United States
kS^laMIjk Environmental Protection
^J^iniiil m11 Agency
EPA/690/R-17/001F
Final
1-13-2017
Provisional Peer-Reviewed Toxicity Values for
/>-Chlorobenzenesulfonic Acid
(CASRN 98-66-8)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER
Jason C. Lambert, PhD, DABT
National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY
SRC, Inc.
7502 Round Pond Road
North Syracuse, NY 13212
PRIMARY INTERNAL REVIEWERS
J. Phillip Kaiser, PhD, DABT
National Center for Environmental Assessment, Cincinnati, OH
Jeff Swartout, MS
National Center for Environmental Assessment, Cincinnati, OH
This document was externally peer reviewed under contract to:
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02421-3136
Questions regarding the content of this PPRTV assessment should be directed to the EPA Office
of Research and Development's National Center for Environmental Assessment, Superfund
Health Risk Technical Support Center (513-569-7300).
li
/;-Chlorobenzenesulfonic acid

-------
TABLE OF CONTENTS
COMMONLY USED ABBREVIATIONS AND ACRONYMS	iv
BACKGROUND	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVs	1
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (NONCANCER AND CANCER)	6
HUMAN STUDIES	10
ANIMAL STUDIES	10
Oral Exposures	10
Inhalation Exposures	13
OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)	13
Supporting Animal Studies	13
Genotoxicity	13
Mode-of-Action/Mechanistic Studies	15
DERIVATION 01 PROVISIONAL VALUES	15
DERIVATION OF ORAL REFERENCE DOSES	16
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS	16
CANCER WEIGHT-OF-EVIDENCE DESCRIPTOR	16
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES	17
APPENDIX A. SCREENING PROVISIONAL VALUES	18
APPENDIX B. DATA TABLES	22
APPENDIX C. REFERENCES	26
in
/;-Chlorobenzenesulfonic acid

-------
COMMONLY USED ABBREVIATIONS AND ACRONYMS
a2u-g
alpha 2u-globulin
MN
micronuclei
ACGIH
American Conference of Governmental
MNPCE
micronucleated polychromatic

Industrial Hygienists

erythrocyte
AIC
Akaike's information criterion
MOA
mode of action
ALD
approximate lethal dosage
MTD
maximum tolerated dose
ALT
alanine aminotransferase
NAG
N-acetyl-P-D-glucosaminidase
AST
aspartate aminotransferase
NCEA
National Center for Environmental
atm
atmosphere

Assessment
ATSDR
Agency for Toxic Substances and
NCI
National Cancer Institute

Disease Registry
NOAEL
no-observed-adverse-effect level
BMD
benchmark dose
NTP
National Toxicology Program
BMDL
benchmark dose lower confidence limit
NZW
New Zealand White (rabbit breed)
BMDS
Benchmark Dose Software
OCT
ornithine carbamoyl transferase
BMR
benchmark response
ORD
Office of Research and Development
BUN
blood urea nitrogen
PBPK
physiologically based pharmacokinetic
BW
body weight
PCNA
proliferating cell nuclear antigen
CA
chromosomal aberration
PND
postnatal day
CAS
Chemical Abstracts Service
POD
point of departure
CASRN
Chemical Abstracts Service Registry
PODadj
duration-adjusted POD

Number
QSAR
quantitative structure-activity
CBI
covalent binding index

relationship
CHO
Chinese hamster ovary (cell line cells)
RBC
red blood cell
CL
confidence limit
RDS
replicative DNA synthesis
CNS
central nervous system
RfC
inhalation reference concentration
CPN
chronic progressive nephropathy
RfD
oral reference dose
CYP450
cytochrome P450
RGDR
regional gas dose ratio
DAF
dosimetric adjustment factor
RNA
ribonucleic acid
DEN
diethylnitrosamine
SAR
structure activity relationship
DMSO
dimethylsulfoxide
SCE
sister chromatid exchange
DNA
deoxyribonucleic acid
SD
standard deviation
EPA
Environmental Protection Agency
SDH
sorbitol dehydrogenase
FDA
Food and Drug Administration
SE
standard error
FEVi
forced expiratory volume of 1 second
SGOT
glutamic oxaloacetic transaminase, also
GD
gestation day

known as AST
GDH
glutamate dehydrogenase
SGPT
glutamic pyruvic transaminase, also
GGT
y-glutamyl transferase

known as ALT
GSH
glutathione
SSD
systemic scleroderma
GST
glutathione-S-transferase
TCA
trichloroacetic acid
Hb/g-A
animal blood-gas partition coefficient
TCE
trichloroethylene
Hb/g-H
human blood-gas partition coefficient
TWA
time-weighted average
HEC
human equivalent concentration
UF
uncertainty factor
HED
human equivalent dose
UFa
interspecies uncertainty factor
i.p.
intraperitoneal
UFh
intraspecies uncertainty factor
IRIS
Integrated Risk Information System
UFS
subchronic-to-chronic uncertainty factor
IVF
in vitro fertilization
UFd
database uncertainty factor
LC50
median lethal concentration
U.S.
United States of America
LD50
median lethal dose
WBC
white blood cell
LOAEL
lowest-observed-adverse-effect level


iv
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
/j-CHLOROBENZENESULFONIC ACID (CASRN 98-66-8)
BACKGROUND
A Provisional Peer-Reviewed Toxicity Value (PPRTV) is defined as a toxicity value
derived for use in the Superfund Program. PPRTVs are derived after a review of the relevant
scientific literature using established Agency guidance on human health toxicity value
derivations. All PPRTV assessments receive internal review by a standing panel of National
Center for Environment Assessment (NCEA) scientists and an independent external peer review
by three scientific experts.
The purpose of this document is to provide support for the hazard and dose-response
assessment pertaining to chronic and subchronic exposures to substances of concern, to present
the major conclusions reached in the hazard identification and derivation of the PPRTVs, and to
characterize the overall confidence in these conclusions and toxicity values. It is not intended to
be a comprehensive treatise on the chemical or toxicological nature of this substance.
PPRTV assessments are eligible to be updated on a 5-year cycle to incorporate new data
or methodologies that might impact the toxicity values or characterization of potential for
adverse human-health effects and are revised as appropriate. Questions regarding nomination of
chemicals for update can be sent to the appropriate U.S. Environmental Protection Agency
(EPA) Superfund and Technology Liaison (https://www.epa.gov/research/fact-sheets-regional-
science).
DISCLAIMERS
The PPRTV document provides toxicity values and information about the adverse effects
of the chemical and the evidence on which the value is based, including the strengths and
limitations of the data. All users are advised to review the information provided in this
document to ensure that the PPRTV used is appropriate for the types of exposures and
circumstances at the site in question and the risk management decision that would be supported
by the risk assessment.
Other U.S. EPA programs or external parties who may choose to use PPRTVs are
advised that Superfund resources will not generally be used to respond to challenges, if any, of
PPRTVs used in a context outside of the Superfund program.
This document has been reviewed in accordance with U.S. EPA policy and approved for
publication. Mention of trade names or commercial products does not constitute endorsement or
recommendation for use.
QUESTIONS REGARDING PPRTVs
Questions regarding the content of this PPRTV assessment should be directed to the EPA
Office of Research and Development's (ORD's) NCEA, Superfund Health Risk Technical
Support Center (513-569-7300).
1
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
INTRODUCTION
^-Chlorobenzenesulfonic acid (p-CBSA), CASRN 98-66-8, belongs to the class of
compounds known as benzenesulfonic acids. p-CBSA is produced by the sulfonation of
chlorobenzene with sulfuric acid and involves the continuous removal of water during the
reaction and is used as an intermediate in the manufacture of 4-chloro-3-nitrobenzenesulfonic
acid (Linder and Rodefeld. 2012). /?-CBSA is listed on the public inventory of the U.S. EPA's
Toxic Substances Control Act (U.S. EPA 2015); it is not, however, registered with Europe's
Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) program
(ECHA. 2016).
The empirical formula for/?-CBSA is C6H5CIO3S. The chemical structure is shown in
Figure 1. Table 1 summarizes the physicochemical properties of/?-CBSA. /?-CBSA exists as
deliquescent needles at room temperature (Linder and Rodefeld, 2012). /;-CBSA's low
estimated vapor pressure and low estimated Henry's law constant indicate that it is not expected
to volatilize from either dry or moist surfaces. /?-CBSA's vapor pressure indicates that it will
exist in both the vapor and particulate phases in the atmosphere. The estimated half-life of
vapor-phase p-CBSA in air by reaction with photochemically produced hydroxyl radicals is
25 days. The estimated high water solubility and low soil adsorption coefficient for /;-CBSA
indicate that it may leach to groundwater or undergo runoff after a rain event.
o
ci
o H
Figure l./7-Chlorobenzenesulfonic Acid Structure
2
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 1. Physicochemical Properties of/7-Chlorobenzenesulfonic Acid (CASRN 98-66-8)
Property (unit)
Value
Physical state
Solid
Boiling point (°C at 25 mm Hg)
UT
Melting point (°C)
67b
Density (g/cm3 at 20°C)
ND
Vapor pressure (mm Hg at 25 °C)
4.3 x 10 6 (estimated)13
pH (unitless)
ND
pKa (unitless)
ND
Solubility in water (mg/L at 25 °C)
3.1 x io5 (estimated)13
Octanol-water partition coefficient (log Kow)
-0.52 (estimated)13
Henry's law constant (atm-m3/mol at 25°C)
1.9 x 10 9 (estimated)13
Soil adsorption coefficient Koc (L/kg)
16 (estimated)13
Atmospheric OH rate constant (cm3/molecule-sec at 25°C)
4.3 x 10 13 (estimated)13
Atmospheric half-life (d)
25 (estimated)13
Relative vapor density (air = 1)
NA
Molecular weight (g/mol)
193b
Flash point (closed cup in °C)
ND
"Havnes (2014).
bU.S. EPA (2012b).
NA = not applicable; ND = no data.
A summary of available toxicity values for /;-CBSA from U.S. EPA and other
agencies/organizations is provided in Table 2.
3
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 2. Summary of Available Toxicity Values for />-Chlorobenzenesulfonic Acid and
Its Sodium Salt (CASRNs 98-66-8 and 5138-90-9)
Source
(parameter)ab
Value (applicability)
Notes
Reference
Noncancer
IRIS
NV
NA
U.S. EPA (2016)
HEAST
NV
NA
U.S. EPA (2011a)
DWSHA
NV
NA
U.S. EPA (2012a)
ATSDR
NV
NA
ATSDR (2016)
IPCS
NV
NA
IPCS (2016); WHO (2016)
IARC
NV
NA
IARC (2016)
Cal/EPA
Acute Acceptable Daily
Dose = 0.80 mg/kg-d;
Chronic Acceptable Daily
Dose = 0.27 mg/kg-d
Based on BMDLisd of
797 mg/kg-d for reduced
body-weight gain in a 32-d rat
studv bv American Biogenics
CorDOration (1985) and total
UF of 1,000 for the acute
acceptable daily dose and
3,000 for the chronic
acceptable daily dose
Cal/EPA (2015)
MiDEQ
Chronic RfD = 1 mg/kg-d
Based on a NOAEL of
1,000 mg/kg-d in a 32-d rat
studv bv American Biogenics
Corporation (1985) and total
Michigan DEO (2006)

