SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
CHEMICAL CATEGORY NAME
Alkyl Acetates C6 to C13
SPONSORED CHEMICALS
Hexanol, acetate, branched and linear (C6-rich)
Acetic acid, C6-8 branched alkyl esters (C7-rich)
Acetic acid, CI 1-14 branched alkyl esters (C13-rich)
CAS No. 88230-35-7
CAS No. 90438-79-2
CAS No. 108419-35-8
SUPPORTING CHEMICALS
Acetic acid, C7-9 branched alkyl esters (C8-rich)
Acetic acid, C8-10 branched alkyl esters (C9-rich)
Acetic acid, C9-11 branched alkyl esters (ClO-rich)
CAS No. 108419-32-5
CAS No. 108419-33-6
CAS No. 108419-34-7
December 2007
INTERIM
Prepared by
High Production Volume Chemicals Branch
Risk Assessment Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001

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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
The High Production Volume (HPV) Challenge Program1 is a voluntary initiative aimed at developing and making
publicly available screening-level health and environmental effects information on chemicals manufactured in or
imported into the United States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsor chemicals; sponsorship entails the identification and
initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data do
not exist, and making both new and existing data and information available to the public. Each complete data
submission contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'2) endpoints that
are screening-level indicators of potential hazards (toxicity) for humans or the environment.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is evaluating the data
submitted in the HPV Challenge Program on approximately 1400 sponsored chemicals. OPPT is using a hazard-
based screening process to prioritize review of the submissions. The hazard-based screening process consists of two
tiers described below briefly and in more detail on the Hazard Characterization website3.
Tier 1 is a computerized sorting process whereby key elements of a submitted data set are compared to established
criteria to "bin" chemicals/categories for OPPT review. This is an automated process performed on the data as
submitted by the sponsor. It does not include evaluation of the quality or completeness of the data.
In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is
performed according to established EPA guidance2'4 and is based primarily on hazard data provided by sponsors.
EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have
become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent
data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar
chemical structures, properties and biological activities may be grouped together and their data shared across the
resulting category. This approach often significantly reduces the need for conducting tests for all endpoints for all
category members. As part of Tier 2, evaluation of chemical category rationale and composition and data
extrapolation(s) among category members is performed in accord with established EPA2 and OECD5 guidance.
The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing
chemicals review process. These hazard characterizations are technical documents intended to support subsequent
decisions and actions by OPPT. Accordingly, the documents are not written with the goal of informing the general
public. However, they do provide a vehicle for public access to a concise assessment of the raw technical data on
HPV chemicals and provide information previously not readily available to the public. The public, including
sponsors, may offer comments on the hazard characterization documents.
The screening-level hazard characterizations, as the name indicates, do not evaluate the potential risks of a chemical
or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of
and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the
Inventory Update Reporting (IUR) rule. For the chemicals in the HPV Challenge Program, EPA will review the
IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the
screening-level hazard characterizations to develop screening-level risk characterizations4'6. The screening-level
risk characterizations will inform EPA on the need for further work on individual chemicals or categories. Efforts
are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk-
based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production
Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.
1	U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
2	U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
3	U.S. EPA. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html).
4	U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
5	OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf.
6	U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm.
2

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SCREENING-LEVEL HAZARD CHARACTERIZATION
Alkyl Acetates C6 to C13 Category
Introduction
The sponsor, ExxonMobil Chemical Company, submitted a Test Plan and Robust Summaries to EPA for the Alkyl
Acetates C6 to C13 category on December 21, 2000. EPA posted the submission on the ChemRTK HPV Challenge
website on February 7, 2001 (http://www.epa.gov/chemrtk/pubs/summaries/alkvlace/cl2939tc.htm'). EPA
comments on the original submission were posted to the website on June 6, 2001. Public comments were also
received and posted to the website. The sponsor submitted updated/revised documents on August 24, 2005, which
were posted to the ChemRTK website on August 31, 2005. The Alkyl Acetates C6 to C13 category consists of the
following six mixtures:
Sponsored Chemicals:
Hexanol, acetate, branched and linear (C6-rich)
Acetic acid, C6-8 branched alkyl esters (C7-rich)
Acetic acid, CI 1-14 branched alkyl esters (CI3-rich)
Supporting Chemicals:
Acetic acid, C7-9 branched alkyl esters (C8-rich)
Acetic acid, C8-10 branched alkyl esters (C9-rich)
Acetic acid, C9-11 branched alkyl esters (ClO-rich)
CAS No. 88230-35-7
CAS No. 90438-79-2
CAS No. 108419-35-8
CAS No. 108419-32-5
CAS No. 108419-33-6
CAS No. 108419-34-7
This screening-level hazard characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsors) under the HPV Challenge Program. In preparing the hazard characterization,
EPA considered its own comments and public comments on the original submission as well as the sponsor's
responses to comments and revisions made to the submission. Structure(s) of the sponsored chemical(s) is included
in the appendix. The screening-level hazard characterization for environmental and human health toxicity is based
largely on SIDS endpoints and is described according to established EPA or OECD effect level definitions and
hazard assessment practices.
Category Justification
The alkyl acetates category includes six chemicals (named above) that have a common structure consisting of an
acetate ester functional group (CH3COO-R) and a branched alkyl side chain (R). The alkyl side chain varies
incrementally across the members of the category from six to 13 carbons as the main substituent. Each member
typically consists of methyl-branched isomers of various chain lengths, the composition of which depends on the
alcohol feedstock. For example, the Cn-Ci4 alkyl acetates identify the range of possible isomers, although the
predominant one is a Ci3-length side chain. Thus, the upper end of the category boundary is identified as the
predominant isomer (Ci3) in this range. Based on these structural similarities as well as a predictable pattern in
physicochemical and environmental fate properties, environmental effects and mammalian toxicity, the chemicals in
this category can be grouped and evaluated together. Data for the tested category members and supporting
chemicals are extrapolated to provide estimates of similar properties for the untested members.
EPA agreed with the sponsor's support of the category, that the available data tend to be similar and follow a
predictable pattern across the category members. EPA notes that although the CI 1-C14 branched alkyl acetate
esters show less biodegradation and aquatic toxicity compared to the other members of the category, this reflects the
predictable change in certain test-related properties such as water solubility and represents a natural break-point
within the category.
Justification for Supporting Chemicals
The sponsor provided additional data for the following supporting substances to support the endpoints indicated:
3

