EPA-540/1-86-029
vvEPA
untied states
Environmental Protection
Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Superfund
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
HEALTH EFFECTS ASSESSMENT
FOR PHENANTHRENE
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EPA/540/1-86-029
September 1984
HEALTH EFFECTS ASSESSMENT
FOR PHENANTHRENE
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and It has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with phenan-
threne. All estimates of acceptable Intakes and carcinogenic potency
presented 1n this document should be considered as preliminary and reflect
limited resources allocated to this project. Pertinent toxlcologlc and
environmental data were located through on-Hne literature searches of the
Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases.
The basic literature searched supporting this document 1s current up to
September, 1984. Secondary sources of Information have also been relied
upon 1n the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) source has
been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria for Polynuclear
Aromatic Hydrocarbons. Environmental Criteria and Assessment
Office, U.S. EPA, Cincinnati, OH. EPA 440/5-80-069. NTIS PB
81-117806.
The Intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited 1n
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the Interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants {toxicants for which cancer 1s not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants In ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
The AIC, acceptable Intake chronic, 1s similar 1n concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the Hfespan [see U.S. EPA (1980b) for a discussion
of this concept]. The AIC 1s route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes 1s Insignificant.
111
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Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development 1s explained In U.S. EPA (1983).
For compounds for which there Is sufficient evidence of carclnogenldty,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer 1s a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data 1f available.
1v
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ABSTRACT
In order to place the risk assessment evaluation In proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
There are no toxlcologlcal data that address effects of phenanthrene by
either the oral or the Inhalation route. Guidelines concerning PAHs as a
class and PAH-contalnlng mixtures specifically address the carcinogenic
members of this group. Data are not available which adequately assess the
potential carc1nogen1c1ty of phenanthrene. Since no data were available,
acceptable Intakes or carcinogenic potencies could not be estimated.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was the Project
Officer. The final documents 1n this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of Air Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112.
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1.
2.2.
ORAL
INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
Page
1
3
... 3
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4
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4
4
... 4
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, , . 5
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. . . 6
5. REGULATORY STANDARDS AND CRITERIA
vil
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TABLE OF CONTENTS (cont.)
6.1.
6.2.
6.3.
1SESSMENT
ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral
6.1.2. Inhalation
ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral
6.2.2. Inhalation
CARCINOGENIC POTENCY (q^)
6.3.1. Oral
6.3.2. Inhalation
ICES
ummary Table for Phenanthrene
Page
8
8
8
8
8
8
8
8
8
8
9
13
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LIST OF ABBREVIATIONS
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF Bloconcentratlon factor
CAS Chemical abstract service
CS Composite score
GI Gastrointestinal
PAH Polycycllc aromatic hydrocarbon
TLV Threshold limit value
TWA Time-weighted average
1x
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
phenanthrene (CAS No. 85-01-8) are shown below.
Chemical class: PAH
Molecular weight: 178.22
Vapor pressure: 6.8xlO~* mm Hg at 20°C (U.S. EPA, 1980a)
Water solubility: 1 mg/kg at 25°C (Wise et al., 1981)
Log octanol/water
partlon coefficient: 4.46 (U.S. EPA, 1980a)
BCF: 1230 (U.S. EPA, 1980a)
Half-lives In water: 9 hours to 2 days (estimated)
Half-lives In soil: <1 day (estimated)
A quantitative value for the half-life of phenanthrene 1n the atmosphere
could not be located In the available literature. Phenanthrene adsorbed
onto partlculate matter In the air Is expected to be very resistant to both
photochemical and chemical reactions (U.S. EPA, 1981). The processes that
probably account for significant removal of phenanthrene from the atmosphere
are physical removal mechanisms (dry and wet deposition). Although the
estimated half-life value for the latter process Is unknown, It 1s expected
to be several days. Therefore, phenanthrene may persist 1n the atmosphere
long enough to participate 1n long distance aerial transport.
The half-life value for phenanthrene In the aquatic media has been
estimated from the blotransformatlon rate constant value (1.6xlO~7 ml
cell"1 hr"1) given by Mabey et al. (1981) and the concentration range of
microorganisms at 10s to 5xlO~5 cell ml"1 (Burns et al., 1982).
