U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
SPONSORED CHEMICALS
Category Phosphoric Acid Derivatives
SUB-CATEGORY I
SPONSORED CHEMICAL
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
SUB-CATEGORY II
SPONSORED CHEMICALS
Bis(2-ethylhexyl) phosphate (CASRN 298-07-7)
Phosphoric acid, 2-ethylhexyl ester (CASRN 12645-31-7)
(Mixture of CASRN 298-07-7 and CASRN 1070-03-7)
SUPPORTING CHEMICAL
Mono(2-ethylhexyl) phosphate (CASRN 1070-03-7)
SUB-CATEGORY III
SPONSORED CHEMICAL
Triisobutyl phosphate (CASRN 126-71-6)
SUPPORTING CHEMICAL
Tributyl phosphate (CASRN 126-73-8)
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
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.

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Hazard Characterization Document
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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,
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.
3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
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Hazard Characterization Document
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Chemical Abstract
SUB-CATEGORY I
Registry Number

(CASRN)
CASRN 78-42-2

SUB-CATEGORY II

SPONSORED CHEMICALS

CASRN 298-07-7

CASRN 12645-31-7

SUPPORTING CHEMICAL

CASRN 1070-03-7

SUB-CATEGORY III

SPONSORED CHEMICAL

CASRN 126-71-6

SUPPORTING CHEMICAL

CASRN 126-73-8
Chemical Abstract Index
SUB-CATEGORY I
Name
Phosphoric acid, tris(2-ethylhexyl) ester

SUB-CATEGORY II

SPONSORED CHEMICALS

Phosphoric acid, bis(2-ethylhexyl) ester

Phosphoric acid, 2-ethylhexyl ester

SUPPORTING CHEMICAL

Phosphoric acid, mono(2-ethylhexyl) ester

SUB-CATEGORY III

SPONSORED CHEMICAL

Phosphoric acid, tris(2-methylpropyl) ester

SUPPORTING CHEMICAL

Phosphoric acid, tributyl ester
Structural Formula
See Table 1, Section 1.1
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Hazard Characterization Document
September, 2009
Summary
The phosphoric acid derivatives are liquids with moderate water solubility and low vapor
pressure, except for the triisobutyl phosphate, which has moderate vapor pressure, and the
supporting chemical mono(2-ethylhexyl)phosphate, which has a high water solubility. They are
expected to have low to moderate mobility in soil. Volatilization of the phosphoric acid
derivatives is considered low to moderate based upon their Henry's Law constants. The pKa
values of bis(2-ethylhexyl)phosphate and mono(2-ethylhexyl) phosphate indicate that sub-
category II members will exist almost entirely in the anionic form and therefore volatilization
from water surfaces is not expected. The rate of hydrolysis is considered negligible for the
chemicals in this category. The rate of atmospheric photooxidation is considered rapid to
moderate. Compounds in the phosphoric acids derivatives category were found to be readily and
inherently biodegradable. The phosphoric acid derivatives are expected to have low persistence
(PI) and low bioaccumulation potential (Bl).
Sub-Category I: Acute oral toxicity of CASRN 78-42-2 to rats and rabbits, acute inhalation
toxicity to guinea pigs and acute dermal toxicity to rabbits is low. This chemical is irritating to
rabbit skin, and not irritating to rabbit eyes. In the oral repeated-dose studies, rats and mice
exposed to CASRN 78-42-2 at doses greater than or equal to 1550 mg/kg-day had body weight
losses; the NOAEL for systemic toxicity was 430 mg/kg-day. One study of repeated-dose
inhalation exposures in guinea pigs showed histological changes in the kidney at 0.0096
mg/L/day; the NOAEL for systemic toxicity was 0.0016 mg/L/day. No data are available for the
reproductive/developmental toxicity endpoints. This chemical did not induce gene mutations or
chromosomal aberrations in vitro. CASRN 78-42-2 showed some evidence of carcinogenicity in
rats and mice which is considered equivocal.
Sub-Category IT. Acute oral toxicity of CASRN 298-07-7 and CASRN 12645-31-7 (mixture) to
rats and acute dermal toxicity of CASRN 298-07-7 and supporting chemical CASRN 1070-03-7
to rabbits is low. CASRN 298-07-7 and supporting chemical CASRN 1070-03-7 are irritating to
rabbit skin and corrosive to rabbit eyes. No data are available for the repeated-dose,
reproductive and developmental toxicity endpoints for this sub-category. CASRN 298-07-7 and
CASRN 12645-31-7 did not induce gene mutations in vitro. No data are available for the
chromosomal aberrations endpoint for this sub-category.
Sub-Category III. Acute oral toxicity of CASRN 126-71-6 and CASRN 126-73-8 (supporting
chemical) to rats and mice and acute dermal toxicity to rabbits and guinea pigs are low. Acute
inhalation toxicity of CASRN 126-71-6 in rats is low in one study. Both chemicals in the sub-
category are irritating to rat, rabbit, human and guinea pig skin, are irritating to rabbit eyes and
are dermal sensitizers in guinea pigs but not in humans. Oral repeated-dose studies of rats
administered CASRN 126-71-6 showed limited hematological and clinical chemistry effects at
346 mg/kg-day; the NOAEL for systemic toxicity was 68 mg/kg-day. Oral repeated-dose studies
of rats administered CASRN 126-73-8 (supporting chemical) showed hematology and
histopathological changes of the urinary bladder at 68 mg/kg-day; the NOAEL for systemic
toxicity was 13.8 mg/kg-day. In a two-generation oral reproductive toxicity study in rats,
CASRN 126-73-8 (supporting chemical) showed no reproductive toxicity, and the NOAEL for
reproductive toxicity was 225 mg/kg-day. In the same study, there was developmental (pre- and
4

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September, 2009
postnatal) toxicity at 225 mg/kg-day as demonstrated by reduced pup weights; the NOAEL for
developmental toxicity was 53mg/kg-day. Both chemicals in this sub-category did not induce
gene mutations in vitro and did not induce chromosomal aberrations in vitro or in vivo. No
evidence of neurotoxicity was seen for the supporting chemical, CASRN 126-73-8. The
supporting chemical showed evidence of carcinogenicity in rats.
Sub-Category I: The predicted 96-hour LC50 of CASRN 78-42-2 to fish is 0.000218 mg/L. The
predicted 48-hour EC50 of CASRN 78-42-2 to aquatic invertebrates 0.009 mg/L. The 96-hour
EC50 of CASRN 78-42-2 to aquatic plants is 0.000798 mg/L.
Sub-Category II: The 96-hour LC50 of CASRN 298-07-7 ranged from 20 - 56 mg/L and
CASRN 126-73-8 ranged from greater than 100 to 5018 mg/L to fish.. The 48-hour LC50 of
CASRN 298-07-7 ranged from 42 to 83.7 mg/L to aquatic invertebrates. The 48-hour LC50 of
CASRN 126-73-8 is 110 mg /L to aquatic invertebrates. The 72-hour EC50 of CASRN 298-07-7
to aquatic plants is greater than 100 mg/L. The 48-hour EC50 of CASRN 12645-31-7 to aquatic
plants is 168 mg/L. The 62-day chronic value of the supporting chemical CASRN 12645-31-7 is
20.6 mg/L to fish.
Sub-Category III: The 96-hour LC50 of CASRN 126-71-6 and CASRN 126-73-8 ranged from
11 to 23 mg/L to fish. The 48-hour EC50 of CASRN 126-71-6 CASRN 126-73-8 is 11 and 2.6
mg/L respectively to aquatic invertebrates. The 72-hour EC50 of CASRN 126-71-6 CASRN 126-
73-8 ranged from 1.1 to 33 mg/L (biomass) and 2.8 to 34 mg/L (growth) to aquatic plants. The
95-day MATC of CASRN 126-73-8 is 1.2 mg/L to fish. The 21-day MATC of CASRN 126-73-8
is 1.2 mg/L to aquatic invertebrates.
For sub-category I, the reproductive and developmental toxicity endpoints, as well as the acute
toxicity to fish, aquatic invertebrates, and aquatic plants remain as data gaps. For sub-category
II, the chromosomal aberrations, repeated-dose, reproductive and developmental toxicity
endpoints remain as data gaps.	
5

