EPA-540/1-86-022
                     urmou
                     Environmental Protection
                     Agency
Office of Emergency and
Remedial Response
Washington PC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
environmental Criteria and
Assessment Office
Cincinnati OH 45263
                      Superfund
vvEPA
                       HEALTH EFFECTS  ASSESSMENT
                       FOR  BENZO(a)PYRENE

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                                            EPA/540/1-86-022
                                            September  1984
       HEALTH  EFFECTS ASSESSMENT
            FOR BENZO(A)PYRENE
    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
                              U.S. Environmental Protection Agency
                              Region V, Library
                              230 South Dearborn Street  >-""
                              Chicago,  Illinois  60604

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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.
U.S. Envircnrno^aS Protection Agency
                                         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  benzo(a)-
 pyrene.    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.   Pertinent  toxlcologlc and
 environmental  data were located  through  on line  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  the 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)  sources  have
 been extensively utilized:

     U.S.  EPA.   1980b.  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.   1981.   Hazard  Profile for  PAH.   Prepared by the Environ-
     mental  Criteria  and Assessment  Office, Cincinnati, OH, OHEA for  the
     Office  of Solid Waste  and  Emergency Response, Washington,  DC.

     U.S. EPA.   1983a.  Review  of Toxlcologlc Data  In Support of Evalua-
     tion  for Carcinogenic Potential of:   Benzo[a]pyrene.   Prepared by
     the  Carcinogen  Assessment  Group,   OHEA,  -Washington,   DC for   the
     Office  of Solid Waste  and  Emergency Response, Washington, DC.

     U.S.   EPA.     1983b.    Reportable   Quantity   for   Benzo[a]pyrene.
     Prepared  by   the  Environmental  Criteria  and  Assessment  Office,
     Cincinnati, OH,  OHEA  for  the Office  of Solid Waste  and  Emergency
     Response, Washington,  DC.

     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  was 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 Is  not the endpolnt  of  concern).
The  first,  the AIS  or acceptable  Intake subchronlc,  1s  an estimate of an
exposure  level  which  would  not  be  expected  to  cause adverse  effects  when
exposure occurs during a  limited time Interval  (I.e.,  for  an  Interval which
does not  constitute a significant  portion  of  the llfespan).   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 1n  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.
                                      111

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    The  AIC,  acceptable  Intake  chronic,  1s  similar  In  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 (1980a) 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 Is Insignificant.

    Composite scores (CS)  for noncarclnogens have  also  been calculated where
data permitted.   These values  are used  for  ranking reportable  quantities;
the methodology for their  development 1s explained In  U.S. EPA (1983c).

    For  compounds for which there  Is sufficient evidence  of cardnogenlcHy,
AIS  and AIC values  are  not derived.   For  a  discussion  of  risk  assessment
methodology  for  carcinogens refer  to  U.S.  EPA (1980a).   Since cancer  Is  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  1n  proper  context, the
reader 1s  referred to  the  preface of  this  document.  The  preface outlines
limitations applicable to all documents of this  series as well as the appro-
priate Interpretation and use of the quantitative estimates presented.
       M
    Animal  data  Indicate  that  benzo(a)pyrene  1s  a  potent  carcinogen  via
Inhalation,  oral   and  dermal  routes.   Human  data  concerning  exposure  to
benzo(a)pyrene  and  cancer   are  lacking;  however,  human  data  concerning
Increased cancer  risk and exposure to PAH containing mixtures are convincing.

    U.S.   EPA  (1980b)  used  the  mouse  data  of  Neal  and  Rlgdon  (1967)  to
compute  a  q-|* of  11.53  (mg/kg/day)"1.   This  risk  assessment  has  been
extensively peer  reviewed.

    The same methodology was used  In  the present document  to compute a q-j*
of  6.11   (mg/kg/day)"1  from  Inhalation  exposure  data  1n  Golden  Syrian
hamsters.

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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  OeRosa 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 01 sen 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
                                      v1

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TABLE OF CONTENTS

1.
2.


3.










4.








5.


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 	
REGULATORY STANDARDS AND CRITERIA 	
Page
... 1
... 3
. . . 3
. . . 3
... 4
... 4
... 4
... 4
... 4
... 4
. . . 4
... 4
. . . 4
. . . 5
. . . 5
. . . 7
. . . 7
. . . 7
. . . 7
. . . 8
. . . 8
. . . 8
. . . 15
. . . 16
. . . 17
       V11

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                           TABLE  OF  CONTENTS (cont.)
                                                                        Page
 6.  RISK ASSESSMENT	    19
     6.1.   ACCEPTABLE INTAKE SUBCHRONIC (AIS) 	    19
     6.2.   ACCEPTABLE INTAKE CHRONIC (AIC)	    19
     6.3.   CARCINOGENIC POTENCY (q^)	    19
            6.3.1.   Oral	    19
            6.3.2.   Inhalation	    19
 7.  REFERENCES	    21
APPENDIX A: Summary Table for Benzo[a]pyrene 	    28
APPENDIX B: Cancer Data Sheet for Derivation of q-|*	    29
APPENDIX C: Cancer Data Sheet for Derivation of q-j*	    31

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                               LIST OF TABLES

No.                               Title                                Page

1-1     Selected Physical and Chemical Properties  and  Half-lives
        for Benzo[a]pyrene	       2
4-1     CarclnogenlcHy of Benzo[a]pyrene Administered  1n  the  Diet
        to Male and Female CFW Mice at  Levels  of  1-250  ppm	      9

4-2     CarclnogenlcHy of Benzo[a]pyrene Administered  1n  the  Diet
        to Male and Female Swiss  Mice at  Levels of  250-1000 ppm  .  .     10

4-3     Carc1nogen1c1ty of Benzo[a]pyrene Administered  1n  the  Diet
        to Male and Female Swiss  CFW Mice at a Level  of 250 ppm  .  .     11

4-4     CarclnogenlcHy of Benzo[a]pyrene to Male Syrian Golden
        Hamsters by Inhalation	     12

4-5     CarclnogenlcHy of Benzo[a]pyrene 1n Syrian Hamsters
        Following Intratracheal Administration of
        0.10-1.0 mg/week	     13

4-6     CarclnogenlcHy of Benzo[a]pyrene 1n Golden Syrian
        Hamsters Following Intratracheal  Administration of
        18.2-36.4 mg/an1mal  	     14
                                    1x

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                             LIST OF  ABBREVIATIONS

