United States
Environmental Protection
1=1 m m Agency
EPA/690/R-07/022F
Final
9-18-2007
Provisional Peer Reviewed Toxicity Values for
2-Methylnaphthalene
(CASRN 91-57-6)
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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Acronyms and Abbreviations
bw
body weight
cc
cubic centimeters
CD
Caesarean Delivered
CERCLA
Comprehensive Environmental Response, Compensation and Liability Act

of 1980
CNS
central nervous system
cu.m
cubic meter
DWEL
Drinking Water Equivalent Level
FEL
frank-effect level
FIFRA
Federal Insecticide, Fungicide, and Rodenticide Act
g
grams
GI
gastrointestinal
HEC
human equivalent concentration
Hgb
hemoglobin
i.m.
intramuscular
i.p.
intraperitoneal
IRIS
Integrated Risk Information System
IUR
inhalation unit risk
i.v.
intravenous
kg
kilogram
L
liter
LEL
lowest-effect level
LOAEL
lowest-observed-adverse-effect level
LOAEL(ADJ)
LOAEL adjusted to continuous exposure duration
LOAEL(HEC)
LOAEL adjusted for dosimetric differences across species to a human
m
meter
MCL
maximum contaminant level
MCLG
maximum contaminant level goal
MF
modifying factor
mg
milligram
mg/kg
milligrams per kilogram
mg/L
milligrams per liter
MRL
minimal risk level
MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-ob served-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
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
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PBPK
physiologically based pharmacokinetic
ppb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
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PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
2-METHYLNAPHTHALENE (CASRN 91-57-6)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) 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 (PPRTV) 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 Integrated Risk Information System (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 two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program 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 five-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 manuscripts 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 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 manuscript 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
The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System
(IRIS) (U.S. EPA, 2003) for 2-Methylnaphthalene (2-MN) included an RfD of 4xl0"3 mg/kg-day
based on a BMDL0s of 3.5 mg/kg-day and an uncertainty factor of 1000. IRIS also included a
carcinogenicity assessment that concluded data were inadequate to assess human carcinogenic
potential. ATSDR (2005) derived a chronic MRL of 4xl0"2 mg/kg-day based on a BMDLqs of
4.3 mg/kg-day in mice (Murata et al., 1997) and an uncertainty factor of 100. ATSDR also had
derived an MRL of 7xl0"2 mg/kg-day for chronic duration oral exposure to 1-MN based on a
LOAEL of 71.6 mg/kg-day for increased incidence of alveolar proteinosis in mice (Murata et al.,
1993) and an uncertainty factor of 1000.
Updated literature searches for oral noncancer data were conducted from 1983 to 2007.
The databases searched were TOXLINE, MEDLINE, CANCERLIT, CCRIS, TSCATS, HSDB,
RTECS, GENETOX, DART/ETICBACK, and EMIC/EMICBACK.
This document has passed the STSC quality review and peer review evaluation indicating
that the quality is consistent with the SOPs and standards of the STSC and is suitable for use by
registered users of the PPRTV system.
REVIEW OF THE PERTINENT LITERATURE
Human Studies
No relevant human studies were found in the literature.
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Animal Studies
Lifetime Exposure
The chronic toxicity of 2-MN was investigated in mice by Murata et al. (1997). Groups
of 50 male and 50 female B6C3F1 mice were given diets containing 0, 0.075, or 0.15% 2-MN
for 81 weeks. Food consumption and body weight were recorded throughout the experimental
period. At necropsy organ weights were recorded for brain, liver, kidney, heart, spleen, lungs,
testes, pancreas, thymus, and salivary glands. Gross pathology and histopathology were
conducted for these tissues and for adrenals, trachea, stomach, large and small intestines, seminal
vesicles, ovaries, uterus, vagina, mammary glands, skeletal muscle, eye, Harderian glands, spinal
cord, bone, skin, and other tissues with abnormal appearance. A complete clinical chemistry
examination was performed, including hematology, serology, and enzyme analysis. Incidence
data were statistically evaluated using a Fisher's exact test and analysis of variance. Continuous
endpoints (organ weights, blood, and serum parameters) were evaluated using a multiple
comparison post-test with the Dunnett procedure.
Average 2-MN intakes of 50.3 (males) and 54.3 (females) mg/kg-day were calculated
from food consumption data reported in Murata et al. (1997) for the 0.075% 2-MN dose group.
Similarly, 2-MN intakes for the 0.15% 2-MN dose group were 107.6 (males) and 113.8 (females)
mg/kg-day.