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Similarly, the half-life value for phenanthrene 1n soils has been estimated
from the corresponding value 1n water and the assumption that soils provide
much better conditions for blodegradatlon than aquatic systems (Callahan et
al., 1979).
No Information pertaining to the mobility of this compound In soil could
be located In the literature searched. Based on the soil adsorption
coefficient (K = 23,000) (Kenaga and Goring, 1980) and the ability to
(Jv*
blodegrade In soils, It Is unlikely that significant amounts of phenanthrene
will leach Into groundwater from soils.
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Specific data regarding GI absorption of phenanthrene are not available,
but such data from other structurally related PAHs suggest that phenanthrene
1s absorbed readily from the GI tract, primarily by passive diffusion (Rees
et al., 1971). Also, systemic toxic effects observed following oral admin-
istration of related PAHs (Smyth et al., 1962), and the high llpld solubil-
ity and ability to cross epithelial membranes of PAH as a class, lend
further support to this conclusion (U.S. EPA, 1980a).
2.2. INHALATION
Specific data regarding the pulmonary absorption of phenanthrene are not
available, but such data from other structurally related PAHs suggest that
phenanthrene Is absorbed readily through the lungs (Kotln et al., 1969;
Vainio et al., 1976). As a class, PAHs are highly lipid-soluble and can
pass across epithelial membranes (U.S. EPA, 1980a).
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Pertinent data regarding the subchronlc oral toxldty of
phenanthrene In humans and experimental animals could not be located 1n the
available literature.
3.1.2. Inhalation. Pertinent data regarding the subchronlc Inhalation
toxldty of phenanthrene In humans and experimental animals could not be
located 1n the available literature.
3.2. CHRONIC
3.2.1. Oral. Pertinent data regarding the chronic oral toxldty of
phenanthrene 1n humans and experimental animals could not be located In the
available literature.
3.2.2. Inhalation. Pertinent data regarding the chronic Inhalation
toxldty of phenanthrene In humans and experimental animals could not be
located In the available literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenlclty of orally
administered phenanthrene could not be located In the available literature.
3.3.2. Inhalation. Pertinent data regarding the teratogenlclty of
Inhalation exposure to phenanthrene could not be located 1n the available
literature.
3.4. TOXICANT INTERACTIONS
Pertinent data regarding the toxicant Interactions of phenanthrene could
not be located In the available literature.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the cardnogenlcHy 1n humans of
oral exposure to phenanthrene could not be located In the available litera-
ture.
4.1.2. Inhalation. Pertinent data regarding the cardnogenlcHy In
humans of Inhalation exposure to phenanthrene could not be located 1n the
available literature.
4.2. BIOASSAYS
4.2.1. Oral. Pertinent data regarding the cardnogenlcHy In experi-
mental animals of oral exposure to phenanthrene could not be located In the
available literature.
4.2.2. Inhalation. Pertinent data regarding the carclnogenlclty In
experimental animals of Inhalation exposure to phenanthrene could not be
located In the available literature.
4.3. OTHER RELEVANT DATA
Phenanthrene was negative 1n the Salmonella typhlmurlum reverse mutation
assay, with or without a metabolic activation system (LaVole et a!., 1981;
Oesch et al., 1981). Oesch et al. (1981) noted, however, that positive
results could be obtained with phenanthrene In this assay 1f the amount of
the metabolizing enzyme system was Increased. Phenanthrene did not Induce
mutations In cultured mammalian cells, but did Increase the Incidence of
sister-chromatld exchanges In the bone marrow of Chinese hamsters (Oesch et
al., 1981).
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4.4. WEIGHT OF EVIDENCE
There Is no evidence of the carclnogenlclty of phenanthrene to humans
exposed by the oral or Inhalation routes, and this compound has not been
tested for carclnogenlclty 1n experimental animals by oral or Inhalation
exposure. Administration of phenanthrene 1n three Intraperltoneal Injec-
tions on days 1, 8 and 15 of life at levels of 0.2, 0.4 and 0.8 jimol did
not result In an Increased Incidence of tumors In 100 Swiss-Webster mice
(Buenlng et al., 1979). Phenanthrene 1s regarded as noncarclnogenlc by the
U.S. EPA (1980a). IARC (1983) reported that there was Insufficient evidence
of carcinogenic risk to humans and experimental animals associated with oral
or Inhalation exposure to phenanthrene. Applying the criteria for evaluat-
ing the overall weight of evidence for carclnogenlclty In humans proposed by
the Carcinogen Assessment Group of the U.S. EPA (Federal Register, 1984),
phenanthrene Is most appropriately designated a Group D - Not Classified
chemical.
