TECHNICAL REPORT DATA
(fteue n*d Instructions on the revert* btfort compienngj
1 REPORT NO.
EPA/600/5-88/040
3. RECIPIENT'S ACCESSION NO
PB88-182860/AS
4. TITLE AND SUBTITLE
Health Effects Assessment for Fluorenes
5. REPORT DATE
«. PERFORMING ORGANIZATION CODE
7 AUTHOH(S)
I. PERFORMING ORGANIZATION REPORT NO
9. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
13. TYPE OF REPORT AND PERIOD COVERED
Environmental Criteria and Assessment Office
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. OH 45268
14. SPONSORING AGENCY CODE
EPA/600/22
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund) uses these documents in
preparing cost-benefit analyses under Executive Order 32991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the ""elative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicants for which cancer is not the endpoint of
concern). The first, RfDs or subchronic reference dose, is an estimate of an exposure
level that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD is an estimate of an exposure level that would not
be expected to cause adverse effects when exposure occurs for a significant portion
of the lifespan. For compounds for which there is sufficient evidence of
carcinogenicity, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
7.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lOENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
18. DISTRIBUTION STATEMENT
Public
1». SECURITY CLASS (This Report/
Unclassified
21. NO. Of PAGES
20. SECURITY CLASS (Tttiipagei
Unclassified
22. PRICE
EPA Form 2220.1 (Re*. 4-77) PREVIOUS COITION is OBSOLETE
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EPA/600/8-88/040
May, 1987
HEALTH EFFECTS ASSESSMENT
FOR FLUORENES
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
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DISCLAIMER
This document has been reviewed In accordance with the U.S.
Environmental Protection Agency's peer and administrative review policies
and approved for publication. Mention of trade names or commercial products
does not constitute endorsement 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 Fluorenes.
Pertinent toxlcologlc and environmental data were located through online
literature searches of the TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data
bases. The basic literature searched supporting this document 1s current up
to May 1986. Secondary sources of Information have also been relied upon In
the preparation of this report and represent large-scale health assessment
efforts that entail extens.lve peer and Agency review. The following Office
of Health and Environmental Assessment (OHEA) sources have been extensively
utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria for Fluoranthene.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Water Regulations and Standards, Washington, DC. EPA
440/5-80-049. NTIS PB81-117608.
U.S. EPA. 1980b. Ambient Water Quality Criteria for Polynuclear
Aromatic Hydrocarbons. Prepared by the Office of Health and
Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Water Regulations and
Standards, Washington, DC. €PA 440/5-80-069. NITS PB81-117806.
U.S. EPA. 1980c. Hazard Profile for Polynuclear Aromatic Hydro-
carbons (PAH). Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste, Washington, DC.
U.S. EPA. 1983a. Reportable Quantity Document for Fluorene.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1983b. Reportable Quantity Document for Fluoranthene.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
111
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ABSTRACT
Oral and Inhalation toxldty data were not sufficient to derive risk
assessment values for fluorene or benzo( j ,k)fluorene. Short-term test data
Indicate that benzofluorene has the potential to be carcinogenic In humans.
The available short-term data for fluorene, however 1s Insufficient to
address Us carcinogenic potential.
1v
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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 John Helms (Office of
Toxic Substances) was the Project Officer. The final documents In 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 A1r 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 the following:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Jacky Bohanon and K1m Davidson
Environmental Criteria and Assessment Office
Cincinnati, OH
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TABLE OF CONTENTS
1
?
T
4
s
ft
7.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
CARCINOGENICITY
4.1. OTHER RELEVANT DATA
4.2. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RECOMMENDATIONS
REFERENCES
Page
. . 1
5
. . . 6
. . 7
. . . 7
. . . 10
. . . 11
. . . 12
. . . 14
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LIST OF ABBREVIATIONS
CHO Chinese hamster ovary
DMSO Dimethyl sulfoxlde
DNA Deoxyr1bonucle1c add
HGPRT Hypoxanth1ne-guan1ne phosphorbosyl transferase
RfD Reference dose
RfD§ Subchronlc reference dose
SCE Sister chromatld exchange
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Selected physical and chemical properties and environmental fate of
selected fluorenes are presented In Tables 1-1 and 1-2.
