Toxicity Profiles
Toxicity Summary for BENZ[A]ANTHRACENE
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- EXECUTIVE SUMMARY
- 1. INTRODUCTION
- 2. METABOLISM AND DISPOSITION
- 2.1 ABSORPTION
2.2 DISTRIBUTION
2.3 METABOLISM
2.4 EXCRETION
- 3. NONCARCINOGENIC HEALTH EFFECTS
- 3.1 ORAL EXPOSURES
3.2 INHALATION EXPOSURES
3.3 OTHER ROUTES OF EXPOSURE
3.4 TARGET ORGANS/CRITICAL EFFECTS
- 4. CARCINOGENICITY
- 4.1 ORAL EXPOSURES
4.2 INHALATION EXPOSURES
4.3 OTHER ROUTES OF EXPOSURE
4.4 EPA WEIGHT-OF-EVIDENCE
4.5 CARCINOGENICITY SLOPE FACTORS
- 5. REFERENCES
September 1992
Prepared by: Andrew Francis, Chemical Hazard Evaluation Group, Biomedical Environmental Information Analysis Section, Health and Safety Research Division, *, Oak Ridge, Tennessee.
Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM.
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No.
DE-AC05-84OR21400.
EXECUTIVE SUMMARY
Benz[a]anthracene, along with a number of other polycyclic aromatic hydrocarbons, are natural
products produced by the incomplete combustion of organic material. The arrangement of the
aromatic rings in the benz[a]anthracene molecule gives it a "bay region" often correlated with
carcinogenic properties. In general, the bay-region polycyclic aromatic hydrocarbons and some of
their metabolites are known to react with cellular macromolecules, including DNA, which may
account for both their toxicity and carcinogenicity. The inducible mixed-function oxidase enzymes
oxidize benz[a]anthracene to form metabolites with increased water solubility that can be efficiently
excreted in the urine. A minor product of this oxidation, a bay-region diol epoxide, reacts readily
with DNA and has been shown to be highly carcinogenic (U.S. EPA, 1980; 1984; Jerina, et al., 1977).
The toxic effects of benz[a]anthracene and similar polycyclic aromatic hydrocarbons are
primarily directed toward tissues that contain proliferating cells. Animal studies indicate that
exposure to bay-region polycyclic aromatic hydrocarbons can damage the hematopoietic system
leading to progressive anemia as well as agranulocytosis (Robinson, et al., 1975; Cawein and Sydnor,
1968). The lymphoid system can also be affected resulting in lymphopenia. Toxic effects have been
observed in the rapidly dividing cells of the intestinal epithelium, spermatogonia and resting
spermatocytes in the testis and primary oocytes of the ovary (Philips et al., 1973; Mackinzie and
Angevine, 1981; Kraup, 1970; Ford and Huggins, 1963; Mattison and Thorgeirsson, 1977; U.S. EPA, 1980;
1984). Most of these effects have occurred following both oral and parenteral exposure. Epithelial
proliferation and cell hyperplasia in the respiratory tract have been reported following subchronic
inhalation exposure (Reznik-Schuller and Mohr, 1974; Saffiotti et al., 1968). However, because of the
lack of quantitative data, neither a reference dose nor a reference concentration have been derived
(U.S. EPA, 1991).
The primary concern with benz[a]anthracene exposure is its potential carcinogenicity. There is
no unequivocal, direct evidence of the carcinogenicity of the compound to humans, however,
benz[a]anthracene and other known carcinogenic polycyclic aromatic hydrocarbons are components
of coal tar, soot, coke oven emissions and tobacco smoke. There is adequate evidence of its
carcinogenic properties in animals. Oral exposures of mice to benz[a]anthracene have resulted in
hepatomas, pulmonary adenomas and forestomach papillomas (Klein, 1963; Bock and King, 1959; U.S.
