The Risk Assessment Information System

Toxicity Profiles

Formal Toxicity Summary for CHRYSENE

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: 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

December 1994

Prepared by: H. T. Borges, Ph.D., MT(ASCP), D.A.B.T., 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.

TOXICITY SUMMARY UPDATE

This report is an update of the Toxicity Summary for Chrysene (CAS Registry No. 218-01-9). The original summary for this chemical was submitted in November 1991. The update was performed by incorporating any new human health toxicity data published since the original submittal of the report. Pertinent pharmacokinetic, toxicologic, carcinogenic, and epidemiologic data were obtained through on-line searches of the TOXLINE database from 1991 through 1994. In addition, any changes to EPA-approved toxicity values (reference doses, reference concentrations, or cancer slope factors) from the Integrated Risk Information System (IRIS) (current as of December 1994) and/or the Health Effects Assessment Summary Tables, Annual FY-94 and July Supplement No. 1, for this chemical were incorporated in this update.

EXECUTIVE SUMMARY

Chrysene, a polycyclic aromatic hydrocarbon, is a ubiquitous environmental contaminant formed primarily by the incomplete combustion of organic compounds. Although present in coal and oil, the presence of chrysene in the environment is the result of anthropogenic activities such as coal combustion and gasification; gasoline exhaust; diesel and aircraft exhaust; and emissions from coke ovens, wood burning stoves, and waste incineration (IARC, 1983; ATSDR, 1990). Chrysene is not produced or used commercially, and its use is limited strictly to research applications.

Little information on the absorption, distribution, metabolism and excretion of chrysene in humans is available. Animal studies have shown that approximately 75% of the administered chrysene may be absorbed by oral, dermal, or inhalation routes (Grimmer et al., 1988; Modica et al., 1983; Chang, 1943). Following its absorption, chrysene is preferentially distributed to highly lipophilic regions of the body, most notably adipose and mammary tissue (Bartosek et al., 1984; Modica et al., 1983). Phase I metabolism of chrysene, whether in the lung, skin, or liver, is mediated by the mixed function oxidases. The metabolism results in the formation of 1,2-, 3,4-, and 5,6-dihydrodiols as well as the formation of 1-, 3-, and 4-phenol metabolites (Sims, 1970; Nordquist et al., 1981; Jacob et al., 1982, 1987). Additional Phase I metabolism of chrysene 1,2-dihydrodiol forms chrysene 1,2-dihydrodiol-3,4-epoxide and 9-hydroxychrysene 1,2-diol-3,4-oxide. These metabolites were shown to have mutagenic and alkylating activity (Hodgson et al., 1983; Wood et al., 1977; Wood et al., 1979). Phase II metabolism of chrysene results in the formation of glucuronide and sulfate ester conjugates; however, glutathione conjugates of diol- and triol-epoxides are also formed (Sims and Grover, 1974, 1981; Hodgson et al., 1986; Robertson and Jernström, 1986). Hepatobiliary secretion with elimination in the feces is the predominant route of excretion (Schlede et al., 1970; Grimmer et al., 1988).

Human or animal systemic, developmental, and reproductive health effects following exposure to chrysene were not identified. Because of the lack of systemic toxicity data, the reference dose (RfD) and the reference concentration (RfC) for chrysene have not been derived (EPA, 1994a, b). Target organs have not been described, although chrysene may induce immunosuppression similar to certain other PAHs. Oral and inhalation carcinogenic bioassays were not identified. In mouse skin painting studies, chrysene was an initiator of papillomas and carcinomas. In addition, intraperitoneal injections of chrysene have induced liver adenomas and carcinomas in male CD-1 and BLU/Ha Swiss mice. Although oral and inhalation slope factors have not been derived, EPA (1994a,b) has classified chrysene in weight-of-evidence Group B2, probable human carcinogen, based on the induction of liver tumors and skin papillomas and carcinomas following treatment and the mutagenicity and chromosomal abnormalities induced in in vitro tests.