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5. REGULATORY STANDARDS AND CRITERIA
Exposure criteria and TLVs have been developed for PAHs as a class, as
well as for several Individual PAHs. The OSHA has set an 8-hour TWA concen-
tration limit of 0.2 mg/m3 for the benzene-soluble fraction of coal tar
pitch volatlles (anthracene, benzo[a]pyrene, phenanthrene, acrldlne, chry-
sene, pyrene) (Code of Federal Regulations, 1981). NIOSH (1977) recommends
a concentration limit for coal tar, coal tar pitch, creosote and mixtures of
these substances at 0.1 mg/m3 of the cyclohexane-extractable fraction of
the sample, determined as a 10-hour TWA. NIOSH (1977) concluded that these
specific coal tar products, as well as coke oven emissions, are carcinogenic
and can Increase the risk of lung and skin cancer In workers. NIOSH (1977)
also recommends a celling limit for exposure to asphalt fumes of 5 mg
airborne part1culates/m3 of air.
Environmental quality criteria for PAHs, which specify concentration
limits Intended to protect humans against adverse health effects, have been
recommended for ambient water. The U.S. EPA (1980a) has recommended a
concentration limit of 28 ng/a. for the sum of all carcinogenic PAHs 1n
ambient water. This value Is based on a mathematical extrapolation of the
results from studies with mice treated orally with benzo[a]pyrene, and
acknowledges the conservative assumption that all carcinogenic PAHs are
equal In potency to benzo[a]pyrene. On the basis of the animal bloassay
data, dally consumption of water containing 28 ng/8. of carcinogenic PAHs
over an entire lifetime Is estimated to keep the lifetime risk of cancer
development below one chance 1n 100,000.
The U.S. EPA (1980a) has not recommended an ambient water quality crite-
rion for noncarclnogenlc PAHs as a class. The EPA acknowledged that data
suitable for quantitative risk assessment of noncarclnogenlc PAHs are essen-
tially nonexistent.
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. The lack of subchronlc oral data precludes the derivation
of an oral AIS for phenanthrene.
6.1.2. Inhalation. The lack of subchronlc Inhalation data precludes the
derivation of an Inhalation AIS for phenanthrene.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
The paucity of data regarding the subchronlc and chronic toxldty of
phenanthrene precludes the derivation of a CS.
6.2.1. Oral. The lack of chronic and subchronlc oral data precludes the
derivation of an oral AIC for phenanthrene.
6.2.2. Inhalation. The lack of chronic and subchronlc Inhalation data
precludes the derivation of an Inhalation AIC for phenanthrene.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. The lack of oral carclnogenlcHy data precludes the deriva-
tion of a unit carcinogenic risk for phenanthrene.
6.3.2. Inhalation. The lack of Inhalation carclnogenlcHy data precludes
the derivation of a unit carcinogenic risk for phenanthrene.
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7. REFERENCES
Buenlng, M.K., W. Levin, 3.M. Karle, H. Yagl, D.M. Jerlna and A.H. Conney.
1979. Tumorlgenlc of bay-region epoxldes and other derivatives of chrysene
and phenanthrene 1n newborn mice. Cancer Res. 39: 5063-5068. (Cited 1n
IARC, 1983)
Burns, L.A., D.M. Cllne and R.R. Lasslter. 1982. Exposure Analysis
Modeling System (EXAMS): User Manual and System Documentation. U.S. EPA,
Environmental Research Laboratory, Office of Research and Development,
Athens, GA. EPA 600/3-82-023.
Callahan, M.A., M.W. SUmak, N.W. Gabel, et al. 1979. Water-Related
Environmental Fate of 129 Priority Pollutants. Vol. II. U.S. EPA, Office of
Water Planning and Standards, Office of Water and Waste Management,
Washington, DC. EPA 440/4-79-029b.
