TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0136
Number: P-19-0136
TSCA Section 5(a)(3) Determination: The chemical substance is not likely to present an
unreasonable risk (5(a)(3)(C))
Chemical Name:
Generic: iso-alkylamine, N-isoalkyl-N-methyl
Conditions of Use (intended, known, or reasonably foreseen)1:
Intended conditions of use (specific): Import for use and use as a chemical intermediate,
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 uses other than as a chemical intermediate as reasonably foreseen, based on
a patent search and prior TSCA submissions.
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.2 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
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.
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
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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0136
estimated that the new chemical substance could be persistent, the new chemical 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 physical/chemical properties of
the new chemical substance, other structural information, and test data on analogous chemical
substances, EPA estimates that the chemical substance has low environmental hazard and
potential for the following human health hazards: skin irritation, eye irritation, 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 Significant New Use Notice
(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
estimated physical/chemical and fate properties of the new chemical substance using 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 90% due to sorption and possible biodegradation. Removal
of the new chemical substance by biodegradation is negligible to high. Sorption of the new
chemical substance to sludge, soil, and sediment is expected to be strong. Migration of the new
chemical substance to groundwater is expected to be slow due to strong sorption to soil and
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-19-0136
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.
-2
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 EPI Suite™. EPA
estimated that the new chemical substance's aerobic and anaerobic biodegradation half-lives are
2 to 6 months. These estimates indicate that the new chemical substance may be persistent in
aerobic environments (e.g., surface water) and 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 = 3 [estimated] and bioaccumulation
factor = 1 [estimated]). Although EPA estimated that the new chemical substance could be
persistent, the substance has a low potential for bioaccumulation, such that repeated exposures
are not expected to cause food-chain effects via accumulation in exposed organisms.
Human Health Hazard5: Human health hazard is relevant to whether a new chemical substance
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 if 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	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
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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0136
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, by comparing it to structurally analogous chemical
substances for which there is information on human health hazard, and other structural
information. Absorption is expected to be poor through the skin and nil through the GI tract and
lungs based on physical/chemical properties and analogue data. For the new chemical substance,
EPA identified irritation to skin, eyes and respiratory tract; systemic effects; and developmental
effects (if the new chemical is bioavailable) as hazards, based on analogue data. EPA identified
lung effects (surfactancy) as a hazard based on a structural alert if the substance is inhaled. No
test data were submitted on the new chemical substance. EPA identified an oral NOAEL of 50
mg/kg-day and a dermal NOAEL of 5 mg/kg-day, based on systemic effects (the NOAELs are
also protective of developmental effects) that were used to derive exposure route- and
population-specific points of departure.
Environmental Hazard6: 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 chemical substance. This substance
falls within the TSCA New Chemicals Category of Aliphatic Amines. 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 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
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.
6 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-19-0136
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 contact; 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, fish ingestion, and groundwater via landfill
leachate. Exposure to the general population via stack air inhalation was not assessed because
releases to air were expected to be negligible (below modeling thresholds) or via fugitive air
inhalation because no releases are expected. Consumer exposures were not assessed because
consumer uses were not identified as conditions of use.
Risk Characterization: EPA applies a margin of exposure (MOE) 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 substance were evaluated using the route-specific
effect levels (i.e., NOAELs) described above. Risks were identified for workers for systemic
effects via dermal exposure based on quantitative hazard data for an analogue (MOE = 0.25;
Benchmark MOE = 100). However, the new chemical substance is expected to be severely
irritating via dermal exposure, thus reducing the likelihood of repeated, sustained exposures
required for systemic effects to occur. Irritation hazards to workers were identified based on a
structural alert for aliphatic amines and analogue data. Risks for these endpoints were not
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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0136
quantified due to a lack of dose-response for these hazards. However, exposures and risks 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 (SDS) prepared by the new chemical
submitter, in a manner adequate to protect them. Risks were not evaluated for workers via
inhalation because inhalation exposures are expected to be negligible.
Risks were not identified for the general population for systemic effects via drinking water, fish
ingestion, or groundwater impacted by landfill leaching based on quantitative hazard data for an
analogue (All MOEs > 51,000; Benchmark MOE = 100). Irritation hazards to the general
population are not expected via drinking water, fish ingestion, or groundwater impacted by
landfill leaching due to dilution of the chemical substance in the media. Risks were not evaluated
for the general population via stack air inhalation because inhalation exposures are expected to
be negligible or via fugitive air inhalation because no releases are expected. Risks to consumer
were not evaluated because consumer uses were not identified as conditions of use.
Risks from acute and chronic exposures to the environment are not expected at any concentration
of the new chemical substance soluble in water (i.e., no effects at saturation).
It is reasonably foreseen, based on a patent search and prior TSCA submissions, that the new
chemical substance could be used other than as a chemical intermediate. 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 uses other than as a chemical intermediate.
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).
4/29/2020			ls[	
Date:	Tala R. Henry, Ph.D.
Deputy Director for Programs
Office of Pollution Prevention and Toxics
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