United States
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EPA/690/R-09/010F
Final
9-03-2009
Provisional Peer-Reviewed Toxicity Values for
2-Chloronaphthalene
(CASRN 91-58-7)
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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Commonly Used Abbreviations
BMD
Benchmark Dose
IRIS
Integrated Risk Information System
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 inhalation reference concentration
p-RfD
provisional oral reference dose
RfC
inhalation reference concentration
RfD
oral reference dose
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
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PEER-REVIEWED PROVISIONAL TOXICITY VALUES FOR
2-CHLORONAPHTHALENE (CASRN 91-58-7)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (U.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)	U.S. EPA's Integrated Risk Information System (IRIS).
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in U.S. 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 U.S. 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 U.S. EPA IRIS Program. All provisional toxicity values receive internal review by
two U.S. 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 U.S. 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.
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
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and limitations of the derived provisional values. PPRTVs are developed by the U.S. EPA
Office of Research and Development's National Center for Environmental Assessment,
Superfund Health Risk Technical Support Center for OSRTI. Other U.S. 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 U.S. EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
A chronic RfD of 8 x 10" mg/kg-day is available for 2-chloronaphthalene (chemical
structure shown in Figure 1) on IRIS (U.S. EPA, 2009). The RfD is based on a subchronic oral
gavage study in mice (U.S. EPA, 1989) that identified a LOAEL of 600 mg/kg-day and a
NOAEL of 250 mg/kg-day for dyspnea, abnormal appearance, and liver enlargement. This
assessment, which was posted 02/21/1990, is not presented in any other U.S. EPA document.
This RfD is not listed in Health Effects Assessment Summary Tables (HEAST, U.S. EPA, 1997)
or in the Drinking Water Standards and Health Advisories (DWHA) list (U.S. EPA, 2006). No
RfC or cancer assessment for 2-chloronaphthalene is available on IRIS (U.S. EPA, 2009) or in
the HEAST (U.S. EPA, 1997) or DWHA list (U.S. EPA, 2006). The only relevant document in
the Chemical Assessments and Related Activities (CARA) list (U.S. EPA 1991, 1994) is an
Ambient Water Quality Criteria Document (AWQCD) for chlorinated naphthalenes
(U.S. EPA, 1980) that includes few data and no assessment for 2-chloronaphthalene. The World
Health Organization (WHO, 2001) developed a Concise International Chemical Assessment
Document (CICAD) for chlorinated naphthalenes that declined to derive tolerable intakes due to
inadequate data. The Agency for Toxic Substances Disease Registry (ATSDR, 2009) has not
published a Toxicological Profile for 2-chloronaphthalene. The American Conference of
Governmental Industrial Hygienists (ACGIH, 2008), the National Institute for Occupational
Safety and Health (NIOSH, 2005), and the Occupational Safety and Health Administration
(OSHA, 2009) have not established occupational exposure limits for 2-chloronaphthalene. The
carcinogenicity of 2-chloronapthalene has not been assessed by the International Agency for
Research on Cancer (IARC, 2009) or by the National Toxicology Program (NTP, 2005, 2009).
Literature searches were conducted from the 1960s through August 2009 for studies
relevant to the derivation of provisional toxicity values for 2-chloronaphthalene. Databases
searched include MEDLINE, TOXLINE (with NTIS), BIOSIS, TSCATS/TSCATS2, CCRIS,
DART, GENETOX, HSDB, RTECS, Chemical Abstracts, and Current Contents (last 6 months).
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Figure 1. Chemical Structure of 2-Chloronaphthalene
REVIEW OF PERTINENT DATA
Human Studies
No data have been located regarding the effects of 2-chloronaphthalene in humans
exposed by any route.
