United States
kS^laMIjk Environmental Protection
^J^iniiil m11 Agency
EPA/690/R-10/005F
Final
9-29-2010
Provisional Peer-Reviewed Toxicity Values for
/>-Chlorotoluene
(CASRN 106-43-4)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER
Nina Ching Y. Wang, Ph.D.
National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY
ICF International
9300 Lee Highway
Fairfax, VA 22031
PRIMARY INTERNAL REVIEWERS
Q. Jay Zhao, Ph.D., M.P.H., DABT
National Center for Environmental Assessment, Cincinnati, OH
Paul G. Reinhart, Ph.D., DABT
National Center for Environmental Assessment, Research Triangle Park, NC
This document was externally peer reviewed under contract to
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02421-3136
Questions regarding the contents of this document may be directed to the U.S. EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center (513-569-7300)
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TABLE OF CONTENTS
COMMONLY USED ABBREVIATIONS	iii
BACKGROUND	1
HISTORY	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVS	2
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER)	4
HUMAN STUDIES	8
Oral and Inhalation Exposure	8
ANIMAL STUDIES	8
Oral Exposure	8
Short-term Study	8
Subchronic Studies	9
Chronic Studies	11
Developmental and Reproduction Studies	11
Inhalation Exposure	12
Developmental and Reproduction Studies	12
OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)	12
DERIVATION 01 PROVISIONAL VALUES	15
DERIVATION OF ORAL REFERENCE DOSE	15
Derivation of Subchronic p-RfD	15
Adjusted Doses for Daily Exposure	17
Derivation of Chronic p-RfD	18
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS	18
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR	18
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES	18
APPENDIX A. PROVISIONAL SCREENING VALUES	19
APPENDIX B. DATA TABLES	20
APPENDIX C. BMD MODELING OUTPUTS FOR^-CHLOROTOLUENE	21
APPENDIX D. REFERENCES	22
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COMMONLY USED ABBREVIATIONS
BMC
benchmark concentration
BMD
benchmark dose
BMCL
benchmark concentration lower bound 95% confidence interval
BMDL
benchmark dose lower bound 95% confidence interval
HEC
human equivalent concentration
HED
human equivalent dose
IUR
inhalation unit risk
LOAEL
lowest-observed-adverse-effect level
LOAELadj
LOAEL adjusted to continuous exposure duration
LOAELhec
LOAEL adjusted for dosimetric differences across species to a human
NOAEL
no-ob served-adverse-effect level
NOAELadj
NOAEL adjusted to continuous exposure duration
NOAELhec
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-ob served-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional reference concentration (inhalation)
p-RfD
provisional reference dose (oral)
POD
point of departure
RfC
reference concentration (inhalation)
RfD
reference dose (oral)
UF
uncertainty factor
UFa
animal-to-human uncertainty factor
UFC
composite uncertainty factor
UFd
incomplete-to-complete database uncertainty factor
UFh
interhuman uncertainty factor
UFl
LOAEL-to-NOAEL uncertainty factor
UFS
subchronic-to-chronic uncertainty factor
WOE
weight of evidence
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PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
/j-CHLOROTOLUENE (CASRN 106-43-4)
BACKGROUND
HISTORY
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1)	EPA's Integrated Risk Information System (IRIS)
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in EPA's Superfund
Program
3)	Other (peer-reviewed) toxicity values, including
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR);
~	California Environmental Protection Agency (CalEPA) values; and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's IRIS. PPRTVs are developed according to a Standard
Operating Procedure (SOP) and are derived after a review of the relevant scientific literature
using the same methods, sources of data, and Agency guidance for value derivation generally
used by the EPA IRIS Program. All provisional toxicity values receive internal review by a
panel of six EPA scientists and external peer review by three independently selected scientific
experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the multiprogram
consensus review provided for IRIS values. This is because IRIS values are generally intended
to be used in all EPA programs, while PPRTVs are developed specifically for the Superfund
Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a 5-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV documents conclude that
a PPRTV cannot be derived based on inadequate data.
DISCLAIMERS
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and Resource Conservation and Recovery Act (RCRA) program offices are advised to
carefully review the information provided in this document to ensure that the PPRTVs used are
appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility
in question. PPRTVs are periodically updated; therefore, users should ensure that the values
contained in the PPRTV are current at the time of use.
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It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV document and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
QUESTIONS REGARDING PPRTVS
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may 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), or OSRTI.
INTRODUCTION
/;-Chlorotoluene is a disubstituted benzene ring with a chlorine and a methyl group in a
para (1,4) configuration (see Figure 1). p-Chlorotoluene (sometimes as a mixture with
o-chlorotoluene) is used in the production of agrochemicals, plasticizers, flame retardants for
plastics, material preservatives, pigments and optical brighteners, antiaging agents,
pharmaceuticals, capacitor oils, thermal oils, perfumes, and flavorings (BUA, 1989). The
empirical formula for /;-chlorotoluene is C7H7CI. A table of chemicophysical properties is
provided below (see Table 1). In this document, "statistically significant" denotes ap-walue of
<0.05.
9H3
ci
Figure 1. /7-Chlorotoluene Structure
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Table 1. Physical Properties Table (p-Chlorotoluene)a
Property (Unit)
Value
Boiling point (°C)
161.5
Melting point (°C)
7.6
Density (g/cm3)
1.0677
Vapor pressure (Pa at 20°C)
3.1 mm Hg
pH (unitless)
NA
Solubility in water (g/L at 20°C)
0.040
Relative vapor density (air =1)
4.37
Molecular weight (g/mol)
126.59
Flash point (°C)
49.5
Octanol/water partition coefficient (unitless;
(Log Kow)
3.504
aBUA (1989); HSDB (2002)
A reference dose (RfD) of 0.02 mg/kg-day and a Drinking Water Equivalent Level
(DWEL) of 0.7 mg/L are included on the Drinking Water Standards and Health Advisories List
(U.S. EPA, 2006) for/;-chlorotoluene. The DWEL is a lifetime exposure concentration
protective against adverse, noncancer health effects, assuming all of the exposure comes from
drinking water. The DWEL is based on the RfD and a consumption of 2 L/day for a 70-kg
individual. The Drinking Water Standards and Health Advisories (DWSHA) List also provides a
Lifetime Health Advisory of 0.1 mg/L (U.S. EPA, 2006), which is derived from the DWEL using
a relative source contribution value. No RfD or reference concentration (RfC) is included in the
IRIS database (U.S. EPA, 2010). No toxicological reference values are reported in the HEAST,
and a comment in HEAST states that data are inadequate to support a quantitative risk
assessment for/;-chlorotoluene (U.S. EPA, 1997). The Chemical Assessments and Related
Activities (CARA) list (U.S. EPA, 1994) includes a Health and Environmental Effects Profile
(HEEP) for chlorotoluenes, but no HEEP has been issued specifically for /;-chlorotoluene. The
toxicity of />chlorotoluene has not been reviewed by ATSDR (2008) or the World Health
Organization (WHO, 2010). CalEPA (2008a,b) has not derived toxicity values for exposure to
/;-chlorotoluene in air or water. No occupational exposure limits for /;-chlorotoluene have been
derived by the American Conference of Governmental Industrial Hygienists (ACGIH, 2009), the
National Institute of Occupational Safety and Health (NIOSH, 2003), or the Occupational Safety
and Health Administration (OSHA, 2005).
No IRIS cancer assessment has been performed for/>-chlorotoluene (U.S. EPA, 2010).
/;-Chlorotoluene has not been evaluated under the 2005 Guidelines for Carcinogen Risk
Assessment (U.S. EPA, 2005); the DWSHA List provides a Cancer Descriptor of "D" (Not
Classifiable as to Human Carcinogenicity) for /;-chlorotoluene (U.S. EPA, 2006). The
International Agency for Research on Cancer (IARC, 2010) has not assessed the carcinogenic
potential of />chlorotoluene. /;-Chlorotoluene is not included in the National Toxicology
Program's (NTP's) 11th Report on Carcinogens (NTP, 2005). However, an NTP genotoxicity
study (Ames assay) of />chlorotoluene produced negative results with and without metabolic
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activation (NTP, 1986; Zeiger et al., 1992). CalEPA (2008b) has not prepared a quantitative
estimate of the carcinogenic potential of />chlorotoluene.
Literature searches were conducted on sources published from 1900 through September,
2010 for studies relevant to the derivation of provisional toxicity values for /;-chlorotoluene,
CAS No. 106-43-4. Searches were conducted using EPA's Health and Environmental Research
Online (HERO) evergreen database of scientific literature. HERO searches the following
databases: AGRICOLA; American Chemical Society; BioOne; Cochrane Library; DOE: Energy
Information Administration, Information Bridge, and Energy Citations Database; EBSCO:
Academic Search Complete; GeoRef Preview; GPO: Government Printing Office;
Informaworld; IngentaConnect; J-STAGE: Japan Science & Technology; JSTOR: Mathematics
& Statistics and Life Sciences; NSCEP/NEPIS (EPA publications available through the National
Service Center for Environmental Publications [NSCEP] and National Environmental
Publications Internet Site [NEPIS] database); PubMed: MEDLINE and CANCERLIT databases;
SAGE; Science Direct; Scirus; Scitopia; SpringerLink; TOXNET (Toxicology Data Network):
ANEUPL, CCRIS, ChemlDplus, CIS, CRISP, DART, EMIC, EPIDEM, ETICBACK, FEDRIP,
GENE-TOX, HAPAB, HEEP, HMTC, HSDB, IRIS, ITER, LactMed, MultiDatabase Search,
NIOSH, NTIS, PESTAB, PPBIB, RISKLINE, TRI; and TSCATS; Virtual Health Library; Web
of Science (searches Current Content database among others); World Health Organization; and
Worldwide Science. The following databases outside of HERO were searched for risk
assessment values: ACGM, AT SDR, CalEPA, EPA IRIS, EPA HEAST, EPA HEEP, EPA OW,
EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS.
REVIEW OF POTENTIALLY RELEVANT DATA
(CANCER AND NONCANCER)
Table 2 provides information for all of the potentially relevant studies identified through
the literature search. Entries for the selected principal studies (PS) are highlighted in bold.
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Table 2. Summary of Potentially Relevant Data for />-Chlorotoluene (CASRN 106-43-4)
Notes3
Category
Number of
Male/Female,
Species, Study Type,
and Duration
Dosimetry13
Critical Effects
NOAELb
BMDL/
BMCLb
LOAELb'°
Reference
(Comments)
Human
1. Oral (mg/kg-day)b
None
2. Inhalation (mg/m3)b

