NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
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.
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).
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).
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.
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).
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).
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).
Direct evidence of acute toxicity resulting from oral exposure of humans to benz[a]anthracene is unavailable.
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).
No relevant reports of human subchronic oral exposure to benz[a]anthracene were available.
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).
No relevant reports of human chronic oral exposure to benz[a]anthracene were available.
Chronic experiments designed to demonstrate the carcinogenic nature of polycyclic aromatic hydrocarbons were inadequate to determine non-carcinogenic effects (U.S. EPA, 1984).
Studies describing developmental and reproductive effects in humans following oral exposure to benz[a]anthracene were not available.
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).
A reference dose for chronic or subchronic oral exposure to benz[a]anthracene is not available.
Information on the acute toxicity resulting from the inhalation exposure of humans to benz[a]anthracene was unavailable.
Information on the acute toxicity resulting from the inhalation exposure of animals to benz[a]anthracene was unavailable.
Information on the toxicity resulting from the subchronic inhalation exposure of humans to benz[a]anthracene was unavailable.
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).
Information on the toxicity resulting from the chronic inhalation exposure of humans to benz[a]anthracene was unavailable.
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.
No reports were available on developmental and reproductive effects in humans following inhalation exposure to benz[a]anthracene.
No reports were available on developmental and reproductive effects in animals following inhalation exposure to benz[a]anthracene.
A reference concentration for chronic or subchronic inhalation exposure to benz[a]anthracene is not available.
Direct evidence of acute toxicity resulting from exposure of humans to benz[a]anthracene by other routes is unavailable.
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.
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).
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.
Subchronic or chronic exposure of the skin to polycyclic aromatic hydrocarbon-containing materials can cause dermatitis in humans (see section 184.108.40.206.).
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).
Information on the developmental and reproductive toxicity of benz[a]anthracene in humans by other routes of exposure was unavailable.
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).
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).
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).
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).
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).
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).
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.
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).
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).
An oral slope factor has not been calculated specifically for benz[a]anthracene (U.S. EPA, 1991).
An inhalation slope factor has not been calculated specifically for benz[a]anthracene (U.S. EPA, 1991).
Bock, F.G. 1964. Early effects of hydrocarbons on mammalian skin. Progr. Exp. Tumor Res. 4: 126.
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.
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.
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 mutagenic and carcinogenic activity of benzo[a]pyrene and benzo[a]anthracene. in: Origins of Human Cancer. Cold Spring Harbor Laboratory. pp. 639-657.
Klein, M. 1963. Susceptibility of strain B6AF1/J hybrid infant mice to tumorigenesis with 1,2-benzanthracene, deoxycholic acid, and 3-methylcholanthrene. Cancer Res. 23: 1701-1707.
Kotin, p., et al. 1969. Distribution, retention, and elimination of 14C-3,4-benzpyrene after administration to mice and rats. J. Natl. Cancer Inst. 23: 541.
Kraup, T. 1970. Oocyte survival in the mouse ovary after treatment with 9,10-dimethyl-1,2-benz[a]anthracene. J. Endocrinol. 46: 483.
Lasnitzki, A. and D.L. Woodhouse. 1944. The effect of 1,2,5,6-dibenzanthracene on the lymph nodes of the rat. J. Anat. 78: 121.
Levin, W., R.L. Chang, A.W. Wood, H. Yagi, D.R. Thakker, D.M. Jerina and A. H. Conney. 1984. High Stereoselectivity among the optical isomers of the diastereomeric bay-region diol-epoxides of benz[a]anthracene in the expression of tumorigenic activity in murine tumor models. Cancer Res. 44: 929-933.
MacKenzie, K.M. and D.M. Angevine. 1981. Infertility in mice exposed in utero to benzo[a]pyrene. Biol. Reprod. 24: 183-191.
Mattison, D.R. and S.S. Thorgeirsson. 1977. Ovarian metabolism of polycyclic aromatic hydrocarbons and associated ototoxicity in the mouse. Gynecol. Invest. 8: 11.
Mitchell, C.E. and K. W. Tu. 1979. Distribution, retention and elimination of pyrene in rats after inhalation. J. Toxicol. Environ. Health. 5: 1171-1179.