Animal Studies
Oral Exposure
A subchronic study (U.S. EPA, 1989), as cited in IRIS (U.S. EPA, 2009), is the only
available study of oral exposure. The following description is reproduced from
U.S. EPA (2009):
"CD-I mice (20/sex/group) were administered oral gavage dosages of 0,
100, 250, or 600 mg/kg/day beta-chloronaphthalene in corn oil for
13 weeks. Parameters examined included mortality, body and organ weight
changes, food consumption, clinical signs, opthalmologic changes,
hematology, clinical chemistry, and gross histopathology. Mortality was
reported in one male and one female low- dose mice and in three male and
two female high-dose mice, although no statistical significance was found
when compared with controls. Daily observations revealed dyspnea, rough
hair coat, and languid, thin, hunched appearance of high-dose animals; these
signs were more prevalent among females than males. Similar symptoms
were also observed in other treatment groups, but the incidence was not
statistically significant. Although total food consumption was significantly
increased in high-dose males throughout the study, this did not result in a
significant increase in body weight gain, compared with controls. Absolute
and relative liver and gall bladder weights were significantly increased in
both sexes at the high-dose level and were accompanied by centrilobular
hepatocellular enlargement. Both absolute and relative adrenal weights
were significantly increased in low-dose females, but no dose-response
relationship could be established, nor was there any corresponding
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histopathologic changes. No other effects were observed. The LOAEL was
identified as 600 mg/kg/day and the NOAEL was 250 mg/kg/day."
Inhalation Exposure
No data have been located regarding inhalation exposure of animals to
2-chloronaphthalene.
Other Studies
Parenteral Exposure
In an acute hepatoxicity study of halogenated aromatic hydrocarbons, Brodie et al. (1971)
injected male Sprague-Dawley rats (180 g) intraperitoneally with saline or 80 mg
phenobarbital/kg bw for 3 successive days, followed by an injection of 100 mg (555 mg/kg bw)
2-chloronaphthalene the next day. Livers were removed 24 hours after the injection of
2-chloronaphthalene and examined. "Extensive" to "massive" necrosis was found in the rats
pretreated with phenobarbital. Only occasional glycogen loss was noted in rats pretreated with
saline.
Genotoxicity
2-Chloronaphthalene (99% purity) did not induce mutations in Salmonella typhimurium
strains TA97, TA98, TA100, TA102, TA1535, TA1537, or TA1538 with or without metabolic
activation (Zeiger et al., 1992).
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC ORAL RfD
VALUES FOR 2-CHLORONAPHTHALENE
Subchronic p-RfD
Only one study (i.e., U.S. EPA, 1989, as cited in U.S. EPA, 2009) potentially suitable for
derivation of a subchronic p-RfD for 2-chloronaphthalene has been located. As described by
U.S. EPA (2009), the study was a 13-week subchronic exposure study in CD-I mice
(20/sex/dose). The NOAEL and LOAEL values are 250 and 600 mg/kg-day, respectively. The
basis for the LOAEL includes dyspnea, abnormal appearance, and liver enlargement. Use of this
study based on the description provided by U.S. EPA (2009) is limited by incomplete reporting
of methods and results. Because the data are not shown, it was not possible to use benchmark
dose modeling to derive a point of departure (POD). Therefore, the NOAEL (250 mg/kg-day)
has been selected as the POD.
The subchronic p-RfD is calculated as follows:
Subchronic p-RfD = NOAEL UF
= 50 mg/kg-day 1000
= 0.2 mg/kg-day or 2 x 10"1 mg/kg-day
The composite uncertainty factor of 1000 is composed of the following:
• UFa: A factor of 10 is applied for animal-to-human extrapolation because data for
evaluating relative interspecies sensitivity are insufficient.
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•	UFr: A factor of 10 is applied for extrapolation to a potentially susceptible human
subpopulation because data for evaluating susceptible human response are
insufficient.
•	UFd: A factor of 10 is applied for database inadequacies because data for
evaluating developmental and reproductive toxicity are not available.
As reported on IRIS (U.S. EPA, 2009), confidence in the principal study is medium. The
study is well-designed and identified both a LOAEL and NOAEL for multiple endpoints using
CD-I mice (20/sex/group) at 4 dose levels including one control group. The liver effects seen at
the LOAEL are also supported by the liver toxicity observed by Brodie et al. (1971). Confidence
in the database is low because developmental, reproductive, and other long-term toxicity
following oral exposure to beta-chloronaphthalene have not been tested. Confidence in the RfD
is accordingly low.