Acute
None
None
None
None
None
None
None

Subchronic
None
None
None
None
None
None
None

Chronic
None
None
None
None
None
None
None

Developmental
None
None
None
None
None
None
None

Reproductive
None
None
None
None
None
None
None

Carcinogenic
None
None
None
None
None
None
None
Animal
1. Oral (mg/kg-day)b

Short-term
10 animals per sex per
dose group, Sprague-
Dawley rat, gavage,
14 days
0, 200, 600,
1800
Decreased body-weight gain
200
NA
600
Terrill etal. (1990)
PS
Subchronic
10 animals per sex
per dose group,
Sprague-Dawley rat,
gavage, 90 days
0, 50, 200,
800
Mortality; decreased body
weight; increased blood
urea nitrogen (BUN),
creatinine, alkaline
phosphatase (ALP),
bilirubin, relative liver
weight, relative kidney
weight, and relative
adrenal weight at high-
dose only
200
NA
None; 800 is
the frank
effect level
(FEL)
Terrill et al. (1990)
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Table 2. Summary of Potentially Relevant Data for />-Chlorotoluene (CASRN 106-43-4)
Notes3
Category
Number of
Male/Female,
Species, Study Type,
and Duration
Dosimetry13
Critical Effects
NOAELb
BMDL/
BMCLb
LOAELb'°
Reference
(Comments)