EPA, 1991). The EPA weight-of-evidence classification is: B2, probable human carcinogen, for both
oral and inhalation exposure based on adequate animal evidence and no human evidence (U.S. EPA,
1991). A slope factor has not been derived specifically for benz[a]anthracene by the EPA (U.S. EPA,
1991). However, an oral slope factor of 7.3 (mg/kg/day)-1 has been calculated for benzo[a]pyrene
based on the incidence of stomach tumors in mice treated with benzo[a]pyrene (Neal and Rigdon,
1967; U.S. EPA, 1980; 1984; 1992a). A drinking water unit risk of 2.1E-4 (g/L)-1 has also been
calculated for benzo[a]pyrene (U.S. EPA, 1992a). An inhalation slope factor of 6.1 (mg/kg/day)-1
(U.S. EPA, 1992b) was calculated for benzo[a]pyrene based on the incidence of respiratory tumors in
golden hamsters treated with benzo[a]pyrene (Thyssen et al., 1981; U.S. EPA, 1980; 1984). An
inhalation unit risk of 1.7E-3 (g/m3)-1 has also been calculated for benzo[a]pyrene (U.S. EPA,
1992b).
1. INTRODUCTION
Benz[a]anthracene (CAS registry number 56-55-3) is a polycyclic aromatic hydrocarbon containing
four aromatic rings two of which share carbons with only one other ring. It is soluble in alcohol, ether
and benzene but practically insoluble in water (9.4 g/kg @ 25oC) (U.S. EPA, 1984; Weast, 1987). There
is no commercial application for benz[a]anthracene, however, it is a ubiquitous contaminant formed
during the incomplete combustion of organic material. Benz[a]anthracene is found in various kinds of
smoke and flue gases, tobacco smoke, tobacco smoke condensate, automobile exhaust, roasted coffee
and in charcoal broiled, barbecued or smoked meats. It is also found in creosote, coal tar, petroleum
asphalt, and a variety of foods, including vegetable oils and baker's yeast. It is an atmospheric
contaminant near power plants and busy highways, and tends to bind to particulate matter in the
atmosphere. The primary removal mechanism from the atmosphere is thought to be ozonolysis
reactions, where the expected half-life is less than 1 day to several weeks dependent on the nature of
the particulate matter to which it is adsorbed. Benz[a]anthracene is also adsorbed to soil particulates
where it undergoes degradation by microorganisms. It can persist in the soil from days to years
depending on the adsorbent and the microorganisms present. The water insolubility of
benz[a]anthracene limits its movement through the soil (Sittig, 1985; Sax, 1981; U.S. EPA, 1984).
2. METABOLISM AND DISPOSITION
2.1. ABSORPTION
Animal studies have shown that polycyclic aromatic hydrocarbons in general and benz[a]anthracene
in particular are absorbed from the gastrointestinal tract (Rees et al., 1971). Specific inhalation studies
on benz[a]anthracene were not available, but polyaromatic hydrocarbons as a class are considered
capable of crossing epithelial membranes. Studies with benzo[a]pyrene and pyrene have shown rapid
pulmonary absorption by rats (Kotin et al., 1969; Vainio et al., 1976; Mitchell and Tu, 1979). Quantitative
data on benz[a]anthracene absorption are not available for either the oral or inhalation routes.
2.2. DISTRIBUTION
Specific studies on the distribution of benz[a]anthracene in humans were not available. However,
animal studies using related polycyclic aromatic hydrocarbons, chiefly benzo[a]pyrene, indicate that
these compounds are distributed in a wide variety of body tissues, eventually becoming localized
primarily in fatty tissues. Approximately 80 to 90% of the administered benzo[a]pyrene disappeared
from the blood within 6 minutes following a single intravenous 10 g injection. A rapid equilibrium was
reached between the blood and liver. The half time for benzo[a]pyrene removal from the liver was about
10 minutes; however, the disappearance was biphasic with a rapid initial phase followed by a slower
phase lasting 6 hours or longer. Removal from the brain was slower than from the liver with
benzo[a]pyrene concentration increasing in fat tissues for over 6 hours (Schlede, et al., 1970a). The
disappearance of benzo[a]pyrene from all tissues is accelerated by pretreatment with benzo[a]pyrene.
This pretreatment induces microsomal enzyme activities that are involved in the oxidation and
detoxification of polycyclic aromatic hydrocarbons (Schlede, et al., 1970b; U.S. EPA, 1980).
