U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
Substituted Diphenylamines Category
Benzenamine, 4-(l-methyl-l-phenylethyl)-N-4[4-(l-methyl-l-phenylethyl)phenyl]-
(CASRN 10081-67-1)
Benzenamine, ar-nonyl-N-nonylphenyl (CASRN 36878-20-3)
Benzenamine, N-phenyl-, reaction products with 2,4,4-trimethylpentene (CASRN 68411-
46-1)
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
Benzenamine, 2-ethyl-N-(2-ethylphenyl)-, (tripropenyl) derivatives (CASRN 68608-77-5)
Benzenamine, N-phenyl-, reaction products with styrene and 2,4,4-trimethylpentene
(CASRN 68921-45-9)
Benzenamine, N-phenyl- reaction products with 2,4,4-trimethylpentene and isobutylene
(CASRN 184378-08-3)
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 Set1'2)
endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the
environment.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is
evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored
chemicals 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 guidance2'3 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,
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.

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U.S. Environmental Protection Agency
Hazard Characterization Document
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Merck, etc.) and Science Direct. 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.
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.
2

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Chemical Abstract Service
Registry Number
(CASRN)
10081-67-1
36878-20-3
68411-46-1
68442-68-2
68608-77-5
68921-45-9
184378-08-3
Chemical Abstract Index
Name
Benzeneamine, 4-(l-methyl-l-phenylethyl)-N-4[4-(l-methyl-l-
phenyllethyl) phenyl]-
Benzeneamine, AR-nonyl-N-(nonylphenyl)-
Benzeneamine, N-phenyl-, reaction products with
2,4,4-trimethylpentene
Benzeneamine, N-phenyl-, styrenated
Benzeneamine, 2-ethyl-N-(2-ethylphenyl)-(tripropynyl)
derivatives
N-phenyl-, reaction products with styrene and 2,4,4-
trimethylpentene
Benzeneamine, N-phenyl- with 2,4,4-trimethylpentene and
isobutene
Structural Formula
See Section 1
Summary
Substituted diphenylamines are solids and viscous liquids with negligible to low water solubility,
except for the supporting chemical, Diphenylamine(CASRN 122-39-4) which has moderate
water solubility. Substituted diphenylamines have negligible to moderate vapor pressures. They
are expected to have low mobility in soil. Volatilization of most members of substituted
diphenylamines from water and moist soil is considered low-to-moderate based on their
estimated Henry's Law constant, except for CASRN 10081-67-1, CASRN 68442-68-2 and
CASRN 68921-45-9 which are expected to volatilize slowly. The rate of hydrolysis is
considered negligible. The rate of atmospheric photooxidation is considered rapid. Persistence
of substituted diphenylamines is expected to range from low to high (PI to P3). The
bioaccumulation potential for the category members also ranges from low (Bl) to high (B3).
The acute oral toxicity of category members CASRN 68442-68-2, 184378-08-3, 101-67-7 and
68608-77-5 in rats is low, and the acute dermal toxicity of three of them (CASRN 68442-68-2,
101-67-7 and 68608-77-5) in rabbits is also low. A combined repeated-dose/ reproductive/
developmental toxicity study by the oral route in rats with category member CASRN 184378-08-
3 showed hematological and hepatic toxicity at 125 mg/kg/day in males and hepatic toxicity at
25 mg/kg/day in females; the NOAEL for systemic toxicity for male rats was 25 mg/kg/day; the
NOAEL for systemic and maternal toxicity for female rats was 5 mg/kg/day. In the same study,
there was reproductive toxicity at 125 mg/kg/day as demonstrated by shorter gestations lengths
and lower viability indices; the NOAEL for reproductive toxicity was 25 mg/kg/day. There was
evidence of developmental toxicity in this study as demonstrated by decreases in offspring
viability and body weights at 125 mg/kg/day; the NOAEL for developmental toxicity was 25
mg/kg/day. A repeated-dose toxicity study by the oral route in rats with CASRN 68921-45-9
3

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
showed decreased body weights and liver toxicity at 125 mg/kg/day, the lowest dose, the
NOAEL for systemic toxicity is not established. An oral combined repeated-dose/reproductive/
developmental toxicity screening study in rats with category member 68442-68-2 showed
increased liver and adrenal weights and toxicity of the liver and thyroid glands-at 600 mg/kg/day;
the NOAEL for systemic and maternal toxicity was 250 mg/kg-bw/day. In the same study, there
was reproductive toxicity at 600 mg/kg/day as demonstrated by higher pre-implantation losses;
the NOAEL for reproductive toxicity was 250 mg/kg/day. There was evidence of developmental
toxicity as demonstrated by diminished surface righting at 600 mg/kg-bw/day; the NOAEL for
developmental toxicity was 250 mg/kg/day. Category members did not induce gene mutations
or chromosomal abberrations when tested in vitro or in vivo. Category member CASRN 68442-
68-2 is slightly irritating to both the eyes and skin; category members CASRN 101-67-7 and
68608-77-5 are slightly irritating to the eyes. Skin irritation was not observed with category
members CASRN 68921-45-9 and 101-67-7. Category members CASRN 68921-45-9 and
184378-08-3 are not dermal sensitizers.
The measured acute toxicity values of substituted diphenylamines to fish aquatic invertebrate and
aquatic plants have no effects at the saturation limit (4.2 x 10"7 mg/L).
No data gaps were identified in the HPV Challenge Program.	
4

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
The sponsor, the American Chemistry Council, Rubber and Plastic Additives (RAPA) Panel,
submitted a Test Plan and Robust Summaries to EPA for the Substituted Diphenylamines
Category on December 18, 2001. EPA posted the submission on the ChemRTK HPV Challenge
website on January 15, 2002
(http://www.epa.gov/chemrtk/pubs/summaries/subdipha/cl3378tc.htm). EPA comments on the
original submission were posted to the website on December 3, 2002. Public comments were
also received and posted to the website. The sponsor submitted updated/revised documents on
August 25, 2003 and November 17, 2006, which were posted to the ChemRTK website on
October 24, 2003 and January 19, 2007 respectively. The substituted diphenylamines category
consists of 7 chemicals as shown in Table 1.
Category Justification
The eight members of the substituted diphenylamines category are diphenylamines with various
degrees of phenyl or alkyl substitution; some of which are complex mixtures, also called Class 2
substances. Class 2 substances are composed of several chemicals whose concentration is
variable depending on the degree of their synthesis. All substances in the category share a
common starting material, diphenylamine (benzenamine, N-phenyl-; CASRN 122-39-4) and a
common synthetic pathway. The sponsor grouped the chemicals into one category based on the
similarities in structure, physical-chemical and environmental fate properties and aquatic and
mammalian toxicities. EPA has arrayed the category chemicals roughly according to trends in
the submitted physical-chemical properties, because they are expected to correlate with toxicity.
1 Chemical Identity
1.1 Identification and Purity
The following description is taken from the final Test Plan (2003):
All of these chemicals share a common starting material; Diphenylamine (Benzenamine, N-
phenyl-, CAS# 122-39-4), a common synthetic pathway, and all compounds in this category are
diamines with various substitutions. The chemical structures of these chemicals in this category
are listed in Table 1.
5