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Acetic acid, C7-9 branched alkyl esters (predominantly C8), data submitted for acute toxicity, repeated-
dose toxicity, reproductive toxicity, developmental toxicity and genetic toxicity.
Acetic acid, C8-10 branched alkyl esters (predominantly C9), data submitted for acute toxicity.
Acetic acid, C9-11 branched alkyl esters (predominantly CIO), data submitted for ready biodegradation,
aquatic toxicity, acute toxicity,
The supporting substances have similar chemical structures and their component composition overlap with the
category substance composition.
Sum m ;m-Conclusion
I lie Inn k \allies I'm-CM' I I mollis I-branched ;ilk\ I aeelale and ( I I-( 14 mollis l-braiiched alk\ I aeelale esier
indicate llial llicir potential in binacciiniiilale is c\pecled In he limli I levmnl. acetate. branched and linear. (<>-X
branched ;ilk\ I esters and \celic acid. CM I branched alk\ I esiers are readiK bmdeunidable iiidicaliim llial lhe> are
nnl e\pecled In persisi m ilie en\ irniinieiii The CI l-C 14 alk\ I aeelale ester is nni iiihereiiiK nr readiK
bindcuradable iiidicaliim llial il ise\pecled In persist in I he en\ irniinieiii
The e\ ahialinn nl' I he a\ ailahle aquatic ln\ieil> dala I'nr fish. aqnalic iii\ eriehrales and aqnalic plains mdieales llial
I he pnlenlial aenle ha/ard nl' llie members i»l" l he \lk\ I \eelales ('<> in C H ( aleunrs In aqnalic nruamsnis is likels In
he mnderale
The aenle nral dermal ln\ieil> nl'the nienihei's nl' ilns ealeunrs is Inw The calcunr\ nienibeiY he\;iiH. I )e\ elnpnienial ln\ieil>
eharaeleri/ed as a slmhi increase in I'elal niaHnrnialinns and enibrsn in\ieil\. was seen al ilie nialernalls in\ie dnses
nl' ( branched alk\ I aeelale esiers ( looo nm ku-bw da>) bill nnl al Inwer dnses I Apnsnre nl' nils in C I I -14
branched alk\ I aeelale esiershnwed prnnniineed nialernal u<\ieil\ al IiiuIi dnses. bin nn sialisiicalls smnilieaiii
ellccls mi I'elal snr\ i\ al. bnd> weiuln and ernw n-riinip lenuih were nnied There were nn ireainieni-relaled
niaMnrnialinns The ealeunrs nienibei's. he\annl. aeelale. branched and linear. C<>-X branched alk\ I aeelale esiers.
( ~-'i branched alk\ I aeelale esier. and CI 1-14 branched alk\ I aeelale esier. did nnl slinw niiiiauenie pnlenlial when
lesied in bacterial cells. I levninl. aeelale. branched and linear and ( <>-X branched alk\ I aeelale esier did nnl mdiiee
ehrniiinsniiial aberralinns m in viim and C~-lJ branched alk\ I aeelale esierand CI 1-14 branched alk\ I aeelale esier
did nnl increase I he mean iiiinibcrnl' niiernniielealed piilsehrnnialie er\ llirnes les in vivu
The pnlenlial health ha/ard nl'lhe ('<> in CI ^ alk\ I acetates ('<> in C I ^ calcunr\ is Inw
( limine aqnalie ln\ieil> has been identified as a dala nap 1'nraeelie acid. CI l-( 14 alk\ I esiers under the I IPX
( hallenue I'rnmani.
1 The presence of nephropathy in association with the hyaline droplet accumulation in male rats suggests that the
nephropathy in the males is occurring by an alpha2u-globulin-mediated mechanism which is male rat pecific and not
considered relevant to humans. EPA's Risk Assessment Forum has outlined the key events and the data that are
necessary to demonstrate this mode of action (Alpha2u-Globulin: Association with Chemically Induced Renal
Toxicity and Neoplasia in the Rat, EPA/625/3-91/019F). One of the key events, alpha2u-globulin accumulation, has
not been demonstrated. Therefore, the nephropathy is assumed to be relevant to human health.
4

