Toxicity Profiles
Formal Toxicity Summary for 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.
- EXECUTIVE SUMMARY
- 1. INTRODUCTION
- 2. METABOLISM AND DISPOSITION
- 1. INTRODUCTION
- 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
AUGUST 1993
Prepared by: Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation Group, Biomedical and Environmental Information Analysis Section, Health Sciences Research Division, Oak Ridge National Laboratory*, 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
Pyrene, also referred to as benzo(def)phenanthrene and -pyrene, is a polycyclic aromatic hydrocarbon (PAH) that can be derived from coal tar. Currently, there is no commercial production or use of this compound. Pyrene is ubiquitous in the environment as a product of incomplete combustion of fossil fuels and has been identified in surface and drinking water, numerous foods, and in ambient air (U.S. EPA, 1988, 1987; IARC, 1983).
Although a large body of literature exists on the toxicity and carcinogenicity of PAHs, toxicity data for pyrene are limited. No human data were available that addressed the toxicity of pyrene. Subchronic oral exposure to pyrene produced nephropathy, decreased kidney weights, increased liver weights, and slight hematological changes in mice (TRL, 1989) and produced fatty livers in rats (White and White, 1939). A single intraperitoneal injection of pyrene produced swelling and congestion of the liver and increased serum aspartate amino transferase (AST) and bilirubin levels in rats (Yoshikawa et al., 1985). No data were available concerning the toxic effects of inhalation exposure to pyrene or data regarding teratogenicity or other reproductive effects by any route of exposure.
A Reference Dose (RfD) of 3E-1 mg/kg/day for subchronic (U.S. EPA, 1993a) and 3E-2 mg/kg/day for chronic oral exposure (U.S. EPA, 1993b) to pyrene was calculated from a no-observed-adverse-effect level (NOAEL) of 75 mg/kg/day in a 13-week gavage study with mice (TRL, 1989). Data were insufficient to derive an inhalation Reference Concentration (RfC) for pyrene (U.S. EPA, 1993a,b).
No oral or inhalation bioassays were available to assess the carcinogenicity of pyrene. Studies involving other routes of exposure (intratracheal, dermal, and subcutaneous) generally gave negative results. Intratracheal administration of pyrene in combination with Fe2O3 particles did not induce tumors in hamsters (Sellakumar and Shubik, 1974). Skin painting assays evaluating complete carcinogenesis in mice (Van Duuren and Goldschmidt, 1976; Horton and Christian, 1974; Roe and Grant, 1964; Wynder and Hoffman, 1959); or initiating (Roe and Grant, 1964); or promoting capacity (Wood et al., 1980; Scribner, 1973; Salaman and Roe, 1956) have been negative or inconclusive. Mice injected subcutaneously with pyrene did not develop tumors (Shear and Leiter, 1941), but there is evidence that pyrene enhances the tumorigenicity of topically applied benzo[a]pyrene (Slaga et al., 1979; Van Duuren and Goldschmidt, 1976; Goldschmidt et al., 1973).
Based on no human data and inadequate data from animal bioassays, U.S. EPA (1993a,b) has placed pyrene in weight-of-evidence group D, not classifiable as to human carcinogenicity.
1. INTRODUCTION
Pyrene (CAS No. 129-00-00), also known as benzo(def)phenanthrene and -pyrene, is a polycyclic aromatic hydrocarbon (PAH) with four aromatic rings. It has a chemical formula of C16H10 and a molecular weight of 202.26. Pure pyrene is a colorless crystalline solid at ambient temperature; the presence of tetracene, a common contaminant, gives it a yellow color. Pyrene has a melting point of 156C, a boiling point of 404C, a density of 1.271 at 23C, and a vapor pressure of 6.86x10-7 mm Hg. It is almost insoluble in water, but is soluble in benzene, carbon disulfide, diethyl ether, ethanol, petroleum ether, toluene, and acetone. Pyrene has a log octanol/water partition coefficient of 4.88 (ATSDR, 1990; U.S. EPA, 1988; U.S. EPA, 1987; IARC, 1983).
Pyrene can be derived from coal tar, but there is no commercial production or known commercial use of this compound. Pyrene from coal tar has been used as the starting material for the synthesis of benzo[a]pyrene (IARC, 1983).