190, rat (sex and strain
not specified), gavage,
6 months
0.01,0.1, 1.0
Increased hemoglobin;
increased erythrocyte and
leukocyte counts; changes
in cholinesterase, alanine,
and aspartate
aminotransferase (AST)
levels; increased BUN
levels; disrupted
carbohydrate metabolism;
marked reduction in liver
glucose levels; elevated
cholinesterase activity and
an increased content of
aspartic and glutamic acids
in brain homogenates;
impaired texture of brain
substance due to dilated
perivascular spaces;
capillary hyperemia and
slight hemorrhage; enlarged
cell nuclei and swelling of
the cytoplasm in brain cells
0.01
NA
0.1
Pis'ko et al. (1981) as
cited in BUA (1989)
No control was
specified; no details
on the specific
methods used,
including the dosing
frequency or medium,
sample size per
treatment group, and
the sex and strain of
the animals

Chronic
None
None
None
None
None
None
None

Developmental/
Reproductive
83 sexually mature
female rats and 357
fetuses, gavage, single
dose to 6 months
1100 or 1833
single; 55 or
550 for
2 months;
0.01, 0.1, or
1.0 for
6 months
Embryo mortality via
preimplantation loss and
liver abnormalities
55 for
2 months
1.0 for
6 months
NA
550 for
2 months
NA for 6
months
Pis'ko et al. (1981) as
cited in BUA (1989)
No control was
specified; no details on
the specific methods
used, including the
dosing frequency or
medium, sample size
per treatment group,
and the sex and strain
of the animals
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Table 2. Summary of Potentially Relevant Data for />-Chlorotoluene (CASRN 106-43-4)


Number of








Male/Female,








Species, Study Type,



BMDL/
LOAELb'°
Reference
Notes3
Category
and Duration
Dosimetry13
Critical Effects
NOAELb
BMCLb
(Comments)