In both air and water, fluorene and benzo(J,k)fluorene are largely asso-
ciated with participate matter. When adsorbed to participate matter, the
fluorenes could potentially be transported long distances before ultimately
being removed by chemical reaction or wet and dry deposition (HSOB, 1986).
Vapor-phase fluoranthene has an estimated photodegradatlon half-life of 4-5
days (HSDB, 1986) and fluorene may have a similarly short reaction half-
life. In water, the fluorenes should rapidly adsorb onto sediments and
partlculate matter In the water column and bloconcentrate 1n aquatic organ-
Isms. Physical properties Indicate that adsorption and bloconcentratlon of
benzo(j,k)fluorene should be greater than that of fluorene. The fluorenes
are apparently stable In sediments for .decades or more (BJoerseth et al.,
1979). In the unadsorbed state 1n water, benzo(j,k)fluorene Is predicted to
photodegrade (half-life days to weeks); unadsorbed fluorene may also photo-
chemlcally degrade (HSDB, 1986; Sadtler, n.d.). The fluorenes are expected
to adsorb strongly to soil and to blodegrade 1n the presence of acclimated
microorganisms. Fluorene should degrade faster than benzo(j,k)fluorene
(HSDB, 1986).
0068h -1- 07/31/86
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TABLE 1-1
Selected Physical and Chemical Properties and Half-Lives for Fluorene
(CAS 86-73-7)
Property
Value
Reference
Chemical class:
Molecular weight:
Vapor pressure at 25°C:
Log octanol/water
partition coefficient:
Bloconcentratlon factor:
Soil adsorption
coefficient:
Half-lives In
Air:
Water:
Soil:
polynuclear aromatic
hydrocarbon
166.22
6.6xlO"4 mm Hg,
estimated
Water solubility at 25°C: 1.90 mg/l
4.18
1290 (blueglll
sunflsh)
3070
NR
NR
years (adsorbed to
sediments)
NR
Mackay and Shul, 1981
Mackay and Shul, 1981
Hansch and Leo, 1985
Velth et al., 1979
Lyn»n et al., 1982
Bjoerseth et al., 1979
NR = Not reported
0068h
-2-
10/07/86
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TABLE 1-2
Selected Physical and Chemical Properties and
Half-Lives for Benzo(j ,k)fluorene
Property
Value
Reference
Compound:
CAS number:
Chemical class:
Molecular weight:
Vapor pressure at 25°C:
Water solubility at 25°C:
Log octanol/water
partition coefficient:
B1oconcentrat1on factor:
Soil adsorption coefflcent:
Half-lives In
Air:
Water:
Soil:
benzo(j,k)fluorene
206-44-0
polynuclear aromatic
hydrocarbon
202.26
1.91xlO~3 mm Hg,
estimated
0.26 mg/j.
5.20
380 (rainbow trout)
3981 (fathead minnow)
9160
4-5 days (vapor phase)
days to weeks
(unadsorbed state)
years (adsorbed to
sediments)
NR
Hackay and Shu1,
1981
Hackay and Shu1,
1981
Hansch and Leo,
1985
NLM, 1986
Lyman et al.,
1982
NLM, 1986
NLM, 1986
Bjoerseth et al.,
1979
NR = Not reported
0068h
-3-
10/07/86
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Because fluorene and benzo(J ,k)fluorene have been found 1n ambient air
and water, exposure by Inhalation and 1ngest1on are of concern. Estimates
of total dally human exposure to benzo(J,k)fluorene are as follows (U.S.EPA,
1980a):
Source Estimated Exposure
(mq/day)
Water 0.017
Food 1.6-16
Air 0.040-0.080
These data Indicate that food Is the greatest source of benzo(j,k)fluorene.
Pertinent exposure data for fluorene could not be located In the available
literature.
0068h -4- 07/31/86
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2. ABSORPTION FACTORS IN HUMAN AND EXPERIMENTAL ANIMALS
Pertinent data regarding the absorption of fluorene or benzo(j.k)-
fluorene following oral or Inhalation exposure could not be located In the
available literature. The relatively high llpld solubility of both
compounds Indicates that they are likely to be absorbed following oral or
Inhalation exposure.
