U.S. Environmental Protection Agency
Hazard Characterization Document
December, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
Triglycidyl Isocyanurate
CASRN 2451-62-9
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
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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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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Chemical Abstract Service Registry Number
(CASRN)
2451-62-9
Chemical Abstract Index Name
l,3,5-Triazine-2,4,6(lH,3H,5H)-trione,
l,3,5-tris(oxiranylmethyl)-
Structural Formula
V
\ /
r\	\_
Summary
Commercial triglycidyl isocyanurate (TGIC) is a solid material consisting of approximately 76 to
80% of the a-isomer, and approximately 20 to 24% of the P-isomer, with high water solubility
and low vapor pressure. This chemical is expected to have high mobility in soil. Volatilization
of this chemical is considered low based on the estimated Henry's Law constant. The rate of
hydrolysis is considered moderate at neutral pH and rapid under acidic conditions. The rate of
atmospheric photooxidation is considered moderate. This chemical is expected to have low
persistence (PI) and low bioaccumulation potential (Bl). The a- and P-isomers would be
expected to have the same low persistence and low bioaccumulation potential but there are no
data to substantiate this assumption.
The acute toxicity of triglycidyl isocyanurate is moderate in rats by the oral route, high in mice
by the inhalation route, and low in rats by the dermal route. A repeated-dose toxicity study in
male rats showed decreases in body weight gain at 4.36 mg/kg-bw/day; the NOAEL for systemic
toxicity was 1.30 mg/kg-bw/day. No one- or two-generation reproductive or prenatal
developmental toxicity studies are available. However, decreases in sperm counts were observed
at 0.72 mg/kg-bw/day in another repeated-dose toxicity study in males, the lowest dose tested.
This chemical did not induce dominant lethality. This chemical was slightly to moderately
irritating to rabbit and guinea pig skin, severely irritating to rabbit eye, and a dermal sensitizer in
guinea pigs. This chemical induced gene mutations in vitro but not in vivo; and induced
chromosomal aberrations in vivo but was equivocal in vitro. There was no evidence of
carcinogenicity in a two-year bioassay.
For acute hazard of CASRN 2451-62-9, the 96-hour LC50 to fish is >77 mg/L, the measured 24-
hour EC50 to aquatic invertebrates is >90.6 mg/L, and the measured 72-hour EC50 (biomass) to
aquatic plants is 29 mg/L.
Reproductive and prenatal developmental toxicity studies were identified as data gaps under the
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HPV Challenge Program.
The sponsor, Huntsman-Nissan-TGIC Consortium, submitted a Test Plan and Robust Summaries
to EPA for triglycidyl isocyanurate (Araldite PT-810, CASRN 2451-62-9) on December 27,
2004. EPA posted the submission on the ChemRTK HPV Challenge website on January 19,
2005 (http://www.epa.gov/chemrtk/pubs/summaries/triglvis/cl5759tc.htm). EPA comments on
the original submission were posted to the website on April 28, 2006. Public comments were
received and posted to the website. The sponsor submitted updated/re vised documents on June
25, 2006, which were posted to the ChemRTK website on September 17, 2007.
1 Chemical Identity
1.1	Identification and Purity
Technical grade triglycidyl isocyanurate is a trifunctional epoxide resin containing
approximately 76 - 80% of the alpha-isomer and approximately 20 - 24% of the beta-isomer.
Excess epichlorhydrin reactant (oxirane, chloromethyl) may be present at concentrations up to
100 ppm.
1.2	Physical-Chemical Properties
The physical-chemical properties of commercial triglycidyl isocyanurate and the diastereomer
racemates (a-triglycidyl isocyanurate and P-triglycidyl isocyanurate) are summarized in Table 1.
Commercial triglycidyl isocyanurate (TGIC) is a solid material consisting of approximately 76 to
80%) of the a-isomer, and approximately 20 to 24%> of the P-isomer, with high water solubility
and low vapor pressure.
Table 1. Physical-Chemical Properties of Triglycidyl Isocyanurate1
Property
Triglycidyl isocyanurate2
CASRN
2451-62-9
Molecular Weight
297.27
Physical State
Solid
Melting Point
95°C (measured; may decompose)
Boiling Point
Decomposes at >250°C (measured)
Vapor Pressure
5.4* 10"8mm Hg at 20°C (measured)
Water Solubility
10,000 mg/L at 25°C (measured)
Dissociation Constant (pKa)
Not applicable
Henry's Law Constant
9.4/10-21 atm-m3/mole (estimated)3
Log Kow
-0.8 (measured)
'Huntsman-Nissan-TGIC. November 2, 2006. Revised Robust Summaries and
Test Plans for Triglycidyl Isocyanurate.
http://www.epa.gov/chemrtk/pubs/summaries/triglvis/cl5759tc.htm.
technical grade TGIC contains approximately 76to 80% of the a-isomer, and
approximately 20 to 24% of the P-isomer and may also contain excess
epichlorohydrin.
