TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-16-0420

Number: P-16-0420

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

Chemical Name:

Generic: Dimethyl cyclohexenyl propanol

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

Intended conditions of use (specific): Import in solution at a concentration of approximately 10%
for processing and use as a fragrance ingredient that will be incorporated into soaps,
detergents, cleaners and other similar household and consumer products at a maximum
concentration of 0.5% by weight in the formulation of the final product, 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
evaluated whether there are reasonably foreseen conditions of use and found none.

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.
Although EPA estimated that the new chemical substance could be very persistent, the new
chemical substance has low potential for bioaccumulation, such that repeated exposures are not
expected to be cumulative. Based on test data on the chemical substance, EPA estimates that the
chemical substance has moderate environmental hazard and potential for the following human

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-16-0420

health hazards: systemic toxicity and eye irritation. EPA concludes that the new chemical
substance is not likely to present an unreasonable risk under the conditions of use.

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 this new chemical substance using test data on
the new chemical substance and data for analogous chemicals. The chemical substance is
estimated to be removed during wastewater treatment with an efficiency of 17% via sorption.
Removal by biodegradation is estimated to be negligible based on test data the new chemical
substance. Sorption to sludge, soil and sediment is estimated to be weak, resulting in rapid
migration to groundwater for the new chemical substance. Volatilization to air is estimated to be
low based on its estimated Henry's law constant. Overall, these estimates are indicative of low
potential for this chemical substance to volatilize into the air and high potential for this chemical
substance to migrate into groundwater.

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. Based on
data for the new chemical substance, EPA estimated the anaerobic and aerobic biodegradation
half-lives to be greater than six months. These estimates for biodegradation indicate that the new
chemical substance may be very persistent in aerobic environments (e.g., surface water) or
anaerobic environments (e.g., sediment).

-2

Bioaccumulation : 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 on the new chemical substance and EPI Suite™. These estimates indicate that the chemical
substance has low bioaccumulation potential (bioconcentration factor = 125; bioaccumulation
factor = 224). Although EPA estimated that the new chemical substance could be very persistent,
the chemical substance has low potential for bioaccumulation, such that the repeated exposures
are not expected to cause food chain effects via accumulation in exposed organisms.

2	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)

3	Bioaccumulation: A chemical substance is considered to have a low potential for bioaccumulation if there are
bioconcentration factors (BCF) or bioaccumulation factors (B AF) 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)

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-16-0420

Human Health Hazard4: 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 new chemical substance based on its
estimated physical/chemical properties, data submitted 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 good through
all routes of exposure based on physical/chemical properties. EPA identified eye irritation and
systematic toxicity as hazards based on submitted test data on the new chemical substance. EPA
identified a NOAEL of 72 mg/kg for systemic toxicity based on reductions in body weight, body
weight change, and food consumption in a submitted OECD 422 study conducted on the new
chemical substance, which was used to derive exposure route and population-specific points of
departure for quantitative risk assessment, described below.

Environmental Hazard5: 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 test data
on the new chemical substance. Based on submitted test data, acute toxicity values for fish,
aquatic invertebrate and algae are 8.45 mg/L, 5.5 mg/L and 6.5 mg/L respectively. Based on
submitted test data on the new chemical substance (with the application of acute to chronic ratio

4	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.

5	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-fiitures-p2-
framework-manual).

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-16-0420

assessment factors of 10 for fish and aquatic invertebrates), chronic toxicity values for fish,
aquatic invertebrates and algae are 0.85 mg/L, 0.55 mg/L and 3.48 mg/L, respectively. These
toxicity values indicate that the new chemical substance is expected to have moderate
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 1.1 mg/L
(1,100 ppb) and 0.055 mg/L (55 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 new chemical assessment, EPA assessed exposure to workers via the dermal route and
inhalation routes. Releases to water and air were estimated. Exposure to the general population
was assessed via drinking water. Exposure to the general population via inhalation was not
assessed because releases to air were below modeling thresholds. EPA assessed exposures to
consumers via the dermal and inhalation routes.

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 1000 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

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TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-16-0420

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., NOAEL) described above. Risks were not identified for workers for systemic
toxicity via inhalation (MOE = 94426, benchmark MOE = 100). Risks were identified for
workers for systemic toxicity via dermal exposure (MOE = 32, benchmark MOE = 100).
However, risks can be mitigated by the use of appropriate PPE, including impervious gloves.
Eye irritation was identified as a hazard based on submitted data. Risks for this hazard endpoint
cannot be quantified due to a lack of dose-response for this hazard. However, exposures can be
mitigated by the use of appropriate PPE, i.e., eye protection. EPA expects 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 systemic toxicity via drinking water
(MOEAduit = 81,540; MOEinfant = 19,554, benchmark MOE = 100) or fish ingestion (MOE =
21,114, benchmark MOE = 100). Risks were not identified for consumers for systemic toxicity
via dermal (MOE>245, benchmark MOE = 100) or inhalation exposure (MOE>181, benchmark
MOE = 100).

Risks to the environment were evaluated by comparing estimated surface water concentrations
with the estimated acute and chronic concentrations of concern. Risks to the environment were
not identified due to relevant estimated surface water concentrations that do not exceed the acute
COC or the chronic COC.

Because worker exposures can be controlled by PPE, and no unreasonable risks to the general
population, consumers or environment were identified, EPA has determined that the new
chemical substance is not likely to present unreasonable risk to human health or the environment
under the conditions of use.

03/26/2019	/s/

Date:	Tala R. Henry, Ph D

Acting Deputy Director for Programs
Office of Pollution Prevention and Toxics

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