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
2-Amino-2,3-dimethylbutanenitrile (CASRN 13893-53-3)
(9th CI and CA Index Name: Butanenitrile, 2-amino-2,3-dimethyl-)
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
2-Amino-2,3-dimethylbutanenitrile (CAS No. 13893-53-3)
[9th CI Name: Butanenitrile, 2-amino-2,3-dimethyl-]
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
2-Amino-2,3-dimethylbutanenitrile (CAS No. 13893-53-3)
1. Physical-Chemical Properties and Environmental Fate
2-Amino-2,3-dimethylbutanenitrile is a liquid at room temperature that has a high estimated
water solubility and moderate estimated vapor pressure. 2-Amino-2,3-dimethylbutanenitrile has
high mobility in soil and minimal volatility. The rate of atmospheric photooxidation is
considered moderate. The bioaccumulation potential is ranked low (Bl). No measured data on
the biodegradability of 2-amino-2,3-dimethylbutanenitrile were provided by the sponsor.
However, based on professional judgment, EPA judges the persistence of the chemical as
moderate (P2).
2. Hazard Characterization
Aquatic Organism Toxicity. The acute toxicity of 2-amino-2, 3-dimethylbutanenitrile to fish and
aquatic plants is high, and to aquatic invertebrates is moderate.
Human Health Toxicity. The acute oral toxicity of 2-amino-2, 3-dimethylbutanenitrile in rats is
moderate. The acute inhalation toxicity of 2-amino-2, 3-dimethylbutanenitrile in rats and acute
dermal in rabbits is high. Mortality was observed following instillation of 2-amino-2,3-
dimethylbutanenitrile into the eyes of rabbits. Repeated-dose and reproductive data were not
required for the HPV Challenge Program because 2-amino-2, 3-dimethylbutanenitrile is a closed-
system intermediate. However, a dermal repeated-dose toxicity study in rats was submitted and
showed skin irritation, but there were no signs of toxicity in any treatment group. 2-Amino-2,3-
dimethylbutanenitrile did not induce gene mutations.
3. Exposure Characterization
2-amino-2,3-dimethyl-butanenitrile (CAS # 13893-53-3) has an aggregated production and/or
import volume in the United States of 1 million to 10 million pounds. Non-confidential IUR
information for this chemical indicates that it is used as a site-limited intermediate. No
commercial/consumer uses were reported in the IUR or any other data sources.
Potential Exposures to Humans and the Environment:
Based on the information considered, including IUR data and information from the HPV
Challenge Program information, and in combination with the Agency's professional judgment,
EPA identifies, for the purposes of risk-based prioritization, a low relative ranking for the
potentially exposed groups (including workers, general population, consumers and children) and
the environment. The Agency has reviewed the information in the HPV submission test plan and
determined that the HPV chemical satisfies the guidance to demonstrate that the chemical is a
closed system intermediate. The chemical is manufactured and processed in systems that are
expected to reduce the potential for worker exposure and environmental releases that could lead
to other human and environmental exposure. The guidance for identifying this chemical
substance as a closed-system intermediate was satisfied at all sites for which this chemical was
reported.
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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 for a closed system intermediate. 2-Amino-2, 3-
dimethylbutanenitrile was determined to be manufactured and processed in closed systems that
are expected to reduce the potential for worker exposure and environmental releases that could
lead to other human and environmental exposure. The guidance for identifying this chemical
substance as a closed-system intermediate was satisfied at all sites reporting this chemical in
accordance with IUR requirements. Therefore, there is a low concern for potential risks to
aquatic organisms and the general population from environmental releases, and also low risk 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
2-Amino-2,3-dimethylbutanenitrile (CAS No. 13893-53-3)
[9th CI Name: Butanenitrile, 2-amino-2,3-dimethyl-]
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
7
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
SCREENING-LEVEL HAZARD CHARACTERIZATION
2-Amino-2,3-dimethylbutanenitrile (CAS No. 13893-53-3)
Introduction
The sponsor, Cytec Industries, Inc., submitted a Test Plan and Robust Summaries to EPA for 2-amino-2,3-
dimethylbutanenitrile (CAS No. 13893-53-3; 9th CI name: butanenitrile, 2-amino-2,3-dimethyl-) on May 21, 2001.