3U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft®
Windows, v3.20. United States Environmental Protection Agency, Washington,
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DC, USA. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
2 General Information on Exposure
2.1	Production Volume and Use Pattern
This chemical has an aggregated production and/or import volume in the United States of 1 to 10
million pounds.
Non-confidential information in the IUR indicated that the industrial processing and uses of this
chemical include adhesive and binding agents and intermediates. Non-confidential information
in the IUR indicated that the commercial and consumer products containing this chemical
include paints and coatings. The HSDB states this chemical is primarily used as a three-
dimensional cross linking or curing agent in polyester powder coatings (paints); it is also used in
solder "mask" inks in the printed circuit board industry. The HPV submission also states this
chemical is primarily used as a hardener for polyester-based powder coatings.
2.2	Environmental Exposure and Fate
No quantitative information is available on environmental releases.
The environmental fate properties are provided in Table 2. Triglycidyl isocyanurate is expected
to have high mobility in soil. A commercial mixture consisting of approximately 76 to 80% of
the a-isomer, and approximately 20 to 24% of the P-isomer was not readily biodegradable using
a modified Sturm (OECD 301B) or MITI (OECD 301C) test. This preparation was also not
inherently biodegradable using a modified Zahn-Wellens test (OECD 302B); however, these
results likely measured the biodegradation of triglycidyl isocyanurate and its hydrolysis product,
l,3,5-tris(2,3-dihydroxypropyl)-l,3,5-triazine-2,4,6 (lH,3H,5H)-trione. Volatilization of
triglycidyl isocyanurate is considered low based on the estimated Henry's Law constant. The
rate of hydrolysis is considered moderate at neutral pH and rapid under acidic conditions.
Triglycidyl isocyanurate is expected to have low persistence (PI) and low bioaccumulation
potential (Bl).
Table 2. Environmental Fate Characteristics of Triglycidyl Isocyanurate1
Property
Triglycidyl isocyanurate
CASRN
2451-62-9
Photodegradation Half-life
No direct photolysis expected;
7 hours (estimated)2
Hydrolysis Half-life
160 hours at pH 7 and 25°C (measured);
1 hour at pH 2 and 25 °C (measured)
Biodegradation
0% after 28 days (not readily biodegradable);
9-48% after 28 days (not readily biodegradable);
44% after 28 days (not inherently biodegradable);
0-3% after 28 days (not readily biodegradable)3
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Bioconcentration
BCF = 3.2 (estimated)2
Log Koc
1 (estimated)2
Fugacity

(Level III Model)

Air
0.665%
Water
47.8%
Soil
51.5%
Sediment
0.102%
Persistence4
PI (low)
Bioaccumulation4
B1 (low)
1 Huntsman-Nissan-TGIC. November 2, 2006. Revised Robust Summaries and Test
Plans for Triglycidyl Isocyanurate.
http://www.epa.gov/chemrtk/pubs/summaries/triglvis/cl5759tc.htm.
2U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows,
v3.20. United States Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
3National Institute of Technology and Evaluation. 2002. Biodegradation and
Bioaccumulation of the Existing Chemical Substances under the Chemical Substances
Control Law. http://www.safe.nite.go.ip/english/kizon/KIZON start hazkizon.html.
4Federal 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
A summary of the available health effects data submitted for SIDS endpoints is provided in
Table 3.
Acute Oral Toxicity
(1)	TIF:RAIF (SPF) rats (5/sex/dose) were administered triglycidyl isocyanurate (in 0.5% CMC,
carboxymethyl cellulose) via gavage at 20 mg/kg-bw (females only), 100 mg/kg-bw (both sexes)
or 500 mg/kg-bw (females only) and observed for 14 days. Mortality occurred in males at 100
mg/kg-bw and females at 500 mg/kg-bw.