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Table 1. Chemical structures of Substituted Dipenylamines
Chemical Name
CASRN
Structure
Benzenamine, 4-octyl-iV-
(4-octylphenyl)
101-67-7
C„H.
// \\
-NH-
// \\
-c,h17
Benzenamine, 4-(l-methyl-
1-phenylethyl)-jV-4[4-(l-
methyl-1-phenylethyl)
phenyl]-
10081-67-1
Benzenamine, ar-nonyl-
A-nonylphenyl
36878-20-3
c9h19.
w
-NH	^
¦ C9H19
Benzenamine, A'-phenyl-,
reaction products with
2,4,4-trimethylpentene
68411-46-1
CH,
CH,
/
CH,
~CHr-C— CH
2 I
CH,
ru CH,
9H3	II 2
I ^C\
3 CH —C—CH2 CH3
CH,
—NH	v
According to the Test Plan attachment occurs at
the * Carbon
Benzenamine, A'-phenyl-,
styrenated
68442-68-2


CH,
-CH
,CH
w
-NH-
//
"CH,
Benzenamine, 2-ethyl-A'-
(2-ethylphenyl)-,
(tripropenyl) derivatives
68608-77-5
c9h19

c9h19
CH, CH,
/ 2 \ '
CH,
CH,
6

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Table 1. Chemical structures of Substituted Dipenylamines
Chemical Name
CASRN
Structure
Benzenamine, A'-phenyl-,
reaction products with
styrene and 2,4,4-
trimethylpentene
68921-45-9
9 9
1 CH*
^ CHj CH-C-CH, XH,
sc* 1 CH
CH
According to the Test Plan attachment occurs at
the * Carbon
Benzenamine, A'-phenyl -
reaction products with
2,4,4-trimethylpentene and
isobutylene
184378-08-3
CH7 ru „u CH,
}l ^3 ^ 3 11
C\( ^CH2-C-CH3 CH3-C-CHf VCH3
ChL / v j \ ChL
X* 11
CH, *CH,
CH3 CH3
According to the Test Plan attachment occurs at
the * Carbon
1.2 Physical-Chemical Properties
The physical-chemical properties of the substituted diphenylamines category are summarized in
Table 2. Substituted diphenylamines are solids and viscous liquids with negligible to low water
solubility, except for the supporting chemical, diphenylamine (CASRN 122-39-4) which has
moderate water solubility. Substituted diphenylamines have negligible to moderate vapor
pressures.
7

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Tabic 2. Phvsical-chcmical Properties of Substituted Diphcnvlamincs Category1







Ben/en amine,
Bcn/cnamine,



Bcn/cnaminc,

Bcn/cnaminc,


A^-phenyl-,
/V-phcnyl-



4-(l-mcthyl-

/V-phcnyl-,

Bcn/cnaminc,
reaetion
rcaction



1-phcnvlcthvl)-

reaction

2-cthvl-
produets with
products w ith


Bcn/cnaminc,
iV-[4-(l-
Bcn/cnaminc,
products with

/V-(2-cthyl-
stvrene and
isobutvlcnc
Diphenyl-

4-octvl-
methvl-1-
ar-nonvl-
2,4,4-tri-
Bcn/cnaminc,
phcnyl)-, (tri-
2,4,4-tri-
and 2,4,4-tri-
aminc

7V-(4-octvl-
phenylethyl)
/V-(nonyl-
methvl-
/V-phcnyl-,
propenyl)
methvl-
mcthvl-
(Supporting
Property
phcnyl)-
phenvl|-
phcnvl)-
pcntcnc
stvrenated
derivs.
pentene
pentene
Chemical)
CASRN
101-67-7
10081-67-1
36878-20-3
68411-46-1
68442-68-2
68608-77-5
68921-45-9
184378-08-3
122-39-4
Molecular
393.722
406
422
298-350
320
225-479
225-633
225-393
169
Weight









Physical State
Solid2
Solid
Thick liquid
Liquid3
Liquid
Liquid
Liquid
Solid/ Viscous
liquid
Solid
Melting Point
87-95°C
98.5°C
<0°C
<20°C
~6°C
<0°C
<0°C
10°C
52.5-55.5°C

(measured)2
(measured)
(estimated)
(estimated;)3
(measured)
(estimated)
(estimated)
(measured
pour point
(measured)4
Boiling Point
200°C at 0.5
507°C
258°C at 375
362°C
>300°C
221°C
>198°C
Decomposes at
~159°C at 91.5

mmHg
(measured)2
extrapolated to
419°C at 760
mmHg6
(estimated)5
mmHg
(measured)
extrapolated to
285°C at 760
mmHg6;
Decomposes
around 260°C
at 760 mm Hg
(estimated for
lowest weight
material)2
(estimated);
393 °C
(estimated for
lowest weight
material)5
(measured);
520°C
(estimated for
lowest weight
material)5
(measured);
175°C
(measured);
275°C; 302 to
>360
(estimated)
mmHg4;
~261°C at 300
mmHg4;
302°C at 760
mmHg
(measured)4
Vapor Pressure
2.3 xlO"7 mm
3 5x1Q-9mm
0.003 mmHg
2xl0"5 mmHg
1.25xl0-5
1.8xl0"8-
7.5 xlO"7-
7 1 xlQ"7 mm
1.61xl0"4 mm

Hg at 25°C
(estimated
from reduced
Hg (estimate)5
at 25 °C
(estimated
from reduced
at 25°C2;
8.6 xlO-5-
3.8xl0"8mm
(estimated)5
6 9x10 12mm
Hg at 25°C
(estimated)2
1 4x1Q-15mm
Hg (estimated)
Hg at 25°C
(measured);
8.56xl0-5-
Hg at 20°C4
(measured);
0.98 mmHg at

boiling point)6

boiling point)6
Hg
(estimated)2



3.79xl0"8 mm
Hg (estimated)
108°C4
Dissociation
1.97
1.32
0.95-1.61
1.25-1.43
1.32
1.28
0.48-0.77
1.25-1.43
0.78
Constant (pKa)
(estimated)7
(estimated)7
(estimated for
mono- and di-
substitutions)7
(estimated)7
(estimated)7
(estimated)7
(estimated)7
(estimated)7
(measured)8

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Hazard Characterization Document
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Tabic 2. Phvsical-chcmical Properties of Substituted Diphcnvlamincs Category1







Ben/en amine,
Ben/en amine,



Bcn/cnaminc,

Bcn/cnaminc,


A^-phenyl-,
/V-phcnyl-



4-(l-mcthyl-

/V-phcnyl-,

Ben/en amine,
reaction
rcaction



1-phcnvlcthvl)-

reaction

2-cthvl-
products with
products with


Bcn/cnaminc,
7V-[4-(l-
Bcn/cnaminc,
products with

A^-(2-cthyl-
stvrcnc and
isobutvlcne
Diphenyl-

4-octvl-
methvl-1-
ar-nonvl-
2,4,4-tri-
Ben/en amine,
phcnyl)-, (tri-
2,4,4-tri-
and 2,4,4-tri-
amine

