iPs	United States
Environmental Protection
m»Agency
EPA/690/R-11/001F
Final
4-6-2011
Provisional Peer-Reviewed Toxicity Values for
Acenaphthene
(CASRN 83-32-9)
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
J. Phillip Kaiser, PhD
National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY
ICF International
9300 Lee Highway
Fairfax, VA 22031
PRIMARY INTERNAL REVIEWERS
Paul G. Reinhart, PhD, DABT
National Center for Environmental Assessment, Research Triangle Park, NC
Q. Jay Zhao, PhD, MPH, DABT
National Center for Environmental Assessment, Cincinnati, OH
This document was externally peer reviewed under contract to
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02421-3136
Questions regarding the 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	ii
BACKGROUND	1
HISTORY	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVS	2
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER)	5
HUMAN STUDIES	5
ANIMAL STUDIES	5
Oral Exposures	5
Sub chronic-duration Studies	5
Chronic-duration Studies	9
Inhalation Exposures	9
OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)	10
DERIVATION 01 PROVISIONAL VALUES	15
DERIVATION OF ORAL REFERENCE DOSES	15
Derivation of Subchronic Provisional RfD (Subchronic p-RfD)	15
Derivation of Chronic Provisional RfD (Chronic p-RfD)	20
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS	20
Derivation of Subchronic Provisional RfC (Subchronic p-RfC)	20
Derivation of Chronic Provisional RfC (Chronic p-RfC)	21
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR	21
GENOTOXIC STUDIES	21
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES	22
Derivation of Provisional Oral Slope Factor (p-OSF)	22
Derivation of Provisional Inhalation Unit Risk (p-IUR)	22
APPENDIX A. PROVISIONAL SCREENING VALUES	23
APPENDIX B. DATA TABLES	24
APPENDIX C. BENCHMARK DOSE CALCULATIONS FOR THE RfD	27
APPENDIX D. REFERENCES	35
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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
ACENAPHTHENE (CASRN 83-32-9)
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
Acenaphthene (1,2-dihydroacenaphthylene), a white-to-light yellowish solid, is an
ethylene-bridged, three-ring unsaturated hydrocarbon derived from naphthalene. Acenaphthene
is a polycyclic aromatic hydrocarbon (PAH), a compound having two or more single or fused
aromatic rings. It is one of the simplest PAHs in structure and is generally grouped with up to
16 other PAHs (acenaphthylene, anthracene, benz[a]anthracene, benzo[a]pyrene,
benzo[e]pyrene, benzo[b]fluoranthene, benzo[g,h,i]perylene, benzo[j]fluoranthene,
benzo[k]fluoranthene, chrysene, dibenz[a,h]anthracene, fluoranthene, fluorene,
indeno[l,2,3-c,d]pyrene, phenanthrene, and pyrene). These PAHs occur at the highest
concentrations at National Priorities List (NPL) hazardous waste sites and are the PAHs to which
the general public is most likely to be exposed (ATSDR, 1995). Acenaphthene is one of the few
PAHs, along with naphthalene, acenaphthylene, and anthracene, produced commercially in the
United States. It is used as an intermediate for naphthalic acids, naphthalic anhydride
(intermediate for pigments), and acenaphthylene (intermediate for resins). Acenaphthene is also
used as an intermediate in the production of soaps and pharmaceuticals, as an insecticide,
fungicide, and herbicide; in plastics manufacturing; and as an agent for inducing polyploidy
(U.S. EPA, 1982; ATSDR, 1995). Exposure to PAHs is common throughout the environment,
and generally occurs through incomplete fuel combustion (coal, gas, oil, wood, and other organic
substances such as food and tobacco). Outside of manufacturing, exposure generally involves a
mixture of PAHs instead of individual compounds. Exposure can occur by inhalation, oral
(eating and drinking), placental, transfer via breast milk, and dermal routes, and the route and
magnitude of exposure are dependent on a variety of factors such as geography, occupation, and
culture. Acenaphthene can be a constituent of tar, coal tar creosote oil, and asphalt (U.S. EPA,
1982; ATSDR, 1995), and occupational exposure to acenaphthene and other PAHs has been
documented (Ares, 1993; Omland et al., 1994; Petry et al., 1996; Brandt et al., 2000;
Bieniek et al., 2004; Campo et al., 2006). Benzo[a]pyrene, a common PAH, is a known
carcinogen. However, acenaphthene is categorized as Group 3, "Unclassifiable as to
Carcinogenicity to Humans'' (IARC, 2010 [Vol. 92]), and Group D, "Not Classified as to Human
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Carcinogenicity" (U.S. EPA, 1987). In this document, "statistically significant" denotes a
p-walue of <0.05, unless otherwise noted.
The empirical formula for acenaphthene is C12H10 (see Figure 1). Table 1 provides a list
of physicochemical properties.
Figure 1. Acenaphthene Structure
Table 1. Physicochemical Properties Table—Acenapthenea'b'c (CASRN 83-32-9)
Property (unit)
Value
Boiling point (°C)
278-280°
Melting point (°C)
90-943, 95-97°
Density (g/cm3)
1.06a
Vapor pressure (Pa at 25°C)
0.595953
pH (unitless)
NAa
Solubility in water (g/L at 25°C)
0.00347-0.003883
Relative vapor density (air =1)
5.32a
Molecular weight (g/mol)
154.2 lb
Log Octanol/water partition coefficient
3.92b
aChemical Book(2010).
bU.S. EPA (1987).
°Sittig (1980).
NA = Not available.
A chronic RfD of 0.06 mg/kg-day for acenaphthene is included in the EPA's IRIS
database (U.S. EPA, 1994a). This RfD value is based on increased liver weights accompanied
by cellular hypertrophy and increased cholesterol levels observed in the 350- and 700-mg/kg-day
dose groups of male and female CD-I mice administered acenaphthene by gavage. An
uncertainty factor (UF) of 3000 has been applied to the NOAEL of 175 mg/kg-day from this
study to derive the RfD value. No RfC or cancer assessment for acenaphthene is included in the
IRIS database (U.S. EPA, 1994a).
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The Drinking Water Standards and Health Advisories List (U.S. EPA, 2009) reports an
RfD of 0.06 mg/kg-day for acenaphthene, and a drinking water equivalent level (DWEL) value
for acenaphthene of 2 mg/L, which is approximately equivalent to the RfD value for a 70-kg
adult drinking 2 liters of water per day (2 mg/L x 2 L = 4 mg ~ 0,06 mg/kg-day x 70 kg =
4.2 mg). No standards, exposures for a 10-kg child, cancer risk value, or cancer descriptor are
listed for acenaphthene. The HEAST (U.S. EPA, 2010) does not report RfD or RfC values. The
Chemical Assessments and Related Activities (CARA) list (U.S. EPA, 1994b) does not include a
Health and Environmental Effects Profile (HEEP) for acenaphthene. The CARA lists
(U.S. EPA, 1994b) include an Ambient Water Quality Criteria document (AWQCD) for
acenaphthene (U.S. EPA, 1980), an AWQCD addendum (U.S. EPA, 1990), and a Health Effects
Assessment (HEA) document for PAHs (U.S. EPA, 1984). In addition, a HEA document for
acenaphthene (U.S. EPA, 1987) and an AWQCD document for PAHs (U.S. EPA, 1980) are
available (although not listed on the CARA). These five documents report a lack of data
regarding chronic-duration exposure or carcinogenicity for acenaphthene, but a lower limit of
0.02 ppm (0.02 mg/L) in drinking water was proposed based on organoleptic, not toxic,
considerations. ATSDR (2008) has not reviewed the toxicity of acenaphthene individually but
has included it in the review of PAHs (ATSDR, 1995). A recommended oral minimum risk
level (MRL) for acenaphthene of 0.6 mg/kg-day is reported for intermediate-duration exposure
(15 to 364 days); no inhalation MRL values are reported for any PAH. Although this value is
based on the same study in the CD-I mouse as cited for the chronic RfD value in the IRIS
database, the ATSDR document reports the 175-mg/kg-day dose level as the LOAEL for hepatic
effects. This is based on increased liver weights without the accompanying hepatocellular
hypertrophy noted after administration of acenaphthene at 350 and 700 mg/kg-day. The ATSDR
document also reports that acenaphthene is negative for genotoxicity in the Salmonella
typhimurium and Escherichia coli SOS chromotest gene mutation screens. A World Health
Organization (WHO, 1998) Environmental Health Criteria (EHC) document on PAHs reports the
NOAEL and LOAEL values cited by IRIS (175 and 350 mg/kg-day, respectively); no EHC
document exists for acenaphthene. CalEPA (2008a,b, 2009a) has not derived toxicity values for
exposure to acenaphthene. No occupational exposure limits for acenaphthene as an individual
PAH have been derived by the American Conference of Governmental Industrial Hygienists
(ACGIH, 2010), the National Institute of Occupational Safety and Health (NIOSH, 2005), or the
Occupational Safety and Health Administration (OSHA, 2010). The Hazardous Substances Data
Bank recognizes acenaphthene as a skin, eye, and mucous membrane irritant. Acenaphthene is a
potential component of PAH mixtures (coal tar and creosote) that have a threshold limit value
(TLV) level of 0.2-mg/m3 time-weighted average (TWA) (ACGIH, 2010), a relative exposure
limit (REL) value of 0.1-mg/m3 TWA (NIOSH, 2005), and a permissible exposure limit (PEL)
value of 0.2-mg/m3 TWA (OSHA, 2010).
The HEAST (U.S. EPA, 2010) does not report an EPA (1986) cancer weight-of-evidence
(WOE) classification for acenaphthene, although a HEA document (U.S. EPA, 1987) indicated
that the appropriate classification for acenaphthene was in Group D ("Not Classified as to
Human Carcinogenicity"). IARC (2010) categorizes the carcinogenic potential of acenaphthene
as Group 3, "Unclassifiable as to Carcinogenicity to Humans". Results from two experiments in
the mouse examining carcinogenicity by dermal application are inadequate for evaluation
because of poor survival and/or the lack of a control group. Acenaphthene is not included as an
individual PAH in the 11th Report on Carcinogens (NTP, 2005). CalEPA (2009b) has not
prepared a quantitative estimate of carcinogenic potential for acenaphthene.
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Literature searches were conducted on sources published from 1900 through
December 2010 for studies relevant to the derivation of provisional toxicity values for
acenaphthene, CAS No. 83-32-9. Searches were conducted using EPA's Health and
Environmental Research Online (HERO) 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, Multi-Database 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 toxicity
information: ACGM, ATSDR, 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 an overview of the relevant database for acenaphthene and includes all
potentially relevant studies. NOAELs, LOAELs, and BMDL/BMCLs are provided in
HED/HEC units for comparison except that oral noncancer values are not converted to HEDs
and are identified as adjusted (ADJ) rather than HED/HECs. Principal studies are identified.
Entries for the principal studies (PS) are bolded.
HUMAN STUDIES
No data on the effects of acenaphthene in humans following inhalation or oral exposure
have been located in the literature searches.
ANIMAL STUDIES
Oral Exposures
The effects of oral exposure of animals to acenaphthene have been evaluated in two
subchronic-duration studies (i.e., U.S. EPA, 1989; Knobloch et al., 1969 [as cited in U.S. EPA,
1980]), but not in any chronic-duration, developmental, reproductive, or carcinogenicity studies.
Subchronic-duration Studies
A study submitted to the EPA (1989) is discussed in the IRIS document for acenaphthene
(U.S. EPA, 1994a) and used to derive a chronic RfD value. Because this is the only study that
provides suitable data for derivation of a subchronic p-RfD value, a summary of the study's
methodology and results is presented in this document.
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Table 2. Summary of Potentially Relevant Data for Acenaphthene (CASRN 83-32-9)