LD50 (male rats) <100 mg/kg-bw
LD50 (female rats) = 171 mg/kg-bw
(2)	TIF:RAIF (SPF) rats (5/sex/dose) were administered triglycidyl isocyanurate (in arachis oil)
via gavage at 100, 250, 500 or 1000 mg/kg-bw and observed for 14 days. Mortality occurred at
and above 250 mg/kg-bw.
LD50 = 305 mg/kg-bw
(3)	TIF:RAIF (SPF) rats (5/sex/dose) were administered triglycidyl isocyanurate (in 0.5% CMC)
via gavage at 20 mg/kg-bw (females), 100 mg/kg-bw (both sexes), 200 mg/kg-bw (both sexes) or
500 mg/kg-bw (females) and observed for 14 days. Mortality occurred in males at 100 and 200
mg/kg-bw and in females at 200 and 500 mg/kg-bw.
LD50 (male rats) <100 mg/kg-bw
LD50 (female rats) = 255 mg/kg-bw
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(4) TIF:RAIF (SPF) rats (5/sex/dose) were administered triglycidyl isocyanurate (in 2% CMC)
via gavage at 100, 215, 317, 464, 600 or 1290 mg/kg-bw and observed for 14 days. Mortality
occurred at and above 215 mg/kg-bw.
LD50 = 431 mg/kg-bw
Acute Inhalation Toxicity
(1)	CD-I mice (5 males/concentration) were exposed to triglycidyl isocyanurate dust at
concentrations of 1.05, 2.39 or 3.88 mg/L for 4 hours and observed for 14 days. Mortality
occurred at 2.39 and 3.88 mg/L.
LC50 = 2.0 mg/L
(2)	Wistar rats (8 males/concentration) were exposed (whole-body) to triglycidyl isocyanurate at
4.16 mg/L for 4 hours and observed for 8 days. No deaths were observed.
LC50 > 4.16 mg/L
(3)	CD-I mice (10 males/concentration) were exposed to triglycidyl isocyanurate dust at 100,
350 or 750 mg/m3 (corresponding to 0.100, 0.350 or 0.750 mg/L) for 5 days (duration per day
not stated) and were observed for 14 days. Mortality occurred at all concentrations (5/10, 10/10
and 9/10 at 100, 300 and 750 mg/m3, respectively).
LC50 = 0.100 mg/L
(4)	TIF:RAIF (SPF) rats (10/sex/concentration) were exposed to triglycidyl isocyanurate aerosol
at 0, 410 or 656 mg/m3 (0, 0.410 or 0.656 mg/L) for 4 hours and observed for 14 days. Mortality
occurred in females at 656 mg/m3.
LC50 (male) > 0.650 mg/L
LC50 (female) = 0.650 mg/L
(5)	TIF:RAIF (SPF) rats (10/sex/concentration) were exposed to triglycidyl isocyanurate dust at
309 mg/m3 (corresponding to 0.309 mg/L) for 4 hours and observed for 14 days. No deaths were
observed.
LC50 > 0.309 mg/L
Acute Dermal Toxicity
(1)	TIF:RAIF rats (3/sex/dose) were administered triglycidyl isocyanurate dermally at 215, 1000,
2150 or 3170 mg/kg-bw on clipped, intact skin under occlusive conditions for 24 hours and were
observed for 14 days. No mortality was observed.
LD50 >3100 mg/kg-bw
(2)	Sprague-Dawley CFY rats (5/sex) were administered triglycidyl isocyanurate dermally at
2000 mg/kg-bw on clipped, intact skin under semi-occluded conditions for 24-hours and were
observed for 14 days. No deaths were observed.
LD50 > 2000 mg/kg-bw
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(3) TIF:RAIF (SPF) rats (5/sex/dose) were administered triglycidyl isocyanurate dermally at 200
mg/kg-bw (males only) or 2000 mg/kg-bw (both sexes) dermally on shaved, intact skin under
semi-occluded conditions for 24 hours and were observed for 14 days. No deaths were observed.
LD50 > 2000 mg/kg-bw
Repeated-Dose Toxicity
(1)	In a repeated-dose toxicity study, Sprague-Dawley rats (10 males/dose) were administered
triglycidyl isocyanurate via the diet at 0, 10, 30 or 100 ppm (approximately 0.72, 2.08 and 7.32
mg/kg-bw/day, respectively) for up to 94 days. After treatment day 64, treated males were
mated with untreated females (20/concentration) in order to assess male fertility. Slightly lower
leukocyte and lymphocyte counts were noted in 2 out of 10 males at 100 ppm. Reddish
coloration of mesenteric lymph nodes with hemosiderosis and congestion were seen in some
animals at 100 ppm. The magnitude and significance of these changes were not provided. No
mortalities were reported and no significant differences were noted for clinical signs, body
weight/body weight gain, food consumption, blood chemistry or urinalysis parameters in the
males.