ADI                     Acceptable dally Intake
AIC                     Acceptable Intake chronic
AIS                     Acceptable Intake subchronlc
bw                      Body weight
CAS                     Chemical Abstract Service
CS                      Composite score
DNA                     Deoxyrlbonuclelc add
GI                      Gastrointestinal
PAH                     Polycycllc aromatic hydrocarbon
SCE                     Sister chromatld exchange
TLV                     Threshold limit value
TWA                     Time-weighted average

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                     1.  ENVIRONMENTAL CHEMISTRY AND FATE

    The relevant  physical  and  chemical properties and environmental  fate  of
benzo[a]pyrene (CAS Registry No.  50-32-8)  are given  1n Table 1-1.
    The half-life  for benzo[a]pyrene  1n  the atmosphere has been  estimated
from  the  discussion  In  the  NAS  (1983) document  regarding the chemical and
Us  photochemical  reaction  and  the  estimation  of   Us  half-life  due  to
physical removal  processes  as discussed by CupHt  (1980).
    Pertinent  data  regarding  the  Teachability  of  this  compound  1n  soils
could  not  be  located 1n  the  available  literature.   Considering  the  high
octanol/water partition  coefficient  and  low  water  solubility, the compound
1s expected  to  have  very  low  mobility 1n soils,  particularly In soils  with
high organic matter  content.
                                     -1-

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                                                 TABLE  1-1
                 Selected Physical  and  Chemical Properties and Half-lives for Ben2o[a]pyrene
       Properties
                Values
       Reference
Chemical class:
Molecular weight:
Vapor pressure:
Mater solubility:
Log octanol/water
  partition coefficient:
Bloconcentratlon factor:
Half-lives In:
     Air:
     Water:

     Soil:
Polycycllc aromatic hydrocarbons (PAH)
252
5.6 x 1(T» mm Hg at 25°C
1.2 ng/kg at 25°C
6.06
28,200 (estimated)

14-16 months for complete degradation
NA
Mabey et al., 1961
Nabey et al., 1981
Ulse et al.. 1981

U.S. EPA, 1980b
U.S. EPA, 1980b

HAS, 1983; Cupltt, 1980
Smith et al.. 1978
Smith et al., 1978
U.S. EPA, 1981
NA = Not applicable

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           2.   ABSORPTION  FACTORS  IN  HUMANS AND  EXPERIMENTAL ANIMALS
2.1.   ORAL
    Data  regarding  oral- absorption  of  benzo[a]pyrene are  limited;  however,
observed  toxldty  following  oral  administration  Indicates  that  benzofa]-
pyrene 1s absorbed  by this  route  (Smyth  et al.,  1962; U.S.  EPA,  1980b,  1981;
Santodonato et al.,  1981).
    Absorption of orally  administered  UpophlUc  PAH can be hampered by  the
mucous layer lining the 61  tract  (Grimmer, 1983).   Rats  given  benzo[a]pyrene
1n starch  solution  (100 mg) by gavage or In the  diet  (250 mg) absorbed -50%
of the administered  compound (Chang,  1943).
    Regardless of   the  type of  solvent  used,  benzo[a]pyrene  readily  pene-
trates  the  forestomach   epithelium  of  mice.   In  the  glandular   stomach,
however,  the type of solvent used plays  a decisive  role  1n  the absorption of
benzo[a]pyrene (Ekwall  et  al.,  1951;  Setala,  1954).  Hydroph1l1c   solvents
enhance  the absorption  of  benzo[a]pyrene   from the glandular  stomach  as
               ;
compared  to UpophlUc  solvents.
2.2.   INHALATION
    Data   regarding  the  pulmonary absorption  of  benzo[a]pyrene are  limited;
however,   observed toxldty  after Inhalation  exposure Indicates  that benzo-
[a]pyrene 1s readily absorbed  through  the  lungs (Kotln et al., 1969; Va1n1o
et al.,  1976).   As  a  class,  PAHs are  highly llpld  soluble  and  capable of
passing across  epithelial  membranes  (U.S. EPA, 1980b).
                                     -3-

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                3.  TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.   SUBCHRONIC
3.1.1.   Oral.   Differences  1n  genetic constitutions  appear  to  Influence
the  subchronlc  oral  toxldty of  benzo[a]pyrene  1n mice.  Specifically,  the
Ah locus, which determines the 1nduc1b111ty of aryl  hydrocarbon  hydroxylase,
plays  a  major  role  1n  determining  the oral  toxldty  of  benzo[a]pyrene,
presumably by Influencing the pathways of blotransformatlon.   Robinson  et
al.  (1975) administered  benzo[a]pyrene  In  the diet  at  a level of  120  mg/kg
bw  to nonresponslve  (poorly  Indudble) AKR/N  mice  (Ah /Ah  type)  and  to
responsive  (markedly   Indudble)  mice  (Ah /Ah   type).   Nonresponslve  mice
developed aplastlc anemia  and  died within 4  weeks,  whereas  responsive  mice
remained healthy for  at least  6 months.
3.1.2.   Inhalation.    Pertinent   data   regarding   the   non-tumor-related
subchronlc toxldty  of benzo[a]pyrene  administered  by  Inhalation  could  not
be located 1n the available literature.
3.2.   CHRONIC
3.2.1.   Oral.  The  only available chronic bloassays  for  oral  exposure  of
benzo[a]pyrene are Investigations of cardnogenlclty (U.S. EPA,  1980b).   The
lack  of  appropriate   protocols   (I.e.,  non-tumor  pathology)  and  detailed
reporting of  symptoms  render  these cardnogenlclty bloassays  Inadequate  for
use 1n evaluating non-carcinogenic endpolnts.
3.2.2.   Inhalation..   There  are  no  reports  available  concerning  the  non-
tumor-related chronic toxldty  of  benzo[a]pyrene  administered by  Inhalation.
3.3.   TERATOGENICITY AND OTHER  REPRODUCTIVE EFFECTS
3.3.1.   Oral.  Rlgdon and Rennels  (1964)  fed female rats a  diet  containing
benzo[a]pyrene at a  level  of  1000 mg/kg (equivalent to 50 mg/kg/day)  for  up
to  3.5 months.   Of  seven  pregnant  treated  animals,  only  one  dam  carried
viable fetuses  to term,  delivering  four pups  on the 23rd day of  pregnancy.

