U.S. Environmental Protection Agency
Hazard Characterization Document

September, 2014

SCREENING-LEVEL HAZARD CHARACTERIZATION

SPONSORED CHEMICAL

CI2, Branched Ketones

CASRN 68514-41-0

SUPPORTING CHEMICALS

Trimethyl 4-nonanone

2-Dodecanone

Methylheptenone

CASRN 123-18-2
CASRN 6175-49-1
CASRN 409-02-9

The High Production Volume (HPV) Challenge Program1 was conceived as 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 sponsored chemicals; sponsorship entailed the identification and initial
assessment of the adequacy of existing toxicity data/information, conducting new testing if
adequate data did 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 Set l 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 by developing hazard characterizations (HCs). These HCs consist of an evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions. They
are not intended to be definitive statements regarding the possibility of unreasonable risk of injury
to health or the environment.

The evaluation is performed according to established EPA guidance23 and is based primarily on
hazard data provided by sponsors; however, 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. In order to determine
whether any new hazard information was developed since the time of the HPV submission, a
search of the following databases was made from one year prior to the date of the HPV Challenge
submission to the present: (ChemID to locate available data sources including Medline/PubMed,
Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.), STN/CAS online
databases (Registry file for locators, ChemAbs for toxicology data, RTECS, Merck, etc.), Science
Direct and ECHA4. OPPT's focus on these specific sources is based on their being of high quality,
highly relevant to hazard characterization, and publicly available.

OPPT does not develop HCs for those HPV chemicals which have already been assessed
internationally through the HPV program of the Organization for Economic Cooperation and

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. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.

4	European Chemicals Agency, http://echa.europa.eu.


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Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment Reports
(SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are presented
in an international forum that involves review and endorsement by governmental authorities
around the world. OPPT is an active participant in these meetings and accepts these documents as
reliable screening-level hazard assessments.

These hazard characterizations are technical documents intended to inform 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.

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Sponsored Chemical



68514-41-0

Chemical Abstract Service Registry Number



(CASRN)

Supporting Chemicals
123-18-2
6175-49-1
409-02-9



Sponsored Chemical



C12, Branched Ketones

Chemical Abstract Index Name

Supporting Chemicals
4-Nonanone, 2,6,8-trimethyl-
2-Dodecanone
Heptenone, methyl-



Sponsored Chemical



ch3



H3C^ yv /V i.



ch3 o



Representative



SMILES:CC(C)CCC(=0)CCCC(C)C



Supporting Chemicals

Structural Formula

ch3 ch3 0 ch3



SMILES: CC(C)CC(=0)CC(C)CC(C)C

o

SMILES: CCCCCCCCCCC(C)=0









SMILES: CC(C)=CCCC(C)=0

Summary

Ketones, C12-branched is a mixture of branched ketones that is a co-product of methyl ethyl

ketone (MEK) production and is never isolated from the waste MEK production stream. It is a

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liquid that is expected to have moderate vapor pressure and moderate water solubility. The
components of this mixture are expected to have moderate mobility in soil. A representative
component of this mixture was not readily biodegradable using a standard OECD test. The rate
of degradation is expected to decrease with the degree of branching of the components of this
mixture. Volatilization is considered high based on the Henry's Law constant of representative
components of this mixture. The rate of hydrolysis is considered negligible since the constituents
of this mixture do not contain functional groups that are expected to hydrolyze under
environmental conditions. The rate of atmospheric photooxidation is considered moderate for the
components of this mixture. The constituents of ketones, C12-branched are expected to have low
persistence (PI) with the exception of the most highly branched isomers which may have
moderate persistence (P2). All the constituents of this mixture are expected to possess low
bioaccumulation potential (Bl).

