U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
SCREENING-LEVEL HAZARD CHARACTERIZATION
6-Amino-4-chloro-m-toluenesulfonic acid (2B Acid) and 2-Amino-5-chloro-/?-
toluenesulfonic acid (C Amine) Category
6-Amino-4-chloro-m-toluenesulfonic acid (2B Acid; CASRN 88-51-7)
2-Amino-5-chloro-/?-toluenesulfonic acid	(C Amine; CASRN 88-53-9)
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.) Science Direct and ECHA4. OPPT's focus on these specific sources is based on
their being of high quality, highly relevant to hazard characterization, and publicly available.
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.
4	European Chemicals Agency, http://echa.europa.eu.

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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
OPPT does not develop HCs for those HPV chemicals which have already been assessed
internationally through the HPV program of the Organization for Economic Cooperation and
Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment
Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are
presented in an international forum that involves review and endorsement by governmental
authorities around the world. OPPT is an active participant in these meetings and accepts these
documents as reliable screening-level hazard assessments.
These hazard characterizations are technical documents intended to inform subsequent decisions
and actions by OPPT. Accordingly, the documents are not written with the goal of informing the
general public. However, they do provide a vehicle for public access to a concise assessment of
the raw technical data on HPV chemicals and provide information previously not readily
available to the public.
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U.S. Environmental Protection Agency September, 2014
Hazard Characterization Document	
Chemical Abstract
Service Registry Number
(CASRN)
88-51-7
88-53-9
Chemical Abstract Index
Name
Benzenesulfonic acid, 2-amino-4-chloro-5-methyl-
Benzenesulfonic acid, 2-amino-5-chloro-4-methyl-
Structural Formula
OH
1
o=s=o
£T
h3c T
CI
SMILES: 0=S(=0)(0)c(c(N)cc(c 1 C)Cl)c 1
OH
1
o=s=o
ch3
SMILES: 0=S(=0)(0)c(c(N)cc(c 1 Cl)C)c 1
Summary
2B acid and C amine are solids possessing negligible vapor pressure and moderate water
solubility. Both are expected to have high mobility in soil. C amine was not readily
biodegradable using a standard OECD screening test and did not degrade in an activated
sludge from a sewage treatment plant. Volatilization is expected to be low since these
substances are expected to exist as anions in the environment and anions do not volatilize.
The rate of hydrolysis is negligible. The rate of atmospheric photooxidation is moderate;
however, this is not a relevant environmental degradation pathway since these substances are
not expected to exist in the vapor phase in the atmosphere. 2B acid and C amine are expected
to have moderate persistence (P2) and low bioaccumulation potential (Bl).
2B Acid
The acute oral toxicity of 2B Acid in rats is low. The acute inhalation toxicity of 2B Acid is
moderate. 2B Acid is mildly irritating to rabbit skin and eyes.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
The potential hazard of 2B Acid to aquatic organisms could not be evaluated because no
adequate data were available.
The repeated-dose, reproductive and developmental toxicity, genetic toxicity (gene mutations
and chromosomal aberrations), acute toxicity to fish and aquatic invertebrates and toxicity to
aquatic plants were identified as data gaps under the HPV Challenge Program.
C Amine
The acute oral toxicity of C Amine in rats is low. C Amine is mildly irritating to rabbit skin
and irritating to rabbit eyes. C Amine did not induce mutagenicity in bacterial cells.
The potential hazard of C Amine to aquatic organisms could not be evaluated because no
adequate data were available.
The repeated-dose, reproductive and developmental toxicity, chromosomal aberrations, acute
toxicity to fish and aquatic invertebrates, and toxicity to aquatic plants endpoints were
identified as data gaps under the HPV Challenge Program.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
The sponsor, Color Pigment Manufacturers Association, Inc., submitted a Test Plan and Robust
Summaries to EPA for 6-ainino-4-chloro-/??-toluenesulfonic acid (2B Acid; CASRN 88-51-7; 9th
CI name: benzenesulfonic acid, 2-amino-4-chloro-5-methyl-) and 2-amino-5-chloro-/>
toluenesulfonic acid (C Amine; CASRN 88-53-9; 9th CI name: C amine) dated June 2006. EPA
posted the submission on the ChemRTK HPV Challenge website on August 29, 2006
(http://www.epa.gov/chemrtk/pubs/summaries/6amino4/cl6298tc.htm). EPA comments on the
original submission were posted to the website on March 5, 2009. Public comments were also
received and posted to the website. The sponsor provided responses to EPA comments on April
27, 2009; however, these responses have not yet been posted to the HPV Challenge site.