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The sponsor, American Chemistry Council (ACC) Phosphoric Acid Derivatives Panel, submitted
a Test Plan and Robust Summaries to EPA for phosphoric acid derivatives on December 13,
2001. EPA posted the submission on the ChemRTK HPV Challenge website on January 15,
2002 (http://www.epa.gov/chemrtk/pubs/summaries/phsacdde/cl3356tc.htm). EPA comments
on the original submission were posted to the website on November 19, 2002. Public comments
were also received and posted to the website. The sponsor submitted updated/revised documents
on December 22, 2005, which were posted to the ChemRTK website on March 21, 2006.
Category Justification
EPA did not agree with the sponsor's proposed category or the adequacy of several of the
proposed supporting chemicals. EPA has divided the four sponsored chemicals and two
supporting chemicals into three sub-groups for assessment of data adequacy for endpoints under
the HPV Challenge Program. Structures of the chemicals are presented in Table 4. Read-across
between the sub-categories I, II and III is not supported.
Justification for Supporting Chemicals
EPA did not agree with the adequacy of several of the sponsor's proposed supporting chemicals.
For sub-category II, EPA did agree to the use of supporting chemical CASRN 1070-03-7, since it
is a component of the HPV sub-category member CASRN 12645-31-7 (a mixture of CASRN
298-07-7 and CASRN 1070-03-7). Toxicity data for supporting chemical CASRN 1070-03-7 is
not used to support the hazard characterization for aquatic organisms.
For sub-category III, EPA used the supporting chemical CASRN 126-73-8. Both CASRN 126-
73-8 and CASRN 126-71-6 are tri-esters and the supporting chemical is expected to be
metabolized similarly to CASRN 126-71-6 to produce methoxypropanol as the alcohol
metabolite.
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Hazard Characterization Document
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1 Chemical Identity
1.1 Identification and Purity
Table 1. Structures
Chemical Name
CASRN
Chemical Structure
Sub-Category I
Sponsored Chemical
Tris(2-ethylhexyl) phosphate
78-42-2
~\ / V u ~
°^T \ T\
Sub-Category II
Sponsored Chemical
Phosphoric acid, 2-ethyl-
hexyl ester (mixture)
12645-31-7
f
%	' O—P—O /	4
^\Z
s	f Q—l»-OH
OH
Bis(2-ethylhexyl) phosphate
298-07-7
	¦' O-P-O t—x
6h ^	^—*
Supporting Chemical
Mono(2-ethylhexyl)
phosphate
1070-03-7
Vr	J _ Ql |—[
1
OH
Suh-Catc^orv III
Sponsored Chemical
Triisobutyl phosphate
126-71-6
/ \ II
' 1 O-P-O /
Supporting Chemical
Tributyl phosphate
126-73-8
	, O
	/ \ 11
The sponsor did not discuss purity of the chemicals in this category in the Test Plan.
1.2 Physical-Chemical Properties
The substances in the phosphoric acid derivatives category are liquids at room temperature.
They have moderate water solubility and low vapor pressure, except for the triisobutyl phosphate
which has moderate vapor pressure and the supporting chemical mono(2-ethylhexyl)phosphate
which has a high water solubility. The physical-chemical properties of the category members are
summarized in Table 2.
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2 General Information on Exposure
2.1	Production Volume and Use Pattern
The four chemicals in the phosphoric acid derivatives category had a combined production
volume, including both manufactured and imported volumes, in the United States of up to 30
million pounds during calendar year 2005.2 CASRN 78-42-2 had a production and import
volume of less than 500,000 pounds. CASRN 12645-31-7, CASRN 298-07-7 and CASRN 126-
71-6 each had production and import volumes of 1 million to 10 million pounds.
The HSDB information for CASRN 78-42-2 (Sub-category I) states that the chemical is
primarily used in solvents, anti-foaming agents, or plasticizers.4 The HPV submission states that
this chemical is used in catalysts for polypropylene at concentrations of approximately one
percent.5
The HSDB for CASRN 298-07-7 (Sub-category II) states that the chemical is primarily used as
an additive to lubrication oils, corrosion inhibitor and antioxidant, intermediate for wetting
agents and detergents, fire retardant in polymeric materials, and extraction fluid for metal salts.4
The HPV submission states that CASRN 298-07-7 and CASRN 12645-31-7 are used as
components in industrial and automotive gear oil additive packages. CASRN 298-07-7 can also
be used as an industrial metal extraction agent and in the production of nylon.5 Non-confidential
information in the IUR indicated that the industrial processing and uses of CASRN 12645-31-7
included processing as functional fluids and "other" in all other chemical product and
preparation manufacturing.2 Non-confidential information in the IUR indicated that the
commercial and consumer products containing CASRN 12645-31-7 included "other."
CASRN 126-71-6 (Sub-category III) does not have any 2006 IUR submissions. The HPV
submission states that CASRN 126-71-6 is primarily used in solvents, antifoam agents in
hydraulic fluids, extraction agents, and the production of plastics.
2.2	Environmental Exposure and Fate
No quantitative information is available on releases of the chemicals in this category to the
environment.
The environmental fate properties are provided in Table 3. The substances in the phosphoric
acid derivatives category are liquids at room temperature. They have moderate water solubility
and low vapor pressure, except for the triisobutyl phosphate which has moderate vapor pressure
and the supporting chemical mono(2-ethylhexyl)phosphate which has a high water solubility.
4	HSDB, 2008. Hazardous Substances Data Bank. Accessed, 11/13/08. http://toxnet.nlm.nih.gov/
5	January 19, 2006. Phosphoric Acid Derivatives Category Test Plan and Data Assessment. Accessed, 11/13/2008.
http://www.epa.gov/chemrtk/pubs/summaries/phsacdde/cl3356rt2.pdf
8

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Environmental Fate Characterization
The substances in the phosphoric acid derivatives category are expected to have low to moderate
mobility in soil. Compounds in the phosphoric acids derivatives category were found to be
readily and inherently biodegradable. If released to air, the phosphoric acid derivatives may
exist in the vapor-phase and the rate of atmospheric photooxidation for these substances is
considered moderate. The rate of hydrolysis is considered negligible for the chemicals in this
category. Direct photolysis experiments resulted in degradation of 80% and 85% upon
irradiation in 1 hour for tris(2-ethylhexyl)phosphate and the supporting chemical tributyl
phosphate, respectively, but these experiments were performed with low and high pressure Hg
lamps which do not simulate sunlight. The phosphoric acid derivatives are expected to have low
persistence (PI) and low bioaccumulation potential (Bl).
9

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U.S. Environmental Protection Agency
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Tabic 2. Phvsical-Chcmical Properties of Phosphoric Acid Derivatives Category1

Sub-Category I
Sub-Category II
Sub-Catcgorv III
Property
Tris(2-cthylhcxyl)
phosphate
Phosphoric acid,
2-cthylhcxyl ester
(mixture)
Bis(2-cthylhexyl)
phosphate
IVIono(2-cthylhcxyl)
phosphate
(supporting
chemical)
Triisobutyl
phosphate
Tributyl phosphate
(supporting
chemical)
CASRN
78-42-2
12645-31-7
298-07-7
1070-03-7
126-71-6
126-73-8
Molecular Weight
434.65
210.21
322.43
210.12
266.32
266.32
Physical State
Liquid
Liquid
Liquid
Liquid
Liquid
Liquid
Melting Point
<-70°C
<-20°C
-60°C
No data
<-50°C
<-70°C
Boiling Point
210°C at 5 hPa;
Decomposes
215°C at 4 torr5
186°C at 1 torr5
354.5°C at 1,013 hPa
(estimated);
Decomposes
240°C
(decomposition
temperature)
354.5°C at 1,013
hPa
(estimated);
Decomposes
272°C at 1,013 hPa
(measured)
264°C at 760 torr6
209°C at 150 torr6
196°C at 100 torr6
177°C at 50 torr6
138°C at 10 torr6
117°C at 5.5 torr6
130°C at 5 hPa
(decomposes)
289°C at 760 torr7
(begins to
decompose)227°C at
150 torr7
211°C at 100 torr7
196°C at 50 torr7
150°C at 10 torr7
138.5°Cat6torr7
98°C at 0.1 torr7
Vapor Pressure
(mm Hg)
1.54xl0"7
(estimated)
5.34><10"7
(estimated)
1.8xl0"7 (estimated)
4.0xlO"7 (estimated)
1	hPa at 92°C
2	hPa at 103°C
(which converts to
0.0068 torr at room
temperature)
10 hPa at 133°C
50 hPa at 170°C
130 hPa at 200°C
500 hPa at 243 °C
2.6xlO"6 (measured)
Dissociation
Constant (pKa)
Not Applicable
3.49 (measured);
1.41 (estimated)2'3;
6.09 (estimated)2'3
3.49 (measured)
1.41 (estimated)2;
6.09 (estimated)2
Not Applicable
Not Applicable
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Hazard Characterization Document
Henry's Law
Constant
(atm-m3/mole)
9.56xl0-5
(estimated)4
1.77X10"11
(estimated)4
4.1 x 10"8 (estimated)4
1.77X10"11
(estimated)4
3.19xl0"6
(estimated)4
1.41xl0"6
(estimated)4
Water Solubility
(mg/L)
2.0 (measured)
211.3 (estimated);
2.19xl03
(measured)3;
182 (measured)3
182 (measured)
2.19xl03 (measured)
265 (measured)
400 (measured)
285 mg/L at 50°C 8
390 mg/L at 25°C 8
380 mg/L at 22°C 8
420 mg/L at 16°C 8
1075 mg/L at 3.4°C
8
Log Kow
4.1—4.2
(measured)
2.65
(estimated)
2.67
(measured)
2.65
(estimated)
3.72
(measured)
2.5-4.0
(measured)
1Rhodia Inc. January 16, 2006. Revised Robust Summary for Phosphoric Acid Derivatives Category.
http://www.epa. gov/chemrtk/pubs/summaries/phsacdde/c 13 3 56tc.htm.
2Sparc On-Line Calculator. Version 4.2. Accessed November 2008. http://ibmlc2.chem.uga.edu/sparc.
3Phosphoric acid, 2-ethylhexyl ester is a mixture of bis(2-ethylhexyl) phosphate (CASRN 298-07-7) and mono(2-ethylhexyl) phosphate (CASRN 1070-03-7)
and therefore, properties for these chemicals are reported.
4U.S. EPA. 2008. Estimation Programs Interface Suite™ (version 3.20). United States Environmental Protection Agency, Washington, DC, USA. Available
online at: http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
5Beilstein, E4, Volume 1, part 3, page 1786
6Beilstein, E3, Volume 1, part 2, page 1563
7Beilstein, E3, Volume 1, part 2, page 1511
8Beilstein, E4, Volume 1, part 3, page 1531
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Tabic 3. Environmental Fate Characteristics of Phosphoric Acid Derivatives Category1

