Screening-level Hazard Characterization for High Production Volume Chemicals Sponsored Chemical C.i. Disperse Blue 79:1 (cas No. 3618-72-2) [9th Ci Name: Acetamide, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-dinitrophenyl)azo]-4-methoxyphenyl]-]


SCREENING-LEVEL HAZARD CHARACTERIZATION
FOR HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
[9th CI Name: Acetamide, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-
dinitrophenyl)azo]-4-methoxyphenyl]-]
SUPPORTING CHEMICAL
C.I. Disperse Blue 79 (CAS No. 12239-34-8)
[9th CI Name: Acetamide, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-
dinitrophenyl)azo] -4-ethoxyphenyl] -
December 2007
INTERIM
Prepared by
High Production Volume Chemicals Branch
Risk Assessment Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001

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SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
The High Production Volume (HPV) Challenge Program1 is 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 sponsor chemicals; sponsorship entails the identification and
initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data do
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. OPPT is using a hazard-
based screening process to prioritize review of the submissions. The hazard-based screening process consists of two
tiers described below briefly and in more detail on the Hazard Characterization website3.
Tier 1 is a computerized sorting process whereby key elements of a submitted data set are compared to established
criteria to "bin" chemicals/categories for OPPT review. This is an automated process performed on the data as
submitted by the sponsor. It does not include evaluation of the quality or completeness of the data.
In Tier 2, a screening-level hazard characterization is developed by EPA that consists of an objective evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions. The evaluation is
performed according to established EPA guidance2'4 and is based primarily on hazard data provided by sponsors.
EPA may also include additional or updated hazard information of which EPA, sponsors or other parties have
become aware. The hazard characterization may also identify data gaps that will become the basis for a subsequent
data needs assessment where deemed necessary. Under the HPV Challenge Program, chemicals that have similar
chemical structures, properties and biological activities may be grouped together and their data shared across the
resulting category. This approach often significantly reduces the need for conducting tests for all endpoints for all
category members. As part of Tier 2, evaluation of chemical category rationale and composition and data
extrapolation(s) among category members is performed in accord with established EPA2 and OECD5 guidance.
The screening-level hazard characterizations that emerge from Tier 2 are important contributors to OPPT's existing
chemicals review process. These hazard characterizations are technical documents intended to support 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. The public, including
sponsors, may offer comments on the hazard characterization documents.
The screening-level hazard characterizations, as the name indicates, do not evaluate the potential risks of a chemical
or a chemical category, but will serve as a starting point for such reviews. In 2007, EPA received data on uses of
and exposures to high-volume TSCA existing chemicals, submitted in accordance with the requirements of the
Inventory Update Reporting (IUR) rule. For the chemicals in the HPV Challenge Program, EPA will review the
IUR data to evaluate exposure potential. The resulting exposure information will then be combined with the
screening-level hazard characterizations to develop screening-level risk characterizations4'6. The screening-level
risk characterizations will inform EPA on the need for further work on individual chemicals or categories. Efforts
are currently underway to consider how best to utilize these screening-level risk characterizations as part of a risk-
based decision-making process on HPV chemicals which applies the results of the successful U.S. High Production
Volume Challenge Program and the IUR to support judgments concerning the need, if any, for further action.
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. HPV Chemicals Hazard Characterization website (http://www.epa.gov/hpvis/abouthc.html).
4 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
5 OECD. Guidance on the Development and Use of Chemical Categories; http://www.oecd.org/dataoecd/60/47/1947509.pdf.
6 U.S. EPA. Risk Characterization Program; http://www.epa.gov/osa/spc/2riskchr.htm.
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SCREENING-LEVEL HAZARD CHARACTERIZATION
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
Introduction
The sponsor, ETAD North America, submitted a Test Plan and Robust Summaries to EPA for C.I. Disperse Blue
79:1 (CAS No. 3618-72-2; 9th CI name: acetamide, N-[5-[bis[2-(acetyloxy)ethyl]amino]-2-[(2-bromo-4,6-
dinitrophenyl)azo]-4-methoxyphenyl]-) on January 7, 2002. EPA posted the submission on the ChemRTK HPV
Challenge website on February 20, 2002
(http://www.epa.gov/oppt/chemrtk/pubs/summaries/acetamid/cl3461tc.htm'). EPA comments on the original
submission were posted to the website on October 3, 2002. The sponsor submitted updated/revised documents on
June 6, 2003, which were posted to the ChemRTK website on June 30, 2003.