Number of








Male/Female, Strain








Species, Study Type,


NOAELb'c
BMDL/
LOAELb c
Reference
Notes3
Category
Study Duration
Dosimetryb
Critical Effects
BMCLb
(Comments)
Human
1. Oral (mg/kg-d)
None
2. Inhalation (mg/m3)
None
Animal
1. Oral (mg/kg-d)
PS
Subchronic
20/20, CD-I mouse,
Male/Female
Increased absolute and relative liver
N/A
161
175
U.S. EPA (1989)
IRIS

daily gavage, 90 d
ADJ: 0,175,
weight, increased serum total

mg/kg-d;
mg/kg-d;

(U.S.


350, or
cholesterol, minimal-to-slight

identified
identified

EPA,


700 mg/kg-d
centrilobular hepatocellular

in female
in female

1994a)



hypertrophy

mice for
mice for







increased
increased







relative
absolute







liver
and







weight
relative








liver








weight

IRIS
Subchronic
Number of animals not
2000 mg/kg-d
Weight loss, peripheral blood changes,
Not
Not run
2000
Knobloch et al.
(U.S.

reported, rat and mouse

increased serum aminotransferase
established

mg/kg-d
(1969) (in Polish, as
EPA,

(strain not reported),

levels (alanine or aspartate not


(only dose)
cited in U.S. EPA,
1994a)

oral, 32 d

specified), mild morphological



1980)




damage to liver/kidney, mild








bronchitis/bronchial tissue








inflammation





Chronic
None
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Table 2. Summary of Potentially Relevant Data for Acenaphthene (CASRN 83-32-9)
Notes3
Category
Number of
Male/Female, Strain
Species, Study Type,
Study Duration
Dosimetryb
Critical Effects
NOAELb'c
BMDL/
BMCLb
LOAELb c
Reference
(Comments)

Developmental
None

Reproductive
None

Carcinogenic
None
2. Inhalation (mg/m3)

Subchronic
None
IRIS
(U.S.
EPA,
1994a)
Chronic
Unknown number of
rats (strain not
reported), inhalation,
5 mo
12 ± 1.5 mg/m3
(4 hr/d, 6 d/wk)
or
HEC: 1.7
mg/m3
Chronic aspecific pneumonia,
circulatory alterations, desquamation
of alveolar epithelium, focal bronchitis
with hyperplasia and metaplasia
Not
established
Not run
1.7 mg/m3
(only dose)
Reshetycek et al.
(1970) (in Russian,
translation not
available)