Human exposure to pyrene occurs primarily through inhalation of tobacco smoke and polluted air and by ingestion of water polluted by combustion effluents and food, such as smoked fish and meats (IARC, 1983). Pyrene is ubiquitous in the environment as a product of incomplete combustion and has been identified in surface and drinking water, in many foods, and in the ambient atmosphere (U.S. EPA, 1988, 1987). Pyrene is one of a number of PAHs on EPA's priority pollutant list (ATSDR, 1990; U.S. EPA, 1987). Although a large body of literature exists on the toxicity and carcinogenicity of other PAHs, primarily benzo[a]pyrene, toxicity data for pyrene are limited.
2. METABOLISM AND DISPOSITION
2.1. ABSORPTION
Pyrene can be absorbed following oral, inhalation, and dermal exposure. Absorption from the gastrointestinal tract appears to be relatively poor; approximately 50% of pyrene was present in the gastrointestinal tract 24 hours after gavage administration to rats. Rapid absorption of inhaled pyrene was indicated by the presence of pyrene in tissues 30 minutes following exposure to pyrene (Mitchell and Tu, 1979). Following dermal application of 2% crude tar to humans for eight hours on two consecutive days, pyrene was detected in the blood, providing evidence of percutaneous absorption (Storer et al., 1984).
2.2. DISTRIBUTION
Twenty-four hours after oral administration of pyrene to rats, pyrene was found in the gastrointestinal tract, but not in the kidneys, liver, lungs, or trachea (Mitchell and Tu, 1979).
Thirty minutes after a 1-hour inhalation exposure, pyrene was detected in respiratory tract tissues, liver, kidneys, carcass, and muscle of rats. Pyrene was rapidly cleared from these tissues, levels in the lungs were 65 and 6% of the initial (30-minute) concentrations after 24 and 48 hours, respectively, and concentrations in the liver and kidneys were 6 and 14% of the initial concentrations, respectively, after 48 hours. Concentrations in the gastrointestinal tract 24 hours after inhalation exposure were about 4 times higher than the initial value, suggesting clearance from the respiratory tract by mucociliary action. Biliary contribution to gastrointestinal concentrations was not determined, but pyrene was largely cleared from the gastrointestinal tract after 4 days (Mitchell and Tu, 1979).
Pyrene was detected in the blood of humans following topical applications of 2% crude tar on two consecutive days (Storer et al., 1984). Very small amounts were found in the kidneys, liver, and trachea of rats 24 hours after a single application of pyrene to the fur. No pyrene or metabolites were detected in the lung (Mitchell and Tu, 1979).
Hyperplastic changes in embryonic kidney cells obtained from mice that had been injected intramuscularly with pyrene during the last week of gestation, indicate that pyrene has the ability to pass through the placenta (Shabad et al., 1972).
2.3. METABOLISM
Metabolism of pyrene proceeds primarily via oxidation at the 1-2 and 4-5 bonds, with 1-hydroxypyrene as the principal metabolite. 1-Hydroxypyrene has been detected in the urine of pigs that were given single oral doses of pyrene (Keimig et al., 1983). Boyland and Sims (1964) identified the sulfuric acid and glucuronic acid conjugates of 1-hydroxypyrene, 1,6-, and 1,8-dihydroxypyrene and trans-4,5-dihydro-4,5-dihydroxypyrene, as well as N-acetyl-S-(4,5-dihydro-4-hydroxy-5-pyrenyl)-L-cysteine in the urine of rats and rabbits that were injected intraperitoneally with pyrene. Most of these metabolites as well as two trihydroxy derivatives were isolated following incubation of pyrene with rat liver microsomes (Jacob et al., 1982; Sims, 1970).
2.4. EXCRETION
No studies were located regarding the excretion of pyrene in humans. Although fecal and urine analyses were not conducted, oral and inhalation experiments with rats by Mitchell and Tu (1979) suggest that fecal elimination appears to reflect unabsorbed pyrene, and pyrene resulting from mucociliary clearance and biliary elimination (U.S. EPA, 1987).
