TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0060

Number: P-18-0060

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

Chemical Name:

Specific: 1-Butanaminium, 4-amino-N-(2-hydroxy-3-sulfopropyl)-N,N-dimethyl-4-oxo-, N-coco
alkyl derivs., inner salts; CASRN 2041102-83-2

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

Intended conditions of use (specific): Manufacture for use as a surfactant for consumer and

commercial liquid dish detergents (60%), for consumer liquid laundry detergents (25%)
and for industrial hand washing cleaners (15%), with 90% of the production volume for
FDA uses, and 40% of the production volume for TSCA uses for export, 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 none.

Reasonably foreseen conditions of use: Applying such factors as described in footnote 1, EPA
has identified whether there are reasonably foreseen conditions of use and identified,
based on an amendment to the PMN, that it is reasonably foreseen the chemical substance
could be used in industrial detergents which may result in greater water releases than
those resulting from the intended conditions of use described in the amended PMN.

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

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
hypotheticals 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.

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0060

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the terms of the proposed Significant New Use Rule (SNUR) signed by EPA. Although EPA
estimated that the new chemical substance could be persistent, the substance has low potential
for bioaccumulation, such that repeated exposures are not expected to cause food-chain effects
via accumulation in exposed organisms. Based on its estimated physical/chemical properties,
available data on the new chemical substance, and by comparing it to structurally analogous
chemical substances, EPA estimates that the chemical substance has high environmental hazard
and potential for the following human health hazards: skin and eye irritation, reproductive
toxicity, and specific target organ toxicity. The PMN describes conditions of use that mitigate
the human health and environmental 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 found no 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

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
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.

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0060

estimated physical/chemical and fate properties of the new chemical substance using data
submitted for the new chemical substance and EPI (Estimation Program Interface) Suite™
(http://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-programinterface). In
wastewater treatment, the new chemical substance is expected to be removed with an efficiency
of 75% to 90% due to sorption and biodegradation. Removal of the new chemical substance by
biodegradation is moderate to high. Sorption of the new chemical substance to sludge is expected
to be low to moderate and to soil and sediment is expected to be moderate to strong. Migration of
the new chemical substance to groundwater is expected to be negligible due to moderate to
strong sorption to soil and sediment, mitigated by biodegradation. 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.

•j

Persistence : 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 submitted for the new
chemical substance. EPA estimated that the new chemical substance's aerobic biodegradation
half-life is < 2 months and anaerobic biodegradation half-life is 2 to 6 months. These estimates
indicate that the new chemical substance may have limited persistence in aerobic environments
(e.g., surface water) and may be persistent in anaerobic environments (e.g., sediment).

Bioaccumulation4: 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
EPI Suite™. EPA estimated that the new chemical substance has low bioaccumulation potential
based on BCFBAF model result < 1000 (bioconcentration factor = 71 [estimated by linear
regression from log Kow] and bioaccumulation factor = 1 [estimated by the Arnot-Gobas method
(2003)5]). Although EPA estimated that the new chemical substance could be persistent, the

3	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)

4	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)

5	Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals
in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0060

substance has low potential for bioaccumulation, such that 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
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 of 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 hazard. Absorption of the new chemical substance is expected to be nil through the
skin, and poor through the gastrointestinal (GI) tract and lungs based on physical/chemical
properties and analogues. For the new chemical substance, EPA identified irritation of the skin,
eye, and respiratory tract, and maternal and developmental effects as hazards based on submitted
data on the new chemical substance and/or analogue data, and surfactant effects if the new
chemical substance is inhaled. Submitted data on the new chemical substance reported the test
substance as positive for skin irritation (OECD 439) and eye irritation (OECD 492) in vitro,
negative for skin sensitization, no acute oral toxicity identified in female rats, negative for
mutagenicity in bacteria and mammalian cells, and negative for chromosomal aberrations in
mammalian cells. EPA identified a no-observed-adverse-effect-level (NOAEL) of 95 mg/kg-
bw/day based on gastrointestinal (GI) tract ulcers and maternal body weight loss and a lowest-
observed-adverse-effect-concentration (LOAEC) of 0.08 mg/m3 based on lung effects (surfactant
effects), which were protective for systemic effects (including maternal toxicity) and
developmental toxicity and were used to derive exposure route- and population-specific points of
departure for quantitative risk assessment. EPA qualitatively evaluated the irritation.