1. INTRODUCTION

Chrysene (CAS Number 218-01-9), a polycyclic aromatic hydrocarbon (PAH), is also known by the synonyms 1,2-benzophenanthrene, benzo[a]phenanthrene, 1,2-benzphenanthrene, 1,2-benz[a]phenanthrene, and 1,2,5,6-dibenzonaphthalene. Pure chrysene has a molecular weight of 228 g/mol and is a colorless ortho-rhombic bipyramidal crystalline solid that strongly fluoresces red-blue under ultraviolet light. Chrysene has a melting point of 255C, a boiling point of 448C, a density of 1.274 g/cm³, and a vapor pressure of 6.3x10^-9 mm Hg (Weast, 1988). It is virtually insoluble in water; only slightly soluble in alcohol, ether, carbon bisulfide or glacial acetic acid; and moderately soluble in benzene (Budavari et al., 1989). Chrysene is not used or produced commercially; it is used primarily in research applications.

Chrysene is a ubiquitous environmental contaminant that occurs as a product of the incomplete combustion of organic compounds. Environmental anthropogenic sources of chrysene include gasoline, diesel, and aircraft turbine exhausts; coal combustion and gasification; emissions from coke ovens, wood burning stoves, and waste incineration; and various industrial applications such as iron, aluminum, and steel production. Chrysene is also a constituent of coal, oil, and their distillates such as coal tar, and creosote (IARC, 1983; ATSDR, 1990). Nonanthropogenic sources of chrysene include forest and grass fires, as well as volcanoes; however, these latter sources do not contribute significantly to the total environmental concentration of chrysene (ATSDR, 1990).

Humans are exposed to chrysene by oral, inhalation, and dermal routes. Exposure occurs through the consumption of fruits and vegetables grown in areas with high soil or atmospheric concentrations of chrysene and from drinking or using water contaminated with chrysene. Meats, particularly those with high fat contents, contribute significant quantities of chrysene to the diet from the pyrolysis of fats during the cooking process. Foods smoked or cooked over open coals contain even greater concentrations. Significant exposure to chrysene also occurs through the inhalation of mainstream and sidestream cigarette smoke (IARC, 1983). Occupational exposure to chrysene occurs during tar production or from coking plants, coal gasification, smoke houses and smoked meat production, road and roof-tarring, incinerators, and aluminum production.

2. METABOLISM AND DISPOSITION

2.1 ABSORPTION

Information on the absorption of chrysene in humans was not found. However, the detection of PAHs, including chrysene and its metabolites, in the urine of individuals who smoke (Becher, 1986), work in industrial environments having high atmospheric concentrations (Becher and Bjorseth, 1983), or use therapeutic coal-tar creams (Clonfero et al., 1986) provides indirect evidence of inhalation and dermal absorption. Animal studies show that oral, inhalation, and dermal absorption of chrysene does occur. Up to 74% of the administered dose of chrysene was recovered in the urine and feces of rats following oral, gavage or intratracheal instillation (Grimmer et al., 1988; Modica et al., 1983; Chang, 1943). Chrysene was detected in the urine of Osborne-Mendel rats following intrapulmonary instillation (Grimmer et al., 1988).

2.2 DISTRIBUTION

The distribution of chrysene has not been studied in humans. After oral treatment, peak concentrations of chrysene were found in rat blood and liver one hour after treatment. The concentration in the liver was 4-10 times higher than that in the blood (Bartosek et al., 1984; Modica et al., 1983). After redistribution, the tissue concentration of chrysene was related to the lipid content. The highest concentrations were found 3 hours after treatment in the adipose tissue followed in order by mammary tissue, brain, liver, and blood (Bartosek et al., 1984; Modica et al., 1983). The concentration of chrysene in tissues was not dose-related. This suggests saturation of absorption mechanisms.