                                     -4-

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Two of the  four  pups  were  stillborn,  one of which was grossly malformed (not
necessarily  treatment-related).   A  third  pup -was  killed  for  observational
purposes, and evidently  the  fourth  pup  died of starvation 3 days after birth
because  the  dam did  not  appear   to  be  lactatlng.   The  authors were  not
certain whether this absence of lactation was treatment-related.
    At autopsy,  four  dead  fetuses  were  found  1n  the  right  uterine horn of a
second dam.  Signs  of  toxlclty  (body  weight  changes  or  hlstopathologlcal
changes)  were not observed 1n the treated dams.
    In a  teratogenldty  and reproduction  study,  Rlgdon and Neal  (1965)  fed
male and  female  mice diets  containing  benzo[a]pyrene at a  level  of  0, 250,
500  or  1000  mg/kg  over  various  time  spans  during  mating,   gestation  and
lactation.  No apparent  reproductive, teratogenlc, embryotoxlc or fetotoxlc
effects were observed 1n the experimental animals.
    Mackenzie and  Angevlne  (1981)  administered  benzo[a]pyrene orally at  a
level  of  10 mg/kg  bw to CO-1 mice  during  pregnancy.   There was no effect  on
fetal  body  weights, but  there was  a marked and specific reduction of gonadal
weight, and reduced fertility  and  reproductive capacity  were  observed among
the offspring.   At a  level  of 40  mg/kg/day,  almost  complete  sterility  was
observed 1n both sexes of offspring.
3.3.2.   Inhalation.   Pertinent  data   regarding  the   teratogenlc   effects
resulting from Inhalation  exposure  to benzo[a]pyrene  could  not  be located  1n
the available literature.
3.4.   TOXICANT INTERACTIONS
    U.S.   EPA  (1980b)  has  described extensively  the  synerglstlc  and  antago-
nistic Interactions among  different PAHs and between  PAH and  non-PAH chemi-
cals.  Briefly,  metabolism of  PAH  by  the  mlcrosomal  mixed  function  oxldase
                                      -5-

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enzyme system  yields  several  types  of reactive and  potentially  carcinogenic
Intermediates.   Chemicals  that Induce  or Inhibit  this  enzyme  system  alter
the patterns of  PAH metabolism  and,  hence,  alter  their toxic  and  carcino-
genic  properties.
                                      -6-

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                              4.   CARCINOGENICITY

    The  cardnogenldty  of  benzo[a]pyrene  has  been  tested extensively  by
applying  It  to the  skin  of  mice, and  only  Infrequently by other  routes  of
administration.   The studies  discussed below have  been summarized  1n  U.S.
EPA  (1983a);  however, more complete  reviews  of the cardnogenldty bloassays
of benzo[a]pyrene  are  provided by IARC (1973, 1983).  U.S.  EPA  (1980b,  1981,
1983b) and Santodonato et al.  (1981).
4.1.   HUMAN DATA
    Few case  reports are  available regarding the direct  carcinogenic effects
of  benzo[a]pyrene  on   humans.   Cott1n1  and  Mazzone  (1939)  applied  a  IX
solution  of  benzo[a]pyrene  1n benzene to  small  areas  of  the exposed  and
unexposed  skin  of 26  patients.   Up   to 120  dally applications were applied
over a  4-month  period,  within which  time,  regressive verrucae developed  1n
each of  the  26 patients.  Although  reversible and apparently'benign,  these
changes were  thought to represent early stages  of  neoplastlc proliferation.
Similar cases of epidermal changes were reported by  Rhoads  et al.  (1954)  and
Klar (1938) to  have  occurred 1n  men   accidentally exposed to benzo[a]pyrene.
Numerous  ep1dem1olog1c   studies  of   human   populations   (primarily worker
groups) have  shown  a  clear  association between  exposure to PAH-contalnlng
materials  (e.g.,  soots, tars, oils)  and  Increased cancer risk  (Santodonato
et al., 1981;  IARC, 1973,  1983; U.S.  EPA,  1981).
4.1.1.    Oral.  Pertinent  data regarding  the cardnogenldty  of  benzo[a]-
pyrene to humans  following oral  exposure  could not be located  1n  the avail-
able literature.
4.1.2.    Inhalation.    Pertinent  data  regarding   the  cardnogenldty  of
benzo[a]pyrene to  humans  following Inhalation exposure could not be  located
1n the  available literature.

                                      -7-

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4.2.   BIOASSAYS
4.2.1.   Oral.   Benzo[a]pyrene  was  administered  1n  various  concentrations
1n  the  diets of  mice  to test  Us carc1nogen1c1ty  (Neal  and Rlgdon,  1967;
Rlgdon and  Neal,  1966,  1969).  These  studies  are summarized 1n  Tables  4-1.
4-2 and  4-3.  A  dose-response  relationship was  noted  for the Incidence  of
stomach tumors (paplllomas and carcinomas)  In male and  female CFW-SwUs  mice
treated with  1-250  ppm benzo[a]pyrene for  up  to  197 days (Neal  and  Rlgdon,
1967).  Stomach tumors were reported 1n animals treated with  20,  40,  45, 50,
100 and  250 ppm  benzo[a]pyrene  (5/23, 1/40,  4/40,  24/34, 19/23 and  66/73,
respectively), while  control  animals  (0/289)  and those  treated  with 1,  10
and 30  ppm benzo[a]pyrene (0/25,  0/24 and  0/37,  respectively) did not  have
stomach  tumors.   In addition to  the  Increase  1n stomach tumors.  Increased
Incidences of lung  adenoma  and  leukemia  were noted  1n mice treated with 250
and 1000 ppm benzo[a]pyrene (Rlgdon and Neal, 1966,  1969).
4.2.2.   Inhalation.  Thyssen et  al.  (1981)  exposed' groups  of   24  hamsters
by  Inhalation  to benzo[a]pyrene at  levels  of  2.2,   9.5 or 45 mg/m3  for 4.5
hours/day for 10 weeks and 3  hours/day 7  days/week  thereafter,  for  up to 675
days  (Table  4-4).   No  treatment-related  tumors  were observed  In  animals
exposed  to  2.2  mg/m3.    Animals  exposed to 9.5 mg/m3,   however,  developed
tumors  of  the  nasal  cavity  (12%),  larynx   (31%),  trachea (4%)   and  pharynx
(23%).   Hamsters  exposed  to  44.8 mg/m3  benzo[a]pyrene  developed tumors  of
the respiratory  tract  (13/25) and upper  digestive tract  (14/25).  No tumors
of these types were seen  1n control animals  (Thyssen et al.,  1981).
    Intratracheal administration  of  benzo[a]pyrene  resulted 1n an  Increased
Incidence  of respiratory tract  neoplasms  1n both  sexes  of Syrian  hamsters
(Ketkar  et al.,  1978;  Feron and  Kruysse,   1978)  (Tables 4-5  and  4-6).   A
dose-related  response  was reported  for hamsters  treated  with 18.2 and  36.4
mg/an1ma1  (total  dose)  for 52  weeks followed  by a  29-week  latency  period.