No data are available on the sponsored substance for the human health endpoints. The acute oral
toxicity is low for supporting chemicals trimethyl 4-nonanone and methylheptenone in rats. The
acute dermal toxicity in rabbits is low for supporting chemical trimethyl 4-nonanone. A combined
oral gavage repeated-dose/reproductive/developmental toxicity study in rats with the supporting
chemical, methylheptenone, showed decreased motor activity in a functional observational battery
and thyroid follicular cell hypertrophy in males at 100 mg/kg-day, decreased food consumption
during lactation and thyroid follicular cell hypertrophy in females at 300 mg/kg-day; the NOAEL
for systemic toxicity in males is not established and in females is 100 mg/kg-day. Irregular cycles
and increased gestation period were observed at 500 mg/kg-day; the NOAEL for reproductive
toxicity is 300 mg/kg-day. No treatment-related developmental effects were observed at the
highest-dose tested; the NOAEL for developmental toxicity is 500 mg/kg-day. The supporting
chemical, methylheptenone, was not mutagenic in bacteria in vitro and did not induce
chromosomal aberrations in mammalian cells in vitro. The supporting chemical,
methylheptenone, is severely irritating to rabbit skin.

No data are available on the sponsored substance for the ecotoxicity endpoints. For the supporting
chemical, 2-dodecanone, the 96-h LCso for fish is 1.18 mg/L. For the supporting chemical
methylheptenone, the 48-h EC so for aquatic invertebrates is 5.2 mg/L. Toxicity to aquatic plants,
based on the supporting chemical methylheptenone, is 16 mg/L and 8 mg/L for growth rate and
biomass, respectively.

No data gaps were identified under the HPV Challenge Program.	

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The sponsor, ExxonMobil Chemical Company, submitted a Test Plan and Robust Summaries to
EPA for C12, branched ketones (CASRN 68514-41-0; 9th CI name: Ketones, C12-branched) on
December 15, 2009. EPA posted the submission on the ChemRTK HPV Challenge website on
January 25, 2010

(http://www.epa.gov/oppt/chemrtk/pubs/summaries/cl2brchketones/cl6825tc.htm). Public
comments were received and posted to the website.

Justification for Supporting Chemicals

The sponsor proposed the use of methylheptenone (C8 ketone; CASRN 409-02-9) as a supporting
chemical for both human health and aquatic toxicity endpoints because it and the sponsored
chemical comprise two fractions created from the same starting material, methylethyl ketone
(MEK), and are formed via the same condensation reaction pathway. Methylheptenone is
branched and formed from the condensation of two MEK molecules, while the sponsored chemical
is also branched and formed from the condensation of three MEK molecules. Methylheptenone is
therefore expected to have similar activities to the sponsored chemical. The sponsor also proposed
the use of trimethyl 4-nonanone (CI2 ketone; CASRN 123-18-2) as a supporting chemical for
acute human health toxicity endpoints since it is a C12 branched ketone with a C9 carbon backbone
containing methyl groups at carbons 2, 6, and 8. EPA agrees that the use of data for both of these
two supporting chemicals is justified based on structural similarities.

Another proposed supporting chemical for the aquatic toxicity endpoints, 2-dodecanone (C12
ketone; CASRN 6175-49-1), is a linear C12 ketone with the ketone group at the second carbon.
Since branching is not considered to be a critical attribute for ecotoxicity testing, EPA agrees that
the use of 2-dodecanone as a supporting chemical is justified for the aquatic toxicity endpoints.

1. Chemical Identity

1.1	Identification and Purity

Ketones, C12-branched is liquid that is expected to have moderate vapor pressure and moderate
water solubility. It is a high-boiling byproduct of the manufacture of methyl ethyl ketone and is
not isolated from other byproducts. This mixture of byproducts is subsequently used as a feedstock
to produce syngas (50/50 carbon monoxide/ hydrogen blend).

1.2	Physical-Chemical Properties

The physical-chemical properties of Ketones, C12-branched are summarized in Table 1.