This screening level hazard characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsor(s) under the HPV Challenge Program. 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. A summary table of SIDS endpoint data with the
structure(s) of the sponsored chemical(s) is included in the appendix. The screening-level hazard characterization
for environmental and human health effects is based largely on SIDS endpoints and is described according to
established EPA or OECD effect level definitions and hazard assessment practices.
Justification for Supporting Chemical
In some instances, test data do not exist for C.I. Disperse Blue 79:1. The sponsor provided data for the supporting
chemical, C.I. Disperse Blue 79 (CAS No. 12239-34-8) for these endpoints. Nearly identical structure and physical-
chemical properties, such as log Kow, water solubility and modeled fate parameters, provide rationale for the use of
C.I. Disperse Blue 79 as a supporting chemical.
Sum man-Conclusion
The log k I'orC I Disperse I Slue I indicates that its potential lo hioacciininlale is expected lo he high
\dct|iulc hiodegradalioii dala were not pro\ ided. howe\er. hased on reads hiodegradalioii dala lor chemical
analogs. ( I Disperse lilne ~l) I is considered noi readils biodegradable, iiidicaling dial il is expected lo persist in
llic cn\ iroiimciii
\cnic aquatic to\icil> is noi expected al I lie chemical's solnhihis limn  t>u52 nig I.). I !\ alnalion ol'dala Ironi an
earls life siage (chronic) to\icit> lesi lor ramhow ironi mdicales ilial llie poieniial acnie lia/ard of (' I Disperse lilne
I lo aquatic organisms is high
I lie acnie oral lo\icil> of C I Disperse lilne I lo rals is low \o ireainieiii-relaled adserse effects were found in
a l><>-da> repealed-dose gasage siiitlv in rals Mihongh a icprodiictis e to\icit> studs was noi asailahle. examination
of tissues organs from ihe repealed-dose to\icils studs showed ilial icprodiictis e organs were noi affecled In
exposure lo llie lesi chemical In unexposed hs ga\ageon gesialion da>s(¦ 15. no nialernal lo\icil\ i>r
de\elopnienial ellecls were reported In rahhils e\posed h\ ga\age on gesialion da>s (¦ IS. a slighi decrease
nialernal and lelal hods weight per liner was seen CI Disperse lilne ~l> I is mutagenic mi multiple simms of
\i/iiinih //.i iin viini). hnt iicgali\e in the in \ i\ " I 'nixi/'hi/.i se\-hnked recessi\e lethal niiitageincils test The
supporting chemical. CI I )isperse I Sine \ lelded negati\ e results m hotli in viini and in viva genetic lo\icil> tests
I lie weight of e\ idence indicates a low concern lor genetic lo\icil>
I lie potential health lia/ard ( I Dispeise lilne ~'i I is low.
No dala gaps were identified under the I ll'V ( hallenge I'rogiani
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1. Physical-Chemical Properties and Environmental Fate
Octanol-Water Partition Coefficient
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
Log K„w: 4.44
Biodegradation
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
The sponsor provided municipal waste treatment test data; ready biodegradation test data were not provided. In
comments on the original test plan, EPA stated that the sponsor's biodegradation data are inadequate. However,
ready biodegradation data for chemical analogs lead EPA to consider this chemical to be not readily
biodegradable.
C.I. Disperse Blue 79:1 is not readily biodegradable.
Conclusion: The log Kow for C.I. Disperse Blue 79:1 indicates that its potential to bioaccumulate is expected to
be high. Adequate biodegradation data were not provided; however, based on ready biodegradation data for
chemical analogs, C.I. Disperse Blue 79:1 is considered not readily biodegradable, indicating that it is expected to
persist in the environment.
2. Environmental Effects - Aquatic Toxicity
The submitted acute data for aquatic invertebrates and aquatic plants were judged inadequate because endpoints
were tested above the chemical's aqueous water solubility, test durations were inadequate and chemical purity was
not characterized. However, chronic test data are preferable in this case because acute effects are not expected at the
chemical's solubility limit. The available chronic fish data for C.I. Disperse Blue 79:1 are adequate for assessing
aquatic toxicity endpoints for the purpose of the HPV Challenge Program.