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1. Physical-Chemical Properties
A summary of physical-chemical properties and environmental fate data submitted is provided in the Appendix. For
the purpose of the screening-level hazard characterization, the review and summary of these data was limited to the
octanol-water partition coefficient and biodegradation endpoints as indictors of bioaccumulation and persistence,
respectively.
Octanol-Water Partition Coefficient
C9-C11 methyl-branched alkyl acetate (predominantly CIO, CAS No. 108419-34-7)
Log Kow	4.65 (estimated)
C11-C14 methyl-branched alkyl acetate ester (predominantly C13, CAS No. 108419-35-8)
Log Kow	6.05 (estimated)
Biodegradation
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Acetic acid, C6-8 branched alkyl esters (C7-rich, CAS No. 90438-79-2)
Acetic acid, C9-11 branched alkyl esters (ClO-rich, CAS No. 108419-34-7)
In separately conducted Manometric Respirometery tests using activated sludge as inoculum, 77 - 85% of the above
listed test substances had degraded after 28 days.
Hexanol, acetate, branched and linear (C6-rich), Acetic acid, C6-8 branched alkyl esters (C7-rich), and Acetic
acid, C9-11 branched alkyl esters (ClO-rich) are readily biodegradable.
C11-C14 methyl-branched alkyl acetate ester (predominantly C13, CAS No. 108419-35-8)
In an inherent biodegradation test using acclimated inoculum, 31% of the test substance had degraded after 28 days.
The C11-C14 alkyl acetate ester is not inherently or readily biodegradable.
Conclusion: The log Kow values for C9-C11 methyl-branched alkyl acetate and CI 1-C14 methyl-branched alkyl
acetate ester indicate that their potential to bioaccumulate is expected to be high. Hexanol, acetate, branched and
linear, C6-8 branched alkyl esters and Acetic acid, C9-11 branched alkyl esters are readily biodegradable indicating
that they are not expected to persist in the environment. The CI 1-C14 alkyl acetate ester is not inherently or readily
biodegradable indicating that it is expected to persist in the environment.
5

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Tahle 1. Siimman of Ph\sic;il-( hemical Properlies and llinii'onmenlal l-'alc Dala
Endpoints
Hexanol, acetate,
branched and
linear
(88230-35-7)
C6-8 branched
alkyl acetate
esters
(90438-79-2)
C7-9 branched
alkyl acetate
esters
(108419-32-5)
C8-10 branched
alkyl acetate
esters
(108419-33-6)
C9-11 branched
alkyl acetate
esters
008419-34-7)
Cll-14 branched
alkyl acetate
esters
(108419-35-8)
Melting
Point (°C)
-592
-502
-302
-202
-8.82
-22
Boiling Point
Range (°C)
164 to 1761
176 to 2001
186 to 2151
205 to 2351
220- to 2501
240 to 2851
Vapor
Pressure
(hPa)
1.932
1.0351
0.932
0.352
0.132
0.012
Log Kow
2.832
3.9 to 4.21
3.662
4.152
4.652
6.052
Water
Solubility
(mg/L)
3092
1581
452
14.52
4.72
0.22
Direct
Photodegra-
dation
Direct photolysis will not contribute to degradation
Indirect (OH"
)
Photodegra-
dation tl/2
(hr)
17.32
14.52
12.52
10.52
9.32
6.92
Hydrolysis
Stable in water and are not subject to hydrolysis at environmentally relevant pH values and time periods
Distribution
Predominantly in air compartment
Predominantly in soil compartment
Biodegra-
dation
76.91
Readily
Biodegradable
77.11
Readily
Biodegradable
No data
77.1 to 84.7
Readily
Biodegradable
(RA)
No data
77.1 to 84.7
Readily
Biodegradable
(RA)
84.71
Readily
Biodegradable
31.01
Not readily
biodegradable
Bioconcentra
tion Factor
302
632
1512
3162
7542
3252
RA = Read Across; 'Measured data; Calculated data
2. Environmental Effects - Aquatic Toxicity
A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 1. The table also indicates
where data for tested category members are read-across (RA) to untested members of the category.
Acute Toxicity to Fish
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Rainbow trout (Oncorhynchus mykiss, 15/concentration) were exposed to the test substance as water accommodated
fractions (WAFs) under semi static conditions for 96 hours. The nominal concentrations were 0, 0.5, 1.3, 3.2, 8.0
and 20 mg/L (measured as Total Organic Carbon, or TOC). Mortality was seen at 8 mg/L (1/15 fish) and 20 mg/L
where 100% fish died.
96-h LC50 = 11.9 mg/L (expressed as Total Organic Carbon)
6