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Table 1. Physical-Chemical Properties of Ketones, C12-branched and Supporting

Chemicals1'2

Property

SPONSORED CHEMICAL
Ketones, C12-branched

SUPPORTING CHEMICAL
Trimethyl 4-nonanone

CASRN

68514-41-0

123-18-2

Molecular Weight

184.32

184.32

Physical State

Liquid

Liquid

Melting Point

<0°C (estimated)3 4

<0°C (estimated)3

Boiling Point

220°C (estimated)3 4

217°C (measured)5

Vapor Pressure

0.20 mm Hg at 25°C
(estimated)3-4

0.03 mm Hg at 20°C (measured)5;
0.06 mm Hg at 25°C (estimated)6

Dissociation Constant

Not applicable

Not applicable

Henry's Law Constant

0.00128 atm-m3/mol
(estimated)3-4

0.00154 atm-m3/mol (estimated)3

Water Solubility

31.9 mg/L (estimated)3-4

22 mg/L (measured)7

Log Kow

4.04 (estimated)3-4

3.96 (estimated)3

ExxonMobil Chemical Company. 2009. Test Plan and Robust Summary for C12, Branched Ketones. Available
online at http://www.epa.gov/oppt/chemrtk/pubs/summaries/cl2brcliketones/cl6825tc.htm as of August 16, 2012.
2The sponsor also proposed using heptenone, methyl- and 2-dodecanone as a supporting chemicals.

3U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Enviromnental
Protection Agency, Washington, DC, USA. Available online at
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of August 16, 2012.

4The sponsor proposed the branched ketone 4-decanone, 2,9-dimethyl- (CASRN unknown not on TSCA) as a
typical representative structure for the sponsored chemical.

5The Dow Chemical Company. 2002. Technical Bulletin for ECOSOFT™ solvent IK (2,6,8-Trimethyl-nonan-4-
one). Available online at

http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh 0119/090lb8038011948e.pdf?filepath=oxvsolvents
/pdfs/noreg/327-00050.pdf&fromPage=GetDoc as of August 16, 2012.

6N0M05. 1987. Programs to Enhance PC-Gems Estimates of Physical Properties for Organic Compounds. The
Mitre Corp.

7The Dow Chemical Company. 2006. Test Plan and Robust Summary for 4-Nonanone, 2,6,8-Trimethyl-.

Available online at http://www.epa.gov/oppt/chemrtk/pubs/summaries/4non268t/cl5003tc.htm as of August 16,
2012.

2. General Information on Exposure

2.1	Production Volume and Use

CASRN 68514-41-0 had an aggregated production and/or import volume in the United States
between 1 and 10 million pounds during calendar year 2005.

Industrial processing and uses for the chemical were claimed confidential. No commercial and
consumer uses were reported for the chemical.

2.2	Environmental Exposure and Fate

The components of ketones, C 12-branched are expected to have moderate mobility in soil. Though
no biodegradation studies could be located for the sponsored mixture, a representative component

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of this mixture - a branched C12 ketone, 4-nonanone, 2,6,8-trimethyl- exhibited 48% degradation
over 28 days by biochemical oxygen demand (BOD) using the closed bottle test (OECD guideline
301D). In addition, a C8 ketone fraction was nearly 60% degraded after 28 days using the
Manometric respirometry (OECD 30 IF) test. These data suggest that the components of ketones,
C12-branched will not be highly persistent in the environment. Volatilization is expected to be
high given the estimated Henry's Law constant. Hydrolysis is expected to be negligible since the
components of this mixture do not possess functional groups that are expected to hydrolyze under
environmental conditions. The rate of atmospheric photooxidation is moderate. The constituents
of ketones, C 12-branched are expected to have low persistence (PI) with the exception of the most
highly branched isomers which may have moderate persistence (P2). All the constituents of this
mixture are expected to possess low bioaccumulation potential (Bl).

The environmental fate properties of Ketones, C 12-branched are provided in Table 2.

Table 2. Environmental Fate Properties of Ketones, C12-branched and Supporting

Chemical1'2

Property

SPONSORED CHEMICAL

SUPPORTING CHEMICAL



Ketones, C12-branched

Trimethyl 4-nonanone

CASRN

68514-41-0

123-18-2

Photodegradation Half-
life

7.3 hours (estimated)3

5.5 hours (estimated)3

Hydrolysis Half-life

Stable

Stable

Biodegradation

No data

48% degradation over 28 days by
BOD (not readily biodegradable)4

Bioaccumulation Factor

BAF = 2.3 (estimated)3

BAF = 2.3 (estimated)3

Log Koc

2.61 (estimated)5

2.55 (estimated)3

Fugacity

(Level III Model)5

Air (%)

3.4

3.1

Water (%)

22.5

24.5

Soil (%)

73.6

72.0

Sediment (%)

0.4

0.4

Persistence5

PI (low) to P2 (moderate)

PI (low)

Bi oaccumul ati on5

Bl (low)

Bl (low)

ExxonMobil Chemical Company. 2009. Test Plan and Robust Summary for C12, Branched Ketones. Available
online at http://www.epa.gov/oppt/chemrtk/pubs/summaries/cl2brchketones/cl6825tc.htm as of August 16, 2012.