LOAEL (systemic toxicity; males only) = not established
NOAEL (systemic toxicity; males only) = 7.32mg/kg/day (based on no adverse effects at the
highest dose tested)
(2)	In a repeated-dose toxicity study, Sprague-Dawley rats (50 males/concentration) were
administered triglycidyl isocyanurate via the diet at 0, 10, 30, 100 or 300 ppm (approximately 0,
0.43, 1.30, 4.36 or 13.6 mg/kg-bw/day, respectively) for 104 weeks. However, due to a high rate
of mortality, dosing was discontinued in the 300 ppm group at week 63 (44% mortality), and for
the remaining doses at weeks 98/99 (60% mortality at 10 ppm). At the end of the treatment
period, all surviving animals were killed and underwent a macro- and microscopic evaluation.
Decreased food consumption and body weight gain were noted at 100 and 300 ppm. Signs of
poor clinical condition were noted in the 300 ppm group. An increase in neutrophil percentage
and a decrease in lymphocyte percentage were noted at 300 ppm. At 300 ppm, a high incidence
of mastocytosis, hemosiderosis and sinusoidal hemorrhage in mesenteric lymph nodes, high
incidence of lymphoid depletion in the spleen, moderate to marked dilation of some intestinal
segments and hypo-secretion with small tubulo-alveolar units in the prostate were reported. No
treatment-related differences were seen at 10, 30 and 100 ppm. The study authors concluded that
the mortality observed in the 300 ppm dose group was possibly due to a histamine-related
hypotension, but the mortality in the remaining dose groups was not treatment-related because it
was similar in the control group and is commonly recorded in this strain and age of rats.
LOAEL (systemic toxicity; males only) = 4.36 mg/kg-bw/day (based on decreased body
weight gain)
NOAEL (systemic toxicity; males only) = 1.30 mg/kg-bw/day
Reproductive/Developmental Toxicity
There are no standard one- or two-generation reproductive or prenatal developmental toxicity
studies with triglycidyl isocyanurate. However, a repeated-dose toxicity study in Sprague-
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Dawley rats addressed fertility (males only; previously described in #1 above) and several
dominant lethal assays are available.
There was a slight, but dose-related decrease in the mean number of spermatozoa in all treated
groups (5, 13 and 23% for 10, 30 and 100 ppm, respectively; statistical significance not
provided). The mean spermatozoa viability was similar compared to controls, the mating index
was 100% in all groups, and no treatment-related infertility was reported. Longer-term
exposures (98/99 weeks) did not reveal any effect on male reproductive organs. Although the
decrease in sperm number in this study did not appear have an adverse affect on fertility, human
male fertility is generally lower than that of test species and therefore, statistically significant
changes in sperm count would be considered adverse.
In this same study, treated males were mated with untreated females and a variety of
observations were made on the dams and fetuses. For the dams, no clinical signs and no
unscheduled mortalities occurred. The gestation index was 100% in all groups, and no
significant differences were noted for the mean number of corpora lutea, implantation sites, and
pre-implantation losses. For the fetuses, no dead fetuses were reported, no external anomalies or
malformations were observed, and no significant differences were noted for the following:
number of fetuses, mean fetal body weight, sex-ratio of live fetuses, mean number of live born
pups, viability index of pups on days 4 and 21 postpartum, lactation index, mean pup body
weight, pinna unfolding, hair growth, tooth eruption, eye opening, auditory canal opening, reflex
development, surface righting, cliff avoidance, and air righting.
In vivo Dominant Lethal Assays
1) In a dominant lethal assay, male ICR mice (20/dose) were administered triglycidyl
isocyanurate via gavage at 137.5, 275 or 550 mg/kg-bw and were mated with untreated female
mice (40/dose) for 3 weeks. Positive controls were also tested and responded appropriately. No
toxic effects were noted in any of the animals after dosing. Three males in the high-dose group
and one male of the vehicle control group died during the first week of mating. Several animals
in the low- and high-dose groups were observed to have scruffy coats during the first week of
mating. There were no treatment-related effects on any of the measured implantation indices.
Triglycidyl isocyanurate did not induce dominant lethal effects in this assay.