3. NONCARCINOGENIC HEALTH EFFECTS
3.1. ORAL EXPOSURES
3.1.1. Acute Toxicity
Information on the acute oral toxicity of pyrene in humans or animals was not available.
3.1.2. Subchronic Toxicity
3.1.2.1. Human
Information on the subchronic oral toxicity of pyrene in humans was not available.
3.1.2.2. Animal
In a subchronic gavage study, male and female Crl:CD-1 mice were given suspensions of pyrene in corn oil at doses of 0, 75, 125, or 250 mg/kg/day for 13 weeks (TRL, 1989). Dose-related increases of nephropathy (up to 50% at the highest dose) were observed in females; nephropathy was also seen in high-dosed males. The nephropathy, described as minimal to mild, was characterized by the presence of multiple foci of renal tubular regeneration, often accompanied by interstitial lymphocytic infiltrates and/or foci of interstitial fibrosis. Absolute and relative kidney weights were reduced in the two higher dose groups. Relative liver weights were increased in males exposed to 250 mg/kg/day and in females exposed to 125 mg/kg/day. Treated male mice exhibited slight hematological changes that consisted of decreased red blood cell count (RBC), packed cell volume (PCV), and hemoglobin levels (HGB).
White and White (1939) reported inhibition of growth and enlarged fatty livers in young male rats maintained on diets containing 2000 mg/kg of pyrene for 100 days. The growth inhibition was reversible upon addition of cystine or methionine.
Gershbein (1975) examined the extent of liver regeneration in partially hepatectomized rats exposed to pyrene in the diet at doses of 514 mg/kg/day for 10 days. Treated rats showed no increase in liver regeneration, suggesting that the chemical does not induce a proliferative response.
3.1.3. Chronic Toxicity
Information on the chronic oral toxicity of pyrene in humans or animals was not available.
3.1.4. Developmental and Reproductive Toxicity
Information on the developmental and reproductive toxicity of pyrene in humans or animals following oral exposure was not available.
3.1.5. Reference Dose
3.1.5.1. Subchronic
ORAL RfD: 3E-1 mg/kg/day (U.S. EPA, 1993a)
NOAEL: 75 mg/kg/day
LOAEL: 125 mg/kg/day
UNCERTAINTY FACTOR: 300
PRINCIPAL STUDY: TRL, 1989
COMMENTS: The same study, described in section 3.1.2.2., was used for the derivation of the subchronic and chronic RfD. An uncertainty factor of 300 reflects 10 each for intra- and interspecies variability and an additional 3 accounts for the lack of toxicity studies in a second species and of developmental/reproductive studies.
3.1.5.2. Chronic
ORAL RfD: 3E-2 mg/kg/day (U.S. EPA, 1991)
NOAEL: 75 mg/kg/day
LOAEL: 125 mg/kg/day
UNCERTAINTY FACTOR: 3000
CONFIDENCE:
Study: Medium
Data Base: Low
RfD: Low
VERIFICATION DATE: 11/15/89
PRINCIPAL STUDY: TRL, 1989
COMMENTS: The RfD is based on a 13-week gavage study with mice described in Section 3.1.2.2., with renal tubular pathology and decreased kidney weights as critical effects. An uncertainty factor of 3000 reflects 10 each for intra- and interspecies variability, 10 for the use of a subchronic study for chronic RfD derivation, and an additional 3 accounts for the lack of toxicity studies in a second species and of developmental/reproductive studies.
3.2. INHALATION EXPOSURES
3.2.1. Acute Toxicity
Information on the acute toxicity of pyrene in humans or animals following inhalation exposure was not available.
3.2.2. Subchronic Toxicity
Information on the subchronic toxicity of pyrene in humans or animals following inhalation exposure was not available.
3.2.3. Chronic Toxicity
Information on the chronic toxicity of pyrene in humans or animals following inhalation exposure was not available.
3.2.4. Developmental and Reproductive Toxicity
Information on the developmental and reproductive toxicity of pyrene in humans or animals following inhalation exposure was not available.
3.2.5. Reference Concentration
Data were insufficient to calculate a Reference Concentration (RfC) for pyrene (U.S EPA, 1993a,b).
3.3. OTHER ROUTES OF EXPOSURE
3.3.1. Acute Toxicity
3.3.1.1. Human
Information on the acute toxicity of pyrene in humans by other routes of exposure was not available.