2The sponsor proposed the branched ketone 4-decanone, 2,9-dimethyl- (CASRN unknown not on TSCA) as a
typical representative structure for the sponsored chemical.

3U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Enviromnental
Protection Agency, Washington DC, USA. Available online at
http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of August 16, 2012.

4The Dow Chemical Company. 2006. Test Plan and Robust Summary for 4-Nonanone, 2,6,8-Trimethyl-.

Available online at http://www.epa.gov/oppt/chemrtk/pubs/summaries/4non268t/cl5003tc.htm as of August 16,
2012.

^Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal
Register 64, Number 213 (November 4, 1999) pp. 60194-60204.

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Conclusion: Ketones, C12-branched is a mixture of branched ketones that is a co-product of
methyl ethyl ketone (MEK) production and is never isolated from the waste MEK production
stream. It is a liquid that is expected to have moderate vapor pressure and moderate water
solubility. The components of this mixture are expected to have moderate mobility in soil. A
representative component of this mixture was not readily biodegradable using a standard OECD
test. The rate of degradation is expected to decrease with the degree of branching of the
components of this mixture. Volatilization is considered high based on the Henry's Law constant
of representative components of this mixture. The rate of hydrolysis is considered negligible since
the constituents of this mixture do not contain functional groups that are expected to hydrolyze
under environmental conditions. The rate of atmospheric photooxidation is considered moderate
for the components of this mixture. The constituents of ketones, C12-branched are expected to
have low persistence (PI) with the exception of the most highly branched isomers which may have
moderate persistence (P2). All the constituents of this mixture are expected to possess low
bioaccumulation potential (Bl).

3. Human Health Hazard

A summary of health effects data submitted for SIDS endpoints is provided in Table 3. The table
also indicates where data for the supporting chemical are read-across (RA) to the sponsored
chemical.

Acute Oral Toxicity

Trimethyl 4-nonanone (CASRN123-18-2, supporting chemical)

Albino rats (10 males/dose; strain not specified) were administered CASRN 123-18-2 (purity not
specified) as a 20% dispersion in 1% Tergitol 7 via gavage at 6300, 7950, 10,000 or 12,600 mg/kg
and observed for up to 14 days. Mortalities were observed at all dose levels: 3/10 at 6300 mg/kg,
4/10 at 7,900 mg/kg, 6/10 at 10,000 mg/kg and all animals at 12,600 mg/kg.

LDso = 8470 mg/kg

Methylheptenone (CASRN 409-02-9, supporting chemical)

Crl:CD SD rats (5 females/dose) were administered CASRN 409-02-9 in corn oil via the oral route
at 2000 mg/kg and observed for 15 days. No mortalities were observed.

LD50 > 2000 mg/kg

Acute Dermal Toxicity

Trimethyl 4-nonanone (CASRN 123-18-2, supporting chemical)

Rabbits (10 males/dose; strain not specified) were administered undiluted CASRN 123-18-2
(purity not specified) via the dermal route at 6500, 8180, 10,300 or 12,900 mg/kg under an
impervious sheeting for 24 hours and observed for up tol4 days. Mortalities were observed at all
dose levels: 2/10 at 7950 mg/kg; 4/10 at 10,000 mg/kg; 5/10 at 12,600 mg/kg, and 9/10 at 15,800
mg/kg.

