TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0320
Number: P-18-0320
TSCA Section 5(a)(3) Determination: The chemical substance is not likely to present an
unreasonable risk (5(a)(3)(C))
Chemical Name:
Generic: Alkane, diisocyanato-(isocyanatoalkyl)-
Conditions of Use (intended, known, or reasonably foreseen)1:
Intended conditions of use (generic): Import and process for use as and use as a hardner,
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 a number of coating and adhesive uses as reasonably foreseen based on a
patent search.
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 EPA estimated
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-18-0320
that the new chemical substance could have limited persistence and low potential for
bioaccumulation, such that repeated exposures are not expected to cause food-chain effects via
accumulation in exposed organisms. Although EPA estimated that the hydrolysis product 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
test data on the new chemical substance, EPA estimates that the chemical substance has low
environmental hazard and potential for the following human health hazards: skin irritation,
serious eye damage, respiratory sensitization, skin sensitization, 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 data
for analogues (isocyanates) and of the hydrolysis product using data for analogue(s) (another
new chemical substance and other alkylamines) and EPI (Estimation Program Interface) Suite™
(http://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-program-interface). In
wastewater treatment, the new chemical substance is expected to be removed with an efficiency
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 to present an unreasonable risk.
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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0320
of 90% to 99% due to rapid hydrolysis and the hydrolysis product is expected to be removed
with an efficiency of 0% to 90% due to possible biodegradation. Removal of the hydrolysis
product by biodegradation is negligible to high and destruction (mineralization) of the hydrolysis
product by biodegradation is partial to complete. Sorption of the hydrolysis product to sludge is
expected to be low and to soil and sediment is expected to be low to moderate. Migration of the
new chemical substance to groundwater is expected to be negligible due to rapid hydrolysis and
migration of the hydrolysis product to groundwater is expected to be moderate to rapid due to
low to moderate sorption to soil and sediment. Due to low estimated vapor pressure and Henry's
law constant, the new chemical substance and the hydrolysis product are 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; and that the hydrolysis product
has low potential to volatilize to air and has moderate to high potential to 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 data for analogues
(isocyanates) and of the hydrolysis product using data for analogue(s) (another new chemical
substance and other alkylamines) and EPI Suite™. EPA estimated that the new chemical
substance's hydrolysis half-life is minutes to hours; and that the hydrolysis product's aerobic and
anaerobic biodegradation half-lives are 2 to 6 months. These estimates indicate that the new
chemical substance may have limited persistence in aerobic environments (e.g., surface water)
and anaerobic environments (e.g., sediments) due to hydrolysis. Further, these estimates indicate
that the hydrolysis product 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
data for analogues (isocyanates) and of the hydrolysis product to bioaccumulate using EPI
Suite™. EPA estimated that the new chemical substance has low bioaccumulation potential
based on rapid hydrolysis and the hydrolysis product has low bioaccumulation potential based on
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 if 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)
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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0320
BCF/BAF model result < 1000 (hydrolysis product bioconcentration factor = 3 (estimated by
linear regression from log Kow) and bioaccumulation factor = 1 [estimated by the Arnot-Gobas
method (2003)5]). EPA estimated that the new chemical substance could have limited persistence
and low potential for bioaccumulation, such that repeated exposures are not expected to cause
food-chain effects via accumulation in exposed organisms. Although EPA estimated that the
hydrolysis product 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.
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 the new chemical substance based on its
estimated physical/chemical properties, available data on the new chemical substance, by
comparing it to structurally analogous chemical substances for which there is information on
human health hazard, and other structural information. Absorption is poor via all routes based on
physical/chemical properties. For the new chemical substance, EPA identified hazards for skin,
eye, and respiratory tract irritation, skin and respiratory sensitization, and lung effects based on
data on the new chemical substance. The new chemical substance is expected to hydrolyze
rapidly in water; however, no hazards were identified for the oral route of exposure for an
analogue of the hydrolysis product up to 500 mg/kg-bw/day. EPA identified a NOAEC of 2.1
mg/m based on lung effects, which was used to derive exposure route- and population-specific
points of departure for quantitative risk assessment. EPA qualitatively evaluated irritation and
sensitization effects.
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Environmental Hazard : Environmental hazard is relevant to whether a new chemical
substance is likely to present unreasonable risks because the significance of the risk is dependent
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.
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
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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0320
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 based on acute
toxicity data submitted for the new chemical substance. 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
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 exposures via the dermal and inhalation routes.
Releases to water, air, and landfill were estimated. Exposures to the general population were
assessed via drinking water, groundwater ingestion impacted by landfill leaching, fish ingestion,
and fugitive air. Exposure to the general population via stack air inhalation was not assessed
because releases to air were expected to be negligible (below modeling thresholds). Consumer
exposures were not assessed because consumer uses were not identified as 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 (MOE) is
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-18-0320
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 level (i.e., NOAEC) described above. Based on the hazard determination and available
quantitative and qualitative risk information, EPA concludes that there is risk for the new
chemical substance. Risks were identified for workers for lung effects via inhalation exposure
based on quantitative hazard data for the new chemical substance (MOE = 2; Benchmark MOE =
100; Fold factor = 48). Irritation and sensitization hazards to workers via inhalation and dermal
contact were identified based on data on the new chemical substance. Risks for these endpoints
were not quantified due to a lack of dose-response for these hazards. However, exposures and
risks can be mitigated by the use of appropriatePPE, including impervious gloves, eye protection,
protective clothing, and respiratory protection with an APF of at least 1,000. EPA expects that
employers will require and that workers will use appropriate PPE consistent with the Safety Data
Sheet (SDS) prepared by the submitter, in a manner adequate to protect them.
Risks were not identified for the general population for lung effects via inhalation exposure
based on quantitative hazard data for the new chemical substance (MOE = 393; Benchmark
MOE = 100). No hazards were identified for a hydrolysis product of the new chemical substance;
therefore, risks were not calculated. Based on no identified hazards, risks are not expected via
drinking water, groundwater ingestion impacted by landfill leaching, and fish ingestion. Irritation
and sensitization hazards to the general population are not expected via drinking water ingestion
or fugitive air releases due to dilution of the new chemical substance in the media. Risks to
consumers were not evaluated because consumer uses were not identified as intended conditions
of use.
Risk 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, that the new chemical substance could be
used in a number of different uses than the intended use, including for consumer use, and it is
reasonably foreseen that not all workers would use the recommended PPE including respiratory
protection with APF 1,000. The SNUR that has been proposed for this chemical substance
defines certain conditions of use as significant new uses. The proposed significant new uses
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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-18-0320
include: (i) use without worker protections including respiratory protection of at least APF 1,000,
impervious gloves, protective clothing, and eye protection; and, (ii) Use in 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).
06/30/2020			Is/
Date:	Madison H. Le, Director
Chemical Control Division
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
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