|
Benzo[b]fluoranthene
CASRN 205-99-2
Contents
0453
Benzo[b]fluoranthene; CASRN 205-99-2
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[b]fluoranthene
File On-Line 12/01/1990
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[b]fluoranthene
CASRN -- 205-99-2
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Benzo[b]fluoranthene
CASRN -- 205-99-2
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Benzo[b]fluoranthene
CASRN -- 205-99-2
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[b]fluoranthene produced tumors in mice after lung implantation,
intraperitoneal (i.p.) or subcutaneous (s.c.) injection, and skin painting.
___II.A.2. HUMAN CARCINOGENICITY DATA
None. Although there are no human data that specifically link exposure to
benzo[b]fluoranthene to human cancers, benzo[b]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, 3-month-old female Osborne-
Mendel rats (35/group) received a single lung implant of either 0.1 mg (0.4
mg/kg), 0.3 mg (1.2 mg/kg) or 1 mg (4.1 mg/kg) benzo[b]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. The median survival times were: 118, 104, 110, 113
and 112 weeks, for the untreated, vehicle control, low-, mid- and high-dose
groups, respectively. The incidences of epidermoid carcinomas and pleomorphic
sarcomas in the lung and thorax (combined) were: untreated controls, 0/35;
vehicle controls, 0/35; low-dose group, 1/35; mid-dose group, 3/35; and high-
dose group, 13/35. These incidences showed a statistically significant dose-
response relationship.
Groups of 15-17 male and 17-18 female CD-1 mice received i.p. injections
of benzo[b]fluoranthene in DMSO on days 1, 8 and 15 after birth (total dose
was approximately 126 ug/mouse) and were sacrificed at 52 weeks of age (LaVoie
et al., 1987). A statistically significant increase in the incidence of liver
adenomas and hepatomas (combined) occurred in treated males (8/15) relative to
vehicle controls (1/17), but not in females. Lung adenomas (2/15 males, 3/17
females) were reported in treated animals, whereas none were found in
controls.
Injection site sarcomas occurred in 18/24 survivors of a total of 16 male
and 14 female XVIInc/Z mice that received three s.c. injections of
benzo[b]fluoranthene (total dose = 2.6 mg) over a period of 2 months
(Lacassagne et al., 1963).
Benzo[b]fluoranthene has yielded positive results for complete
carcinogenic activity and initiating activity in mouse skin-painting assays.
In skin-painting assays groups of 20 female Swiss mice were treated 3
times/week with 0.01, 0.1 or 0.5% solutions of benzo[b]fluoranthene in acetone
(Wynder and Hoffmann, 1959). The high dose produced papillomas in 100% of the
mice and carcinomas in 90% of the mice within 8 months. The middle dose
produced papillomas in 65% and carcinomas in 85% within 12 months, while the
low dose produced a papilloma in only 1 animal among 10 survivors at 14
months. No concurrent controls were observed. LaVoie et al. (1982) applied
solutions of 0, 10, 30 or 100 ug benzo[b]fluoranthene in 0.1 mL acetone (10
doses, one every other day) to the skins of groups of 20 Crl:CD-1 mice. This
regimen was followed by treatment with 2.5 ug 12-0-tetradecanoyl-phorbol-13-
acetone (TPA) (a tumor promoter), 3 times/week for 20 weeks. Increases in the
percentage of tumor-bearing animals (0, 45, 60, 80) as well as the number of
skin tumors/animal (0, 0.9, 2.3, 7.1) appeared to be dose-related. Similar
studies by Amin et al. (1985a,b) resulted in comparable elevations of tumor
incidence.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Positive results have been reported for a reverse mutation assay in
Salmonella TA98 and the results for Salmonella TA100 have been positive and
not positive (Mossanda et al., 1979; LaVoie et al., 1979; Hermann, 1981; Amin
et al., 1985a,b).
Current theories on mechanisms of metabolic activation of polycyclic
aromatic hydrocarbons are consistent with a carcinogenic potential for
benzo[b]fluoranthene. Benzo[b]fluoranthene does not have a "classic bay-
region" structure (Jerina et al., 1978). It is metabolized by mixed function
oxidases to dihydrodiols (Amin et al., 1982). The 9,10-dihydrodiol is
tumorigenic in mouse skin-painting assays, suggesting the possible formation
of a reactive diol-epoxide (LaVoie et al., 1982).
__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[b]fluoranthene
CASRN -- 205-99-2
Last Revised -- 12/01/1990
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Amin, S., E.J. LaVoie and S.S. Hecht. 1982. Identification of metabolites of
benzo[b]fluoranthene. Carcinogenesis. 3(2): 171-174.
Amin, S., K. Huie and S.S. Hecht. 1985a. Mutagenicity and tumor initiating
activity of methylated benzo[b]fluoranthene. 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. 1981. Synergistic effects of individual polycyclic aromatic
hydrocarbons on the mutagenicity of their mixtures. Mutat. Res. 90: 399-409.
IARC (International Agency for Research on Cancer). 1984. Monographs on the
Evaluation of the Carcinogenic Risk of the Chemical to Man. Polynuclear
Aromatic Hydrocarbons. Part 3. Industrial Exposures in Aluminum Production,
Coal Gasification, Coke Production, and Iron and Steel Founding. Vol. 34.
World Health Organization.
Jerina, D.M., H. Yagi, R.E. Lehr, et al. 1978. The Bay-region theory of
carcinogenisis by polycyclic aromatic hydrocarbons. In: Polycyclic
Hydrocarbons and Cancer, Vol. 1. Environment, Chemistry and Metabolism, H.V.
Gelboin and P.O.P. Ts'o, Ed. Academic Press, NY.
Lacassagne, A., N.P. Buu-Hoi, F. Zajdela, D. Lavit-Lamy and O. Chalvet. 1963.
Activite cancerogene d'hydrocarbures aromatiques polycycliques a noyau
fluoranthene. Un. Int. Cancer Acta. 19(3-4): 490-496. (Fre.)
LaVoie, E.J., E.V. Bedenko, N. Hirota, S.S. Hecht and D. Hoffmann. 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.
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.
Mossanda, K., F. Poncelet, A. Fouassin and M. Mercier. 1979. Detection of
mutagenic polycyclic aromatic hydrocarbons in African smoked fish. Food
Cosmet. Toxicol. 17: 141-143.
U.S. EPA. 1984. Carcinogen Assessment of Coke Oven Emissions. Office of
Health and Environmental Assessment, Washington, DC. EPA 600/6-82-003F. NTIS
PB 84-170181.
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.
Wynder, E.L. and D. Hoffmann. 1959. A study of tobacco carcinogenesis. VII.
The role of higher polycyclic hydrocarbons. Cancer. 12: 1079-1086.
_VII. REVISION HISTORY
Substance Name -- Benzo[b]fluoranthene
CASRN -- 205-99-2
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
12/01/1990 II. Carcinogen assessment on-line
12/01/1990 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
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[b]fluoranthene
CASRN -- 205-99-2
Last Revised -- 12/01/1990
205-99-2
Benz(e)acephenanthrylene
B(b)F
BENZ(e)ACEPHENANTHRYLENE
Benzo(b)fluoranthene
Benzo(e)fluoranthene
HSDB 4035
NSC 89265
2,3-BENZFLUORANTHENE
2,3-BENZOFLUORANTHENE
2,3-BENZOFLUORANTHRENE
3,4-BENZ(e)ACEPHENANTHRYLENE
3,4-BENZFLUORANTHENE
3,4-Benzofluoranthene
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0453.HTM
|