Developmental
None

Reproductive
None

Carcinogenic
None
aNotes: IRIS = Utilized by IRIS, date of last update; PS = Principal study, N/A = Not applicable.
bDosimetry: Where appropriate, 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.
HECexresp = (ppm x MW ^ 24.45) x (hours per day exposed ^ 24) x (days per week exposed ^ 7) x blood gas partition coefficient.
°Not reported by the study author but determined from the data.
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The nonpeer-reviewed study conducted in compliance with Good Laboratory
Practice (GLP) regulations by Hazleton Laboratories America, Inc. and submitted to the
EPA (1989) is selected as the principal study for deriving the subchronic p-RfD. Although
this study has not been peer reviewed, it was selected for development of a chronic RfD by IRIS
(U.S. EPA, 1990a) and is deemed appropriate for the development of a subchronic p-RfD value.
This study examined the sub chronic-duration toxicity of acenaphthene in the CD-1®(ICR)BR
mouse (Charles River Breeding Laboratories). After acclimation and physical examinations,
80 mice/sex (males, 22.3-30.8 g and females, 17.8-24.6 g; 43 days old) were used. The mice
were housed individually in stainless steel, hanging-wire cages. Food and tap water were
available ad libitum, and a 12:12 hour light:dark cycle was maintained. Animals were
randomized by weight into one of four groups (three treatment groups and a vehicle control
group, 20/group/sex). The study authors conducted baseline clinical pathology measurements on
nonstudy animals prior to study initiation. Dosing solutions of acenaphthene (purity not
reported) were formulated in corn oil at 0, 35, 70, and 140 mg/mL (0, 175, 350, and
700 mg/kg-day, respectively, at a dose volume of 5 mL/kg), with stability determined for at least
21 days. The 175- and 350-mg/kg-day formulations were prepared as solutions, and the
high-dose formulation (700 mg/kg-day) was prepared as a suspension. The mice were dosed
once daily by gavage for 90 days. All animals were observed for clinical signs daily, including
mortality/moribundity checks twice daily. Body weight and food consumption were recorded
weekly, and ophthalmology examinations were conducted prior to treatment initiation and during
the final week of the study. At the end of the study, half of the study animals/group/sex (n = 10)
were bled for hematology determinations, and the remaining mice were bled for clinical
chemistry analyses. All mice remaining on study were euthanized by exsanguination, and all
sacrificed animals, as well as mice that died during the study, underwent a full necropsy.
Selected organs (liver/gallbladder, kidneys, heart, spleen, brain/brainstem, testes/epididymides,
ovaries, and adrenals) were weighed, and the terminal organ and body weights were used to
calculate relative organ/body-weight ratios. Tissues were collected and prepared for
histopathological examination; all tissues from the control and high-dose group mice were
examined. Additionally, gross lesions, lungs, liver, and kidneys from the low- and mid-dose
animals were prepared for analysis and examined.
Four unscheduled deaths occurred during the study (U.S. EPA, 1989); three high-dose
female deaths were considered treatment related, but one accidental death in a high-dose male
was not. No significant toxicological findings were noted in the surviving mice during the daily
and weekly clinical observations. No statistically significant effects on weekly body weight,
total body-weight gain, or weekly and total food consumption were observed in the study.
Clinical hematology and chemistry results from blood draws at study termination indicated
statistically significant elevations in total cholesterol levels in high-dose males and females (50
and 121% over control, respectively), and mid-dose females (48%), as well as a statistically
significant increase in eosinophil count in the low- and high-dose females (p < 0.05, see
Appendix B, Table B. 1). Absolute and relative liver weights were increased in a dose-dependent
manner in both sexes in all treatment groups at study termination (low dose, 9—13%; mid dose,
14—19%; and high dose, 28—37%; p < 0.05, see Appendix B, Table B.2) with the exception of
absolute liver weight in low-dose males. Other statistically significant organ-weight changes
included decreased absolute spleen weight (all dose groups in males), decreased relative spleen
weight (mid-dose males), decreased absolute adrenal and ovary weights (mid- and high-dose
females), and decreased relative adrenal and ovary weights in all treated female mice (p < 0.05,
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see Appendix B, Table B.2). No treatment-related findings were noted in gross pathology at
necropsy. Minimal-to-slight centrilobular hepatocellular hypertrophy was seen in nearly all of
the high-dose animals (all terminally-sacrificed animals and three out of four unscheduled
deaths) during the histopathology evaluations and was observed to a lesser degree in the mid-
and low-dose groups (see Appendix B, Table B.3). Additionally, increased incidence and degree
of ovarian and uterine inactivity were seen in the high-dose female but these increases were not
statistically significant.
EPA (1989) noted that increased absolute and relative liver weights in female mice at all
dose groups correlated with the increased incidence of hepatocellular hypertrophy and increased
serum total cholesterol concentrations observed in the mid- and high-dose groups. Although the
study author did not specify a NOAEL or LOAEL, a LOAEL is identified as 175 mg/kg-day for
statistically and biologically significant increased absolute and relative liver weight in female
mice at the lowest dose; no NOAEL is identified. Data for all statistically significant changes
(e.g., organ weight changes, hepatocellular hypertrophy, etc.) observed in this study have been
further evaluated, when appropriate, with the BMDS modeling program for determination of a
point of departure (POD) for the subchronic p-RfD (see DERIVATION OF REFERENCE
DOSES).
The study by Knobloch et al. (1969 [as cited in U.S. EPA, 1980]) is discussed in the IRIS
document for acenaphthene (U.S. EPA, 1994a). Because this study is not used for the derivation
of a provisional toxicity value in this document, and because an English translation of the
original study written in Polish is not available, this study is not discussed further. However, this
study can still be considered supporting based on a review of this study by the U.S. EPA (1980).
As summarized from this review, Knobloch et al. (1969) determined that the severity of the liver
effects caused by this chemical increased with repeated exposures, supporting the concern for
greater sensitivity from prolonged exposure. Furthermore, acenaphthene-induced liver toxicity
was observed in this study, similar to effects observed in the study by the U.S. EPA (1989),
suggesting that the liver is indeed a target organ for acenaphthene toxicity. Refer to the IRIS
document for acenaphthene for further study details (U.S. EPA, 1994a).
Chronic-duration Studies
IRIS (U.S. EPA, 1994a) has provided an RfD. The principal study used by IRIS (i.e.,
U.S. EPA, 1989) is also utilized in the derivation of a subchronic p-RfD for this document.
Inhalation Exposures
The effects of inhalation exposure of animals to acenaphthene have been evaluated in
both a chronic-duration intraperitoneal and intratracheal study (Reshetycek et al., 1970)—but not
in any subchronic-duration, developmental, reproductive, or carcinogenicity studies.
The inhalation study by Reshetycek et al. (1970) is discussed in the IRIS document for
acenaphthene (U.S. EPA, 1994a). Because this study is not used for the derivation of a
provisional toxicity value in this document, and because a translation from Russian is not
available, it is not discussed further. Refer to the IRIS document for acenaphthene for further
study details (U.S. EPA, 1994a).
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OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)
Various studies (see Table 3) have investigated the mutagenicity of acenaphthene
including Gibson et al. (1978), Pahlman and Pelkonen (1987), Zeiger et al. (1992),
Kangsadalampai et al. (1996), and Yan et al. (2004). The nonenzymatic mutagenic activation of
acenaphthene and other PAHs was examined after exposure to 60Co irradiation in S. typhimurium
strains TA98, TA1535, TA1537, and TA1538 (Gibson et al., 1978). Cytotoxicity in all four
S. typhimurium strains, and at all of the tested acenaphthene concentrations, precluded the
determination of acenaphthene mutagenicity in this study. The mutagenicity of acenaphthene
and other PAHs was examined in S. typhimurium strain TA100 in the presence of S9 prepared
from mouse or rat liver after in vivo i.p. pretreatment with 3-methylcholanthrene or
2,3, 7,8-tetrachl orodi benzo-/>dioxin (Pahlman and Pelkonen, 1987). Acenaphthene was not
mutagenic in S. typhimurium in the absence or presence of any S9 fraction up to a toxic
concentration of 324 nmol/plate. The mutagenicity of acenaphthene was investigated in
S. typhimurium strains TA97, TA98, TA100, TA1535, and TA1537 with and without
S9 activation (Zeiger et al., 1992). S9 fractions were prepared from Aroclor 1254-induced male
Sprague-Dawley rat and male Syrian hamster livers. Acenaphthene demonstrated negative
results in mutagenicity studies with S. typhimurium with S9 activation (at concentrations of 10
and 30%) and in the absence of S9. Kangsadalampai et al. (1996) investigated the mutagenicity
of PAH alone or in cooked food, in the presence or absence of sodium nitrite, with
S. typhimurium strains TA98 and TA100. Acenaphthene tested negative for mutagenicity in the
absence of nitrite treatment but was positive in combination with sodium nitrite. These data
support the designation that acenaphthene is not a direct mutagen.
Yan et al. (2004) investigated the photomutagenicity of acenaphthene in S. typhimurium
strain TA102 with UVA plus visible light irradiation. Photomutagenicity tests were conducted in
duplicate on separate occasions. Aroclor 1254-induced S9 activation of mutagenicity also was
evaluated in S. typhimurium strain TA102 in separate experiments. Acenaphthene was negative
for mutagenicity in the absence or presence of S9 activation, but it was weakly positive in the
presence of UVA and visible light irradiation. The results of this study underscore the potential
value for considering "actual" exposure conditions in risk assessment (e.g., environmental
factors).
The structural basis for the genotoxicity of acenaphthene and other PAHs (as determined
by induction of the SOS repair system in E. coli PQ37) was investigated by
Mersch-Sundermann et al. (1992) with the Computer Automated Structure Evaluation (CASE)
system. Experimental negative genotoxicity results for acenaphthene are supported by a CASE
prediction of nongenotoxicity. The lack of genotoxicity was correlated with the chemical
structure of acenaphthene (the lack of active fragments or biophores such as a bay or fjord
region).
A second study by Mersch-Sundermann et al. (1993) investigated the genotoxicity of
acenaphthene and other PAHs by induction of the SOS system in E. coli strain PQ37 with and
without activation (S9 fraction prepared from Aroclor 1254-induced male rat liver).
Acenaphthene was negative for genotoxicity as determined with E. coli strain PQ37 and
S9 metabolic activation.
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Table 3. Other Studies
Test
Materials and Methods
Results
Conclusions
References
Mutagenicity
Nonenzymatic mutagenic activation of
acenaphthene and other PAHs was examined after
exposure to 60Co irradiation in S. typhimurium
strains TA98, TA1535, TA1537, and TA1538.
Cytotoxicity in all S. typhimurium strains
at all of the tested acenaphthene
concentrations precluded determination
of mutagenicity by acenaphthene.
Results inconclusive due to
cytotoxicity.
Gibson etal. (1978)
Mutagenicity
Mutagenicity of acenaphthene and other PAHs was
examined in S. typhimurium strain TA100 in the
presence of S9 prepared from mouse or rat liver.
Animals were pretreated (intraperitoneal [i.p.])
with corn oil (control), 3-methylcholanthrene, or
2,3,7,8-tetrachlorodibenzo-p-dioxin.
Acenaphthene was not mutagenic in
S. typhimurium TA100 in the absence or
presence of either S9 fraction (up to a
toxic concentration of 324 nmol/plate).
Acenaphthene was
nonmutagenic under the
conditions examined, as were
other nonbay-region PAHs.
Pahlman and Pelkonen
(1987)
Mutagenicity
Mutagenicity of acenaphthene was examined in
S. typhimurium strains TA97, TA98, TA100,
TA1535, and TA1537, with and without S9
activation (S9 prepared from Aroclor 1254-
induced male Sprague-Dawley rat and male Syrian
hamster livers).
Acenaphthene tested negative in all
strains, with and without S9 activation (at
10% and 30% S9).
Acenaphthene was
nonmutagenic under the
conditions examined.
Zeigeretal. (1992)
Mutagenicity
Mutagenicity of PAHs alone or in cooked food,
and with or without sodium nitrite, was
investigated w ith ,V. typhimurium strains TA98 and
TA100.
Acenaphthene tested negative for
mutagenicity in S. typhimurium strains
TA98 and TA100 in the absence of
nitrite treatment but was positive in
combination with sodium nitrite.
Acenaphthene was mutagenic in
the presence of nitrite under the
conditions examined.
Kangsadalampai et al.
(1996)
Mutagenicity
Photomutagenicity of acenaphthene was examined
in S. typhimurium strain TA102 with UVA plus
visible light irradiation. Mutagenicity after
Aroclor 1254-induced S9 activation also was
investigated.
Acenaphthene mutagenicity in the
absence or presence of S9 activation was
negative. Acenaphthene mutagenicity in
the presence of UVA and visible light
irradiation was positive.
Acenaphthene tested positive for
photomutagenicity in
S. typhimurium strain TA102
with UVA and visible light
irradiation.
Yan et al. (2004)
Genotoxicity
The structural basis for genotoxicity of
