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Benz[a]anthracene
CASRN 56-55-3
Contents
0454
Benz[a]anthracene; CASRN 56-55-3
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 Benz[a]anthracene
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 09/01/1994
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 -- Benz[a]anthracene
CASRN -- 56-55-3
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Benz[a]anthracene
CASRN -- 56-55-3
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Benz[a]anthracene
CASRN -- 56-55-3
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.
Benz[a]anthracene produced tumors in mice exposed by gavage; intraperitoneal,
subcutaneous or intramuscular injection; and topical application.
Benz[a]anthracene produced mutations in bacteria and in mammalian cells, and
transformed mammalian cells in culture.
___II.A.2. HUMAN CARCINOGENICITY DATA
None. Although there are no human data that specifically link exposure to
benz[a]anthracene to human cancers, benz[a]anthracene 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; Lee et al., 1976; Brockhaus and Tomingas, 1976).
___II.A.3. ANIMAL CARCINOGENICITY DATA
Sufficient. Benz[a]anthracene administration caused an increase in the
incidence of tumors by gavage (Klein, 1963); dermal application (IARC, 1973);
and both subcutaneous injection (Steiner and Faulk, 1951; Steiner and
Edgecomb, 1952) and intraperitoneal injection (Wislocki et al., 1986) assays.
A group of male B6AF1/J mice was exposed to gavage solutions containing 3%
benz[a]anthracene in Methocel-Aerosol O.T. (dioctyl ester of sodium sulfo-
succinic acid), 3 doses/week for 5 weeks (total dose of approximately 225
mg/mouse, 500 mg/kg/day) or the vehicle (Klein, 1963). Mice were evaluated
for tumors on days 437-444 and 547 after treatment was initiated. A
statistical analysis was not reported. Increased incidences of pulmonary
adenoma and hepatoma in treated vs. control mice were reported by the authors
at both observation times. The incidence of pulmonary adenoma at 437-444 days
was 37/39 (95%) in treated animals vs. 10/38 (26%) in controls; whereas at 547
days, 19/20 (95%) treated animals and 7/20 (35%) controls had pulmonary
adenomas. The incidence of hepatomas at 437 to 440 days was 18/39 (46%) in
treated animals compared with 0/38 among the vehicle controls. After 547
days, the hepatoma incidences increased to 20/20 for the treated animals
versus 2/20 (10%) for vehicle controls.
Mice (strain and sex not specified) were exposed to a single gavage dose
of 0.5 mg benz[a]anthracene in mineral oil (approximately 17 mg/kg). No
tumors were reported in 13 mice examined 16 months after exposure. In another
part of the study, multiple gavage treatments, 8 or 16 treatments at 3-7 day
intervals over a 16-month period, resulted in forestomach papillomas in 2/27
treated mice compared with 0/16 in vehicle controls (Bock and King, 1959).
Groups of male and female CD-1 mice (n=90-100) received intraperitoneal
injections of benz[a]anthracene in DMSO on days 1, 8, and 15 of age (total
dose = 638 ug/mouse) (Wislocki et al., 1986). Tumors were evaluated in
animals that died spontaneously after weaning and in all remaining animals at
1 year after exposure. In treated male mice, a statistically significant
increase in the incidence of liver adenomas or carcinomas (31/39 treated vs.
2/28 controls) occurred; 25/39 had carcinomas. Female mice did not develop
liver tumors. The incidence of pulmonary adenomas or carcinomas in
benz[a]anthracene-treated males (6/39, with a majority of adenomas) was
increased but not statistically significantly relative to the vehicle controls
(1/28). In the female mice, however, the incidence of pulmonary adenomas was
significantly elevated in the treated group (6/32) when compared with vehicle
controls (0/31).
Benz[a]anthracene yielded positive results in tests for complete
carcinogenicity and initiating activity in skin painting assays in C3H/He,
CAF1 and ICR/Ha mouse strains. These studies are reviewed in IARC (1973).
Subcutaneous injection of benz[a]anthracene in tricaprylin into C57Bl mice
(40-50/group) produced injection site sarcomas 9 months after treatment
(Steiner and Falk, 1951; Steiner and Edgecomb, 1952). The sarcoma incidences
were: uninjected controls, 0/76; tricaprylin controls, 3/28 (11%); 0.05 mg,
5/43 (12%); 0.2 mg, 11/43 (26%); 1.0 mg, 15/31 (48%); 5.0 mg, 49/145 (34%);
and 10 mg, 5/16 (31%). The results of similar experiments in this series were
combined (Steiner and Edgecomb, 1952). A statistical analysis of the results
was not reported. Survival was roughly equivalent in all groups (70%).
