U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
Supporting Documents for Initial Risk-Based Prioritization of
High Production Volume Chemicals
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate (CASRN 64667-33-0)
(9th CI and CA Index Name: Hexanoic acid, 4,6,6,6-tetrachloro-3,3-dimethyl-, methyl
ester)
Contents:
• Page 2: Background
• Page 4: Screening-Level Risk Characterization: September 2008
• Page 7: Screening-Level Hazard Characterization: September 2008
• Page 14: Screening-Level Exposure Characterization: September 2008
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
BACKGROUND
Screening-level hazard, exposure and risk characterizations for high production volume chemicals (HPV)
are important contributions to the chemicals cooperation work being done in North America1 through the
EPA Chemical Assessment and Management Program (ChAMP)2. These screening-level
characterizations are developed by EPA for individual chemicals or chemical categories to support initial
Risk-Based Prioritizations (RBPs) for HPV chemicals. These screening-level characterizations are
technical documents intended primarily to inform the Agency's internal decision-making process.
Accordingly, they are written for assessment professionals and assume a degree of technical
understanding. Each of the support documents is described below.
The Risk-Based Prioritizations are found in an accompanying document and are written for a general
audience. They present EPA's initial thinking regarding the potential risks presented by these chemicals
and future possible actions that may be needed.
Hazard Characterizations for HPV Chemicals
EPA's screening-level hazard characterizations are based primarily on the review of the summaries of
studies and other information submitted by the chemical sponsor(s) under the HPV Challenge Program3.
These studies included in the scope of the HPV Challenge comprise the Screening Information Data Set
(SIDS) of the Organization for Economic Cooperation and Development (OECD)4, an internationally
recognized battery of tests that provides the basic data necessary to make an initial evaluation of a
chemical's hazards and fate. In preparing the initial hazard characterizations, EPA also consulted a
variety of reliable sources5 for additional relevant information and 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 an HPV submission, EPA also searched publicly available databases6 for information entered
from one year prior to the HPV submission through May 2008. The screening-level hazard
characterization is performed according to established EPA guidance7. A more detailed description of the
hazard characterization process is available on the EPA website8.
With respect to chemicals for which internationally-accepted OECD SIDS Initial Assessment Profiles
(SIAP) and Initial Assessment Reports (SIAR) were available, EPA did not generate its own screening-
level hazard characterization, but did check for and incorporate updated information in the risk
characterization.
Exposure Characterizations for HPV Chemicals
EPA recently received exposure-related data on chemicals submitted in accordance with the requirements
of Inventory Update Reporting (IUR)9. The 2006 IUR submissions pertain to chemicals manufactured in
1 U.S. EPA - U.S. Commitments to North American Chemicals Cooperation:
http://www.epa.gov/hpv/pubs/general/sppframework.htm.
2 U.S. EPA - ChAMP information: http://www.epa.gov/champ/.
3 U.S. EPA - HPV Challenge Program information: http://www.epa.gov/hpy.
4 U.S. EPA - Technical Guidance Document, OECD SIDS Manual Sections 3.4 and 3.5:
http://www.epa.gov/chemrtk/pubs/general/sidsappb.htm.
5 U.S. EPA - Public Database Hazard Information: http://www.epa.gov/hpvis/hazardinfo.htm.
6 U.S. EPA - Public Database Update Information: http://www.epa.gov/chemrtk/hpvis/updateinfo.htm.
7 U.S. EPA - Risk Assessment Guidelines: http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
8 U.S. EPA - About HPV Chemical Hazard Characterizations: http://www.epa.gov/hpvis/abouthc.htm.
9 U.S. EPA - Basic IUR Information: http://www.epa.gov/opptintr/iur/pubs/guidance/basic-infonnation.h1m.
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
(including imported into) the U.S. during calendar year 2005 in quantities of 25,000 pounds or more at a
single site. The reports include the identity, the quantity, and the physical form of the chemical
manufactured or imported, and the number of workers reasonably likely to be exposed during
manufacture of the chemical. For chemicals manufactured or imported in quantities of 300,000 pounds or
more at a single site, additional reported information includes: the industrial processing and uses of the
chemical; the number of industrial processing sites and workers reasonably likely to be exposed to the
chemical at those sites; the consumer and commercial uses of the chemical; and an indication whether the
chemical was used in products intended for use by children under 14 years of age.
