U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
Phosphonic acid, P-[[bis(2-hydroxyethyl)amino]methyl]-, diethyl ester
(Fyrol 6, CASRN 2781-11-5)
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,
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
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
September, 2009
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 information previously not readily available to the
public.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Chemical Abstract Service Registry Number
(CASRN)
2781-11-5
Chemical Abstracts Index Name
Phosphonic acid, [[bis(2-
hydroxyethyl)amino]methyl]-, diethyl
ester
Structural Formula
OH
Summary
CASRN 2781-11-5 is a liquid with high water solubility and low vapor pressure. It is expected
to have moderate mobility in soil. Volatilization of this chemical is considered low. The rate of
hydrolysis is considered negligible at acidic and neutral pH; however, the rate of hydrolysis is
rapid under alkaline conditions. The rate of atmospheric photooxidation is considered rapid. It
is expected to have low persistence (PI) and low bioaccumulation potential (Bl).
The acute oral toxicity of CASRN 2781-11-5 to rats and acute dermal toxicity to rabbits is low.
CASRN 2781-11-5 is slightly irritating to rabbit eyes, and not irritating or sensitizing to rabbit
skin. Repeated oral exposure of rats to CASRN 2781-11-5 for 13 weeks showed no systemic
toxicity up to 500 mg/kg-bw/day (highest dose tested). An oral combined
developmental/reproductive toxicity screening test in rats showed no maternal, reproductive or
developmental (prenatal and limited postnatal) toxicity up to 750 mg/kg-bw/day (highest dose
tested). CASRN 2781-11-5 did not induce gene mutations in bacteria. It did induce some gene
mutations in an in vitro mouse lymphoma assay and was positive in an in vitro chromosomal
aberrations assay. It did not cause acute delayed neurotoxicity in hens when tested up to 10
g/kg-bw.
For CASRN 2781-11-5, the measured 96-hour LC50 for fish is > 10,000 mg/L, the measured 48-hour EC50
for aquatic invertebrates is > 936 mg/L, and the measured 96-hour EC50 for aquatic plants is > 86 mg/L.
No data gaps were identified under the HPV Challenge Program.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
The sponsor, Akzo Nobel Functional Chemicals LLC., submitted a Test Plan and Robust
Summaries to EPA for phosphonic acid, P-[[bis(2-hydroxyethyl)amino]methyl]-, diethyl ester
(Fyrol 6, CASRN 2781-11-5) on December 19, 2003. EPA posted the submission on the
ChemRTK HPV Challenge website on February 10, 2004
(http://www.epa.gov/chemrtk/pubs/summaries/phsacdb2/cl4938tc.htm). EPA comments on the
original submission were posted to the website on June 13, 2004. Public comments were also
received and posted to the website. Supresta U.S. LLC purchased the Akzo Nobel Functional
Chemicals LLC. phosphorus chemicals flame retardant operations in July 2004 and assumed
responsibility for submitting a response and revised summaries on August 22, 2006, which were
posted to the ChemRTK website on September 21, 2006.
1. Chemical Identity
1.1	Identification and Purity
No information on purity of Fyrol 6 is indicated in the Test Plan (2003); however, where indicated in
the revised robust summaries, the purity of the test substance was approximately 75-97% (2006).
1.2	Physical-Chemical Properties
The physical-chemical properties of Fyrol 6 are summarized in Table 1.
Fyrol 6 is a liquid with high water solubility. The reported moderate vapor pressure is due to the
low molecular weight component partial pressure because the test substance vapor pressure is
estimated to be low (< lx 10"7 mm Hg).
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Table 1. Physical-Chemical Properties of Fyrol 6 (Phosphonic Acid, P-[[Bis(2-
hydroxyethyl)aminol methyl]-, Diethyl Ester1)
Property
Value
CASRN
2781-11-5
Molecular Weight
255.25
Physical State
Liquid
Melting Point
Liquid at room temperature
Boiling Point
196°C (meas. for mixture); 379 °C (est. EPIWIN)
Vapor Pressure
0.43 mm Hg at 20°C (meas. for mixture); < IE"7 (est.
