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Benzo[k]fluoranthene
CASRN 207-08-9
Contents
0452
Benzo[k]fluoranthene; CASRN 207-08-9
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Benzo[k]fluoranthene
File On-Line 11/01/1990
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 03/01/1994
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Benzo[k]fluoranthene
CASRN -- 207-08-9
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Benzo[k]fluoranthene
CASRN -- 207-08-9
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Benzo[k]fluoranthene
CASRN -- 207-08-9
Last Revised -- 03/01/1994
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- B2; probable human carcinogen
Basis -- Based on no human data and sufficient data from animal bioassays.
Benzo[k]fluoranthene produced tumors after lung implantation in mice and when
administered with a promoting agent in skin-painting studies. Equivocal
results have been found in a lung adenoma assay in mice.
Benzo[k]fluoranthene is mutagenic in bacteria.
___II.A.2. HUMAN CARCINOGENICITY DATA
None. Although there are no human data that specifically link exposure
to benzo[k]fluoranthene to human cancers, benzo[k]fluoranthene is a component
of mixtures that have been associated with human cancer. These include coal
tar, soots, coke oven emissions and cigarette smoke (U.S. EPA, 1984, 1990;
IARC, 1984).
___II.A.3. ANIMAL CARCINOGENICITY DATA
Sufficient. In a lifetime implant study, female Osborne-Mendel rats
(27-35/group) received lung implants of 0.16 mg (0.65 mg/kg), 0.83 mg (3.4
mg/kg) or 4.15 mg (17 mg/kg) benzo[k]fluoranthene in 0.05 mL of a 1:1 (v:v)
mixture of beeswax and trioctanoin (Deutsch-Wenzel et al., 1983). Controls
consisted of an untreated group and a group receiving an implant of the
vehicle. Median survival times (weeks) were: 118 (untreated controls), 104
(vehicle controls); 114 (0.16 mg dose); 95 (0.83 mg dose); 98 (4.15 mg
dose). The incidences of epidermoid carcinomas in the lung and thorax
(combined) showed a statistically significant dose-related increase. The
observed incidences were: untreated controls, 0/35; vehicle controls, 0/35;
low-dose, 0/35; mid-dose, 3/31; high-dose, 12/27.
Groups of 16-17 male and 18 female newborn CD-1 mice received
intraperitoneal injections of benzo[k]fluoranthene in DMSO on days 1, 8 and
15 after birth (total dose approximately 126 ug/mouse) and were sacrificed at
52 weeks of age (LaVoie et al., 1987). The incidence of hepatic adenomas and
hepatomas was increased in treated male mice (3/16) relative to vehicle
controls (1/17), although this increase was not statistically significant.
No liver tumors were found in females. Lung adenomas were found in treated
male (1/16) and female (3/18) mice, whereas none were reported for the
controls. This assay is considered to be a short-term, in vivo, lung tumor
assay.
Benzo[k]fluoranthene has yielded positive results for initiating activity
in several mouse skin-painting assays. A single dermal application of 11 mg
benzo[k]fluoranthene to 20 Swiss mice in a 63-week study did not induce tumors
(Van Duuren et al., 1966). However, when the same dose was followed by
promoting treatments with croton resin, 18/20 animals developed papillomas and
5/20 developed carcinomas. LaVoie et al. (1982) applied doses of 0, 30, 100
or 1000 ug benzo[k]fluoranthene (10 doses each, every other day, in 0.1 mL
acetone) to the skin of groups of 20 Crl:CD-1 mice. This regimen was followed
by treatment with 2.5 ug 12-O-tetradecanoyl phorbol-13-acetate (TPA) (a tumor
promoter), 3 times/week for 20 weeks. Increases in the percentage of tumor-
bearing animals (0, 5, 25, 75), as well as the number of tumors per animal (0,
0.1, 0.4, 2.8), appeared to be dose-related. These results were corroborated
by reports of Amin et al. (1985a,b).