7V-(4-octvl-
phenylethyl)
/V-(nonyl-
mcthvl-
/V-phcnyl-,
propcnyl)
mcthvl-
mcthvl-
(Supporting
Property
phcnyl)-
phcnyl|-
phcnyl)-
pcntcnc
stvrcnated
dcrivs.
pentcnc
pentcnc
Chemical)
CASRN
101-67-7
10081-67-1
36878-20-3
68411-46-1
68442-68-2
68608-77-5
68921-45-9
184378-08-3
122-39-4
Henry's Law
6.676><10"5
2.6><10"8atm-
1.12xl0-5-
8.42 xlO"6 atm-
1.47xl0-8-
2.4 x 10-5-
5.54xlO-10-
5.23 xlO"5-
2.82 xlO"6 atm-
Constant
atm-m3/mole
m3/mole
1.2xl0"4 atm-
m3/mole
1.24xl0"7 atm-
2.56 xlO"4 atm-
2.41xl0"8atm-
7.4 xlO"6 atm-
m3/mole

(estimated)2
(estimated)5
m3/mole
(estimated for
mono- and di-
substitutions)5
(estimated)5
m3/mole
(estimated for
mono- and di-
styryl
components)5
m3/mole
(estimated for
mono- and di-
substitutions)5
m3/mole
(estimated for
mono- and di-
substitutions)5
m3/mole
(estimated for
mono- and di-
substitutions)5
(estimated)5
Water
Solubility
4.215><10"7
mg/L
(estimated)2
1.5xl0-4
(estimate)5
1.7xl0"7 mg/L
(estimate)5
0.015 mg/L
(estimated for
lowest weight
material)5
0.41 mg/L at
20°C
(measured);
20.6 ng/L
(measured for
p-SDPA);
<58.8 (ig/L
(measured for
p,p'-diSDPA);
<27.6 ng/L
(measured for
o,p,p'-
triSDPA)
2.3 xlO"5 to
5.8xlO"10 mg/L
(estimated)
(insoluble)
Negligible;
0.39 to 1.9x0"
11 mg/L at
25°C
(estimated)
0.0909-
5.93 xlO"5 mg/L
at 20°C
(measured);
1.167-
1.939xl0"6
mg/L
(estimated)
40 mg/L at
25°C4
(measured);
~50 mg /L at
25°C4
Log Kow
11.26
8.51
12.24
>6
4.64 at 22°C
9.84
5.2
3.13 to >6.2
3.5

(estimated)2
(estimated)5
(estimated)5
(measured)2;
7.05
(estimated,
lowest weight
material)5
(measured)
(estimated)
(measured);
5.45-15.13
(estimated)
(measured);
5.2-10.82
(estimated)
(measured)4;
3.6
(estimated)4
9

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U.S. Environmental Protection Agency
Hazard Characterization Document
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Tabic 2. Phvsical-chcmical Properties of Substituted Diphcnvlamincs Category1
Property
Benzenamine,
4-octyl-
7V-(4-octvl-
phcnyl)-
Benzenamine,
4-(l-mcthyl-
1-phcnvlcthvl)-
7V-[4-(l-
methyl-1-
phenylcthyl)
phcnyl|-
Benzenamine,
ar-nonyl-
/V-(nonyl-
phenyl)-
Benzenamine,
/V-phenyl-,
reaetion
products with
2,4,4-tri-
mcthyl-
pentene
Benzenamine,
/V-phcnyl-,
stvrenated
Benzenamine,
2-ethvl-
/V-(2-cthvl-
phenyl)-, (tri-
propenyl)
derivs.
Benzenamine,
/V-phenyl-,
reaetion
products with
stvrene and
2,4,4-tri-
methyl-
pentcnc
Benzenamine,
/V-phenyl-
reaetion
products with
isobutylene
and 2,4,4-tri-
methyl-
pentene
Diphenyl-
amine
(Supporting
Chemical)
CASRN
101-67-7
10081-67-1
36878-20-3
68411-46-1
68442-68-2
68608-77-5
68921-45-9
184378-08-3
122-39-4
'The Rubber and Plastic Additive Panel. December 21, 2006. Revised Robust Summary and Test Plan for Substituted Diphenylamine Category.
http://www.epa.gov/chemrtk/pubs/summaries/subdipha/cl3378tc.htm.
2The Rubber and Plastic Additive Panel. August 2003. Revised Robust Summary for Substituted Diphenylamine Category.
http://www.epa. gov/hpv/pubs/summaries/subdipha/c 13378rr.pdf.
3The sponsor indicated that major components of the reaction melt at 44-107°C. However, the sponsor reported that it is a liquid at standard conditions.
4The Rubber and Plastic Additive Panel. December 2001. Robust Summary and Test Plan for Substituted Diphenylamine Category.
http: //www. epa. gov/hpv/pub s/summaries/subdipha/c 13 3 78tc. htm.
5	U.S. 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.
6	NOM05, 1987. Programs to Enhance PC-GEMS Estimates of Physical Properties for Organic Compounds. The Mitre Corp.
7SPARC. 2008. Online pKa and Property Calculator v. 4.2.1405-s4.2.1408. Accessed September 7, 2008.
http://ibmlc2.chem.uga.edu/sparc/index.cfm?CFID=32727&CFTOKEN=65477992.
8SRC. The Physical Properties Database (PHYSPROP). Syracuse, NY: Syracuse Research Corporation. Available from
http://www.svrres.com/esc/phvsprop.htm as of September 25, 2008.
*In some instances it could not be determined whether a value was estimated or measured. The original Test Plan included Benzenamine, 4-(l,l,3,3-tetra-
methylbutyl)-7V-[4-(l,l,3,3-tetramethylbutyl)phenyl]- (CASRN 15721-78-5); however, this compound was removed in the subsequent revisions and is no longer
sponsored by the Rubber and Plastic Additive Panel.
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2 General Information on Exposure
2.1 Production Volume and Use Pattern
This category has an aggregated production and/or import volume in the United States of 22
million to 112.5 million pounds. This aggregated production volume does not include CASRNs
10081-67-1 and 184378-08-3 which did not have IUR reports. The volumes for the category
members were:
Non-confidential IUR information indicates that the industrial processing and uses of these
chemicals include stabilizers, lubricants and reactants. Non-confidential information in the IUR
indicates that the commercial and consumer products containing the chemicals include
lubricants, greases and fuel additives. The HPV submission for this category states that these
chemicals are used as antidegradants in rubber, foamed polymers and high-temperature fluids, such
as lubricants, gear oils, and hydraulic fluids. The HSDB information for CASRN 101-67-7 states
that the chemical is used as an antioxidant for rubbers, plastics, and petroleum-based & synthetic
lubricants.
2.2 Environmental Exposure and Fate
No quantitative information is available on releases of these chemicals to the environment.
Based on EPA experience with the new chemicals program, there is generally a low potential for
environmental releases to water for lubricants, greases and fuel.
The environmental fate properties of the category chemicals are provided in Table 3. Substituted
diphenylamines are expected to have low mobility in soil. Volatilization of most members of
substituted diphenylamines from water and moist soil is considered moderate based on their
estimated Henry's Law constant, except for CASRNs 10081-67-1 and 68442-68-2 which are
expected to volatilize slowly. The rate of hydrolysis is considered negligible. The rate of
atmospheric photooxidation is considered rapid. Persistence of substituted diphenylamines is
expected to range from low to high (PI to P3). The bioaccumulation potential for the category
members also ranges from low (Bl) to high (B3).
CASRN 101-67-7
CASRN 68442-68-2
CASRN 68608-77-5
CASRN 68921-45-9
CASRN 36878-20-3
CASRN 68411-46-1
CASRN 184378-08-3
CASRN 10081-67-1
<500,000 pounds
500,000 to 1 million pounds
500,000 to 1 million pounds
1 million to 10 million pounds
10 million to 50 million pounds
10 million to 50 million pounds
No 2006 IUR data
No 2006 IUR data