Sub-Category I
Sub-Category II
Sub-Category III
Property
Tris(2-ethylhexyl)
phosphate
Phosphoric acid,
2-ethylhexyl ester
(mixture)
Bis(2-ethylhexyl)
phosphate
Mono(2-cthylhcxyl)
phosphate
(supporting
ehcmical)
Triisobutvl
phosphate
Tributyl phosphate
(supporting
chemical)
CASRN
78-42-2
12645-31-7
298-07-7
1070-03-7
126-71-6
126-73-8
Photodegradation
Half-life
1.3 hours
(estimated)
3.9 hours (estimated)
3.9 hours (estimated)
3.9 hours (estimated)
4.3 hours
(estimated)
1.6 hours (estimated)
Direct
Photodegradation
80% degradation by
UV light after 1
hour (measured)
(using mercury
lamp; not
environmentally
relevant)
No Data
No Data
No Data
No Data
85% degradation by
UV light after 1 hour
(measured) (using
mercury lamp; not
environmentally
relevant)
Biodegradation2
0% in 28 days (not
readily
biodegradable);
55-60% in 2 days
following
acclimation
(inherent, primary
biodegradable)
52% in 28 days (not
readily
biodegradable)
75% in 28 days
(readily
biodegradable);
0-17% in 28 days
(not readily
biodegradable)
No Data
97% in 14 days
(readily
biodegradable);
70% in 35 days
(readily
biodegradable)
77-92% in 28 days
(readily
biodegradable)
Hydrolysis Half-life
No Data
>1 year (pH 4, 7, 9)
(measured)
No Data
No Data
170 days (pH 4,
50°C);
303 days (pH 7,
50°C)
(measured)
Stable after 30 days
(pH 3, 7, 11)
(measured)
Log Koc
3.66 (estimated)3
2.11 (estimated)3
1.12 pH 7
(estimated);
4.2 (estimated);
2.28 (estimated)
2.11 (estimated)3
3.05 (estimated)3
3.16 (measured);
3.07 (measured);
2.58 (measured)
Bioconcentration
2.4-22 (measured in
carp)
21.92 (estimated)
1.1-6.0 (measured in
carp)
21.92 (estimated)
19.51 (estimated)
5.5-49 (measured in
carp)
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Fugacity
(Level III Model)
Air (%)
0.312
0.000783
0.302
0.000783
0.518
0.0737
Water (%)
10.9
29.0
24.5
29.0
38.8
41.0
Soil (%)
31.2
70.8
75.0
70.8
59.5
56.7
Sediment (%)
57.6
0.188
0.226
0.188
1.14
1.52

