U.S. Environmental Protection Agency
Hazard Characterization Document
December, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
SPONSORED CHEMICAL
2,2',2",2m-(l-Ethane-diyldinitrilo)tetrakisacetonitrile (CASRN 5766-67-6)
SUPPORTING CHEMICAL
Propylenediaminetetraacetonitrile (CASRN 110057-45-9)
The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary
initiative aimed at developing and making publicly available screening-level health and
environmental effects information on chemicals manufactured in or imported into the United
States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship
entailed the identification and initial assessment of the adequacy of existing toxicity
data/information, conducting new testing if adequate data did not exist, and making both new
and existing data and information available to the public. Each complete data submission
contains data on 18 internationally agreed to "SIDS" (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
1	U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
2	U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
3	U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.

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U.S. Environmental Protection Agency
Hazard Characterization Document
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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.
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Hazard Characterization Document
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Chemical Abstract Service
Registry Number
(CASRN)
Sponsored Chemcial
5766-67-6
Supporting Chemical
110057-45-9
Chemical Abstract Index
Name
Sponsored Chemcial
2,2,,2M,2,M-(l-Ethane-diyldinitrilo)tetrakisacetonitrile
(EDTN)
Supporting Chemical
Propylenediaminetetraacetonitrile (PDTN)
Structural Formula
\
r\ a
-J	\	N
V
(EDTN)
1	N	N
V
(PDTN)
CASRN 5766-67-6 is a solid material that has high water solubility and low vapor pressure. It is
expected to have moderate mobility in soil. Volatilization is considered low based on the
estimated Henry's Law constant. The rate of hydrolysis is considered negligible based upon data
from the supporting chemical, CASRN 110057-45-9. The rate of atmospheric photooxidation is
considered moderate. It is expected to have moderate persistence (P2) and low bioaccumulation
potential (Bl).
Acute oral and acute dermal toxicity of the supporting chemical, CASRN 110057-45-9, to rats is
low. CASRN 110057-45-9 is not irritating to rabbit skin and is not a dermal sensitizer in guinea
pigs. Repeated oral exposure of rats to CASRN 110057-45-9 resulted in a slightly decreased
survival in females and increased liver enzyme, increased relative liver weight (males only) and
minimal hepatocellular hypertrophy in both sexes with a LOAEL of 1000 mg/kg-bw/day. In a
combined reproductive/developmental toxicity screening test, maternal toxicity was seen at 500
mg/kg-bw/day; however, no reproductive or developmental effects were noted with aNOAEL of
500 mg/kg-bw/day, the highest dose tested. CASRN 110057-45-9 did not induce gene mutations
in bacteria and did not induce chromosomal aberrations in mammalian cells in vitro.
The acute toxicity values of CASRN 110057-45-9 (supporting chemical) for fish, aquatic
invertebrates, and aquatic plants are >100 mg/L.	
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Hazard Characterization Document
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The sponsor, Akzo Nobel Functional Chemicals, Inc., submitted a Test Plan and Robust
Summaries to EPA for 2,2',2",2"'-(l-ethane-diyldinitrilo)tetrakisacetonitrile (EDTN) [CASRN
5766-67-6] on December 26, 2002. EPA posted the submission on the ChemRTK HPV
Challenge website on January 24, 2003
(http ://www. epa. gov/chemrtk/pub s/ summaries/acetonit/c 1417 9tc.htm).
EPA comments on the original submission were posted to the website on May 28, 2003. Public
comments were also received and posted to the website. The sponsor submitted updated/revised
documents on July 11, 2003, which were posted to the ChemRTK website on August 21, 2003.
The sponsor proposed reduced health effects testing, claiming that EDTN is a closed-system
intermediate (CSI) under the HPV Challenge Program. EPA's evaluation of the original and
revised/updated information indicated that the chemical does not meet the criteria to fully
support the CSI status for this chemical and that the chemical does not qualify for reduced
testing. Therefore data for reproductive toxicity are needed for the purposes of the HPV
Challenge Program. The sponsor did not submit data for developmental toxicity and proposed in
its revised test plan (dated July 11, 2003) to conduct a combined reproductive/developmental
toxicity screening test on EDTN. EPA has not received these data to date.