(2)	In dominant lethal assay, male albino mice (Tif: MAG f (SPF)) were administered triglycidyl
isocyanurate via gavage at 0, 160 and 480 mg/kg-bw and were mated with untreated females. At
160 mg/kg-bw, there was no difference in mating ratio, the number of implantations and
resorptions between the treated and the control groups. At 480 mg/kg-bw, there was a
significant increase in the number of resorptions compared with the control group.
Triglycidyl isocyanurate induced dominant lethal effects in this assay.
(3)	In a dominant lethal assay, CD-I mice (30 males/dose) were exposed to triglycidyl
isocyanurate via whole-body inhalation at 0, 2.5, 10 or 50 mg/m3 (measured concentrations 1.79,
10.3 or 49.6 mg/m3) for 6 hours/day for 5 days. Positive controls were tested concurrently and
responded accordingly. There was 10% mortality, reduced body weight gain and ocular
discharge and swelling in the high-dose group. Effects on male fertility were observed at
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50 mg/m3 as evidenced by reduced number of males impregnating females, reduced number of
pregnant females and females with copulation plugs for the first 3 mating weeks, indicative of
effects on mature sperm and maturing spermatids. No effects on male fertility were observed for
the spermatocyte stages.
Triglycidyl isocyanurate did not induce dominant lethal effects in this assay.
(4) CD-I (ICR) mice (10 males/concentration) were exposed to triglycidyl isocyanurate dust via
whole-body inhalation at target concentrations of 0 (air), 100, 1000 and 1700 mg/m3 (115, 975,
1575 mg/m3, measured-gravimetric) 6 hours/day for 5 consecutive days and mated with
untreated females of the same strain approximately 24 hours after the last exposure. On
gestation day 15, females were sacrificed and the number of implantation sites counted. A
positive control was included in the test. There was a marked decrease in body weight of the
treated mice. No effects on male fertility were evident at any exposure concentration. There was
no effect on the numbers of resorptions per litter, total number of implants, number of viable
implants or percent post-implantation loss.
Triglycidyl isocyanurate did not induce dominant lethal effects in this assay.
Genetic Toxicity — Gene Mutation
In vitro
(1)	In five bacterial reverse mutation assays, Salmonella typhimurium strains TA98, TA100,
TA1535, TA1537 and TA1538 and Escherichia coli, WP2wvr^4 were exposed to triglycidyl
isocyanurate at concentrations ranging from 1.0 to 10,000 |j,g/plate in the presence and absence
of metabolic activation. Positive controls were tested concurrently and responded appropriately.
Concentrations exhibiting cytotoxicity or precipitation were not identified.
Triglycidyl isocyanurate was mutagenic in these assays.
(2)	Mouse lymphoma cells (L5178Y) were exposed to triglycidyl isocyanurate at 0.375, 0.75,
1.50, 3.00 and 6.00 |ig/mL with metabolic activation and at 0.175, 0.35, 0.70 1.40 and 2.80
|ig/mL without metabolic activation. In the absence of metabolic activation, at 1.40 and 2.80
|ig/mL a markedly elevated mutation frequency was noted. Similarly, in the presence of
metabolic activation, the highest concentration, 6.0 jag/m L led to the markedly elevated mutant
frequency when compared with the solvent control. The negative and positive controls
responded appropriately.
Triglycidyl isocyanurate was mutagenic in this assay.
(3)	In two NTP studies, Salmonella typhimurium strains TA98 and TA100 were exposed to
triglycidyl isocyanurate at concentrations ranging from 10 to 2000 |j,g/plate in the presence and
absence of metabolic activation. Positive controls were tested concurrently and responded
appropriately.
Triglycidyl isocyanurate was mutagenic in these assays.
Genetic Toxicity — Chromosomal Aberrations
In vitro
(1) Primary human lymphocytes were exposed to triglycidyl isocyanurate at 0.0625, 0.125, 0.25,
0.5 or 1.0 |j,g/mL in the absence of metabolic activation or 0.625, 1.25, 2.5, 5.0 or 10 |j,g/mL in
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the presence of metabolic activation. Positive controls were tested concurrently and responded
appropriately. Cytotoxic concentration was 10 |j,g/mL in the presence of metabolic activation
and 1.0 |j,g/mL in the absence of activation.
Triglycidyl isocyanurate did not induce chromosomal aberrations in this assay.