(estimated)
(estimated)
(estimated)
(estimated)
(estimated)3
(estimated)3
Persistence4
PI
PI
PI
PI
PI
PI
Bioaccumulation4
B1
B1
B1
B1
B1
B1
1Rhodia Inc. January 19, 2006. Revised Robust Summary for Phosphoric Acid Derivatives Category.
http://www.epa. gov/chemrtk/pubs/summaries/phsacdde/c 13 3 56tc.htm
Conflicting results from two separate modified MITI tests were provided in the robust summary.
3U.S. EPA. 2008. Estimation Programs Interface Suite™ (version 3.20). United States Environmental Protection Agency, Washington, DC, USA. Available
online at: http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
4Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64, Number 213 (November 4,
1999) pp. 60194-60204.
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Conclusion: The phosphoric acid derivatives are liquids with moderate water solubility
and low vapor pressure, except for the triisobutyl phosphate, which has moderate vapor
pressure, and the supporting chemical mono(2-ethylhexyl)phosphate, which has a high
water solubility. They are expected to have low to moderate mobility in soil.
Volatilization of the phosphoric acid derivatives is considered low to moderate based
upon their Henry's Law constants. The pKa values of bis(2-ethylhexyl)phosphate and
mono(2-ethylhexyl) phosphate indicate that sub-category II members will exist almost
entirely in the anionic form and therefore volatilization from water surfaces is not
expected. The rate of hydrolysis is considered negligible for the chemicals in this
category. The rate of atmospheric photooxidation is considered rapid to moderate.
Compounds in the phosphoric acids derivatives category were found to be readily and
inherently biodegradable. The phosphoric acid derivatives are expected to have low
persistence (PI) and low bioaccumulation potential (Bl).
3 Human Health Hazard
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 within the subcategories.
Acute Oral Toxicity
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
(1)	In three studies, rats (strain and number not stated) were administered tris{2-
ethylhexyl) phosphate via the oral route. Mortality and time of death was not reported.
LD50 > 10,000 - 37,080 mg/kg-bw
(2)	In two studies, rabbits (strain and number not stated) were administered tris(2-
ethylhexyl) phosphate via the oral route. Mortality and time of death was not reported.
LD50 ~ 46,000 mg/kg-bw
Sub-Category II
Bis (2-ethylhexyl)phosphate (CASRN298-07-7)
(1)	Wistar rats (5/sex/dose) were administered /?/.s(2-ethylhexyl) phosphate via gavage at
500, 880, 1260, 2000 or 3000 mg/kg-bw and observed for 14 days. Mortalities were
observed at all dose levels.
LD50 = 1400 mg/kg-bw
(2)	Sprague-Dawley rats (5/sex/dose) were administered A/.v(2-ethylhexyl) phosphate via
gavage at 500 or 5000 mg/kg-bw and observed for 14 days. All animals at the high-dose
died within 24 hours. None of the low dose animals died within 14 days observation.
LD50> 500 mg/kg-bw (but < 5000 mg/kg-bw)
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(3) Sprague-Dawley rats (number and doses not specified) were administered liquid
/?/.s(2-ethylhexyl) phosphate via gavage and observed for 14 days. Study only available
in a secondary source and reliability is not assignable.
LD50 = 4742 mg/kg-bw
Phosphoric acid, 2-ethylhexyl ester (CASRN12645-31-7)
Sprague-Dawley rats (3 females/dose) were administered phosphoric acid, 2-ethylhexyl
ester via gavage at 300 mg/kg-bw in arachis oil BP (two groups) or 2000 mg/kg-bw,
undiluted (1 group) and observed for 14 days. Mortalities were observed at the high-dose
(2/3 animals found dead one or 2 days after dosing). No animals died at 300mg/kg.
LD50 < 2000 mg/kg-bw
Mono(2-ethylhexyl) phosphate (CASRN 1070-03-7, Supporting Chemical)
(1)	Sprague-Dawley rats (5/dose, sex not specified) were administered mono(2-
ethylhexyl) phosphate via gavage at 464, 1000, 2150 or 4640 mg/kg-bw and observed for
up to 14 days. Mortalities were observed at the 2 higher doses, but not specified by dose
or time of death.
LD50 = 2710 mg/kg-bw
(2)	Sprague-Dawley rats (2 or 3/sex/dose) were administered mono(2-
ethylhexyl)phosphate via gavage at 2000, 3160, 5010 or 7940 mg/kg-bw and observed
for up to 7 days. No mortalities were observed at the low-dose. Number and time of
deaths are not specified for the higher dose groups.
LD50 = 4100 mg/kg-bw
Sub-Category III
Triisobutylphosphate (CASRN 126-71-6)
(1)	In four studies, rats (strain, sex and group size not specified) were administered
triisobutyl phosphate via the oral route. Mortality and time of death was not reported.
LD50 = 3072 - 12,800 mg/kg-bw
(2)	Mice (strain, sex and group size not specified) were administered triisobutyl
phosphate via the oral route. Mortality and time of death was not reported.
LD50 = 3200 - 6400 mg/kg-bw
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
Sprague-Dawley rats (5 males/dose) were administered tributyl phosphate via gavage at
464, 1000, 2150 or 4640 mg/kg-bw and observed for up to 14 days. All of the animals
from the high-dose group died during the study by day 4; no mortality occurred at lower
doses.
LD50 = 3160 mg/kg-bw
Acute Inhalation Toxicity
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
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Summaries of two acute inhalation toxicity studies in rats (exposure duration was 4 hours
in one study and not indicated in the other) and two acute inhalation toxicity studies in
guinea pigs (exposure duration was 1 hour in one study and not indicated in the other)
were provided by the sponsor, but were missing all other information. Three of these
studies noted LC50 values of > 0.447, > 0.45 and > 0.46 mg/L, but the remaining study in
guinea pigs noted an LC50 of 450 mg/L (exposure duration not indicated).
LC50 (duration not indicated) = 450 mg/L
Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
Results of an acute inhalation study in rats (strain, sex, number and concentrations not
specified) with an exposure duration of 4 hours were provided by the sponsor. No
mention of mortality and no other study details were provided.
LC50 (4-hour) > 5.14 mg/L
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
Rats (5/sex/concentration, strain not specified) were exposed to tributyl phosphate at
unspecified concentrations for 4 hours. Mortality was seen in males (2/5 died), but not in
females. No other data was provided.
LC5o(4-hour) > 4.24 mg/L
Acute Dermal Toxicity
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
Rabbits (strain, sex and group size not specified) were administered //7.s(2-ethylhexyl)
phosphate by the dermal route. No other study details were provided.
LD50 ~ 20,000 mg/kg-bw
Sub-Category II
Bis(2-ethylhexyl)phosphate (CASRN298-07-7)
New Zealand white rabbits (3/sex/dose) were administered />/.v(2-ethylhexyl) phosphate
dermally at 2000 mg/kg-bw on to clipped intact or abraded skin under occlusive
conditions for 24 hours and observed for 14 days. No mortalities or clinical signs of
toxicity were observed. Severe dermal irritation including crusty scabbing and swelling
(eschar and edema) were observed in all animals.
LD50 > 2000 mg/kg-bw
Mono(2-ethylhexyl) phosphate (CASRN 1070-03-7, Supporting Chemical)
New Zealand White rabbits (4, sex, strain not specified) were administered mono(2-
ethylhexyl) phosphate dermally at 4640 mg/kg-bw on to clipped intact skin. No
mortalities or clinical signs of toxicity were observed. Severe redness and swelling
(erythema and edema) were noted.
LD50 > 4640 mg/kg-bw
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Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
Rabbits and guinea pigs (strain, sex, group size, and doses not specified) were
administered triisobutyl phosphate dermally. No study details are provided.
LD50 (rabbits) > 5000 mg/kg-bw
LD50 (guinea pigs) > 9600 mg/kg-bw
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
In five studies, rabbits and guinea pigs (strain, sex, group size, and doses not specified)
were administered tributyl phosphate dermally. No study details are provided.
LD50 (rabbits) >3100 mg/kg-bw
LD50 (guinea pigs) = 9700 - 19,400 mg/kg-bw
Repeated-Dose Toxicity
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
(1)	In an National Toxicology Program (NTP) study, F344/N rats (10/sex/dose) were
administered /ra(2-ethylhexyl) phosphate in corn oil via gavage at 0 (vehicle control),
250, 500, 1000, 2000 or 4000 mg/kg-bw/day 5 days/week for 13 weeks. Slight to
moderate decrease in weight gain was noted at the two highest doses (significance and
magnitude not quantified in robust summary). No mortality or treatment-related
histopathological effects were observed.
LOAEL = 2000 mg/kg-bw/day (based on decreased weight gain)
NOAEL = 1000 mg/kg-bw/day
(2)	In an NTP study, B6C3F1 mice (10/sex/dose) were administered /ra(2-ethylhexyl)
phosphate in corn oil via gavage at 0 (vehicle control), 500, 1000, 2000, 4000 or 8000
mg/kg-bw/day for 13 weeks. Slight to moderate decrease in weight gain was noted at the
two highest dose levels (significance and magnitude not quantified in robust summary).
Inflammatory lesions in the gastric mucosa were seen at all doses with increased severity
at higher doses. Ulceration was seen in the forestomach of 1 male at 2000 mg/kg-
bw/day, 1 female at 4000 mg/kg-bw/day and 1 male and 3 females at 8000 mg/kg-
bw/day. No mortalities were observed.
LOAEL = 2000 mg/kg-bw/day (based on ulceration in the forestomach)
NOAEL = 1000 mg/kg-bw/day
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(3)	Rats (strain, sex and group size not specified) were administered /m(2-ethylhexyl)
phosphate in the diet at 10 - 1550 mg/kg-bw/day for 30 days. Weight loss was noted at
1550 mg/kg-bw/day. (Only study results were provided.)
LOAEL = 1550 mg/kg-bw/day (based on weight loss)
NOAEL = 430 mg/kg-bw/day
(4)	Guinea pigs (males, group size not specified) were exposed to /ra(2-ethylhexyl)
phosphate via inhalation at 0, 1.6 or 9.6 mg/m3 (0, 0.0016, 0.0096 mg/L) 6 hours/day, 5
days/week for 3 months. Increased terminal body weight and microscopic changes of
kidney tissue were noted at the highest concentration. Sections of the spinal cord and
sciatic nerve stained to demonstrate the myelin sheaths showed no pathologic alteration.
LOAEL = 0.0096 mg/L (based on histological changes of kidney)
NOAEL = 0.0016 mg/L
(5)	Rhesus monkeys (number and sex not specified) were exposed to //7.s(2-ethylhexyl)
phosphate via inhalation at 0, 10.8, 26.4 or 85 mg/m3 (0, 0.0108, 0.0264 or 0.085 mg/L) 6
hours/day, 5 days/week for 3 months. No deaths and no effects were noted on weight
gain, hematological and biochemical parameters, evaluation of trained behavior (visual
discrimination test) and histopathological findings.
NOAEL = 0.085 mg/L (based on no effects at the highest dose tested)
Sub-Category II
Data gap
Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
Sprague-Dawley rats (10/sex for low- and mid-dose, 30/sex for control and high-dose)
were administered triisobutyl phosphate in the diet at 0 (control), 200, 1000 or 5000 ppm
(equivalent to 0, 13.9 - 16.8, 68.4 - 84.3 or 346.1 - 403.9 mg/kg-bw/day) for 13 weeks.
Control and the high-dose animals were observed for 8 weeks post-exposure. High-dose
animals exhibited reduced food intake, limited hematological effects (slight reduction in
neutrophiles - significance and magnitude of change not reported) and clinical chemistry
changes (elevated cholesterol - significance and magnitude of change not reported). No
mortality, changes in body weight or organ weight or hematological effects were
observed.
LOAEL = 346.1 - 403.9 mg/kg-bw/day (based on limited hematological and clinical
chemistry effects)
NOAEL = 68.4 - 84.3 mg/kg-bw/day
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
Sprague-Dawley rats (15/sex/dose) were administered tributyl phosphate via the diet at 0,
8, 40, 200, 1000 or 5000 ppm (equivalent to approximately 0, 0.6, 3, 15, 75 or 375
mg/kg-bw/day) for up to 13 weeks. After 45 days, blood was collected from 5/sex/dose
for hematology and clinical chemistry and these animals were then sacrificed for
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histologic examinations. Decreased body weights and decreased food consumption in
375 mg/kg-bw/day animals were observed. At interim sacrifice, treatment-related effects
included elevated mean serum gamma-glutamyl transferase (SGGT) activity at 375
mg/kg-bw/day males and females and increased mean albumin and calcium values for
375 mg/kg-bw males. At terminal sacrifice, effects included increased mean SGGT
values in 75 mg/kg-bw/day males (actual measured concentration 68.2 mg/kg-
bw/day)and 375 mg/kg-bw/day males and females. Animals at 375 mg/kg-bw/day also
exhibited increased partial thromboplastin time and increased mean serum glutamic
pyruvic transaminase (SGPT) activity (males only). Histopathology revealed generalized
transitional cell hyperplasia of the urinary bladder in 75 mg/kg-bw/day males and 375
mg/kg-bw/day males and females.
LOAEL = 68.2 mg/kg-bw/day (based on hematology and histopathological changes of
the urinary bladder)
NOAEL = 13.8 mg/kg-bw/day
Reproductive Toxicity
Sub-Category I
Data gap
Sub-Category II
Data gap
Sub-Category III
Tributylphosphate (CASRN126-73-8, Supporting Chemical)
In a two-generation study, Sprague-Dawley rats (30/sex/concentration) were
administered tributyl phosphate in the diet at 0, 200, 700 or 3000 ppm (approximately 0,
15, 53 and 225 mg/kg-bw/day) for 13 weeks for the F0 generation and 11 weeks for the
F1 generation. Systemic effects included reduced body weight gains in high-dose F0 and
F1 generation males and females and mid-dose F1 females, reduced food consumption in
high-dose F0 and F1 males and females, urinary bladder epithelial hyperplasia in low-
dose (generation and sex not specified) and in mid- and high-dose F0 and F1 males and
females. Hepatic centrilobular hypertrophy was noted in mid-dose F0 and F1 generation
females and high-dose F0 and F1 males and females. Developmental effects included
"occasional" reduced pup weights in mid-dose and consistently and significantly reduced
bodyweights in the high-dose pups. No mortalities or clinical signs of toxicity were
observed. No reproductive effects were noted for mating indices, fertility indices,
gestation length, litter size, pup sex ratio and pre- and postnatal loss.
LOAEL (systemic toxicity) = 15 mg/kg-bw/day (based on urinary bladder hyperplasia)
NOAEL (systemic toxicity) = Not established
NOAEL (reproductive toxicity) = 225 mg/kg-bw/day (based on no effects at the
highest dose tested)
LOAEL (developmental toxicity) = 225 mg/kg-bw/day (based on reduced pup weights)