EPA posted the submission on the ChemRTK HPV Challenge Web site on September 18, 2001
(http://www.epa.gov/chemrtk/pubs/summaries/2amindi/cl313 ltc.htm). EPA comments on the original submission
were posted to the website on February 19, 2002. The sponsor submitted updated/revised documents on July 2001
and April 5, 2002, which were posted to the ChemRTK website on July 20, 2001 and April 25, 2002. Public
comments were also received and posted to the website.
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. 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.
The sponsor proposed reduced health effects testing under the HPV Challenge Program claiming that 2-amino-2,3-
dimethylbutanenitrile is a closed-system intermediate (CSI). EPA's evaluation of the original and revised/updated
information indicated that the chemical meets the guidance to fully support the CSI status for this chemical -
waiving of repeated-dose and reproductive toxicity testing for the purposes of the HPV Challenge Program.
In the revised submission, the sponsor provided a robust summary for a chromosomal aberrations study in
mammalian cells for two aliphatic nitriles, but did not provide chromosomal aberrations data for the sponsored
chemical. The sponsor also provided developmental toxicity robust summaries for the following proposed
supporting chemicals: four saturated aliphatic nitriles (acetonitrile, CAS No. 75-05-8; propionitrile, CAS No. 107-
12-0; n-butyronitrile, CAS No. 109-74-0 and isobutyronitrile, CAS No. 78-82-0); four unsaturated aliphatic nitriles
(acrylonitrile, CAS No. 107-13-l;methacrylonitrile, CAS No. 126-98-7; allylnitrile, CAS No. 109-75-1 and cis-2-
pentenenitrile, CAS No. 920-37-6) and a chlorine-substituted unsaturated aliphatic nitrile (2-chloroacrylonitrile,
CAS No. 920-37-6).
EPA did not consider the submitted data for chromosomal aberrations and developmental toxicity adequate for the
following reasons: (1) The sponsor did not provide a rationale for using data for saturated aliphatic nitriles,
unsaturated aliphatic nitriles or a chlorine-substituted unsaturated aliphatic nitrile to characterize the chromosomal
aberration induction potential or developmental toxicity of the sponsored chemical, an amine-substituted saturated
aliphatic nitrile. (2) There is uncertainty that data for the proposed supporting nitriles could be extrapolated to
determine the dose-response characteristics of the sponsored chemical because slight changes in the structures of
these nitriles produced large differences in effect levels in an inhalation developmental toxicity study (for example,
the NOAECs for acetonitrile and propionitrile were different by a factor of 10). (3) Although all of the proposed
supporting chemicals produced developmental effects, the sponsor indicated that the mechanism by which nitriles
produce developmental effects is uncertain and provided no discussion about whether or not the amine moiety of the
sponsored chemical would affect developmental toxicity potential. (4) The sponsor provided no data or discussion
to indicate if structural variations in nitriles may affect their potential to induce chromosomal aberrations.
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U.S. Environmental Protection Agency
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September 2008
11 ;i/;i I'd (ha racleri/al ion
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niodemie esiinialed \ apor pressure 2- \niiuo-2. i-dinielh\ Ihiilaiieuiirile h;is hmli niohihls in soil ;ind mi in iii;i I
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km (l>h \o measured d;il;i on i lie hiodeuradahihis of 2-;iiniiK»-2. ^-dinielhs Ihiilaiieuiirile were pro\ ided In I lie
sponsor I lowe\ er. hnsed on professional iiidmiieui. IP \ indues ilie persisienee of ilie eliemie;il ;is iiK>cler;iie (l'21
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iu\ eriehrales is moderate
I lie ;ieule oral lo\ieil> of 2-;iniiuo-2. ^-dinielhs lhiil;iiieinirile in r;ils is moderate The aeule inhalation lo\ieil\ ol'2-
aniuio-2. ^-dinielhs Ihiilaiieuiirile in mis and ;ienle derni;il lo\ieil> in r;ihhils is high \1orialil> was ohser\ ed
follow uig i iisi 11 l;ii kiii of 2-;iniiuo-2. ^-dinielhs lhiii;iiieinirile inio I he e\ es of r;ihhiis kepealed-dose ;md reprodueli\ e
d;il;i were nol required lor I he I ll'V ("h;il lenize lJi\iizr;i in lve;iiise 2-aniiuo-2. ^-dinielhs lhiil;iiieinirile is ;i elosed-
s\ siem iiilerniediale I lowe\er. ;i derm;il repe;iled-dose siucl\ in r;ils w;is siihmiiied ;md showed skin irrilaliou. hill
I here were no si mis of io\ieil> in am ireainieui group 2- \niiuo-2. ^-dinielhs lbiii;iiieinirile did nol induce gene
niiiialious
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I ll'Y Challenge I'rograni
1. Physical-Chemical Properties and Environmental Fate
The physical-chemical properties of 2-amino-2,3-dimethylbutanenitrile 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
2-Amino-2,3-dimethylbutanenitrile is a liquid at room temperature that has high estimated water solubility and
moderate estimated vapor pressure.