                                      -8-

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                                                                  TABLE 4-1
                 Carclnogenlclty of Benio[a]pyrene Administered In the Diet to Hale and FeMle  CFU Nice at Levels of 1-250 ppm*
Dose
1 ppM (0.48 Mg
total dose)
10 ppM (4.48 mg
total dose)
20 ppm (8.88 mg
total dose)
30 ppm (13.32 mg
total dose)
40 ppm (17.76 mg
total dose)
45 ppm (19.8 mg
i total dose)
50 ppm (21.4-29.4
mg total dose)
100 ppm (39.2-48.8
mg total dose)
250 ppm (70-165 mg
total dose)
0.0 ppm
Duration of
Treatment
(days)
110
110
110
110
110
110
107-197
98-122
70-165
NA
Duration
of Study
(days)
140
140
226
143-177
143-211
141-183
124-219
118-146
88-185
70-300
Purity of
Compound
NR
NR
NR
NR
NR
NR
NR
NR
NR
NA
Vehicle or
Physical
State
diet
diet
diet
diet
diet
diet
diet
diet
diet
basal diet
only
Target
Organ
stomach
stomach
stomach
stomach
stomach
stomach
stomach
stomach
stomach
stomach
Tumor Type
paplllomas/carclnomas
paplllomas/carclnomas
papt 1 lomas/carc Inomas
paplllomas/carclnomas
paplllomas/carclnomas
papl 1 lomas/carc tnomas
papl 1 lomas/carc Inomas
papt 1 lomas/carc Inomas
papl 1 lomas/carc Inomas
paplllomas/carclnomas
Tumor
Incidence
0/25
0/24
5/23
0/37
1/40
4/40
24/34
19/23
66/73
0/289
'Source: Neal and Rlgdon.  1967
NA - Not applicable;  NR .  Not reported

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                                                                   TAIL! 4-2
               Carctnogenlctty of  Benzol a ]pyrene Administered In the Diet to Male and FeMle Swiss Nice at Levels of 250-1000 pom*


1
0


Dose
1000 ppm
(1 mg/g food)
1000 ppM
(1 mg/g food)
2SO ppm
(0.25 mg/g food)
250 ppm
(0.25 mg/g food)
0.0 ppa
Duration of
Treatment
(days)
73-83
121-187
72-99
147-196
NA
Duration
of Study
(days)
73-83
127-187
72-99
147-196
111-120
Purity of
Compound
NR
NR
NR
NR
NA
Vehicle or
Physical
State
diet
diet
diet
diet
diet only
Target
Organ
StOMCh
lung
stomach
lung
s touch
lung
stomach
lung
stomach
lung
Tumor Type
paptlloma/carclnoma
adenoma
paptlloma/carclnoma
adenoma
papl lloma/carc Inoma
adenoma
paptlloma/carclnoma
adenoma
papllloma/carclnoma
adenoma
Tumor
Incidence
5/9
7/9
13/13
3/13
12/52
26/52
9/13
10/13
2/108
25/108
•Source: Rlgdon and Meal. 1966
NA . Not applicable; NR - Not reported

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                                                                   TABLE 4-3
               Carclnogentclty of Benzo[a)pyrene Administered In the Diet to (tale and female Swiss CM Nice at a Level of 2SO ppm*
Duration of Duration
Dose Treatment of Study

250 ppm 80-140 days 80-140 days
(0.2S mg/g food)


0.0 ppM NA 62-300 days



Purity of
Compound

NR



NA



Vehicle or
Physical
State
diet



diet only




Target Organ

stomach
lung
hematopoletlc
system
stomach
lung
hematopoletlc
system
.,
Tumor Type

papllloma/carclnoma
adenoma
leukemia

papllloma/carclnoma
adenoma
leukemia

Tumor
Incidence

69/108
52/108
40/108

2/1 75b
33/151
0/1 75b

'Source: Rlgdon and Neal, 1969
DInctdence of tumors In a control group reported previously by Rlgdon and Heal  (1966).
NA - Not applicable; NR - Not reported

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                                                                            TABLE  4-4
                                        Carclnogenlclty of Benio(a]pyrene to Male' Syrian Golden toasters by Inhalation'*0
ro
r
Dose
2.2 mg/m«
(29 mg total dose)
9.5 mg/m»
(127 mg total dose)
46.5 mg/m»
(383 mg total dose)
0.0 mg/m»
Duration of
Treatment
(weeks)
95.2
96.4
59.5
NA
Duration
of Study
(weeks)
95.2
96.4
59.5
96.4
Purity of
Compound
NR
MR
NR
NA
Vehicle or
Physical
State
NaCI vapor
In air
NaCI vapor
In air
NaCI vapor
In air
NaCI vapor
only
Target Organ
respiratory tract
upper digestive
tract
respiratory tract
upper digestive
tract
respiratory tract
upper digestive
tract
respiratory tract
upper digestive
tract
Tumor
Type*
turns
turcrs
tumors
tuMors
tumors
tumors
tumors
tumors
Tumor
Incidence
0/27
0/27
9/26*
7/26d
13/25*
14/25*
0/27
0/27
         'Source:  Thyssen  et  al.,  1981
         ^Exposure was  for 4.5  hours/day  for  the  first 10 weeks, 3 hours/day thereafter for 7 days/week.
         cTumors were paplllomas.  papillary polyps, and squamous cell carcinomas.
         d3 nasal  cavity,  8 laryngeal,  1  tracheal, 6 pharyngeal and 1 forestomach tumors
         el nasal  cavity,  13 laryngeal, 3 tracheal, 14 pharyngeal, 2 esophageal and 1 forestomach tumor
         NA .  Not  applicable; NR - Not  reported

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                                                                    TABLf  4-5
                Carclnogentclty of Benio[a]pyrene In Syrian Hamsters Following Intratracheal Administration of 0.10-1.0 mg/week*
Dose Duration of
Sex (mg/week) Treatment6
(weeks)
N 0.10 40
F 0.10 34
H 0.33 24
F 0.33 28
N 1.0 10
F 1.0 IS
N 0.0 41
F 0.0 35
Duration Purity of Vehicle or
of Study** Compound Physical
(weeks) State
40 97* bovine
albumin
34 97X bovine
albumin
24 97X bovine
albumin
28 97X bovine
albumin
10 97X bovine
albumin
15 97X bovine
albumin
41 NA bovine
albumin
only
35 NA bovine
albumin
only
Target Organ
respiratory tract
respiratory tract
respiratory tract
respiratory tract
respiratory tract
respiratory tract
respiratory tract
respiratory tract
Tumor Typec
various neoplasms
various neoplasms •
various neoplasms
various neoplasms
various neoplasms
various neoplasms
various neoplasms
various neoplasms
Tumor
Incidence
5/26
12/30
7/29
10/28
6/27
6/30
0/29
0/30
'Source: Ketkar et al.. 1978
'•Mean survival time
cCarctnomas. adenomas, adenocarclnomas and paplllomas were reported.
NA . Not applicable