Category Justification
The sponsor asserted that the proposed category was reasonable for ecological effects endpoints
on the basis of the structural similarity of 2B Acid and C Amine, and EPA agrees. For health
effects, however, EPA commented that the category was not adequately supported.
Toxicological similarity of 2B Acid and C Amine depends on: (1) the nature of the complex
stereoelectronic relationships of the substituents; (2) the expected zwitterionic character of the
two substances; and (3) how susceptible the two unsubstituted ring positions are to metabolic
attack and how this relative reactivity may differ in the two proposed category members. These
issues were not addressed in the test plan and robust summaries. EPA commented that the
sponsor needed to provide evidence (such as pharmacokinetic or non-acute toxicity data) that
supported read-across of data between the two proposed category members. Since the sponsor
did not provide substantive evidence in their response to support read-across of health data
between the two proposed category members, adequacy of health data was assessed
independently for the sponsored chemicals, 2B Acid and C Amine.
Justification for Supporting Chemical
The sponsor proposed the use of 2-amino-5-methylbenzenesulfonic acid (4B Acid; CASRN 88-
44-8) as a supporting chemical for 2B Acid and C Amine on the basis of similar structures,
functions and characteristics among the three substances; however, 4B Acid lacks the chlorine
substituent present in the two sponsored chemicals. The sponsor did not provide evidence in the
original test plan or in their response to EPA comments to address the potential differences in the
reactivity, persistence or toxicity of the proposed non-chlorinated supporting chemical, 4B Acid,
relative to the sponsored chlorinated substances, 2B Acid and C Amine, and has not provided
sufficient data to support the claimed toxicological similarities of the two types of substances.
Therefore, EPA did not consider the proposed supporting chemical adequate to characterize
health effects endpoints for the sponsored substances. For ecological effects, 4B Acid may be an
acceptable supporting chemical, but all of the ecological effects data provided for 4B Acid were
inadequate because testing was performed at only a single, nontoxic concentration (10 mg/L) that
was below limit test concentrations and below the expected water solubility limit. Therefore,
data submitted on 4B Acid were not used in the preparation of this hazard characterization.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
1. Chemical Identity
1.1	Identification and Purity
The purity of the substance, when given in the robust summary, varied from 95% to > 99.9%.
1.2	Physical-Chemical Properties
The physical-chemical properties of 2B acid and C amine are summarized in Table 1. The
structures of these compounds are provided in the Appendix. 2B acid and C amine are solids
possessing negligible vapor pressure and moderate water solubility. These substances are used
as closed system intermediates in the production of color pigments.
Table 1. Physical-Chemical Properties of 2B acid and C amine1
Property
2B acid
C amine
CASRN
88-51-7
88-53-9
Molecular Weight
221.66
221.66
Physical State
Solid powder
Solid powder
Melting Point
330°C (measured)
No data
Boiling Point
>300°C (estimated)2
>300°C (estimated)2
Vapor Pressure
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
•	CASRN 88-51-7:	500,000 to < 1 million pounds ;
•	CASRN 88-53-9:	< 500.000 pounds ;
CASRN 88-51-7 and 88-53-9:
No industrial processing and use, and commercial and consumer uses were reported for the
chemicals.
2.2 Environmental Exposure and Fate
The environmental fate properties are provided in Table 2.
2B acid and C amine are expected to have high mobility in soil. No biodegradation data were
located for 2B acid. C amine achieved 0-2% of its theoretical biochemical oxygen demand
(BOD) after 14 days using an activated sludge inoculum and the MITI (OECD 301C) test. It was
also not degraded using activated sludge from a sewage treatment plant in Japan over an
unspecified time frame. Volatilization is expected to be low since these substances are expected
to exist as anions in the environment and anions do not volatilize. The rate of hydrolysis is
negligible. The rate of atmospheric photooxidation is moderate; however, this is not a relevant
environmental degradation pathway since these substances are not expected to exist in the vapor
phase in the atmosphere. C amine did not bioconcentrate in carp when studied over a 6-week
incubation period at two different nominal concentrations. 2B acid and C amine are expected to
have moderate persistence (P2) and low bioaccumulation potential (Bl).