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Acetic acid, C6-8 branched alkyl esters (C7-rich, CAS No. 90438-79-2)
Rainbow trout (Oncorhynchus mykiss, 10/concentration) were exposed to the test substance as water accommodated
fractions (WAFs) under static conditions for 96 hours. The nominal concentrations were 0, 2.0, 4.5, 10.0, 23.0 and
50.0 mg/L (measured concentrations: not detectable, 1.2, 1.49, 5.39, 21.1 and 43.6 mg/L respectively). Mortality
was seen at 5.39 mg/L and above.
96-h LCS0 = 8.18 mg/L
Acetic acid, C7-9 branched alkyl esters (C8-rich, CAS No. 108419-32-5, supporting chemical)
Fathead minnows (Pimephales promelas, 20/concentration) were exposed to the test substance as water
accommodated fractions (WAFs) under flow-through conditions for 96 hours. Nominal concentrations were 0, 4.4,
8.8, 17.5, 35.0 and 70.0% WAF, which measured as 0, 1.39, 2.71, 4.90, 9.91 and 19.86 mg/L of total carbon.
Mortality was seen only at 19.86 mg/L at which all fish died.
96-h LC50 = 14.9 mg/L (expressed as Total Carbon)
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
Fathead minnows (Pimephales promelas, 20/concentration) were exposed to the test substance as water
accommodated fractions (WAFs) under flow-through conditions for 96 hours. The loading rates were 0, 6.25, 125,
25, 50, and 100% WAF and no analytical measurements were made on the WAFs. No effects were noted at any of
the WAF loading rates. The sponsor reported the 96-hour LC0 (no deaths observed) to be 5800 mg/L - the estimated
highest concentration tested - based on nominal loading levels. EPA does not consider the loading rate as the no
effect concentration when the concentration exceeds the water solubility of the substance. Assuming exposure
concentration in the WAF is the water solubility limit (saturation) for CI 1-C14 methyl-branched alkyl acetate ester,
the no effect concentration would be approximately 0.2 mg/L.
No effects at saturation
Acute Toxicity to Aquatic Invertebrates
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Daphnia magna (20/concentration) were exposed to the test substance as water accommodated fractions (WAFs)
under static conditions for 48 hours at nominal concentrations of 0, 0.1, 0.5, 1 .0, 5.0 and 10.0 mg/L. Although the
robust summary states that samples were analyzed for Total Organic Carbon, no measured values were listed.
Mortality was 1, 2, 1, 3, 5 and 14 at 0, 0.1, 0.5, 1 .0, 5.0 and 10.0 mg/L, respectively.
48-h EC50 = 7.6 mg/L (expressed as nominal organic carbon loading rates)
Acetic acid, C7-9 branched alkyl esters (C8-rich, CAS No. 108419-32-5, supporting chemical)
Daphnia magna (20/concentration) were exposed to the test substance as water accommodated fractions (WAFs)
under flow-through conditions for 48 hours at nominal concentrations of 0, 6.25, 12.5, 25, 50 and 100% WAF which
were measured as 0, 1.87, 4.13, 10.24, 20.21, and 39.95 mg/L total carbon, respectively. Treatment-related
mortality was observed at the two highest concentrations (3/20 and 17/20 for 20.21 and 39.95 mg/L, respectively)
48-h ECS0 = 29.4 mg/L (expressed as Total Organic Carbon)
Acetic acid, C9-C11 branched alkyl esters (ClO-rich, CAS No. 108419-34-7, supporting chemical)
Daphnia magna (20/concentration), were exposed to the test substance as water accommodated fractions (WAFs)
under static conditions for 48 hours at nominal concentrations of 0, 1.3, 3.2, 8.0, 20.0 and 50.0 mg/L (measured
concentrations: not detectable, 0.44, 1.3, 2.1, 1.9 and 2.2 mg/L, respectively). Mortality was 0, 0, 20%, 55%, 95%,
and 100%, respectively at 0, 0.44, 1.3, 2.1, 1.9 and 2.2 mg/L.
48-h ECS0 = 1.8 mg/L
7

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Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
Daphnia magna (40/concentration), were exposed to the test substance as water accommodated fractions (WAFs)
under static conditions for 48 hours at nominal concentrations. The loading rates were 0, 6.25, 125, 25, 50, and
100% and no analytical measurements were made on the WAFs. No effects were noted at any of the WAF loading
rates. The sponsor reported the 96-hour LC0 (no deaths observed) to be 5829 mg/L - the estimated highest
concentration tested - based on nominal loading levels. EPA does not consider the loading rate as the no effect
concentration when the concentration exceeds the water solubility of the substance. Assuming exposure
concentration in the WAF is the water solubility limit (saturation) for CI 1-C14 methyl-branched alkyl acetate ester,
the no effect concentration would be approximately 0.2 mg/L.
No effects at saturation
Toxicity to Aquatic Plants
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Green algae (Selenastrum capricornutum) were exposed to the test substance as water accommodated fractions
(WAFs) under static conditions for 96 hours at nominal concentrations of 0, 8, 31, 62, 125 and 250 mg/L reported as
loading rates. Although samples were analyzed for test substance, the measurement was for dissolved organic
carbon only and the results were not reported in the submitted robust summary. Both growth rate and biomass were
inhibited at the top three concentrations.
96-h EC50 (biomass) = 40.1 (expressed as nominal organic carbon loading rates)
96-h EC50 (growth) = 32.1 mg/L (expressed as nominal organic carbon loading rates)
Acetic acid, C9-C11 branched alkyl esters (ClO-rich, CAS No. 108419-34-7, supporting chemical)
Green algae (Pseudokirchneriella subcapitata) were exposed to the test substance as water accommodated fractions
(WAFs) under static conditions for 72 hours at nominal concentrations of 0, 64.5, 130, 254, 522 and 1021 mg/L as
carbon loading levels; but measured concentrations at the start of the study were 0, 4.8, 5.0, 5.2, 5.2, and 5.6 mg/L,
respectively. Essentially, these values reflect the approximate water solubility limit (4.7 mg/L) and show there was
no essential difference across test groups in terms of starting concentration. There were no effects at this
concentration.
No effects at saturation
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
Green algae (Selenastrum capricornutum) were exposed to the test substance as water accommodated fractions
(WAFs) under static conditions for 96 hours. The loading rates were 0, 6.25, 125, 25, 50, and 100% WAF and
measured values (as Total Carbon) were reported as 0, 0.058, 0.219, 0.492, and 0.873 mg/L. No effects were noted
at any of the WAF loading rates. The sponsor reported the 96-hour LC0 (no inhibition of algal growth) to be 5829
mg/L - the estimated highest concentration tested - based on nominal loading levels. Assuming exposure
concentration in the WAF is the water solubility limit (saturation) for CI 1-C14 methyl-branched alkyl acetate ester,
the no effect concentration would be approximately 0.2 mg/L.
No effects at saturation
Conclusion: The evaluation of the available aquatic toxicity data for fish, aquatic invertebrates and aquatic plants
indicates that the potential acute hazard of the members of the Alkyl Acetates C6 to C13 Category to aquatic
organisms is likely to be moderate. This is because the reported values in the most of the studies were expressed as
carbon load and so the actual chemical concentrations are not known but are probably lower than the total carbon
values. It is uncertain how much lower, but it is probably less than an order of magnitude. The largest (in terms of
molecular weight) member of the category (the CI 1-C14) showed no effects at the water solubility estimate of 0.2
mg/L, but because of its persistence and other chemical/physical properties, as stated in the Agency comments in
2001, chronic aquatic toxicity has been identified as a data gap for acetic acid, CI 1-C14 alkyl esters under the HPV
Challenge Program.
8

