U.S. Environmental Protection Agency
Hazard Characterization Document
December, 2012
SCREENING-LEVEL HAZARD CHARACTERIZATION
2,4,4-Trimethyl-2-pentanamine
(CASRN 107-45-9)
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"
12*
(Screening Information Data Setl ' ) 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 guidance ' 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
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.
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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U.S. Environmental Protection Agency
Hazard Characterization Document
December, 2012
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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Hazard Characterization Document
December, 2012
Chemical Abstract Service
Registry Number
(CASRN)
107-45-9
Chemical Abstract Index
Name
2-Pentanamine, 2,4,4-trimethyl-
Structural Formula
CH, CH,
2 ch3 ch3 3
SMILES: NC(CC(C)(C)C)(C)C
Summary
2,4,4-Trimethyl-2-pentanamine is a liquid with high vapor pressure and high water solubility. It
is expected to have moderate mobility in soil. Volatilization of 2,4,4-trimethyl-2-pentanamine is
low since this substance predominantly exists as a cation under environmental pH. It is not
expected to hydrolyze and it is not expected to be readily biodegradable. The rate of
atmospheric photooxidation is moderate. This chemical is expected to have moderate
persistence (P2) and low bioaccumulation potential (Bl).
The acute oral toxicity of 2,4,4-trimethyl-2-pentanamine to rats is moderate and acute dermal
toxicity to rabbits is low. In a combined repeated-dose, reproductive and developmental toxicity
screening test, no effects were seen in parents resulting in a systemic toxicity NOAEL of 30
mg/kg-day. In this study, postnatal survival and lower mean body weights at post-natal day 4
were reduced in offspring at 30 mg/kg-day; the NOAEL for reproductive and developmental
toxicity is 7 mg/kg-day. The compound is corrosive to the skin and eyes of rabbits. 2,4,4-
Trimethyl-2-pentamine did not induce gene mutations in bacteria in vitro or micronuclei in mice
in vivo. Some neurotoxic signs have been observed in acute oral and dermal studies.
For 2,4,4-trimethyl-2-pentanamine, the 96-h LC50 for fish is 24.6 mg/L. There are no adequate
data for the evaluation of acute toxicity to aquatic invertebrates or toxicity to aquatic plants.
The acute toxicity to aquatic invertebrates and toxicity to aquatic plants have been identified as
data gaps under the HPV Challenge program.
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Introduction
The sponsor, Rohm and Haas Chemicals, LLC submitted a Test Plan and Robust Summaries to
EPA for 2-pentanamine, 2,4,4-trimethyl- (CASRN 107-45-9; CA name: 2-pentanamine, 2,4,4-
trimethyl-) on August 18, 2006. EPA posted the submission on the ChemRTK HPV Challenge
website on September 7, 2006
("http://www.epa.gov/chemrtk/pubs/summarii n). EPA comments on the
original submission were posted to the website on September 17, 2007. Public comments were
also received and posted to the website.
1. Chemical Identity
1.1 Identification and Purity
2,4,4-Trimethyl-2-pentanamine is a liquid at room temperature and has a purity of 97-100%.
One potential impurity (water) was identified.
1.2 Physical-Chemical Properties
The physical-chemical properties of 2,4,4-trimethyl-2-pentanamine are summarized in Table 1.
2,4,4-Trimethyl-2-pentanamine is a liquid with high vapor pressure and high water solubility.
Table la. Physical-Chemical Properties of 2,4,4-Trimethyl-2-pentanamine 1
Property
Value
CASRN
107-45-9
Molecular Weight
129.25
Physical State
Liquid
Melting Point
<-75°C (measured)
Boiling Point
130.4°C (measured)
Vapor Pressure
11.5 mm Hg at 25°C (measured)
Dissociation Constant
pKb = 3.5 (measured)
Henry's Law Constant
2.5xl0"4atm-m3/mole (estimated)2
Water Solubility
7.99x 103 mg/L at 20°C (measured)
Log Kow
1.09 (measured)
'Rohm and Haas Company. 2010. Test Plan and Robust Summary for 2,4,4-trimethyl-2-pentanamine. Available online at
http://www.epa.aov/chemrtk/pubs/summaries/2pent244/cl6328tc.htm as of June 12,2012.
2U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental Protection
Agency, Washington, DC, USA. Available online at http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of June 12,
2012.