2.3. METABOLISM
The arrangement of the aromatic rings in the molecule creates what has been termed a "bay
region" imparting certain properties to the polycyclic aromatic hydrocarbons. Benz[a]anthracene and
other bay-region polycyclic aromatic hydrocarbons undergo oxidation by microsomal enzymes
(cytochrome P-450 mixed-function oxidase system) to excretable metabolites. Unfortunately, some
intermediary metabolites, chiefly the bay-region diol epoxides, can readily react with DNA and greatly
increase carcinogenic activity. The benz[a]anthracene 3,4-diol-epoxide is a very minor metabolite of
benz[a]anthracene oxidation, which may account for its weak tumorigenic properties when compared
to some other bay region polycyclic aromatic hydrocarbons (Levin, et al., 1984; Jerina, et al., 1977).
2.4. EXCRETION
The oxidized products produced by the cytochrome P-450 mixed-function oxidase system exhibit
increased reactivity and will undergo conjugation with intracellular molecules such as glutathione
resulting in compounds that have increased solubility in water and can be excreted efficiently in the
urine. Less soluble metabolites and the parent compound can be excreted through the hepatobiliary
system in the feces. Prior exposure to a polycyclic aromatic hydrocarbon results in the induction of
the mixed-function oxidase enzymes and greatly increases the rate of excretion by increasing the
formation of water soluble metabolites (U.S. EPA, 1980).
3. NONCARCINOGENIC HEALTH EFFECTS
3.1. ORAL EXPOSURES
3.1.1. Acute Toxicity
3.1.1.1. Human
Direct evidence of acute toxicity resulting from oral exposure of humans to benz[a]anthracene is
unavailable.
3.1.1.2. Animal
Specific studies on the acute oral toxicity of benz[a]anthracene in animals were not available,
however, several effects are common to the polycyclic aromatic hydrocarbon class of compounds.
Generally these compounds and their metabolites are most toxic to targets that contain rapidly
proliferating cells. They are known to bind to proteins and nucleic acids and may interfere with the
processes involved in cell growth and division (U.S. EPA, 1980). The hematopoietic and lymphoid systems
are common targets, as well as the intestinal epithelium and the testis.
Single feedings of 112 or 133 mg dimethyl benz[a]anthracene/kg body weight of female rats
resulted in severe depression of hematopoietic and lymphoid precursors. Since only the more rapidly
proliferating cells were affected by benz[a]anthracene, the authors suggested inhibition of DNA
replication was involved in the toxicologic response (Cawein and Sydnor, 1968; U.S. EPA, 1980). In
another experiment, female rats given 300 mg dimethyl benz[a]anthracene/kg by gavage displayed injury
to the intestinal epithelium and developed a progressive anemia. Mortality of rats was about 65% at this
dose (Philips et al., 1973).
3.1.2. Subchronic Toxicity
3.1.2.1. Human
No relevant reports of human subchronic oral exposure to benz[a]anthracene were available.
3.1.2.2. Animal
Specific data on the toxic effects of subchronic exposure of animals to benz[a]anthracene were not
available. Experiments with other polycyclic aromatic hydrocarbons indicate that subchronic and acute
exposures result in similar effects. Oral exposure of mice to 120 mg benzo[a]pyrene/kg body
weight/day for 6 months resulted in severe aplastic anemia. The inducibility of the microsomal mixed-function oxidase enzymes was shown to influence survival. Poorly inducible mice (AKR/N mice, Ahd/Ahd
type) died within 4 weeks, whereas the inducible mice survived for the 6 month period. This experiment
demonstrates the detoxification of a polycyclic aromatic hydrocarbon by the mixed-function oxidase
system (Robinson et al., 1975; U.S. EPA, 1984).
3.1.3. Chronic Toxicity
3.1.3.1. Human
No relevant reports of human chronic oral exposure to benz[a]anthracene were available.
3.1.3.2. Animal
Chronic experiments designed to demonstrate the carcinogenic nature of polycyclic aromatic
hydrocarbons were inadequate to determine non-carcinogenic effects (U.S. EPA, 1984).
3.1.4. Developmental and Reproductive Toxicity
3.1.4.1. Human
Studies describing developmental and reproductive effects in humans following oral exposure to
benz[a]anthracene were not available.
3.1.4.2. Animal
Specific data on developmental and reproductive toxicity resulting from exposure of animals to
benz[a]anthracene were unavailable. However, studies using similar polycyclic aromatic hydrocarbons
indicate that exposure to these compounds may result in reproductive effects. Rigdon and Rennels
(1964) fed female rats 50 mg benzo[a]pyrene/kg/day for 3.5, months including the gestation period.