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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

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
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

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0060

upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the
substance. EPA determined the environmental hazard for this new chemical substance based
on acute toxicity data submitted for the new chemical substance. Acute toxicity values measured
for fish, aquatic invertebrates, and algae are 0.73 mg/L, 7.3 mg/L, and 1.0 mg/L, respectively.
Chronic toxicity values measured for fish, aquatic invertebrates, and algae are 0.073 mg/L, 0.73
mg/L, and 0.79 mg/L, respectively. These toxicity values indicate that the new chemical
substance is expected to have high environmental hazard. Application of assessment factors of 5
and 10 to acute and chronic toxicity values, respectively, results in acute and chronic
concentrations of concern of 0.146 mg/L (146 ppb) and 0.007 mg/L (7 ppb), respectively.

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 assessment, EPA assessed worker exposure via dermal exposure and inhalation
exposures to workers are not expected. Releases to water, air, and landfill were estimated.
Exposure to the general population was assessed via drinking water (from direct releases and
down-the drain uses) and fish ingestion. Exposure to the general population via groundwater
impacted by landfill leaching or inhalation was not assessed because releases were expected to
be negligible (below modeling thresholds). Exposure to consumers was assessed via dermal and
inhalation routes of exposure.

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-
framcwork-manual).

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0060

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
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 substances were evaluated using the route-specific
effect levels (i.e., NOAEL and LOAEC) described above. Risks were not identified for workers
for maternal and systemic toxicity via dermal exposures based on quantitative hazard data for an
analogue (MOE = 13,468; benchmark MOE = 100). Risks were not evaluated for workers via
inhalation exposures, including for lung effects (surfactant effects) because exposures are
expected to be negligible. Irritation hazards to workers via dermal contact were identified based
on submitted data on the new chemical substance and analogues. Risks for these endpoints were
not quantified due to a lack of dose-response for these hazards. However, exposures can be
mitigated by the use of appropriate personal protective equipment (PPE), including impervious
gloves and eye protection. EPA expects that employers will require and that workers will use
appropriate PPE consistent with the Safety Data Sheet prepared by the new chemical submitter,
in a manner adequate to protect them.

Risks were not identified for the general population for maternal and systemic toxicity via
drinking or fish ingestion based on quantitative hazard data for an analogue (MOEAdult =

211,817; MOEinfant = 50,433; MOEpish > 6 million; Benchmark MOE = 100). Risks were not
evaluated for the general population for lung effects (surfactant effects) via drinking water or fish
ingestion because the hazard is not to oral exposures. Risks were not evaluated for the general
population via groundwater impacted by landfill leaching or inhalation because exposures are
expected to be negligible via these media. Irritation hazards to the general population are not
expected via drinking water and fish ingestion due to dilution of the chemical substance in the
media.

Risks were not identified for consumers for maternal and systemic toxicity via exposure to
drinking water or fish ingestion impacted by down-the-drain releases based on quantitative
hazard data for an analogue (MOEs > 1 million; Benchmark MOE = 100). Risks were not
identified for consumers for maternal and systemic toxicity via dermal exposure to laundry
detergent based on quantitative hazard data for an analogue (MOE > 23 million; Benchmark
MOE = 100). Risks were not evaluated for consumers for lung effects (surfactant effects) via

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0060

drinking water, fish ingestion, or via dermal contact because the hazard is not relevant for oral
exposures. Risks were not identified for consumers for lung effects (surfactant effects) from
inhalation exposures to laundry detergent based on quantitative hazard data for an analogue
(MOE > 4 million; Benchmark MOE = 1000). Irritation hazards for are not expected via drinking
water and fish ingestion and via dermal contact or via inhalation exposure as laundry detergent
due to dilution of the new chemical substance in the media.

Risks to the environment were evaluated by comparing estimated surface water concentrations
with the acute and chronic concentrations of concern. Risks from acute exposure to the
environment were not identified due to releases to water that did not exceed the acute COC.

Risks from chronic exposure to the environment were not identified since the chronic COC is

o

exceeded less than 20 days per year.

Based on an amendment to the PMN, it is reasonably foreseen that the chemical substance could
be used other than as described in the PMN, including as an industrial detergent which may
result in greater and more frequent environmental releases, which may present an unreasonable
risk to the environment. 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
other than as described in the PMN and releases to water which exceed a surface water
concentration of 7.3 ppb. 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).

3/31/2020	/s/

Date:	Tala R. Henry, Ph.D.

Deputy Director for Programs

Office of Pollution Prevention and Toxics

8 The 20-day criterion for concluding chronic risk is not likely is based on partial life cycle tests (daphnid chronic
and fish early life stage tests) that typically range from 21 to 28 days in duration.

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