United States
kS^laMIjk Environmental Protection
^J^iniiil m11 Agency
EPA/690/R-02/002F
Final
4-30-2002
Provisional Peer Reviewed Toxicity Values for
Benzo [b] fluoranthene
(CASRN 205-99-2)
Derivation of an Oral RfD
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
MTL	median threshold limit
1

-------
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor

microgram
(.imol
micromoles
voc
volatile organic compound
11

-------
4-30-2002
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
BENZO [b] FLUORANTHENE (CASRN 205-99-2)
Derivation of an Oral RfD
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude
that a PPRTV cannot be derived based on inadequate data.
1

-------
4-30-2002
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
An RfD for benzo[b]fluoranthene (B[b]F) is not available on IRIS (U.S. EPA, 2001), in
the HEAST (U.S. EPA, 1997), or in the Drinking Water Regulations and Health Advisory list
(U.S. EPA, 2000), and the chemical was never reviewed by the RfD/RfC Work Group (U.S.
EPA, 1995). A HEA for Polycyclic Aromatic Hydrocarbons (PAH) (U.S. EPA, 1984), a
Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1991a)
and a Multimedia Document for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1992) did not
derive an RfD for B[b]F. No other pertinent EPA documents were located in the CARA lists
(U.S. EPA, 1991b, 1994). The ATSDR (1995) Toxicological Profile for PAHs and the ATSDR
(1987) Toxicological Profile for Benzo[b]fluoranthene declined to derive oral MRLs for B[b]F
due to lack of suitable data. The NTP (2001) Management Status Report, WHO (1997), the
IARC monograph series (IARC, 1973, 1983, 1987), and Patty's Toxicology (Warshawsky, 2001)
were searched for relevant information. Literature searches of the following databases were
conducted from 1989 to April 2001 for relevant studies: TOXLINE, MEDLINE, TSCATS,
2

-------
4-30-2002
GENETOX, HSDB, CANCERLIT, CCRIS, EMIC/EMICBACK, DART/ETICBACK, and
RTECS.
REVIEW OF THE PERTINENT LITERATURE
Human Studies
The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984, 1991a,
1992; WHO, 1997) found no available human data regarding the toxicity of B[b]F following oral
exposure. The literature search identified no new studies regarding the toxicity of B[b]F in
humans following oral exposure.
Animal Studies
The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984, 1991a,
1992; WHO, 1997) found no available animal data that could be used as the basis for derivation
of an RfD for B[b]F. B[b]F suppressed the antibody response in a dose-related manner in an
acute study in which male C57BL/6J mice (2/group) were administered B[b]F in corn oil as a
single oral gavage at 0.1, 1.0, 10 or 100 mg/kg (Silkworth et al., 1995). Twelve hours after
treatment, the mice were immunized i.v. with sheep erythrocytes. The splenic primary direct
(IgM) antibody response was evaluated 5 days after immunization using a plaque assay. At the
highest dose, B[b]F suppressed the immune response by approximately 84% of control.
However, this study is not adequate for derivation of an RfD, because it only addresses one
endpoint and is of inadequate duration.
FEASIBILITY OF DERIVING A
PROVISIONAL RfD FOR BENZO[b]FLUORANTHENE
A provisional RfD for B[b]F cannot be derived because of the lack of human and
adequate animal oral data.
REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 1987. Toxicological Profile for
Benzo[b]fluoranthene. U.S. Department of Health and Human Services, Public Health Service,
Atlanta, GA.
ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for
Polycyclic Aromatic Hydrocarbons (PAH). U.S. Department of Health and Human Services,
Public Health Service, Atlanta, GA.
3