Chronic p-RfD
A chronic oral RfD of 8 x 10"2 mg/kg-day for 2-chloronapthalene is available on IRIS
(U.S. EPA, 2009) based on the subchronic mouse study (U.S. EPA, 1989).
FEASIBILITY OF DERIVING PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfC VALUES FOR 2-CHLORONAPHTHALENE
Provisional RfC values for 2-chloronaphthalene cannot be derived because of the lack of
human and animal inhalation data.
PROVISIONAL CARCINOGENICITY ASSESSMENT
FOR 2-CHLORONAPHTHALENE
Weight-of-Evidence Descriptor
Under the 2005 Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005), there is
"Inadequate Information to Assess [the] Carcinogenic Potential' of 2-chloronaphthalene based
on the lack of carcinogenicity studies.
Quantitative Estimates of Carcinogenic Risk
There are no data with which to quantify estimates of carcinogenic risk for
2-chl oronaphthal ene.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2008. 2008 Threshold
Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices.
ACGIH, Cincinnati, OH.
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ATSDR (Agency for Toxic Substances and Disease Registry). 2009. Toxicological Profile
Information Sheet. U.S. Department of Health and Human Services, Public Health Service.
Online, http://www.atsdr.cdc.gov/toxpro2.html.
Brodie, B.B., W.D. Reid, A.K. Cho et al. 1971. Possible mechanism of liver necrosis caused by
aromatic organic compounds. Proc. Nat. Acad. Sci. 68:150-164.
IARC (International Agency for Research on Cancer). 2009. Search IARC monographs.
Online. http://monoeraphs.iarc.fr/ENG/Monoeraphs/allmonos90.php.
NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to
Chemical Hazards. Index by CASRN. Online, http://www2.cdc.gov/nioshtic-2/nioshtic2.htm.
NTP (National Toxicology Program). 2005. 11th Report on Carcinogens. U.S. Department of
Health and Human Services, Public Health Service, National Institutes of Health, Research
Triangle Park, NC. Online, http://ntp-server.niehs.nih.gov/.
NTP (National Toxicology Program). 2009. Management Status Report. Online.
http://ntp.niehs.nih.gov/index.cfm?objectid=78CC7E4C-FlF6-975E-72940974DE301C3F.
OSHA (Occupational Safety and Health Administration). 2009. OSHA Standard 1910.1000
Table Z-l. Part Z, Toxic and Hazardous Substances. Online, http://www.osha-slc.gov/
OshStd data/1910 1000 TABLE Z-l.html.
U.S. EPA. 1980. Ambient Water Quality Criteria for Chlorinated Naphthalene. Office of Water
Regulations and Standards, Criteria and Standards Division, Washington, DC.
EPA 440/5-80-031.
U.S. EPA. 1989. Subchronic study in mice with beta-chloronaphthalene. HLA Study No.
2399-124. Prepared by Hazleton Laboratories America, Inc. for U.S. EPA, Office of Solid
Waste, Washington, DC.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati OH for the Office of Emergency and Remedial Response, Washington, DC. July.
EPA/540/R-97/036. NTIS PB97-921199.
U.S. EPA. 2005. Guidelines for Carcinogen Risk Assessment. Risk Assessment Forum,
Washington, DC; EPA/630/P-03/001F. Federal Register 70(66): 17765-17817. Online.
http://www.epa.gov/raf.
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U.S. EPA. 2006. 2006 Edition of the Drinking Water Standards and Health Advisories. Office
of Water, Washington, DC. EPA 822-R-06-013. Washington, DC. Online.
http://www.epa.gov/waterscience/drinkine/standards/dwstandards.pdf.
U.S. EPA. 2009. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
http ://www. epa. gov/iris/.
WHO (World Health Organization). 2001. Concise International Chemical Assessment
Document 34. Chlorinated Naphthalenes. International Programme on Chemical Safety,
Geneva, Switzerland. Online, http://www.inchem.org/documents/cicads/cicads/cicad34.htm.
Zeiger, E., B. Anderson, S. Haworth et al. 1992. Salmonella mutagenicity tests: V. results from
the testing of 311 chemicals. Environ. Mol. Mutagen. 19:2-141.
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