Table la. Phvsical-Chemical Properties of 2-Amino-2,3-dimcthvll)utancnitrilc'
Property
Value
CAS No.
13893-53-3
Molecular Weight
112.18
Physical State
Liquid
Melting Point
Unavailable, liquid at room temperature
Boiling Point
186.88°C (with decomposition) (estimated)2
Vapor Pressure
23.42 mm Hg (measured; 60% solution of 2-amino-2,3-
dimethylbutanenitrile in toluene)
0.69 mm Hg at 25°C (estimated)2
Water Solubility
1.07x 105 mg/L at 25°C (estimated)2
Henry's Law Constant
9.8x 10"9 atm-m3/mole (estimated)2
Log Kow
0.87 (estimated)2
1CYTEC Industries Inc. 2002. Revised Robust Summary for 2-Amino-2,3-Dimethylbutanenitrile.
http://www.epa.gov/chemrtk/pubs/summaries/2amindi/cl3131tc.htm.
2USEPA. 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.
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Supporting Documents for Risk-Based Prioritization
September 2008
Environmental Fate Characterization
2-Amino-2,3-dimethylbutanenitrile is expected to partition primarily to soil and water, according to the results of a
Level III fugacity model that assumes equal emissions to air, water, and soil. Based on its estimated vapor pressure
2-amino-2,3-dimethylbutanenitrile will exist in the vapor phase in the atmosphere. The rate of atmospheric
photodegradation of vapor-phase 2-amino-2,3-dimethylbutanenitrile with photochemically generated hydroxyl
radicals is considered moderate. Volatilization of 2-amino-2,3-dimethylbutanenitrile is considered minimal based
on its Henry's Law constant. It is highly mobile in soil, does not bioaccumulate, and partially hydrolyzes at
environmental pH although no rates were provided. No measured data on the ready biodegradability of 2-amino-
2,3-dimethylbutanenitrile were provided by the sponsor. Although some simple aliphatic nitriles are readily
biodegradable, no data were available to demonstrate that branched amino nitriles or nitriles containing quaternary
carbons biodegrade rapidly. In some cases the presence of a quaternary carbon reduces biodegradability. Therefore,
based on professional judgment EPA rates the persistence of the chemical as moderate (P2). 2-Amino-2,3-
dimethylbutanenitrile was reported to partially hydrolyze in water; however, no rate for this reaction was provided.
The bioaccumulation potential is ranked low (Bl) based on an estimated BCF of 3.
Table lb. Environmental Fate Characteristics of Z-Amino-Z^-dimcthvlbutancnitrilc1
Property
Value
Photodegradation Half-life
44.4 hours (estimated)2
Hydrolysis Half-life
Partially hydrolyses in water to HCN
Biodegradation
No data
Bioconcentration
BCF = 3 (estimated)2
Koc
44 (estimated)2
Fugacity
(Level III Model)2
Air =0.16%
Water = 46.2%
Soil = 53.5%
Sediment = 0.09%
Persistence
P2 (moderate)3
Bioaccumulation
Bl (low)3
1CYTEC Industries Inc. 2002. Revised Robust Summary for 2-Amino-2,3-Dimethylbutanenitrile.
http://www.epa.gov/chemrtk/pubs/summaries/2amindi/cl3131tc.htm.
2USEPA. 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.
3Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal
Register 64, Number 213 (November 4, 1999) pp. 60194-60204.
Conclusion: 2-Amino-2,3-dimethylbutanenitrile is a liquid at room temperature that has a high estimated water
solubility and moderate estimated vapor pressure. 2-Amino-2,3-dimethylbutanenitrile has high mobility in soil and
minimal volatility. The rate of atmospheric photooxidation is considered moderate. The bioaccumulation potential
is ranked low (Bl). No measured data on the biodegradability of 2-amino-2,3-dimethylbutanenitrile were provided
by the sponsor. However, based on professional judgment, EPA rates the persistence of the chemical as moderate
(P2).
2. Environmental Effects - Aquatic Toxicity
Acute Toxicity to Fish
Bluegill sunfish (Lepomis macrochirus, 10/concentration) were exposed to 2-amino-2,3-dimethylbutanenitrile at
nominal concentrations of 0, 0.10, 0.18, 0.32, 0.56 or 1.0 mg/L under static conditions for 96 hours. All of the fish
at 1.0 mg/L died before the end of the 24-hour observation period. No deaths or signs of toxicity occurred at lower
concentrations.
96-h LCS0 = 0.75 mg/L
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September 2008
Acute Toxicity to Aquatic Invertebrates
Water fleas (Daphnia magna, 20/concentration, 10/replicate) were exposed to 2-amino-2,3-dimethylbutanenitrile at
nominal concentrations of 0, 0.56, 1.0, 1.8, 3.2, 5.6 or 10 mg/L under static conditions for 48 hours. Concentrations
were not measured. No mortality or abnormal effects were noted at concentrations up to 3.2 mg/L. Mortality or
immobilization were observed at 5.6 mg/L after 24 and 48 hours of exposure (2/20 and 3/20 dead, respectively) and
at 10 mg/L after 24 and 48 hours of exposure (15/20 and 20/20 dead, respectively).
48-h ECS0=6.9 mg/L
Toxicity to Aquatic Plants
Green algae (Pseudokirchneriella subcapitata) were exposed to 2-amino-2,3-dimethylbutanenitrile at nominal
concentrations of 0, 0.01, 0.1, 0.5, 1.0 or 10 mg/L under static conditions for 96 hours. Concentrations were not
measured. Growth was inhibited at concentrations >0.5 mg/L.
96-h ECS0 (growth) = 0.36 mg/L
Conclusion: The acute toxicity of 2-amino-2,3-dimethylbutanenitrile to fish and aquatic plants is high, and to
aquatic invertebrates is moderate.
3. Human Health Effects
Acute Oral Toxicity
Sprague-Dawley rats (10 males/dose) were administered 2-amino-2,3-dimethylbutanenitrile via gavage at 31.3, 62.5
or 125 mg/kg-bw in corn oil and were observed for 14 days. Signs of toxicity included tremors, tonic convulsions,
salivation and prostration at the highest dose and in one rat at 62.5-mg/kg-bw. All of the rats administered 125
mg/kg-bw and one rat at 62.5 mg/kg-bw died within 8 hours of exposure.
LDS0 = 83 mg/kg-bw
Acute Inhalation Toxicity
(1) Rats (5/sex/concentration) were exposed to 2-amino-2,3-dimethylbutanenitrile vapor at measured concentrations
of 21, 58, 71 or 77 ppm (approximately 0.10, 0.27, 0.33 or 0.35 mg/L, respectively) for 4 hours and observed for 14
days. Deaths occurred at > 0.33 mg/L, all during the first day of exposure. Clinical signs included hypoactivity,
ataxia, prostration and respiratory irritation on the day of exposure at concentrations > 0.27 mg/L. No clinical signs
were seen in rats of any exposure group for the rest of the 14-day post-exposure period. No macroscopic
abnormalities were observed in rats that died during the exposure or in rats sacrificed at the end of the 14-day
observation period.
