet prepared by the PMN submitter, in a manner
adequate to protect them.

Risks were not identified for the general population for neurotoxicity via oral exposure based on
quantitative hazard data for manganese, a constituent of the new chemical substance present at
2.43% (MOEAduits = 57,671; MOEin|ants = 13,731; benchmark MOE = 1). Risks were not
evaluated for the general population via fish ingestion, groundwater ingestion (landfill leaching),
or stack or fugitive air inhalation because these exposures are not expected (below modeling
thresholds).

Risks were not evaluated for consumers for neurotoxicity via dermal exposure under the
intended conditions of use since absorption is expected to be nil through the skin. Risks were
identified for consumers for lung effects via inhalation exposure based quantitative hazard data
for an analogue (MOEaerosoi = 5, benchmark MOE = 100) using a generic consumer spray
application scenario, because EPA identified consumer spray application as a reasonably
foreseen condition of use.

Risks to the environment from acute and chronic exposure are not expected at any concentration
of the new chemical substance soluble in the water (i.e., no effects at saturation).

It is reasonably foreseen, based on the submitter's history of manufacturing similar products for
industrial and consumer use, that the new chemical substance could be used in sprayable
commercial and/or consumer products. The SNUR that has been proposed for this chemical
substance defines certain conditions of use as significant new uses. The proposed significant new
uses include use in spray applications in industrial and consumer products. Conditions of use that
fall under the restrictions of the proposed SNUR are not likely to present unreasonable risk of
injury to health or the environment because (1) those conditions of use are not likely to be
commenced during the pendency of the proposed SNUR, and (2) upon finalization of the SNUR,
those conditions of use would be prohibited unless and until EPA makes an affirmative
determination that the significant new use is not likely to present an unreasonable risk or takes
appropriate action under section 5(e) or 5(f).

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0381

3/31/2020		Is/

Date:	Tala R. Henry, Ph.D.

Deputy Director for Programs

Office of Pollution Prevention and Toxics

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