EPIWIN)
Water Solubility
900,000 mg/L at 25°C (measured)
Dissociation Constant (pKa)
5.6 (estimated)2
Henry's Law Constant
1,6x 10"7 atm-mVmole (estimated)2
Log Kow
-0.72 (measured)
1 Supresta U.S. LLC. September 21, 2006. Revised Robust Summary and Test Plan for
Phosphonic Acid, [[Bis(2- Hydroxyethyl) Ami no] Methyl]-, Diethyl Ester (Fyrol 63).
http://www.epa.gov/oppt/chemrtk/pubs/summaries/phsacdb2/cl4938tc.htm.
2HSDB. 2008. Hazardous Substances Data Bank. Accessed August 22, 2008.
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB.
3Fyrol 6 product used for testing P-Chem properties was only 70 - 90% pure containing many
impurities & solvents.
http://www.supresta.com/pdfs/FYRQL%206-MSDS.pdf
2. General Information on Exposure
2.1	Production Volume and Use Pattern
This chemical had an aggregated production and/or imported volume in the United States of less
than 500,000 pounds in 2005. It was an HPV chemical in previous reporting years. Both the
HSDB and the HPV submission indicate that the chemical is primarily used as a flame retardant
for urethane and electronic laminate resin systems. The HPV submission states that this
chemical reacts with, and becomes, an integral part of the resin system during processing.
2.2	Environmental Exposure and Fate
No quantitative information is available on releases of this chemical to the environment.
The environmental fate properties are provided in Table 2. Fyrol 6 is a liquid with high water
solubility and low vapor pressure. It is expected to have high mobility in soil. Volatilization of
Fyrol 6 is considered low. The rate of hydrolysis is considered negligible at acidic and neutral
pH; however, the rate of hydrolysis is rapid under alkaline conditions. The rate of atmospheric
photooxidation is considered rapid. Fyrol 6 is expected to have low persistence (PI) and low
bioaccumulation potential (Bl).
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Table 2. Environmental Fate Characteristics of Fyrol 6 (Phosphonic acid, P-[[Bis(2-
hydroxyethyl)aminolmethyll-, Diethyl Ester1)
Property
Value
Photodegradation Half-life
0.9 hours (estimated)
Hydrolysis Half-life
5,159 days at pH 4 and 15°C (measured);
179 days at pH 4 and 25°C (measured);
87 days at pH 7 and 15°C (measured);
26 days at pH 7 and 25 °C (measured);
38 hours at pH 9 and 15 °C (measured);
14 hours at pH 9 and 25 °C (measured)
Biodegradation
15-19% in 28 days (not readily biodegradable)
Bioconcentration
BCF = 3 (estimated)2
Log Koc
1.0 (estimated)2
Fugacity
(Level III Model)
Air = 0.2%
Water = 58.3%
Soil = 41.4%
Sediment = 0.1%
Persistence3
PI (low)
•>
Bioaccumulation
B1 (low)
^upresta U.S. LLC. September 21, 2006. Revised Robust Summary and Test Plan for
Phosphonic Acid, [[bis(2- Hydroxyethyl) AminoJMethyl]-, Diethyl Ester (Fyrol 6).
http://www.epa.gov/oppt/chemrtk/pubs/summaries/phsacdb2/cl4938tc.htm.
2US EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.0.
United States Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
3Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical
Substances. Federal Register 64, Number 213 (November 4, 1999) pp. 60194-60204.
3. Human Health Hazard
The human health hazard data are summarized in Table 3.
Acute Oral Toxicity
Sprague-Dawley rats (10/sex) were administered a single oral dose of Fyrol 6 in corn oil via
gavage at 5000 mg/kg-bw and were observed for 14 days. No mortality occurred.
LD50 > 5,000 mg/kg-bw
Acute Dermal Toxicity
Stauffland albino rabbits (5/sex) were administered a single dermal dose of Fyrol 6 at 2000mg/kg
bw for 24 hours and were observed for 14 days. No mortality occurred.