2.3 METABOLISM

In vitro studies have established that Phase I metabolism of chrysene is mediated by the mixed function oxidase system. In rat liver preparations, the 1,2-, 3,4-, and 5,6-dihydrodiol, as well as the 1-, 3-, and 4-phenol derivatives were the primary metabolites formed (Sims, 1970; Nordquist et al., 1981; Jacob et al., 1982, 1987). These same metabolites were also identified in human (Weston et al., 1985) and mouse skin studies (Weston et al., 1985, Hodgson et al., 1983). Arene oxide intermediates of chrysene have not been isolated, although the metabolic formation of the dihydrodiols and phenols provides indirect evidence of their existence (Sims and Grover, 1974; 1981). In mouse and human skin preparations (Weston et al., 1985; Hodgson et al., 1986), hamster cells (Phillips et al., 1986) and rat liver preparations (Hodgson et al., 1985; Nordquist et al., 1981), further oxidation of the 1,2-dihydrodiol of chrysene by cytochrome P-450 yields 1,2-dihydrodiol-3,4-epoxide. Additional metabolism of chrysene to form 9-hydroxychrysene 1,2-dihydrodiol-3,4-oxide has not been detected in humans but has been reported to occur in mouse skin (Weston et al., 1985; Hodgson et al., 1986), hamster cells (Phillips et al., 1986) and rat liver preparations (Hodgson et al., 1985; Nordquist et al., 1981). In recent in vivo and in vitro studies, it was reported that chrysene can undergo bioalkylation and hydroxylation to form 6-methylchrysene and 6-hydroxymethylchrysene in rat liver cytosol and rat dorsal subcutaneous tissue (Myers and Flesher, 1991). Chrysene 1,2-dihydrodiol-3,4-epoxide and 9-hydroxychrysene 1,2-dihydrodiol-3,4-oxide are alkylating agents (Hodgson et al., 1985) and, along with metabolically activated chrysene 1,2-dihydrodiol, possess mutagenic activity in in vitro bacterial and mammalian cell systems (Wood et al., 1977; Wood et al., 1979, Cheung et al., 1993).

Phase II metabolism of chrysene results in the formation of sulfate ester and glucuronide conjugates of the dihydrodiols and phenols formed during Phase I metabolism (Sims and Grover, 1974, 1981). Glutathione conjugates, from the conjugation of diol- and triol-epoxides of chrysene, have also been identified (Hodgson et al., 1986; Robertson and Jernström, 1986).

2.4 EXCRETION

The excretion of chrysene has not been extensively studied. However, it is likely similar to the hepatobiliary excretion with elimination in the feces as reported for other PAHs (Schlede et al., 1970). In rats treated with 50 ug chrysene by gavage or with 400 or 800 ng chrysene by intratracheal instillation, 74%, 53%, and 73%, respectively, of the dose were excreted within 3 days of treatment (Grimmer et al., 1988). Approximately 90% of the excreted chrysene was recovered in the feces within 24 hours of treatment.

3. NONCARCINOGENIC HEALTH EFFECTS

3.1 ORAL EXPOSURES

3.1.1 Acute Toxicity

Information on the acute oral toxicity of chrysene to humans or animals is not available.

3.1.2 Subchronic Toxicity

Information on the subchronic oral toxicity of chrysene to humans or animals is not available.

3.1.3 Chronic Toxicity

Information on the chronic oral toxicity of chrysene to humans or animals is not available.

3.1.4 Dvelopmental and Reproductive Toxicology

Information on the developmental and reproductive toxicity of chrysene to humans or animals following oral exposure is not available.

3.1.5 Reference Dose

A Reference Dose for chrysene is unavailable at this time (EPA, 1994a,b).

3.2 INHALATION EXPOSURES

3.2.1 Acute Toxicity

Information on the acute inhalation toxicity of chrysene to humans or animals is not available.

3.2.2 Subchronic Toxicity

Information on the subchronic inhalation toxicity of chrysene to humans or animals is not available.

3.2.3 Chronic Toxicity

Information on the chronic inhalation toxicity of chrysene to humans or animals is not available.

3.2.4 Developmental and Reproductive Toxicity

Information on the developmental and reproductive toxicity of chrysene to humans or animals following inhalation exposure is not available.

3.2.5 Reference Concentration

A Reference Concentration for chrysene is unavailable at this time (EPA, 1994a,b).

3.3 OTHER ROUTES OF EXPOSURE

Information on the toxicity of chrysene to humans or animals from other routes of exposure is not available.

3.4 TARGET ORGANS/CRITICAL EFFECTS

3.4.1 Oral Exposures

3.4.1.1 Primary target organs

Studies that describe specific target organs of chrysene toxicity after oral treatments were not identified. However, inferences from the study of other PAHs can be made.

Immune System: Typically, carcinogenic PAHs induce immunosuppression in laboratory animals, whereas noncarcinogenic PAHs do not (Dean et al., 1986). Whether chrysene, a weakly carcinogenic PAH, induces immunosuppression after oral treatment is not known. White et al. (1985) has reported that antibody formation was not decreased in female B6C3F₁ mice that received chrysene by subcutaneous injection.