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Tests for mutagenicity in prokaryotic cells have produced positive
results. Tests for reverse mutation in Salmonella typhimurium strain TA100
and TA98 yielded positive results for benzo[k]fluoranthene in the presence of
a metabolic activation system (rat liver S9) (LaVoie et al., 1980; Hermann et
al., 1980).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
Not available.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
Not available.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1984, 1990
The 1990 Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons
has received Agency and external review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 02/07/1990, 08/05/1993, 09/21/1993, 02/02/1994
Verification Date -- 02/07/1990
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Benzo[k]fluoranthene
CASRN -- 207-08-9
Last Revised -- 11/01/1990
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Amin, S., K. Huie and S.S. Hecht. 1985a. Mutagenicity and tumor initiating
activity of methylated benzo[b]fluoranthenes. Carcinogenesis. 6(7):
1023-1025.
Amin, S., N. Hussain, G. Balanikas, K. Huie and S.S. Hecht. 1985b.
Mutagenicity and tumor initiating activity of methylated
benzo[k]fluoranthenes. Cancer Lett. 26: 343-347.
Deutsch-Wenzel, R., H. Brune, G. Grimmer, G. Dettbarn and J. Misfeld. 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(3): 539-543.
Hermann, M., J.P. Durand, J.M. Charpentier, et al. 1980. Correlations of
mutagenic activity with polynuclear aromatic hydrocarbon content of various
mineral oils. In: Polynuclear Aromatic Hydrocarbons: Chemistry and
Biological Effects, 4th Int. Symp., A. Bjorseth and A.J. Dennis, Ed.
Battelle Press, Columbus, OH. p. 899-916.
IARC (International Agency for Research on Cancer). 1984. Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Man. Polynuclear
Aromaitc Hydrocarbons. Part 3. Industrial Exposures in Aluminum Production,
Coal Gasification, Coke Production, and Iron and Steel Founding. Vol. 34.
World Health Organization.
LaVoie, E.J., S.S. Hecht, S. Amin, V. Bedenko and D. Hoffmann. 1980.
Identification of mutagenic dihydrodiols as metabolites of
benzo(j)fluoranthene and benzo(k)fluoranthene. Cancer Res. 40: 4528-4532.
LaVoie, E.J., S. Amin., S.S. Hecht, K. Furuya and D. Hoffmann. 1982. Tumor
initiating activity of dihydrodiols of benzo[b]fluoranthene,
benzo[j]fluoranthene and benzo[k]fluoranthene. Carcinogenesis. 3(1): 49-52.
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.
U.S. EPA. 1984. Carcinogen Assessment of Coke Oven Emissions. Office of
Health and Environmental Assessment, Washington, DC. EPA 600/6-82-003F.
NTIS PB84-170181.
U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic
Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Drinking Water, Washington, DC. Final Draft. ECAO-CIN-D010,
September, 1990.
Van Duuren, B.L., A. Sivak, A. Segal, L. Orris and L. Langseth. 1966. The
tumor-promoting agents of tobacco leaf and tobacco smoke condensate. J.
Natl. Cancer Inst. 37(4): 519-526.
_VII. REVISION HISTORY
Substance Name -- Benzo[k]fluoranthene
CASRN -- 207-08-9
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
11/01/1990 II. Carcinogen assessment on-line
11/01/1990 VI. Bibliography on-line
01/01/1992 IV. Regulatory action section on-line
09/01/1993 II. Carcinogenicity assessment noted as pending change
09/01/1993 II.D.2. Work group review date added
11/01/1993 II.D.2. Work group review date added
02/01/1994 II.D.3. Secondary contact's phone number changed
03/01/1994 II. Pending change note removed; no change
03/01/1994 II.D.2. Work group review date added
VIII. SYNONYMS
Substance Name -- Benzo[k]fluoranthene
CASRN -- 207-08-9
Last Revised -- 11/01/1990
207-08-9
Benzo(k)fluoranthene
Dibenzo(b,jk)fluorene
HSDB 6012
11,12-BENZO(k)FLUORANTHENE
11,12-Benzofluoranthene
2,3,1',8'-Binaphthylene
8,9-BENZOFLUORANTHENE
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0452.HTM
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