Carcinogenic
None
None
None
None
None
None
None
2. Inhalation (mg/m3)b
None
aIRIS = Utilized by IRIS, date of last update; PS = Principal study; NPR = Not peer reviewed.
bDosimetry, NOAEL, BMDL/BMCL, and LOAEL values are converted to human equivalent dose (HED in mg/kg-day) or human equivalent concentration
(HEC in mg/m3) units. Noncancer oral data are only adjusted for continuous exposure.
°Not reported by the study author but determined from data.
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HUMAN STUDIES
Oral and Inhalation Exposure
There are no oral or inhalation single-chemical studies available in humans. However,
Goldblatt (1955) states that acute mixture studies conducted by their laboratory indicate that a
"3
60-minute exposure to a concentration of 400-ppm (equivalent to 2106 mg/m at 20°C)
chlorotoluene (all three isomers in unspecified proportions) causes severe (unspecified) toxicity
in humans. The concentration stated to cause illness if exposure continued for more than a short
time (not specified what was meant by a "short time" or "illness") was 200 ppm (equivalent to
1053 mg/m3 at20°C).
ANIMAL STUDIES
Oral Exposure
The effects of oral exposure of animals to ^-chlorotoluene have been evaluated in a
short-term study (Terrill et al., 1990), two subchronic-duration studies (Pis'ko et al., 1981 as
cited in BUA, 1989; Terrill et al., 1990), and a developmental/reproductive study (Pis'ko et al.,
1981 as cited in BUA, 1989). The studies by Pis'ko et al. (1981) are not adequately documented
and, therefore, cannot be used to support the development of a PPRTV. There are also
two subchronic studies available that used a mixture of o- and ^-chlorotoluene
(Industrial Bio-test Labs Inc., 1987a,b). These studies, likewise, are not suitable for
dose-response estimation without detailed mixture-interaction studies (e.g., additive, antagonist,
or synergistic). Terrill et al. (1990) presented data for 14-day and 90-day exposures with similar
methods in the same publication, but results are presented as separate studies under short-term
and subchronic studies.
Short-term Study—Terrill et al. (1990) administered ^-chlorotoluene (>98% pure) via
gavage at doses of 0 (vehicle only), 200, 600, or 1800 mg/kg-day in corn oil for 14 days to adult
Sprague-Dawley rats (10/sex/dose). The following parameters were examined at the end of the
14-day treatment period: clinical signs of toxicity, body weight and food consumption,
hematology (leukocyte and erythrocyte counts, hematocrit, hemoglobin, leukocyte differential,
and cell morphology), clinical chemistry (sodium, potassium, total protein, albumin calcium,
total bilirubin, creatinine, aspartate aminotransferase [AST], alanine aminotransferase [ALT],
alkaline phosphatase [ALP], lactate dehydrogenase [LDH], and blood urea nitrogen [BUN]),
urinalysis (pH, glucose, bilirubin, occult blood and uribilirubin), gross pathology, organ weights
(liver, kidneys, spleen, adrenal glands, thymus, brain, heart, lungs, testes with epididymis, and
ovaries), and histopathology (from all of the animals in the 600-mg/kg-day and five randomly
selected controls; adrenal glands, thyroid, esophagus, trachea, larynx, heart, spleen, liver,
kidneys, stomach, duodenum, jejunum, colon, pancreas, and gross lesions).
Eight of the 10 high-dose males and females died during treatment (Terrill et al., 1990).
Clinical signs in this group included prostration, salivation, and tremors after dosing. Body
weight and body-weight gain were biologically significantly reduced in both sexes administered
1800 mg/kg-day. Male rats administered 600-mg/kg-day also displayed a statistically significant
decrease in body-weight gain (body-weight data not reported). There was a statistically
significant decrease in food consumption in the mid- and high-dose males during the first week.
There were no other findings related to treatment after 14 days of treatment. The authors did not
report a NOAEL. However, a NOAEL of 200 mg/kg-day and a LOAEL of 600 mg/kg-day can
be derived based on decreased body weight and body-weight gain.
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Subchronic Studies—The 90-day study by Terrill et al. (1990) has been selected as
the principal study for deriving the subchronic and chronic p-RfD. Terrill et al. (1990)
administered />chlorotoluene (>98% pure) via gavage at doses of 0 (vehicle only), 50, 200, or
800 mg/kg-day in corn oil for 90 days to Sprague-Dawley rats (10/sex/dose). The same
parameters measured in the 14-day study were measured in the 90-day study, except
ophthalmology (preformed using indirect ophthalmoscopic techniques with 1% Mydriacyl) was
also examined in the 90-day study. Forty percent (4/10) of the males and 20% (2/10) of the
females in the high-dose group died prior to termination. Clinical signs of toxicity observed in
the high-dose group an hour after dosing included languid behavior, prostration, sensitivity to
touch, tremors, epistaxis, dyspnea, and/or polypnea. The study authors stated that these clinical
signs were closely related to the time of the animals' death. In surviving animals, these signs
were less severe at the weekly detailed observations, which were conducted prior to dosing.
Weekly body weights were lower in treated animals compared to the controls (all male treatment
groups and high-dose females). Statistically significant reductions were only reported for
body-weight gain in high-dose males and terminal body weight in high-dose females. Food
consumption was not significantly different across the dose groups. The authors reported no
treatment-related findings in ophthalmology or hematology.
There were several significant changes in clinical chemistry parameters (BUN, creatinine,
ALP, and bilirubin) in the high-dose males (see Table B-l) (Terrill et al., 1990). LDH levels
increased in a dose-related manner in the low- and mid-dose males but were comparable to
controls in the high-dose group and were not statistically significant. Although there were no
significant increases for any endpoint noted in the females, there was a dose-related increase in
AST (not statistically signficiant) and a nearly 2-fold increase in ALT in the high-dose group.
There was a significant decrease in urinary pH in mid- and high-dose males and females, but the
results were not monotonic. Gross lesions (depressed areas, pale areas, mottled appearance,
dilated renal pelvis, and/or granular/pitted/rough texture) accompanied by histopathological
findings (chronic progressive nephropathy) were noted in high-dose males. Although all groups
had dark areas in the glandular stomach, there was a slight increase in the frequency in the
high-dose males and females. Although there were a number of statistically significant changes
in organ weights, many were correlated with reduced body weight in the high-dose groups.
Statistically significant changes in organ weights that appeared to be related to treatment
independent of nutritional status occurred in the high-dose groups and included relative liver
weight in males, relative kidney weight in both sexes, and absolute and relative adrenal weight in
males. Histopathological changes were seen at higher frequencies in both sexes in the high-dose
groups and included centrilobular hypertrophy in the liver of both animals that died during
treatment and animals that were sacrified at termination, chronic progressive nephropathy, and
hyperplasia of the zona fasciculata in the adrenals. There was also minimal mucosal erosion in
the glandular stomach in two high-dose males, three high-dose females, and in one each of the
low- and mid-dose females. Liver and kidneys are likely to be the target organs via oral
exposure to />chlorotoluene in both sexes. The study authors stated that the NOEL
(no-observed-effect-level) was 200 mg/kg-day. Based on an increased mortality, the
800-mg/kg—day dose is a frank effect level (FEL), therefore, no LOAEL can be identified. A
NOAEL of 200 mg/kg-day is identified.
BUA (1989) stated that there was a poorly documented 6-month study (Pis'ko et al.,
1981) in rats. The original source (Pis'ko et al., 1981) is unavailable for review at this time (no
direct English translation). The study was published in a foreign language journal (Russian), and
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the publication is only two pages long, suggesting that only minimal information is available.
BUA (1989) summarized the results from the original study into English. In this study, a total of
190 rats received p-chlorotoluene (purity not reported; control not specified) via gavage at doses
of 0.01, 0.1, or 1.0 mg/kg-day in an oily solution for 6 months (specific details, e.g., dose
frequency, dosing medium, and sample size per treatment group were not provided). Similar
effects were noted in both the 0.1- and 1.0-mg/kg-day groups, but effects were less pronounced
in the 0.1-mg/kg-day group. Effects stated to have occurred included increased hemoglobin;
increased erythrocyte and leukocyte counts; impaired liver function as measured by changes in