Klein (1952) showed that an intramuscular injection of benz[a]anthracene
in combination with 1 or 3% croton oil produced injection site fibrosarcomas
and hemangioendotheliomas in Strain A-derived albino mice; 3/24 mice injected
with benz[a]anthracene and 1% croton oil and 1/26 mice injected with
benz[a]anthracene and 3% croton oil developed tumors. None of the 30 mice
injected with benz[a]anthracene and 0.1% croton oil and none of the 30 mice
injected with benz[a]anthracene and 5% croton oil developed tumors. In the
control groups none of the 35 mice injected only with 1% croton oil and none
of the 32 mice injected only with benz[a]anthracene developed tumors. The
survival rate for all groups was roughly equivalent (74%).
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
The results of tests for DNA damage in Escherichia coli have not been
positive at concentrations of benz[a]anthracene up to 250 ug/mL and 1000
ug/well (Rosenkrantz and Poirier, 1979; DeFlora et al., 1984). Positive
results were obtained in tests for reverse mutation in five different strains
of Salmonella typhimurium and for forward mutation in one strain (McCann et
al., 1975; Coombs et al., 1976; Simmon, 1979; Salamone et al., 1979; Bartsch
et al., 1980; DeFlora et al., 1984; Norpoth et al., 1984; Utesch et al., 1987;
Bos et al., 1988; Kaden et al. 1979).
Benz[a]anthracene produced positive results in an assay for mutations in
Drosophila melongaster (Fahmy and Fahmy, 1973).
Tests for DNA damage, mutation, chromosomal effects and cell
transformation in a variety of eukaryotic cell preparations have yielded
mostly positive results. Benz[a]anthracene tested positive for DNA damage in
primary rat hepatocytes and HeLa cells (Probst et al., 1981; Martin et al.,
1978). It also tested positive for forward mutation in Chinese hamster cells,
V79 cells, mouse lymphoma L5178Y cells and rat liver epithelial cells (Slaga
et al., 1978; Krahn and Heidelberger, 1977; Amacher et al., 1980; Amacher and
Turner, 1980; Tong et al., 1981). Benz[a]anthracene tested positive for
chromosomal affects in Chinese hamster ovary cells (Pal, 1981). Tests for
cell transformation (cell morphology) have yielded positive results in Syrian
hamster embryo cells and mouse prostate C3HG23 cells (Pienta et al., 1977;
DiPaolo et al., 1969, 1971; Marquardt and Heidelberger, 1972).
Current theories on mechanisms of metabolic activation of polycyclic
aromatic hydrocarbons are consistent with a carcinogenic potential for
benz[a]anthracene. Benz[a]anthracene has a "bay-region" structure (Jerina et
al., 1978). It is metabolized by mixed function oxidases to reactive "bay-
region" diol epoxides that are mutagenic in bacteria and tumorigenic in mouse
skin painting assays (Booth and Sims, 1974; Wood et al., 1977a,b).
__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
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 -- Benz[a]anthracene
CASRN -- 56-55-3
Last Revised -- 12/01/1990
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Amacher, D.E. and G.N. Turner. 1980. Promutagen activation by rodent-liver
post mitochondrial fractions in the L5178Y/TK cell mutation assay. Mutat.
Res. 74: 485-501.
Amacher, D.E., S.C. Paillet, G.N. Turner and D.S. Salsburg. 1980. Point
mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells. II.
Test validation and interpretation. Mutat. Res. 72: 447-474.
Bartsch, H., C. Malaveille, A.M. Camus, et. al. 1980. Validation and
comparative studies on 180 chemicals with S. typhimurium strains and V79
Chinese hamster cells in the presence of various metabolizing systems. Mutat.
Res. 76: 1-50.
Bock, F.G. and D.W. King. 1959. A study of the sensitivity of the mouse
forestomach toward certain polycyclic hydrocarbons. J. Natl. Cancer Inst.
23(4): 833-839.
Booth, J. and P. Sims. 1974. 8,9-Dihydro-8,9-dihydroxybenz[a]anthracene
10,11-oxide: A new type of polycyclic aromatic hydrocarbon metabolite. FEBS
Lett. 47(1): 30-33.
Bos, R.P., J.L.G. Theuws, F.J. Jongeneelen and P.Th. Henderson. 1988.
Mutagenicity of bi-, tri and tetra-cyclic aromatic hydrocarbons in the "taped-
plate assay" and in the conventional Salmonella mutagenicity assay. Mutat.