3.3.1.2. Animal
The intraperitoneal LD50(7) and LD50(4) (dose lethal to half the animals in 7 and 4 days, respectively) for pyrene was 514 and 678 mg/kg, respectively, for mice (Salamone, 1981). A single intraperitoneal injection of 150 mg/kg of pyrene to male Sprague-Dawley rats resulted in elevated aspartate aminotransferase (AST) and bilirubin levels as well as slight swelling and congestion of livers (Yoshikawa et al., 1985).
3.3.2. Subchronic Toxicity
Information on the subchronic toxicity of pyrene by other routes of exposure in humans or animals was not available.
3.3.3. Chronic Toxicity
Information on the chronic toxicity of pyrene by other routes of exposure in humans or animals was not available.
3.3.4. Developmental and Reproductive Toxicity
3.3.4.1. Human
Information on the developmental or reproductive toxicity of pyrene by other routes of exposure in humans was not available.
3.3.4.2. Animal
Administration of two subcutaneous injections of 6 mg pyrene on days 18 and 19 of gestation to strain A mice did not increase the incidence of lung or mammary gland tumors in the offspring 1 year after weaning (Nikinova, 1977).
When several strains of mice were injected intramuscularly with 4 mg pyrene in sunflower oil once daily during the last week of gestation, hyperplastic changes were seen in fetal kidney cells established in culture. No hyperplastic changes were seen in cells obtained from untreated animals (Shabad et al., 1972).
3.4. TARGET ORGANS/CRITICAL EFFECTS
3.4.1. Oral Exposures
3.4.1.1. Primary Target Organ(s)
Kidney: Subchronic oral exposure to pyrene produced nephropathy and decreased kidney weights in mice.
3.4.1.2. Other Target Organs
1. Liver: Subchronic oral exposure to pyrene produced increased liver weights in rats and mice and fatty livers changes in rats.
2. Blood: Subchronic oral exposure to pyrene produced slight hematologic effects (decreased RBC, PVC, and HGB) in mice.
3.4.2. Inhalation Exposures
Information on target organs for inhalation exposure to pyrene was not available.
3.4.3. Other Routes of Exposure
Information on target organs for other routes of exposure to pyrene was not available.
4. CARCINOGENICITY
4.1. ORAL EXPOSURES
Information on the carcinogenicity of pyrene in humans or animals following oral exposure was not available.
4.2. INHALATION EXPOSURES
Information on the carcinogenicity of pyrene in humans or animals following inhalation exposure was not available.
4.3. OTHER ROUTES OF EXPOSURE
4.3.1. Human
Information on the carcinogenicity of pyrene in humans by other routes of exposure was not available.
4.3.2. Animal
Intratracheal instillation of 3 mg pyrene [mixed with equal parts of hematite dust (Fe2O3) and suspended in saline] at weekly intervals for 30 weeks did not produce tumors of the respiratory system (histologic examination) or other tissues (gross examination) in male Syrian golden hamsters (Sellakumar and Shubik, 1974).
Several dermal application studies showed that pyrene applied 2-3 times weekly for 1-2 years to the skin of mice does not induce skin tumors (Van Duuren and Goldschmidt, 1976; Horton and Christian, 1974; Roe and Grant, 1964; Wynder and Hoffman, 1959). Mouse skin initiation-promotion studies involving initiation with benzo[a]pyrene (Roe and Grant, 1964), promotion with croton oil (Salaman and Roe, 1956) or promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) (Scribner, 1973; Wood et al., 1980) were negative or inconclusive (Scribner, 1973). However, the dermal carcinogenicity of benzo[a]pyrene in ICR/Ha mice was enhanced by pretreatment with or coadministration of pyrene (Slaga et al., 1979; Van Duuren and Goldschmidt, 1976; Goldschmidt et al., 1973), suggesting possible cocarcinogenicity of pyrene. A 56% increase of DNA adducts observed in CD-1 mice receiving dermal applications of benzo[a]pyrene and pyrene above the level found following benzo[a]pyrene-treatment alone (Rice et al., 1984) also suggests that pyrene has cocarcinogenic potential.