EPA's screening-level exposure characterizations are based largely on the information submitted under
the IUR reporting, although other exposure information submitted to the Agency (for example, in HPV
submissions) or readily available through a limited set of publicly accessible databases10 was also
considered. The screening-level exposure characterizations identify a potential (high, medium, or low)
that each of five populations - the environment, the general population, workers, consumers, and children
- might be exposed to the chemical. In most cases, this potential doesn't address the quantity, frequency,
or duration of exposure, but refers only to the likelihood that an exposure could occur.
In many instances EPA is not able to fully disclose to the public all the IUR exposure-related data
reviewed or relied upon in the development of the screening-level documents because some of the
material was claimed as confidential business information (CBI) when it was submitted to the Agency.
These CBI claims do limit the Agency's ability to be completely transparent in presenting some
underlying exposure and use data for chemicals in public documents. EPA does consider all data,
including data considered to be CBI, in the screening-level exposure and risk characterization process,
and endeavors whenever possible to broadly characterize supporting materials claimed as confidential in
ways that do not disclose actual CBI.
Risk Characterizations for HPV Chemicals
EPA combines the information from the screening-level exposure characterization with the screening-
level hazard characterization to develop a qualitative screening-level risk characterization, as described in
the Agency's guidance on drafting risk characterizations11. These screening-level risk characterizations
are technical documents intended to support subsequent priority-setting decisions and actions by OPPT.
The purpose of the qualitative screening-level risk characterization is two-fold: to support initial risk-
based decisions to prioritize chemicals, identify potential concerns, and inform risk management options;
and to identify data needs for individual chemicals or chemical categories.
These initial characterization and prioritization documents do not constitute a final Agency determination
as to risk, nor do they determine whether sufficient data are available to characterize risk. Recommended
actions reflect EPA's relative judgment regarding this chemical or chemical category in comparison with
others evaluated under this program, as well as the uncertainties presented by gaps that may exist in the
available data.
10 U.S. EPA - Summary of Public Databases Routinely Searched:
http://www.epa.gov/chemrtk/hpvis/pubdtsum.htm.
11 U.S. EPA - Risk Characterization Program: http://www.epa.gov/osa/spc/2riskchr.htm.
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate (CAS No. 64667-33-0)
[9th CI Name: Hexanoic acid, 4,6,6,6-tetrachloro-3,3-dimethyl-, methyl ester]
September 2008
Prepared by
Risk Assessment Division
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION FOR
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate (CAS No. 64667-33-0)
1. Physical-Chemical Properties and Environmental Fate
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate is a clear, colorless liquid at room
temperature. It has moderate vapor pressure. The water solubility is considered moderate, based
on an estimated value. It has moderate mobility in soil and moderate volatility. Hydrolysis is
considered negligible under environmental conditions. Ready biodegradability data for methyl
4,6,6,6-tetrachloro-3,3-dimethylhexanoate are not available but it is assumed to be persistent in
the environment (P3). Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate bioaccumulation
potential is estimated to be moderate (B2).
2. Hazard Characterization
Aquatic Organism Toxicity. The potential hazard of methyl 4,6,6,6,-tetrachloro-3,3-
dimethylhexanoate to aquatic organisms could not be assessed because of data gaps.
Human Health Toxicity. Acute oral and inhalation toxicity of methyl 4, 6,6,6,-tetrachloro-3,3-
dimethylhexanoate in rats are low. Acute dermal toxicity in rabbits may be low but there is
uncertainty because the highest concentration tested is below the limit dose generally used for
such tests. Repeated-dose and reproductive data were not required for the HPV Challenge
Program because methyl 4, 6,6,6,-tetrachloro-3,3-dimethylhexanoate is a closed-system
intermediate. No data was submitted for developmental toxicity. In vitro studies were negative
for mutagenic potential of methyl 4, 6,6,6,-tetrachloro-3,3-dimethylhexanoate. Data for
chromosomal aberrations were not submitted. The potential health hazard of methyl 4, 6,6,6,-
tetrachloro-3,3-dimethylhexanoate could not be determined.