0068h -5- 07/31/86
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
Pertinent data regarding subchronlc, chronic, teratogenlc or other
reproductive effects of fluorene or benzo(j,k)fluorene following oral or
Inhalation exposure could not be located In the available literature.
Mixtures of polynuclear aromatic hydrocarbons, Including benzo(j.k)-
fluorene, have been tested for their Interactive toxic effects In mice by
subcutaneous exposure (Pfelffer, 1973, 1977) and by dermal application
(Schmahl et al., 1977). No synerglstlc or antagonistic effects were noted
by either exposure method.
0068h -6- 10/07/86
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4. CARCINOGENICITY
•
Pertinent data regarding the carcinogenic potential of fluorene or
benzo(j,k)fluorene 1n humans or laboratory animals by either the oral or
Inhalation routes of exposure could not be located In the available
literature.
4.1. OTHER RELEVANT DATA
Morton and Christian (1974) made bi-weekly applications of benzo(j.k)-
fluorene 1n decalln or In a 1:1 mixture (by volume) of decalln and the
cocarclnogen n-dodecane to the Interscapular skin of 15-20 two-month-old C3H
male mice. The mice received 50/mg application and were treated for 82
weeks. No skin tumors were observed 1n mice treated with benzo(j,k)fluorene
In either decalln or the decal1n-n-dodecane mixture.
Van Ouurren and Goldschmldt (1976) tested benzo(j,k)fluorene for Us
tumor promoting and cocardnogenlc activity. In the tumor promoting study,
benzo(a)pyrene (150 mg) was applied to the skin of 50 female ZCR/Ha Swiss
mice (6-8 weeks of age). Fourteen days after the benzo(a)pyrene applica-
tion, benzo(j,k)fluorene 1n acetone at 40 mg was applied 3 times/week for
the duration of the study (440 days). In this system, benzo(j,k)fluorene
showed no tumor-promoting activity.
In the cocardnogenldty study (Van Ouuren and Goldschmldt, 1976),
benzo(a)pyrene (5 mg) was applied to the skin of mice simultaneously with
benzo(j,k)fluorene (50 mg) In acetone. The compounds were applied 3 times/
week over a test period of 440 days. The number of mice with paplllomas and
carcinomas more than doubled with benzo(j,k)fluorene as compared with benzo-
(a)pyrene controls (16/50 benzo(a)pyrene; 39/50 benzo(a)pyrene + benzo(j.k)-
fluorene). Benzo(j,k)fluorene also Increased the number of tumors per mouse
0068h -7- 10/07/86
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and decreased the days to the appearance of the first tumor as compared with
the benzo(a)pyrene controls (210 days to first tumor, benzo(a)pyrene; 99
days, benzo(a)pyrene * benzo(j,k)fluorene).
R1ce et al. (1984) applied [3H]-benzo(a)pyrene (15-22 nmol=3.8-5.5
yg) In acetone or a mixture of [3H]-benzo(a)pyrene (3.8-5.5 yg) and
benzo(j,k)fluorene (37 yg) In acetone to the skin of 5-10 female CD-I
mice. After 24 hours, the mice were killed and the treated skin removed and
analyzed for DNA adducts, evidence of DNA disruption. Co-application of
benzo(j,k)fluorene with [3H]-benzo(a)pyrene resulted In an average
Increase of DNA adduct formation of 66% as compared with [3H]-benzo{a)-
pyrene treatment alone.
A study by Busby et al. (1984) provides evidence that benzo(J,k)fluorene
has activity as a complete carcinogen. In the mouse lung adenoma bloassay,
at least 50 Swiss-Webster BLU:Ha newborn male and female mice were Injected
IntraperHoneally with 1/7 of the dose on day 1, 2/7 of the dose on day 8
and the remaining 4/7 of the dose on day 15. Vehicle control mice received
DMSO; positive control mice received benzo(a)pyrene; and the benzo(j.k)-
fluorene-treated mice received a total dose of 700 yg (163 yg/kg) or 3.5
mg (815 mg/kg). At 24 weeks of age, treated mice were sacrificed, gross
observations were recorded and lungs were fixed for hlstopathologlcal
examination.