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                                                                   TABLE 4-6
           Carcinogenic I ty of Benzo(a)pyrene In fiolden Syrian Hamsters Following Intratracbeal Administration of 18.2-36.4 mg/antmal*
Sex Dose
N 18.2 mg/hamster
total dose
M 36.4 mg/hamster
total dose
N 0.0 mg/hamster
total dose

^ F 18.2 mg/hamster
4b total dose
i
F 36.4 mg/hamster
total dose
F 0.0 mg/hamster
total dose

Duration of Duration
Treatment of Study
(weeks) (weeks)
52 81
(1 dose/week)
52 81
(1 dose/week)
52 81
(1 dose/week)

52 81
(1 dose/week)

52 81
(1 dose/week)
52 81
(1 dose/week)

Purity of Vehicle or
Compound Physical
State
>99* 0.9X NaCI

>99X 0.9X NaCI
•
>99X saline
vehicle
only
>99X 0.9X NaCI


>99X 0.9X NaCI

>99X saline
vehicle
only
Tumor
Target Organ Type"
respiratory tract .' various

respiratory tract various

respiratory tract various


respiratory tract various


respiratory tract various

respiratory tract various


Tumor
Incidence
4/29

19/30

0/30C


3/27


7/24

0/28C


•Source: feron and Kruysse. 1978
bpaplllomas and carcinomas of the trachea and pulmonary  ademonas were most  prevalent.
cComblned tumor Incidence of untreated and vehicle controls

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The Incidence of trachea! papHlomas and carcinomas,  collectively,  with  lung
adenomas was 4/29 and 3/27 for low  dose males  and  females,  respectively,  and
19/30 -and  7/24  for  high  dose males  and  females,  respectively  (Feron  and
Kruysse, 1978).  Ketkar  et al.   (1978) reported a high  dose-related  mortal-
ity 1n  hamsters  treated at dose  levels  lower, than  those  used by  Feron  and
Kruysse (1978).  Mean survival times  ranged  from 40  weeks  for  male hamsters
treated with  0.1  mg  benzo[a]pyrene/week to  10 weeks for males treated  with
1.0 mg  benzo[a]pyrene/week.    An  Increase  1n  the  Incidence of  respiratory
tract carcinoma,  adenoma  and  papllloma  In  both  sexes  of  hamsters  1n  the
treatment groups was reported, but  a  definite dose-related  response  was  not
evident (Ketkar et al.,  1978).
4.3.   OTHER RELEVANT DATA
    The mutagenlcHy of benzo[a]pyrene has  been  summarized by IARC  (1982),
U.S. EPA (19805, 1981),  Santodonato et al. (1981), deSerres  and Ashby (1981)
and Hollsteln  and McCann  (1979).   The reader  1s  referred  to  these  reviews
for further Information.
    Benzo[a]pyrene 1s  an Indirect  acting  carcinogen, undergoing metabolism
to a reactive electrophlle capable  of  covalently binding to  DNA (IARC,  1982;
Lutz, 1979).  Benzo[a]pyrene has been  used extensively as  a  model carcinogen
and  as  a   positive  control  In  a variety  of  short-term  tests,   yielding
positive results  1n assays for bacterial ONA repair, bacterlophage  Induction
and  bacterial  mutation, mutation  1n   DrosophUa  melanoqaster; ONA  binding,
DNA  repair,  SCE, chromosomal  aberration,  point mutation  and  transformation
1n  mammalian  cells  1n  culture;  and 1n tests  In  mammals \n_ vivo.  Including
ONA binding,  SCE, chromosomal  aberration,  sperm abnormality  and the specific
locus  (spot)   test  (IARC,  1982;  deSerres  and  Ashby,   1981;  Hollsteln  and
McCann, 1979).
                                     -15-

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4.4.   WEIGHT OF EVIDENCE
    Benzo[a]pyrene  1s  both  a  local  and  a' systemic  carcinogen,  producing
tumors 1n  rats,  mice,  hamsters, guinea  pigs,  rabbits  and monkeys  following
oral, Inhalation or dermal exposure.  Benzo[a]pyrene 1s an  Initiator  of skin
cardnogenesls  1n  mice and also  produces  tumors  following  single doses  or
prenatal  exposure.   Benzo[a]pyrene  has been  used  extensively  as  a  model
carcinogen and as a positive  control  1n  a  variety  of  short-term tests.   IARC
(1982) reported  that there  1s sufficient evidence that benzo[a]pyrene  1s  an
animal  carcinogen  and  limited  evidence  that  It Is  a  human  carcinogen.
Applying the  classification criteria  for weight  of evidence proposed by  the
Carcinogen  Assessment   Group   of   the U.S.  EPA   (Federal  Register,   1984),
benzo[a]pyrene Is most  appropriately designated a Group 82 chemical.
                                     -16-

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                     5.   REGULATORY  STANDARDS  AND  CRITERIA

    Exposure criteria  and TLVs  have  been developed  for  PAH as a  class,  as
well as  for several  Individual PAHs.   The  Occupational  Safety and  Health
Administration has  set an 8-hour  TWA concentration  limit of 0.2  mg/m3  for
the  benzene-soluble  fraction  of   coal   tar   pitch  volatHes  {anthracene,
benzo[a]pyrene, phenanthrene,  acrldlne,   chrysene,  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/ma 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 1n workers.   NIOSH (1977) also recommends a
celling  limit  for   exposure  to asphalt  fumes  of  5  ntg  airborne  partlcu-
lates/m3 of air.
    Environmental  quality criteria  for PAH have  been  recommended for  ambient
water, which specify concentration  limits Intended  to protect humans  against
adverse health effects.   The U.S.   EPA  (1980b)  has recommended  a  concentra-
tion  limit  of 28  ng/j,   for  the sum  of  all  carcinogenic  PAHs In  ambient
water.  This value 1s 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  1n  potency
to  benzo[a]pyrene.   Dally  consumption  of  water  containing  28  ng/i  of
carcinogenic PAH  over an entire  lifetime 1s estimated on the  basis  of  the
animal bloassay data  to  keep  the lifetime risk  of cancer development below 1
chance In 100,000.
                                     -17-

