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-
-------
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
-------
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
-------
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
-------
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
-------
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.
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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-
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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.
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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-
-------
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-
-------
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-
-------
,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-
-------
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-
-------
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-
-------
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)
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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.
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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
-------
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
-------
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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