UF of 1,000
OSHA
NV
NA
OSHA (2006):
OSHA (2011)
NIOSH
NV
NA
NIOSH (2016)
ACGIH
NV
NA
ACGIH (2015)
DOE (PAC)
PAC-3: 99 mg/m3;
PAC-2: 17 mg/m3;
PAC-1: 1.5 mg/m3
(for p-CBSA)
PAC-1 and PAC-2 based on
adjustments to 1-hr TEEL-1
and TEEL-2; PAC-3 based on
rat oral LD5o
DOE (2016)
USAPHC (air-MEG)
1-hr critical: 200 mg/m3;
1-hr marginal: 40 mg/m3;
1-hr negligible: 6 mg/m3
(for />-CBSA)
Based on 1-hr TEELs.
Documentation of the TEEL
derivations was not located
U.S. APHC (2013)
4
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 2. Summary of Available Toxicity Values for />-Chlorobenzenesulfonic Acid and
Its Sodium Salt (CASRNs 98-66-8 and 5138-90-9)
Source
(parameter)ab
Value (applicability)
Notes
Reference
Cancer
IRIS
NV
NA
U.S. EPA (2016)
HEAST
NV
NA
U.S. EPA (201 la)
DWSHA
NV
NA
U.S. EPA (2012a)
NTP
NV
NA
NTP (2014)
IARC
NV
NA
IARC (2015)
Cal/EPA
NV
NA
Cal/EPA (2011); Cal/EPA
(2016a): Cal/EPA (2016b)
ACGIH
NV
NA
ACGIH (2015)
aSources: ACGIH = American Conference of Governmental Industrial Hygienists; ATSDR = Agency for Toxic
Substances and Disease Registry; Cal/EPA = California Environmental Protection Agency; DOE = Department of
Energy; DWSHA = Drinking Water Standards and Health Advisories; HEAST = Health Effects Assessment
Summary Tables; IARC = International Agency for Research on Cancer; IPCS = International Programme on
Chemical Safety; IRIS = Integrated Risk Information System; MiDEQ = Michigan Department of Environmental
Quality; NIOSH = National Institute for Occupational Safety and Health; NTP = National Toxicology Program;
OSHA = Occupational Safety and Health Administration; USAPHC = U.S. Army Public Health Center.
Parameters: MEG = military exposure guideline; PAC = protective action criteria.
BMDL = benchmark dose lower confidence limit; /?-CBS A = /j-chlorobcnzcncsulfonic acid; LD50 = median lethal
dose; NA = not applicable; NOAEL = no-observed-adverse-effect level; NV = not available; RfD = reference dose;
SD = standard deviation; TEEL = temporary emergency exposure limit; UF = uncertainty factor.
Non-date-limited literature searches were conducted in May 2015 and updated in
June 2016 for studies relevant to the derivation of provisional toxicity values for /;-CBSA
(CASRN 98-66-8) and its sodium salt (CASRN 5138-90-9). Searches were conducted using the
U.S. EPA's Health and Environmental Research Online (HERO) database of scientific literature.
HERO searches the following databases: PubMed, ToxLine (including TSCATS1), and Web of
Science. The following databases were searched outside of HERO for health-related data:
ACGIH, ATSDR, Cal/EPA, EPA IRIS, EPA HEAST, EPA Office of Water (OW), EPA
TSCATS2/TSCATS8e, EPA High Production Volume (HPV), ECETOC, Japan Existing
Chemical Data Base (JECDB), European Chemicals Agency (ECHA), Organisation for
Economic Cooperation and Development (OECD) Screening Information Data Sets (SIDS),
OECD International Uniform Chemical Information Database (IUCLID), OECD HPV, NIOSH,
NTP, OSHA, and Defense Technical Information Center (DTIC).
5
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
REVIEW OF POTENTIALLY RELEVANT DATA
(NONCANCER AND CANCER)
Tables 3A and 3B provide overviews of the relevant noncancer and cancer databases,
respectively, for /;-CBSA and include all potentially relevant repeated-dose short-term-,
subchronic-, and chronic-duration studies, as well as reproductive and developmental toxicity
studies. Principal studies are identified in bold. The phrase "statistical significance," used
throughout the document, indicates ap-walue of < 0.05 unless otherwise specified.
6
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 3A. Summary of Potentially Relevant Noncancer Data for />-Chlorobenzenesulfonic Acid (CASRN 98-66-8)
Category3
Number of
Male/Female, Strain
Species, Study Type,
Reported Doses, Study
Duration
Dosimetryb
Critical Effects
NOAEL
BMDL/
BMCL
LOAEL
Reference
(comments)
Notes0
Human
1. Oral (mg/kg-d)
ND
2. Inhalation (mg/m3)
ND
Animal
1. Oral (mg/kg-d)
Subchronic
10 M/10 F, S-D rat,
gavage administration
of 0,10,50,500,1,000,
or 2,000 /7-CBSA
sodium salt for
31-32 consecutive d
0,9.0,45,
449,898,
1,800 as
/7-CBSA
No effects clearly related to
/j-CBSA exposure were
observed.
1,800
NDr
NDr
American Biogenics NPR,
Corporation (1985) PS
Observations in rats
included: Increased
(8.5-11% compared
to control) group
mean relative kidney
weight, clinical signs
of toxicity (salivation,
gasping, irregular
breathing), and
decreased
body-weight gain in
two males, as well as
ileal enteritis in
one male. These
effects may have all
been confounded by
issues unrelated to
/j-CBSA exposure.
7
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 3A. Summary of Potentially Relevant Noncancer Data for />-Chlorobenzenesulfonic Acid (CASRN 98-66-8)
Category3
Number of
Male/Female, Strain
Species, Study Type,
Reported Doses, Study
Duration
Dosimetryb
Critical Effects
NOAEL
BMDL/
BMCL
LOAEL
Reference
(comments)
Notes0
Chronic
Rabbit; number, sex,
strain, frequency and
mode of administration,
and formulation not
reported; 0, 0.1, 1,
10 mg/kg for 7 mo
ND
Authors reported significant
changes in hematology, clinical
chemistry, and liver and kidney
function tests; however, study
design details and quantitative
data were lacking.
NDr
NDr
NDr
Krvatov (1970)
(Lack of study design
details and quantitative
data preclude
affirmation of actual
dosimetry [e.g., ADD]
or effect level
identification)
PR
Developmental
25 F, CD rat, gavage
administration of 0,
1,000, or 2,000/?-CBSA
sodium salt on
GDs 7-16
0, 898, 1,800
as p-CBS A
No effects on maternal weight
gain, average litter size, or pup
weight on PNDs 1 or 3.
1,800
(based on
very limited
evaluations)
NDr
NDr
Chernoff and Rosen
(1985) as cited in U.S.
EPA (1986)
NPR
2. Inhalation (mg/m3)
ND
aTreatment/exposure duration (unless otherwise noted): Short-term = repeated exposure for 24 hours to <30 days; long-term (subchronic) = repeated exposure for
>30 days and <10% lifespan for humans (>30 days up to approximately 90 days in typically used laboratory animal species); and chronic = repeated exposure for >10%
lifespan for humans (>~90 days to 2 years in typically used laboratory animal species) (U.S. EPA. 2002).
bDosimetry values are presented as ADDs (mg/kg-day) for oral noncancer studies. In contrast to other repeated dose studies, dosimetry values from gestational exposure
studies are not adjusted for duration in the calculation of an ADD. Where applicable, the dose of /?-CBSA was calculated from the dose of /?-CBSA sodium salt by
multiplying the ratio of the molecular weights of the two compounds (192.6 g/mol /?-CBSA:214.6 g/mol /j-CBSA sodium salt).
°Notes: NPR = not peer reviewed; PR = peer reviewed; PS = principal study.
ADD = adjusted daily dose; BMCL = benchmark concentration lower confidence limit; BMDL = benchmark dose lower confidence limit;
/?-CBS A = /j-chlorobenzenesulfonic acid; F = female(s); GD = gestation day; LOAEL = lowest-observed-adverse-effect level; M = male(s); ND = no data; NDr = not
determined; NOAEL = no-observed-adverse-effect level; PND = postnatal day; S-D = Sprague-Dawley.
8
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 3B. Summary of Potentially Relevant Cancer Data for />-Chlorobenzenesulfonic Acid (CASRN 98-66-8)
Category
Number of Male/Female, Strain,
Species, Study Type and Duration
Dosimetry
Critical Effects
NOAEL
BMDL/BMCL
LOAEL
Reference
Notes
Human
1. Oral (mg/kg-d)
ND
2. Inhalation (mg/m3)
ND
Animal
1. Oral (mg/kg-d)
ND
2. Inhalation (mg/m3)
ND
BMCL = benchmark concentration lower confidence limit; BMDL = benchmark dose lower confidence limit; LOAEL = lowest-observed-adverse-effect level; ND = no
data; NOAEL = no-observed-adverse-effect level.
9
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
HUMAN STUDIES
No relevant data have been located regarding the toxicity of p-CBSA to humans
following oral or inhalation exposure.
ANIMAL STUDIES
Oral Exposures
Subchronic-Duration Studies
American Biogenics Corporation (1985)
In an unpublished, good laboratory practice (GLP)-compliant study, American
Biogenics Corporation (1985) examined the effects of/>-CBSA sodium salt (purity not
reported) administered by gavage in distilled water to Sprague-Dawley (S-D) rats. Groups of
10 rats/sex/dose were given doses of 0, 10, 50, 500, 1,000, or 2,000 mg/kg-day for 31 or
32 consecutive days (beginning at 45 days of age). Equivalent doses of/?-CBSA are 0, 9.0, 45,
449, 898, or 1,800 mg/kg-day1. In-life evaluations included twice-daily observations and
weekly detailed examinations for clinical signs and weekly body-weight and
food-consumption measurements. On study Day 28, all rats were given ophthalmologic
examinations. At the end of exposure, blood samples were collected for evaluation of
hematology (red blood cell [RBC] count, hemoglobin [Hb], hematocrit [Hct], mean
corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular
hemoglobin count [MCHC], platelet count, and total and differential leukocyte counts) and
serum chemistry (electrolytes, glucose, blood urea nitrogen [BUN], creatinine, aspartate
aminotransaminase [AST], alanine aminotransaminase [ALT], y-glutamyl transferase [GGT],
total protein, albumin, globulin, and total bilirubin). At sacrifice on study Days 32 or 33, gross
necropsies were performed on all animals, and the following organs were weighed: adrenals,
testes with epididymides, ovaries, kidneys, and liver. Microscopic examination of the
following organs was performed in control and animals in the highest-dose group: adrenals,
bone and marrow, brain, gonads, heart, small and large intestines, kidneys, liver, pancreas,
spleen, stomach, thyroid and parathyroid, urinary bladder, uterus, and cervix, and any other
tissue exhibiting grossly observed changes. Statistical analyses consisted of analysis of
variance (ANOVA) with the Tukey or Scheffe's test of multiple comparisons for parametric
data and the Kruskal-Wallis test with the Kruskal-Wallis multiple comparison test for
nonparametric data; these tests are considered to be appropriate for the nature of the data.
No rats in any exposure group died prior to study termination ( American Biogenics
Corporation. 1985). Clinical signs possibly related to/>-CBSA exposure were salivation,
gasping, and irregular breathing observed in one highest-dose male rat on Day 8 (only), and
irregular breathing observed in a second male from the highest-dose group, along with crusty
nose and eye, on Day 33 (the day of sacrifice for this rat). Necropsy findings in the latter rat (a
fractured snout and black crusted material around nose and mouth) suggest that the animal may
have experienced trauma, which may have been responsible for, or contributed to, the irregular
breathing in this animal. Due to the low incidence of affected animals, the transitory
occurrence of signs in one animal, and possible confounding cause of signs (potentially related
to physical trauma) in the other, these clinical signs are not considered to be related top-CBSA
exposure. Further, crusty nose or eye and misaligned or missing incisor(s) were also noted in
two male rats exposed to 898 mg/kg-day, one male rat exposed to 449 mg/kg-day, and one
'The dose of p-CBS A sodium salt was multiplied by the ratio of molecular weights
(192.6 g/mol /?-CBSA:214.6 g/mol /j-CBSA sodium salt) to yield an equivalent dose of p-CBSA.
10
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
female rat exposed to 45 mg/kg-day, and were considered by the study authors to be unrelated
to exposure.
The same two male rats from the highest-dose group that showed clinical signs of