3. Exposure Characterization
There were no 2002 or 2006 IUR reports for Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate
(CAS # 64667-33-0). No information on commercial/consumer uses were found in the IUR or
any other sources.
Potential Exposures to Humans and the Environment:
Based on the information considered (including information from the HPV Challenge Program)
and in combination with the Agency's professional judgment, EPA identifies, for the purposes of
risk-based prioritization, a low relative ranking for each of the potentially exposed groups
(including workers, general population, consumers and children) and the environment. In 2003,
the Agency reviewed the information in the HPV submission and test plan and determined that
the information satisfies the guidance to demonstrate that the chemical is a closed system
intermediate. The chemical was determined to be manufactured and processed in systems which
are expected to reduce the potential for worker exposure and environmental releases that could
lead to other human and environmental exposure.
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
4. Risk Characterization
The statements and rationale provided below are intended solely for the purpose of this
screening-level and qualitative risk characterization and will be used for prioritizing substances
for future work in the Chemical Assessment and Management Program (ChAMP).
Risk Statement and Rationale
The Agency reviewed the information in the HPV submission and test plan and determined that
the HPV chemical satisfied the guidance to demonstrate that the chemical is a closed-system
intermediate. Methyl 4, 6,6,6,-tetrachloro-3,3-dimethylhexanoate was determined to be
manufactured and processed in closed systems which are expected to reduce the potential for
worker exposure and environmental releases that could lead to other human and environmental
exposure. Therefore, there is a low concern for potential risks to aquatic organisms and the
general population from environmental releases, and also to workers, consumers, and children.
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate (CAS No. 64667-33-0)
[9th CI Name: Hexanoic acid, 4,6,6,6-tetrachloro-3,3-dimethyl-, methyl ester]
September 2008
Prepared by
Risk Assessment Division
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SCREENING-LEVEL HAZARD CHARACTERIZATION
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate (CAS No. 64667-33-0)
Introduction
The sponsor, the FMC Corporation, submitted a Test Plan and Robust Summaries to EPA for methyl 4,6,6,6-tetrachloro-3,3-
dimethylhexanoate (CAS No. 64667-33-0; 9th CI name: hexanoic acid, 4,6,6,6-tetrachloro-3,3-dimethyl-, methyl ester) on
December 30, 2002. EPA posted the submission on the ChemRTK HPV Challenge website on January 28, 2003
('http://www.epa.gov/chemrtk/pubs/summaries/methvl46/cl4189tc.htm'). EPA comments on the original submission were posted
to the website on June 3, 2002. Public comments were also received and posted to the website. The sponsor submitted
updated/revised documents on July 30, 2003, which were posted to the ChemRTK website on September 5, 2003.
The sponsor proposed reduced health testing, claiming that methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate is a closed-system
intermediate (CSI). EPA's evaluation of the original and revised/updated information indicated that the sponsor adequately
supported the "closed system intermediate" claim for the substance. Therefore, EPA has determined that the chemical qualifies
for reduced testing - waiving of repeated-dose and reproductive toxicity testing.
On July 1, 2004, the sponsor informed EPA that they no longer manufactured or imported methyl 4,6,6,6-tetrachloro-3,3-
dimethylhexanoate and had no plans to in the future. The sponsor stated that for this reason, they do not believe conducting the
additional tests identified in their test plans would be an appropriate allocation of human, animal and financial resources and that
EPA should consider their submission based on existing data to be final.
This screening level hazard characterization is based primarily on the review of the test plan and robust summaries of studies
submitted by the sponsor(s) 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. 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 2004 to May 2008: the NLM databases (ChemID to locate
available data sources including Medline/PubMed, Toxline, HSDB, IRIS, NTP, ATSDR, EXTOXNET, EPA SRS, etc.),
STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS, Merck, etc.) and Science Direct. A
summary table of SIDS endpoint data with the structure(s) of the sponsored chemical(s) is included in the appendix. The
screening-level hazard characterization for environmental and human health effects is based largely on SIDS endpoints and is
described according to established EPA or OECD effect level definitions and hazard assessment practices.