LD50 > 2,000 mg/kg-bw
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Repeated-Dose Toxicity
Sprague-Dawley rats (22/sex/dose) were administered Fyrol 6 in corn oil via gavage at doses of
0, 20, 100 and 500 mg/kg-bw/day once daily, 7 days/week, for 13 weeks. No treatment-related
effects were noted..
NOAEL = 500 mg/kg-bw/day (based on no effects at the highest dose tested)
Reproductive/Developmental Toxicity
In a combined reproductive/developmental toxicity screening test, Sprague-Dawley rats
(12/sex/dose) were administered Fyrol 6 via oral gavage at doses of 0, 50, 250 and 750 mg/kg
bw/day for two weeks prior to mating, during mating period, through gestation, lactation
(females) and until sacrifice. There were no signs of systemic, reproductive or developmental
toxicity noted in either dams or pups.
NOAEL (systemic toxicity) = 750 mg/kg-bw/day (based on no effects at the highest dose
tested)
NOAEL (reproductive toxicity) = 750 mg/kg-bw/day (based on no effects at the highest dose
tested)
NOAEL (developmental toxicity) = 750 mg/kg-bw/day (based on no effects at the highest dose
tested)
Genetic Toxicity — Gene Mutation
In vitro
(1)	Salmonella typhimurium strains TA98, TA100, TA1535, TA 1537, T1538 and
saccharomyces cerevisiae D4 were exposed to Fyrol 6 at concentrations ranging from 0.01 to
10|iL/plate in the presence and absence of metabolic activation. DMSO was the vehicle. No
information on positive controls was presented in the robust summary.
Fyrol 6 was not mutagenic in this assay.
(2)	In two in vitro forward mutation assays mouse lymphoma cells (L2178Y) were exposed to
Fyrol 6 in the presence and absence of metabolic activation. The concentrations in the first assay
were 0.626 -2.5 |iL/mL (with metabolic activation) and 1.25-5 |iL/mL (without metabolic
activation). Sterile water was the vehicle. Cytotoxicity was seen at 2.5 and 5 |iL/mL. In the
second assay, the concentrations were 0.25 -1.0 |iL/mL (with metabolic activation and 0.0313 -
0.5 |iL/mL (without metabolic activation). Cytotoxicity was seen at the 0.5 |iL/mL. In both
assays, Fyrol 6 was weakly mutagenic in the presence and absence of metabolic activation.
Fyrol 6 was weakly mutagenic in these assays.
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Hazard Characterization Document
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Genetic Toxicity - Chromosomal Aberrations
In vitro
Mouse lymphoma cells (L5178Y) were reposed to Fyrol 6 at concentrations ranging from 0.25 -
2.0 |iL/mL with metabolic activation and 0.0313 - 0.5 |iL/mL without metabolic activation.
Increases in both structural and numerical chromosomal aberrations were observed at the two
highest concentrations in the presence and absence of metabolic activation.
Fyrol 6 was clastogenic in this assay.
Additional Information
Skin Irritation
Stauffland albino rabbits (6/sex) were dermally exposed to 0.5 mL Fyrol 6 for 4 hours. Irritation
was scored using Draize scoring method at 4 and 48 hours of exposure. Neither erythema nor
edema was present at any observation period.
Fyrol 6 was not irritating to rabbit skin.
Eye Irritation
Fyrol 6 (0. lmL) was instilled in the eyes of Stauffland albino rabbits (9/sex). Eyes of 3 rabbits
were washed after 20-30 seconds of exposure. Eyes of the remaining rabbits were not washed.
Irritation was scored using Draize scoring method at 24, 48, 72 hours and 4 days and 7 days
following exposure. No effects were seen in the 3 rabbits with washed eyes. The 6 rabbits with
unwashed eyes showed mild conjunctival irritation. By 72 hours, the irritation had cleared.
Fyrol 6 was slightly irritating to rabbit eyes.