Two subcutaneous injections of 10 mg pyrene 4 months apart did not produce local tumors in male and female Jackson A strain mice after 12-18 months (Shear and Leiter, 1941). A mixture of pyrene, anthracene, and phenanthrene was shown to reduce the ability of benzo[a]pyrene to produce injection site sarcomas in C57B1 mice following single subcutaneous injections of benzo[a]pyrene in combination with the PAH mixture (Falk et al., 1964).
Because some chemical carcinogens have been shown to induce melanogenesis in melanoblasts of skin, several PAHS, including pyrene, were examined for their ability to induce melanocyte activation (Iwata et al., 1981). Topical application of pyrene to the backs of mice for 1 or 2 consecutive days produced no increases in the number of active melanocytes.
4.4. EPA WEIGHT-OF-EVIDENCE
Classification -- D, not classifiable as to human carcinogenicity (U.S. EPA, 1993b).
Basis -- Based on no human data and inadequate data from animal bioassays.
4.5. CARCINOGENICITY SLOPE FACTORS
None were calculated.
5. REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 1990. Toxicological Profile for Polycyclic Aromatic Hydrocarbons. Acenaphthene, Acenaphthylene, Anthracene, Benzo(a)anthracene, Benzo(a)pyrene, Benzo(b)fluoranthene, Benzo(g,i,h)perylene, Benzo(k)fluoranthene, Chrysene, Dibenzo(a,h)anthracene, Fluoranthene, Fluorene, Indeno(1,2,3-c,d)pyrene, Phenanthrene, Pyrene. Prepared by Clement International Corporation, under Contract No. 205-88-0608. ATSDR/TP-90-20.
Boyland, E. and P. Sims. 1964. Metabolism of polycyclic compounds. The metabolism of pyrene in rats and rabbits. Biochem. J. 90: 391-398.
Falk, H.L., P. Kotin and S. Thompson. 1964. Inhibition of carcinogenesis. The effects of polycyclic hydrocarbons and related compounds. Arch. Environ. Health 9: 169-179.
Gershbein, L.L. 1975. Liver regeneration as influenced by the structure of aromatic and heterocyclic hydrocarbons. Res. Commun. Chem. Pathol. Pharmacol. 11: 445-466. (Cited in ATSDR, 1990)
Goldschmidt, B.M., C. Katz and B.L. Van Duuren. 1973. The cocarcinogenic activity of non-carcinogenic aromatic hydrocarbons (Abstract No. 334). Proc. Am. Assoc. Cancer Res. 17: 84.
Horton, A.W. and G.M. Christian. 1974. Cocarcinogenic versus incomplete carcinogenic activity among aromatic hydrocarbons: Contrast between chrysenes and benzo[b]triphylene. J. Natl. Cancer Inst. 53: 1017-1020.
IARC (International Agency for Research on Cancer). 1983. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Polynuclear Aromatic Compounds. Part 1. Chemical, Environmental and Experimental Data, Vol. 32. World Health Organization, Lyon, France, pp. 431-445.
Iwata, K., N. Inui and T. Takeuchi. 1981. Induction of active melanocytes in mouse skin by skin carcinogens: A new method for the detection of skin carcinogens. Carcinogenesis 2: 589-594.
Jacob, J., G. Grimmer, G. Raab and A. Schmoldt. 1982. The metabolism of pyrene by rat liver microsomes and the influence of various mono-oxygenase inducers. Xenobiotica 12: 45-53.
Keimig, S.D., K.W. Kirby, D.P. Morgan, et al. 1983. Identification of 1-hydroxypyrene as a major metabolite of pyrene in pig urine. Xenobiotica 13: 415-420.
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.
Nikonova, T.V. 1977. Transplacental action of benzo[a]pyrene and pyrene. Bull. Exp. Biol. Med. 84: 1025-1027. (Cited in IARC, 1983)
Rice, J.E., T.J. Hosted and L.J. LaVoie. 1984. Fluoranthene and pyrene enhance benzo(a)pyrene--DNA adduct formation in vivo in mouse skin. Cancer Letters 24: 327-333.