3.4.1.2 Other target organs

Other target organs following oral exposure to chrysene have not been described.

3.4.2 Inhalation Exposures

3.4.2.1 Primary target organs

Studies that describe specific target organs of chrysene toxicity after inhalation exposures were not identified. However, inferences from the study of other PAHs can be made.

Immune System: Typically, carcinogenic PAHs induce immunosuppression in laboratory animals, whereas noncarcinogenic PAHs do not (Dean et al., 1986). Whether chrysene, a weakly carcinogenic PAH, induces immunosuppression after inhalation exposure is not known. White et al. (1985) has reported that antibody formation was not decreased in female B6C3F₁ mice that received chrysene by subcutaneous injection.

3.4.2.2 Other Target Organs

Other target organs following inhalation exposure to chrysene have not been described.

4. CARCINOGENICITY

Numerous epidemiologic studies have been done that investigated the increased incidence of tumors in individuals exposed to PAH emissions from coke ovens and various tars (Lloyd, 1971, Redmond et al., 1972, Mazumdar et al., 1975; Hammond et al., 1976; Maclure and MacMahon, 1980). It must be remembered that these studies are conducted on mixtures containing other PAHs and known carcinogens from chemically unrelated species. Therefore, these studies do not provide direct evidence for the carcinogenicity of chrysene.

4.1 ORAL EXPOSURES

Information on the carcinogenicity of chrysene following oral exposure to humans or animals is not available.

4.2 INHALATION EXPOSURES

Information on the carcinogenicity of chrysene following inhalation exposure to humans or animals is not available. However, Wenzel-Hartung et al. (1990) studied the carcinogenicity of chrysene in female Osborne-Mendel rats that received a single intrapulmonary injection of 1 mg or 3 mg chrysene in a beeswax/trioctanoin vehicle. The median survival time of rats treated with chrysene was slightly decreased (96 weeks and 95 weeks for rats treated with 1 mg and 3 mg, respectively) when compared to control rats (100 weeks and 105 weeks for vehicle-treated and untreated rats, respectively). Dose-dependent increases in the incidence of lung carcinomas were observed in chrysene-treated rats [5/35 (14.3%) and 10/35 (28.6%) in rats treated with 1 mg and 3 mg chrysene, respectively]; however, the tumor types were not described. No tumors were observed in either group of control rats. Based on the results of this study, the authors calculated a carcinogenic potency of 0.03 for chrysene relative to benzo[a]pyrene (1.0) and an effective dose in 10% of the animals (ED₁₀) for carcinogenicity of 1.015 mg.

4.3 OTHER ROUTES OF EXPOSURE

Numerous bioassays assessing the carcinogenicity of chrysene in rats and mice following dermal, subcutaneous, and intraperitoneal treatment have been conducted. In general, these assays have established chrysene as a weak carcinogen relative to other PAHs. However, two metabolites of chrysene, chrysene-1,2-diol-3,4-epoxide and 9-hydroxychrysene 1,2-diol-3,4-oxide, have been shown to induce more tumors than chrysene, to be stronger alkylating agents, and to possess mutagenic activity in in vitro bacterial assays (Chang et al., 1983; Slaga et al., 1980; Buening et al., 1979; Levin et al., 1978).

In two carcinogenicity bioassays, chrysene administered by intraperitoneal injection produced a significant dose-related increase in the incidence of liver adenomas and carcinomas in treated CD-1 and BLU/Ha male mice (Wislocki et al., 1986; Buening et al., 1979). Additionally, chrysene increased the incidence of malignant lymphoma in low-dose male mice (160 ug/mouse) and lung adenomas/carcinomas in high-dose male mice (640 ug/mouse) relative to concurrent control CD-1 mice (Wislocki et al., 1986). Increased tumor incidences were not found in female mice in the Wislocki et al. (1986) or Buening et al. (1979) studies.