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2. General Information on Exposure
2.1 Production Volume and Use Pattern
2,4,4-Trimethyl-2-pentanamine had a production and/or import volume in the United States
between 50 million and 100 million pounds during calendar year 2005.
Non-confidential information submitted to EPA through TSCA Inventory update reporting (IUR)
indicated that the industrial processing and uses of the chemical include other basic organic
chemical manufacturing as fuels. Commercial and consumer uses were listed as 'other.'
2.2 Environmental Exposure and Fate
The environmental fate properties are provided in Table 2. 2,4,4-Trimethyl-2-pentanamine is
expected to have moderate mobility in soil. 2,4,4-Trimethyl-2-pentanamine achieved 0%
degradation over the course of a 28-day incubation period using an activated sludge inoculum
during the closed bottle test (OECD 301D) test and is considered not readily biodegradable.
Volatilization of 2,4,4-trimethyl-2-pentanamine is low since this substance will exist primarily as
a cation under environmental conditions and cations are not expected to volatilize. It is not
expected to hydrolyze under environmental conditions. The rate of atmospheric photooxidation
is moderate. This chemical is expected to have moderate persistence (P2) and low
bioaccumulation potential (Bl).
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Hazard Characterization Document
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Table lb. Environmental Fate Characteristics of 2,4,4-Trimethyl-2-pentanamine 1
Property
Value
CASRN
107-45-9
Photodegradation Half-life
5.5 hours (estimated)2
Hydrolysis Half-life
Stable at pH 4 and 50°C;
Stable at pH 7 and 50°C;
14.7 days at pH 9 and 51.2°C
Biodegradation
0% after 28 days (not readily biodegradable)
Bioaccumulation Factor
BAF = 2.1 (estimated)2
Log Koc
2.3 (estimated)2
Fugacity
(Level III Model)2
Air (%)
Water (%)
Soil (%)
Sediment (%)
1.2
18.1
80.5
0.2
Persistence3
P2 (moderate)
Bioaccumulation3
Bl (low)
'Rohm and Haas Company. 2010. Test Plan and Robust Summary for 2,4,4-Trimethyl-2-pentanamine. Available online at
http://www.epa.gov/chemrtk/pubs/summaries/2pent244/cl6328tc.htm as of June 12,2012.
2U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental Protection
Agency, Washington, DC, USA. Available online at http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of June 12,
2012.
3Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64,
Number 213 (November 4,1999) pp. 60194-60204.
Conclusion: 2,4,4-Trimethyl-2-pentanamine is a liquid with high vapor pressure and high
water solubility. It is expected to have moderate mobility in soil. Volatilization of 2,4,4-
trimethyl-2-pentanamine is low since this substance predominantly exists as a cation under
environmental pH. It is not expected to hydrolyze and it is not expected to be readily
biodegradable. The rate of atmospheric photooxidation is moderate. This chemical is expected
to have moderate persistence (P2) and low bioaccumulation potential (Bl).
3. Human Health Hazard
A summary of health effects data for SIDS and other endpoints is provided in Table 3.
Acute Oral Toxicity
(1) Crl:CD BR rats (6/sex/dose) were administered 2,4,4-trimethyl-2-pentanamine via gavage at
50, 150, 200, 500 or 2000 mg/kg and observed for 14 days following dosing. Mortality occurred
at all doses.
LD50 = 218 mg/kg
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(2) Sprague-Dawley rats (5/sex/dose) were administered undiluted 2,4,4-trimethyl-2-
pentanamine via gavage at 100, 144, 207, 298 or 429 mg/kg and observed for 14 days following
dosing. Mortality occurred at all doses. Study details are from TSCATS (OTS0545711).
LD5o = 309 mg/kg
Acute Dermal Toxicity
New Zealand White rabbits (5/sex/dose) were administered 2,4,4-trimethyl-2-pentanamine via
the dermal route at 2000, 2450 or 3000 mg/kg for 24 hours and observed for 14 days following
dosing. Mortality occurred at all doses. Study details are from TSCATS (OTS0545711).
LD50 = 2442 mg/kg
Repeated-Dose Toxicity
Crl:CD(SD) rats (10/sex/dose) were administered 2,4,4-trimethyl-2-pentanamine at 0, 2, 4, and
30 mg/kg-day via oral gavage in corn oil. Males were dosed for 14 days prior to pairing and
throughout mating for a total of 28 days. Females received the test substance beginning 14 days
prior to mating and continued through lactation day 3 for a total of 39-47 doses. Females that
did not deliver were dosed through the day prior to sacrifice for a total of 40-47 doses. No
effects were observed at any dose, including effects of a functional observational battery
evaluation.