Acute Toxicity to Aquatic Invertebrates
C.I. Disperse Blue 79 (CAS No. 12239-34-8, supporting chemical)
The aquatic toxicity test submitted was conducted above the aqueous solubility limit of C.I. Disperse Blue 79:1.
Given the low water solubility of C.I. Disperse Blue 79:1, chronic toxicity data are preferable; the available chronic
fish data for C.I. Disperse Blue 79:1 are adequate for assessing aquatic toxicity endpoints for the purpose of the
HPV Challenge Program.
Toxicity to Aquatic Plants
C.I. Disperse Blue 79 (CAS No. 12239-34-8, supporting chemical)
The aquatic toxicity test submitted was conducted above the aqueous solubility limit of C.I. Disperse Blue 79:1.
Given the low water solubility of C.I. Disperse Blue 79:1, chronic toxicity data are preferable; the available chronic
fish data for C.I. Disperse Blue 79:1 are adequate for assessing aquatic toxicity endpoints for the purpose of the
HPV Challenge Program.
Chronic Toxicity to Fish
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
In an early life stage test, newly fertilized eggs (fertilized < 4 hours before study initiation) from rainbow trout
(Oncorhynchus mykiss) were exposed to C.I. Disperse Blue 79:1 at nominal test concentrations of 0.31, 0.63, 1.3,
2.5 and 5.0 |ig/L under flow-through conditions for 122 days post-hatch. The mean measured concentrations of test
substance were 0.36, 0.58, 1.2, 2.5 and 4.8 (ig/L. The highest test concentration was considered the limit of
solubility for the test substance. Hatchability, survival and fry growth (length and weight) were not affected by any
concentration tested.
122-d NOEC = 0.0048 mg/L (measured)
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Conclusion: Acute effects are not expected at the chemical's solubility limit. Evaluation of data from an early life
stage (chronic) toxicity test for rainbow trout indicates that the potential acute hazard of C.I. Disperse Blue 79:1 to
aquatic organisms is high.
3. Human Health Effects
Acute Oral Toxicity
Acute oral toxicity study was not provided. Instead the sponsor provided data for a two-week range-finding study.
Sprague-Dawley rats (5/sex/dose) were administered C.I. Disperse Blue (in corn oil) via gavage at 100, 500, 1000 or
2500 mg/kg-bw for 5 days/week for two weeks for a total of 11 doses. No treatment-related effects on daily clinical
signs, body weights, body weight gains, food consumption and necropsy were observed at any dose level.
LDS0 > 2500 mg/kg-bw
Repeated-Dose Toxicity
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
(1) Male and female Sprague-Dawley rats (number per group not specified) were administered C.I. Disperse Blue
79:1 via gavage at doses of 0, 250, 1250 or 2500 mg/kg-bw/day, 5 days/week for 13 weeks. Blue coloration of the
body and/or tail was observed in some animals; however, this coloration is not considered biologically significant
since the test substance is a dye with an intense blue color. No reported treatment-related effects on food
consumption, mortality, clinical pathology, ophthalmic examinations, body weight or body weight gain, organ
weights, necropsy or histopathology were observed at any dose.
NOAEL = 2500 mg/kg-bw/day (based no effects at highest dose tested)
(2) Male and female rats (5/group) were administered C.I. Disperse Blue 79:1 via gavage at doses of 0, 100, 500,
1000 or 2500 mg/kg-bw/day, 5 days/week for 2 weeks plus an additional dose on the following Monday (11 doses).
No treatment-related effects on daily clinical signs, body weights, body weight gains, food consumption or necropsy
were observed at any dose level.
NOAEL = 2500 mg/kg-bw/day (based on no effects at highest dose tested)
Reproductive Toxicity
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
A reproductive toxicity study was not provided; however, the histopathological evaluation of reproductive organs in
the 13-week repeated-dose toxicity study described above and available developmental toxicity data address the
endpoint for the purpose of the HPV Challenge Program.
Histopatholgical evaluation was performed on all tissues including reproductive organs from each dose group and
the control group. There were no gross or microscopic lesions attributed to treatment for either sex animal at any
dose level.