Increased fetal mortality was seen in all 7 treated females. The treated dams did not show gross signs
of toxicity, although failure to lactate resulted in the death of the only surviving offspring within 3 days
of birth.
Decreased fertility and gonadal weights in both sexes were seen in the offspring of mice treated
orally with 10 mg/kg/day benzo[a]pyrene during gestation. A dose of 40 mg/kg/day resulted in almost
complete sterility. No effect on fetal body weight or survival of the pups was reported (Mackenzie and
Angevine, 1981).
Kraup (1970) reported the destruction of small oocytes and the reduction of the numbers of
growing and large oocytes following oral administration of dimethyl benz[a]anthracene to mice (U.S. EPA,
1980).
3.1.5. Reference Dose
A reference dose for chronic or subchronic oral exposure to benz[a]anthracene is not available.
3.2. INHALATION EXPOSURES
3.2.1. Acute Toxicity
3.2.1.1. Human
Information on the acute toxicity resulting from the inhalation exposure of humans to
benz[a]anthracene was unavailable.
3.2.1.2. Animal
Information on the acute toxicity resulting from the inhalation exposure of animals to
benz[a]anthracene was unavailable.
3.2.2. Subchronic Toxicity
3.2.2.1. Human
Information on the toxicity resulting from the subchronic inhalation exposure of humans to
benz[a]anthracene was unavailable.
3.2.2.2. Animal
Information on the toxicity resulting from the subchronic inhalation exposure of animals to
benz[a]anthracene was unavailable. However, subchronic inhalation exposures of golden hamsters to
other polycyclic aromatic hydrocarbons, including dimethyl benz[a]anthracene, benzo[a]pyrene, and
dibenzo[a,i)]pyrene, caused epithelial proliferation and cell hyperplasia in the respiratory tract (total
weekly dose of benzo[a]pyrene was 0.63 mg). These effects are usually seen without marked
inflammation or necrosis by the 11th week of exposure, and precede the development of respiratory
tract tumors (Reznik-Schuller and Mohr, 1974; Saffiotti, et al., 1968; U.S. EPA 1980).
3.2.3. Chronic Toxicity
3.2.3.1. Human
Information on the toxicity resulting from the chronic inhalation exposure of humans to
benz[a]anthracene was unavailable.
3.2.3.2. Animal
Information on the toxicity resulting from the chronic inhalation exposure of animals to
benz[a]anthracene was unavailable. Experiments utilizing the chronic exposure of animals to other
polycyclic aromatic hydrocarbons were designed to study carcinogenesis and are not suitable for
describing toxicity effects.
3.2.4. Developmental and Reproductive Toxicity
3.2.4.1. Human
No reports were available on developmental and reproductive effects in humans following inhalation
exposure to benz[a]anthracene.
3.2.4.2. Animal
No reports were available on developmental and reproductive effects in animals following inhalation
exposure to benz[a]anthracene.
3.2.5. Reference Concentration
A reference concentration for chronic or subchronic inhalation exposure to benz[a]anthracene is
not available.
3.3. OTHER ROUTES OF EXPOSURE
3.3.1. Acute Toxicity
3.3.1.1. Human
Direct evidence of acute toxicity resulting from exposure of humans to benz[a]anthracene by other
routes is unavailable.
3.3.1.2. Animal
Single injections of polycyclic aromatic hydrocarbons have demonstrated the toxic effects of these
compounds on rapidly proliferating cells. An intraperitoneal injection of 3-methylcholanthrene (0.3 to
1.0 mg) in 12 hour to 9 day-old mice resulted in severe degeneration of the thymus, reduction in weight
of the spleen and mesenteric lymph nodes, degeneration of bone marrow cells, and retardation of
thyroid gland development. Increased mortality was observed with newborn mice after treatment
(Yasuhira, 1964).