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Table 2. Summary of Environmental Effects - Aquatic Toxicity Data
Endpoints
Hexanol,
Acetic acid,
Acetic acid,
Acetic acid,
Acetic acid,
Acetic Acid,

acetate,
C6-C8
C7-C9
C8-C10
C9-C11
C11-C14

branched and
branched alkvl
branched alkvl
branched alkvl
branched alkvl
branched alkyl

linear
esters
esters
esters
esters
esters

(C6-rich)
(C7-rich)
(C8-rich)
(C9-rich)
(ClO-rich)
(C13-rich)



(supporting
(supporting
(supporting




chemical)
chemical)
chemical)


(88230-35-7)
(90438-79-2)
(108419-32-5)
(108419-33-6)
(108419-34-7)
(108419-35-8)
Fish






96-h LCS0
11.9 (m)
8.18 (m)
14.9 (m)
No data
No data
NES (m)
(mg/L)
(expressed as

(expressed as
8.18
8.18


total carbon)

total carbon)
(RA)
(RA)

Aquatic

No data




Invertebrates
7.6 (m)
7.6
29.4 (m)
No data
1.8 (m)
NES (m)
48-h ECS0
(expressed as
(RA)
(expressed as
7.6


(mg/L)
total carbon)

total carbon)
(RA)


Aquatic Plants






72-h ECS0

No data
No data
No data
NES (m)
NES (m)
(mg/L)
32.1 (m)
32.1
32.1
32.1


(growth)
40.1 (m)
40.1
40.1
40.1


(biomass)
(expressed as
(RA)
(RA)
(RA)



total carbon)





(m) = measured data (i.e., derived from testing); (RA) = Read Across; NES = No effects at saturation;
— indicates endpoint not addressed for this substance.
3. Human Health Effects
A summary of health effects data submitted for SIDS endpoints is provided in Table 2. The table also indicates
where data for tested category members are read-across (RA) to untested members of the category.
Acute Oral Toxicity
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Acetic acid, C8-C10 branched alkyl esters (C9-rich, CAS No. 108419-33-6, supporting chemical)
Acetic acid, Cll-14 branched alkyl esters (C13-rich,CAS No. 108419-35-8)
Acute oral toxicity to rats is low.
LDS0 > 2000 - 5000 mg/kg-bw
Acute Dermal Toxicity
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Acetic acid, C6-8 branched alkyl esters (C7-rich, CAS No. 90438-79-2)
Acetic acid, C7-9 branched alkyl esters (C8-rich,CAS No. 108419-32-5, supporting chemical)
Acetic acid, C8-C10 branched alkyl esters (C9-rich, CAS No. 108419-33-6, supporting chemical)
Acetic acid, C9-C11 branched alkyl esters (ClO-rich, AS No. 108419-34-7, supporting chemical)
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
Acute dermal toxicity to rabbits is low.
LDS0 > 2000 - 3160 mg/kg-bw
9

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Repeated-Dose Toxicity
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Crl:CD BR rats were administered the test substance in corn oil via gavage at 0, 100, 500 and 1000 mg/kg-bw/day
for 28 days. No adverse effects were noted on body weight, food consumption, clinical laboratory parameters, organ
weights or gross or microscopic examination.
LOAEL > 1000 mg/kg-bw/day
NOAEL = 1000 mg/kg-bw/day (based on no effects at the highest dose tested)
Acetic acid, C7-9 branched alkyl esters (C8-rich, CAS No. 108419-32-5, supporting chemical)
Sprague-Dawley rats were administered the test substance via gavage at 0, 100, 500 or 1000 mg/kg-bw/day, 5
days/week for 13 weeks. There was no treatment-related mortality; clinical signs included oral and dermal irritation.
There were no effects on body weight, food consumption, hematology or clinical chemistry parameters. At study
termination, there was a dose-related increase in liver and kidney weights; however, microscopic evaluation of liver
did not show any corresponding findings. Microscopic evaluation of kidneys showed evidence of mild tubular
nephropathy in the high-dose male rats consistent with alpha2M-globulin effect1. Histopathological evaluation of all
other tissues and organs was normal.
LOAEL = 1000 mg/kg-bw/day (based on nephropathy in males)
NOAEL = 500 mg/kg-bw/day
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
Sprague-Dawley rats were administered the test substance via gavage at 0, 100, 500 or 1000 mg/kg-bw/day, 5
days/week for 13 weeks. There was no treatment-related mortality; clinical signs included oral and dermal irritation.
There were no effects on body weight, food consumption, hematology or clinical chemistry parameters. At study
termination, there was a dose-related increase in liver and kidney weights; however, this was considered to be an
adaptive response. There was no correlation between increased liver weight and corresponding microscopic
findings. Microscopic evaluation of kidneys showed evidence of mild tubular nephropathy in the high-dose male
rats consistent with alpha2|J-globulin effect1. Histopathological evaluation of all other tissues and organs was
normal.
LOAEL =1000 mg/kg-bw/day (based on nephropathy in males)
NOAEL = 500 mg/kg-bw/day
Reproductive Toxicity
Acetic acid, C7-9 branched alkyl esters (C8-rich, CAS No. 108419-32-5, supporting chemical)
In the repeated-dose toxicity study with C7-9 branched alkyl acetate esters described previously, histopathological
examination of reproductive organs—testes, epididymides, prostate, seminal vesicles, ovaries, uterine horns, cervix
and corpus of the uterus and vagina—showed no effects at study termination.
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
In the repeated-dose study with Cll-14 branched alkyl acetate esters described previously, histopathological
examination of reproductive organs—testes, epididymides, prostate, seminal vesicles, ovaries, uterine horns, cervix
and corpus of the uterus and vagina—showed no effects at study termination.
1 The presence of nephropathy in association with the hyaline droplet accumulation in male rats suggests that the
nephropathy in the males is occurring by an alpha2u-globulin-mediated mechanism which is male rat pecific and not
considered relevant to humans. EPA's Risk Assessment Forum has outlined the key events and the data that are
necessary to demonstrate this mode of action (Alpha2u-Globulin: Association with Chemically Induced Renal
Toxicity and Neoplasia in the Rat, EPA/625/3-91/019F). One of the key events, alpha2u-globulin accumulation, has
not been demonstrated. Therefore, the nephropathy is assumed to be relevant to human health.
10