In numerous skin painting carcinogenicity bioassays, chrysene was shown to initiate skin papillomas and carcinomas in various mouse strains (C3H, ICR/Ha Swiss, Ha/ICR/Mil Swiss, CD-1, and Sencar) when treatments were followed by decahydronaphthalene, croton oil, or phorbol myristate acetate promotion (Van Duuren et al., 1966; Hecht et al., 1974; Levin et al., 1978; Wood et al., 1979; Wood et al., 1980). One study reported that chrysene is a complete carcinogen (possessing initiating and promoting activity) (Wynder and Hoffmann, 1959). In this study, application of 1% chrysene to the backs of female Swiss mice 3 times/week for the remainder of their life increased the incidence of skin papillomas and carcinomas. Since the purity of the chrysene was not reported, the tumors may have been induced by other PAHs or non-metabolic methyl derivatives of chrysene. Therefore, the results of this study are not conclusive.

4.4 EPA WEIGHT-OF-EVIDENCE

Classification: B2; probable human carcinogen (EPA, 1994a).
Basis: No human data were available, but sufficient animal bioassays show chrysene induces carcinomas and malignant lymphomas in mice following intraperitoneal injection and skin carcinomas following dermal exposure. Chrysene produced chromosomal abnormalities in hamster and mouse germ cells after gavage exposure and produced positive results in bacterial mutagenicity assays and transformed mammalian cells exposed in culture (EPA, 1990a).

4.5 CARCINOGENICITY SLOPE FACTORS

4.5.1 Oral

A slope factor for chrysene following oral exposure is unavailable (EPA, 1994a,b).

4.5.2 Inhalation

A slope factor for chrysene following inhalation exposure is unavailable (EPA, 1994a,b).

5. REFERENCES

ATSDR (Agency for Toxic Substances and Disease Registry). 1990. Toxicological Profile for Chrysene. Prepared by Clement Assoc., Inc. under contract 205-88-0608. U.S. Public Health Service. ATSDR/TP-88/11.

Bartosek, I., A. Guaitani, R. Modica, M. Fiume and R. Urso. 1984. Comparative kinetics of oral benz(a)anthracene, chrysene and triphenylene in rats: Study with hydrocarbon mixtures. Toxicol. Lett. 23: 333-339.

Becher, G. and A. Bjorseth. 1983. Determination of exposure to polycyclic aromatic hydrocarbons by analysis of human urine. Cancer Lett. 17: 301-311.

Becher, G. 1986. Determination of exposure to PAH by analysis of urine samples. In: Mechanisms in Tobacco Carcinogenesis, D. Hoffmann and C.C. Harris, Eds., Banbury Report, Cold Spring Harbor Laboratory, New York.

Budavari, S., M.J. O'Neil, A. Smith and P.E. Heckelman. 1989. In: The Merck Index, 11th ed., Merck & Co., Inc., Rahway, NJ, p. 350.

Buening, M.K., W. Levin, J.M. Karle, H. Yagi, D.M. Jerina, and A.H. Conney. 1979. Tumorigenicity of bay-region epoxides and other derivatives of chrysene and phenanthrene in newborn mice. Cancer Res. 39: 5063-5068.

Chang, R.L., W. Levin, A.W. Wood, et al. 1983. Tumorigenicity of enantiomers of chrysene 1,2-dihydrodiol and of the diastereomeric bay-region chrysene 1,2-diol-3,4-epoxides on mouse skin and in newborn mice. Cancer Res. 43: 192-196.

Chang, L.H. 1943. The fecal excretion of polycyclic hydrocarbons following their administration to the rat. J. Biol. Chem. 151: 93-99. (Cited in ATSDR, 1990)

Cheung, Y-L., T.J.B. Gray, and C. Ioannides. 1993. Mutagenicity of chrysene, its methyl and benzo derivatives, and their interactions with cytochromes P-450 and the Ah-receptor; relevance to their carcinogenic potency. Toxicology 81: 69-86.

Clonfero, E., M. Zordan, D. Cottica, et al. 1986. Mutagenic activity and polycyclic aromatic hydrocarbon levels in urine of humans exposed to therapeutical coal tar. Carcinogenesis 7: 819-823.

Dean, J.H., M. J. Murray and E.C. Ward. 1986. Toxic Responses of the Immune System. In: Casarett and Doull's Toxicology: The Basic Science of Poisons, Third Edition, C.D. Klaassen, M.O. Amdur and J. Doull, Eds., Macmillian Publishing Co., New York, NY, pp. 271-272.