Philips et al. (1973) gave male rats a single intravenous injection of 50 mg/kg of 7,12-dimethylbenz[a]anthracene. The targets that were affected included damage to the intestinal epithelium,
atrophy of the hematopoietic elements, decreased weight of lymphoid organs, agranulocytosis,
lymphopenia, and progressive anemia. A similar experiment demonstrated a decreased [14C]-labeled
thymidine incorporation into the DNA in the cells of small and large intestine, spleen, bone marrow,
cervical lymph nodes, thymus, and testis. This inhibition, which was as high as 90%, was seen 6 hours
after treatment and indicated a reduction in DNA synthesis in these organs, which normally contain
rapidly dividing cells.
3.3.2. Subchronic Toxicity
3.3.2.1. Human
Subchronic or chronic dermal exposure of workers to materials such as coal tar, mineral oil, and
petroleum waxes containing benz[a]anthracene and other polycyclic aromatic hydrocarbons resulted in
the development of dermatitis and hyperkeratoses (Hueper, 1963; NAS, 1972).
3.3.2.2. Animal
Topical application of benz[a]anthracene and other polycyclic aromatic hydrocarbons to mouse skin
results in the destruction of sebaceous glands, hyperplasia, hyperkeratosis, and ulceration of the skin.
The sebaceous glands are the most sensitive structures to polycyclic hydrocarbons. A correlation exists
between the carcinogenic activity of benz[a]anthracene and its toxicity toward the sebaceous glands
(Bock, 1964).
Weekly subcutaneous injections of dibenz[a,h]anthracene, benz[a]anthracene and anthracene in mice
resulted in dilated lymph sinuses and a decrease of lymphoid cells within 40 weeks. The lymph glands
contained increased numbers of reticulum (stem) cells and an accumulation of iron. Decreased spleen
weight was observed in the mice receiving dibenz[a,h]anthracene (Hoch-Ligeti, 1941).
Lasnitzki and Woodhouse (1944) studied the effects of subcutaneous injections of
dibenz[a,h)anthracene, benzo[a]pyrene, 3-methylcholanthrene, and anthracene on lymph nodes in rats.
Injections were given 5 times weekly for several weeks and, with the exception of anthracene, resulted
in extravascular red blood cells in the lymph spaces and the presence of large pigmented cells.
3.3.3. Chronic Toxicity
3.3.3.1. Human
Subchronic or chronic exposure of the skin to polycyclic aromatic hydrocarbon-containing
materials can cause dermatitis in humans (see section 3.3.2.1.).
3.3.3.2. Animal
Chronic exposure experiments using various routes were designed to examine cancer end points
and are not generally useful as toxicity studies. The qualitative results, however, generally reflect those
observed for the effects from single or subchronic exposures to polycyclic aromatic hydrocarbons (U.S.
EPA, 1980).
3.3.4. Developmental and Reproductive Toxicity
3.3.4.1. Human
Information on the developmental and reproductive toxicity of benz[a]anthracene in humans by
other routes of exposure was unavailable.
3.3.4.2. Animal
Single intravenous injections of 0.5 to 2.0 mg dimethyl benz[a]anthracene in 25-day old rats or
injections of 5.0 mg in 60-day old rats resulted in degenerative changes in the testis 38 to 40 days after
treatment. These lesions included the destruction of spermatogonia and resting spermatocytes (Ford
and Huggins, 1963). In a similar experiment, the destruction of primary oocytes in mice was also seen
after injection of 3-methylcholanthrene. The effect in this experiment was correlated with the ability
of the mice to induce the microsomal mixed-function oxidase enzymes following treatment (Mattison
and Thorgeirsson, 1977).
3.4. TARGET ORGANS/CRITICAL EFFECTS
3.4.1. Oral Exposures
3.4.1.1. Primary Target(s)
- Hematopoietic system: Animal studies have shown atrophy of the hematopoietic elements
leading to progressive anemia and agranulocytosis after exposure to polycyclic aromatic
hydrocarbons.
- Lymphoid system: Shrinkage of lymphoid organs and lymphopenia have been noted in animals
exposed to polycyclic aromatic hydrocarbons.
- Intestinal epithelium: Damage to the rapidly growing epithelial cells of animals has been
observed following exposure to polycyclic aromatic hydrocarbons.
- Testis or ovary: Destruction of the spermatogonia and resting spermatocytes in males and the
primary oocytes in females following exposure to polycyclic aromatic hydrocarbons.
3.4.1.2. Other Target(s)
- Fetus: Increased fetal mortality has been observed in animal experiments with benzo[a]pyrene
exposure during gestation.
