Toxicity Profiles
Condensed Toxicity Summary for BENZO[A]PYRENE
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.
December 1994
Prepared by: Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences 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.
Benzo[a]pyrene is a polycyclic aromatic hydrocarbon (PAH) that can be derived from coal tar. Benzo[a]pyrene occurs ubiquitously in products of incomplete combustion of fossil fuels and has been identified in ambient air, surface water, drinking water, waste water, and char-broiled foods (IARC, 1983). Benzo[a]pyrene is primarily released to the air and removed from the atmosphere by photochemical oxidation and dry deposition to land or water. Biodegradation is the most important transformation process in soil or sediment (ATSDR, 1990).
Benzo[a]pyrene is readily absorbed following inhalation, oral, and dermal routes of administration (ATSDR, 1990). Following inhalation exposure, benzo[a]pyrene is rapidly distributed to several tissues in rats (Sun et al., 1982; Weyand and Bevan, 1986). The metabolism of benzo[a]pyrene is complex and includes the formation of a proposed ultimate carcinogen, benzo[a]pyrene 7,8 diol-9,10-epoxide (IARC, 1983). The major route of excretion is hepatobiliary followed by elimination in the feces (EPA, 1991).
No data are available on the systemic (non-carcinogenic) effects of benzo[a]pyrene in humans. In mice, genetic differences appear to influence the toxicity of benzo[a]pyrene. Subchronic dietary administration of 120 mg/kg benzo[a]pyrene for up to 180 days resulted in decreased survival due to hematopoietic effects (bone narrow depression) in a "nonresponsive" strain of mice (i.e., a strain whose cytochrome P-450 mediated enzyme activity is not induced as a consequence of PAH exposure). No adverse effects were noted in "responsive" mice (i.e., a strain capable of inducing increased cytochrome P-450 mediated enzyme activity as a consequence of PAH exposure) (Robinson et al., 1975). Immunosuppression has been reported in mice administered daily intraperitoneal injections of 40 or 160 mg/kg of benzo[a]pyrene for 2 weeks, with more pronounced effects apparent in "nonresponsive" mice (Blanton et al., 1986; White et al., 1985). In utero exposure to benzo[a]pyrene has produced adverse developmental/reproductive effects in mice. Dietary administration of doses as low as 10 mg/kg during gestation caused reduced fertility and reproductive capacity in offspring (Mackenzie and Angevine, 1981), and treatment by gavage with 120 mg/kg/day during gestation caused stillbirths, resorptions, and malformations (Legraverend et al., 1984). Similar effects have been reported in intraperitoneal injection studies (ATSDR, 1990). Neither a reference dose (RfD) nor a reference concentration (RfC) has been derived for benzo[a]pyrene.
Numerous epidemiologic studies have shown a clear association between exposure to various mixtures of PAHs containing benzo[a]pyrene (e.g., coke oven emissions, roofing tar emissions, and cigarette smoke) and increased risk of lung cancer and other tumors. However, each of the mixtures also contained other potentially carcinogenic PAHs; therefore, it is not possible to evaluate the contribution of benzo[a]pyrene to the carcinogenicity of these mixtures (IARC, 1983; EPA, 1991). An extensive data base is available for the carcinogenicity of benzo[a]pyrene in experimental animals. Dietary administration of benzo[a]pyrene has produced papillomas and carcinomas of the forestomach in mice (Neal and Rigdon, 1967), and treatment by gavage has produced mammary tumors in rats (McCormick et al., 1981) and pulmonary adenomas in mice (Wattenberg and Leong, 1970). Exposure by inhalation and intratracheal instillation has resulted in benign and malignant tumors of the respiratory and upper digestive tracts of hamsters (Ketkar et al., 1978; Thyssen et al., 1981). Numerous topical application studies have shown that benzo[a]pyrene induces skin tumors in several species, although mice appear to be the most sensitive species. Benzo[a]pyrene is a complete carcinogen and also an initiator of skin tumors (IARC, 1973; EPA, 1991). Benzo[a]pyrene has also been reported to induce tumors in animals when administered by other routes, such as intravenous, intraperitoneal, subcutaneous, intrapulmonary, and transplacental.
Based on United States Environmental Protection Agency (EPA) guidelines, benzo[a]pyrene was
assigned to weight-of-evidence group B2, probable human carcinogen. For oral exposure, the slope
factor and unit risk are 7.3E+0 (mg/kg/day)-1 and 2.1E-4 (ug/L)-1, respectively (EPA, 1994).
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