acenaphthene and other PAHs with the SOS
chromotest in E. coli PQ37 was investigated with
the Computer Automated Structure Evaluation
(CASE) system.
Experimental negative genotoxicity
results were supported by a CASE
prediction for acenaphthene of
nongenotoxic.
The lack of genotoxicity by
acenaphthene in the SOS
chromotest was correlated with
its structure.
Mersch-
Sundermann et al.
(1992)
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Table 3. Other Studies
Test
Materials and Methods
Results
Conclusions
References
Genotoxicity
The genotoxicity of acenaphthene and other PAHs
was investigated with the SOS chromotest in
E. coli PQ37 activated with S9 fractions prepared
from Aroclor 1254-induced male rat liver.
Acenaphthene with S9 metabolic
activation in the SOS chromotest with
E. coli strain PQ37 was negative.
Acenaphthene was negative for
genotoxicity under the
conditions examined.
Mersch-
Sundermann et al.
(1993)
Cytotoxicity
Acute cytotoxicity of acenaphthene and other
PAHs was investigated in the human hepatoma cell
line (HepG2), noninduced or Arochlor-induced
(3 d), and analyzed with the Neutral Red
cytotoxicity assay.
Acenaphthene in noninduced and
Arochlor-induced cells (25 and
50 ng/mL) was negative for cytotoxicity.
The negative cytotoxicity results
for acenaphthene conflict with
previous findings from this
laboratory for acenaphthene and
other chemicals in the presence
of S9 fractions.
Babichetal. (1988)
Metabolism
Acenaphthene and other PAHs were administered
to B6C3Fi mice by single i.p. injection.
Microsomes were prepared after animal sacrifice.
Methoxyresorufin-O-demethylase (MROD)
activity, as well as mouse hepatic cytosolic Ah
receptor and 4S carcinogen-binding protein
competitive binding, were evaluated.
Acenaphthene (50-400 mg/kg)
statistically significantly induced MROD
activity (p < 0.05), but did not
competitively displace radioligands from
the Ah receptor or the 4S carcinogen-
binding protein.
Induction of hepatic CYP1A2 by
acenaphthene is independent of
the Ah receptor pathway.
Chaloupka et al.
(1994)
Metabolism
Acenaphthene was administered to male rats
(species not identified) in the diet. Urine was
collected daily, filtered, and refrigerated for future
analysis.
Upon numerous chemical extractions, a
solid compound was isolated from rat
urine. Based on its physical and
chemical properties, the compound was
identified to be the anhydride of
naphthalene-1,8-dicarboxylie acid.
Acenaphthene is metabolized
and further excreted in the urine
of rats as an anhydride of
naphthalene-1,8-dicarboxylic
acid. Fission of the 5-membered
carbon ring of acenaphthene can
occur in vivo.
Chang and Young
(1943)
Mitochondrial
Respiration
The inhibition of bovine heart mitochondrial
respiration by acenaphthene and other
hydrocarbons with one or two aromatic rings was
examined. The effect of the aromatic
hydrocarbons on the spectra of ubiquinone also
was determined.
Acenaphthene was a relatively potent
inhibitor of NADH:02 oxidoreductase
activity in a dose-dependent manner
(EC50 = 3.9 ppm, 25.3 jiM).
Acenaphthene affected the spectra of
ubiquinone. The inhibitory effects of the
tested aromatic hydrocarbons were
additive.
Acenaphthene was shown to be a
potent inhibitor of mitochondrial
respiration.
Beach and Harmon
(1992)
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Table 3. Other Studies
Test
Materials and Methods
Results
Conclusions
References
Dermal
Absorption
The correlation between physicochemical
properties and in vitro percutaneous absorption
values of various industrial chemicals, including
acenaphthene and other PAHs, was investigated.
Permeability coefficient (Kp) and lag time
estimates were determined, and correlations were
fit with a multiple linear regression model.
Statistically significant correlations were
observed for all chemicals tested between
experimental values for Kp and the
natural log of the octanol:water partition
coefficient (In Kow) values, and lag time
and In Kow. Acenaphthene and other
PAHs, excluding naphthalene, also
correlated well between Kp and lag time
versus solubility in water.
The multiple linear regression
model was predictive of
permeability and lag time
estimates based on the water
solubility and Kow values for the
chemicals examined.
Sartorelli et al. (1998)
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The acute cytotoxicity of acenaphthene and other PAHs was investigated in the human
hepatoma cell line (HepG2), noninduced or Arochlor-induced for 3 days (Babich et al., 1988).
Cytotoxicity was determined after incubation for 3 days with individual PAHs with the Neutral
Red cytotoxicity assay. Results indicated that acenaphthene was negative at concentrations of 25
and 50 |ag/m L in noninduced and Arochlor-induced cells. These data conflict with previous
reports from this laboratory of acenaphthene cytotoxicity determined in cell cultures with added
S9 fraction.
Chaloupka et al. (1994) investigated the metabolism and intracellular binding of
acenaphthene and other PAHs. B6C3F1 mice were obtained after in-laboratory breeding
(C57BL/6 females and C3H males), and compounds dissolved in corn oil were administered by
i.p. injection as a single dose. Microsomes were prepared after animal sacrifice, and induction
potential was evaluated with a methoxyresorufin-O-demethylase (MROD) activity assay. Mouse
hepatic cytosolic Ah receptor and 4S carcinogen-binding protein competitive binding assays
3	3
were conducted with [ HJTCDD and [ H]benzo[a]pyrene alone or with acenaphthene or the other
PAHs. Acenaphthene at concentrations of 50-400 mg/kg statistically significantly induced
MROD activity (p < 0.05) but did not competitively displace radioligands from the Ah receptor
or the 4S carcinogen-binding protein. These data indicate that induction of hepatic CYP1A2 by
acenaphthene is independent of the Ah receptor pathway.
Chang and Young (1943) observed the metabolism of dietary 1% acenaphthene in rats.
Urine was collected daily and then filtered and stored for future use. After analysis of urine, it
was determined that acenaphthene is metabolized to an anhydride of naphthalene-1,8-
dicarboxylic acid and then further excreted. Based on this observation, it was determined that
fission of acenaphthene's carbon ring can occur in the body of an animal.
Beach and Harmon (1992) examined the inhibition of bovine heart mitochondrial
respiration by acenaphthene and other hydrocarbons with one or two aromatic rings. Inhibition
was determined individually or in various combinations as mixtures. The effect of the aromatic
hydrocarbons on the spectra of ubiquinone also was determined. Acenaphthene was a relatively
potent inhibitor of NADHO2 oxidoreductase activity in a dose-dependent manner
(EC50 = 3.9 ppm, 25.3 |iM) and affected the spectra of ubiquinone. The inhibitory effects of the
tested aromatic hydrocarbons on mitochondrial respiration were additive with acenaphthene for
mixtures of two, three, and all four test compounds. Acenaphthene was shown to be a potent
inhibitor of mitochondrial respiration, and the potential for additive effects by acenaphthene and
other hydrocarbon compounds is important because exposure to these compounds in the
environment (outside of an industrial setting) would be as mixtures.
Sartorelli et al. (1998) reported the correlation between physicochemical properties and in
vitro percutaneous absorption values of various industrial chemicals—including acenaphthene
and other PAHs. Permeability coefficient (Kp) and lag time estimates were determined, and
correlations were fit with a multiple linear regression model. Statistically significant correlations
(p < 0.001) were observed for all chemicals tested between experimental values for Kp and the
natural log of the octanol: water partition coefficient (In Kow), and between lag time and In Kow-
Acenaphthene and other PAHs, excluding naphthalene, also correlated well between Kp and lag
time versus solubility in water. The multiple linear regression model was predictive of
permeability and lag time estimates based on the water solubility and Kow values for the
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chemicals examined. The study authors recognized the potential influence from different
experimental systems.
DERIVATION OF PROVISIONAL VALUES
Table 4 presents a summary of noncancer reference values. Table 5 presents a summary
of cancer values.
Table 4. Summary of Noncancer Reference Values for Acenaphthene (CASRN 83-32-9)
Toxicity Type
(Units)
Species/
Sex
Critical Effect
Reference
Value
POD
Method
POD
(mg/kg-d)
UFc
Principal Study
Subchronic
p-RfD (mg/kg-d)
Mouse/M
andF
Increased relative
liver weight in
female mice
2 x 10"1
BMDL
161,
BMDL10 for
increased
relative liver
weight in female
mice
1000
(U.S. EPA, 1989)
Chronic RfD
(mg/kg-d)
Previously determined by IRIS (U.S. EPA, 1990a)
Subchronic
p-RfC (mg/m3)
None
Chronic p-RfC
(mg/m3)
None
Table 5. Summary of Cancer Values for Acenaphthene (CASRN 83-32-9)
Toxicity Type
Species/Sex
Tumor Type
Cancer Value
Principal Study
p-OSF
None
p-IUR
None
DERIVATION OF ORAL REFERENCE DOSES
Derivation of Subchronic Provisional RfD (Subchronic p-RfD)
The 90-day toxicity study in the mouse (U.S. EPA, 1989) is selected as the principal
study for derivation of the subchronic p-RfD. The study was conducted according to GLP
regulations and otherwise meets the standards of study design and performance, with respect to
the numbers of animals and presentation of information. Although this study has not been peer
reviewed, it was selected for development of a chronic RfD by IRIS (U.S. EPA, 1990a) and is
deemed appropriate for the development of a subchronic p-RfD value. The number of potential
toxicity endpoints that were examined includes body and organ weights, clinical hematology and
chemistry measurements, and histopathology. This study provides the lowest POD from the data
set for increased relative liver weight in female mice, for derivation of a subchronic p-RfD value.
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The following dosimetric adjustments were made for each dose in the principal study for
gavage administration. The dosimetric adjustment for 175 mg/kg-day is presented below.
(DOSEadj) = DOSEu.s. EPA, 1989 x [conversion to daily dose]
= 175 mg/kg-day x (days of week dosed ^ 7)
= 175 mg/kg-day x (7 -h 7)
= 175 mg/kg-day
As detailed in the section "Review of Potentially Relevant Data," statistically significant
changes included increased absolute and relative liver weights in female mice at all dose groups
that correlated with the increased incidence of centrilobular hepatocellular hypertrophy, and
statistically significant changes in serum total cholesterol, eosinophil count, spleen weight,
adrenal weight, and ovary weight also occurred. However, increased serum cholesterol cannot
be used for derivation of a reference value because the concentration at which this parameter is
considered adverse is unknown. Also, it is unknown how cholesterol levels found in mice would
compare to those of humans. The same principle applies to the data for increased eosinophil
count. The level for which increased an increased eosinophil count could be toxicologically
relevant is unclear. With regards to the spleen data in male mice, there is no clear dose response
pattern for decreased relative or absolute spleen weights which is necessary for BMDS.
Therefore, these data were not modeled by BMD. An potential POD for spleen weight changes
can be determined by the NOAEL/LOAEL method as described below. The BMD modeling for
liver, adrenal, and ovary weight changes and incidence of hepatocellular hypertrophy are
described below.
The EPA Benchmark Dose Software (BMDS version 2.1.2) continuous data models with
constant variance are fit to the data using a default BMR of 10% extra risk for increased absolute
and relative liver weight. For adrenal and ovary weight changes, continuous data models with
constant and model variance are fit to the data using a default BMR of one standard deviation.
The dichotomous data models are fit to the increased incidence of hepatocellular hypertrophy
according to the current EPA technical guidance using a default BMR of 10% extra risk
(U.S. EPA, 2000). After completion of BMD modeling, the modeling output is reviewed for
elimination of models that failed acceptability criteria (see Tables 6, 7, and B.l for BMD
modeling results). An adequate fit was judged based on the % goodness-of-fitp-value (p> 0.1),
the magnitude of the scaled residuals in the vicinity of the BMR, and visual inspection of the
model fit. Table 8 shows the models that yielded the lowest AIC (and the associated BMDL
values) after elimination of failed models. The POD was selected based on the model with the
lowest AIC value because the range of remaining BMDL values was <3-fold.
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Table 6. Model Predictions for Increased Relative Liver Weight in CD-I Male Mice in a
90-Day Toxicity Study with Acenaphthene"
Model Name
Homogeneity
Variance fit
p-Value
Goodness of
Fit
p-Value
AIC
BMDio
(mg/kg-d)
BMDL10
(mg/kg-d)
Hill
0.993
0.142
-113.76
187.85
134.33
Linear
0.993
0.152
-114.15b
236.94
209.20
Polynomial
0.993
0.152
-114.15b
236.94
209.20
Power
0.993
0.152
-114.15b
236.94
209.20
aU.S. EPA (1989).
bLowest AIC.
Table 7. UFs for Subchronic p-RfD for Acenaphthene
UF
Value
Justification
UFa
10
A UFa of 10 is applied for interspecies extrapolation to account for potential
toxicokinetic and toxicodynamic differences between the mouse and humans. There
are no data to determine whether humans are more or less sensitive than the mouse to
acenaphthene hepatotoxicity.
UFd
10
A UFd of 10 is selected because there are no acceptable two-generation reproduction
studies or developmental studies.
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.
UFl
1
A UFl of 1 is applied because the POD was derived by using a BMDL.
UFs
1
A UFs of 1 is applied because a sub chronic-duration study (U.S. EPA, 1989) was
utilized as the principal study.
UFC
1000