3.4.2. Inhalation Exposures
3.4.2.1. Primary Targets
- Respiratory tract: Animal experiments have shown epithelial proliferation and cell hyperplasia
following subchronic exposure to polycyclic aromatic hydrocarbons. This effect may be a
preneoplastic lesion.
4. CARCINOGENICITY
4.1. ORAL EXPOSURES
4.1.1. Human
Data relating human oral exposure to benz[a]anthracene and subsequent cancer development was
not available. Benz[a]anthracene is a component of mixtures that have been associated with human
cancers such as coal tar, soots, coke oven emissions, automobile exhaust, and cigarette smoke (U.S.EPA,
1980; 1984).
4.1.2. Animal
Klein (1963) treated male mice with 3% benz[a]anthracene in Methocel-aerosol O.T. by gavage 3
times/week for 5 weeks. Tumors were evaluated on days 437-444 and 547 after the initiation of
treatment. An increased incidence of pulmonary adenomas and hepatomas was noted at all observation
times when compared with controls. The incidence of pulmonary adenomas reached 95% and the
incidence of hepatoma reached 100% after 547 days. Bock and King (1959) administered 8 or 16 gavage
treatments of benz[a]anthracene to mice at 3-7 day intervals over a 16-month period. They found
forestomach papillomas in the treated groups (2/27) and none in the control group (0/16).
Treatment of Swiss mice with benzo[a]pyrene, a related polycyclic aromatic hydrocarbon, also
resulted in stomach tumors. Mice were fed doses ranging between 1 and 250 ppm in the diet for 110
days. The appearance of squamous cell papillomas and carcinomas was roughly dose dependent. The
cancer incidences observed were 0/289 for the control, 1/23 for 2.6 mg/kg/day, 1/40 for 5.2
mg/kg/day, 4/40 for 5.85 mg/kg/day, and 19/23 for 13.0 mg/kg/day (Neal and Rigdon, 1967).
4.2. INHALATION EXPOSURES
4.2.1. Human
Data on human inhalation exposure to benz[a]anthracene and subsequent cancer development was
not available. Benz[a]anthracene is a component of mixtures containing other polycyclic aromatic
hydrocarbons that have been associated with human cancers such as coal tar, soots, coke oven
emissions, automobile exhaust, and cigarette smoke (U.S. EPA, 1980; 1984).
4.2.2. Animal
Data on inhalation exposure of animals to benz[a]anthracene and subsequent cancer development
were not available. There are studies, however, that show tumor development following inhalation of
related polycyclic aromatic hydrocarbons. Golden hamsters exposed by inhalation to 9.5 mg/m3
benzo[a]pyrene for 4.5 hours/day for 10 weeks, followed by 3 hours/day for up to 675 days, developed
tumors of the nasal cavity, larynx, trachea and pharynx. The high dose also caused tumors of the
upper digestive tract (Thyssen et al., 1981).
4.3. OTHER ROUTES OF EXPOSURE
4.3.1. Human
Data relating other routes of exposure to benz[a]anthracene and subsequent cancer development
were not available. Benz[a]anthracene is a component of mixtures that have been associated with
human cancers such as coal tar, soots, coke oven emissions, automobile exhaust, and cigarette smoke
(U.S. EPA, 1980; 1984).
4.3.2. Animal
Intraperitoneal injections of mice with benz[a]anthracene in dimethylsulfoxide on days 1, 8, and
15 of age (total dose of 638 g/mouse) resulted in liver adenomas and carcinomas in male mice (31/39
total tumors treated, 25/39 adenomas, 2/28 total controls) and pulmonary adenomas in female mice
(6/32 treated, 0/32 controls) 1 year after exposure (Wislocki et al., 1986).
Subcutaneous injection of mice with benz[a]anthracene resulted in sarcomas at the site of injection
9 months following treatment. Injection of 5.0 mg produced a sarcoma incidence of 34% with no tumors
seen in controls (Steiner and Edgecomb, 1952).
A number of studies have shown benz[a]anthracene to have initiating activity and to act as a
complete carcinogen in skin painting assays in several strains of mice (IARC, 1973; U.S. EPA, 1991b).