toxicity (and trauma in one) also exhibited lower body-weight gain than others in their group
(90 and 117 g total weight change compared with 141-194 g in the remaining rats), as well as
markedly lower total food consumption (572 and 650 g total food consumed vs. 725-839 g for
the remaining rats). Thus, while the lower body-weight gain was likely attributable to lower
food intake, it is unclear whether the reduction in food intake reflected generalized diminished
health in one of these animals, and a more traumatic physical condition (e.g., fractured snout)
in the other. There were no statistically significant differences among the groups in mean body
weight or food consumption at any time point. Although the American Biogenics Corporation
(1985) ANOVA analysis of total body-weight change in males indicated a statistically
significant difference among the mean values for all of the groups, there were no biologically
significant (difference >10% compared with control) changes in body weight in any group.
Mean Week 4 and terminal (fasted) body weights were within 5% of control means in all
exposure groups (see Tables B-l and B-2).
Hematology and clinical chemistry results did not reveal any treatment-related changes;
a significant increase in white blood cell (WBC) count was seen in females exposed to
449 mg/kg-day, but not at higher doses or in males (see Tables B-l and B-2) (American
Biogenics Corporation. 1985). Ophthalmology examinations were unremarkable. At gross
necropsy, one of the two males from the highest-dose group, exhibiting clinical signs and
body-weight decrements, was observed to have dark contents in the stomach, ileum, and
cecum, as well as a discolored testis, enlarged lymph node, fractured snout, and black crusted
material about the nose and mouth.
The only statistically significant organ-weight changes were decreases in the absolute
and relative weights of the left adrenal gland in males exposed to 449 mg/kg-day; these effects
were not seen at higher doses, in the right adrenal weights, or in female rats (see Tables B-l
and B-2). An increase of 11% (compared with controls; not statistically significant) in mean
relative left kidney weight was observed in male rats of the highest dose; mean relative right
kidney weight was increased by 8.5% at the same dose. Absolute left and right kidney weights
were increased by 5 and 3%, respectively, in highest dose males. In contrast, absolute and
relative kidney weights were decreased at lower doses in males and at all doses in females.
Fluctuations in relative and absolute ovary weights as high as 31% difference from
control were also observed; these changes did not exhibit a dose-response relationship and
were not statistically significant (/>values > 0.05 for Jonckheere-Terpstra tests and linear
regression analyses performed for this review) ( American Biogenics Corporation. 1985).
Further, the biological significance of ovarian-weight changes can be difficult to interpret
because ovarian weights are highly variable in control populations and are influenced by both
reproductive cycling and stress (Sellers et al.. 2007).
One male rat from the highest-dose group exhibited slight bilateral testicular tubular
degeneration and epididymal aspermia. Another male rat from the highest-dose group
exhibited slight ileal enteritis. The study authors considered these and other observed changes
to be common in rats and unrelated to exposure.
11
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
In summary, observations at the highest dose included clinical signs of toxicity and
decreased body-weight gain in 2/10 males, a marginally biologically significant increase in
group mean relative kidney weight in males, testicular tubular degeneration (1/10 males vs.
0/10 male controls), and enteritis of the ileum (1/10 males vs. 0/10 male controls). As
described above, the relationship between clinical signs potentially indicative of an effect
(salivation, gasping, and irregular breathing) and exposure to />CBSA is uncertain due to the
low incidence of affected animals, transitory occurrence of signs in one animal, and possible
confounding signs of physical trauma in the other. Decreased body-weight gain was seen only
in the two males exhibiting clinical signs of toxicity, and there were no statistically or
biologically significant differences among treatment groups in mean body weight at any time
during the study. The increase in relative kidney weight was observed only in males, was not
statistically significant, was only marginally biologically significant (11% increase in the left
kidney and 8.5% increase in the right kidney), and reflects, in part, 4% decreased body weight
in males from the highest-dose group (increases in absolute kidney weight were only 3-5% in
males from the highest-dose group). It should be noted that the increases in kidney weight in
males from the highest-dose group stand in contrast to decreases in kidney weight in lower
dose males and in females. However, histopathology findings in individual male rats from the
highest-dose group were not correlated with organ-weight changes; the study authors
characterized the findings as common and unrelated to treatment.
Based on the lack of a clear (nonconfounded) relationship between potential toxic
effects and/>CBSA exposure, a no-observed-adverse-effect level (NOAEL) of
1,800 mg/kg-day is identified for this study.
Chronic-Duration Studies
Kryotov (1970)
In a chronic-duration toxicity study, originally published in Russian but with an
available English translation, Krvatov (1970) administered 0, 0.1, 1.0, or 10 mg/kg of/>-CBSA
(purity and formulation not reported) orally (presumably by gavage based on the description of
the short-term-duration experiment described elsewhere in the report) to rabbits for 7 months.
The strain, sex, number of rabbits per group, vehicle, and frequency of administration were not
reported. Parameters measured include body weight, behavior, conditioned reflexes,
hematology (RBC, WBC, Hb, phagocytic activity) and clinical chemistry (AST, ALT, serum
cholesterol), liver and kidney function tests (bromosulfophthalein [BSP] in the liver and
phenol red [phenolsulfonphthalein] in the kidney), organ weight, and vitamin C content of
organs. Histopathology was not conducted. No mortality data were presented, and no
quantitative values were presented for any of the results. Statistical analyses were limited to
Student's t-tests.
Apart from graphical reporting of BSP retention data, no quantitative results were
provided. The study author reported that exposure to 10 mg/kg-day p-CBSA significantly
decreased erythrocyte counts and hemoglobin, and increased reticulocyte counts, plasma
transaminase activities, serum urea, and serum cholesterol (Krvatov. 1970). The text of the
translation reported that treatment with the high dose also decreased BSP retention in the liver;
however, data shown graphically indicate that BSP retention was increased. Krvatov (1970)
also reported decreased phenol red in the kidneys and decreased vitamin C content in the
adrenal glands at this dose. Observations at the mid dose of 1 mg/kg-day included
nonsignificant increases in the activity of plasma transaminases and a significant increase in
12
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
BSP retention in the liver in the third and sixth months on study. The study author considered
1 mg/kg-day to be a "threshold" dose for/?-CBSA in rabbits and 0.1 mg/kg-day to be a
"subliminal" (i.e., ineffective) dose. The methods and results were not presented with enough
detail to allow for a full evaluation of this study; in addition, quantitative results were
presented graphically (and without any measure of variability) and only for BSP retention, not
for other endpoints. Therefore, effect levels cannot be identified for this study.
Developmental Studies
Chernoff and Rosen (1985) as cited in U.S. EPA (1986)
C hern off and Rosen (1985) as cited in U.S. EPA (1986) conducted a screening-level
teratology study of />CBSA sodium salt in rats. Mated female CD rats were given gavage
doses of 0, 1,000, or 2,000 mg/kg-day/?-CBSA sodium salt on Gestation Days (GDs) 7-16.
Equivalent doses of />CBSA are 0, 898, and 1,800 mg/kg-day1. Maternal-weight gain during
pregnancy was recorded, as were average litter sizes and average pup weights on Postnatal
Days (PNDs) 1 and 3; no other endpoints were evaluated. No differences in maternal-weight
gain, average litter size, or pup weights were observed among the exposed and control groups.
While a NOAEL of 1,800 mg/kg-day is identified for the study, the lack of detailed maternal
and offspring evaluations limits the confidence in this effect level determination.
Inhalation Exposures
No relevant data have been located regarding the toxicity of p-CBSA to animals
following inhalation exposure.
OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)
Other supporting studies on /;-CBSA include an acute lethality study in multiple species,
two poorly reported acute or short-term-duration oral toxicity studies, and genotoxicity data;
these are described below. Table 4 provides an overview of genotoxicity studies of />CBSA,
Supporting Animal Studies
Kryatov (1970) reported oral median lethal dose (LD50) values of 8,350 (white mice),
11,100 (albino rats), 7,100 (rabbits), and 16,000 mg/kg (guinea pigs) for/>-CBSA; no details of
the study design were reported. Mortalities occurred within 2 days of administration. The
author also briefly reported repeated-dose experiments in rats and rabbits (numbers of animals
not reported) exposed to/?-CBSA by gavage to doses of l/5th and 1/10th the animals' LD50
values (equivalent to -2,220 and 1,110 mg/kg-day, respectively, in rats and -1,400 and
710 mg/kg-day, respectively, in rabbits) for 20 days (Kryatov, 1970). No "marked cumulative
properties" were observed, although at necropsy the author did indicate evidence of hemorrhage
in the gastrointestinal tract and visceral hyperemia; however, it is unclear in the original report
whether this was in reference to/>CBSA exposure or another chemical (chloral) evaluated in the
study. One animal in the highest-dose group died (species not reported). No additional
information on this experiment was provided in the report. In addition, Krvatov (1970) briefly
noted an experiment in rats exposed to 0.1 or 1 mg/kg/;-CBSA and tested for effects on
conditioned reflexes; the results of this experiment were either not reported or of unclear
biological relevance (e.g., 'slower fixation of differentiation reaction').
Genotoxicity
/?-CBSA has been tested for genotoxicity in Ames assays, in a mammalian cell
mutagenicity assay, and in rats exposed in vivo [all tests conducted by Pharmakon Research
13
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
International (1985) as cited in U.S. EPA (1986)1. with uniformly negative results (see Table 4).
/;-CBSA did not increase the frequency of mutations in Salmonella typhimurium strains TA98,
TA100, TA1535, TA1537, and TA1538 or in L5178Y mouse lymphoma cells when tested with
or without metabolic activation, or the frequency of chromosomal aberrations (CAs) in bone
marrow in male rats given a single oral gavage dose of 2,000 mg/kg/>CBSA.
Table 4. Summary of/7-Chlorobenzenesulfonic Acid (CASRN 98-66-8) Genotoxicity
Endpoint
Test System
Doses/
Concentrations
Tested
Results
Without
Activation3
Results
With
Activation3
Comments
Reference
Genotoxicity studies in prokaryotic organisms
Mutation
Salmonella
typhimurium strains
TA98, TA100,
TA1535, TA1537,
TA1538
50, 167, 500, 1,667,
5,000 mg/plate