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Table 3. Environmental Fate Characteristics of Substituted Diphenylamines Category
CASRN
10081-67-1
68411-46-1
68442-68-2
68608-77-5
68921-45-9
184378-08-3
Persistence
P2
(moderate)
P2-3
(moderate-
high)
P2 (moderate)
P2-3
(moderate-
high)
P2-3
(moderate-
high)
P2-3
(moderate-
high)
Bioaccumulation
B1 (low)
B1-B3
(low-high)
B2-B3
(moderate-
high)
B1 (low)
B2-B3
(moderate-
high)
B1-B3 (low-
high)
12

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3. Human Health Effects
A summary of health effects data submitted for SIDS endpoints is provided in Table 4. The table
also indicates where data for tested category members are read-across (RA) to untested members
of the category.
Acute Oral Toxicity
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN101-67-7)
Male and female Sprague-Dawley rats (5/dose) were administered benzenamine, 4-octyl-N-(4-
octylphenyl) as a 20.0% suspension in corn oil at 6310 or 7940 mg/kg-bw. No animals died
during the 14 days observation period.
LD50> 7940 mg/kg-bw
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
(1)	Rats (5/dose, strain not specified) were administered benzenamine, N-phenyl-, styrenated as a
25% solution in corn oil via gavage at doses of 2500, 5000, 10,000, 20,000 and 40,000 mg/kg-
bw and were observed for 14 days. At each of the two highest doses, two animals died.
LD50 > 20,000 mg/kg-bw
(2)	Rats (5/sex/dose, strain not specified) were administered benzenamine, N-phenyl-, styrenated
dispersed in corn oil via gavage at 500 mg/kg-bw. No animals died during the 14 days
observation period.
LD50 > 500 mg/kg-bw
Benzenamine, 2-ethyl-N-(2-ethylphenyl)~, (tripropenyl) derivatives (CASRN 68608-77-5)
Rats (2/dose, strain not specified) were administered benzenamine, 2-ethyl-N-(2-ethylphenyl)-,
(tripropenyl) derivatives via gavage at 10,250, 15,380, 23,070 and 34,600 mg/kg-bw and were
observed for 14 days. No deaths were reported at any dose.
LD50 > 34,600 mg/kg-bw
Benzenamine, N-phenyl- reaction product with 2,4,4-trimethylpentene and isobutylene
(CASRN 1843 78-08-3)
A group of three female Sprague-Dawley rats were administered a solution of benzenamine, N-
phenyl- reaction product with 2,4,4-trimethylpentene and isobutylene in arachis oil via gavage as
a single dose of 2000 mg/kg-bw and observed for 14 days. No deaths were observed.
LD50 > 2000 mg/kg-bw
Acute Dermal Toxicity
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN 101-67-7)
New Zealand white rabbits (2 males and 1 female) were administered benzenamine, 4-octyl-N-
(4-octylphenyl) dermally as a single application of 40.0% suspension in corn oil at 5010 or 7940
mg/kg-bw to the shaved skin under occlusive conditions for 24 hours. All animals survived
until sacrifice on day 14.
LD50 > 7940 mg/kg-bw
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September, 2009
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
Rabbits (5/dose, strain not specified) were administered benzenamine, N-phenyl-, styrenated
dermally at 10,000 mg/kg-bw. No mortality was reported.
LD50 > 10,000 mg/kg-bw
Benzenamine, 2-ethyl-N-(2-ethylphenyl)~, (tripropenyl) derivatives (CASRN 68608-77-5)
A group of four New Zealand rabbits (sex not specified) were administered benzenamine, 2-
ethyl-N-(2-ethylphenyl)-, (tripropenyl) derivatives at 3000 mg/kg-bw dermally to a shaved area
on the backs under occlusive conditions for 4 hours and observed for 14 days. No mortality was
observed.
LD50 > 3000 mg/kg-bw
Repeated-Dose Toxicity
Benzenamine, N-phenyl- reaction products with 2,4,4-trimethylpentene and isobutylene
(CASRN 1843 78-08-3)
In a combined repeated-dose/reproductive/developmental toxicity screening test, Sprague-
Dawley (10/sex/dose) were administered benzenamine, N-phenyl-, reaction products with 2,4,4-
trimethylpentene and isobutylene via gavage at 0, 5, 25 and 125 mg/kg-bw/day for 43 (males)
and 54 (females) days. Pairing of animal within each dose group was undertaken on a one male
to one female basis on Day 15 of the study. Males were terminated on Day 43 and all females
were terminated on Day 5 post partum (with exposures before and after mating, during gestation
and lactation for 4 days). No deaths or treatment-related behavioral changes, functional
performance or sensory reactivity were noted at any dose. At 125 mg/kg-bw/day, there was
decreased food intake and body weight gain in females during lactation. Hematological
evaluation indicated increased levels of activated partial thromboplastin time at 125 mg/kg-
bw/day in both sexes. There was a decreased platelet count in both sexes prior to mating. At
125 mg/kg-bw/day, males had elevated absolute and relative liver weights and females had
reduced spleen weights. Females at 25 and 125mg/kg-bw/day and males at 125 mg/kg-bw/day
had decreased total plasma protein, albumin and the albumin/ globulin ratio and elevated
aspartate aminotransferase and alkaline phosphatase activities. Consistent with these
biochemical and enzymic effects (indicative of liver toxicity), histopathological evaluation
revealed centrilobular hepatocytes enlargement in females at > 25 mg/kg-bw/day and in males at
125 mg/kg-bw/day.
LOAEL (females) = 25 mg/kg-bw/day (based on liver toxicity)
NOAEL (females) = 5 mg/kg-bw/day
LOAEL (males) = 125 mg/kg-bw/day (based on changes in hematological parameters and liver
toxicity)
NOAEL (males) = 25 mg/kg-bw/day
Benzenamine, N-phenyl-, reaction products with styrene and 2,4,4-trimethylpentene (CASRN
68921-45-9)
Carworth rats (25/sex/dose) were administered benzenamine, N-phenyl-, reaction products with
styrene and 2,4,4-trimethylpentene in the diet at 2500, 5000 and 10,000 ppm (~ 125, 250 and 500
mg/kg-bw/day, respectively) for 64 weeks. Growth retardation (decrease in body weight) was
14