Developmental Toxicity
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
(1) Pregnant Sprague-Dawley rats (number per group not specified) were administered C.I. Disperse Blue 79:1 via
gavage (in corn oil) at doses of 0, 500, 1000 or 2000 mg/kg-bw/day on days 6 - 15 of gestation and were sacrificed
on gestation day 20. No treatment-related effects were reported for maternal weight or weight gain, food
consumption, gestational parameters (pre- and post-implantation loss and fetal body weights/litter) or incidences of
gross, visceral or skeletal malformations or variations.
NOAEL (maternal/developmental toxicity) = 2000 mg/kg-bw/day (based on no effects at highest dose tested)
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(2) Pregnant New Zealand White rabbits (16/group) were administered C.I. Disperse Blue 79:1 via gavage (in corn
oil) at doses of 0, 100, 300 or 600 mg/kg-bw/day on days 6 - 18 of gestation and were sacrificed on gestation day
30. Maternal weight gain during gestation was decreased in rabbits given 300 or 600 mg/kg-bw/day. No treatment-
related effects were seen for food consumption, gravid uterine or liver weights in dams, or pre- and post-
implantation loss. A slight decrease in fetal body weights per litter was observed at 600 mg/kg-bw/day. No
treatment-related increase in the incidence of gross, visceral or skeletal malformations or variations was observed.
LOAEL (maternal toxicity) = 300 mg/kg-bw/day (based on decreased maternal weight gain)
NOAEL (maternal toxicity) = 100 mg/kg-bw/day
NOAEL (developmental toxicity) = 600 mg/kg-bw/day (based on no effects at the highest dose tested)
Genetic Toxicity - Gene Mutation
In vitro
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
Salmonella typhimurium TA98, TA100, TA1537 and TA1538 strains were exposed to Foron Navy SE-2GRL (purity
not known) at concentrations ranging from 1 to 1000 |.ig/platc in the presence and absence of metabolic activation.
Information on the use of controls and cytotoxic concentration is not provided.
Foron Navy SE-2GRL was mutagenic in this assay.
C.I. Disperse Blue 79 (CAS No. 12239-34-8, supporting chemical)
C.I. Mammalian cells V79 were exposed to Disperse Blue 79 at concentrations ranging from 0.05 - 1.0 (ig/mL
without metabolica activation and 2.5 - 750 (ig/mL with metabolic activation. Information of the use of controls
and cytotoxic concentration is not provided. C.I. Disperse Blue 79 was not mutagenic in this assay.
Genetic Toxicity - Chromosomal Aberrations
In vivo
C.I. Disperse Blue 79 (CAS No. 12239-34-8, supporting chemical)
NMRI mice (male and female) were administered C.I. Disperse Blue 79 via gavage at 5000 mg/kg-bw. C.I.
Disperse Blue did not induce chromosomal mutations. The details on this study were limited.
C.I. Dipserse Blue 79 did not cause chromosomal aberrations in this assay.
C.I. Disperse Blue 79:1 (CAS No. 3618-72-2)
In a Drosophila (fruit fly) sex-linked recessive lethal mutagenicity test, males were injected with 50 ppm of C.I.
Disperse Blue 79:1 and were mated with untreated females (Base females crossed with Canton-S wild type males) to
assess lethal mutations in post-meiotic germ cells.
C.I. Disperse Blue 79:1 was not mutagenic in this assay.
Conclusion: The acute oral toxicity of C.I. Disperse Blue 79:1 to rats is low. No treatment-related adverse effects
were found in a 90-day repeated-dose gavage study in rats. Although a reproductive toxicity study was not
available, examination of tissues/organs from the repeated-dose toxicity study showed that reproductive organs were
not affected by exposure to the test chemical. In rats exposed by gavage on gestation days 6 - 15, no maternal
toxicity or developmental effects were reported. In rabbits exposed by gavage on gestation days 6 - 18, a slight
decrease maternal and fetal body weight per litter was seen. C.I. Disperse Blue 79:1 is mutagenic in multiple strains
of Salmonella {in vitro), but negative in the in vivo Drosophila sex-linked recessive lethal mutagenicity test. The
supporting chemical, C.I. Disperse Blue 79, yielded negative results in both in vitro and in vivo genetic toxicity tests.
The weight of evidence indicates a low concern for genetic toxicity.
The potential health hazard C.I. Disperse Blue 79:1 is low.
4. Hazard Characterization
The log Kow for C.I. Disperse Blue 79:1 indicates that its potential to bioaccumulate is expected to be high.