Positive and
solvent
controls gave
expected
responses.
Pharmakon
Research
International
(1985)	as cited
in U.S. EPA
(1986)
Genotoxicity studies in mammalian cells—in vitro
Mutation
L5178Y mouse
lymphoma
50, 125, 250, 500,
1,000 mg/mL


Positive and
solvent
controls gave
expected
responses.
Pharmakon
Research
International
(1985)	as cited
in U.S. EPA
(1986)
Genotoxicity studies—in vivo
CAs
Male rats given
single dose by
gavage and
sacrificed 6, 12, and
24 hr after dosing for
scoring of CAs in
bone marrow smears
2,000 mg/kg


Positive and
solvent
controls gave
expected
responses.
Pharmakon
Research
International
(1985)	as cited
in U.S. EPA
(1986)
a- = negative.
CA = chromosomal aberration.
14
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Mode-of-Action/Mechanistic Studies
/;-CBSA gave uniformly negative results in a large number of high-throughput screening
assays under the National Toxicology Program's (NTP's) Tox21 program2: 21 cell cycle assays,
86 nuclear receptor assays, 2 cell morphology assays, 78 deoxyribonucleic acid (DNA) binding
assays, 2 growth factor assays, 3 cytochrome assays, and 1 hydrolase assay. These
high-throughput assays are designed to survey the potential for a given xenobiotic to be bioactive
across a broad array of modes of action (MO As) known to be associated with altering the
structure and/or function of mammalian cells. The negative results for p-CBSA across the
specific assays listed here suggest a low potential for bioactivity in MO As involving
direct/indirect interaction with DNA, cell cycle activation/deactivation, or nuclear or growth
factor-dependent cell signaling.
DERIVATION OF PROVISIONAL VALUES
Tables 5 and 6 present summaries of noncancer and cancer references values,
respectively.
Table 5. Summary of Noncancer Reference Values for />-Chlorobenzenesulfonic Acid
(CASRN 98-66-8)
Toxicity Type (units)
Species/Sex
Critical Effect
p-Reference
Value
POD
Method
POD
(HED)
UFc
Principal
Study
Screening subchronic
p-RfD (mg/kg-d)
S-D rat/M
No effects clearly
related to p-CBSA
exposure were
observed.
1
NOAEL
432
300
American
Biogenics
Corporation
(1985)
Screening chronic
p-RfD (mg/kg-d)
S-D rat/M
No effects clearly
related to p-CBSA
exposure were
observed.
1 x KT1
NOAEL
432
3,000
American
Biogenics
Corporation
(1985)
Subchronic p-RfC
(mg/m3)
NDr
Chronic p-RfC
(mg/m3)
NDr
HED = human equivalent dose; M = male(s); NDr = not determined; NOAEL = no-observed-adverse-effect level;
/?-CBS A = /j-chlorobcnzcncsulfonic acid; POD = point of departure; p-RfC = provisional reference concentration;
p-RfD = provisional reference dose; S-D = Sprague-Dawley; UFC = composite uncertainty factor.
2Data are available online at http://actor.epa.gOv/dashboard/#chemical/98-66-8.
15
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 6. Summary of Cancer Reference Values for />-Chlorobenzenesulfonic Acid
(CASRN 98-66-8)
Toxicity Type (units)
Species/Sex
Tumor Type
Cancer Value
Principal Study
p-OSF (mg/kg-d) 1
NDr
p-IUR (mg/m3) 1
NDr
NDr = not determined; p-IUR = provisional inhalation unit risk; p-OSF = provisional oral slope factor.
DERIVATION OF ORAL REFERENCE DOSES
No data have been located on the effects of oral exposure to />CBSA in humans.
Information on the toxicity of repeated oral exposure to />CBSA is limited to an unpublished
32-day gavage study (although referred to in various literature as a "28-day" study, the actual
length of gavage exposure was 31-32 days) in rats (American Biogenics Corporation. 1985). an
unpublished screening-level developmental toxicity study in rats exposed by gavage [Chernoff
and Rosen (1985) as cited in U.S. EPA (1986)1. and the translated version of a paper published in
Russian describing a 7-month study in rabbits (Krvatov. 1970). Kryatov (1970) did not report
the sex or strain of rabbit exposed, nor the frequency or mode of p-CBSA administration. In
addition, Krvatov (1970) reported data on BSP retention graphically and without any measure of
variability, while quantitative results for other endpoints were not reported. Thus, effect levels
could not be determined. The available studies were unpublished and/or not peer reviewed and
thus were determined to be unsuitable for use in deriving provisional toxicity values. However,
the unpublished study by American Biogenics Corporation (1985) was well conducted and
reported adequate information with which to derive screening subchronic and chronic
provisional reference doses (p-RfDs) for /;-CBSA (see Appendix A).
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS
There are no studies of p-CBSA toxicity in humans or animals exposed by inhalation,
thus precluding derivation of provisional reference concentrations (p-RfCs).
CANCER WEIGHT-OF-EVIDENCE DESCRIPTOR
No studies were located examining possible associations between exposure to />CBSA
and cancer in humans or animals. Studies in animals (one 32-day study in rats, a poorly reported
7-month study in rabbits, and a developmental toxicity screening study in rats) are inadequate to
assess the carcinogenicity of/?-CBSA. In vitro bacterial and mammalian mutagenicity assays
and an in vivo CA assay were uniformly negative. The cancer weight-of-evidence (WOE)
descriptor forp-CBSA is provided in Table 7.
16
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table 7. Cancer WOE Descriptor for/7-Chlorobenzenesulfonic Acid (CASRN 98-66-8)
Possible WOE Descriptor
Designation
Route of Entry
(oral, inhalation, or
both)
Comments
"Carcinogenic to Humans "
NS
NA
There are no human data to support this.
"Likely to Be Carcinogenic to
Humans "
NS
NA
There are no sufficient animal studies to
support this.
"Suggestive Evidence of
Carcinogenic Potential"
NS
NA
There are no sufficient animal studies to
support this.
"Inadequate Information to
Assess Carcinogenic Potential"
Selected
Both
No carcinogenicity studies of />-CBSA
are available.
"Not Likely to Be Carcinogenic
to Humans "
NS
NA
No evidence of noncarcinogenicity is
available.
NA = not applicable; NS = not selected; /?-CBSA = /j-chlorobcnzcnesulfonic acid; WOE = weight of evidence.
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES
The lack of data on the carcinogenicity of p-CBSA following oral or inhalation exposure
precludes the derivation of quantitative estimates of carcinogenic potency.
17
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
APPENDIX A. SCREENING PROVISIONAL VALUES
For reasons noted in the main provisional peer-reviewed toxicity value (PPRTV)
document, it is inappropriate to derive provisional toxicity values for /;-chlorobenzenesulfonic
acid (p-CBSA). However, information is available for this chemical which, although insufficient
to support derivation of a provisional toxicity value under current guidelines, may be of limited
use to risk assessors. In such cases, the Superfund Health Risk Technical Support Center
summarizes available information in an appendix and develops a "screening value." Appendices
receive the same level of internal and external scientific peer review as the PPRTV documents to
ensure their appropriateness within the limitations detailed in the document. Users of screening
toxicity values in an appendix to a PPRTV assessment should understand that there is
considerably more uncertainty associated with the derivation of an appendix screening toxicity
value than for a value presented in the body of the assessment. Questions or concerns about the
appropriate use of screening values should be directed to the Superfund Health Risk Technical
Support Center.
DERIVATION OF A SCREENING SUBCHRONIC PROVISIONAL REFERENCE
DOSE
Information on the toxicity of repeated oral exposure to />CBSA is limited to a 32-day
gavage study in rats (American Biogenics Corporation, 1985), a screening-level developmental
toxicity study in rats exposed by gavage [Chernoff and Rosen (1985) as cited in U.S. EPA
(1986)1, and a 7-month study in rabbits (Krvatov. 1970) with significant deficiencies in
reporting. In the study by Krvatov (1970). the methods and results were not presented with
enough detail to allow for a full evaluation of the findings; quantitative results were presented
graphically (and without any measure of variability) and only for bromosulfophthalein (BSP)
retention, not for other endpoints. Thus, effect levels could not be determined from this study.
The developmental toxicity study in rats [Chernoff and Rosen (1985) as cited in U.S. EPA
