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

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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.
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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,
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Busby,  H.F.,   Jr.,,  M.E.  Goldman,  P.M.  Newberne  and  G.N.   Wogan.    1984.
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Crespl,  C.L.  and W.G.  ThUly.   1984.   Assay  for  gene  mutation  1n  a  human
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Epler,  3.L.,  F.W. Larimer,  T.K.  Rao,   C..E.  Nix  and  T.  Ho.    1978.   Energy-
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Hansch,  C. and  A.J.  Leo.   1985.  Medchem Project.   Issue  #26.   Pomona
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Hoffmann, 0.,  G.  Rathkamp,  S.  Nesnow and  E.L. Hynder.  1972.   Fluoranthenes:
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Horton, A.W.  and G.M.  Christian.   1974.   Cocarclnogenlc  versus  Incomplete
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Hoy,  C.A.,   E.P.  Salazar  and  L.H.  Thompson.   1984.   Rapid  detection  of
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Kaden,  D.A.,  R.A.  H1tes and  U.G.  ThUly.   1979.   MutagenlcHy  of soot and
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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
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6(4): 539-544.


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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.
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Mackay, 0. and W.Y.  Shlu.  1981.  A  critical  review  of  Henry's  Law Constants
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Mamber S.W., V. Bryson and S.E.  Katz.  1983.   The  Escher1ch1a  coll HP2/WP100
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McCann,  J.,  E.  Choi,  E.  Yamasakl  and'  B.N.   Ames.   1975.   Detection  of
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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.
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Neal,  S.B.  and  G.S.  Probst.   1983.   Chemically-Induced  slster-chromatld
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NLM  (National  Library of Medicine).   1986.   Hazardous Substance  Data  Base.
Online.

Oberly,  T.J.,  8.J.  Bewsey  and  G.S.   Probst.   1984.  An  evaluation of  the
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Mutat. Res.  125(2): 291-306.

Pfelffer,  E.H.   1973.   Investigations  on  the  carcinogenic  burden by  air
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U.S. EPA, 1980a)

Pfelffer, E.H.   1977.  Oncogenlc Interaction of  carcinogenic and noncarclno-
genlc  polycycllc   aromatic  hydrocarbons   In  mice.   In:   Air  Pollution  and
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R1ce,  J.E.,  T.O.  Hosted,  Jr.  and  E.J.  Lavole.    1984.   Fluoranthene  and
pyrene  enhance  benzo[a]pyrene-ONA adduct  formation jji  vivo  1n mouse  skin.
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243-246.

Sadtler.   n.d.   Sadtler  Standard  UV  Spectra  No.  2114.    Sadtler  Research
Laboratory, Philadelphia, PA.


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Sakal, M.,  0.  Yoshlda and  S.  M1zujak1.   1985.   MutagenlcHy of  polycycllc
aromatic hydrocarbons  and  qulnones on  Salmonella typhlmuMum TA97.   Mutat.
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Schmahl, 0.,  et  al.    1977.   Syncardnogenlc  action of  polycycllc  hydro-
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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  Assess-
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U.S.  EPA.   1980c.  Hazard  Profile  for  Polynuclear  Aromatic  Hydrocarbons
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of  Solid Waste, Washington, DC.
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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
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U.S.  EPA.    1986.   Guidelines  for  Carcinogenic   Risk  Assessment.   Federal
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Van  Duuren,  B.L.  and  .8.M.  Goldschmldt.    1976.   Cocarclnogenlc and  tumor-
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VeHh,  G.D., D.L.  Delore and B.V. Bergstedt.  1979.  Measuring  and  estimat-
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