-------
4-30-2002
IARC (International Agency for Research on Cancer). 1973. IARC Monographs on the
Evaluation of Carcinogenic Risk of the Chemical to Man. Certain Polycyclic Aromatic
Hydrocarbons and Heterocyclic Compounds. Vol. 3, p. 45-68.
IARC (International Agency for Research on Cancer). 1983. IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans. Polynuclear Aromatic
Compounds. Part 1. Chemical, Environmental and Experimental Data. Vol. 32,
p. 135.
IARC (International Agency for Research on Cancer). 1987. IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans. Suppl. 7. p. 58.
NTP (National Toxicology Program). 2001. Management Status Report. Examined April 9,
2001. Online, http://ntp-server.niehs.nih.gov/main pages/NTP ALL STDY PG.html
Silkworth, J.B., T. Lipinskas and C.R. Stoner. 1995. Immunosuppressive potential of several
polycyclic aromatic hydrocarbons (PAH) found at a superfund site: New model used to evaluate
additive interactions between benzo[a]pyrene and TCDD. Toxicology. 105: 375-386.
U.S. EPA. 1984. Health Effects Assessment for Polycyclic Aromatic Hydrocarbons (PAH).
Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Emergency and Remedial Response,
Washington, DC. EPA/540/1-86/013.
U.S. EPA. 1991a. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons
(PAH). Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington,
DC.
U.S. EPA. 1991b. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April 1991.
U.S. EPA. 1992. Multimedia Document for Polycyclic Aromatic Hydrocarbons. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH. August.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December 1994.
U.S. EPA. 1995. Monthly Status Report of RfD/RfC and CRAVE Work Groups (as of
09/01/95). Office of Research and Development, National Center for Environmental
Assessment, Washington, DC.
4

-------
4-30-2002
U.S. EPA. 1997. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update.
Prepared by the Office of Research and Development, National Center for Environmental
Assessment, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington,
DC. July 1997. EPA-540-R-97-036. NTIS PB97-921199.
U.S. EPA. 2000. Drinking Water Regulations and Health Advisories. Summer 2000. Office of
Water, Washington, DC. Examined April 9, 2001. Online.
http://www.epa. gov/ ost/drinking/ standards/
U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined
April 9, 2001. Online, http://www.epa.gov/iris/
Warshawsky, D. 2001. Polycyclic and heterocyclic aromatic hydrocarbons. In: Patty's
Toxicology, 5th ed., E. Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley and Sons, New
York. p. 303-382.
WHO (World Health Organization). 1997. Environmental Health Criteria. 202: WHO
Non-heterocyclic Polycyclic Aromatic Hydrocarbons. International Programme on Chemical
Safety, Geneva, Switzerland.
5

-------
11-30-2001
Provisional Peer Reviewed Toxicity Values for
Benzo [b] fluoranthene
(CASRN 205-99-2)
Derivation of an Oral Slope Factor
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
MTL	median threshold limit
1

-------
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor

microgram
(.imol
micromoles
voc
volatile organic compound
11

-------
11-30-2001
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
BENZO [b] FLUORANTHENE (CASRN 205-99-2)
Derivation of an Oral Slope Factor
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude
that a PPRTV cannot be derived based on inadequate data.
1

-------
11-30-2001
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
A carcinogenicity assessment for benzo[b]fluoranthene (B[b]F) is available on IRIS (U.S.
EPA, 2001). This assessment, verified 02/07/1990, was based on a Carcinogen Assessment of
Coke Oven Emissions (U.S. EPA, 1984a) and a Drinking Water Criteria Document for
Polycyclic Aromatic Hydrocarbons (PAH) (U.S. EPA, 1991a). B[b]F was assigned to weight-of-
evidence Group B2, probable human carcinogen, based on increased incidences of epidermoid
carcinomas and pleomorphic sarcomas in a lung implantation study in rats (Deutsch-Wenzel et
al., 1983), injection site sarcomas in a subcutaneous injection assay in mice (Lacassagne et al.,
1963), liver adenomas and hepatomas in male mice following intraperitoneal injection (LaVoie et
al., 1987), and skin tumors in dermal application studies in mice (Amin et al., 1985; LaVoie et
al., 1982; Wynder and Hoffmann, 1959). Supporting data from genotoxicity tests included
positive results mutations in bacteria (Amin et al., 1985; Hecht et al., 1980; Hermann, 1981;
LaVoie et al., 1979). It was noted that B[b]F is a component of mixtures that are known to
produce cancer in humans, although there are no human data that specifically link B[b]F with
2