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Table 8. Selected Models and BMDL Values after Benchmark Dose Modeling of Hepatic
Data from a 90-Day Acenaphthene Toxicity Study in CD-I Mice"

Lowest AIC
BMDLio (mg/kg-d)
Male
Absolute Liver Wt
Linear/Polynomial/Power
211
Relative Liver Wt
Linear/Polynomial/Power
209
Female
Absolute Liver Wt
Linear/Polynomial/Power
176
Relative Liver Wt
Linear/Polynomial
161
Hypertrophy
Log-Logistic
263
aU.S. EPA (1989).
As mentioned above the data for spleen weight changes cannot be modeled by BMD.
Therefore, an alternate POD for splenic effects is a LOAEL of 175 mg/kg-day for decreased
absolute spleen weight and aNOAEL of 175 mg/kg-day for decreased relative spleen weight,
both in male mice. For adrenal weight, a potential POD is a BMDLisd of 452 mg/kg-day for
decreased relative adrenal weight in female mice. For ovary weight changes, the data failed to
provide model fit. Thus, an alternate POD for ovarian effects is a NOAEL of 175 mg/kg-day for
decreased absolute ovary weight and a LOAEL of 175 mg/kg-day for decreased relative ovary
weight, both in female mice. For the increased incidence of hepatocellular hypertrophy,
modeling yields a BMDL value of 155 mg/kg-day in male mice. However, the data for increased
incidence of hepatocellular hypertrophy in male mice are not amenable to BMD modeling
because there are no data at the low response range, which is necessary for BMD modeling. Due
to the lack of dose-response data for this parameter, an alternate POD for increased incidence of
hepatocellular hypertrophy in the male mice is a NOAEL of 175 m/kg-day. For liver weight
changes, the most sensitive potential POD is a BMDL value of 161 mg/kg-day for increased
relative liver weight in female mice. Table 9 lists the possible PODs from the principal study
(U.S. EPA, 1989).
Of the toxicological effects observed in the principal study, the most sensitive POD is a
BMDL value of 161 mg/kg-day for increased relative liver weight in female mice. The selection
of increased relative liver weight as the critical effect is also supported by the observation that
the liver appears to be a target organ of acenaphthene toxicity. Specifically, not only did
acenaphthene cause hepatocellular hypertrophy in both sexes of mice but also biologically and
statistically significantly increased absolute and relative liver weights in both sexes of mice as
mentioned in the section "Review of Potentially Relevant Data." Therefore, the BMDLio of
161 mg/kg-day based on increased relative liver weight in female mice (U.S. EPA, 1989) is
chosen as the POD to derive a subchronic p-RfD.
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Table 9. Possible PODs in Mice from the U.S. EPA (1989) Study
Effect
Sex
NOAEL
LOAEL
BMDL10
Comment
Increased
Absolute Liver
Weight
Males
175
350
211