National Academy of Sciences. 1972. Biological effects of atmospheric pollutants: Particulate polycyclic organic matter. Washington, D.C.
Neal, J. and R.H. Rigdon. 1967. Gastric tumors in mice fed benzo[a]pyrene: A quantitative study. Tex. Rep. Biol. Med. 25: 553.
Philips, F.S., et al. 1973. In vivo cytotoxicity of polycyclic hydrocarbons. In: Pharmacology and the Future of Man. Proc. 5th Intl. Congr. Pharmacol., 1972, San Francisco. 2: 75.
Rees, E.O., et al. 1971. A study of the mechanism of intestinal absorption of benzo[a]pyrene. Biochem. Biophys. Acta. 225: 96.
Reznik-Schuller, H. and U. Mohr. 1974. Investigations on the carcinogenic burden by air pollution in man. IX. Early pathological alterations of the bronchial epithelium in Syrian golden hamsters after intratracheal instillation of benzo[a]pyrene. Zbl. Bakt. Hyg., I. Abt. Orig. B. 159: 493.
Rigdon, R.H. and E.G. Rennels. 1964. Effect of feeding benzpyrene on reproduction in the rat. Experientia. 20: 224-226.
Robinson, J.R., J.S. Felton, R.C. Levitt, S.S. Thorgiersson and D.W. Nebert. 1975. Relationship between "aromatic hydrocarbon responsiveness" and the survival times in mice treated with various drugs and environmental compounds. Mol. Pharmacol. 11: 850-865.
Saffiotti, U., et al. 1968. A method for the experimental induction of bronchogenic carcinoma. Cancer Res. 28: 104.
Sax, N.I. 1981. Cancer Causing Chemicals. Van Nostrand Reinhold, New York, p. 299.
Schlede, E., et al. 1970b. Stimulatory effect of benzo[a]pyrene and phenobarbital pretreatment on the biliary excretion of benzo[a]pyrene metabolites in the rat. Cancer Res. 30: 2898.
Schlede, E., et al. 1970a. Effect of enzyme induction on the metabolism and tissue distribution of benzo[a]pyrene. Cancer Res. 30: 2893.
Sittig, M. 1985. Handbook of Toxic and Hazardous Chemicals and Carcinogens, Second Edition. Noyes Publications, Park Ridge, New Jersey, pp.109-110.
Steiner, P.E. and J.H. Edgecomb. 1952. Carcinogenicity of 1,2-benzanthracene. Cancer Res. 12: 657-659.
Thyssen, F., J. Althoff, G. Kimmerle and U. Mohr. 1981. Inhalation studies with Benzo[a]pyrene in Syrian golden hamsters. J. Natl Cancer Inst. 66: 575-577.
U.S. EPA. 1980. Water Quality Criteria Document for Polynuclear Aromatic Hydrocarbons. Prepared by the Office of Research and Development, Environmental Criteria And Assessment Office, Cincinnati, OH for the Office of Water Regulations and Standards, Washington, DC.
U.S. EPA. 1984. Health Effects Assessment for Polycyclic Aromatic Hydrocarbons. 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. E.P.A./540/1-86-013.
U.S. EPA. 1991. Integrated Risk Information System (IRIS). Health Risk Assessment for Benz[a]anthracene. OnLine. Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1992a. Integrated Risk Information System (IRIS). Health Risk Assessment for Benzo[a]pyrene. OnLine. Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1992b. Health Effects Assessment Summary Tables, 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.
Vainio, H., et al. 1976. The fate of intratracheally installed benzo[a]pyrene in the isolated perfused rat lung of both control and 20-methylcholanthrene pretreated rats. Res. Comm. Chem. Pathol. Pharmacol. 13: 259.
Weast, R.C., J.A. Melvin and W.H. Beyer (ed). 1987. CRC Handbook of Chemistry and Physics. CRC Press, Inc., Boca Raton, Florida, pp C-105.
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: 1317-1322.
Yasuhira, K. 1964. Damage to the thymus and other lymphoid tissues from 3-methylcholanthrene, and subsequent thymoma production, in mice. Cancer Res. 24: 558. Retrieve Toxicity Profiles Condensed Version
Last Updated 8/29/97