-------
11-30-2001
human cancers. However, due to the lack of adequate oral data for B[b]F, an oral slope factor
was not included on IRIS (U.S. EPA, 2001).
U.S. EPA (1991a) explored the use of a relative potency factor approach to derive slope
factors for B[b]F and other PAHs from the existing slope factor for benzo[a]pyrene. However,
the CRAVE Work Group decided not to include relative potency information for PAHs on IRIS
because the methodology was not sufficiently developed, the underlying database had not been
sufficiently reviewed, and surrounding issues (e.g., route-to-route extrapolation) had not received
sufficient peer review (U.S. EPA, 1994a). The HEAST (U.S. EPA, 1997) reports the availability
of the weight-of-evidence assessment on IRIS, but contains no additional information. The
Drinking Water Standards and Health Advisories list (U.S. EPA, 2000) includes the cancer
Group B2 designation for B[b]F, but does not include additional cancer risk information. A
Health Effects Assessment for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1984b) was
located, but no relevant documents specific to B[b]F were found in the CARA lists (U.S. EPA,
1991b, 1994b).
The International Agency for Research on Cancer (IARC, 1973, 1983, 1987) evaluated
B[b]F for carcinogenicity and placed the chemical in Group 2B (possible human carcinogen),
finding that there is sufficient evidence that B[b]F is carcinogenic to experimental animals, that
the chemical was mutagenic to Salmonella typhimurium in the presence of an exogenous
metabolic system, and induced sister chromatid exchange in bone-marrow cells of hamsters
treated in vivo. CalEPA derived an oral slope factor for B[b]F, but it is based on a relative
potency factor approach (CalEPA, 1999). ACGIH (2000) has classified B[b]F as A2-suspected
human carcinogen. The NTP (2001) Management Status Report, WHO (1997), Patty's
Toxicology (Warshawsky, 2001), the ATSDR (1995) Toxicological Profile for Polycyclic
Aromatic Hydrocarbons, the ATSDR (1987) Toxicological Profile for Benzo(b)fluoranthene, and
a Multimedia Document for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1992) were searched
for relevant information. Literature searches of the following databases were conducted from
1989 to April 2001 for relevant studies: TOXLINE, MEDLINE, TSCATS, GENETOX, HSDB,
CANCERLIT, CCRIS, EMIC/EMICBACK, DART/ETICBACK, and RTECS.
REVIEW OF THE PERTINENT LITERATURE
Human Studies
The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984b, 1991a,
1992; WHO, 1997) found no available human data regarding the carcinogenic potential of B[b]F.
The literature search identified no new studies regarding carcinogenicity of B[b]F in humans
following oral exposure.
3