cholinesterase, alanine, and AST levels; increased BUN levels; disrupted carbohydrate
metabolism; and marked reduction in liver glucose levels. The following effects on the central
nervous system were reported elevated cholinesterase activity and increased content of aspartic
and glutamic acids in brain homogenates, impaired texture of brain substance due to dilated
perivascular spaces, capillary hyperemia and slight hemorrhage, and enlarged cell nuclei and
swelling of the cytoplasm in brain cells. Histopathological findings included parenchymal
dystrophy and small necrotic foci in the liver. Pronounced plethora and thickening of the arterial
walls occurred in the liver, as well as the lungs. Additional findings included granular dystrophy
in the epithelium of convoluted renal tubules, atrophy in the lungs and ruptured alveolar walls,
and marked narrowing of the zona fasciculata in the adrenal glands. The NOAEL was
0.01 mg/kg-day. A LOAEL was not reported, but a LOAEL of 0.1 mg/kg-day can be derived
based on the numerous effects listed.
There are two subchronic unpublished studies (Toxic Substance Control Act submission)
available that used a mixture of o- and p-chlorotoluene (Industrial Bio-test Labs Inc, 1987a,b).
In the first study (Industrial Bio-test Labs Inc., 1987a), albino rats (15/sex/dose; 38 days old)
were administered 0, 100, 300, or 1,000 mg/kg-day of chlorotoluene (51% o-chlorotoluene and
48% /;-chlorotoluene) via gavage in corn oil for 90 days. Animals were weighed 2-3 times a
week, and weekly food consumption was measured in five rats per sex. Blood and urine were
obtained from 10 rats per sex in the control and high-dose groups at 40 and 90 days to test for
hematology and clinical chemistry. Urine was also obtained from the 10 rats per sex in the
remaining two groups at 90 days. Animals were sacrificed on Day 90 and necropsied. At
sacrifice, all rats were autopsied, and their brain, gonads, heart, kidneys, liver, and spleen were
weighed. Histopathology of the major organs and tissues was conducted on tissues from 10 rats
per sex in the control and high-dose groups.
Four animals died during the study due to intubation error (Industrial Bio-test Labs Inc.,
1987a). Beginning 3 days after study initiation, high-dose animals developed a resistance to
dosing and excessive salivation. Excessive urination also occurred in this group beginning in the
7th week of treatment. High-dose males had reduced body weight that was significantly different
from the controls on a number of occasions. The body-weight gain in the high-dose males was
10%) lower than the controls. There was a dose-dependent decrease in body-weight gain in the
females with a 10%> reduction observed in the 300-mg/kg-day group and a 19%> reduction in the
1000-mg/kg-day group. In addition, no change in food consumption was observed. Although
there were some statistically significant changes in hematology and clinical chemistry, the study
authors stated that the values were within normal ranges. Decreased blood glucose levels,
however, were consistently observed in high-dose males and females at both time points.
Urinalysis findings were reported to be unremarkable. No treatment-related changes were noted
in gross pathology, organ weight, or histopathology. The authors did not estimate a NOAEL.
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However, a NOAEL of 300 mg/kg-day and a LOAEL of 1000 mg/kg-day can be derived, based
on clinical signs of toxicity and reduced body weight.
The second study (Industrial Bio-test Labs Inc., 1987b) was conducted using dogs
(beagles). Dogs (4/sex/dose; 5-5.5 months old) were administered gelatin capsules containing a
corn oil suspension of 30, 100, or 300 mg/kg-day of chlorotoluene (51% o-chlorotoluene and
48% /;-chlorotoluene) for 90 days. Controls received vehicle only. Blood and urine was
collected on Days 42 and 85 for testing. At study termination, animals were sacrificed,
autopsied, and their brain, gonads, heart, kidneys, liver, spleen, adrenal glands, thyroid gland,
and pituitary gland were weighed. Histopathology of the major organs and tissues were
conducted.
None of the animals died, and no clinical signs of toxicity were observed
(Industrial Bio-test Labs Inc., 1987b). There was a 21% reduction in body-weight gain in
high-dose males, and food consumption was unaffected. High-dose males had slightly lower
erythrocyte counts (-8%), hemoglobin (-10%), and hematocrit (-11%). The study authors stated
that these were not related to treatment because the results were on the low end of the normal
range. It was stated that there were no treatment-related changes in clinical chemistry, gross
pathology, organ weight, or histopathology. The authors did not provide a NOAEL. However, a
NOAEL of 100 mg/kg-day and a LOAEL of 300 mg/kg-day can be derived from the data, based
on decreased body-weight gain.
Chronic Studies—No chronic studies of ^-chlorotoluene were identified.
Developmental and Reproduction Studies—BUA (1989) provided information on a
reproduction/developmental study (Pis'ko et al., 1981). The original source (Pis'ko et al., 1981)
is unavailable for review at this time (no direct English translation). The study was published in
a foreign language journal (Russian). However, the publication is only two pages long, which
suggests that only minimal documentation was provided. Very few details are provided on the
study design. Eighty-three sexually mature rats with 357 fetuses were examined (control was not
specified). Animals received either a single dose of 1100 or 1833 mg/kg; 55 or 550 mg/kg-day
for 2 months; or 0.01, 0.1, or 1.0 mg/kg-day for 6 months. No details on mating or the
relationship of dosing to time of mating were provided. Animals were sacrificed on Gestational
Day 20. The number of corpora lutea, implantations, malformed fetuses, and interuterine and
postnatal deaths were evaluated. Statistically significant effects were seen only in the group
receiving the 550 mg/kg-day dose for 2 months. At this dose, there was a significant increase in
embryo mortality caused by preimplantation loss, 12.1% of the embryos developed liver
hypertrophy while 47% had hypotrophy. No teratogenic or cytogenic effects were noted, but
offspring from of the 1833-mg/kg dose displayed a slight tendency for chromosomal
fragmentation (method not specified). The authors did not provide a NOAEL. Although details
are lacking in the study, a NOAEL of 55 mg/kg-day and a LOAEL of 550 mg/kg-day for a
2-month exposure can be tentatively derived from the data, based on embryo mortality via
preimplantation loss and liver hypertrophy in the embryos. A NOAEL of 1 mg/kg-day for a
6-month exposure based on minimal biological significance can be identified; a LOAEL is not
identified.
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Inhalation Exposure
There are no short-term, subchronic, or chronic inhalation studies available for
/;-chlorotoluene.
Developmental and Reproduction Studies—No studies could be located regarding the
effects of inhaled />chlorotoluene on reproduction and fetal development.
OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)
Undiluted />chlorotoluene (purity not specified) was administered to five male Wistar
rats (10-12 weeks of age; approximately 230 grams), for 5 days, at a dose of 250 mg/kg-day
(Bomhard et al., 1991). A number of compounds were tested, and the control consisted of a
peanut oil vehicle. Animals were sacrificed 2-3 hours after the last dose, and the kidneys were
removed for histopathology. Semiquantitative analysis of hyaline droplet accumulation on a
scale of 0 (no droplets) to 4 (extensive response with marked increase and widespread
distribution) and renal marker protein measurements were conducted. />Chlorotoluene had a
mean hyaline droplet accumulation score of 2.0, which was the same as the peanut oil control.
The protein level after /;-chlorotoluene exposure (2.69 ± 0.71 |ig) was also similar to the control
(2.45 ± 0.39 |ig). The study authors judged />chlorotoluene to be inactive.
Stadler and Kennedy (1996) tested 11 compounds found in carpet samples, including
/;-chlorotoluene, for sensory irritation potential by measuring the airborne concentration that
caused a 50% decrease in the respiration rate (RDso)- Male Swiss-Webster mice (number not
specified) were used. The RD50 for /;-chlorotoluene can be estimated to be approximately
"3
750 ppm (3880 mg/m ) from the figure presented in the study. There was a steep decrease in
respiration rate with increasing concentration of />chlorotoluene.
The genotoxicity of />chlorotoluene has been tested in numerous in vitro and in vivo
studies (see Table 3). These eight tests indicate that/>chlorotoluene is not mutagenic or
clastogenic in the large majority of test systems. The only exception was Huang et al. (1997)
who found />chlorotoluene to be active in a micronuclei test (however, a positive control was not
used; the negative control was dimethyl sulfoxide [DMSO]). This study contradicts the other