NOAEL (developmental toxicity) = 53 mg/kg-bw/day
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Developmental Toxicity
Sub-Category I
Data gap
Sub-Category II
Data gap
Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
In a prenatal developmental toxicity test, pregnant CD(SD) BR VAF/Plus rats (25/dose)
were administered triisobutyl phosphate via gavage at 0, 100, 300 or 1000 mg/kg-bw/day
on gestation days 6-15. Clinical signs of toxicity included an increased salivation at all
doses. Increased water consumption was observed during the treatment phase of the
high-dose group. Slightly decreased body weight gains were seen at the high dose after
day 8 of gestation but returned to control levels by the study's end. No changes in the
number of fetal abnormalities were observed. In the robust summary, it is not clear what
developmental endpoints were evaluated.
NOAEL (maternal toxicity) = 1000 mg/kg-bw/day(based on no effects at the highest
dose tested)
NOAEL (developmental toxicity) = 1000 mg/kg-bw/day (based on no effects at the
highest dose tested)
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
In a prenatal developmental toxicity test, pregnant Sprague-Dawley rats (24/dose) were
administered tributyl phosphate in corn oil via gavage at 0, 188, 375 or 750 mg/kg-
bw/day on days 6 - 15 of gestation. Mortality was noted in high-dose dams (7 of 24 died
[29.2%]). Decreased mean body weight gain and body weights were noted in low-, mid-
and high-dose dams, decreased food consumption was noted in mid- and high-dose dams
and increased relative (to body weight) liver weights were noted in high-dose dams.
Reported developmental effects are limited to decreased mean fetal body weight in high-
dose pups.
LOAEL (maternal toxicity) = 188 mg/kg-bw/day (based on decreased body weight and
body weight gain)
NOAEL (maternal toxicity) = Not established
LOAEL (developmental toxicity) = 750 mg/kg-bw/day (based on decreased mean fetal
body weights)
NOAEL (developmental toxicity) = 375 mg/kg-bw/day
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Genetic Toxicity - Gene Mutation
In vitro
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
(1)	In four bacterial reverse mutation assays, Salmonella typhimurium strains TA98,
TA100, TA1535 and TA1537 were exposed to ^ra(2-ethylhexyl) phosphate in the
presence or absence of metabolic activation. Negative results are reported but no other
information was provided.
Tris(2-ethylhexyl) phosphate was not mutagenic in these assays.
(2)	In an NTP study, Salmonella typhimurium strains TA98, TA100, TA 1535 and
TA1537 were exposed to /ro(2-ethylhexyl) phosphate at 100, 333, 1000, 3333, and
10,000 |ig/plate in the presence and absence of metabolic activation. Positive and
negative controls were included and responded appropriately. Tris(2-ethylhexyl)
phosphate was negative.
Tris(2-ethylhexyl) phosphate was not mutagenic in this assay.
Sub-Category II
Bis(2-ethylhexyl)phosphate (CASRN298-07-7)
(1)	In reverse mutation assays, Salmonella typhimurium strains TA1535, TA1537,
TA1538, TA98 and TA100 and Saccharomyces cerevisiae D4 were exposed to bis(2-
ethylhexyl) phosphate at 0, 0.001, 0.01, 0.1, 1.0 or 5.0 |iL/plate in the presence and
absence of metabolic activation. Positive controls were tested, but their response was not
provided. The cytotoxic concentration was 5 |iL/plate. /?/.s(2-ethylhexyl) phosphate was
negative for genotoxic effects.
Z?is(2-ethylhexyl)phosphate was not mutagenic in this assay.
(2)	In bacterial reverse mutation assays, Salmonella typhimurium strains TA98, TA100,
TA1535 and TA1537 were exposed to 6/'s(2-ethylhexyl) phosphate at 0, 4, 20, 100, 500
or 2500 |ig/plate in the presence and absence of metabolic activation. Positive controls
were used and produced an appropriate response. The cytotoxic concentration was 100
|ig/plate. /?/.s(2-ethylhexyl) phosphate was negative for genotoxic effects.
Z?is(2-ethylhexyl)phosphate was not mutagenic in this assay.
(3)	Mouse lymphoma L5178Y/TK+/- cells were exposed to A/.s(2-ethylhexyl) phosphate
at 0, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085 or 0.9 |iL/mL in the absence of metabolic
activation and 0, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075 or 0.085 |iL/mL in the presence of
metabolic activation. Positive controls were tested, but responses were not provided.
The cytotoxic concentration was 1 |iL/mL. /?/.s(2-ethylhexyl) phosphate was negative for
genotoxic effects.
Z?is(2-ethylhexyl)phosphate was not mutagenic in this assay.
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Phosphoric acid, 2-ethylhexyl ester (CASRN12645-31-7)
(1)	In bacterial reverse mutation assays, Salmonella typhimurium strains TA1535,
TA1537, TA98 and TA100 and Escherichia coli strain WP2uvrA- were exposed to
phosphoric acid, 2-ethylhexyl ester at 0, 15, 50, 150, 500, 1500 or 5000 |ig/plate for all
Salmonella strains and 0, 50, 150, 500, 1500 or 5000 |ig/plate for the Escherichia .coli
strain in the presence and absence of metabolic activation. Vehicle and positive controls
were used and produced appropriate responses. The cytotoxic concentration was 5000
|ig/plate for TA100 in the presence and absence of metabolic activation. No cytotoxic
concentration was noted for Wp2uvrA-. No increase in revertants was evident.
Phosphoric acid, 2-ethylhexyl ester was not mutagenic in this assay.
(2)	In mutation assays, Salmonella typhimurium strains TA1535, TA1537, TA1538,
TA98 and TA100 and Saccharomyces strain D4 were exposed to phosphoric acid, 2-
ethylhexyl ester at 0.001 - 5 |ig/plate (solvent control) in the presence and absence of
metabolic activation. Positive controls were tested but their responses were not provided.
The cytotoxic concentration was 5 |ig/plate, in the presence and absence of metabolic
activation for the bacterial tester strains. Phosphoric acid, 2-ethylhexyl ester was
negative in these assays.
Phosphoric acid, 2-ethylhexyl ester was not mutagenic in this assay.
Sub-Category III
Triisobutylphosphate (CASRN 126-71-6)
In three bacterial reverse mutation assays, Salmonella typhimurium strains TA98, TA100,
TA1535, TA1537 and TA1538 (only present in one of the three studies) were exposed to
triisobutyl phosphate at 20 - 5000 |ig/plate (Standard Plate Assay) and at 15 - 5000
|ig/plate (Preincubation Test) in assay one, 10 - 5000 |ig/plate in study two and up to 5
mg/plate in assay three, all in the presence and absence of metabolic activation. No other
information was provided. Triisobutyl phosphate showed negative results in these
assays.
Triisobutyl phosphate was not mutagenic in these assays.
Tributylphosphate (CASRN 126-73-8, supporting chemical)
Salmonella typhimurium strains TA102 and TA2638 and Escherichia coli strains
WP2/pKM101 and WP2uvr/pKM101were exposed to tributyl phosphate at 0, 31.3, 78,
125, 250, 313, 500, 625, 1000, 1250, 2000, 2500 or 5000 |ig/plate in the presence and
absence of metabolic activation. Positive controls were tested, but their responses were
not provided. No cytotoxic concentration was provided. Tributyl phosphate showed
negative results in these assay.
Tributyl phosphate was not mutagenic in this assay.
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Genetic Toxicity - Chromosomal Aberrations
In vitro
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
In NTP studies, Chinese hamster ovary cells were exposed to //7.s(2-ethylhexyl)
phosphate at 25.1, 37.5 and 50 |ig/mL in the absence of metabolic activation and at 839,
1253 and 1670 |ig/mL in the presence of metabolic activation. There was no significant
increase in cell with aberrations. Positive and negative controls responded appropriately.
No increase in aberrant cells was noted at any concentration.
7ra(2-ethylhexyl) phosphate did not induce chromosomal aberrations in these
assays.
Sub-Category II
Data gap
Sub-Category III
Tributylphosphate (CASRN 126-73-8, supporting chemical)
Two cytogenetic assays were conducted, one using CHO-K1 cells and concentrations up
to 0.15 |iL/mL and the other with mouse embryos at 45 and 144 hours after conception.
No other details were provided.
Tributyl phosphate did not induce chromosomal aberrations in these assays.
In vivo
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
(1)	In an NTP study, B6C3F1 mice (5 males/dose) were administered //'/.s(2-ethylhexyl)
phosphate via intraperitoneal injection at 0 (corn oil control), 500, 1000, 2000 or 3000
mg/kg-bw. At 24 and 48 hours, animals were sacrificed, bone marrow samples collected
and scored for the occurrence of micronucleated PCE and PCE/erythrocyte ratios. A
positive control was tested and produced an appropriate response. No increase in
micronuclei was noted at any concentration.
7ra(2-ethylhexyl) phosphate did not induce chromosomal aberrations in this assay.
(2)	In an NTP study, B6C3F1 mice (8 males/dose) were exposed to /m(2-ethylhexyl)
phosphate via intraperitoneal injection at 0 (vehicle control), 1250, 2500 or 5000 mg/kg-
bw. At 24 and 48 hours, animals were sacrificed, bone marrow samples collected and
scored for the occurrence of micronucleated PCE and PCE/erythrocyte ratios. Positive
controls were used and produced an appropriate response. 7ra(2-ethylhexyl) phosphate
was negative in this assay.
Tris(2-ethylhexyl) phosphate did not induce chromosomal aberrations in this assay.
Sub-Category III
Triisobutylphosphate (CASRN 126-71-6)
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CD-I mice (5/sex/dose/sampling time) were administered triisobutyl phosphate by the
intraperitoneally at 0, 300, 600 or 1200 mg/kg-bw. At 24, 48 and 72 hours, animals were
sacrificed, bone marrow samples collected and scored for the occurrence of
micronucleated PCE and PCE/erythrocyte ratios. The high dose did not induce increases
in frequency of micronucleated PCEs. Positive controls were tested, but their responses
were not provided.
Triisobutyl phosphate did not induce chromosomal aberrations in this assay.
Additional Information
Skin Irritation
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
In two skin irritation studies in rabbits, //7.s(2-ethylhexyl) phosphate was considered
irritating. One test, (dose and number of animals unspecified), treated skin on the
rabbit's ear. Moderate erythema (redness) that persisted for 1 week was noted in a study
where 250 mg was applied to clipped skin on the back study. (Limited study details were
provided)
7ra(2-ethylhexyl) phosphate was irritating to rabbit skin in this study.
Sub-Category II
Bis(2-ethylhexyl)phosphate (CASRN298-07-7)
(1)	Rabbits (6, sex, strain not specified) were administered 0.5 mL of the test substance
dermally on to clipped intact and abraded skin under occluded conditions for 24 hours
and assessed for up to 14 days after exposure. Effects included erythema and edema
(swelling). The study concluded the substance was highly irritating.
Z?is(2-ethylhexyl) phosphate was irritating to rabbit skin in this study.
(2)	Rabbits (6, sex, strain not specified) were administered 0.5 mL of the test substance
dermally on to clipped, intact skin under occluded conditions for 48 hours. There was
redness and swelling reported. Test sites for all animals were blanched at 4 hours, but
had recovered at the 48-hour observation.
Z?is(2-ethylhexyl) phosphate was irritating to rabbit skin in this study.
(3)	Rabbits (6, sex, strain not specified) were administered 0.5 mL of the test substance
dermally on to clipped, intact skin under occluded conditions for 24 hours and assessed
for up to 72 hours after exposure. There was no irritation observed.
Z?is(2-ethylhexyl) phosphate was not irritating to rabbit skin in this study.
Mono(2-ethylhexyl) phosphate (CASRN 1070-03-7, Supporting Chemical)
Albino rabbits (3, sex, strain not specified) were administered mono(2-ethylhexyl)
phosphate dermally on to clipped, intact skin under occluded conditions and assessed at
4, 24, 48, 72, 120 and 168 hours according to the Draize method. The compound was
classified as corrosive. No change was observed at termination.
Mono(2-ethylhexyl) phosphate was corrosive to rabbit skin in this study.
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Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
Two skin irritation studies were conducted in rabbits. The test substance was irritating to
rabbit skin in one study but not irritating in the second study. (Limited information was
provided.)
Triisobutyl phosphate was irritating to rabbit skin in this study.
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
Ten tests were conducted in rabbits, guinea pigs and rats. Values ranged from slightly
irritating to highly irritating. (Limited details were available.)
Tributyl phosphate was irritating to rabbit, guinea pig and rat skin in this study.
Eye Irritation
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
Rabbits (number, sex, strain not specified) were instilled 0.01 - 0.5 mL //7.s(2-ethylhexyl)
phosphate into the eye . Slight conjunctivitis was seen up to 0.05 mL and moderate
conjunctivitis was seen at > 0.1 mL which cleared up within 24 hours.
7ra(2-ethylhexyl) phosphate was not irritating to rabbit eyes in this study.
Sub-Category II
Bis(2-ethylhexyl)phosphate (CASRN298-07-7)
(1)	Six rabbits (strain, sex not specified) were instilled />/.v(2-ethylhexyl) phosphate (0.1
mL) into the right eye. The treated eyes remained unwashed. Irritation was scored at 1,
2, 3, 4, 5, 6 and 7 days after instillation. Effects on the cornea, iris and conjunctiva were
noted.
Z?is(2-ethylhexyl) phosphate was corrosive to rabbit eyes in this study.
(2)	Six rabbits (strain, sex not specified) were instilled 6/'s(2-ethylhexyl) phosphate (0.1
mL) into one eye. Three treated eyes remained unwashed, while the other three were
washed for 1 minute with warm water 20 seconds after instillation. The treated eyes were
scored for irritation at 1, 24, 48 and 72 hours after treatment. Cornea, iris and
conjunctiva effects were noted in washed and unwashed eyes.
Z?is(2-ethylhexyl) phosphate was highly irritating to rabbit eyes in this study.
Mono(2-ethylhexyl) phosphate (CASRN 1070-03-7, Supporting Chemical)
(1)	Three rabbits (strain, sex not specified) were instilled mono(2-ethylhexyl) phosphate
(0.01 mL) into one eye. Evaluations at 1, 24, 48 and 72 hours after treatment found that
the test substance was corrosive. The corneal opacity did not improve within 10 days,
suggesting possible irreversible/corrosive effects.
Mono(2-ethylhexyl) phosphate was corrosive to rabbit eyes in this study.
(2)	Six rabbits (strain, sex not specified) were instilled mono(2-ethylhexyl) phosphate
(0.01 mL) into one eye. The eyes remained unwashed. Evaluations were made at 1, 24,
25