LOAEL = Not established
NOAEL = 30 mg/kg-day (highest dose tested)
Reproductive/Developmental Toxicity
As noted above, Crl:CD(SD) rats were administered the test substance at 0, 2, 4, and 30 mg/kg-
day via gavage 14 days prior to pairing and throughout mating for a total of 28 days (males) or
14 days prior to mating through lactation day 3 for a total of 39-47 doses (females). At 30
mg/kg-day, postnatal survival was decreased and offspring exhibited lower mean body weights
at post-natal day 4 and lower mean body weight gains compared with controls.
LOAEL (reproductive/developmental) = 30 mg/kg-day (based on decreased post-natal
survival and lower mean body weights in offspring)
NOAEL = 7 mg/kg-day
Genetic Toxicity — Gene Mutations
In vitro
Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to 2,4,4-
trimethyl-2-pentanamine at concentrations of 50, 200, 500, 2000 or 5000 |ig/plate with and
without metabolic activation. Positive and negative controls were tested concurrently and
positive control results were valid. Information on toxicity was not included. No other details
were available in the summary.
2,4,4-Trimethyl-2-pentanamine was not mutagenic in this assay.
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Genetic Toxicity - Chromosomal Aberrations
In a micronucleus test, ICR mice (5/sex/dose) were administered the test substance via oral
gavage with single doses of 0, 125, 250 or 500 mg/kg. Toxicity was observed as mortality,
lethargy, piloerection, tremors, and palpebral closure. Mice were evaluated for presence of
micronucleated polychromatic erythrocytes from bone marrow. No information was provided on
ratios of polychromatic to normochromatic erythrocytes to determine whether the test substance
reached the bone marrow.
2,4,4-Trimethyl-2-pentanamine did not induce micronuclei in this study.
Additional Information
Skin Irritation
(1) Six New Zealand white rabbits were administered 0.5 mL of undiluted 2,4,4-trimethyl-2-
pentanamine to intact skin (occluded) for 4 hours. Severe erythema and severe edema were
noted after 1 hour. Eschar formation was observed after 1 day. By 14 days, irreversible skin
damage had occurred. Study details are from TSCATS (OTS0529785-1).
2,4,4-Trimethyl-2-pentanamine was corrosive to rabbit skin in this study.
(2) New Zealand White rabbits (3/sex) were exposed to 0.5 mL of 2,4,4-trimethyl-2-
pentanamine at semi-occluded (4 hours; 72-hour observation period) and occluded sites (24
hours; 7-day observation period). Severe erythema and severe edema were noted after 30
minutes. Discoloration of the test sites and eschar formation were seen at most observation time
points. Study details are from TSCATS (OTS0545711).
2,4,4-Trimethyl-2-pentanamine was corrosive to rabbit skin in this study.
Eye Irritation
New Zealand White rabbits (3/sex) were administered 0.1 mL of 2,4,4-trimethyl-2-pentanamine
in the right eye. After 24 hours, both eyes of each rabbit were rinsed. Eyes were examined from
1 hour to 21 days after the 24 hour period. Maximum scores were observed for erythema,
edema, discharge and corneal opacity and effects were still observed at 21 days. Study details
are from TSCATS (OTS0545711).
2,4,4-Trimethyl-2-pentanamine was corrosive to rabbit eyes in this study.
Respiratory Irritation
Male OFi mice (10/dose/treatment type) were exposed (head-only) to t-octylamine vapor. Two
types of measures were taken. First, breathing frequency during exposure for 60 minutes at 23,
49, 82 or 133 ppm (0.12, .26, 0.43 or 0.70 mg/L4). This test was used as an index of upper
respiratory tract irritation. In addition, tracheal cannulation (TC) was also conducted to
determine whether the compound led to pulmonary toxicity. During this second procedure, mice
were exposed for 120 minutes to 47, 70 or 130 ppm (0.25, 0. 37, or 0.68 mg/L) and respiratory
4 Conversion: ppm*mw/24.45, where 24.45 is the liters of a mole of the vapor at 1 atmosphere and 25°C; mw = 129.25
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rate was determined 75 minutes after mice recovered from anesthesia. The doses at which
respiratory rates were decreased by 50% were recorded (Gagnaire et al., 1993).