(1986)1 identified a no-observed-adverse-effect level (NOAEL) of 1,800 mg/kg-day (as
/>CBSA) based on limited toxicological evaluations. The unpublished 32-day rat study by
American Biogenics Corporation (1985) provided repeat-dose information on the potential
effects of/>CBSA on body weight, clinical toxicity (e.g., salivation, gasping, and irregular
breathing), and changes in organ weight (e.g., adrenals, ovaries, and kidneys). However, none of
these effects could be attributed solely to/>CBSA exposure. For example, decreased
body-weight gain was associated primarily with two males in the highest-dose group that
consumed significantly less food than control rats and were reported to be in poor physical
condition (e.g., fractured snout). Further, total body weights were not significantly different
between treatment groups in general. Similarly, clinical signs of toxicity were observed in the
same two male rats that suffered apparent trauma, which confounds interpretation of potential
exposure-related effects. Lastly, adrenal-weight changes occurred only in the left adrenal, only
in males, and did not exhibit a dose-response relationship. Similarly, while ovary weights were
increased in treated females, this effect did not have a dose-response relationship and was not
statistically significant compared to control females. Increased relative kidney weight occurred
only in male rats, did not exhibit a dose-response relationship, was not statistically significant,
and may be more an artifact of decreased body weight than an increase in actual kidney weight
(e.g., absolute kidney weights increased by 3-5% and were not biologically significant). As
such, a NOAEL of 1,800 mg/kg-day (as />CBSA) was identified for the 32-day gavage study
( American Biogenics Corporation. 1985) based on the lack of effects clearly related to exposure;
18
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
this study was selected as the principal study for the screening subchronic provisional reference
dose (p-RfD).
The NOAEL of 1,800 mg/kg-day for lack of effects following 32 days of oral gavage
exposure was used to derive the screening subchronic p-RfD for p-CBSA, The NOAEL was
converted to a human equivalent dose (HED) according to current U.S. EPA (2011b) guidance.
In Recommended Use of Body Weight4 as the Default Method in Derivation of the Oral
Reference Dose (U.S. EPA. 2011b). the Agency endorses body-weight scaling to the 3/4 power
(i.e., BW3/4) as a default to extrapolate toxicologically equivalent doses of orally administered
agents from all laboratory animals to humans for the purpose of deriving an RfD from effects
that are not portal-of-entry.
Following U.S. EPA (2011b) guidance, the point of departure (POD) is converted to an
HED through the application of a dosimetric adjustment factor (DAF) derived as follows:
DAF = (BWa1/4 - BWh1/4)
where
DAF = dosimetric adjustment factor
BWa = animal body weight
BWh = human body weight
Using a reference BWa of 0.25 kg for rats and a reference BWh of 70 kg for humans, the
resulting DAF is 0.24 (U.S. EPA. 201 lb). Applying this DAF to the NOAEL of
1,800 mg/kg-day yields a POD (HED) as follows:
POD (HED) = NOAEL (mg/kg-day) x DAF
= 1,800 mg/kg-day x 0.24
= 432 mg/kg-day
The screening subchronic p-RfD for /;-CBSA was derived using the POD (HED) and a
composite uncertainty factor (UFc) of 300 (reflecting an interspecies uncertainty factor [UFa] of
3, an intraspecies uncertainty factor [UFh] of 10, and a database uncertainty factor [UFd] of 10):
Screening Subchronic p-RfD = POD (HED) UFc
= 432 mg/kg-day -^300
= 1 mg/kg-day
Table A-l summarizes the uncertainty factors for the screening subchronic p-RfD for
p-CBSA.
19
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table A-l. Uncertainty Factors for the Screening Subchronic p-RfD for
/J-Chlorobenzenesulfonic Acid (CASRN 98-66-8)
UF
Value
Justification
UFa
3
A UFa of 3 (10°5) is applied to account for uncertainty in characterizing the toxicokinetic or
toxicodynamic differences between rats and humans following /j-CBSA exposure. The toxicokinetic
uncertainty has been accounted for by calculation of a human equivalent dose (HED) through
application of a dosimetric adjustment factor (DAF) as outlined in the EPA's Recommended Use of
Bodv Weight3/4 as the Default Method in Derivation of the Oral Reference Dose ('U.S. EPA. 2011b).
UFh
10
A UFh of 10 is applied for intraspecies variability to account for human-to-human variability in
susceptibility in the absence of quantitative information to assess the toxicokinetics and
toxicodynamics of /?-CBSA in humans.
UFd
10
A UFd of 10 is applied to account for the limited toxicity database for /j-CBSA. which consists of an
unpublished 32-d rat study, an unpublished screening-level teratogenicity study in rats (which does
not suffice for evaluating the potential developmental effects of /?-CBSA exposure), and a poorly
reported chronic-duration toxicity study in rabbits from the Russian literature.
UFl
1
A UFl of 1 is applied because the POD is a NOAEL.
UFS
1
A UFS of 1 is applied because a subchronic-duration study was selected as the principal study.
UFC
300
Composite Uncertainty Factor = UFA x UFH x UFD x UFL x UFS.
HED = human equivalent dose; NOAEL = no-observed-adverse-effect level; /?-CBSA = /j-chlorobcnzcncsulfonic
acid; POD = point of departure; p-RfD = provisional reference dose; UF = uncertainty factor.
DERIVATION OF A SCREENING CHRONIC PROVISIONAL REFERENCE DOSE
The screening chronic p-RfD for />CBSA was derived using the same POD (HED) as the
screening subchronic p-RfD (432 mg/kg-day) and a UFc of 3,000 (reflecting a UFa of 3, a UFh
of 10, a UFd of 10, and a UFs of 10 for extrapolation from a subchronic to a chronic duration):
Screening Chronic p-RfD = POD (HED) UFc
= 432 mg/kg-day ^ 3,000
= 1 x 10"1 mg/kg-day
Table A-2 summarizes the uncertainty factors for the screening chronic p-RfD for
/?-CBSA.
20
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table A-2. Uncertainty Factors for the Screening Chronic p-RfD for
/J-Chlorobenzenesulfonic Acid (CASRN 98-66-8)
UF
Value
Justification
UFa
3
A UFa of 3 (10°5) is applied to account for uncertainty in characterizing the toxicokinetic or
toxicodynamic differences between rats and humans following /j-CBSA exposure. The toxicokinetic
uncertainty has been accounted for by calculation of a human equivalent dose (HED) through
application of a dosimetric adjustment factor (DAF) as outlined in the EPA's Recommended Use of
Bodv Weight3/4 as the Default Method in Derivation of the Oral Reference Dose (U.S. EPA. 2011b).
UFh
10
A UFh of 10 is applied for intraspecies variability to account for human-to-human variability in
susceptibility in the absence of quantitative information to assess the toxicokinetics and
toxicodynamics of /?-CBSA in humans.
UFd
10
A UFd of 10 is applied to account for the limited toxicity database for /j-CBSA. which consists of an
unpublished 32-d rat study, an unpublished screening-level teratogenicity study in rats (which does
not suffice for evaluating the potential developmental effects of /?-CBSA exposure), and a poorly
reported chronic-duration toxicity study in rabbits from the Russian literature.
UFl
1
A UFl of 1 is applied because the POD is a NOAEL.
UFS
10
A UFS of 10 is applied because a subchronic-duration study was selected as the principal study.
UFC
3,000
Composite Uncertainty Factor = UFA x UFH x UFD x UFL x UFS
HED = human equivalent dose; NOAEL = no-observed-adverse-effect level; /?-CBSA = /j-chlorobcnzcncsulfonic
acid; POD = point of departure; p-RfD = provisional reference dose; UF = uncertainty factor.
21
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
APPENDIX B. DATA TABLES
Table B-l. Selected Results in Male S-D Rats Administered p-CBSA Sodium Salt by Gavage for 31-32 Days"
Endpoint
Dose in mg/kg-d as />-CBSA Sodium Salt (mg/kg-d as />-CBSA)b
0
10 (9.0)
50 (45)
500 (449)
1,000 (898)
2,000 (1,800)
Total body-weight change (g)
165 ±20.9
170 ±21.3
(+3.0%)
176 ±9.8
(+6.7%)
160 ± 14.9
(-3.0%)
153 ± 19.6
(-7.3%)
150 + 29.2
(-9.1%)
Wk 4 body weight (g)
379 ± 26
378 ±30.4
(-0.3%)
392 ± 18.5
(+3.4%)
365 ±31.3
(-3.7%)
364 ±35.5
(-4.0%)
365 + 36.1
(-3.7%)
Terminal (fasted) body weight (g)
360.5 ±25.98
357.4 ±29.08
(-0.9%)
374.9 ±20.19
(+4.0%)
349.9 ±29.58
(-2.9%)
349.2 ±34.29
(-3.1%)
344.7 + 34.65
(-4.4%)
WBC count (thousand/mm3)
13.43 ±3.14
12.46 ±2.16
(-7.2%)
12.48 ±4.07
(-7.1%)
14.01 ±3.81
(+4.3%)