Il;i/;ird ( liiii'iiclori/iilion
Mollis I 4.<>.<>.<>-lcir;ichloro-V '-dimelhv lhc\;iiio;ilc is ;i clc;ir. colorless liquid ;il room lcnipcr;iliirc ll li;is niodcr;ilc
\ ;ipor pressure The w;iler soluhiliis is considered iiK>tler;iie. h;ised on ;in esiiin;iied \ ;ilue ll li;is iiK>tler;iie niohihis
mi soil ;ind MK d;il;i lor nielliv I 4.<>.<>.<>-icimchloro-\ '-dimelhv llie\;nio;iie ;ire noi ;i\;nl;ihle hul u is ;issunied lo he
pei'sisieul mi llie eu\ iroiinieul (I'' i \1elli> I 4.<>.<>.<>-leir;ieliloro- V ^-diniellis llie\;iuo;ile hio;ieeiiniul;iliou poleuluil is
esiimiiled lo he niodercile (152)
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assessed hee;iuse of d;il;i mips
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11mil dose ueuer;ill\ used for such lesis kepe;iled-dose ;md rcproducli\ e d;il;i were w;u\ ed for lhe I IPX ( h;illcuuc
houmni hec;iiise nicllis I 4.<>.<>.<>.-icir;ichloro-\ ^-diniclhs lhe\;iuo;iie is ;i closed-s\ sieui iuierniedi;ile \o d;il;i w;is
siihniiued lor dc\ elopnieui;il io\icil>. hi riim siudics were ucu;ili\ e for niuiimcuic poicuiul of nicllis I 4. <>.<>.<>.-
leinichloro-\'-dimelhs lhe\;uio;ile l);il;i lor chroniosoni;il ;iherr;ilioiis were uol suhmilled I lie poleuli;il he;i 11 h
h;i/;ird of nielh\ I 4.(>.(>.(>.-leir;ichloro- V ^-diuielhs lhe\;iuo;ile could uol he determined
kc;id\ hiodeur;id;iliou. lo\icil> lo ;n|ii;ilic iiru;uiisnis. de\elopnieul;il u<\icil\ ;iud chroniosoni;il ;iherr;ilioiis were
ideniil'ied ;is d;il;i u;ips under ihe 111J\ ( h;illeime IJi\"-ir;nii.
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September 2008
1. Physical-Chemical Properties and Environmental Fate
The physical-chemical properties of methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate are summarized in Table la,
while its environmental fate properties are given in Table lb. The structure of the compound is provided in the
Appendix.
Physical-Chemical Properties Characterization
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate is a clear, colorless liquid at room temperature. It has moderate
vapor pressure. The water solubility is considered moderate, based on an estimated value.
Table la. Phvsical-Chemical Properties of Mcthvl 4,6,6,6-tctraehloro-3,3(limcthvlhcxanoatc1
Property
Value
CAS No.
64667-33-0
Molecular Weight
296
Physical State
Liquid
Melting Point
Unavailable, liquid at room temperature
Boiling Point
110-114°C at 0.7 mm Hg (measured)
101-103°C at 0.1 mm Hg (measured)
Vapor Pressure
0.6 mm Hg at 100°C (measured)
0.05 mm Hg at 25°C (estimated)2
Henry's Law Constant
1.48xl0"5 atm-m3/mol (estimated)2
Water Solubility
1.149mg/L (estimated)2
Log Kow
4.74 (estimated)2
1FMC. 2002. Robust Summary for methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate.
http://www.epa.gov/chemrtk/pubs/summaries/methvl46/cl4189rr.pdf.