(2) In a National Toxicology Program (NTP) study, Chinese hamster ovary (CHO) cells were
exposed to triglycidyl isocyanurate in the absence of metabolic activation at 3, 10, 30 or 50
Hg/mL in one trial and at 9.95, 19.9 or 29.9 |j,g/mL in a second trial. CHO cells were also
exposed to 10, 30 or 100 |j,g/mL in the presence of metabolic activation. Positive and negative
controls were tested concurrently and responded appropriately.
Triglycidyl isocyanurate induced chromosomal aberrations in this assay.
In vivo
(1)	ICR mice (10 males/dose) were administered triglycidyl isocyanurate in peanut oil via
gavage at 30, 125 and 350 mg/kg-bw daily for 5 days and were sacrificed 6 hours after the final
dosing. Spermatogonial metaphase cells were analyzed for chromosomal aberrations. The test
substance induced significant frequencies of aberrant cells in spermatogonial cells of mice at 125
and 350 mg/kg-bw. Positive and negative controls responded appropriately.
Triglycidyl isocyanurate induced chromosomal aberrations in these assays.
(2)	TIF:MAGF (SPF) mice (15 males/dose) were administered triglycidyl isocyanurate via
gavage at 42.7 or 128 mg/kg-bw/day for 5 days. Cytotoxicity was seen at the high-dose.
Spermatogonial metaphase cells were analyzed for chromosomal aberrations. The results
indicated that triglycidyl isocyanurate induced chromosomal aberrations in mouse
spermatogonial cells.
Triglycidyl isocyanurate induced chromosomal aberrations in these assays.
(3)	TIF:MAGF (SPF) mice (15 males/dose) were administered triglycidyl isocyanurate (in
Arachis oil) via gavage at 32 or 96 mg/kg-bw/day on days 0, 2, 3, 5 and 9. The results indicated
that triglycidyl isocyanurate induced chromosomal aberrations in mouse spermatocytes.
Negative control (solvent) responded appropriately. Positive control was not included in the test.
Triglycidyl isocyanurate induced chromosomal aberrations in these assays.
(4)	Mice (5 males/dose, strain not specified) were administered triglycidyl isocyanurate via
gavage at 185.2, 555.6, 1667 and 5000 mg/kg-bw daily for 5 days and were sacrificed 6 hours
after the final dose. Spermatogonial metaphase cells were analyzed for chromosomal
aberrations. Negative and positive controls responded appropriately. The number of aberrant
spermatogonial cells in treated mice was not significantly different from those in the negative
control and was within the accepted normal control range.
Triglycidyl isocyanurate did not induce chromosomal aberrations in this assay.
Genetic Toxicity — Other
In vitro
(1) In an unscheduled DNA synthesis assay, human fibroblasts were exposed to triglycidyl
isocyanurate at 2.7, 9, 30, 100, 250 or 400 |j,g/mL in the absence of metabolic activation.
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Cytotoxic concentration was greater than 400 |j,g/mL. Positive controls were tested concurrently
and responded appropriately.
Triglycidyl isocyanurate did not induce unscheduled DNA synthesis in this assay.
(2) In an NTP, sister chromatid exchange assay, Chinese hamster ovary (CHO) cells were
exposed to triglycidyl isocyanurate at 0.066, 0.198, 0.66 or 1.98 |j,g/mL in the absence of
metabolic activation in one trial and at 0.101, 0.303, 0.505 or 0.76 ng/rnL in the second trial.
CHO cells were also exposed to triglycidyl isocyanurate at 1.98, 6.6, 19.8 or 66 |j,g/mL in the
presence of metabolic activation. Positive and negative controls were tested concurrently and
responded appropriately.
Triglycidyl isocyanurate induced sister chromatid exchange in this assay.
In vivo
Several dominant lethal assays (previously described) are available.
Additional Information
Skin Irritation
(1)	New Zealand white rabbits (3/sex) were administered 0.5 g of triglycidyl isocyanurate (in
propylene glycol and saline, 70:30) dermally on intact and abraded skin under occluded
conditions for 24 hours. Skin reactions were assessed upon removal of the patches and during
the 7-day observation period.
Triglycidyl isocyanurate was minimally irritating in this study.
(2)	New Zealand white rabbits (5/sex) were administered 0.5 g of triglycidyl isocyanurate (in
arachis oil) dermally on intact skin under semi-occluded conditions for 24 hours. Skin reactions
were assessed upon removal of the patches and during the 7-day observation period. Very slight
erythema was noted at the application sites at one and 24-hour observation. All treated sites
were normal at the 72-hour observation.