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Developmental Toxicity
Acetic acid, C7-9 branched alkyl esters (C8-rich, CAS No. 108419-32-5, supporting chemical)
Female Sprague-Dawley rats were administered the test substance via gavage at 0, 100, 500 or 1000 mg/kg-bw/day
during days 6 - 15 of gestation. Maternal toxicity was observed (decreased body weight and food consumption) at
500 and 1000 mg/kg-bw/day. Slight increases in fetal malformations and embryotoxicity were seen at 1000 mg/kg-
bw/day. No adverse fetal effects were seen at the 100 and 500 mg/kg-bw/day.
LOAEL (maternal toxicity) = 500 mg/kg-bw/day (based on decreased body weight and food consumption)
NOAEL (maternal toxicity) = 100 mg/kg-bw/day
LOAEL (developmental toxicity) = 1000 mg/kg-bw/day (based on fetal malformations and embryotoxicity)
NOAEL (developmental toxicity) = 500 mg/kg-bw/day
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
Female Sprague-Dawley rats were administered the test substance via gavage at 0, 500, 1300 or 2500 mg/kg-bw/day
during days 6 - 15 of gestation. Maternal toxicity was observed (decreased body weight) at 1300 and 2500 mg/kg-
bw/day. No marked effects on fetal survival or body weight were seen. There was no evidence of treatment-related
malformations.
LOAEL (maternal toxicity) = 1300 mg/kg-bw/day (based on decreased body weight)
NOAEL (maternal toxicity) = 500 mg/kg-bw/day
LOAEL (developmental toxicity) > 2500 mg/kg-bw/day
NOAEL (developmental toxicity) = 2500 mg/kg-bw/day (based on no effects at the highest dose tested)
Genetic Toxicity - Gene Mutation
In vitro
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Acetic acid, C6-8 branched alkyl esters (C7-rich, CAS No. 90438-79-2)
Acetic acid, C7-9 branched alkyl esters (C8-rich, CAS No. 108419-32-5, supporting chemical)
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
In separately conducted Ames assays, five strains of Salmonella typhimurium were exposed to the test substances
listed above at concentrations up to 600 - 10,000 |ig/plate (highest concentrations tested) in the presence and
absence of metabolic activation. At the highest concentration cytotoxicity was seen. The category members did not
induce significant increases in revertant colonies.
The category members listed above were not mutagenic in these assays.
Genetic Toxicity - Chromosomal Aberrations
In vitro
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Chinese hamster ovary cells were exposed to the test substance at concentrations up to 250 - 550 ng/mL with and
without metabolic activation. Appropriate responses were seen for positive, negative and solvent controls.
Hexanol, acetate, branched and linear did not induce chromosomal aberrations in this assay.
Acetic acid, C6-8 branched alkyl esters (C7-rich, CAS No. 90438-79-2)
Chinese hamster ovary cells were exposed to the test substance at concentrations up to 40 - 240 ng/mL with and
without metabolic activation. Appropriate responses were seen for positive, negative and solvent controls.
C6-C8 branched alkyl acetate ester did not induce chromosomal aberrations in this assay.
In vivo
Acetic acid, C7-9 branched alkyl esters (C8-rich, CAS No. 108419-32-5, supporting chemical)
In a bone marrow micronucleus assay, CD-I mice were administered the test substance as a single dose via gavage
up to 2500 mg/kg-bw. Animals were sacrificed at 24, 48 and 72 hours, bone marrow was aspirated and slides were
prepared, stained and evaluated for the presence of micronuclei. Appropriate responses were seen for positive,
negative and solvent controls. No marked increase in the mean number of micronucleated polychromatic
erythrocytes in the bone marrow.
Acetic acid, C7-9 branched alkyl esters (C8-rich) did not increase micronuclei in this assay.
11