independent micronuclei test in mice by Herbold (1992), in which /;-chlorotoluene was found to
be not clastogenic (both a negative control [corn oil] and a positive control [cyclophosphamide]
were indicated).
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Table 3. Other Studies
Tests
Materials and Methods
Results
Conclusions
References
Genotoxicity
/;-Chlorotoluene was tested for mutagenic activity
with five strains of Salmonella typhimurium in a
standard and modified (conducted in a desiccator
to ensure adequate dispersion of a volatile
compound) Ames assay. The assay was
performed in the presence and absence of a
metabolic-activation system. Concentrations
tested were not reported.
/;-Chlorotoluene was not
mutagenic.
/•-Chlorotoluene was not
mutagenic.
Simmon et al.
(1977)
Genotoxicity
/;-Chlorotoluene was tested for mutagenic activity
in yeast (Saccharomyces cerevisiae D3). The
assay was performed in the presence and absence
of a metabolic-activation system. Concentrations
were not reported.
/;-Chlorotoluene was not
mutagenic.
/•-Chlorotoluene was not
mutagenic.
Simmon et al.
(1977)
Genotoxicity
/;-Chlorotoluene was tested for mutagenic activity
with five strains of Salmonella typhimurium in a
standard and modified (conducted in a desiccator
to ensure adequate dispersion of a volatile
compound) Ames assay. The assay was
performed in the presence and absence of a
metabolic-activation system at concentrations
ranging from 10 (ig/plate to 5000 (ig/plate or 0.05
mL to 1.00 mL per desiccator.
Toxicity was observed at
doses of 500 and 1000
(ig/plate. No mutagenic
response was obtained
using either of the
procedures.
/•-Chlorotoluene was not
mutagenic with or
without metabolic
activation.
Simmon and
Kauhanen
(1978)
Genotoxicity
/;-Chlorotoluene was tested for mutagenic activity
in yeast (Saccharomyces cerevisiae D3). The
assay was performed in the presence and absence
of a metabolic-activation system at concentrations
of 0.0005 to 0.05%.
Survival was decreased by
50% at concentration
between 0.02 and 0.03%,
but did not cause an
increase in mitotic
recombinants.
/•-Chlorotoluene was not
recombinogenic in S.
cerevisiae.
Simmon and
Kauhanen
(1978)
Genotoxicity
The genotoxicity of />chlorotolucnc was
determined using the umu-test without activation
in Salmonella typhimurium TA1535/p3K1002.
The umu-test can detect the induction of an error-
prone repair gene when DNA is damaged by
chemicals.
At concentrations of 100-
(ig/ml chlorotoluene, the
toxicity values were 0.77
(+S9) and 0.58 (-S9), where
values of less than 1.0 are
negative.
/•-Chlorotoluene was
considered to be negative
for genotoxicity in this
test.
Ono et al. (1992)
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Table 3. Other Studies
Tests
Materials and Methods
Results
Conclusions
References
Genotoxicity
Three hundred and eleven chemicals were tested
for mutagenicity in Salmonella typhimurium. The
tests were conducted using a preincubation
protocol in the absence of exogenous metabolic
activation, and in the presence of liver S-9 from
Aroclor-induced male Sprague-Dawley rats and
Syrian hamsters.
/;-Chlorotoluene was
negative.
/;-Chlorotoluene was not
mutagenic.
Zeiger et al.
(1992)
Genotoxicity
A mouse micronuclei test was performed. Male
and female mice were administered a single
intraperitoneal dose of 1000 mg/kg ofp-
chlorotoluene and were sacrificed at 16, 24, or
48 hours.
There was no change in the
ratio of polychromatic to
normo -chromatic
erythrocytes.
/;-Chlorotoluene was not
clastogenic.
Herbold (1992)
Genotoxicity
The genotoxicity of 26 hydrocarbons was studied
via a micronuclei test in human lymphocytes.
The micronuclei frequency
was 8, 12, and 17% at
concentrations of 27.2,
54.4, and 108.8 ppm,
respectively.
The study authors
characterized
/;-chlorotolucnc as an
active compound.
Huang et al.
(1997)
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DERIVATION OF PROVISIONAL VALUES
Tables 4 and 5 below present a summary of noncancer and cancer reference values,
respectively. IRIS values are indicated in the table if available.
DERIVATION OF ORAL REFERENCE DOSE
Derivation of Subchronic p-RfD
Of the two subchronic studies available to be considered for the derivation of the
subchronic p-RfD (i.e., Pis'ko et al., 1981; Terrill et al., 1990), only the Terrill et al. (1990)
provides sufficient details even though the results of the Pis'ko et al. (1981) study may be
consistent with a lower NOAEL. The Pis'ko et al. (1981) study is poorly documented (purity of
material not provided), and there was no indication that a control was used. There were no
details on the specific methods used, including the dosing frequency or medium, sample size per
treatment group, and the sex and strain of the animals. In addition, there is no indication that the
study adhered to any standard laboratory practices such as Good Laboratory Practice (GLP).
Furthermore, the neurotoxicity was only observed in the low doses (<0.1 mg/kg-day) in the
Pis'ko et al. (1981) study, while the Terrill et al. (1990) study observed neurotoxicity only at the
highest dose tested (800 mg/kg-day). The two mixture studies (Industrial Bio-test Labs Inc.,
1987a,b) administered with 51% o-chlorotoluene and 48% /;-chlorotoluene did not observe
neurotoxicity after conducting histopathology in the brain. The results from the Pis'ko et al.
(1981) study are inconsistent with other studies that showed similar observations with regards to
neurotoxicity.
The 90-day study by Terrill et al. (1990) is selected as the principal study for derivation
of a subchronic p-RfD. There is no specific critical effect and endpoint. The NOAEL was
200 mg/kg-day. The next highest dose (i.e., 800 mg/kg-day) was the FEL with an increase in
mortality accompanied by statistically significant changes in histopathology, clinical chemistry,
and organ weights, and increases in microscopic lesions (note the steep dose-response
relationship). Details of this study are provided in the Review of Potentially Relevant Data
section. Among the available acceptable studies, the Terrill et al. (1990) study represents the
lowest point-of-departure (POD) for deriving a subchronic p-RfD. The POD is based on the
NOAEL of 200 mg/kg-day. The data from the Terrill et al. (1990) study are not amenable to
BMD analysis because the highest dose tested caused mortality; the lower doses were not
significantly different from the control for all endpoints, and the data did not have a statistically
significant dose-response trend.
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Table 4. Summary of Reference Values for />-Chlorotoluene (CASRN 106-43-4)
Toxicity Type
(Units )a
Species/Sex
Critical Effect
/j-Reference
Value
POD
Method
POD
UFc
Principal Study
Subchronic p-RfD
(mg/kg-day)
Rat/M+F
Next dose was the
FEL, causing an
increase in mortality.
0.2
NOAEL
200
1000
Terrill et al. (1990)
Screening chronic p-RfD
(mg/kg-day)
Rat/M+F
Next dose was the
FEL, causing an
increase in mortality.
2 x 10"2
NOAEL
200
10,000
Terrill et al. (1990)
Subchronic p-RfC
(mg/m3)
None
None
None
None
None
None
None
Chronic p-RfC (mg/m3)
None
None
None
None
None
None
None
aAll the reference values obtained from IRIS are indicated with the latest review date.
Table 5. Summary of Cancer Values for />-Chlorotoluene (CASRN 106-43-4)
Toxicity Type
Species/Sex
Tumor Type
Cancer Value
Principal Study
p-OSF
None
None
None
None
p-IUR
None
None
None
None
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Adjusted Doses for Daily Exposure—No dosimetric adjustments were made for the
dose in the principal study for gavage treatment because p-chlorotoluene was administered
7 days a week. Therefore, the DOSEADJ was the same as the administered dose.
The subchronic p-RfD for /;-chlorotoluene, based on the NOAEL of 200 mg/kg-day in
male and female rats (Terrill et al., 1990) is derived as follows:
Subchronic p-RfD = NOAELadj UFC
= 200 mg/kg-day 1000
= 0.2 mg/kg-day or 2 x 10"1 mg/kg-day
Table 6 summarizes the uncertainty factors (UFs) applied in the derivation of the
subchronic p-RfD along with the rationale for the values that were selected. The overall level of
confidence in the subchronic p-RfD for /;-chlorotoluene is judged to be low for the reasons
summarized in Table 7.
Table 6. UFs for Subchronic p-RfD of/>-Chlorotoluene
UF
Value
Justification
ufa
10
A UFa of 10 is applied for interspecies extrapolation to account for potential
toxicokinetic and toxicodynamic differences between rats and humans. There are no data
to determine whether humans are more or less sensitive than rats to the general toxicity of
p-chlorotoluene.
UFh
10
A UFh of 10 is applied for intraspecies differences to account for potentially susceptible
individuals in the absence of information on the variability of response in humans.
ufd
10
A UFDof 10 is selected because there are no acceptable two-generation reproduction
studies or developmental studies of />chlorotolucnc.
ufl
1
A UFl of 1 is applied from extrapolation from a LOAEL to a NOAEL because the POD
is based on a NOAEL.
UFC
<3000
1,000