Decreased
Absolute Spleen
Weight
Males
Not
Determinable
175
Not Run
No Dose
Response
Increased Relative
Liver Weight
Males
Not
Determinable
175
209

Decreased
Relative Spleen
Weight
Males
175
350
Not Run
No Dose
Response
Increased
Absolute Liver
Weight
Females
Not
Determinable
175
176

Decreased
Absolute Adrenal
Weight
Females
175
350
521

Decreased
Absolute Ovary
Weight
Females
175
350
No fit

Increased
Relative Liver
Weight
Females
175
350
161
Chosen as POD
Decreased
Relative Adrenal
Weight
Females
Not
Determinable
175
452

Decreased
Relative Ovary
Weight
Females
Not
Determinable
175
No fit

Liver
Hypertrophy
Males
175
350
No fit

Liver
Hypertrophy
Females
175
350
263

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Tables B.2 (e.g., liver weights) and B.3 (e.g., incidence of hepatocellular hypertrophy)
present BMD input data for these hepatic data, and Tables 6 and 10 and Appendix C present the
BMD model output data for increased relative liver weight in male and female mice.
Appendix C, Table C. 1 provides BMD model output data for absolute liver weight and increased
incidence of hepatocellular hypertrophy for both sexes of mice.
Table 10. Model Predictions for Increased Relative Liver Weight in CD-I Female Mice in
a 90-Day Toxicity Study with Acenaphthene"
Model Name
Homogeneity
Variance fit
p-Value
Goodness of
Fit
p-Value
AIC
BMDio
(mg/kg-d)
BMDL10
(mg/kg-d)
Hill
0.500
NAb
-55.97
197
129
Linear
0.500
0.921
-59.81c
186
161
Polynomial
0.500
0.921
-59.81c
186
161
Power
0.500
0.685
-57.81
186
161
aU.S. EPA (1989).
bNA = BMDS cannot determine a p-value.
°Lowest AIC.
The subchronic p-RfD for acenaphthene based on the BMDLio of 161 mg/kg-day from
increased relative liver weight in the female mouse (U.S. EPA, 1989) is derived as follows:
Subchronic p-RfD = BMDLioUFC
= 161 mg/kg-day1000
= 2 x 10"1 mg/kg-day
Tables 7 and 11 summarize the UFs and confidence for the subchronic p-RfD for acenaphthene,
respectively.
Derivation of Chronic Provisional RfD (Chronic p-RfD)
A chronic RfD value of 6 x 10"2 mg/kg-day is available in the IRIS database (U.S. EPA,
1994a) based on the 90-day toxicity study in the mouse (U.S. EPA, 1989). The POD for this
chronic RfD was 175 mg/kg-day, identified as a LOAEL in the current PPRTV document. The
critical effect for this chronic p-RfD was increased absolute and relative liver weight coupled
with increased cholesterol and liver hypertrophy in male and female mice.
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS
Derivation of Subchronic Provisional RfC (Subchronic p-RfC)
No published studies investigating the effects of sub chronic-duration inhalation exposure
to acenaphthene in humans or animals were identified that were acceptable for use in risk
assessment.
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Table 11. Confidence Descriptor for Subchronic p-RfD for Acenaphthene
Confidence
Categories
Designation3
Discussion
Confidence in Study
H
The principal study (i.e., U.S. EPA, 1989) assessed an
acceptable number of endpoints including body and
organ weights, hematology and clinical chemistry
measurements, and histopathology. The study duration
of 90 d is considered sufficient to determine subchronic
toxicity.
Confidence in
Database
L
The database does not include any developmental
toxicity studies or studies in a second species, and no
two-generation reproduction studies are available.
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 lowest entry in table.
Derivation of Chronic Provisional RfC (Chronic p-RfC)
No published studies investigating the effects of chronic-duration inhalation exposure to
acenaphthene in humans or animals were identified that were acceptable for use in risk
assessment.
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR
Table 12 identifies the cancer WOE descriptor for acenaphthene: "Inadequate
Information to Assess Carcinogenic Potential.'" No carcinogenicity studies in animals by oral or
inhalation routes have been found. The carcinogenicity of acenaphthene after dermal exposure
in the mouse has been investigated in two studies, but both studies were determined to be
unsuitable for carcinogenicity risk determination due to a lack of control animals or poor survival
in an IARC monograph evaluating some nonheterocyclic polycyclic aromatic hydrocarbons
(IARC, 2010 [Vol. 92]). Two substituted acenaphthene compounds—5-aminoacenaphthene and
5-nitroacenaphthene—were reported to be carcinogenic in animals (IARC, 1998). Because there
are no long-term animal studies to suggest a carcinogenic potential for acenaphthene, a
discussion of the mode of action for carcinogenesis is not appropriate.
GENOTOXIC STUDIES
Acenaphthene has been shown to not be a direct mutagen in several S. typhimurium
strains, although acenaphthene mutagenicity has been reported in the presence of nitrite
(Kangsadalampai et al., 1996) and UVA and visible light irradiation (Yan et al., 2004).
Additionally, the genotoxic potential for acenaphthene was reported to be negative as determined
by induction of SOS repair in E. coli (Mersch-Sundermann et al., 1993).
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Table 12. Cancer WOE Descriptor for Acenaphthene (CASRN 83-32-9)
Possible WOE
Descriptor
Designation
Route of Entry
(Oral, Inhalation,
or Both)
Comments
"Carcinogenic to
Humans "
N/A
N/A
No human studies are available.
"Likely to Be
Carcinogenic to
Humans "
N/A
N/A