RD50 = 80 ppm (0.42 mg/L)
RD(TC)5o = 96 ppm (0.51 mg/L)
Neurotoxicity
Rats (number, sex, and strain not indicated) were administered single oral doses of 50, 150, 200
or 500 mg/kg via gavage. Neurotoxic and other signs included ataxia, tremors, disoriented
behavior, circling, lethargy, ptosis, lacrimation, gasping, and wheezing. Effects were observed
in survivors as well as those that died during the study. Study details are from TSCATS
(OTS0530659). Similar signs were observed in the other acute oral studies. Tremors or
convulsions were also noted in the acute dermal study at 2450 and 3000 mg/kg.
Conclusion: The acute oral toxicity of 2,4,4-trimethyl-2-pentanamine to rats is moderate and
acute dermal toxicity to rabbits is low. In a combined repeated-dose, reproductive and
developmental toxicity screening test, no effects were seen in parents resulting in a systemic
toxicity NOAEL of 30 mg/kg-day. In this study, postnatal survival and lower mean body
weights at post-natal day 4 were reduced in offspring at 30 mg/kg-day; the NOAEL for
reproductive and developmental toxicity is 7 mg/kg-day. The compound is corrosive to the skin
and eyes of rabbits. 2,4,4-Trimethyl-2-pentamine did not induce gene mutations in bacteria in
vitro or micronuclei in mice in vivo. Some neurotoxic signs have been observed in acute oral
and dermal studies.
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Table 3. Summary Table of the Screening Information Data Set
under the U.S. HPV Challenge Program - Human Health Data
Endpoints
2,4,4-Trimethyl-2-pentanamine
(CASRN 107-45-9)
Acute Oral Toxicity
LD5o (mg/kg)
218
Acute Dermal Toxicity
LD50 (mg/kg)
2442
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-day)
NOAEL = 30 (highest dose tested)
Reproductive Toxicity
NOAEL/LOAEL
Oral (mg/kg-day)
NOAEL = 7
LOAEL = 30
Developmental Toxicity
Oral (mg/kg-day)
Maternal
NOAEL = 30 (highest dose tested)
Developmental
NOAEL = 7
LOAEL = 30
Genetic Toxicity - Gene Mutations
In vitro
Negative
Genetic Toxicity - Chromosomal
Aberrations
In vivo
Negative
Additional Information
Skin Irritation
Eye Irritation
Neurotoxicity
Corrosive
Corrosive
Symptoms from acute studies
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4. Hazard to the Environment
A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 4.
Acute Toxicity to Fish
Fathead minnows (Pimephalespromelas) were exposed to 2-pentanamine, 2,4,4-trimethyl-
(purity 95%) at nominal concentrations of 0 (control), 9.94, 15.3, 23.5, 36.1 or 55.6 mg/L for 96
hours under flow-through conditions. Mean measured concentrations were < 1.08 (control),
8.64, 14, 22.7, 35.5 and 56.3 mg/L. Water quality parameters measured were: temperature, DO,
total hardness, total alkalinity and pH.
96-h LC50 = 24.6 mg/L
Acute Toxicity to Aquatic Invertebrates and Toxicity to Aquatic Plants
No adequate data were available.
Conclusion: For 2,4,4-trimethyl-2-pentanamine, the 96-h LC50 for fish is 24.6 mg/L. There are
no adequate data for the evaluation of acute toxicity to aquatic invertebrates or toxicity to aquatic
plants.
Table 4. Summary of the Screening Information Data Set as Submitted
under the U.S. HPV Challenge Program- Aquatic Toxicity Data
Endpoints
SPONSORED CHEMICAL
2-Pentanamine, 2,4,4-trimethyl-
(107-45-9)
Fish
96-h LC50 (mg/L)
24.6
Aquatic Invertebrates
48-h EC50 (mg/L)
No adequate data
Aquatic Plants
72-h EC50 (mg/L)
No adequate data
Bold = experimental data (i.e. derived from testing)
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Reference
Gagnaire, F., Azim, S., Simon, P., Cossec, B., Bonnet, P. and J. De Ceaurriz. 1993. Sensory and
pulmonary irritation of aliphatic amines in mice: A structure-activity relationship study. Journal
of Applied Toxicology. 13(2): 129-135.
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