2US EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
Environmental Fate Characterization
Methyl 4,6,6,6-tetrachloro-3,3,-dimethylhexanoate is expected to partition primarily to soil, according to a Level III
fugacity model that assumes equal emissions to air, water, and soil. Based on its vapor pressure, methyl 4,6,6,6-
tetrachloro-3,3-dimethylhexanoate will exist in the vapor phase in the atmosphere. Vapor-phase methyl 4,6,6,6-
tetrachloro-3,3-dimethylhexanoate has an estimated half-life of 5.2 days due to photooxidation with hydroxyl
radicals. Volatilization of methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate is considered moderate based on its
Henry's Law constant. It has moderate mobility in soil. Hydrolysis is considered negligible under environmental
conditions. Biodegradation data for methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate are not available; but it is
estimated to be persistent (P3). Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate bioaccumulation potential is
ranked moderate (B2) based on an estimated log BCF of 3.0.
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September 2008
Table lb. Environmental Fate Characteristics of IMethvl 4,6,6,6-tctrachloro-3,3-(limcthvlhcxanoatc1
Property
Value1
Photodegradation Half-life
5.2 days (estimated)2
Hydrolysis Half-life
54 years at pH 7 (estimated)
5.4 years at pH 8 (estimated)
Biodegradation
No data - expected to be stable to biodegradation
Bioconcentration
Log BCF = 3.02
Log Koc
2.8 (estimated)2
Fugacity
(Level III Model)
Air = 0.67%
Water =9.71%
Soil = 72%
Sediment = 17.6%
Persistence3
P3 (high)
Bioaccumulation3
B2 (moderate)
1FMC 2002. U.S. High Production Volume (HPV) Chemical Challenge Program. Robust Summary for methyl
4,6,6,6-tetrachloro-3,3-dimethylhexanoate. http://www.epa.gov/chemrtk/pubs/summaries/methYl46/cl4189rr.pdf
2US EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
3FR. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64,
Number 213 (November 4, 1999) Page 60194-60204.
Conclusion: Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate is a clear, colorless liquid at room temperature. It
has moderate vapor pressure. The water solubility is considered moderate, based on an estimated value. It has
moderate mobility in soil and moderate volatility. Hydrolysis is considered negligible under environmental
conditions. Ready biodegradability data for methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate are not available but
it is assumed to be persistent in the environment (P3). Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate
bioaccumulation potential is estimated to be moderate (B2).
2. Environmental Effects - Aquatic Toxicity
In comments on the original test plan, EPA indicated that because of the estimated low water solubility and high log
Kow of methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate only a chronic daphnia test needed to be performed, unless
results of proposed physical-chemical properties and fate testing indicated the estimated properties were greatly
different than predicted, in which case test data for all three acute aquatic toxicity endpoints would need to be
provided.
Acute Toxicity to Fish
No adequate data were submitted.
Acute Toxicity to Aquatic Invertebrates
No data were submitted.
Toxicity to Aquatic Plants
No data were submitted.
Chronic Toxicity to Aquatic Invertebrates
No data were submitted.
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Conclusion: The potential hazard of methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate to aquatic organisms could
not be assessed because of data gaps.
3. Human Health Effects
Acute Oral Toxicity
Sprague-Dawley rats (5/sex) were administered methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate at 5000 mg/kg-
bw and observed for up to 14 days following dosing. No mortality was observed. Clinical signs of toxicity included
abdominogenital staining, diarrhea, exophthalmos, lacrimation, decreased locomotion, nasal discharge and oral
discharge. There were no gross lesions in any animal at gross necropsy.
LDS0 > 5000 mg/kg-bw
Acute Inhalation Toxicity
Sprague-Dawley rats (5/sex) were exposed (whole-body) to methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate at 5.5
ppm (~ 0.07 mg/L) for 6 hours and observed for up to 14 days following dosing. No mortality was observed.
Clinical signs of toxicity included irregular breathing patterns during the first hour of treatment. One rat had red
periocular fur around the left eye immediately following exposure. No gross lesions were noted at necropsy.
LC50 > 0.07 mg/L
Acute Dermal Toxicity
New Zealand White rabbits (5/dose, sex not specified) were administered methyl 4,6,6,6-tetrachloro-
3,3-dimethylhexanoate dermally at 28.2 or 423 mg/kg-bw under occlusive conditions for 24 hours and observed for
14 days. No mortality or body weight change was observed. Slight erythema and desquamation were noted
sporadically. No gross lesions were observed at necropsy.