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U.S. Environmental Protection Agency
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September, 2009
observed in all treated females. Hepatomegaly was observed in both sexes at all doses. Diffuse
hepatic degeneration was observed in all test animals. The degenerative changes in the liver were
described as diffuse cloudy swellings and fatty metamorphosis of the cytoplasm of the
hepatocytes.
LOAEL ~ 125 mg/kg-bw/day (based on growth retardation/decrease in body weight in females
and liver toxicity in both sexes)
NOAEL = Not established
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
In a combined repeated-dose/reproductive/developmental toxicity screening test, Sprague-
Dawley rats (10/sex/dose) were administered benzenamine, N-phenyl-, styrenated suspension in
corn oil, via gavage at 0, 50, 250 and 600 mg/kg-bw/day for 43 (males) and 54 (females) days.
Pairing of animal within each dose group was undertaken on a one male to one female basis on
Day 15 of the study. Males were terminated on Day 43 and all females were terminated on Day
5 post partum (with exposures before and after mating, during gestation and lactation for 4 days).
No deaths or treatment-related changes in body weight, growth, food and water intake or
behavioral assessments were seen in any treatment groups. However, absolute and relative liver
and adrenal weights were increased in both sexes at the 600 mg/kg-bw/day. Reduced cholesterol
levels were reported in males at 250 and 600 mg/kg-bw/day, and an increased activity for
alkaline phosphatase was noted in males at 600 mg/kg-bw/day; both of these effects are
indicative of liver toxicity. Histopathological examination of the liver revealed centrilobular
hepatocyte enlargement in all treated females and in males treated with 250 and 600 mg/kg-
bw/day. In males, follicular cell hypertrophy in the thyroid glands was also observed at 600
mg/kg-bw/day.
LOAEL = 600 mg/kg-bw/day (based on increased liver and adrenal weights and toxicity in
liver and thyroid glands)
NOAEL = 250 mg/kg-bw/day
Reproductive Toxicity
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
In the combined repeated-dose/reproductive/developmental toxicity screening study described
previously, no adverse effects on mating performance, fertility or gestation were observed.
Females treated with 600 mg/kg-bw/day had a higher percentage of pre-implantation losses
compared to controls, resulting in less offspring/litter when compared to controls and lower total
litter weights.
LOAEL (reproductive toxicity) = 600 mg/kg-bw/day (based on higher pre-implantation
losses)
NOAEL (reproductive toxicity) = 250 mg/kg-bw/day
Benzenamine, N-phenyl- reaction product with 2,4,4-trimethylpentene and isobutylene
(CASRN 1843 78-08-3)
In the combined repeated-dose/reproductive/developmental toxicity screening study described
previously, shorter gestation length, lower viability indices and lower total litter weights were
seen at 125 mg/kg-be/day.
15