"Suggestive Evidence of
Carcinogenic Potential"
N/A
N/A

"Inadequate
Information to Assess
Carcinogenic Potential"
Selected
N/A
No long-term oral or inhalation
studies in animals, and no
epidemiological studies, are
available.
"Not Likely to Be
Carcinogenic to
Humans "
N/A
N/A
No strong evidence of
noncarcinogenicity in humans is
available.
Acenaphthene and acenaphthene derivatives have been shown to have nuclear and
cytological effects in microbial and plant species (U.S. EPA, 1980, 1987, 1990; Buidin, 1975a,b,
1976). These changes involve disruption of the spindle mechanism during mitosis and induction
of polyploidy. Although these effects have been demonstrated in plants, fungi, algae, and
bacteria, there is no current correlation to similar effects in mammalian cells (U.S. EPA, 1980;
Sittig, 1980).
The substituted compound, 5-nitroacenaphthene, and several metabolites of
5-nitroacenaphthene have been shown to be mutagenic in S. typhimurium TA 98 and TA100
strains (Yahagi et al., 1975; El-Bayoumy and Hecht, 1982).
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES
Derivation of Provisional Oral Slope Factor (p-OSF)
No human or animal studies examining the carcinogenicity of acenaphthene after oral
exposure have been located. Therefore, derivation of a p-OSF is precluded.
Derivation of Provisional Inhalation Unit Risk (p-IUR)
No human or animal studies examining the carcinogenicity of acenaphthene after
inhalation exposure have been located. Therefore, derivation of a p-IUR is precluded.
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APPENDIX A. PROVISIONAL SCREENING VALUES
No screening values have been derived.
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APPENDIX B. DATA TABLES
Table B.l. Selected Clinical Hematology and Chemistry Parameters in CD-I Mice After
Gavage Administration of Acenaphthene in a 90-Day Subchronic-Duration Toxicity Study3
Sex
Parameter
Dose (mg/kg-d)
0
175
350
700b
Male
Eosinophil—(/ 1(P7|iL. %)
0.1 ±0.07
0.1 ±0.08
0.1 ±0.07
0.1 ± 0.11
(n = 9)
Female
Eosinophil—(/ 10 Vj.iL. %)
0.0 ±0.03
0.1 ±0.10*
(t)c
0.0 ±0.05
0.2 ±0.14*
(t)c (n = 8)
Male
Total cholesterol (mg/dL)
168 ±24.9
160 ±36.8
202 ± 42.6
252 ±45.8*
(T50)
Female
Total cholesterol (mg/dL)
105 ±33.2
136 ±29.8
155 ±28.4*
(T48)
232 ±51.3*
(t 121) (n = 7)
aData were obtained from Tables 6 and 7 on pages 64 and 68 (U.S. EPA, 1989). Directionality of percentage
difference from control is included in parentheses.
hn = 10/group except as noted for the 700-mg/kg-day group.
Percentage increase over control is not calculated because the control value is zero.
*p < 0.05 by Fisher's Exact Test.
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Table B.2. Selected Mean Absolute and Relative Organ Weights in CD-I Mice After Gavag(
Administration of Acenaphthene in a 90-Day Subchronic-Duration Toxicity Study3
Parameter
Dose (mg/kg-d)
0
175
350
700b
Male
Terminal mean body weight (g)
28.7 ±2.8
27.6 ± 1.6
28.3 ± 1.8
27.9 ± 1.7
Absolute Organ weight (g)
Liver/gallbladder
1.20 ±0.13
1.28 ± 0.11
1.37 ±0.12*
(t 14)
1.53 ± 0.11*
(T28)
Spleen
0.7 ±0.01
0.6 ±0.01*
(414)
0.6 ±0.01*
(414)
0.6 ±0.01*
(414)
Relative Organ/body weight ratio (%)
Liver/gallbladder
4.172 ±0.290
4.646 ±0.291*
(til)
4.860 ±0.275*
(t 16)
5.470 ± 0.280*
(T31)
Spleen
0.244 ±0.036
0.231 ±0.061
0.205 ±0.034*
(416)
0.211 ±0.036
Female
Terminal mean body weight (g)
23.0 ±2.1
23.9 ± 1.8
22.5 ± 1.8
22.6 ± 1.9
Organ weight (g)
Liver/gallbladder
0.98 ±0.13
1.11 ± 0.10*
(t 13)
1.15 ±0.14*
(t 17)
1.32 ±0.10*
(T35)
Adrenal
0.014 ±0.004
0.012 ±0.003
0.011 ±0.003*
(421)
0.010 ±0.002*
(429)
Ovary
0.033 ±0.007
0.028 ± 0.006
(415)
0.026 ± 0.005*
(421)
0.026 ± 0.007*
(421)
Organ/body weight ratio (%)
Liver/gallbladder
4.273 ±0.388
4.644 ± 0.339*
(T9)
5.092 ±0.476*
(t 19)
5.856 ±0.409*
(T37)
Adrenal
0.0596 ±0.0157
0.0495 ±0.0114*
(417)
0.0476 ±0.0112*
(420)
0.0457 ±0.0102*
(423)
Ovary
0.1429 ±0.0326
0.1170 ±0.0225*
(418)
0.1171 ±0.0213*
(418)
0.1166 ±0.0270*
(418)
aData were obtained from Tables 8A and 8B on pages 69-74 (U.S. EPA, 1989). Directionality of percentage
difference from control is included in parentheses.
hn = 20/group, except for 700 mg/kg-day male (n = 19) and female (n = 17).
*p < 0.05 by Dunnett's Test.
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Table B.3. Incidence of Centrilobular Hepatocellular Hypertrophy in CD-I Mice After
Gavage Administration of Acenaphthene in a 90-Day Subchronic-Duration Toxicity Study3
Parameter
Dose (mg/kg-d)
0
175
350
700
Male
(# examined)
20
20
20
19
Minimal
2
2
18
0
Slight
0
0
0
19
Total
2
2
18*
19*
% Incidence
10
10
90
100
Female
(# examined)
20
20
20
17
Minimal
0
0
5
10
Slight
0
0
0
7
Total
0
0
5*
17*
% Incidence
0
0
25
100
"Data were obtained from Table I on page 34 (U.S. EPA, 1989).
*p < 0.05 by Fisher's Exact Test.
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APPENDIX C. BENCHMARK DOSE CALCULATIONS FOR THE RFD
Linear Model with 0.95 Confidence Level
Linear
BMDL
0	100 200 300 400 500 600 700
dose
10:13 09/07 2010
Figure C.l. Dose Response Modeling for Increased Relative Liver Weight
in Female CD-I Mice Gavaged with Acenaphthene for 90-Days
Polynomial Model. (Version: 2.16; Date: 05/26/2010)
Input Data File: C:/USEPA/BMDS2l/Data/lin_relliv_acenapthene_f_Lin-
ConstantVariance-BMRlO.(d)
Gnuplot Plotting File: C:/USEPA/BMDS21/Data/lin_relliv_acenapthene_f_Lin-
ConstantVariance-BMRlO.pit
Tue Sep 07 10:13:51 2010
BMDS Model Run
The form of the response function is:
Y[dose] = beta_0 + beta_l*dose + beta_2*dose/s2 + ...
Dependent variable = mean
Independent variable = dose
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rho is set to 0
The polynomial coefficients are restricted to be positive
A constant variance model is fit
Total number of dose groups = 4
Total number of records with missing values = 0
Maximum number of iterations = 250
Relative Function Convergence has been set to: le-008
Parameter Convergence has been set to: le-008
Default Initial Parameter Values
alpha =	0.16473
rho =	0 Specified
beta_0 =	4.2 64
beta 1 = 0.00228898
Asymptotic Correlation Matrix of Parameter Estimates
( *** The model parameter(s) -rho
have been estimated at a boundary point, or have been specified by
the user,
and do not appear in the correlation matrix )
alpha beta_0	beta_l
alpha 1 -1.3e-009	7.2e-009
beta_0 -1.3e-009 1	-0.76
beta 1 7.2e-009 -0.76	1
Parameter Estimates
Interval
Variable
Limit
alpha
0.205945
beta_0
4 .39885
beta_l
0.0026417
95.0% Wald Confidence
Estimate	Std. Err.	Lower Conf. Limit Upper Conf.
0.156508	0.0252235	0.10707
4.26378	0.0689118	4.12872
0.00229056	0.000179155	0.00193942
Table of Data and Estimated Values of Interest
Dose
Obs Mean
Est Mean Obs Std Dev Est Std Dev Scaled Res.
0
175
350
700
20
20
20
17
4.27
4 . 64
5.09
5.86
4.26
4. 66
5.07
5.87
0.388
0.339
0. 476
0.409
0.396
0.396
0.396
0.396
0.0703
-0.278
0.277
-0.0748
Model Descriptions for likelihoods calculated
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Model A1:	Yij = Mu(i) + e(ij)
Var{e(ij)} = SigmaA2
Model A2 :	Yij = Mu(i) + e(ij)
Var{e(ij)} = Sigma(i)^2
Model A3:	Yij = Mu(i) + e(ij)
Var{e(ij)} = Sigma^2
Model A3 uses any fixed variance parameters that
were specified by the user
Model R:	Yi = Mu + e(i)
Var{e(i)} = Sigma^2
Likelihoods of Interest
Model
A1
A2
A3
fitted
R
Log(likelihood)
32.986597
34.169641
32.986597
32.904061
-10.938532
# Param's
5
8
5
3
2
AIC
-55.973195
-52.339282
-55.973195
-59.808122
25.877064
Test 1:
Test
Test
Test
Explanation of Tests
Do responses and/or variances differ among Dose levels?
(A2 vs. R)
Are Variances Homogeneous? (A1 vs A2)
Are variances adeguately modeled? (A2 vs. A3)
Does the Model for the Mean Fit? (A3 vs. fitted)
(Note: When rho=0 the results of Test 3 and Test 2 will be the same.)
Tests of Interest
Test
-2*log(Likelihood Ratio) Test df
p-value
Test
Test
Test
Test
90.2163
2.36609
2.36609
0.165073
<.0001
0.5
0.5
0.9208
The p-value for Test 1 is less than .05. There appears to be a
difference between response and/or variances among the dose levels
It seems appropriate to model the data
The p-value for Test 2 is greater than .1. A homogeneous variance
model appears to be appropriate here
The p-value for Test 3 is greater than .1. The modeled variance appears
to be appropriate here
The p-value for Test 4 is greater than .1. The model chosen seems
to adeguately describe the data
Benchmark Dose Computation
Specified effect =	0.1
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Risk Type =	Relative risk
Confidence level =	0.95
BMD =	18 6.146
BMDL =	161.229
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Table C.l. Benchmark Dose Continuous Modeling Results for Toxicological Effects in CD-I Mice (U.S. EPA, 1989)
Endpointf
Species
Sex
Model
Homogeneity
Variance
/7-Valuea
Goodness-of-Fit
p-V alueb
AIC for
Fitted
Model
BMD10
(mg/kg-d)
BMDL10
(mg/kg-d)
Conclusions
Increased absolute liver weight
Mouse
M
Continuous-Hill
0.8528
N/D
-252.91
252.17
156.34
Invalid p-score 4