-------
    The U.S. EPA has not  recommended  an  ambient  water quality criterion for
noncardnogenlc  PAH as  a class.  The U.S. EPA (1980b) acknowledged that data
suitable  for  quantitative  risk  assessment  of  noncardnogenlc  PAH  are
essentially nonexistent.
                                     -18-

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                              6.   RISK ASSESSMENT
6.1.   ACCEPTABLE INTAKE SUBCHRONIC (AIS)
    Benzo[a]pyrene  1s  a known carcinogen  for  which data  are  sufficient for
computing  a  q,*.   It  1s,  therefore,  Inappropriate to calculate  an  oral or
Inhalation AIS for benzo[a]pyrene.
6.2.   ACCEPTABLE INTAKE CHRONIC (AIC)
    Benzo[a]pyrene  1s  a known carcinogen  for  which data  are  sufficient for
computing  a  q,*.   It  1s,  therefore,  Inappropriate to calculate  an  oral or
Inhalation AIC for benzo[a]pyrene.
6.3.   CARCINOGENIC POTENCY (q.,*)
6.3.1.   Oral.   A  carcinogenic   potency   factor,  q *,  for  humans  can  be
derived from  the study of Neal and  Rlgdon (1967)  1n which benzo[a]pyrene at
dose levels of 1-250 ppm 1n  the  diet was administered to strain. CFW mice for
-110  days.  The  Incidences  of  stomach  tumors  {mostly  squamous-cell  papll-
lomas, but some  carcinomas) were  0/289 for controls, 0/25 at the 1 ppm (0.13
mg/kg/day)  level,  0/24 at  10  ppm   (1.3  mg/kg/day),  1/23 at  20 ppm  (2.6
mg/kg/day), 0/37  at  30 ppm (3.9 mg/kg/day), 1/40  at 40 ppm (5.2 mg/kg/day),
4/40 at  45 ppm  (5.85  mg/kg/day),  24/34  at 50 ppm  (6.5 mg/kg/day),  19/23 at
100 ppm  (13.0 mg/kg/day)  and  66/73 at  250  ppm (32.5 mg/kg/day).   U.S.  EPA
(1980b)  used  these  Incidences  of stomach  tumors  to  derive  a  q * of  11.53
(mg/kg/day)"1.   The  data  used  1n derivation  of  this  q  * are  presented  1n
Appendix C.
6.3.2.   Inhalation.   A carcinogenic  potency  factor,  q *   for  humans  can
be  derived from  the study of  Thyssen et  al.  (1981) In which  Golden  Syrian
hamsters were  exposed  to benzo[a]pyrene by  Inhalation at  levels  of  0,  2.2,
9.5 or  46.5  mg/m3 for  10-96.4  weeks.   The Incidences  of  respiratory  tumors
were 0/27  for  controls, 0/27 for  the low-dose group, 9/26  for  the mid-dose
                                     -19-

-------
group  and 13/25  for  the  high-dose  group.  The  highest exposure  level  did
have  an  adverse  Impact  on  survival  time.   Animals  exposed  to  an  average
concentration  of  46.5  mg benzo[a]pyrene/m3  air  had  an  average  survival
time  of  59.5  weeks,  as  compared with  controls  which survived  for an average
of 96.4  weeks.   Due  to  early  mortality 1n the  highest dose group, these data
were  excluded  from  the  q,*  derivation.   Based  on  the  respiratory  tumor
response  of male hamsters and using the  linearized  multistage model  adopted
by  the U.S.  EPA  (U.S.  EPA,  1980a), a carcinogenic potency factor  {q *)  of
/                                                                       I
6.11   (mg/kg/day)"1  can   be  derived   for  humans.   The  animal   q *  was
derived  using transformed doses based  on an Inhalation rate  of hamsters  of
0.037  mVday  and  assuming 100% absorption.  The  conversion   factor  used  In
the  calculation of the human  q,*  from the animal data was the  cube  root  of
the  body weight ratio,  empirically accepted to  adjust for  species to species
extrapolation.   Complete   data  for derivation  of  the q,*  are  presented  In
Appendix  B.
                                      -20-

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                                7.   REFERENCES

Chang, L.H.  1943.  The fecal  excretion  of  polycycllc  hydrocarbons  following
their  administration   to  the  rat.   J.  B1ol.  Chem.   151:  93.   (Cited  In
Grimmer, 1983)

Code  of  Federal  Regulations.   1981.  OSHA  Safety  and Health Standards.   29
CFR 1910.1000.

Cott1n1,  6.B.  and G.B.  Mazzone.   1939.   The effects  of 3,4-benzpyrene  on
human skin.  Am.  J. Cancer.   37: 186.   (Cited 1n  U.S. EPA, 1983a)

CupUt, L.  1980.  Fate of Toxic and  Hazardous Materials  In  the A1r  Environ-
ment.   Environmental  Sciences  Research  Laboratory,  ORD,  U.S.  EPA,  Research
Triangle Park,  NC.  EPA 600/3-80-084.   NTIS PB 80-221948.

deSerres,  F. and J.  Ashby,  Ed.   1981.   Evaluation  of Short-Term Tests  for
Carcinogens.  Report  of  the  International  Collaborative  Program.   Elsevler/
North-Holland  B1omed1cal  Press, New  York.   p.  180, 190.   (Cited  In  IARC,
1982)

Ekwall, P., P. Ermala,  K.  Setala and L. Sjoblom.  1951.   Gastric absorption
of 3,4-benzpyrene.  II. The  significance of the  solvent  for  the  penetration
of 3,4-benzpyrene  Into the  stomach wall.   Cancer  Res.   11:  758.  (Cited  In
Grimmer, 1983)
                                     -21-

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Federal   Register.    1984.   Environmental   Protection  Agency.    Proposed
guidelines for carcinogenic risk assessment.   49 FR 46294-46299.

Feron, V.J.  and  A.  Kruysse.  1978.   Effects  of exposure to  furfural  vapour
1n  hamsters  simultaneously  treated  with benzo[a]pyrene  or  dlethylnltros-
amlne.  Toxicology.   11: 127-144.  {Cited 1n  U.S. EPA, 1983a)

Grimmer,  G.   1983.   Environmental  Carcinogens:  Polycycllc Aromatic  Hydro-
carbons.  Chemistry,  Occurrence, Biochemistry,  Carc1nogen1c1ty.   CRC  Press,
Inc., Boca Raton, FL.   p. 27-60.