Adequate biodegradation data were not provided; however, based on ready biodegradation data for chemical
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analogs, C.I. Disperse Blue 79:1 is considered not readily biodegradable, indicating that it is expected to persist in
the environment.
Acute aquatic toxicity is not expected at the chemical's solubility limit (0.0052 mg/L). Evaluation of data from an
early life stage (chronic) toxicity test for rainbow trout indicates that the potential acute hazard of C.I. Disperse Blue
79:1 to aquatic organisms is high.
The acute oral toxicity of C.I. Disperse Blue 79:1 to rats is low. No treatment-related adverse effects were found in
a 90-day repeated-dose gavage study in rats. Although a reproductive toxicity study was not available, examination
of tissues/organs from the repeated-dose toxicity study showed that reproductive organs were not affected by
exposure to the test chemical. In rats exposed by gavage on gestation days 6 - 15, no maternal toxicity or
developmental effects were reported. In rabbits exposed by gavage on gestation days 6 - 18, a slight decrease
maternal and fetal body weight per litter was seen. C.I. Disperse Blue 79:1 is mutagenic in multiple strains of
Salmonella {in vitro), but negative in the in vivo Drosophila sex-linked recessive lethal mutagenicity test. The
supporting chemical, C.I. Disperse Blue 79, yielded negative results in both in vitro and in vivo genetic toxicity tests.
The weight of evidence indicates a low concern for genetic toxicity.
The potential health hazard C.I. Disperse Blue 79:1 is low.
5. Data Gaps
No data gaps were identified under the HPV Challenge Program.
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APPENDIX
Summary Tabic of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
C.I. Disperse Blue 79:1
(3618-72-2)
SUPPORTING CHEMICAL
C.I. Disperse Blue 79
(12239-34-8)
Structure
HN 0	H
\ /\
HN O	H
Y_

B- ! 0
" H S /
Br ^ O
Summary of Physical-Chemical Properties and Environmental Fate Data
Melting Point (°C)
> 138 °C
157 °C
Boiling Point (°C)
—
476 °C
Vapor Pressure
(hPa at 25°C)
—
6.0 x 10"9
Log K„w
4.44
4.1
Water Solubility
(mg/L at 25°C)
0.0052
0.0054
Indirect (OH) Photodegradation
Half-life (t1/2)
0.57 h
	*
Stability in Water (Hydrolysis) (t1/2)
25 d (pH 8);
250 d (pH 7)
	*
Fugacity
(Level III Model)
Air (%)
Water (%)
Soil (%)
Sediment (%)
<0.1
6.69
79.4
13.9
<0.1
3.68
60.9
35.4
Biodegradation at 28 days (%)
No Data
Not readily biodegradable
(RA)
Not readily biodegradable
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
	*
	*
Aquatic Invertebrates
48-h ECS0 (mg/L)
	*
	*
Aquatic Plants
72-h ECS0 (mg/L)
(growth)
(biomass)
	*
	*
Chronic Toxicity to Fish
122-d NOEC (mg/L)
0.0048
	*
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Summary Tabic of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program
Endpoints
SPONSORED CHEMICAL
C.I. Disperse Blue 79:1
(3618-72-2)
SUPPORTING CHEMICAL
C.I. Disperse Blue 79
(12239-34-8)
Summary of Human Health Data
Acute Oral Toxicity
LDS0 (mg/kg-bw)
>2500
	*
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
NOAEL = 2500 (14-d)
NOAEL = 2500
	*
Reproductive Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
Evaluation of reproductive organs
from the 90-day study indicated no
effects.
	*
Developmental Toxicity
NOAEL/LOAEL
Oral (mg/L/day)
Maternal Toxicity
(rat)
NOAEL = 2000
(rabbit)
NO A F.I. = 100
LOAEL = 300
	*
Developmental Toxicity
(rat)
NOAEL = 2000
(rabbit)
NOAEL = 600

Genetic Toxicity - Gene Mutation
In vitro
Positive
Negative
Genetic Toxicity - Gene Mutation
In vivo
Negative
	*
Genetic Toxicity - Chromosomal
Aberrations
In vivo
	*
Negative
- indicates endpoint was not addressed for this chemical; * indicates endpoint not required for this chemical; RA =
Read across
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