Neurotoxicity
Acute delayed oral toxicity of Fyrol 6 was tested in White Leghorn hens. The hens were orally
administered two doses, three weeks apart, of Fyrol 6 via gavage in corn oil at 10 g/kg-bw. The
observation period was 43 days. Tri-ortho cresyl phosphate was used as the positive control.
Fyrol 6 did not cause delayed neurotoxicity in hens.
Conclusion: The acute oral toxicity of CASRN 2781-11-5 to rats and acute dermal toxicity to
rabbits is low. CASRN 2781-11-5 is slightly irritating to rabbit eyes, and not irritating or
sensitizing to rabbit skin. Repeated oral exposure of rats to CASRN 2781-11-5 for 13 weeks
showed no systemic toxicity up to 500 mg/kg-bw/day (highest dose tested). An oral combined
developmental/reproductive toxicity screening test in rats showed no maternal, reproductive or
developmental (prenatal and limited postnatal) toxicity up to 750 mg/kg-bw/day (highest dose
tested). CASRN 2781-11-5 did not induce gene mutations in bacteria. It did induce some gene
mutations in an in vitro mouse lymphoma assay and was positive in an in vitro chromosomal
aberrations assay. It did not cause acute delayed neurotoxicity in hens when tested up to
10 g/kg-bw.
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4. Hazards to the Environment
The environmental hazard data are summarized in Table 3.
Acute Toxicity to Fish
Rainbow trout (Oncorhynchus mykiss, 10/concentration) were exposed to Fyrol 6 at nominal test
concentrations of 1000, 1800, 3200, 5600 and 10,000 mg/L under static conditions for 96 hours.
There was 20% mortality at 3200 mg/L but none at the higher concentrations.
96-h LC50 > 10,000 mg/L
Acute Toxicity to Aquatic Invertebrates
Daphnia magna were exposed to Fyrol 6 at nominal concentrations of 63, 125, 250, 500 and
1000 mg/L under flow-through conditions for 48 hours. No treatment-related effects were seen
at any concentration tested. All test concentrations were measured, but only the measured value
for the highest concentration (936 mg/L) was provided in the robust summary.
48-h EC50 > 936 mg/L
Toxicity to Aquatic Plants
Freshwater green algae (Pseudokirchneriella subcapitata) were exposed to Fyrol 6 at nominal
concentrations of 0, 7.5, 15, 30, 60 and 120 mg/L under static conditions for 96 hours. All test
concentrations were measured, but only the measured value for the highest concentration
(86 mg/L) was provided in the robust summary.
96-h EC50 > 86 mg/L
Conclusion: For CASRN 2781-11-5, the measured 96-hour LC50 for fish is > 10,000 mg/L, the
measured 48-hour EC50 for aquatic invertebrates is > 936 mg/L, and the measured 96-hour EC50 for
aquatic plants is > 86 mg/L.
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Table 3. Summary Table of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
Phosphonic acid, P-||bis(2-
hydroxyethyl)amino|methyl|-, diethyl ester
(Fyrol 6)
(2781-11-5)
Summary of Human Health Data
Acute Oral Toxicity
LD5o (mg/kg-bw)
>5000
Acute Dermal Toxicity
LD5o (mg/kg-bw)
>2000
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
NOAEL = 500 (hdt)
Reproductive Toxicity
NOAEL/LOAEL
(mg/kg-bw/day)
Systemic/Reproductive Toxicity
NOAEL = 750 (hdt)
Developmental Toxicity
NOAEL/LOAEL
(mg/kg-bw/day)
Maternal and Developmental Toxicity
NOAEL = 750 (hdt)
Genetic Toxicity - Gene Mutation
In vitro
(Bacterial)
(Mammalian cells)
Negative
Positive
Genetic Toxicity - Chromosomal Aberrations
In vitro
Positive
Additional Information
Acute Delayed Neurotoxicity
(hen)
NOAEL = 10 g/kg
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
> 10,000
Aquatic Invertebrates
48-h ECso (mg/L)
>936
Aquatic Plants
72-h ECso (mg/L)
>86
hdt = highest dose tested; Bold = Measured data
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