The results showed that the 3.5 mg dose of benzo(j,k)fluorene Induced a
significant Increase In the total Incidence (58%, p<0.0001) and number of
lung tumors (1.08 tumors/mouse, p<0.001) as compared with vehicle controls
(9%, 0.09 tumors/mouse). About 20% of the mice with lung tumors 1n the high
dose benzo(j,k)fluorene group had lesions diagnosed as adenocarclnomas. No
0068h -8- 10/07/86
-------
significant " tumor response was observed 1n mice receiving the low benzo-
(j ,k)f luorene dose (20%, 0.24 tumors/mouse). None of the lung tumors In
this group were diagnosed as adenocardnomas. Positive controls responded
appropriately.
Benzo(j,k)fluorene has been shown to be weakly mutagenlc In Salmonella
typhlmurlum strains TA100 (K1nae et al., 1981) and TA98 (Epler et al., 1978)
with S-9 metabolic activation. Benzo(j,k)fluorene was found to be mutagenlc
1n S. typhlmurlum strain TM677 with S-9 metabolic activation (Kaden et al.,
1979). K1nae et al. (1981) observed negative results with benzo(j,k)-
fluorene In S. typhlmurlum strains TA98 and TA1535 with or without metabolic
activation and In the Bacillus subt111s rec assay.
Benzo(j,k)fluorene was negative for unscheduled DNA synthesis 1n the
hepatocyte primary culture/DNA repair test (McQueen and Williams, 1980).
The compound was also negative for gene mutation In the human lymphoblast
line AHH-1, which Is competent for xenoblotlc metabolism (Crespl and Thllly,
1984).
L1 (1984) determined benzo(j,k)fluorene to be weakly mutagenlc 1n the
CHO cell HGPRT assay with S-9 metabolic activation. The number of mutants
was found to Increase with the amount of S-9 added to the culture, although
cell survival was reduced at higher S-9 concentrations. Benzo(j,k)fluorene
was also mutagenlc In repair-deficient CHO cells 1n the presence of rat
mlcrosomes at 0.5-0.7 mg/mi (Hoy et al., 1984).
Pertinent data regarding the carcinogenic potential of fluorene 1n
laboratory animals by any route could not be located In the available
literature. Fluorene has tested negative In mutation assays with S-9
metabolic activation using S. typhlmurlum strains TA98, TA100, TA1535 and
TA1537 (Sakal et al., 1985; Epler et al., 1978; McCann et al., 1975).
0068h -9- 10/07/86
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Fluorene also was negative In the Escherlchla coll WP2/WP100 rec assay
(Mamber et al., 1983). The compound was found to be weakly mutagenlc when
tested with S. typhlmurlum strain TA97 with S-9 metabolic activation (Sakal
et al., 1985).
Fluorene has also been tested In L517847K ~ mouse lymphoma cells for
forward mutation (Oberly et al., 1984^, In Chinese hamster cells for SCE In
bone marrow (Neal and Probst, 1983), 1n negative primary culture/DNA repair
assays using mouse and hamster hepatocytes (McQueen et al., 1983) and 1n the
CHO/HGPRT assay (Hs1e et al., 1979). In all the above tests, fluorene was
negative.
4.2. HEIGHT OF EVIDENCE
Benzo(j,k)fluorene has been shown to have a potential to be a complete
carcinogen In a newborn mouse lung adenoma bloassay (Busby et al., 1984).
This evidence 1s sufficient to classify benzo(j,k)fluorene as an IARC Group
3 chemical and place It 1n EPA Group C, "possible human carcinogen" (U.S.
EPA, 1986).
Because of the lack of studies concerning the carcinogenic potential of
fluorene, It can be classified as an IARC Group 3 chemical and a EPA Group 0
chemical, "not classified" (U.S. EPA, 1986).