13.57 ±4.88
(+1.0%)
14.15 + 2.53
(+5.4%)
Adrenal weight
Right absolute (g)
0.0308 ±0.0109
0.0302 ± 0.0062
(-1.9%)
0.0316 ±0.0081
(+2.6%)
0.0314 + 0.0098
(+1.9%)
0.0312 + 0.0077
(+1.3%)
0.0301 +0.0064
(-2.3%)
Right relative (% body weight)
0.0086 ±0.0033
0.0084 ±0.0015
(-2.3%)
0.0085 ± 0.0023
(-1.2%)
0.0090 ± 0.0029
(+4.7%)
0.0089 + 0.002
(+3.5%)
0.0089 + 0.0026
(+3.5%)
Left absolute (g)
0.0375 ± 0.0042
0.0313 ±0.0062
(-17%)
0.0336 ±0.0048
(-10%)
0.0252 + 0.003**
(-33%)
0.0323 + 0.0086
(-14%)
0.0320 + 0.0044
(-15%)
Left relative (% body weight)
0.0105 ±0.0014
0.0088 ± 0.002
(-16%)
0.0090 ±0.0016
(-14%)
0.0072 ±0.0009**
(-31%)
0.0092 + 0.0022
(-12%)
0.0093 + 0.0014
("11%)
22
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table B-l. Selected Results in Male S-D Rats Administered p-CBSA Sodium Salt by Gavage for 31-32 Days3
Endpoint
Dose in mg/kg-d as />-CBSA Sodium Salt (mg/kg-d as />-CBSA)b
0
10 (9.0)
50 (45)
500 (449)
1,000 (898)
2,000 (1,800)
Kidney weight
Right absolute (g)
1.6435 ±0.199
1.6129 ±0.2155
(-1.9%)
1.6685 + 0.1918
(+1.5%)
1.5122 + 0.159
(-8%)
1.5799 + 0.1807
(-3.9%)
1.6979 + 0.1974
(+3.3%)
Right relative (% body weight)
0.4557 ±0.0408
0.4503 ±0.0389
(-1.2%)
0.4455 + 0.0504
(-2.2%)
0.4326 + 0.0343
(-5.1%)
0.4528 + 0.0319
(-0.6%)
0.4945 + 0.0579
(+8.5%)
Left absolute (g)
1.6012 ±0.1813
1.6132 ±0.1784
(+0.7%)
1.6327 + 0.1769
(+2%)
1.5026 + 0.1415
(-6.2%)
1.5482 + 0.1827
(-3.3%)
1.6835 + 0.1332
(+5.1%)
Left relative (% body weight)
0.4441 ±0.0362
0.4518 ±0.0429
(+1.7%)
0.4362 + 0.0497
(-1.8%)
0.4295 + 0.0184
(-3.3%)
0.4443 + 0.0424
(+0.0%)
0.4913 + 0.0483
(+11%)
"American Biogenics Corporation (1985).
bData reported as mean ± standard deviation (percent change compared with control); % change control = ([treatment mean - control mean] + control mean) x 100.
**Statistically significantly different from control (p < 0.01), as reported by the study authors.
/?-CBSA =/?-chlorobenzenesulfonic acid; S-D = Sprague-Dawley; WBC = white blood cell.
23
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table B-2. Selected Results in Female S-D Rats Administered p-CBSA by Gavage for 31-32 Days3
Endpoint
Dose in mg/kg-d as />-CBSA Sodium Salt (mg/kg-d as />-CBSA)b
0
10 (9.0)
50 (45)
500 (449)
1,000 (898)
2,000 (1,800)
Total body-weight change (g)
66 ±9.6
63 ± 10
(-4.5%)
69 + 20.5
(+4.5%)
68+12
(+3%)
66 + 8.1
(0)
61 + 12.4
(-7.6%)
Wk 4 body weight (g)
223 ± 16.6
217 ±11
(-2.7%)
225 + 26.9
(+0.9%)
220 + 16.6
(-1.3%)
222+ 16.8
(-0.4%)
216 + 21.2
(-3.1%)
Final (fasted) body weight (g)
208.252 ± 14.0241
201.105 ± 11.6435
(-3.4%)
209.344 + 25.2218
(0.5%)
206.477+ 16.1061
(-0.9%)
209.687 + 14.9094
(+0.7%)
202.877 + 20.4691
(-2.6%)
WBC count (thousand/mm3)
7.35 ± 1.5204
7.57 ± 1.82
(+3%)
9.21 + 2.61
(+25%)
11.15 + 4.78*
(+52%)
8.70 + 2.60
(+18%)
9.85 + 2.12
(+34%)
Adrenal weight
Right absolute (g)
0.0352 ±0.0077
0.0417 ±0.0082
(+18%)
0.0414 + 0.0089
(+18%)
0.0364 + 0.0066
(+3.4%)
0.0405 + 0.0086
(+15%)
0.0357 + 0.0068
(+1.4%)
Right relative (% body weight)
0.0169 ±0.0035
0.0208 ±0.0041
(+23%)
0.0200 + 0.0047
(+18%)
0.0176 + 0.0029
(+4.1%)
0.0193 + 0.0039
(+14%)
0.0178 + 0.0041
(+5.3%)
Left absolute (g)
0.0372 ±0.0083
0.0407 ±0.0081
(+9.4%)
0.0383 + 0.0077
(+3%)
0.0372 + 0.0084
(0)
0.0432 + 0.008
(+16%)
0.0373 + 0.0057
(+0.3%)
Left relative (% body weight)
0.0178 ±0.0037
0.0203 ± 0.0044
(+14%)
0.0185 + 0.004
(+3.9%)
0.0180 + 0.0035
(+1.1%)
0.0206 + 0.0038
(+16%)
0.0186 + 0.0035
(+4.5%)
Kidney weight
Right absolute (g)
0.9644 ±0.1053
0.9648 + 0.0818
(0)
0.9563 +0.1316
(-0.84%)
0.9404 + 0.1107
(-2.5%)
0.959 + 0.0782
(-0.56%)
0.901 + 0.1082
(-6.5%)
Right relative (% body weight)
0.4631 ±0.0383
0.48 ±0.0332
(+3.6%)
0.4566 + 0.0294
(-1.4%)
0.4548 + 0.029
(-1.8%)
0.4577 + 0.0255
(-1.2%)
0.45 + 0.0584
(-3.5%)
Left absolute (g)
0.9527 ± 0.0906
0.9689 + 0.812
(+1.7%)
0.9298 + 0.1361
(-2.4%)
0.9149 + 0.01333
("4%)
0.9522 + 0.0586
(-0.1%)
0.9006 + 0.0948
(-5.5%)
Left relative (% body weight)
0.4574 ± 0.0286
0.4819 + 0.0306
(+5.4%)
0.4436 + 0.0355
(-3%)
0.4417 + 0.0411
(-3.4%)
0.4561 +0.0411
(-0.3%)
0.45 + 0.0471
(-2.5%)
24
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
Table B-2. Selected Results in Female S-D Rats Administered p-CBSA by Gavage for 31-32 Days3
Endpoint
Dose in mg/kg-d as />-CBSA Sodium Salt (mg/kg-d as />-CBSA)b
0
10 (9.0)
50 (45)
500 (449)
1,000 (898)
2,000 (1,800)
Ovary weight
Right absolute (g)
0.0459 ±0.012
0.0479 ±0.0104
(+4.4%)
0.056 ± 0.0084
(+22%)
0.0554 + 0.0198
(+21%)
0.0434 + 0.0093
(-5.4%)
0.0534 + 0.0125
(+16%)
Right relative (% body weight)
0.022 ± 0.0055
0.0238 ± 0.0046
(+8.2%)
0.0271 +0.0052
(+23%)
0.0265 + 0.0076
(+20.5%)
0.0207 + 0.0035
(-5.9%)
0.0264 + 0.0058
(+20%)
Left absolute (g)
0.0436 ±0.0115
0.0508 ±0.0177
(+17%)
0.0494 + 0.0123
(+13%)
0.0536 + 0.0141
(+23%)
0.04 + 0.0091
(-8.3%)
0.0557 + 0.0119
(+28%)
Left relative (% body weight)
0.0209 ± 0.0052
0.0252 ± 0.0086
(+21%)
0.024 + 0.0071
(+15%)
0.0258 + 0.0053
(+23%)
0.0191 + 0.0042
(-8.6%)
0.0274 + 0.005
(+31%)
"American Biogenics Corporation (1985).
bData reported as mean ± standard deviation (percent change compared with control); % change control = ([treatment mean - control mean] + control mean) x 100.
* Statistically significantly different from control (p < 0.05), as reported by the study authors.
/?-CBSA =/?-chlorobenzenesulfonic acid; S-D = Sprague-Dawley; WBC = white blood cell.
25
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
APPENDIX C. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2015). 2015 TLVs and
BEIs. Based on the documentation of the threshold limit values for chemical substances
and physical agents and biological exposure indices. Cincinnati, OH.
http://www.acgih.ore/forms/store/ProductFormPublic/20154lvs-and-beis
American Biogenics Corporation. (1985). Twenty-eight day oral (gavage) toxicity study in
Albino rats using A-100. (Study No. 410-2298). American Biogenics Corp.
AT SDR (Agency for Toxic Substances and Disease Registry). (2016). Minimal risk levels
(MRLs). March 2016. Atlanta, GA: Agency for Toxic Substances and Disease Registry
(ATSDR). Retrieved from http://www.atsdr.cdc.gov/mrls/index.asp
Cal/KPA (California Environmental Protection Agency). (201 1). Hot spots unit risk and cancer
potency values. Appendix A. Sacramento, CA: Office of Environmental Health Hazard
Assessment.
http://standards.nsf.org/apps/group public/download, php?document id= 19121
Cal/KPA (California Environmental Protection Agency). (2015). Public health protective
concentration: para-chlorobenzene sulfonic acid in drinking water. Sacramento, CA:
Office of Environmental Health Hazard Assessment, Pesticide and Environmental
Toxicology Branch.
http://oehha.ca.gov/media/downloads/water/report/pcbsapublichealthcon.pdf
Cal/KPA (California Environmental Protection Agency). (2016a). Chemicals known to the state
to cause cancer or reproductive toxicity July 15, 2016. (Proposition 65 list). Sacramento,
CA: California Environmental Protection Agency, Office of Environmental Health
Hazard Assessment, http://oehha.ca.gov/proposition-65/proposition-65-list
Cal/KPA (California Environmental Protection Agency). (2016b). OEHHA toxicity criteria
database [Database], Sacramento, CA: Office of Environmental Health Hazard
Assessment. Retrieved from http://www.oehha.ca.gov/tcdb/index.asp
DOE (U.S. Department of Energy). (2016). Table 3: Protective Action Criteria (PAC) Rev. 28
based on applicable 60-minute AEGLs, ERPGs, or TEELs. The chemicals are listed by
CASRN. February 2016. https://sp.eota.energv.gov/pac/teel/Revision 28A Table3.pdf
KCHA (European Chemicals Agency). (2016). Registered substances. Helsinki, Finland.
Retrieved from http://echa.europa.eu/infonnation-on-chemicals/registered-substances
Haynes, WM. (2014). p-Chlorobenzenesulfonic acid. In WM Haynes (Ed.), CRC handbook of
chemistry and physics (95 ed., pp. 3-98). Boca Raton, FL: CRC Press.
I ARC (International Agency for Research on Cancer). (2015). I ARC Monographs on the
evaluation of carcinogenic risk to humans. Geneva, Switzerland: International Agency for
Research on Cancer, WHO. http://monographs.iarc.fr/KNG/Monographs/PDFs/index.php
I ARC (International Agency for Research on Cancer). (2016). I ARC Monographs on the
evaluation of carcinogenic risk to humans. Geneva, Switzerland: International Agency for
Research on Cancer, WHO. Retrieved from
http://monographs.iarc.fr/KNG/Monographs/PDFs/index.php
26
/;-Chl orobenzenesul foni c acid