Levin et al. (1984) tested the tumor-initiating activity of benz[a]anthracene and a number of its
metabolic products in a mouse skin painting assay. A single dose of 0.4 or 2.5 mole of
benz[a]anthracene followed by 25 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate
resulted in skin tumor incidence of 7% for the controls, 14% for 0.4 mole, and 36% for 2.5 mole.
4.4.1. Oral
CLASSIFICATION: Group B2 -- Probable Human Carcinogen (U.S. EPA, 1991b).
BASIS: Based on no human data and sufficient data from animal experiments. Benz[a]anthracene
has been shown to produce tumors in mice exposed by gavage; topical application; and
intraperitoneal, subcutaneous or intramuscular injection (U.S. EPA 1991).
4.4.2. Inhalation
CLASSIFICATION: Group B2 -- Probable Human Carcinogen (U.S. EPA, 1991b).
BASIS: Based on no human data and sufficient data from animal experiments. Benz[a]anthracene
has been shown to produce tumors in mice exposed by gavage: topical application; and
intraperitoneal, subcutaneous or intramuscular injection (U.S. EPA 1991). A related bay-region
polycyclic aromatic hydrocarbon, benzo[a]pyrene, has been shown to cause respiratory tract tumors
in golden hamsters when given by inhalation exposure (Thyssen et al., 1981).
4.5. CARCINOGENICITY SLOPE FACTORS
4.5.1. Oral
An oral slope factor has not been calculated specifically for benz[a]anthracene (U.S. EPA, 1991).
Benzo[a]pyrene:
- SLOPE FACTOR: 7.3 (mg/kg/day)-1 (U.S. EPA, 1980; 1984; 1992a).
- DRINKING WATER UNIT RISK: 2.1E-4 (g/L)-1 (U.S. EPA, 1992a)
- VERIFICATION DATE: 07/01/92
- PRINCIPAL STUDY: Neal and Rigdon (1967).
- COMMENTS: This slope factor was calculated by the EPA, (1984) from data obtained from
experiments using benzo[a]pyrene and was based on the incidence of stomach tumors in mice. This
slope factor was applied to protect humans from the carcinogenic effects of polycyclic aromatic
hydrocarbons as a chemical class. It is not currently available on IRIS for specific use with
benz[a]anthracene.
4.5.2. Inhalation
An inhalation slope factor has not been calculated specifically for benz[a]anthracene (U.S. EPA, 1991).
Benzo[a]pyrene:
- SLOPE FACTOR: 6.1 (mg/kg/day)-1 (U.S. EPA, 1992b)
- INHALATION UNIT RISK: 1.7E-3 (g/m3) -1 (U.S. EPA 1992b).
- VERIFICATION DATE: Not verified.
- PRINCIPAL STUDY: Thyssen et al. (1981).
- COMMENTS: This slope factor was calculated by the EPA, (1984) from data obtained from
experiments using benzo[a]pyrene and was based on the incidence of respiratory tumors in golden
hamsters. This slope factor was applied to protect humans from the carcinogenic effects of
polycyclic aromatic hydrocarbons as a chemical class. It is not currently available on IRIS for
specific use with benz[a]anthracene.
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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: 833-839.
Cawein, M.J. and K.L. Sydnor. 1968. Suppression of cellular activity in the reticuloendothelial system
of the rat by 7,12-dimethylbenz[a]anthracene. Cancer Res. 28: 320.
Ford, E. and C. Huggins. 1963. Selective destruction in testis induced by 7,12-dimethylbenz[a]anthracene. J. Exp. Med. 118: 27.
Hoch-Ligeti, C. 1941. Studies on the changes in the lymphoid tissues of mice treated with carcinogenic
and non-carcinogenic hydrocarbons. Cancer Res. 1: 484.
Hueper, W.C. 1963. Chemically induced skin cancers in man. Natl. Cancer Inst. Monograph. 10: 377.
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and Heterocyclic Compounds. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Man. Polynuclear Aromatic Compounds. Vol. 3. Lyon, France.
Jerina, D.M., R. Lehr, M. Schaefer-Ridder, H. Yagi, J.M. Karle, D.R. Thakker, A.W. Wood, A.Y.H. Lu, D. Ryan,
S. West, W. Levin and A.H. Conney. 1977. Bay-region epoxides of dihydrodiols: A concept explaining the
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