Res. 204: 203-206.
Brockhaus, A. and R. Tomingas, 1976. Emission of polycyclic hydrocarbons
from combustion processes in small heating units and their concentration in
the atmosphere. Staub-Reinhalt. Luft. 36(3): 96-101.
Coombs, M.M., C. Dixon and A.M. Kissonerghis. 1976. Evaluation of the
mutagenicity of compounds of known carcinogenicity, belonging to the
benz[a]anthracene, chrysene, and cyclopenta[a]phenanthrene series, using Ame's
test. Cancer Res. 36: 4525-4529.
DeFlora, S., P. Zanacchi, A. Camoirano, C. Bennicelli and G.S. Badolati.
1984. Genotoxic activity and potency of 35 compounds in the Ames reversion
test and in a bacterial DNA-repair test. Mutat. Res. 133(3): 161-198.
DiPaolo, J.A., J.P. Donovan and R.L. Nelson. 1969. Quantitative studies of
in vitro transformation by chemical carcinogens. J. Natl. Cancer Inst.
42(5): 867-874.
DiPaolo, J.A., P.J. Donovan and R.L. Nelson. 1971. Transformation of hamster
cells in vitro by polycyclic hydrocarbons without cytotoxicity. Proc. Natl.
Acad. Sci. USA. 68(12): 2958-2961.
Fahmy, O.G. and M.J. Fahmy. 1973. Oxidative activation of benz(a)anthracene
and methylated derivatives in mutagenesis and carcinogenesis. Cancer Res.
33: 2354-2361.
IARC (International Agency for Research on Cancer). 1973. Certain Polycyclic
Aromatic Hydrocarbons and Heterocyclic Compounds. Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Man. Polynuclear Aromatic
Compounds. Vol. 3. Lyon, France.
IARC (International Agency for Research on Cancer). 1984. Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Man. Polynuclear Aromatic
Compounds. 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
carcinogenesis 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. p. 173-188.
Kaden, D.A., R.A. Hites and W.G. Thilly. 1979. Mutagenicity of soot and
associated polycyclic aromatic hydrocarbons to Salmonella typhimurium. Cancer
Res. 39: 4152-4159.
Klein, M. 1952. Effect of croton oil on induction of tumors by 1,2-
benzanthracene, desoxycholic acid, or low doses of 20-methylcholanthrene in
mice. J. Natl. Cancer Inst. 13: 333-341.
Klein, M. 1963. Susceptibility of strain B6AF/J hybrid infant mice to
tumorigenesis with 1,2-benzanthracene, deoxycholic acid, and 3-
methylcholanthrene. Cancer. Res. 23: 1701-1707.
Krahn, D.F. and C. Heidelberger. 1977. Liver homogenate-mediated mutagenesis
in Chinese hamster V79 cells by polycyclic aromatic hydrocarbons and
aflatoxins. Mutat. Res. 46: 27-44.
Lee, M.L., M. Novotny and K.D. Bartle. 1976. Gas chromatography/mass
spectrometric and nuclear magnetic resonance studies of carcinogenic
polynuclear aromatic hydrocarbons in tobacco and marijuana smoke condensates.
Anal. Chem. 48(2): 405-416.
Marquardt, H. and C. Heidelberger. 1972. Influence of "feeder cells" and
inducers and inhibitors of microsomal mixed-function oxidases on hydrocarbon-
induced malignant transformation of cells derived from C3H mouse prostate.
Cancer Res. 32: 721-725.
Martin, C.N., A.C. McDermid and R.C. Garner. 1978. Testing of known
carcinogens and noncarcinogens for their ability to induce unscheduled DNA
synthesis in HeLa cells. Cancer Res. 38: 2621-2627.
McCann, J.E., E. Choi, E. Yamasaki and B.N. Ames. 1975. Detection of
carcinogens as mutagens in the Salmonella/microsome test: Assay of 300
chemicals. Proc. Natl. Acad. Sci. USA. 72(12): 5135-5139.
Norpoth, K., A. Kemena, J. Jacob and C. Schumann. 1984. The influence of
18 environmentally relevant polycyclic aromatic hydrocarbons and Clophen A50,
as liver monooxygenase inducers, on the mutagenic activity of
benz[a]anthracene in the Ames test. Carcinogenesis. 5(6): 747-752.
Pal, K. 1981. The induction of sister-chromatid exchanges in Chinese hamster
ovary cells by K-region epoxides and some dihydrodiols derived from
benz[a]anthracene, dibenz[a,c]anthracene and dibenz[a,h]anthracene. Mutat.