-------
FINAL
01-13-2017
IPC'S (International Programme on Chemical Safety). (2016). INCHEM: Chemical safety
information from intergovernmental organizations [Database]: World Health
Organization. Canadian Centre for Occupational Health and Safety. Inter-Organization
Programme for the Sound Management of Chemicals. Retrieved from
http://www.inchem.org/
Kryatov, IA. (1970). Hygienic evaluation of sodium p-chlorobenzenesulfonate and chloral as
water pollutant. Gig Sanit35: 333-338.
Linder. O; Rodefeld. L. (2012). Benzenesulfonic acids and their derivatives. Weinheim: Wiley-
VCH Verlag GmbH & Co, KGaA. http://dx.doi.org/10.1002/14356007.a03 507
Michigan DEQ (Michigan Department of Environmental Quality). (2006). Toxicological
assessment for Part 201Criteria//213 RBSL development. para-Chlorobenzenesulfonic
acid Cas # 98-66-8. https://www.michigan.gov/documents/deq/deq-rrd-p-
CBSAToxic Assessment 288412 7.pdf
NIOSH (National Institute for Occupational Safety and Health). (2016). NIOSH pocket guide to
chemical hazards. Index of chemical abstracts service registry numbers (CAS No.).
Atlanta, GA: Center for Disease Control and Prevention, U.S. Department of Health,
Education and Welfare, http://www.cdc.gov/niosh/npg/npgdcas.html
NTP (National Toxicology Program). (2014). Report on carcinogens. Thirteenth edition.
Research Triangle Park, NC: U.S. Department of Health and Human Services, Public
Health Service, http://ntp.niehs.nih.gov/pubhealth/roc/rocl3/index.html
OSHA (Occupational Safety & Health Administration). (2006). Table Z-l: Limits for air
contaminants. Occupational safety and health standards, subpart Z, toxic and hazardous
substances. (OSHA standard 1910.1000, 29 CFR). Washington, DC: U.S. Department of
Labor.
http://www.osha.gov/pls/oshaweb/owadisp.show document?p table STAND A R1) S & p
id=9992
OSHA (Occupational Safety & Health Administration). (201 1). Air contaminants: Occupational
safety and health standards for shipyard employment, subpart Z, toxic and hazardous
substances. (OSHA Standard 1915.1000). Washington, DC: U.S. Department of Labor.
https://www.osha.gov/pls/oshaweb/owadisp.show document?p tab 1 e ¦ S T A N D A R D SŁ p
id=10286
Sellers. RS; Mortan. D; Michael. B; Roome. N; Johnson. JK; Yano. BL; Perry. R; Schafer. K.
(2007). Society of toxicologic pathology position paper: Organ weight recommendations
for toxicology studies [Review], Toxicol Pathol 35: 751-755.
http://dx.doi.org/10.1080/0192623070159530Q
U.S. APHC (U.S. Army Public Health Command). (2013). Environmental health risk assessment
and chemical exposure guidelines for deployed military personnel. Technical guide 230,
2013 revision. Aberdeen Proving Ground, MD.
http://phc.amedd.armv.mil/PHC%20Resource%20Library/TG230.pdf
U.S. EPA (U.S. Environmental Protection Agency). (1986). Toxicity testing in chlorobenzene
sulfonic acid.
U.S. EPA (U.S. Environmental Protection Agency). (2002). A review of the reference dose and
reference concentration processes (pp. 1-192). (EPA/630/P-02/002F). Washington, DC:
U.S. Environmental Protection Agency, Risk Assessment Forum.
http://www.epa.gov/osa/review-reference-dose-and-reference-concentration-processes
27
/;-Chlorobenzenesulfonic acid