Justification for Supporting Chemical
The sponsor submitted data for propylenediaminetetraacetonitrile (PDTN) (CASRN 110057-45-
9) as a supporting chemical. EDTN and PDTN have similar chemical structures with the only
difference being that PDTN has one more carbon atom between the two nitrogen atoms. Both
chemicals have four identical acetonitrile groups which determine the function and reactivity of
EDTN and PDTN. Due to the similarity, EDTN and PDTN have similar physical/chemical
properties. As expected, the structural similarity in structure, physical/chemical properties and
reactivity suggests that EDTN and PDTN will be metabolized in similar pathways indicating
that the toxicity profile of these structurally similar chemicals is expected to be the same.
Therefore, EPA agrees with the use of PDTN to address data gaps for EDTN for the purposes of
the HPV Challenge Program, and ChAMP.
1. Chemical Identity
1.1 Identification and Purity
The HPV submission4 for this chemical did not include information on purity in the Test Plan
(2003). However, where indicated in robust summaries the purity of the test material (CASRN
110057-45-9, Supporting Chemical) was 99.2% (July 2003).
4Akzo Nobel Functional Chemicals, Inc.,ny (2003). EDTN Robust SummariesCASRN 5766-67-6.
http ://www. epa. gov/chemrtk/pub s/ summaries/acetonit/c 1417 9tc. htm

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Hazard Characterization Document
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1.2 Physical-Chemical Properties
The physical-chemical properties of CASRN 5766-67-6 (EDTN) and 110057-45-9 (PDTN) are
summarized in Table 1. CASRN 5766-67-6 is a solid material that has high water solubility and
low vapor pressure.
Table 1. Physical-Chemical Properties of EDTN and PDTN1
Property
EDTN
PDTN
CASRN
5766-67-6
110057-45-9
Molecular Weight
216.2
230.2
Physical State
Solid
Solid
Melting Point
159°C (estimated);
128°C (measured)2
73-74°C (measured)
Boiling Point
427°C (estimated)
Decomposes above 231°C
(measured)
Vapor Pressure
7.5x10"" mm Hg at 25°C
(estimated)
3.19x10""mm Hg at 25°C
(estimated)
1.43xl0"3 mm Hg at 20°C
(measured)
Water Solubility
1 x 106 mg/L at 25°C (estimated)
1 x 106 mg/L at 25°C (estimated)
1,670 mg/L at 18°C (measured)
Dissociation Constant
(PKa)
-2.5 (estimated)3
2.5 (estimated)3
Henry's Law Constant
7.1 x 10"22 atm-nrVmole
(estimated)4
9.4xl0"22 atm-m3/mole
(estimated)4
Log K0w
-2.17 (estimated)
-1.68 (estimated)
-1.3 (measured)
1 Akzo Nobel Functional Chemicals, Inc. July 23, 2003. Revised Robust Summary and Test Plan for Acetonitrile,
2,2',2",2"'-(l,2-ethanediyldinitrilo)tetrakis-. http://www.epa.gov/chemrtk/pubs/summaries/acetonit/cl4179tc.htm.
2SRC. The Physical Properties Database (PHYSPROP). Syracuse, NY: Syracuse Research Corporation. Access
October 15, 2008. http://www.svrres.com/esc/phvsprop.htm.
3SPARC. 2008. Online pKa and Property Calculator v. 4.2.1405-s4.2.1408. Accessed October 27, 2008.
http://ibmlc2.chem.uga.edu/sparc/.
4U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. U.S. Environmental
Protection Agency, Washington, DC, USA. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
2. General Information on Exposure
2.1 Production Volume and Use Pattern
EDTN (CASRN 5766-67-6) had an aggregated production and/or import volume in the United
States of 10 to 50 million pounds during the calendar year 2005.