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U.S. Environmental Protection Agency	September, 2009
Hazard Characterization Document
LOAEL (reproductive toxicity) = 125 mg/kg-bw/day (based on shorter gestation lengths and
lower viability indices)
NOAEL (reproductive toxicity) = 25 mg/kg-bw/day
Developmental Toxicity
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
In the combined repeated-dose/reproductive/developmental toxicity screening study described
previously, no clinical signs of toxicity were observed in the offspring. The mean offspring
weights of treated animals were comparable to controls. Offspring from the 600 mg/kg-bw/day
treated animals showed less successful completion of surface righting assessments. No
treatment-related macroscopic abnormalities were observed at necropsy.
LOAEL (maternal toxicity) = 600 mg/kg-bw/day (based on increased liver and adrenal
weights and toxicity in liver and thyroid glands)
NOAEL (maternal toxicity) = 250 mg/kg-bw/day
LOAEL (developmental toxicity) = 600 mg/kg-bw/day (based on diminished surface righting
assessments)
NOAEL (developmental toxicity) = 250 mg/kg-bw/day
Benzenamine, N-phenyl- reaction product with 2,4,4-trimethylpentene and isobutylene
(CASRN 1843 78-08-3)
In the combined repeated-dose/reproductive/developmental toxicity screening study described
previously, the number of interim deaths of offsprings at 125 mg/kg-bw/day was higher than that
observed for controls. At the same dose, the mean offspring body weights were also lower. No
other treatment-related effects were observed on offspring development.
LOAEL (maternal toxicity) = 25 mg/kg-bw/day (based on liver toxicity)
NOAEL (maternal toxicity) = 5 mg/kg-bw/day
LOAEL (developmental toxicity) = 125 mg/kg-bw/day (based on decrease in offspring
viability indices and offspring body weight)
NOAEL (developmental toxicity) = 25 mg/kg-bw/day
Genetic Toxicity — Gene Mutation
In vitro
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN 101-67-7)
(1)	Salmonella typhimurium strains were exposed to benzenamine, 4-octyl-N-(4-octylphenyl) at
concentrations up to 500 |j,g/plate with and without metabolic activation. Positive and negative
controls were used; however, their responses were not provided.
Benzenamine, 4-octyl-N-(4-octylphenyl) was not mutagenic in this assay.
(2)	Saccharomyces cerevisiae, D4, were exposed to benzenamine, 4-octyl-N-(4-octylphenyl) at
concentrations up to 500 |j,g/plate with and without metabolic activation. Positive and negative
controls were used; however, their responses were not provided..
Benzenamine, 4-octyl-N-(4-octylphenyl) was not mutagenic in this assay.
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
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S. typhimurium and Escherichia coli strains were exposed to benzenamine, N-phenyl-, styrenated
at concentrations up to 5000 |j,g/plate with and without metabolic activation. The vehicle and
positive controls responded appropriately.
Benzenamine, N-phenyl-, styrenated was not mutagenic in this assay.
Benzenamine, 2-ethyl-N-(2-ethylphenyl)~, (tripropenyl) derivatives (CASRN 68608-77-5)
S. typhimurium and E. coli strains were exposed to benzenamine, 2-ethyl-N-(2-ethylphenyl)-,
(tripropenyl) derivatives in two separate assays at concentrations up to 5000 |j,g/plate with and
without metabolic activation. The positive controls responded appropriately.
Benzenamine, 2-ethyl-N-(2-ethylphenyl)-, (tripropenyl) derivatives was not mutagenic in
these assays.
Benzenamine, N-phenyl-, reaction products with styrene and 2,4,4-trimethylpentene (CASRN
68921-45-9)
S. typhimurium and E. coli were exposed to benzenamine, N-phenyl-, reaction products with
styrene and 2,4,4-trimethylpentene at concentrations up to 5000 |j,g/plate with and without
metabolic activation. The vehicle and positive controls responded appropriately.
Benzenamine, N-phenyl-, reaction products with styrene and 2,4,4-trimethylpentene was
not mutagenic in this assay.
Benzenamine, N-phenyl- reaction product with 2,4,4-trimethylpentene and isobutylene
(CASRN 1843 78-08-3)
S. typhimurium strains were exposed to benzenamine, N-phenyl-, reaction products with
2,4,4-trimethylpentene and isobutylene at concentrations up to 5000 |j,g/plate with and without
metabolic activation. The vehicle and positive controls responded appropriately.
Benzenamine, N-phenyl-, reaction products with 2,4,4-trimethylpentene and isobutylene
was not mutagenic in this assay.
Genetic Toxicity — Chromosomal Aberrations
In vitro
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN 101-67-7)
Chinese hamster ovary (CHO) and lung (CHL) cells were exposed to benzenamine, 4-octyl-N-
(4-octylphenyl) at concentrations up to 4.45 mg/mL and 0.5 mg/mL, respectively, with and
without metabolic activation. The controls responded appropriately.
Benzenamine, 4-octyl-N-(4-octylphenyl) did not induce chromosomal aberrations in this
assay.
In vivo
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
CD-I mice (5 males/dose) were administered single doses of benzenamine, N-phenyl-,
styrenated in corn oil, via gavage at 0, 500, 1000 and 2000 mg/kg-bw/day. Bone marrow cells
were harvested 24 and 48 hours after dosing. Slides were prepared from the bone marrow
extracts and 2000 micronucleated polychromatic erythrocytes were evaluated for the presence of
micronuclei. The ratio of polychromatic erythrocytes (PCE) to nonchromatic erythrocytes
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September, 2009
(NCE) cells was determined. Low PCE:NCE ratios indicated that benzenamine, N-phenyl-,
styrenated was cytotoxic to bone marrow.
Benzenamine, N-phenyl-, styrenated did not induce chromosomal aberrations in this assay.
Genetic Toxicity — Other
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN101-67-7)
In a sister chromatid exchange assay, CHO cells were exposed to benzenamine, 4-octyl-N-(4-
octylphenyl) at concentrations up to 5 mg/L with and without metabolic activation. The controls
responded appropriately.
Benzenamine, 4-octyl-N-(4-octylphenyl) did not induce sister chromatid exchange in this
assay.
Benzenamine, N-phenyl-, styrenated (CASRN. 68442-68-2)
In an in vitro DNA damage and repair assay, E. coli strains W3110 and p3478 were exposed to
benzenamine, N-phenyl-, styrenated up to 5000 |j,g/L with and without metabolic activation.
Negative and positive controls were used.
Benzenamine, N-phenyl-, styrenated did not damage cellular DNA in this assay.
Additional Information
Eye Irritation
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN 101-67-7)
New Zealand White rabbits (6/dose) were instilled in one eye with 100 mg of benzenamine, 4-
octyl-N-(4-octylphenyl) as a finely ground powder moistened with water. The other eye was not
treated and served as the control. Slight discomfort was noted immediately following
instillation. At 10 minutes, slight erythema and slight discharge were noted. At 24 hours, there
was slight erythema and moderate discharge in all test animals. At 48 hours, two of the six had
slight erythema and slight discharge. All signs of irritation had subsided by the third day post-
exposure.
Benzenamine, 4-octyl-N-(4-octylphenyl) was slightly irritating to rabbit eyes in this study.
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
Albino rabbits (6, sex not stated) were instilled into in one eye with benzenamine, N-phenyl-,
styrenated; the other eye was not treated and served as the control. Three rabbits had the test
substance rinsed out of the eye with water and three rabbits did not. Mild eye irritation was
noted in the eyes that were not rinsed.
Benzenamine, N-phenyl-, styrenated was slightly irritating to rabbit eyes in this study.
Benzenamine, 2-ethyl-N-(2-ethylphenyl)~, (tripropenyl) derivatives (CASRN 68608-77-5)
Benzenamine, 2-ethyl-N-(2-ethylphenyl)-, (tripropenyl) derivatives was slightly irritating to the
eye when tested in New Zealand white rabbits. Additional information was not provided.
Benzenamine, 2-ethyl-N-(2-ethylphenyl)-, (tripropenyl) derivatives was slightly irritating to
rabbit eyes in this study.
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Skin Irritation
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN101-67-7)
New Zealand White rabbits (6/dose) were applied 0.5 g benzenamine, 4-octyl-N-(4-octylphenyl)
as a finely ground powder moistened with water to the shaved dorsal area under occlusive
conditions for 24 hours. Dermal irritation was scored by the Draize method and results were
recorded 24, 48, 72 and 168 hours after application. No irritation was noted.
Benzenamine, 4-octyl-N-(4-octylphenyl) was not irritating to rabbit skin in this study.
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
Benzenamine, N-phenyl-, styrenated was considered a mild irritant to rabbit skin according to
current classifications (it was originally classified as non-irritating). Study details were not
provided.
Benzenamine, N-phenyl-, styrenated was slightly irritating to rabbit skin in this study.
Skin Sensitization
Benzenamine, N-phenyl- reaction product with 2,4,4-trimethylpentene and isobutylene
(CASRN 1843 78-08-3)
In a guinea pig maximization test, Dunkin Hartley guinea pigs (10/dose) were administered
benzenamine, N-phenyl- reaction product with 2,4,4-trimethylpentene and isobutylene as a 25%
solution in either arachis oil BP or 25% in arachis oil BP in a 1:1 preparation of Freund's
Complete Adjuvant in water via intradermal injection during the induction phase. .The
application sites were evaluated at 24 and 48 hours. After 7 days, induction was initiated by
applying undiluted test substance was applied to the same area as the previous injections on the
clipped shoulder region and covered by an occlusive patch. On day 21, topical challenge
proceeded with application of an undiluted test substance and a 75% solution (in arachis oil BP)
to a clipped area and covered with an occlusive patch for 24 hours. No sensitization was
observed.
Benzenamine, N-phenyl-, reaction products with styrene and 2,4,4-trimethylpentene was
not sensitizing in this test.
Benzenamine, N-phenyl-, reaction products with styrene and 2,4,4-trimethylpentene (CASRN
68921-45-9)
In a patch test, volunteers (25/sex) were treated with benzenamine, N-phenyl- reaction product
with 2,4,4-trimethylpentene on the identical spots on the back for 24 hours every other day for 15
applications. Two weeks after the induction period, the sites were challenged with test material
for 24 hours. A minimal transitory reaction was noted in three males and four females. No
depigmentation was noted.
Benzenamine, N-phenyl-, reaction products with styrene and 2,4,4-trimethylpentene was
not considered to be a primary irritant, fatiguing agent or sensitizer in this test.
Conclusion: The acute oral toxicity of category members CASRN 68442-68-2, 184378-08-3,
101-67-7 and 68608-77-5 in rats is low, and the acute dermal toxicity of three of them (CASRN
68442-68-2, 101-67-7 and 68608-77-5) in rabbits is also low. A combined repeated-dose/
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reproductive/ developmental toxicity study by the oral route in rats with category member
CASRN 184378-08-3 showed hematological and hepatic toxicity at 125 mg/kg/day in males and
hepatic toxicity at 25 mg/kg/day in females; the NOAEL for systemic toxicity for male rats was
25 mg/kg/day; the NOAEL for systemic and maternal toxicity for female rats was 5 mg/kg/day.
In the same study, there was reproductive toxicity at 125 mg/kg/day as demonstrated by shorter
gestations lengths and lower viability indices; the NOAEL for reproductive toxicity was 25
mg/kg/day. There was evidence of developmental toxicity in this study as demonstrated by
decreases in offspring viability and body weights at 125 mg/kg/day; the NOAEL for
developmental toxicity was 25 mg/kg/day. A repeated-dose toxicity study by the oral route in
rats with CASRN 68921-45-9 showed decreased body weights and liver toxicity at 125
mg/kg/day, the lowest dose, the NOAEL for systemic toxicity is not established. An oral
combined repeated-dose/reproductive/ developmental toxicity screening study in rats with
category member 68442-68-2 showed increased liver and adrenal weights and toxicity of the
liver and thyroid glands-at 600 mg/kg/day; the NOAEL for systemic and maternal toxicity was
250 mg/kg-bw/day. In the same study, there was reproductive toxicity at 600 mg/kg/day as
demonstrated by higher pre-implantation losses; the NOAEL for reproductive toxicity was 250
mg/kg/day. There was evidence of developmental toxicity as demonstrated by diminished
surface righting at 600 mg/kg-bw/day; the NOAEL for developmental toxicity was 250
mg/kg/day. Category members did not induce gene mutations or chromosomal abberrations
when tested in vitro or in vivo. Category member CASRN 68442-68-2 is slightly irritating to
both the eyes and skin; category members CASRN 101-67-7 and 68608-77-5 are slightly
irritating to the eyes. Skin irritation was not observed with category members CASRN 68921-
45-9 and 101-67-7. Category members CASRN 68921-45-9 and 184378-08-3 are not dermal
sensitizers.
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Table 4. Sum in ;ir\ of lliiiiiiin Health !>;¦(;¦
I.ndpoinls
licn/cnamine.
Vpheinl-.
sl\renaled
(6X442-6X-2)
licn/cnamine.
Vpheinl-.
read ion
products w illi
s(\rcnc and
2.4.4-1 riniol h\ 1-
penlcnc
(6X921-45-9)
licn/cnamine.
Vpheinl-.
rcaclion
products w illi
2.4.4-1 rimet In 1-
pcnlcne
(6S411-46-1)
licn/cnamine.
Vpheinl-
rcaclion
product with
2.4.4-1 rimclln 1-
pcnlcnc and
isobul.t Icnc
(1 X43"7X-OX-3)
licn/cnamine.
4-( l-mellnl-l-
pheinlcllnh-V
4|4-( l-mellnl-l-
pheinlellnh
pheinl|-
(IOOXI-6"7-!)
licn/cnamine.
4-ocl\ l-N-i 4-
ocl.tlpheinh
(KU-C."7-"7)
licn/cnamine.
ar-noin 1-
N-noinlpheinl
(3(iS"7S-20-3)
licn/cnamine.
2-e(h\l-V<2-
ellnlpheinh-.
(Iripropeinh
deri\ali\es
t(»X(»0K-""-5)
Acute Oral Toxicity
LDS0 (mg/kg-bw)
> 20,000
No Data
>2000
(RA)
No Data
>2000
(RA)
>2000
No Data
>2000
(RA)
>7940
No Data
>2000
(RA)
> 34,600
Acute Dermal
Toxicity
LDS0 (mg/kg-bw)
> 10,000
No Data
>3000
(RA)
No Data
>3000
(RA)
No Data
>3000
(RA)
No Data
>3000
(RA)
>7940
No Data
>3000
(RA)
>3000
Repeated-Dose
Toxicity
NOAEL/LOAEL
(mg/kg-bw/day)
NOAEL = 250
LOAEL = 600
NOAEL = Not
established
LOAEL ~ 125
No Data
NOAEL(f) = 5
LOAEL(f) = 25
NOAEL(m) = 25
LOAEL(m) =
125 (RA)
NOAEL(f) = 5
LOAEL(f) = 25
NOAEL(m) =
25
LOAEL(m) =
125
No Data
NOAEL(f) = 5
LOAEL(f) = 25
NOAEL(m) = 25
LOAEL(m) =
125 (RA)
No Data
NOAEL(f) = 5
LOAEL(f) = 25
NOAEL(m) = 25
LOAEL(m) =
125 (RA)
No Data
NOAEL(f) = 5
LOAEL(f) = 25
NOAEL(m) = 25
LOAEL(m) =
125 (RA)
No Data
NOAEL(f) = 5
LOAEL(f) = 25
NOAEL(m) = 25
LOAEL(m) =
125 (RA)
Reproductive Toxicity
NOAEL/LOAEL
(mg/kg-bw/day)
NOAEL = 250
LOAEL = 600
No Data
NOAEL = 25
LOAEL = 125
(RA)
No Data
NOAEL = 25
LOAEL = 125
(RA)
NOAEL = 25
LOAEL = 125
No Data
NOAEL = 25
LOAEL = 125
(RA)
No Data
NOAEL = 25
LOAEL = 125
(RA)
No Data
NOAEL = 25
LOAEL = 125
(RA)
No Data
NOAEL = 25
LOAEL = 125
(RA)
Developmental
Toxicity
NOAEL/LOAEL
(mg/kg-bw/day)
Maternal Toxicity
NOAEL = 250
LOAEL = 600
No Data
NOAEL = 5
LOAEL = 25
No Data
NOAEL = 5
LOAEL = 25
NOAEL = 5
LOAEL = 25
No Data
NOAEL = 5
LOAEL = 25
No Data
NOAEL = 5
LOAEL = 25
No Data
NOAEL = 5
LOAEL = 25
No Data
NOAEL = 5
LOAEL = 25
Developmental
Toxicity
NOAEL = 250
LOAEL = 600
NOAEL = 25
LOAEL = 125
(RA)
NOAEL = 25
LOAEL = 125
(RA)
NOAEL = 25
LOAEL = 125
NOAEL = 25
LOAEL = 125
(RA)
NOAEL = 25
LOAEL = 125
(RA)
NOAEL = 25
LOAEL = 125
(RA)
NOAEL = 25
LOAEL = 125
(RA)
Genetic Toxicity -