Hollsteln, M.  and J.   HcCann.   1979.   Short-term  tests for carcinogens  and
mutagens.  Mutat. Res.  65: 133-226.  (CHed  In IARC, 1982)

IARC  (International  Agency for  Research on  Cancer).  1973.    Certain  poly-
cycllc  aromatic   hydrocarbons  and  heterocycllc  compounds.    In;   IARC  Mono-
graphs on the Evaluation of the  Carcinogenic  Risk  of Chemicals  to Man.   WHO,
IARC, Lyon,  France.   Vol. 3.

IARC  (International   Agency   for Research  on   Cancer).   1982.   Chemicals,
Industrial processes  and Industries  Associated  with Cancer 1n Humans.   Łn:
IARC  Monographs  on  the Evaluation  of  the Carcinogenic Risk of Chemicals to
Humans.  WHO, IARC,  Lyon, France.  Suppl. 4.

IARC  (International   Agency  for  Research on  Cancer).   1983.   Polynuclear
Aromatic  Compounds, Part 1, Chemical,  Environmental and Experimental  Data.
I.n:  IARC  Monographs on the Evaluation of the  Carcinogenic  Risk of Chemicals
to Humans.  WHO, IARC, Lyon,  France.  Vol. 32.

                                     -22-

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,Ketkar,  M.,  G. Resnlk,  P.  Schneider  and U.  Mohr.   1978.   Investigations on
the  carcinogenic  burden  by  air  pollution 1n man.  Intratracheal Instillation
studies  with  benzo[a]pyrene  1n  bovine  serum  albumin  1n  Syrian  hamsters.
Cancer Lett.   4(4): 235-239.  (Cited 1n U.S. EPA, 1983a)

Klar,  E.  1938.   Uber  die  entstehung elnes  epithelloms  belm  menshen  nach
experlmentellan  arbelten mlt benzpyren.   KUn.  Wschr.   17:  1279.   (Ger.)
(Cited 1n IARC, 1973;  U.S. EPA.  1983a)

Kotln,  P.,  H.L.  Falk and  R.  Busser.   1969.    Distribution,  retention,  and
elimination  of  C14-3,4-benzpyrene  after  administration to  mice and  rats.
J. Natl. Cancer Inst.  23: 541-555.  (Cited 1n U.S. EPA, 1980b)

Lutz, W.K.  1979.   In. vivo  covalent  binding of organic chemicals to DNA as a
quantitative  Indication  1n the  process  of chemical  cardnogenesls.   Mutat.
Res.  65: 289-356.  (Cited 1n IARC, 1982)

Mabey, W.R.,  J.H.  Smith,  R-T.  Podoll,  et  al.  1981.   Aquatic  Fate  Process
Data  for Organic  Priority  Pollutants.   Monitoring and Data  Support  Division,
Office of Water Regulations and Standards, Washington, DC.   EPA 440/4-81-014.

MacKenzle, K.M.  and  D.M.  Angevlne.   1981.   Infertility  1n  mice exposed  \n
utero to benzo[a]pyrene.  B1ol.  Reprod.  24: 183-191.  (Cited 1n IARC,  1983)

NAS  (National  Academy  of   Sciences).    1983.    Polycycllc  Aromatic  Hydro-
carbons:  Evaluation  of  Sources  and  Effects.   Committee   on  Pyrene  and
Selected Analogues.   Board on  Toxicology and  Environmental  Health  Hazards,
Commission on Life Sciences, National Research Council, Washington,  DC.

                                     -23-

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Neal, 3. and R.H. Rlgdon.  1967.  Gastric tumors 1n mice  fed  benzo[a]pyrene:
A quantitative  study.   Tex.  Rep.  B1ol. Med.   25:  553.   (Cited In U.S.  EPA,
1983a)

NIOSH  (National  Institute  for  Occupational   Safety  and  Health).    1977.
Criteria  for  a  Recommended  Standard...Occupational  Exposure  to  Coal  Tar
Products.  U.S.  DHEW,  PHS.  CDC,  Rockvllle, HD.

Rhoads.  C.P.,  U.E.  Smith,  N.S.  Cooper  and  R.D.  Sullivan.    1954.    Early
changes  1n  the  skin  of  several species  Including man,  after painting  with
carcinogenic materials.   Proc.  Am.  Assoc.  Cancer Res.   1:  40.   (Cited  In
IARC, 1973; U.S. EPA,  1983a)

Rlgdon,  R.H.  and  3.   Neal.   1965.   Effects  of  feeding  benzo(a)pyrene  on
fertility,  embryos,  and young  mice.   3. Natl.  Cancer  Inst.   34: 297-305.
(Cited 1n U.S.  EPA,  1983b)

Rlgdon, R.H. and J. Neal.   1966.   Gastric carcinomas  and pulmonary adenomas
1n mice  fed benzo[a]pyrene.   Tex.  Rep. B1ol. Med.  24: 195.   (CHed  1n  U.S.
EPA. 1983a)

Rlgdon,  R.H.  and  3.   Neal.   1969.   Relationship  of  leukemia to  lung  and
stomach tumors 1n mice fed benzo[a]pyrene.  Proc. Soc. Exp. B1ol., NY.   130:
146.  (CHed 1n U.S. EPA, 1983a)

Rlgdon,  R.H.  and  E.G.  Rennels.   1964.   Effect of  feeding  benzpyrene  on
reproduction 1n  the  rat.  Exper1ent1a.   20:  224-226.   (CHed  1n U.S.  EPA,
1983b)

                                     -24-

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Robinson, J.R., J.S. Felton, R.C. Levitt, S.S. Thorglersson and  D.W.  Nebert.
1975.   Relationship  between  "aromatic  hydrocarbon  responsiveness"  and  the
survival times  In mice  treated with  various drugs  and environmental  com-
pounds.  Mol. Pharmacol.   11:  850-865.   (Cited 1n IARC,  1983)

Santodonato,  3.,   P.  Howard  and  D.   Basu.   1981.   Health  and  Ecological
Assessment  of Polynuclear Aromatic  Hydrocarbons.   Pathotox  Publishers,  Inc.,
Park Forest South, II.

Setala, K.    1954.  Experimental chemical cardnogenesls  and the  Influence of
solvents.  Nature (London).   174:  873.   (CUed In Grimmer,  1983)

Smith,  J.H.,  W.R.  Mabey,  N. Bohonos,  et  al.  1978.  Environmental  Pathways
of  Selected  Chemicals  In Freshwater Systems.  Part II: Laboratory  Studies.
Environmental  Research  Laboratory,  ORD,  U.S. EPA,  Athens,  GA.    EPA  600/7-
78-074.