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Hazard Characterization Document
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The IUR information submitted on the industrial processing and use, and commercial and
consumer use was all claimed as confidential. The HPV submission states that the chemical is
primarily used as a chemical intermediate.
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. CASRN 5766-67-6 is a solid material
that has high water solubility and low vapor pressure. It is expected to have moderate mobility
in soil. Volatilization is considered low based on the estimated Henry's Law constant. The rate
of hydrolysis is considered negligible based upon data from the supporting chemical, CASRN
110057-45-9. The rate of atmospheric photooxidation is considered moderate. It is expected to
have moderate persistence (P2) and low bioaccumulation potential (Bl).
Table 2. Environmental Fate Characteristics of EDTN and PDTN1
Property
EDTN
PDTN
CASRN
5766-67-6
110057-45-9
Photodegradation Half-
life
4.6 hours (estimated)
4.4 hours (estimated)
Hydrolysis Half-life
No data
5.3 years at pH 4 and 25°C;
3.9 years at pH 7 and 25°C;
0.3 years at pH 9 and 25°C
Biodegradation
No data (not readily
biodegradable) (RA)
0% after 28 days (not readily
biodegradable)
Bioconcentration
BCF = 3.2 (estimated)2
BCF = 3.2 (estimated)2
Log Koc
3.3 (estimated)2
3.6 (estimated)2
Fugacity
(estimated for analogs
using Level III Model)
Air = <0.01%
Water = 39.8%
Soil = 60.2%
Sediment = 0.01%
Air = <0.01%
Water = 49.5%
Soil = 50.4%
Sediment = 0.09%
Persistence3
P2 (moderate)
P2 (moderate)
Bi oaccumul ati on3
Bl (low)
Bl (low)
1 Akzo Nobel Functional Chemicals, Inc. July 23, 2003. Revised Robust Summary and Test Plan for Acetonitrile,
2,2',2",2"'-(l,2-ethanediyldinitrilo)tetrakis-. http://www.epa.gov/chemrtk/pubs/summaries/acetonit/cl4179tc.htm.
2U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. U.S. 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.
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Hazard Characterization Document
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3. Human Health Hazard
The human health hazard data are summarized in Table 3.
Acute Oral Toxicity
PDTN (CASRN110057-45-9, Supporting Chemical)
Wistar rats (3/sex/dose) were administered PDTN in polyethylene glycol via gavage at 2000
mg/kg-bw and observed for 15 days. One of three females died on day 3.
LD50 > 2000 mg/kg-bw
Acute Dermal Toxicity
PDTN (CASRN 110057-45-9, Supporting Chemical)
Wistar rats (5/sex/dose) were administered PDTN dermally at 2000 mg/kg-bw under unspecified
conditions for 24 hours and observed for 15 days. There was no mortality.
LD50 > 2000 mg/kg-bw
Repeated-Dose Toxicity
PDTN (CASRN 110057-45-9, Supporting Chemical)
Wistar rats (10/sex/dose) were administered PDTN in polyethylene glycol via gavage at 50, 200
or 1000 mg/kg-bw/day, once daily, 7 days/week, for 28 days. One female from the high-dose
group died on day 23 of the study. At the high dose, changes in clinical chemistry included a
significant increase in alanine aminotransferase (ALT) activity of males and females. High-dose
males showed a significant increase in liver-to-body-weight ratio and minimal-to-slight
centrilobular hepatocellular hypertrophy was observed in males and females in the high dose
group.