aTerrill et al. (1990).
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Table 7. Confidence Descriptor for Subchronic p-RfD for />-Chlorotoluene
Confidence
Categories
Designation"
Discussion
Confidence in Study
M
The study was given medium confidence because it meets most
of the data requirements. However, frequency and severity
information for histopathological endpoints were not provided.
Confidence in
Database
L
Confidence in the database was low because there are no
supporting studies available. In addition, no acceptable
reproduction/developmental studies were identified in the
available literature.
Confidence in
Subchronic p-RfDb
L
The overall confidence in the subchronic p-RfD is low.
aL = Low, M = Medium, H = High.
bThe overall confidence cannot be greater than the lowest entry in the table.
Derivation of Chronic p-RfD
No chronic p-RfD can be derived because doing so would require the application of a
UFC of 10,000. However, a screening chronic p-RfD is provided in Appendix A.
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS
No subchronic or chronic p-RfC values can be derived because there are no suitable
studies on inhalation exposure to />chlorotoluene.
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR
Table 8 identifies the cancer WOE descriptor for /;-chlorotoluene. Under the 2005
Guidelines for Carcinogen Assessment (U.S. EPA, 2005), there is "Inadequate Information to
Assess [the] Carcinogenic Potential' of />chlorotoluene.
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES
The lack of data on the carcinogenicity of />chlorotoluene precludes the derivation of
quantitative estimates for either oral (p-OSF) or inhalation (p-IUR) exposure.
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APPENDIX A. PROVISIONAL SCREENING VALUES
For reasons noted in the main PPRTV document, it is inappropriate to derive provisional
toxicity values for /;-chlorotoluene. 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 SCREENING CHRONIC ORAL REFERENCE DOSE
Chronic toxicity studies for oral />chlorotoluene exposures are not available. Therefore,
the screening chronic p-RfD is based on the NOAEL of 200 mg/kg-day in male and female rats
exposed to/>chlorotoluene for 90 days (Terrill et al., 1990). The screening chronic p-RfD for
/?-chlorotoluene, is derived as follows:
Screening Chronic p-RfD = NOAELadj ^ UFc
= 200 mg/kg-day 10,000
= 0.02 mg/kg-day or 2 x 10"2 mg/kg-day
Table A-l summarizes the UFs for the screening chronic p-RfD for /;-chlorotoluene.
Table A-l. UFs for Screening Chronic p-RfD for />-Chlorotoluene
UF
Value
Justification
UFa
10
A UFa of 10 is applied for interspecies extrapolation to account for potential
toxicokinetic and toxicodynamic differences between rats and humans. There are no
data to determine whether humans are more or less sensitive than rats to general toxicity
of />chlorotolucnc.
UFh
10
A UFh of 10 is applied for intraspecies differences to account for potentially susceptible
individuals in the absence of information on the variability of response in humans.
ufd
10
A UFDof 10 is selected because there are no acceptable two-generation reproduction
studies or developmental studies.
ufl
1
A UFl of 1 is applied for LOAEL to NOAEL extrapolation because the POD was based
on a NOAEL.
UFS
10
A UFS of 10 is applied for using data from a subchronic study (Terrill et al., 1990) to
assess potential effects from chronic exposure because data for evaluating responses
from chronic exposure are unavailable.
UFC
10,000