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Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
In a bone marrow micronucleus assay, CD-I mice were administered the test substance as a single dose by gavage
up to 2500 mg/kg-bw. Animals were sacrificed at 24, 48 and 72 hours, bone marrow was aspirated and slides were
prepared, stained and evaluated for the presence of micronuclei. Appropriate responses were seen for positive,
negative and solvent controls. Although CI 1-C14 branched alkyl acetate esters was toxic to bone marrow showing
a decrease in the mean percent of polychromatic erythrocytes at the 48-hour sampling time, it did not induce
statistically significant increase in the mean number of micronucleated polychromatic erythrocytes.
C11-C14 branched alkyl acetate esters did not increase micronuclei in this assay.
Additional Information
Eye Irritation
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
The test substances were instilled into the conjunctival sacs of New Zealand White rabbits and observed at 1, 4 and
24 hours post-dosing and at 2, 3, 4 and 7 days (in separate studies). Ocular irritation was most prominent at the 1-
hour observation period. Irritation was confined to the conjunctivae with moderate redness, chemosis and discharge
and corneal ulceration in one animal. Signs of irritation completely subsided in all animals by day 7.
The category chemicals cause mild reversible eye irritation in these assays.
Skin Irritation
Hexanol, acetate, branched and linear (C6-rich, CAS No. 88230-35-7)
Acetic acid, Cll-14 branched alkyl esters (C13-rich, CAS No. 108419-35-8)
In separate assays, New Zealand White rabbits were dermally administered the test substances under semi-occlusive
conditions for 4 hours. The animals were observed and scored for irritation at 1, 24, 48 and 72 hours and 7 days
post-dosing. All animals displayed erythema and/or edema in the first 72 hours. All animals were cleared of
irritation by day 7. The category members listed above are mild (CAS No. 108419-35-8) to moderate (CAS No.
88230-35-7) skin irritants.
The category chemicals listed above cause mild to moderate skin irritation in these assays.
Conclusion: The acute oral dermal toxicity of the members of this category is low. The category members,
hexanol, acetate, branched and linear and Cll-14 branched alkyl acetate esters are mild to moderate skin irritants
and mild eye irritants. Repeated oral exposures to hexanol, acetate, branched and linear, C7-9 branched alkyl
acetate ester and Cll-14 branched alkyl acetate esters were minimally toxic to rats. For the C7-9 branched alkyl
acetate ester and Cll-14 branched alkyl acetate ester, mild tubular nephropathy in the high-dose male rats consistent
with alpha:,,-globulin effect was the only notable effect1. Histopathological evaluation of all other tissues and
organs including reproductive organs was normal when tested at the limit doses of 1000 mg/kg-bw/day.
Developmental toxicity characterized as a slight increase in fetal malformations and embryo toxicity, was seen at the
maternally toxic doses of C7-9 branched alkyl acetate esters (1000 mg/kg-bw/day) but not at lower doses. Exposure
of rats to Cll-14 branched alkyl acetate ester showed pronounced maternal toxicity at high doses; but no statistically
significant effects on fetal survival, body weight and crown-rump length were noted. There were no treatment-
related malformations. The category members, hexanol, acetate, branched and linear, C6-8 branched alkyl acetate
esters, C7-9 branched alkyl acetate ester, and Cll-14 branched alkyl acetate ester, did not show mutagenic potential
when tested in bacterial cells. Hexanol, acetate, branched and linear and C6-8 branched alkyl acetate ester did not
induce chromosomal aberrations in in vitro and C7-9 branched alkyl acetate ester and Cll-14 branched alkyl acetate
ester did not increase the mean number of micronucleated polychromatic erythrocytes in vivo.
1 The presence of nephropathy in association with the hyaline droplet accumulation in male rats suggests that the
nephropathy in the males is occurring by an alpha2u-globulin-mediated mechanism which is male rat pecific and not
considered relevant to humans. EPA's Risk Assessment Forum has outlined the key events and the data that are
necessary to demonstrate this mode of action (Alpha2u-Globulin: Association with Chemically Induced Renal
Toxicity and Neoplasia in the Rat, EPA/625/3-91/019F). One of the key events, alpha2u-globulin accumulation, has
not been demonstrated. Therefore, the nephropathy is assumed to be relevant to human health.
12

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Tabic 3. Summary of Human Health Data
Endpoints
Hcxanol, acetate,
branched and
linear
(C6-rich)
(88230-35-7)
Acetic acid,
C6-C8
branched alkvl
esters
(C7-rich)
(90438-79-2)
Acetic acid,
C7-C9
branched alkvl
esters
(C8-rich)
(supporting
chemical)
(108419-32-5)
Acetic acid,
C8-C10
branched alkvl
esters
(C9-rich)
(supporting
chemical)
(108419-33-6)
Acetic acid,
C9-C11
branched alkvl
esters
(ClO-rich)
(supporting
chemical)
(108419-34-7)
Acetic acid,
C11-C14
branched alkyl
acetate esters
(C13-rich)
(108419-35-8)
Acute Oral
Toxicity
LDS0 (mg/kg-bw)
>2000
No Data
> 5000
(RA)
No Data
> 5000
(RA)
>5000
No Data
> 5000
(RA)-
>3000
Acute Dermal
Toxicity
LDS0 (mg/kg-bw)
>2000
>3160
>3160
>3160
>3160
>3160
Repeated-Dose
Toxicity
NOAEL/ LOAEL
(mg/kg-bw/day)
NOAEL =1000
LOAEL > 1000
No Data
NOAEL = 500
LOAEL = 1000
(RA)
NOAEL = 500
LOAEL =1000
No Data
NOAEL = 500
LOAEL = 1000
(RA)
No Data
NOAEL = 500
LOAEL = 1000
(RA)
NOAEL = 500
LOAEL =1000
Reproductive
Toxicity
NOAEL/ LOAEL
(mg/kg-bw/day)
No Data
No effects on male
and female
reproductive organs
from the 90-day
study
(RA)
No Data
No effects on male
and female
reproductive organs
from the 90-day
study
(RA)
No effects on male
and female
reproductive
organs from the
above 90-day study
No Data
No effects on male
and female
reproductive organs
from the 90-day
study
(RA)
No Data
No effects on male
and female
reproductive organs
from the 90-day
study
(RA)
No effects on male
and female
reproductive
organs from the
above 90-day study
Developmental
Toxicity
NOAEL/ LOAEL
(mg/kg-bw/day)
Maternal
Developmental
No Data
NOAEL = 100
LOAEL = 500
NOAEL = 500
LOAEL = 1000
(RA)
No Data
NOAEL = 100
LOAEL = 500
NOAEL = 500
LOAEL = 1000
(RA)
NOAEL = 100
LOAEL = 500
NOAEL = 500
LOAEL =1000
No Data
NOAEL = 100
LOAEL = 500
NOAEL = 500
LOAEL = 1000
(RA)
No Data
NOAEL = 100
LOAEL = 500
NOAEL = 500
LOAEL = 1000
(RA)
NOAEL = 500
LOAEL = 1300
NOAEL = 2500
LOAEL >2500
Genetic Toxicity -
Gene Mutation
In vitro
Negative
Negative
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
Negative
Genetic Toxicity -
Chromosomal
Aberrations
In vitro
Negative
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
Genetic Toxicity -
Chromosomal
Aberrations
In vivo
No Data
Negative
(RA)
No Data
Negative
(RA)
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
Negative
Eye Irritation
Mild
	