Roe, F.J.C. and G.A. Grant. 1964. Tests of pyrene and phenanthrene for incomplete carcinogenic and anticarcinogenic activity. Br. Empire Cancer Campaign. (Abstract) (Cited in IARC, 1983)
Salaman, M.H. and F.J.C. Roe. 1956. Further tests for tumor-initiating activity: N,N-Di(2-chloroethyl)p-aminophenylbutyric acid (CB1348) as an initiator of skin tumor formation in the mouse. Br. J. Cancer 10: 363-378.
Salamone, M.F. 1981. Toxicity of 41 carcinogenic analogs. In: F.J. de Serres and J. Ashby, Eds., Evaluation of Short-Term Tests for Carcinogens. Report of the International Colloborative Program. Progress in Mutation Research, Vol. 1. Elsevier/North Holland, pp. 682-685.
Scribner, J.D. (1973) Brief communication: Tumor initiation by apparently noncarcinogenic polycyclic aromatic hydrocarbons. J. Natl. Cancer Inst. 50: 1717-1719.
Sellakumar, A. and P. Shubik. 1974. Carcinogenicity of different polycyclic hydrocarbons in the respiratory tract of hamsters. J. Natl. Cancer Inst. 53: 1713-1719.
Shabad, L.M., J.D. Sorokina, N.I. Golub and S.P. Bogovski. 1972. Transplacental effect of some chemical compounds on organ cultures of embryonic kidney tissue. Cancer Res. 32: 617-627.
Shear, M.J. and J. Leiter. 1941. Studies in carcinogenesis. XVI. Production of subcutaneous tumors on mice by miscellaneous polycyclic compounds. J. Natl. Cancer Inst. 11: 241-258.
Sims, P. 1970. Qualitative and quantitative studies on the metabolism of a series of aromatic hydrocarbons by rat-liver preparations. Biochem. Pharmacol. 19: 795-818.
Slaga, T.J., L. Jecker, W.M. Bracken, et al. 1979. The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene skin tumor-initiation. Cancer Lett. 7: 51-59.
Storer, J.S., I. DeLeon, L.E. Millikan, et al. 1984. Human absorption of crude coal tar products. Arch. Dermatol. 120: 874-877. (Cited in ATSDR, 1990)
TRL (Toxicity Research Laboratories). 1989. 13-Week Mouse Oral Subchronic Toxicity Study. TRL Study No. 042-012. Toxicity Research Laboratories, Ltd., Muskegon, MI.
U.S. EPA (U.S. Environmental Protection Agency). 1987. Health and Environmental Effects Profile for Pyrene. Prepared by the Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, Cincinnati, OH, for the Office of Solid Waste and Emergency Response. ECAO-CIN-P277.
U.S. EPA (U.S. Environmental Protection Agency). 1988. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, Cincinnati, OH, for the Office of Drinking Water. ECAO-CIN-D010.
U.S. EPA (U.S. Environmental Protection Agency). 1993a. Health Assessment Summary Tables. Annual FY-93. 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.
U.S. EPA (U.S. Environmental Protection Agency). 1993b. Integrated Risk Information System (IRIS). Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH.
Van Duuren, B.L. and B.M. Goldschmidt. 1976. Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis. J. Natl. Cancer Inst. 56: 1237-1242.
White, J. and A. White. 1939. Inhibition of growth of the rat by oral administration of methylcholanthrene, benzpyrene, or pyrene and the effects of various dietary supplements. J. Biol. Chem. 131: 149-161. (Cited in U.S. EPA, 1990)
Wood, A.W., W. Levin, R.L. Chang, et al. 1980. Mutagenicity and tumor-initiating activity of cyclopenta(c,d)pyrene and structurally related compounds. Cancer Res. 40: 642-649.
Wynder, E.L.. and D. Hoffman. 1959. A study of tobacco carcinogenesis. VII. The role of higher polycyclic aromatic hydrocarbons. Cancer 12: 1079-1086. (Cited in U.S. EPA, 1987)
Yoshikawa, T., L.P. Ruhr, W. Flory, et al. 1985. Toxicity of polycyclic aromatic hydrocarbons. 1. Effect of phenanthrene, pyrene and their ozonized products on blood chemistry in rats. Toxicol. Appl. Pharmacol. 79: 218-226.
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