LOAEL = 1000 mg/kg-bw/day (based on liver effects and decreased survival)
NOAEL = 200 mg/kg-bw/day
Reproductive/Developmental Toxicity
In a combined reproductive/developmental toxicity screening test, Wistar rats (10/sex/dose) were
administered EDTN via gavage at 0, 50, 250 or 750 mg/kg-bw/day, once daily, 7 days/week
during 2 weeks prior to mating, through mating (males), gestation and lactation until post-partum
day 4 (females). The high dose for females was decreased to 500 mg/kg-bw/day after 13 days of
treatment. Males were dosed for 35 days and females were dosed for 42 days. Parental toxicity
indicated by mortality (1 female), trend toward decreased body weight and body gain (both
sexes), decreased food consumption (females) and pigmented, mottled kidneys (females) at
750/500 mg/kg-bw/day. Percent pup survival was decreased at 500 mg/kg-bw/day (because one
dam had only 3 of 14 pups survive). No treatment-related effects were noted in ovaries, testes or
epididymides during microscopic examination. No other reproductive effects were seen. No
statistically significant differences were detected among the groups in mean corpora lutea,
implantation sites, liter size, and mean number of pus born or alive on postnatal day 0. Percent
pre- and post-implantation losses were not statistically different across the groups.
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LOAEL for Parental Toxicity = 750/500 mg/kg-bw/day (based on mortality and effects on
body weight and food consumption)
NAOEL for Maternal Toxicity = 250 mg/kg-bw/day
NOAEL for Reproductive/Developmental Toxicity = 500 mg/kg-bw/day (based on no effects
at the highest dose tested)
Genetic Toxicity — Gene Mutation
In vitro
PDTN (CASRN110057-45-9, Ssupporting chemical)
In a bacterial reverse mutation assay, Salmonella typhimurium strains TA1535, TA1537, TA98
and TA100 and Escherichia coli strain WP2uvrA were exposed to PDTN in dimethyl sulfoxide
at concentrations of 3, 10, 33, 100, 333, 1000, 3330 or 5000 |ig/plate in the absence of metabolic
activation and 100, 333, 1000, 3330 or 5000 |ig/plate in the presence of metabolic activation. No
toxicity was observed at any concentration with or without metabolic activation. No data
regarding the use or response of positive controls or numbers of revertants were provided.
PDTN was not mutagenic in this assay.
Genetic Toxicity — Chromosomal Aberrations
In vitro
PDTN (CASRN 110057-45-9, Supporting Chemical)
Cultured peripheral human lymphocytes were exposed to PDTN in dimethyl sulfoxide at
concentrations of 333, 1000 or 3330 |ig/mL in the absence of metabolic activation for 24- and
48-hour treatments and 100, 333, 1000, 3330 or 5000 |ig/mL in the presence of metabolic
activation for a 3-hour treatment. No toxicity was observed at any dose level with or without
metabolic activation. No data regarding the use or response of positive controls were provided.
PDTN caused no structural chromosome damage.
PDTN did not induce chromosomal aberrations in this assay.
Additional Information
Skin Irritation
PDTN (CASRN 110057-45-9, Supporting Chemical)
New Zealand White rabbits (3 males) were administered PDTN (0.5 g in water) dermally under
semi-occluded conditions for 4 hours and assessed for up to 72 hours after exposure. There were
no signs of erythema or edema at any observation period.
PDTN was not irritating to rabbit skin in this assay.
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Sensitization
PDTN (CASRN110057-45-9, Supporting Chemical)
In a guinea pig maximization test, Dunkin-Hartley guinea pigs (10 females) were administered
0.1% PDTN in the induction phase on day 1; 50% on day 8 and 50% during the challenge phase
on day 21. No further details regarding exposure conditions were provided. There was no
irritation observed at 24 and 48 hours after challenge application.
PDTN was not sensitizing in this assay.