Table 2. Environmental Fate Properties of 2B acid and C amine1
Property
2B acid
C amine
CASRN
88-51-7
88-53-9
Photodegradation Half-
life
6.4 hours (estimated)2
7.2 hours (estimated)2
Hydrolysis Half-life
Stable
Stable
Biodegradation
No data
0-2% after 14 days (not readily
biodegradable)3
No degradation in an activated
sludge4
Bioaccumulation
Factor
BAF = 0.89 (estimated)2
BAF = 0.89 (estimated)2
Did not bioconcentrate in carp after
6 weeks3'5
Log Koc
1.1 (estimated)2
1.1 (estimated)2
Fugacity
(Level III Model)2
Air (%)
Water (%)
Soil (%)
Sediment (%)
<0.1
32.9
68.0
<0.1
<0.1
32.9
68.0
<0.1
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
Table 2. Environmental Fate Properties of 2B acid and C amine1
Property
2B acid
C amine
Persistence6
P2 (moderate)
P2 (moderate)
Bi oaccumul ati on6
Bl (low)
Bl (low)
'Color Pigments Manufacturers Association. 2006. Revised Test Plan and Robust Summary for 6-
Amino-4-chloro-m-toluenesulfonic Acid and 2-Amino-5-chloro-p-toluenesulfonic Acid. Available online
at http://www .epa.gov/hpv/pubs/summarics/6amino4/c 16298tc.htm as of August 13, 2012.
2U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S.
Environmental Protection Agency, Washington, DC, USA. Available online at
http://www.cpa.gov/opptintr/cxposurc/pubs/cpisiiitcdl .htm as of August 13, 2012.
3 Chemical Risk Information Platform (CHRIP) database. Searchable by CASRN online at
http://www.safe .nite.go,ip/english/db.html as of August 22, 2012.
4Matsui M; Murakami T; Sasaki T; et al. 1975. Activated sludge degradability or organic substances in
the waste water of the Kashima petroleum and petrochemical industrial complex in Japan. Prog Water
Technol 7(2-4): 645-660.
5The BCF was not calculated because a negative value was obtained after subtracting for the blank value.
6Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances.
Federal Register 64, Number 213 (November 4, 1999) pp. 60194-60204.
Conclusion: 2B acid and C amine are solids possessing negligible vapor pressure and moderate
water solubility. Both are expected to have high mobility in soil. C amine was not readily
biodegradable using a standard OECD screening test and did not degrade in an activated sludge
from a sewage treatment plant. Volatilization is expected to be low since these substances are
expected to exist as anions in the environment and anions do not volatilize. The rate of
hydrolysis is negligible. The rate of atmospheric photooxidation is moderate; however, this is
not a relevant environmental degradation pathway since these substances are not expected to
exist in the vapor phase in the atmosphere. 2B acid and C amine are expected to have moderate
persistence (P2) and low bioaccumulation potential (Bl).
3. Human Health Hazard
A summary of health effects data submitted for SIDS endpoints is provided in Table 3.
Acute Oral Toxicity
2B Acid (CASRN 88-51-7)
Crl:CD rats (10 males) were administered 2B Acid (97% purity) via gavage as a 40% suspension
in corn oil at 7500 mg/kg and observed for 14 days. One rat died on day 4 post-dosing.
Additional details are from TSCATS (OTS0000944, FYI-OTS-0794-0944).
LDso > 7500 mg/kg
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U.S. Environmental Protection Agency
Hazard Characterization Document
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C Amine (CASRN 88-53-9)
Sprague-Dawley rats (5/sex) were administered C Amine (97% purity) via gavage as a 50%
solution in distilled water at 5000 mg/kg and observed for 14 days. There were no mortalities.
Study details are from TSCATS (OTS0001088, FYI-OTS-0794-1088).
LDso > 5000 mg/kg
Acute Inhalation Toxicity
2B Acid (CASRN 88-51-7)
Crl:CD rats (6 males/dose) were exposed nose-only for 4 hours to dust atmospheres of 2B Acid
(purity not stated) at 4.8, 12 or 13 mg/L and were observed for 14 days. In the three dose
groups, the content of respirable particles varied from 45 to 73%. There were no deaths in any
group. Study details are from TSCATS (OTS0000944, FYI-OTS-0794-0944).
4-h LC50 > 13 mg/L
Repeated-Dose Toxicity
No data were available.
Reproductive Toxicity
No data were available.
Developmental Toxicity
No data were available.