-------
11-30-2001
Animal Studies
The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984b, 1991a,
1992; WHO, 1997) found no available animal oral data regarding the carcinogenic potential of
B[b]F. The literature search identified no new studies regarding carcinogenicity of B[b]F in
animals following oral exposure.
Other Studies
The literature search identified the following supporting data for carcinogenicity of B[b]F
not included on IRIS. Reddy et al. (1991) reported that oral treatment of mice with B[b]F
induced clastogenic responses in the gastrointestinal tract. Groups of 10 male B6C3F1 mice
were given single gavage doses of 0 (control) or 0.76 mmol/kg B[b]F and sections of the
gastrointestinal tract (forestomach, duodenum, proximal colon) were examined for nuclear
anomalies 24 hours after dose administration. Statistically increased (p<0.05) numbers of
nuclear anomalies were observed in the duodenum and proximal colon of treated animals, but not
in the forestomach, compared with control mice. No statistically significant increase in sister
chromatid exchange (SCE) or micronucleus induction was observed in mice orally gavaged with
B[b]F suspended in sunflower oil (100 mg/kg), whereas the number of SCEs/metaphase (but not
micronucleus induction) was statistically significantly increased in animals given a single
intraperitoneal injection of B[b]F (100 mg/kg) (Bryant et al., 1993). Male AJJ mice, given a
single intraperitoneal injection of 0, 10, 50, 100, or 200 mg/kg B[b]F dissolved in tricaprylin,
were evaluated for lung adenomas 8 months after treatment (Mass et al., 1996; Nesnow et al.,
1995, 1998a,b; Ross et al., 1995). Lung adenoma incidence, with mutation types TGT, CGT,
GAT, and GTT induced in the Ki-ras oncogene codon 12, was dose-related and significantly
greater (p<0.05) than the tricaprylin control for B[b]F doses >50 mg/kg. B[b]F formed DNA
adducts in vitro in rat hepatocytes and the tumor cell line NCI-H322 derived from human lung,
but not in V79NH cells (<0.05 adducts/108 nucleotides), a subclone of the Chinese hamster lung
derived cell line V79 (Topinka et al., 1998). B[b]F-DNA adducts also occurred in vivo in the
lungs of mice (Nesnow et al., 1995, 1998b; Ross et al., 1995) and in the lungs, livers, and
peripheral blood lymphocytes of rats (Ross et al., 1992) given B[b]F by intraperitoneal injection.
Sister chromatid exchanges from whole blood cultures from rats administered B[b]F (100 mg/kg
by i.p. injection) were significantly increased relative to controls (Ross et al., 1992). Dermally
applied B[b]F initiated dose-related tumor activity with TP A promotion in mouse skin (Weyland
et al., 1990, 1993). B[b]F induced a dose-unrelated transformation from anchorage-dependent to
independent growth in vitro in hamster (M3E3/C3) and rat (WRBK3) lung cells (Knebel et al.,
1994). B[b]F suspended in corn oil, administered to male C57BL/6J mice as a single oral gavage
at 0.1, 1.0, 10 or 100 mg/kg, suppressed the antibody response to sheep erythrocyte immunization
in a dose-related manner; at the highest dose, suppression was approximately 84% of control
response (Silkworth et al., 1995).
4

-------
11-30-2001
FEASIBILITY OF DERIVING A PROVISIONAL ORAL SLOPE FACTOR FOR
BENZO [b] FLUORANTHENE
A provisional oral slope factor for B[b]F cannot be derived because human and animal
oral cancer data are lacking.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2000. TLVsŪ and
BEIsŪ: Threshold Limit Values for Chemical Substances and Physical Agents, Biological
Exposure Indices. Cincinnati, OH.
Amin, S., K. Huie and S.S. Hecht. 1985. Mutagenicity and tumor initiating activity of
methylated benzo[b]fluoranthene. Carcinogenesis. 6: 1023-1025.
ATSDR (Agency for Toxic Substances and Disease Registry). 1987. Toxicological Profile for
Benzo[b]fluoranthene. U.S. Department of Health and Human Services, Public Health Service,
Atlanta, GA.
ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for
Polycyclic Aromatic Hydrocarbons. U.S. Department of Health and Human Services, Public
Health Service, Atlanta, GA.
Bryant, M.F., P. Kwanyuen, G.L. Erexson and A.D. Kligerman. 1993. Analyses of cytogenetic
damage in mouse peripheral blood lymphocytes after either intraperitoneal or gavage exposure to
five polycyclic aromatic hydrocarbons. Environ. Mol. Mutagen. 21: 9. [Abstract]
CalEPA (California Environmental Protection Agency). 1999. Air Toxics Hot Spots Program
Risk Assessment Guidelines. Part II: Technical Support Document for Describing Available
Cancer Potency Factors. April 1999. Office of Environmental Health Hazard Assessment.
Online.
http ://www. oehha. ca. gov/air/cancer guide/hsca2 .html
Deutsch-Wenzel, R., H. Brune, G. Grimmer et al. 1983. Experimental studies in rat lungs on the
carcinogenicity and dose-response relationships of eight frequently occurring environmental
polycyclic aromatic hydrocarbons. J. Natl. Cancer Inst.
71: 539-544. (Cited in ATSDR, 1995)
Hecht, S.S., E. LaVoie, S. Amin et al. 1980. On the metabolic activation of the
benzofluoranthenes. In: Polynuclear Aromatic Hydrocarbons: Chemistry and Biological Effects,
A. Bjorseth and A.J. Dennis, Ed. Battelle Press, Columbus, OH. p. 417-433. (Cited in WHO,
1997)
5