Animals at the high dose exhibited slight growth retardation over the entire experimental
period. Compared with control animals, final body weights were reduced by 4.5% for females
and 7.5%) for males. Only the male body weight reductions were statistically significant
(p<0.01). Survival was not affected by 2-MN treatment. Pulmonary alveolar proteinosis (PAP)
was reported in both treatment groups. PAP was characterized by the appearance of foamy cells
in the alveoli and the accumulation of protein and lipid in the lungs. On gross examination, the
protenosis appeared as white nodules, 1-5 mm in diameter. Microscopically, the alveolar lumens
contained acidophilic amorphous material, foamy cells, and cholesterol crystals. The incidence
of PAP was 42.9% among males at 50.3 mg/kg-day and 55.1%> among females at 54.3 mg/kg-
day; in the high-dose group, the incidence was 46.9%> for males and 45.8%> for females. The
fraction of lung volume affected for individual treated or control animals was not reported.
Incidence of this effect in the control animals was 8.2%> for males and 10%> for females; the
effects in control animals were less pronounced than those in the treatment groups. The authors
stated that this effect had not been observed previously in more than 5000 B6C3F1 mice housed
in the same room and speculated that the control mice may have been exposed to volatilized 1-
MN and 2-MN from the treatment groups housed in the same room for this experiment. The
authors also concluded that 2-MN was not carcinogenic in this study, although some results were
equivocal. In particular, there appeared to be an increase in the incidence of lung tumors.
Incidence of lung adenomas and adenocarcinomas, combined, was significantly increased (10/49
vs. 2/49 controls; p<0.05) in male mice at 50.3 mg/kg-day; the increase (6/49) was not
significant at the 107.6 mg/kg-day dose. Because they noted association between tumorigenesis
and PAP, the authors concluded that PAP was not a risk factor for carcinogenesis in the mouse.
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A study by the same group (Murata et al., 1993) investigated the effect of 1-MN in the
same strain of mice. Although the study results were published four years apart, the two studies
were conducted at the same time and utilized the same control group. The nominal dose groups
and endpoints were the same in both studies. The actual exposure levels were somewhat higher
for 1-MN (approximately 73 mg/kg-day at 0.075% and 142 mg/kg-day at 0.15%). Results for 1-
MN were similar to those for 2-MN, with PAP occurring in both treatment groups. The
incidence, however, was slightly lower in the 1-MN treated mice (46% in both males and
females at 0.015% 1-MN, and 38 and 35% in males and females, respectively, at 0.15% 1-MN).
Unlike 2-MN, this study concluded 1-MN was a lung carcinogen (adenomas and
adenocarcinomas) for B6C3F1 mice.
Less-than-Lifetime Exposure
A subchronic 2-MN dietary study in B6C3F1 mice was briefly reported in Murata et al.
(1997). This study was preliminary to the chronic study to determine the chronic dosing
regimen. Groups of ten mice of each sex each were fed 2-MN for 13 weeks at dietary
concentrations of 0, 0.0163, 0.049, 0.147, 0.44, or 1.33%. Estimated doses were: 0, 29.4, 88.4,
265, 794, or 2400 mg/kg-day for males and 0, 31.8, 95.6, 287, 859, or 2600 mg/kg-day for
females, respectively. Approximate average doses (across genders) were 0, 31, 92, 276, 827, or
2500 mg/kg-day, respectively (U.S. EPA, 2003). Growth retardation was reported at the three
highest dose levels, but was attributed to food refusal. The authors reported no histopathological
lesions in any organs of the control or treated animals, although it was unclear whether the lungs
were examined. Based on this study, a subchronic NOAEL of 2500 mg/kg-day could be
established, because growth retardation accompanied by reduced food consumption in the
absence of other effects was not considered an adverse effect.
In a number of studies (Reid et al., 1973; Mahvi et al., 1977; Tong et al., 1981; Griffin et
al., 1981, 1982; Warren et al., 1982), intraperitoneal (IP) injection of 2-MN or naphthalene
resulted in lung lesions (Clara cell necrosis) similar to those observed in the long-term dietary
studies of Murata et al. (1993, 1997).
PAP also was observed in mice following dermal exposure to a mixture of 1-MN and 2-
MN for 30 weeks (Murata et al., 1992). A 100% incidence of PAP was observed in 15 B6C3F1
female mice treated dermally with 119 mg MN/kg twice a week. No lesions were observed in
the control animals, which were exposed to the acetone vehicle only.
Developmental/Reproductive
No relevant reproductive or developmental data were found in the literature.