Triglycidyl isocyanurate was mildly irritating in this study.
(3)	New Zealand white rabbits (3/sex) were administered 0.5 g of neat triglycidyl isocyanurate
dermally on intact and abraded skin under occluded conditions for 24 hours. Skin reactions were
assessed upon removal of the patches and during the 7-day observation period.
Triglycidyl isocyanurate was slightly irritating in this study.
(4)	New Zealand white rabbits (3 males) were administered 0.5 g of triglycidyl isocyanurate (in
distilled water) dermally on intact skin under occluded conditions for 24 hours. Skin reactions
were assessed upon removal of the patches and up to 72-hours observation period. Very slight
erythema was noted at the application sites at one and 24-hour observation. All treated sites
were normal at the 72-hour observation.
Triglycidyl isocyanurate was mildly irritating in this study.
(5)	New Zealand white rabbits (1/sex) were administered 1 g of neat triglycidyl isocyanurate or 1
mL of a 4% solution of triglycidyl isocyanurate dermally on shaved skin for 6 hours under
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December, 2009
occluded conditions for 3 consecutive days. One pair of male and female rabbits was treated in a
similar manner, but the application sites were not covered during the exposure. Irritation was
assessed on day 7.
Triglycidyl isocyanurate was moderately irritating in these studies.
(6) Guinea pigs (5/sex) were administered dermally 0.5 mL of triglycidyl isocyanurate on shaved
skin. The application sites remained uncovered.
Triglycidyl isocyanurate was moderately irritating in this study.
Eye Irritation
(1)	CFE rabbits (sex distribution and number not stated) were instilled 100 mg of solid
triglycidyl isocyanurate into one eye; the other eye served as control. The test substance showed
severe irritation with temporary blindness.
Triglycidyl isocyanurate was severely irritating in this assay.
(2)	New Zealand white rabbit (1 male) was instilled 0.1 mL of triglycidyl isocyanurate into the
right eye; the left eye served as control. Severe ocular reactions including diffuse corneal
opacity and iridial inflammation were noted.
Triglycidyl isocyanurate was severely irritating in this assay.
(3)	New Zealand White rabbits (3/sex) were instilled 0.5 g triglycidyl isocyanurate into one eye;
the other eye served as control. An additional group of six rabbits was instilled 0.1 g triglycidyl
isocyanurate and after 30 seconds, the eyes of three animals were rinsed. Marked eye irritation
was observed.
Triglycidyl isocyanurate was severely irritating in this assay.
Sensitization
(1)	In four guinea pig maximization tests, triglycidyl isocyanurate was sensitizing with rates of
sensitization varied from 20 to 90% (weak to extreme sensitizing) in the studies.
Triglycidyl isocyanurate was a dermal sensitizer in these four assays.
(2)	Guinea pigs (30 males: 20 test and 10 control) were administered triglycidyl isocyanurate in
four intradermal injections at 0, 1.0, 3.0 and 5.0% to the neck area. One week later, 0.1 mL of
the test substance in corn oil was applied to the shaved backs of guinea pigs at 10, 15, 25 or 30%.
While a response (erythema) was noted during the challenge period, the study concluded that
triglycidyl isocyanurate was not sensitizing because the skin reactions faded between the 24- and
48-hour readings and were not reproducible during a second challenge. The summary concluded
that skin reactions were a response to a state of hyperactivity.
Triglycidyl isocyanurate in corn oil was not a dermal sensitizer in this assay.
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Carcinogenicity
In the repeated-dose toxicity study in rats previously described (#2), no statistical difference in
tumor formation or latency period of tumor formation between treated and control groups was
observed.
Triglycidyl isocyanurate did not show evidence of carcinogenicity in this study.
Conclusion: The acute toxicity of triglycidyl isocyanurate is moderate in rats by the oral route,
high in mice by the inhalation route, and low in rats by the dermal route. A repeated-dose
toxicity study in male rats showed decreases in body weight gain at 4.36 mg/kg-bw/day; the
NOAEL for systemic toxicity was 1.30 mg/kg-bw/day. No one- or two-generation reproductive
or prenatal developmental toxicity studies are available. However, decreases in sperm counts
were observed at 0.72 mg/kg-bw/day in another repeated-dose toxicity study in males, the lowest
dose tested. This chemical did not induce dominant lethality. This chemical was slightly to
moderately irritating to rabbit and guinea pig skin, severely irritating to rabbit eye, and a dermal
sensitizer in guinea pigs. This chemical induced gene mutations in vitro but not in vivo; and
induced chromosomal aberrations in vivo but was equivocal in vitro. There was no evidence of
carcinogenicity in a two-year bioassay.