LD50 = 9030 mg/kg

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Repeated-Dose Toxicity

September, 2014

Methylheptenone (CASRN 409-02-9, supporting chemical)

In a combined oral gavage repeated-dose/reproductive/developmental toxicity screening test,
Crl:CD (SD) rats (10/sex/dose) were administered CASRN 409-02-9 (purity not specified) in corn
oil at 0, 100, 300 or 500 mg/kg-day during a pre-mating period and continuing throughout gestation
and post-parturition. The high-dose was reduced from 1000 mg/kg-day on day 3. One female in
the mid-dose group and one female in the high-dose group were sacrificed early because they
failed to litter. One female in the high-dose group was sacrificed following litter death. A single
female in the high-dose group was sacrificed due to terminal signs. No additional mortalities were
observed in treated animals. Treatment-related effects observed in the high-dose group prior to its
reduction at day 3 included reduced activity, partially closed eyelids, piloerection, hunched
posture, reduced body tone, prostration for up to 4 hours, mean weight loss and significantly low
food consumption. Treatment-related clinical signs were not observed at any dose level following
reduction of the highest dose. A significant decrease in absolute body weight was observed in
high-dose females during lactation and a slight but not significant decrease in body weight gain
was observed in the mid- and high-dose groups. No treatment-related effects were observed on
hematological parameters. Treatment-related effects on functional observations in the high-dose
group included a high incidence of weak tail pinch response during week 5 of treatment and low
forelimb grip strength values in females only. A dose-related reduction in beam scores (cage floor
activity) for all male treatment groups was observed during the first 6 minutes of recording during
week 5. Treatment-related effects observed at gross pathology included significantly increased
liver weights in mid- and high-dose males, increased adjusted ovarian weights in high-dose
females and pale kidneys and macroscopically enlarged livers in high-dose males. An increased
incidence of aggregations of all alveolar macrophages (minimal grade, excepting a single high-
dose male presenting slight grade) was observed in the lungs of all treated male groups and the
high-dose female group. The increase in incidence was slight and a dose response was not
apparent; therefore, the finding was not considered to be of toxicological significance. Slight
hepatocyte centrilobular hypertrophy was observed during histopathological examination of the
liver in all treated male and female groups. This finding was considered to be an adaptive change
and not a toxic effect of treatment. Increased incidence and minimal to moderate severity of
cortical tubular hyaline droplets deposition5, tubular granular casts, cortical tubular basophilia and
increased incidence of minimal to slight interstitial inflammation was observed in all treated male
groups in conjunction with significantly increased kidney weights. Thyroid follicular cell
hypertrophy (minimal severity) was observed in all male treatment groups and in mid- and high-
dose females. This finding was not considered to be of toxicological significance to humans.
LOAEL (male) = 100 mg/kg-day (based on decreased motor activity in the functional
observational battery and thyroid follicular cell hypertrophy)

NOAEL (male) = Not Established.

LOAEL (female) = 300 mg/kg-day (based on thyroid follicular cell hypertrophy)

NOAEL (female) = 100 mg/kg-day

5 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 appears to be unique to
male rats and the response is probably not relevant to humans for purposes of risk assessment. 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 and it is concluded that a NOAEL for nephropathy in male rats was not established.

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Reproductive Toxicity

September, 2014

Methylheptenone (CASRN 409-02-9, supporting chemical)

In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening
test that described above no treatment-related effects were observed on pre-coital interval, mating
performance and fertility. An increased number of females exhibiting 4/5 day cycles or irregular
cycles was observed at the high-dose. A treatment-related shift in the distribution of gestation
lengths showing longer gestation periods was observed in the high-dose group; however, the
gestation index was unaffected. A significant decrease in food consumption during lactation was
observed in mid- and high-dose females on days 1-3 and 1-7, respectively.

LOAEL (reproductive toxicity) = 500 mg/kg-day (based on irregular cycles, increased gestation
period, and increased ovarian weight)

NOAEL (reproductive toxicity) = 300 mg/kg-day

Developmental Toxicity

Methylheptenone (CASRN 409-02-9, supporting chemical)

In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening
test that described above developmental parameters unaffected by treatment included litter size,
sex ratio, offspring development, survival and body weight performance.