Toxicokinetics and Toxicodynamics
Some evidence suggested that mice may be a sensitive species for the type of lung
toxicity induced by the methylnaphthalenes. Mice were far more sensitive than rats to acute lung
effects arising from exposure to dichloroethylene (Chieco et al., 1981; Krijgsheld et al., 1984),
bromobenzene (Reid et al., 1973), butylated hydroxytoluene (Kehrer & Witschi, 1980),
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naphthalene (Reid et al., 1973; O'Brien et al., 1985), and 2-MN (Griffin et al., 1982). For
naphthalene, Buckpitt and Franklin (1989) suggested that the selective lung cytotoxicity in mice
may be a result of the high degree of stereoselectivity with which naphthalene is epoxidated in
the mouse lung (in vitro microsomal incubations). Rats and humans did not show the same
stereoselectivity (Buckpitt and Bahnson, 1986). Together, these data suggested that mice
exposed to naphthalene might be more sensitive than humans for this particular endpoint. This
conclusion should be considered somewhat speculative, however, particularly because
subchronic oral naphthalene studies in mice did not produce lung effects at dose levels producing
other adverse effects (142 mg/kg-day for decreased body weight, 286 mg/kg-day for mortality
[BCL, 1980b]; 133 mg/kg-day for decreased organ weights [Shopp et al., 1984]). There was,
however, a suggestion that tolerance could be developed for this effect in mice (Shopp et al.,
1984). Also, the role of metabolic activation in the toxicity of the methylnaphthalenes was less
clear than for naphthalene (Griffin and Franklin, 1982; Buckpitt et al., 1984; Buckpitt and
Franklin, 1989). Much less was known about species differences in the metabolism of
methylnaphthalenes, so no firm conclusions could be made regarding the potential for unique
susceptibility mouse to 2-MN-induced lung toxicity. More extensive discussions of the
metabolism of naphthalene and the methylnaphthalenes were found in the Toxicological Review
of Naphthalene on IRIS (U.S. EPA, 2003) and in Buckpitt and Franklin (1989).
DERIVATION OF PROVISIONAL SUBCHRONIC OR CHRONIC
ORAL RfD VALUES FOR 2-METHYLNAPHTHALENE
Fitzhugh and Buschke (1949) evaluated the ability of 2-methylnaphthalene to induce
cataract formation in rats. While no cataracts were found in a group of 5 weanling F344 rats fed
a diet of 2% 2-MN (equivalent to 2000 mg/kg-day) for at least 2 months, cataracts were detected
in rats fed an equivalent concentration of naphthalene. Evaluation of this study was limited by
the lack of experimental details. In this study, 2000 mg/kg-day was an apparent NOAEL for
cataract formation.
Evaluation of the Murata et al. (1997) subchronic data was limited by inadequate
reporting of study results. It appeared that very few potential endpoints were considered. In its
evaluation of these data, IRIS (U.S. EPA, 2003) concluded that 92 mg/kg-day and 276 mg/kg-
day (averaged between genders) were the NOAEL and LOAEL, respectively, for reduced weight
gain in rats, apparently rejecting the study authors' attribution of these effects to food refusal.
However, the study report did not clearly identify what organs were examined or other potential
effects were considered. This raised the possibility that other effects might have resulted from
subchronic dosing that were not observed. Because very few details of the data or methods for
the subchronic study were reported by Murata et al. (1997) and because it was unclear whether
the reduced weight gain resulted from treatment with 2-MN, these data were considered
inadequate for derivation of a subchronic p-RfD. As a result, the chronic RfD of 4x10 3 mg/kg-
day on IRIS was selected as the subchronic p-RfD.
The IRIS chronic RfD (U.S. EPA, 2003) was based on a BMDL05 of 3.5 mg/kg-day for
5% extra risk of pulmonary alveolar proteinosis in male and female mice exposed to 2-MN in the
diet for 81 weeks (Murata et al., 1997). A total UF of 1000 was applied to this effect level: 10
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for interspecies differences (UFA: animal to human); 10 for intraspecies variation (UFH: human
variability); and 10 for deficiencies in the database (UFD).
The subchronic p-RfD for 2-MN was calculated using the same factors as follows:
subchronic p-RfD = BMDLqs ^ UF
= 3.5 mg/kg-day ^ 1000
= 0.004 mg/kg-day = 4 x 10"3 mg/kg-day
In the derivation of the chronic RfD, IRIS (U.S. EPA, 2003) noted that, in addition to the
uncertainties noted above, there was model uncertainty owing to the lack of actual dose-response
information or mode of action information near a dose where the point of departure was
estimated. The responses in 2-MN exposed animals suggested a continuation of the plateau into
the lower exposure region, so using a linear model might have provided a higher benchmark dose
than was appropriate. In addition, while BMDS was used to generate a lower bound on the
estimated benchmark dose, the lower bound probably described too narrow a confidence limit on
the benchmark dose. This was because the uncertainty in the data set could not be adequately
described without the high dose responses.