Code of Federal Regulations. 1981. OSHA Safety and Health Standards. 29
CFR 1910.1000.
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. 49 FR 46294-46299.
IARC (International Agency for Research on Cancer). 1983. Polynuclear Aro-
matic Compounds, Part 1, Chemical, Environmental and Experimental Data. In:
IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. WHO, IARC, Lyon, France. Vol. 32.
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Kenaga, E.E. and C.A.I. Goring. 1980. Relationship between water solu-
bility, soil sorptlon, octanol-water partitioning, and concentration of
chemicals 1n biota. In: Aquatic Toxicology, ASTM STP 707, J.G. Eaton, P.R.
Parrlsh and A.C. Hendrlcks, Ed. ASTM, Philadelphia, PA. p. 78-115.
Kotln, P., H.L. Falk and R. Busser. 1969. Distribution, retention and
elimination of C -3,4-benzpyrene after administration to mice and rats.
J. Natl. Cancer Inst. 23: 541. (Cited In U.S. EPA, 1980a)
LaVole, E.J., L. Tulley-Freller, V. Bedenko and D. Hoffmann. 1981. Muta-
genlclty, tumor-Initiating activity and metabolism of methylphenanthrenes.
Cancer Res. 41: 3441-3447. (Cited In IARC, 1983)
Mabey, W.R., J.H. Smith, R.T. Podoll, et al. 1981. Aquatic Fate Process
Data for Organic Priority Pollutants. U.S. EPA, Monitoring and Data Support
Division, Office of Water Regulations and Standards, Washington, DC. €PA
440/4-81-014.
NIOSH (National Institute for Occupational Safety and Health). 1977.
Criteria for a Recommended Standard...Occupational Exposure to Coal Tar Pro-
ducts. U.S. DHEW, PHS, CDC, Rockvllle, MD.
Oesch, F., M. Bucker and H.R. Glatt. 1981. Activation of phenanthrene to
mutagenlc metabolites and evidence for at least two different activation
pathways. Mutat. Res. 81: 1-10. (Cited 1n IARC, 1983)
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Rees, E.O., et al. 1971. A study of the mechanism of Intestinal absorption
of benzo(a)pyrene. Blochem. Blophys. Act. 225: 96. (Cited 1n U.S. EPA,
1980a)
Smyth, H.F., C.P. Carpenter, C.S. Well, U.C. Pozzanl and J.A. Strlegel.
1962. Range-finding toxlclty data: List VI. Am. Ind. Hyg. Assoc. J. 23:
95-107. (Cited 1n U.S. EPA, 1981)
U.S. EPA. 1980a. Ambient Water Quality Criteria for Polynuclear Aromatic
Hydrocarbons. Environmental Criteria and Assessment Office, Cincinnati,
OH. EPA 440/5-80-069. NTIS PB 81-117806.
U.S. EPA. 1980b. Guidelines and Methodology Used 1n the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45: 79347-79357.
U.S. EPA. 1981. Health and Ecological Assessment of Polynuclear Aromatic
Hydrocarbons. Pathotox Publishers, Inc., Park Forest South, IL.
U.S. EPA. 1983. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxldty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
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Valnlo, H., P. VolUa, 3. Hartlola and 0. Pelkonen. 1976. The fate of
intratracheally Installed benzo[a]pyrene In the Isolated perfused rat lung
of both control and 20-methylcholanthrene pretreated rats. Res. Comm. Chem.
Pathol. Pharmacol. 13: 259-271. (Cited In U.S. EPA, 1980a)
Wise, S.A., W.J. Bonnett, F.R. Guenther and W.E. May. 1981. A relationship
between reversed-phase C,_ liquid chromatographlc retention and the shape
lo
of polycycllc aromatic hydrocarbons. J. Chromatogr. Sc1. 19: 457-465.
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APPENDIX
Summary Table for Phenanthrene
CO
I
Inhalation
AIS
AIC
Oral
AIS
AIC
Species
ND
NO
ND
ND
Experimental Effect
Dose/Exposure
ND ND
ND ND
ND ND
ND ND
Acceptable Intake
(AIS or AIC)
ND
ND
ND
ND
Reference
ND
ND
ND
ND
ND = Not derived
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