NOAEL (developmental toxicity) = 500 mg/kg-day (based on no effects at the highest dose
tested)

Genetic Toxicity — Gene Mutation
In vitro

Methylheptenone (CASRN 409-02-9, supporting chemical)

Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and Escherichia coli strain WP2
uvrA (pKMlOl) were exposed to CASRN 409-02-9 (purity not specified) in dimethylsulfoxide
(DMSO) at seven concentrations ranging from 5 to 5000 |ig/plate with and without metabolic
activation. Positive and solvent controls were included; however, control response was not
indicated. No cytotoxity was observed. No information was provided with respect to observations
of precipitation. No substantial increases in revertant colony numbers over control counts were
obtained in any of the tester strains following exposure to the test substance at any concentration
up to 5000 [j,g/plate, with or without metabolic activation.

Methylheptenone was not mutagenic in this assay.

Genetic Toxicity — Chromosomal Aberrations
In vitro

Methylheptenone (CASRN 409-02-9, supporting chemical)

Human lymphocytes were exposed to CASRN 409-02-9 (purity not specified) at concentrations
ranging from 25 to 200 |ig/ml without metabolic activation or 50 to 1000 |ig/mL with metabolic

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activation. Positive and solvent (DMSO) controls were included. An appropriate response was
observed in the positive control. A statistically significant increase in chromosomal aberrations
was observed at the 600 |ag/m L dose only in the first study with metabolic activation. No
statistically significance increase in chromosomal aberrations was observed in the second test at
any dose level with or without metabolic activation.

Methylheptenone did not induce chromosomal aberrations in this assay.

Additional Information
Skin Irritation

Trimethyl 4-nonanone (CASRN123-18-2, supporting chemical)

In the acute dermal toxicity test described previously, erythema and occasional necrosis was
observed in rabbits following dermal exposure to CASRN 123-18-2.

Trimethyl 4-nonanone was severely irritating to rabbit skin in this assay.

Conclusion: No data are available on the sponsored substance for the human health endpoints.
The acute oral toxicity is low for supporting chemicals trimethyl 4-nonanone and methylheptenone
in rats. The acute dermal toxicity in rabbits is low for supporting chemical trimethyl 4-nonanone.
A combined oral gavage repeated-dose/reproductive/developmental toxicity study in rats with the
supporting chemical, methylheptenone, showed decreased motor activity in a functional
observational battery and thyroid follicular cell hypertrophy in males at 100 mg/kg-day, decreased
food consumption during lactation and thyroid follicular cell hypertrophy in females at 300 mg/kg-
day; the NOAEL for systemic toxicity in males is not established and in females is 100 mg/kg-
day. Irregular cycles and increased gestation period were observed at 500 mg/kg-day; the NOAEL
for reproductive toxicity is 300 mg/kg-day. No treatment-related developmental effects were
observed at the highest-dose tested; the NOAEL for developmental toxicity is 500 mg/kg-day. The
supporting chemical, methylheptenone, was not mutagenic in bacteria in vitro and did not induce
chromosomal aberrations in mammalian cells in vitro. The supporting chemical,
methylheptenone, is severely irritating to rabbit skin.

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Table 3. Summary Table of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program -
Human Health Data

Endpoints

SPONSORED
CHEMICAL
C12, branched

ketones
(68154-41-0)

SUPPORTING
CHEMICAL
Trim ethyl 4-
nonanone
(123-18-2)

SUPPORTING
CHEMICAL
Heptenone, methyl-

(409-02-9)

Acute Toxicity
Oral LDso (mg/kg-bw)

No Data
8470
(RA)

8470

>2000

Acute Toxicity
Dermal LD50 (mg/L)

No Data
9030
(RA)

9030

-

Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)

No Data
NOAEL = Not

Established
LOAEL = 100
(RA)

-

NOAEL = Not

Established
LOAEL = 100

Reproductive Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)

No Data
NOAEL = 300
LOAEL = 500
(RA)

-

NOAEL = 300
LOAEL = 500

Developmental Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)

NOAEL = 500
(hdt)
(RA)

-

NOAEL = 500
(hdt)

Genetic Toxicity -
Gene Mutation
In vitro

No Data
Negative
(RA)

-

Negative

Genetic Toxicity -
Chromosome
Aberrations
In vitro

No Data
Negative
(RA)

-

Negative

Additional Information
Skin Irritation

-

Severely Irritating

-

Bold = measured data (i.e., derived from experiment); (RA) = Read Across; - endpoint not addressed for this
chemical

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4. Hazard to the Environment

A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 4. The
table also indicates where data for the supporting chemical are read-across (RA) to the sponsored
chemical.