Table 3. Summary Table of the Screening Information Data Set as Submitted
under the U.S. HPV Challenge Program: Summary of Human Health Data
Endpoints
Triglycidyl isocyanurate
(2451-62-9)
Acute Oral Toxicity
LDS0 (mg/kg-bw)
< 100
Acute Inhalation Toxicity
LCso (mg/L)
0.65
0.1 (5-d)
Acute Dermal Toxicity
LDS0 (mg/kg-bw)
>2000
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
NOAEL = 1.30
LOAEL = 4.36
Reproductive Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
Reproductive toxicity = Data gap
Developmental Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
Data gap
Genetic Toxicity - Gene Mutation
In vitro
Positive
Genetic Toxicity - Gene Mutation
In vivo
Negative
Genetic Toxicity - Chromosomal
Aberrations
In vitro
Positive
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Table 3. Summary Table of the Screening Information Data Set as Submitted
under the U.S. HPV Challenge Program: Summary of Human Health Data
Endpoints
Triglycidyl isocyanurate
(2451-62-9)
Genetic Toxicity - Chromosomal
Aberrations
In vivo
Positive
Genetic Toxicity - Other
In vitro
Unscheduled DNA Synthesis
Negative
Genetic Toxicity - Other
In vivo
Dominant Lethal Effects
DNA Binding Effects
Negative
Positive
Additional Information
Dermal Irritation
Slightly to moderately irritating
Eye Irritation
Markedly to severely irritating
Dermal Sensitization
Carcinogenicity
Positive
Negative evidence
4. Environmental Effects Aquatic Toxicity
A summary of the available ecological effects data submitted for SIDS endpoints is provided in
Table 4.
Acute Toxicity to Fish
Zebrafish (Brachydanio rerio, 10/concentration) were exposed to triglycidyl isocyanurate at a
nominal concentration of 100 mg/L (average measured concentration approximately 77 mg/L)
under static conditions for 96 hours in a limit test. No mortality occurred and no adverse effects
were noted in any of the fish. DMSO was used as a solvent in this test.
96-h LCso = > 77 mg/L
Acute Toxicity to Aquatic Invertebrates
Water fleas (Daphnia magna, 20/concentration) were exposed to triglycidyl isocyanurate at
nominal concentrations of 10, 18, 32, 58 or 100 mg/L under static conditions for 24 hours.
Measured concentrations were 9.8, 17.1, 30.5, 54.5 or 90.6 mg/L. Immobilization (20%)
occurred at 100 mg/L. The reported 24-hour EC50 was greater than 90.6 mg/L. DMSO was used
as a solvent in this test. EPA used a 48-hour EC50 value estimated using ECOSAR vl ,00a to
support the evaluation of acute toxicity of this chemical.
24-h EC50 = >90.6 mg/L
48-h EC50 = 49 mg/L (estimated)
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Toxicity to Aquatic Plants
Green algae (Scenedesmus subspicatus) were exposed to triglycidyl isocyanurate at nominal
concentrations of 0.41, 1.23, 3.7, 11, 33 or 100 mg/L under static conditions for 72 hours.
Measured concentrations were .21, 0.72, 2.1, 6.3, 19.4 or 63.4 mg/L. Control response was
satisfactory.
72-h EC50 (biomass) = 29 mg/L
Conclusion: For acute hazard of CASRN 2451-62-9, the 96-hour LC50 to fish is >77 mg/L, the
measured 24-hour EC50 to aquatic invertebrates is >90.6 mg/L, and the measured 72-hour EC50
(biomass) to aquatic plants is 29 mg/L.
No data gaps were identified under the HPV Challenge Program.
Table 4. Summary Table of the Screening Information Data Set as Submitted
under the U.S. HPV Challenge Program: Summary of Environmental Effects-
Aquatic Toxicity Data
Endpoints
Triglvcidvl isocyanurate
(2451-62-9)
Fish
96-h LCS0 (mg/L)
>77
Aquatic Invertebrates
48-h EC50 (mg/L)
> 90.6 (24-h)
49 (e)
Aquatic Plants
72-h ECS0 (mg/L)
(growth)
(biomass)
29
Bold= measured data; e= estimated data; -Indicates that endpoint was not addressed.
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