Smyth,  H.F., C.P.  Carpenter,   C.S.  Well,  U.C.  Pozzanl and  J.A.  StMegel.
1962.   Range-finding tox1c1ty  data: List VI.  Am.  Ind. Hyg. Assoc.  3.   23:
95-107.  (Cited 1n Santodonato et al.,  1981)

Thyssen, J.,  J. Althoff, G. Klmmerle and U.  Mohr.   1981.  Inhalation studies
with  benzo[a]pyrene  In   Syrian  golden  hamsters.   J.  Natl.  Cancer  Inst.
66(3):  575-577.  (Cited 1n U.S. EPA, 1983a)

U.S.  EPA.   1980a.  Guidelines  and Methodology  Used In  the  Preparation  of
Health  Effects  Assessment  Chapters  of  the  Consent   Decree  Water  Quality
Criteria.  Federal Register.  45:79347-79357.

                                     -25-

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U.S. EPA.   1980b.   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.   1981.  Hazard  Profile for  PAH.   Prepared  by the  Environmental
Criteria and Assessment  Office,  Cincinnati,  OH,  OHEA,  for  the  Office  of
Solid Waste and Emergency Response.  Washington,  DC.

U.S. EPA.   1983a.   Review of Toxlcologlc Data  1n  Support of  Evaluation  for
Carcinogenic  Potential  of:  Benzo[a]pyrene.    Prepared  by   the  Carcinogen
Assessment  Group,  OHEA, Washington,  DC for  the  Office  of  Solid Waste  and
Emergency Response, Washington,  DC.

U.S. EPA.   1983b.   Reportable  Quantity  for  Benzo[a]pyrene.  Prepared  by  the
Environmental Criteria  and Assessment  Office,  Cincinnati,  OH, OHEA for  the
Office of Solid Waste and Emergency Response,  Washington,  DC.

U.S. EPA.   1983c.  Methodology and Guidelines for  Reportable  Quantity  Deter-
minations  Based  on  Chronic Toxlclty  Data.   Prepared  by the  Environmental
Criteria and Assessment Office, Cincinnati, OH,  OHEA  for  the  Office  of Solid
Waste and Emergency Response, Washington,  DC.

Va1n1o,  H., P.  VotHa,  J.  Hartlala  and  0.  Pelkonen.    1976.   The  fate  of
Intratracheally  Installed  benzo[a]pyrene  1n  the Isolated perfused  rat  lung
of  both  control  and  20-methylcholanthrene pretreated  rats.   Res.  Comm. Chem.
Pathol. Pharmacol.  13: 259271.   (Cited  1n U.S.  EPA,  1980b)
                                     -26-

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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
of polycycllc aromatic hydrocarbons.  J.  Chromatogr.  Sc1.   19:  457-465.
                                     -27-

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                                                     APPENDIX A

                                          Summary Table for 6enzo[a]pyrene
00
I
Carcinogenic
Potency
Inhalation
Oral
Species
hamsters
mice
Experimental
Dose/Exposure
2.2-9.5 mg/m»
1-250 ppm
Effect
respiratory tract
tumors
stomach tumors
qi*
(ing/kg/day)"1
6.11
11.53
Reference
Thyssen
et al., 1981
Neal and
                                                                                                   Rlgdon, 1967

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                                  APPENDIX B
                    Cancer  Data  Sheet  for  Derivation of q-j*
Compound:  Benzo[a]pyrene
Reference:  Thyssen et al.f 1981
Species, strain, sex:  hamsters/Syrian Golden/male
Body weight:  0.12 kg (assumed)
Length of exposure (le)
666.4  days  for  lower dose  and  674.8  days  for
higher dose and controls
Length of experiment (Le) = 666.4  days  for  lower dose  and  674.8  days  for
                            higher dose and controls
Llfespan of animal (L)
666.4  days  for  lower  dose  and  674.8  days  for
higher dose and controls
Tumor site and type:    respiratory  tract/paplllomas,   papillary  polyps  and
                        squamous-cell carcinomas
Route, vehicle:  1nhalat1on/NaCl vapor In air
Experimental Doses or
0 mg/m3
2.2 mg/m3
9.5 mg/m3

Transformed Dose
Exposures* (mg/kg/day)
0
0.0892
0.385
Inbut
Incidence
No". Responding/No. Tested
(or Examined)
0/27
0/27
9/26
*See following page for conversions
qi*A = 0.731101 (mg/kg/day)"1
q]*H = 6.11 (mg/kg/day)'1
                                     -29-

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                                  CONVERSIONS



0 mg/ra3 = 0 mg/kg/day




o 9 m,wm3 v r 10 weeks  v 4>s hours.     85.2 weeks    3 hours..   7 days
2.2 mg/n.3 x [           x          )  * (            x          } x        x
0.037 mVday * 0.12 kg x 666>4 davs x (666>4     )s 0.0892 mg/kg/day
                         666.4 days    666.4 days



9.5 mg/ma x [ 10 ueeks  x 4'5 hours)    86"4 weeks
             96.4 weeks   24 hours      96.4 weeks   24 hours     7 days



0.037 mv
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                                  APPENDIX C
                    Cancer  Data  Sheet  for  Derivation of q-j*

Compound:  Benzo[a]pyrene
Reference:  Neal and Rlgdon, 1967
Species, Strain, Sex:  mouse, CFW, M,F
Body weight:  0.034 kg (assumed)
Length of exposure (le) = 110 days
Length of experiment (Le) » 183 days
Llfespan of animal (L) » 630 days
Tumor site and type:  stomach, papllloma, carcinomas
Route, vehicle:  oral, diet
Experimental Doses
or Exposures
(ppm)
0
1
10
20
30
40
45

Transformed Dose
(mg/kg/day)*
0
0.078
0.781
1.563
2.344
3.126
3.516
Incidence
No. Responding/No. Tested
or Examined
0/289
0/25
0/24
1/23
0/37
1/40
4/40
*Adjusted to reflect treatment on day 110 of a 183-day experimental  period.
Unadjusted q-]* from study = 2.2213189xlO~a  (mg/kg/day)'1
Human q-|* * 11.53 (mg/kg/day)"1
                                                 U.S.. Environmental Protection Agc.T
                                                 Region V, Library
                                                 230 South Dearborn Street r,
                                                 Chicago,  Illinois  60604

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