Conclusion: Acute oral and acute dermal toxicity of the supporting chemical, CASRN 110057-
45-9, to rats is low. CASRN 110057-45-9 is not irritating to rabbit skin and is not a dermal
sensitizer in guinea pigs. Repeated oral exposure of rats to CASRN 110057-45-9 resulted in a
slightly decreased survival in females and increased liver enzyme, increased relative liver weight
(males only) and minimal hepatocellular hypertrophy in both sexes with a LOAEL of 1000
mg/kg-bw/day. In a combined reproductive/developmental toxicity screening test, maternal
toxicity was seen at 500 mg/kg-bw/day; however, no reproductive or developmental effects were
noted with a NOAEL of 500 mg/kg-bw/day, the highest dose tested. CASRN 110057-45-9 did
not induce gene mutations in bacteria and did not induce chromosomal aberrations in
mammalian cells in vitro.
4. Hazard to the Environment
The environmental hazard data are summarized in Table 3.
Acute Toxicity to Fish
PDTN (CASRN 110057-45-9, Supporting chemical)
Zebrafish (Danio rerio, 10/group) were exposed to PDTN at nominal concentrations of 100
mg/L under static conditions for 96 hours. Measured concentrations were 107 - 109 mg/L. No
mortality was observed during the study.
96-h LC50 > 100 mg/L
Acute Toxicity to Aquatic Invertebrates
PDTN (CASRN 110057-45-9, Supporting Chemical)
Water fleas (Daphnia magna, 10 - 20/group) were exposed to PDTN at nominal concentrations
of 1, 10 or 100 mg/L under static conditions for 48 hours. The measured concentration was 110
mg/L (for the nominal concentration of 100 mg/L). There was no mortality during the study.
48-h EC50 > 100 mg/L
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Hazard Characterization Document
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Toxicity to Aquatic Plants
PDTN (CASRN110057-45-9, Supporting Chemical)
Green algae (Pseudokirchneriella subcapitata) were exposed to PDTN at nominal concentrations
of 10, 18, 32, 56, 100 or 180 mg/L under static conditions for 72 hours. Measured
concentrations were 10.5, 34 and 189 mg/L (for the nominal concentrations of 10, 32 and 180
mg/L, respectively). Three replicates were tested per concentration. No data regarding control
growth were provided.
72-h EC50 (growth) = 129 mg/L
72-h EC50 (biomass) = 60 mg/L
Conclusion: The acute toxicity values of CASRN 110057-45-9 (supporting chemical) for fish,
aquatic invertebrates, and aquatic plants are >100 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
2,2\2",2'"-(l-Ethane-
diyldinitrilo)tetrakisacetonitrile
(EDTN)
(5766-67-6)
SUPPORTING CHEMICAL
Propylenediaminetetraacetonitrile
(PDTN)
(110057-45-9)
Summary of Human Health Data
Acute Oral Toxicity
LD5o (mg/kg-bw)
No Data
>2000
(RA)
>2000
Acute Dermal Toxicity
LD5o (mg/kg-bw)
-
>2000
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
No Data
NOAEL = 200 (28-d)
LOAEL= 1000 (28-d)
(RA)
NOAEL = 200 (28-d)
LOAEL = 1000 (28-d)
Reproductive/Developmental
Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
Parental Toxicity
Reproductive/Developmental
Toxicity
NOAEL = 250
LOAEL = 500/750
NOAEL = 500/750

Genetic Toxicity - Gene
Mutation
In vitro
No Data
Negative
(RA)
Negative
Genetic Toxicity -
Chromosomal Aberrations
In vitro
No Data
Negative
(RA)
Negative
Additional Information
Skin Irritation
Skin Sensitization

Not irritating
Not a sensitizer
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
No Data
>100
(RA)
> 100
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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
2,2\2",2'"-(l-Ethane-
diyldinitrilo)tetrakisacetonitrile
(EDTN)
(5766-67-6)
SUPPORTING CHEMICAL
Propylenediaminetetraacetonitrile
(PDTN)
(110057-45-9)
Aquatic Invertebrates
48-h ECso (mg/L)
No Data
>100
(RA)
> 100
Aquatic Plants
72-h ECso (mg/L)
(growth)
(biomass)
No Data
129
60
(RA)
129
60
- indicates that endpoint was not addressed for this chemical; (RA) read across
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