-------
11-30-2001
Hermann, M. 1981. Synergistic effects of individual polycyclic aromatic hydrocarbons on the
mutagenicity of their mixtures. Mutat. Res. 90:399-409. (Cited in WHO, 1997)
IARC (International Agency for Research on Cancer). 1973. IARC Monographs on the
Evaluation of Carcinogenic Risk of the Chemical to Man. Certain Polycyclic Aromatic
Hydrocarbons and Heterocyclic Compounds. Vol. 3, p. 69.
IARC (International Agency for Research on Cancer). 1983. IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans. Polynuclear Aromatic
Compounds. Parti. Chemical, Environmental and Experimental Data. Vol.32,
p. 147.
IARC (International Agency for Research on Cancer). 1987. IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans. Suppl. 7. p. 58.
Knebel, J.W., M. Aufderheide and M. Emura. 1994. Comparison of biological effects of
different polycyclic aromatic hydrocarbons in lung cells of hamster and rat in vitro. Toxicol.
Lett. 72:65-72.
Lacassagne, A., N.P. Buu-Hoi, F. Zajdela et al. 1963. [Carcinogenic activity of
fluoranthene-based polycyclic aromatic hydrocarbons.] Acta. Unio. Int. Contra. Cancrum. 19:
490-496. (French) (Cited in WHO, 1997)
LaVoie, E.J., V. Bedenko, N. Hirota et al. 1979. A comparison of the mutagenicity, tumor-
initiating activity and complete carcinogenicity of polynuclear aromatic hydrocarbons. In:
Polynuclear Aromatic Hydrocarbons, P.W. Jones and P. Leber, Ed. Ann Arbor Science
Publishers, Ann Arbor, MI. p. 705-721. (Cited in WHO, 1997)
LaVoie, E.J., S. Amin, S.S. Hecht et al. 1982. Tumor initiating activity of dihydrodiols of
benzo[b]fluoranthene, benzo[j]fluoranthene and benzo[k]fluoranthene. Carcinogenesis. 3:
49-52. (Cited in WHO, 1997)
LaVoie, E.J., J. Braley, J.E. Rice and A. Rivenson. 1987. Tumorigenic activity for non-alternant
polynuclear aromatic hydrocarbons in newborn mice. Cancer Lett.
34: 15-20. (Cited in ATSDR, 1995)
Mass, M.J., A. Abu-Shakra, B.C. Roop et al. 1996. Benzo[b]fluoranthene: Tumorigenicity in
strain AJJ mouse lungs, DNA adducts and mutations in the Ki-ras oncogene. Carcinogenesis.
17: 1701-1704.
Nesnow, S., J.A. Ross and G.D. Stoner and M.J. Mass. 1995. Mechanistic linkage between
tumorigenesis of carcinogenic environment polycyclic aromatic hydrocarbons in strain AJJ mice.
Toxicology. 105: 403-413.
6