-------
FINAL
01-13-2017
U.S. EPA (U.S. Environmental Protection Agency). (201 la). Health effects assessment summary
tables (HEAST). Washington, DC: U.S. Environmental Protection Agency, Office of
Emergency and Remedial Response, http ://epa-heast.ornl. gov/heast. php
U.S. EPA (U.S. Environmental Protection Agency). (201 lb). Recommended use of body weight
3/4 as the default method in derivation of the oral reference dose (pp. 1-50).
(EPA/100/R11/0001). Washington, DC: U.S. Environmental Protection Agency, Risk
Assessment Forum, Office of the Science Advisor.
https://www.epa.gov/risk/recommended-use-bodv-weight-34-default-method-derivation-
oral-reference-dose
U.S. EPA (U.S. Environmental Protection Agency). (2012a). 2012 Edition of the drinking water
standards and health advisories [EPA Report], (EPA/822/S-12/001). Washington, DC:
U.S. Environmental Protection Agency, Office of Water.
http://www.epa.gov/sites/production/files/2015-09/documents/dwstandards2Q12.pdf
U.S. EPA (U.S. Environmental Protection Agency). (2012b). PHYSPROP. Exposure assessment
tools and models: Estimation program interface (EPI) suite version 4.11. Washington,
DC: Office of Pollution Prevention and Toxics. Retrieved from
http ://www. epa. gov/oppt/exposure/pub s/epi suite.htm
U.S. EPA (U.S. Environmental Protection Agency). (2015). About the TSCA chemical substance
inventory. Download the non-confidential TSCA inventory [Database], Retrieved from
http://www2.epa.gov/tsca-inventorv/how-access-tsca-inventorv
U.S. EPA (U.S. Environmental Protection Agency). (2016). Integrated risk information system.
IRIS assessments [Database], Washington, DC: U.S. Environmental Protection Agency,
Integrated Risk Information System. Retrieved from https://www.epa.gov/iris
WHO (World Health Organization). (2016). Online catalog for the Environmental Health
Criteria (EHC) monographs. Available online at
http://www.who.int/ipcs/publications/ehc/en/
28
/;-Chlorobenzenesulfonic acid

-------