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September, 2009
48, 72, 120 and 168 hours according to the Draize method. The test material was
corrosive. At 240 hours, opalescent areas of corneal cloudiness were still present with
iris hemorrhagic and showing reaction to light.
Mono(2-ethylhexyl) phosphate was corrosive to rabbit eyes in this study.
(3) Three rabbits (strain, sex not specified) were instilled mono(2-ethylhexyl) phosphate
(0.01 mL) into one eye. Evaluations were made at 24, 48 and 72 hours after treatment.
Erythema and edema of the cornea and moderate opacity were observed. The test
substance was classified as corrosive. The irritating effects were reversed in 5 - 7 days.
Mono(2-ethylhexyl) phosphate was corrosive to rabbit eyes in this study.
Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
Two eye irritation studies of triisobutyl phosphate were conducted in rabbits. Results
were not irritating in one study and irritating in a second study. No other information
was provided.
Triisobutyl phosphate was irritating to rabbit eyes in this study.
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
Four studies were conducted in rabbits. Values ranged from slightly irritating to
irritating. No other information was provided.
Tributyl phosphate was irritating to rabbit eyes in this study.
Sensitization
Sub-Category III
Triisobutyl phosphate (CASRN 126-71-6)
Three sensitization studies were conducted in guinea pigs using the Buehler Test, Guinea
Pig Maximization Test and an unspecified method. No other information was provided.
All three studies classified the test substance as sensitizing.
Triisobutyl phosphate was a dermal sensitizer in guinea pigs.
Tributyl phosphate (CASRN 126-73-8, Supporting Chemical)
(1)	Tributyl phosphate was not sensitizing in an open epicutaneous test in guinea pigs. No
additional information available. In a second test a "standard sensitization test" was
positive in 6 out of 15 guinea pigs. No further data was presented.
Tributyl phosphate was a dermal sensitizer in guinea pigs in this study.
(2)	In a patch test, 15 applications of tributyl phosphate were applied as less than 25%
formulation to 53 volunteers, on alternate days. No volunteer gave local reactions 24
hours after the final patch, therefore no evidence of sensitization. No additional
information available.
Tributyl phosphate was not a dermal sensitizer in humans in this study.
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September, 2009
Carcinogenicity
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
(1)	In an NTP study, Fischer 344 rats (50/sex/dose) were administered //7.s(2-ethylhexyl)
phosphate via gavage at 0, 2000 or 4000 mg/kg-bw/day (males) and 0, 1000 or 2000
mg/kg-bw/day (females) in corn oil 5 days/week for 2 years. No clinical signs of
toxicity, changes in survival or evidence of carcinogenicity in female rats were noted.
Treatment-related effects in males included lower mean body weights throughout the
study. A dose-related increase in the incidence of pheochromocytoma of adrenal glands
and a positive trend for increased incidence of thyroid follicular cell hyperplasia was
observed. The NTP study concludes there was equivocal evidence of carcinogenesis
(adrenal gland medulla) in male rats but no evidence in female rats. The high dose of
corn oil (10 ml/kg) used as a vehicle in gavage may have decreased the background of
some age-related tumors in this study and it was not clear the increased neoplasms were
related to treatment with CASRN 78-42-2.
7ra(2-ethylhexyl) phosphate showed equivocal evidence of carcinogenicity in male
rats in this study.
(2)	In an NTP study, B6C3F1 mice (50/sex/dose) were administered /ra(2-ethylhexyl)
phosphate via gavage at 0, 500 or 1000 mg/kg-bw/day in corn oil 5 days/week for 2
years. An increased incidence of follicular cell hyperplasia of the thyroid gland was
noted in males and females and an increased incidence of hepatocellular carcinoma was
noted in females. No clinical signs of toxicity, depression in body weight or changes in
survival were noted. The NTP study concludes there was some evidence of
carcinogenesis in female mice (hepatocellular carcinoma) but no evidence in male mice.
The increased tumor incidence in females was only moderately increased and significant
only at the high dose. There is no mode of action analysis available, but this type of liver
cancer in rodents may involve the peroxisome proliferator-activated receptor a (PPARa).
This mode of action is specific to rodents and would not be not be relevant to humans.
7ra(2-ethylhexyl) phosphate showed some evidence of carcinogenicity in female
mice in this study.
Conclusion
Sub-Category I: Acute oral toxicity of CASRN 78-42-2 to rats and rabbits, acute
inhalation toxicity to guinea pigs and acute dermal toxicity to rabbits is low. This
chemical is irritating to rabbit skin, and not irritating to rabbit eyes. In the oral repeated-
dose studies, rats and mice exposed to CASRN 78-42-2 at doses greater than or equal to
1550 mg/kg-day had body weight losses; the NOAEL for systemic toxicity was 430
mg/kg-day. One study of repeated-dose inhalation exposures in guinea pigs showed
histological changes in the kidney at 0.0096 mg/L/day; the NOAEL for systemic toxicity
was 0.0016 mg/L/day. No data are available for the reproductive/developmental toxicity
endpoints. This chemical did not induce gene mutations or chromosomal aberrations in
vitro. CASRN 78-42-2 showed some evidence of carcinogenicity in rats and mice which
is considered equivocal.
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The reproductive and developmental toxicity endpoints remain as data gaps for the
purposes of the HPV Challenge Program.
Sub-Category IT. Acute oral toxicity of CASRN 298-07-7 and CASRN 12645-31-7
(mixture) to rats and acute dermal toxicity of CASRN 298-07-7 and supporting chemical
CASRN 1070-03-7 to rabbits is low. CASRN 298-07-7 and supporting chemical CASRN
1070-03-7 are irritating to rabbit skin and corrosive to rabbit eyes. No data are available
for the repeated-dose, reproductive and developmental toxicity endpoints for this sub-
category. CASRN 298-07-7 and CASRN 12645-31-7 did not induce gene mutations in
vitro. No data are available for the chromosomal aberrations endpoint for this sub-
category.
The chromosomal aberrations, repeated-dose, reproductive and developmental toxicity
endpoints remain as data gaps for the purposes of the HPV Challenge Program.
Sub-Category III: Acute oral toxicity of CASRN 126-71-6 and CASRN 126-73-8
(supporting chemical) to rats and mice and acute dermal toxicity to rabbits and guinea
pigs are low. Acute inhalation toxicity of CASRN 126-71-6 in rats is low in one study.
Both chemicals in the sub-category are irritating to rat, rabbit, human and guinea pig
skin, are irritating to rabbit eyes and are dermal sensitizers in guinea pigs but not in
humans. Oral repeated-dose studies of rats administered CASRN 126-71-6 showed
limited hematological and clinical chemistry effects at 346 mg/kg-day; the NOAEL for
systemic toxicity was 68 mg/kg-day. Oral repeated-dose studies of rats administered
CASRN 126-73-8 (supporting chemical) showed hematology and histopathological
changes of the urinary bladder at 68 mg/kg-day; the NOAEL for systemic toxicity was
13.8 mg/kg-day. In a two-generation oral reproductive toxicity study in rats, CASRN
126-73-8 (supporting chemical) showed no reproductive toxicity, and the NOAEL for
reproductive toxicity was 225 mg/kg-day. In the same study, there was developmental
(pre- and postnatal) toxicity at 225 mg/kg-day as demonstrated by reduced pup weights;
the NOAEL for developmental toxicity was 53mg/kg-day. Both chemicals in this sub-
category did not induce gene mutations in vitro and did not induce chromosomal
aberrations in vitro or in vivo. No evidence of neurotoxicity was seen for the supporting
chemical, CASRN 126-73-8. The supporting chemical showed evidence of
carcinogenicity in rats.
No data gaps were identified for the purposes of the HPV Challenge Program.
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September, 2009
Tabic 4. Summary of Human Health Data