Res. 84: 389-398.
Pienta, R.J., J.A. Poiley and W.B. Lebherz, III. 1977. Morphological
transformation of early passage golden Syrian hamster embryo cells derived
from cryopreserved primary cultures as a reliable in vitro bioassay for
identifying diverse carcinogens. Int. J. Cancer. 19: 642-655.
Probst, G.S., R.E. McMahon, L.E. Hill, C.Z. Thompson, J.K. Epp and S.B. Neal.
1981. Chemically-induced unscheduled DNA synthesis in primary rat hepatocyte
cultures: A comparison with bacterial mutagenicity using 218 compounds.
Environ. Mutagen. 3: 11-32.
Rosenkrantz, H.S. and L.A. Poirier. 1979. Evaluation of the mutagenicity and
DNA-modifying activity of carcinogens and noncarcinogens in microbial systems.
J. Natl. Cancer Inst. 62(4): 873-892.
Salamone, M.F., J.A. Heddle and M. Katz. 1979. The mutagenic activity of
thirty polycyclic aromatic hydrocarbons (PAH) and oxides in urban airborne
particulates. Environ. Int. 2: 37-43.
Simmon, V.F. 1979. In vitro mutagenicity assays of chemical carcinogens and
related compounds with Salmonella typhimurium. J. Natl. Cancer Inst. 62(4):
893-899.
Slaga, T.J., E. Huberman, J.K. Selkirk, R.G. Harvey and W.M. Braken. 1978.
Carcinogenicity and mutagenicity of benz[a]anthracene diols and diol-epoxides.
Cancer Res. 38: 1699-1704.
Steiner, P.E. and J.H. Edgecomb. 1952. Carcinogenicity of 1,2-
benzanthracene. Cancer Res. 12: 657-659.
Steiner, P.E. and H.L. Falk. 1951. Summation and inhibition effects of weak
and strong carcinogenic hydrocarbons: 1,2-Benzanthracene, chrysene, 1:2:5:6-
dibenzanthracene and 20-methylcholanthrene. Cancer Res. 11: 56-63.
Tong, C., M.F. Laspia, S. Telang and G.M. Williams. 1981. The use of adult
rat liver cultures in the detection of the genotoxicity of various polycyclic
aromatic hydrocarbons. Environ. Mutagen. 3: 477-487.
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.
Utesch, D., H. Glatt and F. Oesch. 1987. Rat hepatocyte-mediated bacterial
mutagenicity in relation to the carcinogenic potency of benz(a)anthracene,
benzo(a)pyrene and twenty-five methylated derivatives. Cancer Res. 47: 1509-
1515.
Wislocki, P.G., E.S. Bagan, A.Y.H. Lu, et al. 1986. Tumorigenicity of
nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene
in the newborn mouse assay. Carcinogenesis. 7(8): 1317-1322.
Wood, A.W., R.L. Chang, W. Levin, et al. 1977a. Mutagenicity and
cytotoxicity of benz[a]anthracene diol epoxides and tetrahydro-epoxides:
Exceptional activity of the bay region 1,2-epoxides. Proc. Natl. Acad. Sci.
USA. 74(7): 2746-2750.
Wood, A.W., W. Leven. R.L. Chang, et al. 1977b. Tumorigenicity of five
dihydrodiols of benz[a]anthracene on mouse skin: Exceptional activity of
benz[a]anthracene 3,4-dihydrodiol. Proc. Natl. Acad. Sci. USA. 74(8):
3137-3179.
_VII. REVISION HISTORY
Substance Name -- Benz[a]anthracene
CASRN -- 56-55-3
-------- -------- --------------------------------------------------------
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
09/01/1994 I.B. Inhalation RfC now under review
VIII. SYNONYMS
Substance Name -- Benz[a]anthracene
CASRN -- 56-55-3
Last Revised -- 12/01/1990
56-55-3
Benz(a)anthracene
benz(a)anthracene
Benzanthracene
Benzanthrene
BENZO(a)ANTHRACENE
BENZO(b)PHENANTHRENE
Benzoanthracene
HSDB 4003
NSC 30970
RCRA WASTE NUMBER U018
Tetraphene
1,2-BENZ(a)ANTHRACENE
1,2-Benzanthracene
1,2-BENZANTHRAZEN [German]
1,2-BENZANTHRENE
1,2-BENZOANTHRACENE
2,3-Benzophenanthrene
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0454.HTM
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