No Data

No Data

No Data

21

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Tal)le4. Sum ill ;ir\ of lliiiiiiin lleallh Diilii
l.udpoiiKs
licn/cnamine.
Vpheinl-.
s(\rcnalcd
<(.X442-(.X-2)
licn/cnamine.
Vpheinl-.
reaction
products w iili
s(\ivne and
2.4.4-1 rimcl In 1-
pciilcne
((iS')21-45-V)
lien/enamine.
Vpheinl-.
rcaclion
products w illi
2.4.4-1 rimcl In 1-
pciilcnc
((•S4 ll-4(>-l)
licn/cnaminc.
Vphcinl-
rcaclion
producl willi
2.4.4-1 rimcl In 1-
pciKcnc and
istihii l> Iciic
(1 X43"7X-OX-3)
licn/cnaminc.
4-( l-mellnl-l-
pheinlcllnh-V
4|4-( 1 -niel h> 1-1 -
phcinlcllnh
plH*ll>l|-
(lOOSI-f."7-!)
lien/enamine.
4-oclj l-\-(4-
oc(>lphcu\h
( 101-f.7-7)
lien/enamine.
ar-noin 1-
Vuninlphcinl
(3(iS7S-20-3)
lien/enamine.
2-c(h\l-V(2-
ellnlphcinh-.
((lipropciivl)
dcri\;i(i\cs
KiSOOS-"7"7-?)
Gene Mutation
In vitro
Negative
Negative
Negative
(RA)
Negative
Negative
(RA)
Negative
Negative
(RA)
Negative
Genetic Toxicity -
Chromosomal
Aberrations
In vitro
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
Genetic Toxicity -
Other
DNA damage and
repair (in vitro)
Mouse micronucleus
(in vivo)
Sister chromatid
exchange
Negative
Negative
	*
	it
	it
	it
	it
	it
	it
	it
	it
	it
	it
	it
	it
	it
	it
Negative
	it
	it
	it
	it
	it
	it
Additional
Information
Skin Irritation
Slightly
irritating
Not irritating
	it
	it
	it
Not irritating
	it
	it
Eye Irritation
Slightly
irritating
	it
	it
	it
	it
Slightly
irritating
	it
Slightly
irritating
Sensitization
	*
Negative
	it
Negative
	it
	it
	it
	it
Measured data in bold text; (RA) = Read Across; (f) = fema
chemical; * indicates endpoint is not included in the base data
es; (m) = males; - indicates endpoint was not addressed for this
set under the HPV Challenge Program.
22