Sub-Category I
Sub-Category II
Sub-Category III
Endpoints
7'ra(2-cthylhcxyl)
phosphate
(78-42-2)
/iis(2-cthvlhc\yl)
phosphate
(298-07-7)
Phosphoric acid,
2-cthylhcxyl ester
(12645-31-7)
Mono(2-cthyl-
hcxyl) phosphate
(1070-03-7,
supporting
chemical)
Triisobutyl
phosphate
(126-71-6)
Tributvl phosphate
(126-73-8,
supporting
chemical)
Acute Oral Toxicity
LD50 (mg/kg-bw)
37,080
1400
>300, <2000
2710
3072
3160
Acute Inhalation Toxicity
LC50 (mg/L)
450
-
-
-
>5.14
>4.24
Acute Dermal Toxicity
LDS0 (mg/kg-bw)
20,000
>2000
-
>4640
9600
9700
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
NOAEL = 430
LOAEL = 1550
Data Gap
Data Gap
-
NOAEL = 68.4 - 84.3
LOAEL = 346.1-
403.9
NOAEL =13.8
LOAEL = 68.2
Repeated-Dose Toxicity
NOAEL/LOAEL
Inhalation (mg/L/day)
NOAEL = 0.0016
LOAEL = 0.0096





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


Reproductive Toxicity




NOAEL = 225
NOAEL = 225 (hdt)
Developmental Toxicity




NOAEL = 53
LOAEL = 225
(RA)
NOAEL = 53
LOAEL = 225
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Table 4. Summary of Human Health Data