LCS0 ~ 0.33 mg/L
(2) Rats (5/sex/concentration) were exposed to 2-amino-2,3-dimethylbutanenitrile vapor at mean measured
concentrations of 63, 75 or 109 ppm (approximately 0.29, 0.34 or 0.5 mg/L, respectively) for 1 hour and observed
for 14 days. Deaths occurred at 0.5 mg/L, all during the first day of exposure. Clinical signs included hypoactivity,
ataxia, prostration and respiratory irritation on the day of exposure at concentrations > 0.34 mg/L. No clinical signs
were seen in rats at any exposure concentration for the rest of the 14-day post-exposure period. No macroscopic
abnormalities were observed in rats that died during the exposure or in rats sacrificed at the end of the 14-day
observation period.
LCS0 (1-h) ~ 0.42 mg/L
Acute Dermal Toxicity
New Zealand White rabbits (5 males/dose) were administered 2-amino-2,3-dimethylbutanenitrile dermally to shaved
skin at 12.5, 25, 50, 100 or 200 mg/kg-bw under occlusive conditions for 24 hours and observed for 14 days. All
rabbits died after exposure to > 50 mg/kg-bw and 3/5 rabbits died after exposure to 25 mg/kg-bw. Signs of toxicity
included ataxia and prostration.
LDS0 = 23 mg/kg-bw
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September 2008
The following information was submitted to EPA under TSCA 8(e):
In an eye irritation study, the instillation of 2-amino-2,3-dimethylbutanenitrile of greater than 95% purity (89 mg)
into the eyes of rabbits resulted in the deaths of five of six animals tested.
Repeated-Dose Toxicity
2-Amino-2, 3-dimethylbutanenitrile is a closed-system intermediate (CSI); therefore, repeated-dose toxicity testing
is waived for this chemical under the HPV Challenge Program. However, the sponsor has submitted a robust
summary for a 28-day repeated-dose dermal toxicity study which is summarized below.
Charles-River CD rats (5/sex/dose) were administered 2-amino-2, 3-dimethylbutanenitrile dermally to unabraded
skin at 0, 3, 10 or 30 mg/kg-bw/day (6 hours/day, 5 days/week) under occlusive conditions for 28 days. After 6
hours of daily exposure, the patch was removed and the treated area was cleansed. No clinical signs of toxicity were
seen at any dose, and body weight gain, food consumption and clinical chemistry values were comparable among all
groups. No treatment-related changes were seen in the liver, kidney, heart, brain or gonads weights. Increased
absolute and relative thyroid weights (dose-response data not provided) were observed in males and females in all
doses; however, no corroborative thyroid pathology was observed upon microscopic examination. No treatment-
related gross or microscopic lesions were observed in other organs. Skin irritation, consisting of erythema, eschar
formation, dry and/or flaky skin and small sores, was observed at the application site in rats at 10- and 30-mg/kg-
bw/day.
NOAEL = 30 mg/kg-bw/day (based on no systemic effects at the highest dose tested)
Reproductive Toxicity
Based on the closed-system intermediate (CSI) status of 2-amino-2,3-dimethylbutanenitrile, reproductive toxicity
testing is waived for this chemical under the HPV Challenge Program.
Developmental Toxicity
No data were submitted for this endpoint. Data gap.
Genetic Toxicity - Gene Mutation
In vitro
Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to 2-amino-2,3-
dimethylbutanenitrile at concentrations of 0.1, 1, 10 or 100 |ig/plate in the presence and absence of metabolic
activation. Positive and negative controls were used which responded appropriately. In the preliminary study
concentrations were tested up to 5000 |ig/plate. Cytotoxicity was observed at 1000 ng/plate and above.
2-Amino-2,3-dimethylbutanenitrile was not mutagenic in this assay.
Genetic Toxicity - Chromosomal Aberrations
No data were submitted for this endpoint. Data gap.
Conclusion: The acute oral toxicity of 2-amino-2, 3-dimethylbutanenitrile in rats is moderate. The acute inhalation
toxicity of 2-amino-2, 3-dimethylbutanenitrile in rats and acute dermal in rabbits is high. Mortality was observed
following instillation of 2-amino-2,3-dimethylbutanenitrile into the eyes of rabbits. Repeated-dose and reproductive
data were not required for the HPV Challenge Program because 2-amino-2, 3-dimethylbutanenitrile is a closed-
system intermediate. A dermal repeated-dose study in rats showed skin irritation, but there were no signs of toxicity
in any treatment group. 2-Amino-2,3-dimethylbutanenitrile did not induce gene mutations.