aTerrill et al. (1990).
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APPENDIX B. DATA TABLES
Table B-l. Selected Clinical Chemistry Parameters and Organ Weights
in Sprague-Dawley Rats Exposed to Oral />-Chlorotoluene for 90 Daysa
Parameter
Exposure Group (Daily Average Dose, mg/kg-day)
0
50 (50)
200 (200)
800 (800)
Males
Sample size
10
10
10
6
Terminal body weight
570.7 ±55.4b
583.3 ±73.5
591.6 ±51.1
488.8 ±80.4
Clinical Chemistry
BUN (mg/dl)
11± 1.3
11 ± 1.7
10 ± 1.6
33 ±28.2C
Creatinine (mg/dl)
0.5 ±0.05
0.6 ±0.06
0.5 ±0.05
1.0 ± 0.47°
LDH (IU/L)
769 ± 267.3
848 ±561.9
1145 ±514.3
658 ± 183.8
ALP (IU/L)
87 ±29.2
93 ± 17.7
106 ±30.4
136 ± 50.3°
Bilirubin (mg/dl)
0.16 ±0.052
0.17 ±0.048
0.16 ±0.052
0.23 ± 0.052°
Organ Weight
Absolute liver (g)
14.97 ±2.46
14.95 ±3.14
15.40 ±2.29
15.11 ±2.0
Relative liver (%)
2.616 ±0.291
2.542 ±0.212
2.579 ±0.242
3.134 ±0.453c
Absolute kidney (g)
3.57 ±0.43
3.66 ±0.56
4.04 ±0.54
4.12 ±0.66
Relative kidney (%)
0.628 ± 0.062
0.629 ± 0.063
0.683 ±0.079
0.878 ±0.299c
Absolute adrenal (g)
0.059 ±0.009
0.060 ±0.010
0.058 ±0.007
0.076 ±0.015c
Relative adrenal (%)
0.0104 ±0.0021
0.0105 ±0.0022
0.0098 ±0.0017
0.0164 ±0.0072c
Females
Sample size
10
10
10
8
Terminal body weight
320.5 ±20.7
301.5 ±23.7
329.7 ±42.9
282.4 ± 17.9C
Clinical Chemistry
AST (IU/L)
85 ± 19.9
97 ± 20.4
103 ±28.6
144 ± 128.6
ALT (IU/L)
34 ±22.6
28 ±6.0
29 ±7.9
61 ±79.2
Organ Weight
Absolute liver (g)
8.83 ± 1.33
8.54 ± 1.03
9.13 ± 1.19
9.82 ±0.96
Relative liver (%)
2.748 ±0.316
2.847 ± 0.409
2.807 ±0.468
3.481 ±0.316
Absolute kidney (g)
2.22 ±0.25
2.08 ±0.20
2.28 ±0.16
2.35 ±0.28
Relative kidney (%)
0.694 ± 0.067
0.692 ±0.071
0.699 ±0.077
0.835 ±0.120c
aTerrill et al. (1990).
bMeans ± SD.
Significantly different from control (p < 0.05) Dunnett's test.
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APPENDIX C. BMD MODELING OUTPUTS FOR/j-CHLOROTOLUENE
There are no BMD modeling outputs.
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APPENDIX D. REFERENCES
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BEIs: Threshold limit values for chemical substances and physical agents and biological
exposure indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
594528
ATSDR (Agency for Toxic Substances and Disease Registry). (2008) Toxicological profile
information sheet. Available online at http://www.atsdr.cdc.gov/toxpro2.html. 595415
Bomhard, E; Marsmann, M; Ruhl-Fehlert, C; Schade-Lehn, R; Schuurmann G. (1991) Screening
of aromatic compounds for their potency of inducing hyaline droplet accumulation in male rat
kidney. In PH Bach; KJ Ullrich (Ed.),Nephrotoxicity: Mechanisms, early diagnosis, and
therapeutic management (pp. 273-278). Michigan: Marcel Dekker. 202135
BUA (Beratergremium fiir Umweltrelevante Altstoffe). (1989) Chlorotoluenes
(Methylchlorobenzenes). GDCh-Advisory Committee on Existing Chemicals of Environmental
Relevance. Weinheim. 38. 399228
CalEPA (2008a) Office of Environmental Health Hazard Assessment. Search Chronic RELs.
Available online at from http://www.oehha.ca.gov/air/allrels.html. 595416
CalEPA (2008b) Office of Environmental Health Hazard Assessment. Search toxicity criteria
database. California Environmental Protection Agency. California. Available online at
http://www.oehha.ca.gov/air/hot_spots/pdf/TSDlookup2002.pdf. 595417
Goldblatt, MW. (1955) Research in industrial health in the chemical industry. Br JIndMed 72:
1-20. 595454
HSDB (Hazardous Substance Data Bank). (2002) 4-Chlorotoluene. Last revised on November 8,
2002. Available online at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~sFtv2Z: 1.
597405
Herbold, BA. (1992) Micronucleus test on the mouse [Final Report] with cover letter date
4/20/92; 03/3 1/92. Miles Inc., on behalf of Bayer AG. Pittsburgh, PA. 597383
Huang, Q-G; Song, W-L; Wang, L-S. (1997) Quantitative relationship between the
physiochemical characteristics as well as genotoxicity of organic pollutants and molecular
autocorrelation topological descriptors. Chemosphere 35: 2849-2855. 399217
IARC (International Agency for Research on Cancer). (2010) IARC Monographs on the
evaluation of carcinogenic risks to humans. Available online at http://monographs.iarc.fr/
index.php. 597416
Industrial Bio-test Labs Inc. (1987a) 90-Day subacute oral toxicity study with
monochlorotoluene isomers in albino rats [With cover letter dated 06/25/87], Occidental
Chemical Corporation. New York. 202632
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Industrial Bio-test Labs Inc. (1987b) 90-Day subacute oral toxicity study with
monochlorotoluene isomers (lot no S-75-1300) in beagle dogs [With cover letter dated
06/25/87], Occidental Chemical Corporation. New York. 202633
NIOSH (National Institute for Occupational Safety and Health). (2003) NIOSH pocket guide to
chemical hazards. Atlanta, GA: Department of Health and Human Services, Centers for Disease
Prevention and Control. 081445
NTP (National Toxicology Program). (1986) Salmonella: Study summary for /;-chlorotoluene.
National Toxicology Program. Research Triangle Park, NC. Study ID 623995. 597410
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