0068h -10- 12/29/86
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5. REGULATORY STANDARDS AND CRITERIA
*
An ambient water quality criterion of 42 yg/l has been calculated
for benzo(j,k)fluorene (U.S. EPA, 1980a). This value was derived from a
study by Hoffmann et al. (1972) 1n which 50 V9. of 1.0% benzo(j ,k)fluorene
applied to the skin of Swiss albino mice 3 times/week for 12 months caused
no Increase In mortality. Other parameters of toxldty were not evaluated.
It 1s uncertain whether this value protects against the carcinogenic
potential of benzo(J,k)fluorene.
No standards or criteria are available for fluorene.
0068h -11- 07/31/86
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6. RECOMMENDATIONS
Because of the lack of data for the cardnogenlcHy and threshold
toxlclty of benzo(],k)fluorene and fluorene by relevant routes of exposure,
risk assessment values for these compounds have not been derived 1n past
health assessment activities. An ambient water quality criterion of 42
vg/l was developed for benzo(j,k)fluorene (U.S. EPA, 1980a), based on
the lack of Increased evidence of mortality In mice dermally exposed 3
times/week for 12 months (Hoffmann et a!., 1972). This study Is Insuffi-
cient for derivations of RfD/RfO- values because the parameters of
toxldty evaluated were not sufficient for estimation of a threshold for
noncarclnogenlc toxldty.
The primary Issue requiring resolution 1s the cardnogenlcHy of fluo-
rene and benzo(j,k)fluorene by oral or Inhalation exposure. According to
exposure data provided by the U.S. EPA (1980a), both routes of exposure may
be Important, at least for benzo(J ,k)fluorene. Human data could not be
located regarding the cardnogenlcHy of fluorene or benzo(j,k)fluorene and
no animal data were located on fluorene. Fluorene was negative 1n mutagen-
•
1dty tests In microorganisms (Mamber et al., 1983; Sakal et al., 1985) and
1n mutagenldty and clastogenldty tests 1n mammalian systems (Oberly et
al., 1984; Neal and Probst, 1983; McQueen et al., 1983; Hs1e et al., 1979).
Benzo(j,k)fluorene, on the other hand, has been shown to be a cocardnogen
with benzo(a)pyrene 1n a dermal test In mice (Van Duuren and Goldschmldt,
1976), a complete carcinogen In the newborn mouse lung adenoma assay (Busby
et al., 1984) and weakly mutagenlc In prokaryotlc (K1nae et al., 1981; Kaden
et al., 1979) and mammalian (LI, 1984; Hoy et al., 1984) test systems.
0068h -12- 05/14/87
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These data, coupled with the fact that other polycycllc aromatic hydro-
carbons are known carcinogens, emphasize the need to ascertain the cardno-
genlclty of fluorene and benzolj,k)fluorene by oral and Inhalation routes of
exposure.
If adequate testing determines that these compounds are not carcino-
genic, efforts should be made to determine thresholds for noncarclnogenlc
toxlclty. Data are needed to determine the target organ(s) or system(s)
most likely to be Injured by exposure to these compounds. Oral exposure to
determine subchronlc, developmental and reproductive toxldty would also be
necessary. Inhalation toxldty would be more difficult to ascertain because
these compounds have relatively low vapor pressures (Mackay and Shu1, 1981)
and occur In the atmosphere largely associated with partlculate matter.
0068h -13- 12/29/86
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7. REFERENCES
Bjoerseth, A., J. Knutzen and J. Ske1. 1979. Determination of polycycllc
aromatic hydrocarbons In sediments and mussels from Saudafjord, VI. Norway,
by glass capillary gas chromatography. Sc1. Toxlcol. Environ. 13: 71-86.
Busby, H.F., Jr.,, M.E. Goldman, P.M. Newberne and G.N. Wogan. 1984.
Tumor1gen1dty of fluoranthene 1n a newborn mouse lung adenoma bloassay.
Cardnogenesls. 5(10): 1311-1316.
Crespl, C.L. and W.G. ThUly. 1984. Assay for gene mutation 1n a human
lymphoblast line, AHH-1, competent for xenoblotlc metabolism. Mutat. Res.
128: 221-230.