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
4 Hazards to the Environment
A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 5. The
table also indicates where data for tested category members are read across (RA) to untested
members of the category.
Acute Toxicity to Fish
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN101-67-7)
(1)	Bluegill sunfish (Lepomis macrochirus) were exposed to benzenamine, 4-octyl-N-(4-
octylphenyl) at a nominal concentration range of 100 - 1000 mg/L, in a closed system under
static conditions for 96 hours. Acetone was used as the solvent and solvent control. A 96-h LC50
of > 1000 mg/L was reported. The results of this test are difficult to interpret because the
substance was tested above its water solubility limit and in the presence of solvent. Therefore,
EPA considers the no effect concentration to be the water solubility limit (saturation), which for
benzenamine, 4-octyl-N-(4-octylphenyl) would be approximately 4.215 x 10"7 mg/L.
No effects at saturation
(2)	Rainbow trout (Salmo gairdneri) were exposed to benzenamine, 4-octyl-N-(4-octylphenyl) at
a nominal concentration range of 100 - 1000 mg/L, in a closed system under static conditions for
96 hours. Acetone was used as the solvent and solvent control. A 96-h LC50 of > 1000 mg/L
was reported. The results of this test are difficult to interpret because the substance was tested
above its water solubility limit and in the presence of solvent. Therefore, EPA considers the no
effect concentration to be the water solubility limit (saturation), which for benzenamine, 4-octyl-
N-(4-octylphenyl) would be approximately 4.215 x 10"7 mg/L.
No effects at saturation
Benzenamine, ar-nonyl-N-nonylphenyl (CASRN 36878-20-3)
Fathead minnows (Pimephalespromelas) were exposed to benzenamine, ar-nonyl-N-
nonylphenyl at a nominal concentration range of 1000 - 10,000 mg/L, under semi-static
conditions for 96 hours. Benzenamine, ar-nonyl-N-nonylphenyl was renewed after 48 hours. No
mortality was observed at the highest concentration tested. The results of this test are difficult to
interpret because the substance was tested above its water solubility limit. Therefore, EPA
considers the no effect concentration as the water solubility limit (saturation).
No effects at saturation
Benzenamine, N-phenyl-, styrenated (CASRN 68442-68-2)
Zebrafish (Brachydanio rerio) were exposed to benzenamine, N-phenyl-, styrenated at nominal
concentrations under static conditions for 96 hours. The benzenamine, N-phenyl-, styrenated
was dispersed in water by means of an Ultra-Turrax. Mortality increased with increasing
concentration of benzenamine, N-phenyl-, styrenated added to the test solution and the sponsor
reported 96-h LC50 of 920 mg/L. The results of this test are difficult to interpret because the
substance was tested above its water solubility limit, but are likely due to physical effects
because tested concentrations vastly exceeded the water solubility limit (saturation), which for
benzenamine, N-phenyl-, styrenated is 0.41 mg/L.
No effects at saturation
23

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Acute Toxicity to Aquatic Invertebrates
Benzenamine, 4-octyl-N-(4-octylphenyl) (CASRN101-67-7)
Daphnia magna were exposed to benzenamine, 4-octyl-N-(4-octylphenyl) at a nominal
concentration range of 1.8 -32 mg/L, in a closed system under static conditions for 48 hours.
DMF was used as the solvent and solvent control. Mortality increased with increasing
concentration of benzenamine, 4-octyl-N-(4-octylphenyl) added to the test solution and the
sponsor reported 48-h EC50 of 7.7 mg/L. The results of this test are difficult to interpret because
the substance was tested above its water solubility limit and in the presence of solvent, but are
likely due to physical effects because tested concentrations vastly exceeded the water solubility
limit (saturation), which for benzenamine, 4-octyl-N-(4-octylphenyl) is approximately 4.215 x
10"7 mg/L.
No effects at saturation
Benzenamine, ar-nonyl-N-nonylphenyl (CASRN 36878-20-3)
Crustacea (Mysidopsis bahia) were exposed to benzenamine, ar-nonyl-N-nonylphenyl as water
accommodated fractions (WAFs) under semi-static conditions for 96 hours. The loading rates
were 0, 150, 250, 400, 600 or 1000 mg/L and no analytical measurements were made on the
WAFs. EPA does not consider the loading rate as the no effect concentration when the
concentration exceeds the water solubility of the test substance. The results of this test are
difficult to interpret because the substance was tested above its water solubility limit, but are
likely due to physical effects because the tested concentrations vastly exceeded the water
solubility limit (saturation).
No effects at saturation
Toxicity to Aquatic Plants
Benzenamine, ar-nonyl-N-nonylphenyl (CASRN 36878-20-3)
Algae (Pseudokirchneriella subcapitata) were exposed to benzenamine, ar-nonyl-N-nonylphenyl
as water accommodated fractions (WAFs) under static conditions for 96 hours. The loading
rates were 0, 0.3, 3.3, 33, 330 or 3300 mg/L and no analytical measurements were made on the
WAFs. Effects observed at 330 mg/L were determined to be algistatic based on the rapid re-
growth of an aliquot of cells taken from 500 mg/L cultured in fresh control media. EPA does not
consider the loading rate as the no effect concentration when the concentration exceeds the water
solubility of the test substance. The results of this test are difficult to interpret because the
substance was tested above its water solubility limit, but are likely due to physical effects
because the tested concentrations vastly exceeded the water solubility limit (saturation),
No effects at saturation
Conclusion: The measured acute toxicity values of substituted diphenylamines to fish aquatic
invertebrate and aquatic plants have no effects at the saturation limit (4.2 x 10"7 mg/L).
24

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Tal>le5. Siimman of llin immncnlal IHTccls - \(|ii;i 1 ic 1 o\icil> l);K;i
l.ndpoinls
licn/cnamine.
Vpheinl-.
s(\ renaled
<(.X442-(.X-2)
lion/oil ;i ill inc.
Vpheinl-.
reaction
products with
s(\rcnc and
2.4.4-1 rimcl In
l-penlene
(6S')2l-45-')|
licn/cnaminc.
Vpheinl-.
reaclion
products w ith
2.4.4-1 rimcl In
Ipcnlcnc
U>X4I )
licn/cnaniinc.
Vphcinl-
reaclion
products \\ illi
2.4.4-1 rimcl In
Ipenlene and
isohul.t Iciic
(IX43"7X-OX-3)
lien/enamine.
4-( 1-in clln 1-
1-
phcinlcllnh-
V4|4-( i-
IllCllnl-
l-phcinlcllnl
) phcn> 11-
(IIIIIX1-(•*?-1)
lien/enamine.
4-ocl\l-V(4-
nc(\lphcn\l)
(llll-(.'7-'7)
lien/enamine.
ar-noin 1-
Vnoinlphcin
1
(3(iX"7X-20-3)
licn/cnaniinc.
2-ellnl-N-(2-
cl h> lpheii> 1
(Iripropcinl)
dcri\ali\cs
KiXhllX-"7"7-?)
lish
96-h LCS0 (mg/L)
NES
\o Dala
NES
(RA)
\o Dala
NES
(RA)
\o Dala
NES
(RA)
\o Dala
NES
(RA)
NES
NES
\o Dala
NES
(RA)
Aquatic
Invertebrates
48-h ECS0 (mg/L)
NES
No Data
NES
(RA)
No Data
NES
(RA)
No Data
NES
(RA)
No Data
NES
(RA)
NES
No Data
NES
(RA)
No Data
NES
(RA)
Aquatic Plants
72-h ECS0 (mg/L)
No Data
NES
(RA)
No Data
NES
(RA)
No Data
NES
(RA)
No Data
NES
(RA)
No Data
NES
(RA)
No Data
NES
(RA)
NES
No Data
NES
(RA)
RA = read across, NES = No effect at saturation
25

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