LDS0 > 423 mg/kg-bw
Repeated-Dose Toxicity
EPA indicated that the information provided by the sponsor was sufficient to meet the criteria for demonstrating that
methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate is a closed-system intermediate. No repeated-dose toxicity data
were submitted and the EPA agreed that testing was not required for this endpoint.
Reproductive/Developmental Toxicity
No data were submitted. Data Gap.
Genetic Toxicity - Gene Mutation
In vitro
Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100 were exposed to methyl
4,6,6,6-tetrachloro-3,3-dimethylhexanoate at concentrations of 10 - 10,000 |ig/plate in the presence and absence of
metabolic activation. Positive and negative controls were used, but their responses were not provided.
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate was not mutagenic in this assay.
Genetic Toxicity - Chromosomal Aberrations
In vitro
No data were submitted. Data Gap.
Conclusion: Acute oral and inhalation toxicity of methyl 4, 6,6,6,-tetrachloro-3,3-dimethylhexanoate in rats are
low. Acute dermal toxicity in rabbits may be low but there is uncertainty because the highest concentration tested is
below the limit dose generally used for such tests. Repeated-dose and reproductive data were not required for the
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Supporting Documents for Risk-Based Prioritization
HPV Challenge Program because methyl 4, 6,6,6,-tetrachloro-3,3-dimethylhexanoate is a closed-system
intermediate. No data was submitted for developmental toxicity. In vitro studies were negative for mutagenic
potential of methyl 4, 6,6,6,-tetrachloro-3,3-dimethylhexanoate. Data for chromosomal aberrations were not
submitted. The potential health hazard of methyl 4, 6,6,6,-tetrachloro-3,3-dimethylhexanoate could not be
determined.
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APPENDIX
Summary Tabic of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Methyl 4,6,6,6-tctrachloro-3,3-dimcthylhcxanoatc
(CAS No. 64667-33-0)
Structure
CI CI
o 01
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
Data Gap
Aquatic Invertebrates
48-h ECS0 (mg/L)
Data Gap
Aquatic Plants
72-h ECS0 (mg/L)
Data Gap
Chronic Toxicity to Invertebrates
21-day ECS0 (mg/L)
Data Gap
Summary of Human Health Data
Acute Oral Toxicity
LDS0 (mg/kg-bw)
>5000
Acute Inhalation Toxicity
LCS0 (mg/L)
>0.07
Acute Dermal Toxicity
LDS0 (mg/kg-bw)
>423
Developmental Toxicity
NOAEL/LOAEL
Data Gap
Genetic Toxicity - Gene Mutation
In vitro
Negative
Genetic Toxicity - Chromosomal Aberrations
In vitro
Data Gap
— indicates that endpoint was not addressed for this chemical.
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September 2008
Screening Level Exposure Characterization for HPV Challenge
Chemical
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate
CAS # 64667-33-0
September 2008
Prepared by
Exposure Assessment Branch
Chemical Engineering Branch
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
Screening Level Exposure Characterization
Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate (CAS # 64667-33-0)
Non-CBI Executive Summary
There were no 2002 or 2006 IUR reports for Methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate
(CAS # 64667-33-0).
Potential Exposures to Humans and the Environment:
Based on the information considered (including information from the HPV Challenge Program)
and in combination with Agency's professional judgment, EPA identifies, for the purposes of
risk-based prioritization, a low relative ranking for each of the potentially exposed groups
(including workers, general population, consumers and children) and the environment. In 2003,
the Agency reviewed the information in the HPV submission and test plan and determined that
the information satisfies the guidance to demonstrate that the chemical is a closed system
intermediate.12 The chemical was determined to be manufactured and processed in systems
which are expected to reduce the potential for worker exposure and environmental releases that
could lead to other human and environmental exposure. There are no 2002 or 2006 IUR reports
for this chemical. No information on commercial/consumer uses were found in the IUR or any
other sources.
12 USEPA, 2003. EPA Comments on Chemical RTK HPV Challenge Submission. Letter dated May 28, 2003.
Accessed June 16, 2008. http://www.epa.gov/chemrtk/pubs/summaries/methYl46/cl4189rr.pdf.
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