-------
11-30-2001
Nesnow, S., M J. Mass and J.A. Ross. 1998a. Lung tumorigenic interactions in strain A/J mice
of five environmental polycyclic aromatic hydrocarbons. Environ. Health Perspect. 106: 1337-
1346.
Nesnow, S., J.A. Ross and M.J. Mass. 1998b. Mechanistic relationships between DNA adducts,
oncogene mutations, and lung tumorigenesis in strain A mice. Exp. Lung Res. 24: 395-405.
NTP (National Toxicology Program). 2001. Management Status Report. Examined April 9,
2001. Online.
http://ntp-server.niehs.nih.gov/main pages/NTP ALL STDY PG.html
Reddy, T.V., J.A. Stober, G.R. Olsen and F.B. Daniel. 1991. Induction of nuclear anomalies in
the gastrointestinal tract by polycyclic aromatic hydrocarbons. Cancer Lett. 56: 215-224.
Ross, J.A., G.B. Nelson, K.L. Holden et al. 1992. DNA adducts and induction of sister
chromatid exchanges in the rat following benzo(b)fluoranthene administration. Carcinogenesis.
13:1731-1734.
Ross, J.A., G.B. Nelson, K.H. Wilson et al. 1995. Adenomas induced by polycyclic aromatic
hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels. Cancer
Res. 55: 1039-1044.
Silkworth, J.B., T. Lipinskas and C.R. Stoner. 1995. Immunosuppressive potential of several
polycyclic aromatic hydrocarbons (PAH) found at a superfund site: New model used to evaluate
additive interactions between benzo[a]pyrene and TCDD. Toxicology. 105: 375-386.
Topinka, J., L.R. Schwarz, F. Kiefer et al. 1998. DNA adduct formation in mammalian cell
cultures by polycyclic aromatic hydrocarbons (PAH) and nitro-PAH in coke oven emission
extract. Mutat. Res. 419: 91-105.
U.S. EPA. 1984a. Carcinogen Assessment of Coke Oven Emissions. Office of Health and
Environmental Assessment, Washington, DC.
U.S. EPA. 1984b. Health Effects Assessment for Polycyclic Aromatic Hydrocarbons (PAH).
Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Emergency and Remedial Response,
Washington, DC. EPA/540/1-86/013.
U.S. EPA. 1991a. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons
(PAH). Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington,
DC.
7

-------
11-30-2001
U.S. EPA. 1991b. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April 1991.
U.S. EPA. 1992. Multimedia Document for Polycyclic Aromatic Hydrocarbons. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH. August.
U.S. EPA. 1994a. CRAVE meeting notes (February 1994) on Polycyclic Aromatic
Hydrocarbons. Reported May 11, 1994. Available from National Center for Environmental
Assessment, Washington, DC.
U.S. EPA. 1994b. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December 1994.
U.S. EPA. 1997. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update.
Prepared by the Office of Research and Development, National Center for Environmental
Assessment, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington,
DC. July 1997. EPA/540/R-97/036. NTIS PB97-921199.
U.S. EPA. 2000. Drinking Water Regulations and Health Advisories. Summer 2000. Office of
Water, Washington, DC. Examined April 9, 2001. Online.
http://www.epa. gov/ ost/drinking/ standards/
U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined
April 9, 2001. Online, http://www.epa.gov/iris/
Warshawsky, D. 2001. Polycyclic and heterocyclic aromatic hydrocarbons. In: Patty's
Toxicology, 5th ed., E. Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley and Sons, New
York. p. 303-382.
Weyand, E.H., S. Patel, E.J. LaVoie et al. 1990. Relative tumor initiating activity of benzo
[ajfluoranthene, benzo[b]fluoranthene, naphtho[l,2- bjfluoranthene and naphtho[2,l-
ajfluoranthene on mouse skin. Cancer Lett. 52: 229-233.
Weyand, E.H., Z.W. Cai, Y. Wu et al. 1993. Detection of the major DNA adducts of
benzo[b]fluoranthene in mouse skin: Role of phenolic dihydrodiols. Chem. Res. Toxicol. 6:
568-577.
WHO (World Health Organization). 1997. Environmental Health Criteria. 202: WHO Selected
Non-heterocyclic Polycyclic Aromatic Hydrocarbons. International Programme on Chemical
Safety, Geneva, Switzerland.
8

-------
11-30-2001
Wynder, E.L. and D. Hoffmann. 1959. A study of tobacco carcinogenesis. VII. The role of
higher polycyclic hydrocarbons. Cancer. 12:1079-1086.
9

-------