Continuous-
Linear
0.8528
0.9787
-256.86
253.39
210.65
Lowest AIC



Continuous-
Polynomial
0.8528
0.9787
-256.86
253.39
210.65
Lowest AIC



Continuous-
Power
0.8528
0.9787
-256.86
253.39
210.65
Lowest AIC
Increased absolute liver weight
Mouse
F
Continuous-Hill
0.3132
0.1978
-244.54
178.13
100.11




Continuous-
Linear
0.3132
0.3641
-246.17
214.92
175.56
Lowest AIC



Continuous-
Polynomial
0.3132
0.3641
-246.17
214.92
175.56
Lowest AIC



Continuous-
Power
0.3132
0.3641
-246.17
214.92
175.56
Lowest AIC
Increased incidence of
hepatocellular hypertrophy
Mouse
M
Dichotomous-
Gamma0
N/A
0.8969
43.23
194.35
150.7
Data not
amendable to
BMD modeling



Dichotomous-
Multistaged
N/A
0.0227
46.87
137.22
95.09
%2p-value <0.1
Data not
amendable to
BMD modeling



Dichotomous-
Logistic
N/A
0.0149
49.76
115.96
77.52
'/.2 /'-value <0.1
Data not
amendable to
BMD modeling
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Table C.l. Benchmark Dose Continuous Modeling Results for Toxicological Effects in CD-I Mice (U.S. EPA, 1989)



Dichotomous-
Log-logistice
N/A
1
43.01
275.98
154.7
Lowest AIC
Data not
amendable to
BMD modeling



Dichotomous-
Probit
N/A
0.0133
51.32
95.49
65.6
'/.2 /'-value <0.1
Data not
amendable to
BMD modeling



Dichotomous-
Log-probite
N/A
0.9995
45.01
248.03
155.62
Data not
amendable to
BMD modeling



Dichotomous-
Weibulf
N/A
0.9951
45.01
270.21
146.07
Data not
amendable to
BMD modeling



Dichotomous-
Quantal-Linear
N/A
0.0002
64.57
29.91
21.85
y_2 /?-valuc <0.1
Data not
amendable to
BMD modeling
Increased incidence of
hepatocellular hypertrophy
Mouse
F
Dichotomous-
Gamma0
N/A
0.9865
24.76
297.01
246.44




Dichotomous-
Multistaged
N/A
0.5247
28.48
227.9
183.52




Dichotomous-
Logistic
N/A
1
26.49
339.22
249.06




Dichotomous-
Log-logistice
N/A
1
24.49
329.28
263.07
Lowest AIC of
passing models



Dichotomous-
Probit
N/A
1
26.49
329.08
238.77




Dichotomous-
Log-probite
N/A
1
26.49
327.59
258.14

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Table C.l. Benchmark Dose Continuous Modeling Results for Toxicological Effects in CD-I Mice (U.S. EPA, 1989)



Dichotomous-
Weibulf
N/A
1
26.49
328.58
234.14




Dichotomous-
Quantal-Linear
N/A
0.0006
26.49
69.26
48.95
'/.2 /'-value <0.1
Decreased relative adrenal weight
Mouse
F
Continuous-Hill
0.2147
0.9174
-595.33
330.914
1.60E-05




Continuous-
Linear
0.2147
0.1097
-592.92
692.19
451.66
Best fitting model



Continuous-
Polynomial
0.2147
0.1097
-592.92
692.19
451.66
Best fitting model



Continuous-
Power
0.2147
0.1097
-592.92
692.19
451.66
Best fitting model
Decreased absolute adrenal weight
Mouse
F
Continuous-Hill
0.0411
0.6429
-812.97
711.734
244.06




Continuous-
Linear
0.0411
0.4254
-813.47
793.63
520.69
Best fitting model



Continuous-
Polynomial
0.0411
0.4254
-813.47
793.63
520.69
Best fitting model



Continuous-
Power
0.0411
<.0001
727368.26
N/D
N/D
BMD and BMDL
not provided
y2 p-value <0.1
Decreased relative ovary weight
Mouse
F
Continuous-Hill
0.2048
0.6892
-481.47
N/D
N/D
BMD and BMDL
not provided



Continuous-
Linear
0.2048
0.0057
-473.3
1034.14
555.61
y2 p-v alue <0.1



Continuous-
Polynomial
0.2048
0.0057
-473.3
1034.14
555.61
y2 p-v alue <0.1



Continuous-
Power
0.2048
<0001
-465.52
745.39
710.14
y2 p-v alue <0.1
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Table C.l. Benchmark Dose Continuous Modeling Results for Toxicological Effects in CD-I Mice (U.S. EPA, 1989)
Decreased absolute ovary weight
Mouse
F
Continuous-Hill
0.4274

-696.77
205.15
0.059
'/.2 /'-value not
provided



Continuous-
Linear
0.4274
0.04067
-694.47
683.83
407.76
%2p-value <0.1



Continuous-
Polynomial
0.4274
0.04067
-694.47
683.83
407.76
%2p-value <0.1



Continuous-
Power
0.4274
<.0001

N/D
N/D
%2p-value <0.1
AIC, BMD, and
BMDL not
provided
aN/A = Not applicable.
'N/D = Not determined.
cRestrict power >1.
dRestrict betas >0.
eSlope restricted to >1.
fData for decreased absolute adrenal and ovary weights and decreased relative ovary weight were modeled by BMDS using model variance.
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APPENDIX D. REFERENCES
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ATSDR (Agency for Toxic Substances and Disease Registry). (1995) Toxicological profile for
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ATSDR (Agency for Toxic Substances and Disease Registry). (2008) Toxicological profile
information sheet. U.S. Department of Health and Human Services, Public Health Service.
Available online at http://www.atsdr.cdc.gov/toxprofiles/index.asp. Accessed on May 14, 2010.
Babich, H; Sardana, MK; Borenfreund, E. (1988) Acute cytotoxicities of polynuclear aromatic
hydrocarbons determined in vitro with the human liver tumor cell line, HepG2. Cell Biol Toxicol
4(3):295-309. 625719.
Beach, AC; Harmon, HJ. (1992) Additive effects and potential inhibitory mechanism of some
common aromatic pollutants on in vitro mitochondrial respiration. JBiochem Toxicol
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Bieniek, G; Kurkiewicz, S; Wilczok, T; et al. (2004) Occupational exposure to aromatic
hydrocarbons at a coke plant: Part II. Exposure assessment of volatile organic compounds. J
Occup Health 46(3): 181-186. 625722.
Brandt, H; Lafontaine, M; Kriech, AJ; et al. (2000) Inhalation study on exposure to bitumen
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Buidin, VV. (1975a) Polyploid activity of certain acenaphthene derivatives. Cytol Genet
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Bui din, VV. (1975b) Induction of polyploidy by certain acenaphthene derivatives. Cytol Genet
9:25-27. 625727.
Buidin, VV. (1976) Feasibility of producing barley polyploids with the aid of acenaphthene and
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CalEPA (California Environmental Protection Agency). (2008a) OEHHA/ARB approved
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Health Hazard Assessment. Available online at
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CalEPA (California Environmental Protection Agency). (2008b) OEHHA/ARB approved
chronic reference exposure levels and target organs. Sacramento: Office of Environmental
Health Hazard Assessment. Available online at
http://www.arb.ca.gov/toxics/healthval/chronic.pdf. Accessed on May 14, 2010.
CalEPA (California Environmental Protection Agency). (2009a) OEHHA toxicity criteria
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http://oehha.ca.gov/risk/chemicalDB/index.asp. Accessed on May 14, 2010.
CalEPA (California Environmental Protection Agency). (2009b) Hot spots unit risk and cancer
potency values. Office of Environmental Health Hazard Assessment. Available online at
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