Epler, 3.L., F.W. Larimer, T.K. Rao, C..E. Nix and T. Ho. 1978. Energy-
related po.llutants In the environment: Use of short-term tests for mutagen-
Iclty 1n the Isolation and Identification of blohazards. Environ. Health
Perspect. 27: 11-20.
Hansch, C. and A.J. Leo. 1985. Medchem Project. Issue #26. Pomona
College, Claremont, CA.
Hoffmann, 0., G. Rathkamp, S. Nesnow and E.L. Hynder. 1972. Fluoranthenes:
Quantitative determination 1n cigarette smoke, promotion by pyrolysls, and
tumor Initiating activity. J. Natl. Cancer Inst. 49(4): 1165.
0068h -14- . 07/31/86
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Horton, A.W. and G.M. Christian. 1974. Cocarclnogenlc versus Incomplete
carcinogenic activity among aromatic hydrocarbons. Contrast between
chrysene and benzo(b)tr1phenylene. J. Nat"!. Cancer Inst. 53(4): 1017-1020.
Hoy, C.A., E.P. Salazar and L.H. Thompson. 1984. Rapid detection of
DNA-damag1ng agents using repair-deficient CHO cells. Mutat. Res. 130(5):
321-322.
HSOB (Hazardous Substance Data Bank). 1986. No. 5486. On-Hne
Hs1e, A.H., J. O'Neill, J.R. San Sebastian, O.B. Couch and P.A. BMmer.
1979. Quantitative mammalian cell genetic toxicology: Study of the cyto-
toxldty and mutagenlcHy of seventy Individual environmental agents related
to energy technologies and three subfractlons of a crude synthetic oil In
the CHO/HGPRT system. Environ. Scl. Res. 15: 291-315.
Kaden, D.A., R.A. H1tes and U.G. ThUly. 1979. MutagenlcHy of soot and
associated polycycllc aromatic hydrocarbons to Salmonella typhlmurlum.
Cancer Res. 39(10): 4152-4159.
K1nae, N, T. Hashlzume, T. Maklta, I. TomHa, I. Klmura and H. KanamoM.
1981. The toxlclty of pulp and paper mill effluents: 1. MutagenlcHy of the
sediment samples derived from kraft paper mills. Water Res. 15(1): 17-24.
L1, A.P. 1984. Use of Aroclor !254-1nduced rat liver homogenate In the
assaying of promutagens 1n Chinese hamster ovary cells. Environ. Mutagen.
6(4): 539-544.
0068h -15- 07/31/86
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Lyman, W.J., W.F. Reehe and O.H. Rosenblatt. 1982. Handbook of Chemical
Property Estimation Methods Environmental Behavior of Organic Compounds.
McGraw-Hill Book Co.. New York. p. 4-9.
Mackay, 0. and W.Y. Shlu. 1981. A critical review of Henry's Law Constants
for chemicals of environmental Interest. J. Phys. Chem. Ref. Data. 19:
1175-1199.
Mamber S.W., V. Bryson and S.E. Katz. 1983. The Escher1ch1a coll HP2/WP100
rec assay for detection of potential chemical carcinogens. Mutat. Res.
119(1): 135-144.
McCann, J., E. Choi, E. Yamasakl and' B.N. Ames. 1975. Detection of
carcinogens as mutagens In the Salmonella/mlcrosome test. Assay of 300
chemicals. Proc. Natl. Acad. Sc1. U.S.A. 72: 5135-5139.
McQueen, C.A. and G.M. Williams. 1980. Verification of unscheduled DNA
synthesis as DNA repair In the hepatocyte primary culture/DNA repair test.
Ann. N.Y. Acad. Sc1. 5: 349-404.
McQueen, C.A., D.M. Krelser and G.M. Williams. 1983. The hepatocyte
primary culture/DNA assay using mouse or hamster hepatocytes. Environ.
Mutagen. 5: 1-8.
Neal, S.B. and G.S. Probst. 1983. Chemically-Induced slster-chromatld
exchange Vn vivo In bone marrow of Chinese hamsters. An evaluation of 24
compounds. Mutat. Res. 113: 33-43.
0068h -16- 10/07/86
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NLM (National Library of Medicine). 1986. Hazardous Substance Data Base.
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