—
—
—
Mild
Skin Irritation
Moderate
(RA)
—*
—*
—*
Mild
Measured data in bold text; (RA) = read across; — indicates data not required.
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4. Hazard Characterization
The log Kow values for C9-C11 methyl-branched alkyl acetate and CI 1-C14 methyl-branched alkyl acetate ester
indicate that their potential to bioaccumulate is expected to be high. Hexanol, acetate, branched and linear, C6-8
branched alkyl esters and Acetic acid, C9-11 branched alkyl esters are readily biodegradable indicating that they are
not expected to persist in the environment. The CI 1-C14 alkyl acetate ester is not inherently or readily
biodegradable indicating that it is expected to persist in the environment.
The evaluation of the available aquatic toxicity data for fish, aquatic invertebrates and aquatic plants indicates that
the potential acute hazard of the members of the Alkyl Acetates C6 to C13 Category to aquatic organisms is likely to
be moderate.
The acute oral dermal toxicity of the members of this category is low. The category members, hexanol, acetate,
branched and linear and CI 1-14 branched alkyl acetate esters are mild to moderate skin irritants and mild eye
irritants. Repeated oral exposures to hexanol, acetate, branched and linear, C7-9 branched alkyl acetate ester and
CI 1-14 branched alkyl acetate esters were minimally toxic to rats. For the C7-9 branched alkyl acetate ester and
CI 1-14 branched alkyl acetate ester, mild tubular nephropathy in the high-dose male rats consistent with alpha2ll-
globulin effect was the only notable effect1. Histopathological evaluation of all other tissues and organs including
reproductive organs was normal when tested at the limit doses of 1000 mg/kg-bw/day. Developmental toxicity
characterized as a slight increase in fetal malformations and embryo toxicity, was seen at the maternally toxic doses
of C7-9 branched alkyl acetate esters (1000 mg/kg-bw/day) but not at lower doses. Exposure of rats to CI 1-14
branched alkyl acetate ester showed pronounced maternal toxicity at high doses; but no statistically significant
effects on fetal survival, body weight and crown-rump length were noted. There were no treatment-related
malformations. The category members, hexanol, acetate, branched and linear, C6-8 branched alkyl acetate esters,
C7-9 branched alkyl acetate ester, and CI 1-14 branched alkyl acetate ester, did not show mutagenic potential when
tested in bacterial cells. Hexanol, acetate, branched and linear and C6-8 branched alkyl acetate ester did not induce
chromosomal aberrations in in vitro and C7-9 branched alkyl acetate ester and CI 1-14 branched alkyl acetate ester
did not increase the mean number of micronucleated polychromatic erythrocytes in vivo.
The potential health hazard of the C6 to C13 alkyl acetates C6 to C13 category is low.
5. Data Gaps
Chronic aquatic toxicity has been identified as a data gap for acetic acid, CI 1-C14 alkyl esters under the HPV
Challenge Program.
1 The presence of nephropathy in association with the hyaline droplet accumulation in male rats suggests that the
nephropathy in the males is occurring by an alpha2u-globulin-mediated mechanism which is male rat pecific and not
considered relevant to humans. EPA's Risk Assessment Forum has outlined the key events and the data that are
necessary to demonstrate this mode of action (Alpha2u-Globulin: Association with Chemically Induced Renal
Toxicity and Neoplasia in the Rat, EPA/625/3-91/019F). One of the key events, alpha2u-globulin accumulation, has
not been demonstrated. Therefore, the nephropathy is assumed to be relevant to human health.
14

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Appendix
Alkyl Acetates C6 to C13
CAS No.
Chemical Name
Structure
(Representative structures, branching may vary)
SPONSORED CHEMICALS
88230-35-7
Hexanol, acetate,
branched and linear
(C6-rich)
CH,
x
h3c O
c8H16o2
90438-79-2
Acetic acid, C6-8
branched alkyl esters
(C7-rich)
CH,
cr o 3
C9H1802
108419-35-8
Acetic acid, CI 1-14
branched alkyl esters
(CI 3-rich)
0 r
C15H30O2
SUPPORTING CHEMICALS
108419-32-5
Acetic acid, C7-9
branched alkyl esters
(C 8-rich)
A
C10H20O2
108419-33-6
Acetic acid, C8-10
branched alkyl esters
(C9-rich)
y
°Y°
C11H2202
108419-34-7
Acetic acid, C9-11
branched alkyl esters
(ClO-rich)
0^
C12H2402
15

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