CONFIDENCE IN THE SUBCHRONIC ORAL RFD
The principal study for the p-RfD (Murata et al., 1997) examined a comprehensive
number of endpoints, including extensive histopathology, and tested two dietary dose levels
using sufficient numbers (50/gender/group) of B6C3F1 mice. Confidence in the study was
medium because there was potential confounding from possible inhalation exposure of controls
to volatilized 2-MN and 1-MN. This added some uncertainty to the dose-response relationship
between oral exposure to 2-MN and pulmonary alveolar proteinosis described by the results.
Confidence in the oral toxicity database was low. No epidemiology studies or case reports were
located which examined the potential effects of human exposure to 2-MN. Only mice had been
examined in adequate animal studies on toxicity from repeated exposure to 2-MN. No assays of
developmental toxicity, reproductive toxicity, or neurotoxicity following oral exposure to 2-MN
were available. Confidence in the oral RfD was low, principally due to the low confidence in the
database.
FEASIBILITY OF DERIVING PROVISIONAL SUBCHRONIC OR CHRONIC
INHALATION RfC VALUES FOR 2-METHYLNAPHTHALENE
A provisional inhalation RfC could not be derived for 2-MNe because data on adverse
health effects following inhalation exposure were lacking for humans and animals. Without
sufficient pharmacokinetic data and information to rule out portal-of-entry effects, there was no
basis to support a route-to-route extrapolation from the oral data, even if they otherwise were
considered sufficient.
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PROVISIONAL CARCINOGENICITY ASSESSMENT FOR
2-METHYLNAPHTHALENE
Weight-of-Evidence Descriptor
Using the draft revised guidelines for carcinogen risk assessment (U.S. EPA, 1999), the
IRIS assessment (U.S. EPA, 2003) concluded the data were inadequate for an assessment of
human carcinogenic potential of 2-MN. This conclusion was based on the absence of data
concerning the carcinogenic potential of 2-MN in humans, by any route of exposure, and limited,
equivocal oral evidence in animals. Updated literature searches for this assessment identified no
relevant data other than those already considered for the IRIS assessment. Based on the revised
guidelines for carcinogen risk assessment (U.S. EPA, 2005), the equivalent carcinogenicity
descriptor would be "Inadequate Information to Assess Carcinogenic Potential."
Quantitative Estimates of Carcinogenic Risk
Quantitative estimates of cancer risk for 2-MN could not be derived because no data
demonstrating carcinogenicity associated with 2-MN exposure were identified.
REFERENCES
ATSDR. 2005. Toxicological Profile for Naphthalene, 1-Methylnaphthalene, and 2-
Methylnaphthalene. US Public Health Service, Atlanta GA. August 2005. Online:
http://www.atsdr.cdc.gov/toxprofiles/tp67.pdf
BCL (Battelle's Columbus Laboratories). 1980a. Unpublished subchronic toxicity study:
Naphthalene (C52904), Fischer 344 rats. Prepared by Battelle Laboratories under NTP
Subcontract No. 76-34-106002. Available from the Center for Environmental Research
Information, (513) 569-7254.
BCL (Battelle's Columbus Laboratories). 1980b. Unpublished subchronic toxicity study:
Naphthalene (C52904), B6C3F1 mice. Prepared by Battelle Laboratories under NTP Subcontract
No. 76-34-106002.
Buckpitt, A.R. and L.S. Bahnson. 1986. Naphthalene metabolism by human microsomal lung
enzymes. Toxicology. 41:333-341.
Buckpitt, A.R. and R.B. Franklin. 1989. Relationship of naphthalene and 2-methylnaphthalene
metabolism to pulmonary bronchiolar epithelial cell necrosis. Pharm. Ther. 41:393-410.
Buckpitt, A.R., L.S. Bahnson and R.B. Franklin. 1984. Cobalt protoporphyrin (Co-Proto)-
induced alterations in the in vitro metabolism and in vivo bronchiolar necrosis by naphthalene.
Pharmacologist. 26:272.
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Chieco, P., M.T. Moslen and E.S. Reynolds. 1981. Effect of administrative vehicle on 1,1-
dichloroethylene toxicity. Toxicol. Appl. Pharmacol. 57:146-155.