Sub-Category 1
Sub-Category II
Sub-Category III
Endpoints
7'ra(2-cthylhcxvl)
phosphate
(78-42-2)
/i
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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
Sub-Category I
Tris (2-ethylhexyl) phosphate (CASRN 78-42-2)
Zebrafish (Brachydanio rerio) were exposed to tris (2-ethylhexyl) phosphate at unspecified
nominal concentrations under static conditions for 96 hours with a reported LCo of greater than
100 mg/L. The concentration tested was above the water solubility limit; assuming exposure
concentration is the water solubility limit (saturation) for tris (2-ethylhexyl) phosphate, the no
effect concentration would be approximately 2 mg/L.
No effects at saturation
A 96-hour LC50 for fish, estimated by ECOSAR, was 0.000218 mg/L.
96-h LC50 = 0.000218 mg/L (estimated)
Sub-Category II
Bis (2-ethylhexyl) phosphate (CASRN 298-07-7)
(1)	Rainbow trout (Oncorhynchus mykiss) were exposed to bis (2-ethylhexyl) phosphate at
unspecified nominal and measured concentrations under static conditions for 96 hours.
96-h LC50 = 48-54 mg/L
(2)	Rainbow trout (Oncorhynchus mykiss) were exposed to bis (2-ethylhexyl) phosphate at
unspecified nominal concentrations under static conditions for 96 hours.
96-h LC50 = 30 mg/L
(3)	Zebra fish (Brachydanio rerio) were exposed to bis (2-ethylhexyl) phosphate at unspecified
nominal concentrations under static conditions for 96 hours.
96-h LC50 > 56 mg/L
Rainbow trout (Oncorhynchus mykiss) were exposed to bis (2-ethylhexyl) phosphate for 96 hours
in six studies reported in the ECOTOX data base (http://www.epa.gov\ecotox).
96-h LC50 = 20-56 mg/L
Phosphoric acid, 2-ethylhexyl ester (CASRN 12645-31-7)
(1) Rainbow trout {Oncorhynchus mykiss) were exposed to phosphoric acid, 2-ethylhexyl ester at
a measured concentration of 100 mg/L under semi-static conditions for 96 hours. No mortalities
were observed.
96-h LC50 > 100 mg/L
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(2) Rainbow trout (Oncorhynchus mykiss) were exposed to phosphoric acid, 2-ethylhexyl ester at
nominal concentrations of 0, 100, 499, 1026, 2026 or 5018 mg/L under static conditions for 96
hours. Measured concentrations were not provided. No test related mortalities were observed.
Cloudy water was observed.
96-h LCso > 5018 mg/L
Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
In six studies, rainbow trout (Oncorhynchus mykiss), bluegills (Lepomis macrochirus), golden
orfes (Leuciscus idus) or ricefish (Oryzias latipes) were exposed to triisobutyl phosphate under
flow-through or static conditions for 24, 48 or 96 hours. Although the studies were missing
critical data elements, they are acceptable on a weight-of-evidence basis.
96-h LCso = 17.8 - 23 mg/L
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
(1)	Rainbow trout (Oncorhynchus mykiss) were exposed to tributyl phosphate at measured
concentrations of 0 (solvent control), 1.2, 2.1, 4.3, 9.3 and 19 mg/L under static conditions for 96
hours. Mortality was 100% at 19 mg/L; no mortality was seen at lower concentrations.
96-h LCso = 11 mg/L
(2)	Summaries of 17 additional acute fish studies were presented by the sponsor. The median
lethal concentration values found in these studies ranged from 4.2 to 14.2 mg/L, but because
another adequate study was available and because the additional studies were missing critical
information and had no reliability indicators, they were not reviewed further.
Acute Toxicity to Aquatic Invertebrates
Sub-Category I
Tris(2-ethylhexyl) phosphate (CASRN 78-42-2)
No measured data were available. A 48-hour EC50 for Daphnia, estimated by ECOSAR, was
0.009 mg/L.
48-h EC50 = 0.009 mg/L (estimated)
Sub-Category II
Bis (2-ethylhexyl) phosphate (CASRN 298-07-7)
(1)	Water fleas (Daphnia magna) were exposed to his (2-ethylhexyl) phosphate at unspecified
nominal concentrations under static conditions for 48 hours.
48-h EC50 = 60.7 mg/L
(2)	Water fleas (Daphnia magna) were exposed to his (2-ethylhexyl) phosphate at unspecified
nominal concentrations under static conditions for 48 hours.
48-h EC50 > 42 mg/L
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(3) Water fleas (Daphnia magna) were exposed to his (2-ethylhexyl) phosphate in 20 studies
reported in the ECOTOX database (http://www.epa.gov\ecotox).
48-h ECso = 75 - 83.7 mg/L
Phosphoric acid, 2-ethylhexyl ester (CASRN12645-31-7)
Water fleas (Daphnia magna) were exposed to phosphoric acid, 2-ethylhexyl
concentrations of 32, 56, 100, 180 or 320 mg/L under static conditions for 48
concentrations were not provided.
48-h ECso = HO mg/L
Sub-Category III
Triisobutylphosphate (CASRN 126-71-6)
In four studies, Daphnia magna were exposed to triisobutyl phosphate for 24 or 48 hours.
Although the studies were missing critical data elements, they are acceptable on a weight-of-
evidence basis.
48-h ECso = 11 mg/L
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
(1)	Water fleas (Daphnia magna) were exposed to tributyl phosphate at measured concentrations
of 0 (DMF solvent control), 0 (negative control), 0.32, 0.75, 1.8, 3.5 and 7.8 mg/L under flow-
through conditions for 48 hours.
48-h ECso = 2.6 mg/L
(2)	Summaries of 15 additional aquatic invertebrate studies were submitted by the sponsor. The
median lethal concentration values found in these studies ranged from 1.7 to 68 mg/L, however,
the additional studies were missing critical information and had no reliability indicators and as
such, they were not reviewed further.
Toxicity to Aquatic Plants
Sub-Category I
Tris (2-ethylhexyl) phosphate (CASRN 78-42-2)
No measured data were available. A 96-hour EC50 for green algae, estimated by ECOSAR, was
0.000798 mg/L.
48-h EC50 = 0.000798 mg/L (estimated)
Sub-Category II
Bis (2-ethylhexyl)phosphate (CASRN298-07-7)
Algae (Chlorella emersonii) were exposed to his (2-ethylhexyl) phosphate at nominal
concentrations of 0, 50 or 100 mg/L under static conditions for 72 hours. Measured
concentrations were not provided.
72-h EC50 (growth) > 100 mg/L
Phosphoric acid, 2-ethylhexyl ester (CASRN 12645-31-7)
ester at nominal
hours. Measured
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U.S. Environmental Protection Agency	September, 2009
Hazard Characterization Document
(1)	Algae (Pseudokirchneriella subcapitata) were exposed to phosphoric acid, 2-ethylhexyl ester
at unspecified nominal and measured concentrations under static conditions for 72 hours.
72-h EC50 (growth) = 168 mg/L
(2)	Algae (.Pseudokirchneriella subcapitata) were exposed to phosphoric acid, 2-ethylhexyl ester
at unspecified nominal and measured concentrations under static conditions for 72 hours.
72-h EC50 (biomass) = 161 mg/L
Sub-Category III
Triisobutylphosphate (CASRN126-71-6)
In nine studies, algae (Scenedesmus subspicatus) were exposed to triisobutyl phosphate for 72
hours. Although the studies were missing critical data elements, they are acceptable on a weight-
of-evidence basis.
72-h EC50 (biomass) = 33 mg/L
72-h EC50 (growth) = 34 mg/L
Tributylphosphate (CASRN 126-73-8, Supporting Chemical)
In seven different aquatic plants (Chlorella vulgaris, Microcystis aeruginosa, Scenedesmus
quadricauda, Scenedesmus subspicatus, Pseudokirchneriella subcapitata, Chlorella emersonii
and phytoplankton) were exposed to tributyl phosphate for (2, 3, 4, 7, 8 or 14 days). Although
the studies were missing critical data elements, they are acceptable on a weight-of-evidence
basis. Values below are from a study of Scenedesmus subspicatus; other EC50 values ranged
from 3.1 to 10 mg/L.
72-h EC50 (biomass) = 1.1 mg/L
72-h EC50 (growth) = 2.8 mg/L
Chronic Toxicity to Fish
Sub-Category I
Tris (2-ethylhexyl) phosphate (CASRN 78-42-2)
A chronic fish value, estimated by ECOSAR, was 0.000012 mg/L.
Chronic = 0.000012 mg/L (estimated)
Sub-Category II
Bis (2-ethylhexyl) phosphate (CASRN 298-07-7)
Rainbow trout (Oncorhynchus mykiss) were exposed to A/.s(2-ethylhexyl) phosphate at
unspecified nominal and measured concentrations for 62 days.
EC50 (early life stage) = 20.6 mg/L
Sub-Category III
Tributyl phosphate (CASRN 126-73-8, Supporting Chemical)
(1) Rainbow trout (Salmo gairdneri) were exposed to tributyl phosphate at unspecified nominal
and measured concentrations for 50 days under semi-static conditions.
Threshold concentration = 8.3 mg/L
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(2) Rainbow trout (Oncorhynchus mykiss) were exposed to tributyl phosphate at unspecified
nominal and measured concentrations for 95 days.
NOEC = 0.82 mg/L
LOEC = 1.7 mg/L
MATC = 1.2 mg/L
Chronic Toxicity to Invertebrates
Sub-Category III
Tributyl phosphate (CASRN126-73-8, Supporting Chemical)
(1)	Water fleas (Daphnia magna) were exposed to tributyl phosphate at unspecified nominal and
measured concentrations for 21 days.
21-d EC50 (immobilization) > 2.1 mg/L
21-d NOEC (length, days to first brood, Y/D/D) = 0.87 mg/L
21-d LOEC (length, days to first brood, Y/D/D) = 2.1 mg/L
21-d MATC (length, days to first brood, Y/D/D) = 1.35 mg/L
(2)	Water fleas (Daphnia magna) were exposed to tributyl phosphate at unspecified nominal and
measured concentrations for 21 days.
21-d NOEC = 1 mg/L
Conclusions:
Sub-Category I: The predicted 96-hour LC50 of CASRN 78-42-2 to fish is 0.000218 mg/L. The
predicted 48-hour EC50 of CASRN 78-42-2 to aquatic invertebrates 0.009 mg/L. The 96-hour
EC50 of CASRN 78-42-2 to aquatic plants is 0.000798 mg/L.
The acute toxicity to fish, aquatic invertebrates, and aquatic plants remain as data gaps for this
sub-category under the HPV Challenge Program.
Sub-Category II: The 96-hour LC50 of CASRN 298-07-7 ranged from 20 - 56 mg/L and
CASRN 126-73-8 ranged from greater than 100 to 5018 mg/L to fish.. The 48-hour LC50 of
CASRN 298-07-7 ranged from 42 to 83.7 mg/L to aquatic invertebrates. The 48-hour LC50 of
CASRN 126-73-8 is 110 mg /L to aquatic invertebrates. The 72-hour EC50 of CASRN 298-07-7
to aquatic plants is greater than 100 mg/L. The 48-hour EC50 of CASRN 12645-31-7 to aquatic
plants is 168 mg/L. The 62-day chronic value of the supporting chemical CASRN 12645-31-7 is
20.6 mg/L to fish.
Sub-Category III: The 96-hour LC50 of CASRN 126-71-6 and CASRN 126-73-8 ranged from
11 to 23 mg/L to fish. The 48-hour EC50 of CASRN 126-71-6 CASRN 126-73-8 is 11 and 2.6
mg/L respectively to aquatic invertebrates. The 72-hour EC50 of CASRN 126-71-6 CASRN 126-
73-8 ranged from 1.1 to 33 mg/L (biomass) and 2.8 to 34 mg/L (growth) to aquatic plants. The
95-day MATC of CASRN 126-73-8 is 1.2 mg/L to fish. The 21-day MATC of CASRN 126-73-8
is 1.2 mg/L to aquatic invertebrates.
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September, 2009
Table 5. Summary of Environmental Effects - Aquatic Toxicity Data

Sub-Category I
Sub-Catcgorv II
Sub-Catc
40ry III
Endpoints
7W.v(2-ethylhexyl)
phosphate
(78-42-2)
/iis(2-cthylhcxyl)
phosphate
(298-07-7)
Phosphoric acid, 2-
ethylhexyl ester
(12645-31-7)
Triisobutyl
phosphate
(126-71-6)
Tributyl phosphate
(126-73-8,
supporting
chemical)
Fish
96-h LCS0 (mg/L)
0.000218
(e)
30
> 100
17.8 - 21.5
11
Aquatic
Invertebrates
48-h ECS0 (mg/L)
0.002
(e)
60.7
110
11
2.6
Aquatic Plants
72-h ECS0 (mg/L)
(growth)
(biomass)
0.0005
(e)
>100
168
161
34
33
2.8
1.1
Chronic Toxicity
to Fish
0.000012
(e)
20.6
(Threshold
concentration, 62-d)
No Data
20.6
(Threshold
concentration, 62-d)
(RA)
No Data
NOEC (95-d) = 0.82
LOEC (95-d) = 1.7
MATC (95-d) = 1.2
(RA)
NOEC (95-d) = 0.82
LOEC (95-d) = 1.7
MATC (95-d) = 1.2
Chronic Toxicity to
Invertebrates
21-day ECS0 (mg/L)



No Data
>2.1b
NOEC0 = 0.87
LOEC0 = 2.1
MATC0 = 1.35
(RA)
>2.1b
NOEC = 0.87
LOEC = 2.1
MATC = 1.35
aNES = No effects at saturation (water solubility limit); Based on immobilization; °Based on length, days to first brood, (Y/D/D); (m) = measured data (i.e.,
derived from testing); (e) = estimated data (i.e., derived from modeling); (RA) = Read Across; Shaded cells = non-sponsored substances (proposed supporting
chemicals)
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