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
Appendix
Summary Tabic of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
2-Amino-2,3-dimcthylbutancnitrilc
(13893-53-3)
Structure
N;bN
Summary of Environmental Effects-Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
0.75
Aquatic Invertebrates
48-h ECS0 (mg/L)
6.9
Aquatic Plants
72-h ECS0 (mg/L)
(growth)
0.36 (96-h)
Summary of Human Health Data
Acute Oral Toxicity
LDS0 (mg/kg-bw)
83
Acute Inhalation Toxicity
LCS0 (mg/L)
-0.33
Acute Dermal Toxicity
LDS0 (mg/kg-bw)
23
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
N/A this chemical is a Closed System Intermediate.
Repeated-Dose Toxicity
NOAEL/LOAEL
Dermal (mg/kg-bw/day)
NOAEL = 30 (28-day)
Reproductive Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
N/A this chemical is a Closed System Intermediate.
Developmental Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
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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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
Screening Level Exposure Characterization for HPV Challenge
Chemical
Butanenitrile, 2-amino-2,3-dimethyl-
CAS # 13893-53-3
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
Butanenitrile, 2-amino-2,3-dimethyl- (CAS # 13893-53-3)
Non-CBI Executive Summary
Butanenitrile, 2-amino-2,3-dimethyl- (CAS # 13893-53-3) has an aggregated production and/or
import volume in the United States of 1 million to 10 million pounds.12 Non-confidential IUR
information for this chemical indicates that it is used as a site-limited intermediate. No
commercial/consumer uses were reported in the IUR or any other data sources. Information
submitted as part of the HPV Challenge Program indicates that butanenitrile, 2-amino-2,3-
dimethyl- is used solely as an intermediate for the production of a class of herbicides.13 A pre-
manufacture notification for this chemical was submitted to EPA and contains data and
information that are claimed confidential.
Potential Exposures to Humans and the Environment:
Based on the information considered (including IUR data and information from the HPV
Challenge Program information cited above) and in combination with the Agency's professional
judgment, EPA identifies, for the purposes of risk-based prioritization, a low relative ranking for
the potentially exposed groups (including workers, general population, consumers and children)
and the environment. The Agency has reviewed the information in the HPV submission test plan
and determined that the HPV chemical satisfies the guidance to demonstrate that the chemical is
a closed system intermediate.14 The chemical is manufactured and processed in systems that are
expected to reduce the potential for worker exposure and environmental releases that could lead
to other human and environmental exposure. The guidance for identifying this chemical
substance as a closed-system intermediate was satisfied at all sites for which this chemical was
reported.
12 USEPA, 2006. Partial Updating of TSCA Chemical Inventory.
13 USEPA, 2008. High Production Volume Information System (HPVIS). Accessed June 17,2008.
http://www.epa.gov/hpv/hpvis/index.html.
14 USEPA, 2002. EPA Comments on Chemical RTK HPV Challenge Submission. Letter dated January 30, 2002.
http://www.epa.gov/chemrtk/pubs/summaries/2amindi/cl313 lrt.pdf.
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
Non Confidential IUR Data Summary Butanenitrile, 2-amino-2,3-dimethyl-
(CAS# 13893-53-3)
Manufacturing/Import Information
Production and import volume: 1 million to 10 million pounds
List of non-CBI companies/sites:* Cytec Industries Inc./Wagganam, LA
Maximum number of potentially
exposed workers:**
Highest non-CBI maximum concentration:*
Non-CBI physical forms:*
less than 100 (including those in manufacturing,
industrial processing and use)
greater than 90% by weight
liquid
* There may be other companies/ sites, concentrations and physical forms that are claimed
confidential.
** There may be additional potentially exposed industrial workers that are not included in this
estimate since not all submitters were required to report on industrial processing and use and/or
there may be at least one use that contains a "Not Readily Obtainable" (NRO) response among
the submissions.
Table 1
Industrial Processing and Use Information
Reported in 2006 IUR
Processing Activity
Industrial Sector
Functional Use
None reported
Table 2
Commercial/Consumer Uses
Reported in 2006 IUR
Commercial/ Consumer
Highest maximum concentration
Use in Children's Products
Product Category Description
range
None reported
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