Dourson, M.L. 1994. Methods for Establishing Oral Reference Doses. In: Risk Assessment of
Essential Elements, W. Mertz, C.O. Abernathy, and S.S. Olin, Ed. ILSI Press, Washington, DC.
Griffin, K.A. and R.B. Franklin. 1982. The effects of three pulmonary toxic agents:
naphthalene, 2-methylnaphthalene and 4-ipomeanol on the in vivo irreversible binding of 3H-
benzo(a)pyerene. IRCS Med. Sci. 10:373-374.
Griffin, K.A., C.B. Johnson, R.K. Breger et al. 1981. Pulmonary toxicity, hepatic and
extrahepatic metabolism of 2-methylnaphthalene in mice. Toxicol. Appl. Pharmacol.
61:185-196.
Griffin, K.A., C.B. Johnson, R.K. Breger et al. 1982. Effects of inducers and inhibitors of
cytochrome P-450-linked monooxegenases on the toxicity, in vitro metabolism and in vivo
irreversible binding of 2-methylnaphthalene in mice. J. Pharm. Exper. Ther.
221(3):517-524.
Kehrer, J.P. and H.P. Witschi. 1980. Effect of drug metabolisms inhibitors on butylated
hydroxytoluene-induced pulmonary toxicity in mice. Toxicol. Appl. Pharmacol.
53: 333-342.
Krijgsheld, K.R., M.C. Lowe, E.G. Mimnaugh et al. 1984. Selective damage to nonciliated
bronchiolar epithelial cells in relation to impairment of pulmonary monooxegenase activities by
1,1-dichloroethylene in mice. Toxicol. Appl. Pharmacol. 74:201-213.
Mahvi, D., H. Bank and R. Harley. 1977. Morphology of a naphthalene-induced bronchiolar
lesion. Am. J. Path. 886:558-571.
Murata, T., Y. Emi, A. Denda and Y. Konishi. 1992. Ultrastructural analysis of pulmonary
alveolar proteinosis by methylnaphthalene in mice. Exp. Toxic. Pathol.
44:47-54.
Murata, T., A. Denda, H. Maruyama et al. 1993. Chronic toxicity and carcinogenicity studies of
1-methylnaphthalene	in B6C3F1 mice. Fund. Appl. Toxicol. 21:44-51.
Murata, Y., A. Denda, H. Maruyama et al. 1997. Chronic toxicity and carcinogenicity studies of
2-methylnaphthalene	in B6C3F1 mice. Fund. Appl. Toxicol. 36:90-93.
O'Brien, K.A.F., L. Smith and G.M. Cohen. 1985. Differences in naphthalene-induced toxicity
in the mouse and rat. Chem. Biol. Interact. 55:109-122.
Reid, W.D., K.F. Ilett, K.F. Glick et al. 1973. Metabolism and binding of aromatic
hydrocarbons in the lung: Relationship to experimental bronchiolar necrosis. Am. Rev. Resp.
Dis. 17:539-551.
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Shopp, G.M., K.L. White, Jr., M.P. Holsapple et al. 1984. Naphthalene toxicity in CD-I mice:
General toxicology and immunotoxicology. Fund. Appl. Toxicol.
4(3 pt 1):406-419.
Tong, S.S., M.C. Lowe, M.A. Trush et al. 1981. Clara cell damage and inhibition of pulmonary
mixed function oxidase activity by naphthalene. Expl. Molec. Path.
37:358-369.
U.S. EPA. 1999. Guidelines for carcinogen risk assessment, [review draft] NCEA-F-0644, July
1999. Risk Assessment Forum.
U.S. EPA. 2003. Integrated Risk Information System (IRIS). Toxicological Review of 2-
Methylnaphthalene. EPA 635/R-03/010. Office of Research and Development, National Center
for Environmental Assessment, Washington, DC. Accessed 2007. Online:
http://www.epa.gov/iris/toxreviews/1006-tr.pdf
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. Available online
at http://cfpub.epa.gov/ncea/raf/recordisplav.cfm?deid=l 16283.
Van Bladeren, P. J., K.P. Vyas, J.M. Sayer et al. 1984. Stereoselectivity of cytochrome P-450c
in the formation of naphthalene and anthracene 1,2-oxides. J. Biol. Chem.
259:8966-8973.
Warren, D.L., D.L. Brown, Jr. and A.R. Buckpitt. 1982. Evidence for cytochrome P-450
mediated metabolism in the bronchiolar damage by naphthalene. Chem. Biol. Interact. 40:287-
303.
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