Acute Toxicity to Fish

2-Dodecanone (C12) (CASRN 6175-49-1, Supporting Chemical)

Fathead minnow (Pimephales promeIas\ twenty fish per treatment) were exposed to an analog
substance CASRN 6175-49-1 for 96 hours under unspecified condition to nominal concentrations
of 0, 0.9, 1.38, 2.12, 3.26, and 5.01 mg/L. Corresponding mean, measured concentrations were 0,
0.33, 0.55, 0.66, 1.06, and 2.43 mg/L, respectively. Water quality parameters were the following:
temperature=24.8 °C; DO = 6.8 mg/L; pH = 7.6. Mortality was 45 % in the 1.06 mg/L treatment
and 100 % in the 2.43 mg/L treatment.

96-hour LCso = 1.18 mg/L

Acute Toxicity to Aquatic Invertebrates

Methylheptenone (C8) (CASRN 409-02-9, Supporting Chemical)

Daphnids (Daphnia magna) were exposed under unspecified conditions to the analog substance
methyl heptanone for 48 hours according to OECD 202 with WAF prepared nominal
concentrations of 0, 0.75, 2.0, 3.9, 9.1, and 22 mg/L. Measured concentrations were analyzed using
HSGC-FID but no values were reported. Water quality parameters were the following:
temperature= 20.7 - 20.9 °C, DO = 8.2-8.4, pH =7.6 - 7.8, hardness = 142 mg/L as CaC03, and
TOC of the dilution water was 0.54 mg/L. Mortality was 100% at 48 hours in the 9.1 and 22 mg/1
treatment groups
48-hour EC50 = 5.2 mg/L

Toxicity to Aquatic Plants

Methylheptenone (C8) (CASRN 409-02-9, Supporting Chemical)

Green algae (Pseudokirchneriella subcapitata) were exposed under static conditions to the analog

substance methyl heptanone for 72 hours according to OECD 201 with WAF prepared nominal

concentrations of 0, 0.8, 1.6, 4.1, 8.8, and 19.9 mg/L. Measured concentrations were 0, 0.715, 1.42,

3.28, 7.71, and 12.9 mg/L. Water quality parameters were the following: temperature= 23.6 to

23.9°C, pH = 7.6 - 8.7, continuous light intensity = 7,700 - 8,400 lux.

72-hour ErCso = 16 mg/L

72-hour NOErC = 3.28 mg/L

72-hour EbCso = 8 mg/L

72-hour NOEbC = 0.715 mg/L

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U.S. Environmental Protection Agency	September, 2014

Hazard Characterization Document

Conclusion: No data are available on the sponsored substance for the ecotoxicity endpoints. For
the supporting chemical, 2-dodecanone, the 96-h LC50 for fish is 1.18 mg/L. For the supporting
chemical methylheptenone, the 48-h EC50 for aquatic invertebrates is 5.2 mg/L. Toxicity to aquatic
plants, based on the supporting chemical methylheptenone, is 16 mg/L and 8 mg/L for growth rate
and biomass, respectively.

Table 4. Summary of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program -
Aquatic Toxicity Data

Endpoints

SPONSORED
CHEMICAL
C12, Branched
Ketones
(68514-41-0)

SUPPORTING
CHEMICAL
2-Dodecanone
(C12)
(6175-49-1)

SUPPORTING
CHEMICAL
Methyl heptanone
(C8)
(409-02-9)

Fish

96-h LCso (mg/L)

No Data
1.18
(RA)

1.18

-

Aquatic
Invertebrates
48-h ECso (mg/L)

No Data
5.2
(RA)

-

5.2

Aquatic Plants
72-h ECso
growth rate (mg/L)
biomass (mg/L)

No Data
16
8

(RA)

-

16
8

Bold = measured data (i.e. derived from testing), (RA) = read across, - indicates that endpoint not
addressed for this chemical

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