Genetic Toxicity - Gene Mutation
In vitro
C Amine (CASRN 88-53-9)
Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to
C Amine (purity not stated) in DMSO at 1, 10, 100, 500 or 1000 |ig/plate with and without
metabolic activation. Cytotoxicity in strains TA100 and TA1537 occurred at > 5000 |ig/plate.
Positive and negative controls were included and responded appropriately. Study details are
from TSCATS (OTS0001088; FYI-OTS-0794-1088).
C Amine was not mutagenic in this assay.
Genetic Toxicity - Chromosomal Aberrations
No data were available.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
Additional Information
Skin Irritation
2B Acid (CASRN 88-51-7)
Albino rabbits (6 males) were exposed to 2B Acid (> 97% purity) in saline via the dermal route
to intact skin at 0.5 g under occlusive conditions for 24 hours and were observed until 48 hours.
At 24 hours, slight to mild erythema was seen in 3 animals and at 48 hours, slight erythema was
seen in 1 animal. Study details are from TSCATS (OTS0000944, FYI-OTS-0794-0944).
2B Acid was mildly irritating to rabbit skin in this study.
C Amine (CASRN 88-53-9)
Six New Zealand rabbits (sex not indicated) were exposed to C Amine (purity not stated) via the
dermal route to intact and abraded skin at 0.5 g under occlusive conditions for 24 hours and were
observed until 72 hours. Slight erythema was seen at both abraded and intact skin sites, and very
slight edema was seen in one animal. The primary irritation index was 0.3. Study details are
from TSCATS (OTS0001088; FYI-OTS-0794-1088).
C Amine was mildly irritating to rabbit skin in this study.
Eye Irritation
2B Acid (CASRN 88-51-7)
Albino rabbits (2 males) received an ocular administration of 84.9 mg of C Amine (> 97%
purity). After 20 seconds, one of the treated eyes was washed with tap water for 1 minute.
Animals were observed for 7 days. The unwashed eye had corneal cloudiness for up to 3 days,
as well as moderate iritic congestion at 1 day and mild conjunctival redness and swelling. This
eye was normal within 7 days. This animal also had copious conjunctival discharge. The
washed eye had mild conjunctival discharge and swelling at 4 hours. This eye was normal
within 1 day. Study details are from TSCATS (OTS0000944, FYI-OTS-0794-0944).
2B Acid was mildly irritating to rabbit eyes in this study.
C Amine (CASRN 88-53-9)
Nine New Zealand White rabbits (sex not indicated) received an ocular administration of 0.1 g of
C Amine (purity not stated). After 30 seconds, treated eyes of three rabbits were washed with
tap water for 1 minute. Animals were observed for 21 days. One rabbit (with non-rinsed eye)
died on day 4. Effects noted in non-rinsed eyes included corneal opacity (mild to severe), iritis
changes (mild to severe) and conjunctival effects (erythema, edema, and discharge). These
changes were mostly reversible within 7 days. Effects noted in rinsed eyes were conjunctival
effects that had become minimal by day 4. Study details are from TSCATS (OTS0001088, FYI-
OTS-0794-1088).
C Amine was irritating to rabbit eyes in this study.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2014
Table 3. Summary of Screening Information Data Set under the U.S. HPV Challenge
Program - Human Health Data
Endpoints
2B Acid
(88-51-7)
C Amine
(88-53-9)
Acute Oral Toxicity
LDso (mg/kg-bw)
>7500
>5000
Acute Inhalation Toxicity
LC50 (mg/L)
> 13 mg/L
—
Repeated-Dose Toxicity
NOAEL/LOAEL
No Data
No Data
Reproductive/Developmental
Toxicity
NOAEL/LOAEL
No Data
No Data
Genetic Toxicity - Gene
Mutation
In vitro
No Data
Negative
Genetic Toxicity -
Chromosomal Aberrations
In vitro
No Data
No Data
Additional Information
Skin Irritation
Eye Irritation
Mildly irritating
Mildly irritating
Mildly irritating
Irritating
- indicates that endpoint was not addressed for this chemical; measured data are in bold text.
NOTE: For health endpoints, EPA did not consider read-across between these sponsored substances to be
supported (see Category Justification).
4. Hazard to the Environment
Acute Toxicity to Fish and Aquatic Invertebrates and Toxicity to Aquatic Plants
No adequate data were available.
Conclusion: The potential hazard of 2B Acid and C Amine to aquatic organisms could not be
evaluated because no adequate data were available.
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