Grimmer, G., H. Brune, G. Dettbarn, et al. 1988. Urinary and faecal excretion of chrysene and chrysene metabolites by rats after oral, intraperitoneal, intratracheal or intrapulmonary application. Arch. Toxicol. 62: 401-405.

Hammond, E.D., I.J. Selikoff, P.O. Lawther, and H. Seidman. 1976. Inhalation of B[a]P and cancer in man. Ann. NY Acad. Sci. 271: 116-124. (Cited in ATSDR, 1990)

Hecht, S.S., W. E. Bondinell and D. Hoffmann. 1974. Chrysene and methyl chrysenes: Presence in tobacco smoke and carcinogenicity. J. Natl. Cancer Inst. 53: 1121-1133.

Hodgson, R.M., A. Weston, and P.L. Grover. 1983. Metabolic activation of chrysene in mouse skin: Evidence for the involvement of triol-epoxide. Carcinogenesis 4: 1639-1643.

Hodgson, R.M., A. Seidel, W. Bochnitschek, H.R. Glatt, F. Oesch, and P.L. Grover. 1985. The formation of 9-hydroxychrysene-1,2-diol as an intermediate in the metabolic activation of chrysene. Carcinogenesis 6: 135-139.

Hodgson, R.M., A. Seidel, W. Bochnitschek, H.R. Glatt, F. Oesch, and P.L. Grover. 1986. Metabolism of the bay-region diol-epoxide of chrysene to a triol-epoxide and the enzyme-catalyzed conjugation of these epoxides with glutathione. Carcinogenesis 7: 2095-2098.

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Jacob, J., A. Schmoldt and G. Grimmer. 1982. Formation of carcinogenic and inactive chrysene metabolites by rat liver microsomes of various monooxygenase activities. Arch. Toxicol. 51: 255-265.

Jacob, J., A. Schmoldt, M. Hamann, G. Raab, and G. Grimmer. 1987. Monooxygenase induction by various xenobiotics and its influence on rat liver microsomal metabolism of chrysene in comparison to benz[a]anthracene. Cancer Lett. 34: 91-102.

Levin, W., A.W. Wood, R.L. Chang, et al. 1978. Evidence for bay region activation of chrysene 1,2-dihydrodiol to an ultimate carcinogen. Cancer Res. 38: 1831-1834.

Lloyd, J.W. 1971. Long-term mortality study of steel workers. V. Respiratory cancer in coke plant workers. J. Occup. Med. 13: 53-68. (Cited in ATSDR, 1990)

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Mazumdar, S., C.K. Redmond, W. Sollecito, and N. Sussman. 1975. An epidemiological study of exposure to coal tar pitch volatiles among coke oven workers. J. Air Pollut. Control. Assoc. 25: 382-389. (Cited in ATSDR, 1990)

Modica, R., M. Fiume, A. Guaitani and I. Bartosek. 1983. Comparative kinetics of benz(a)anthracene, chrysene and triphenylene in rats after oral administration. I. Study with single compounds. Toxicol. Lett. 18: 103-109.

Myers, S.R. and J.W. Flesher. 1991. Metabolism of chrysene, 5-methylchrysene, 6-methylchrysene and 5,6-dimethylchrysene in rat liver cytosol, in vitro, and in rat subcutaneous tissue, in vivo. Chem.-Biol. Interactions 77: 203-221.

Nordquist, M., D.R. Thakker, K.P. Vyas, et al. 1981. Metabolism of chrysene and phenanthrene to bay-region diol epoxides by rat liver enzymes. Mol. Pharmacol. 19: 168-178.

Phillips, D.H., H. R. Glatt, A. Seidel, W. Bochnitschek, F. Oesch and P.L. Grober. 1986. Mutagenic potential of DNA adducts formed by diol-epoxides, triol-epoxides, and the K-region epoxide of chrysene in mammalian cells. Carcinogenesis 7: 1739-1743.

Redmond, C.K., CA. Ciocco, J.W. Lloyd, and H.W. Rush. 1972. Long-term mortality study of steelworkers. VI. Mortality from malignant neoplasms among coke oven workers. J. Occup. Med. 14: 621-629. (Cited in ATSDR, 1990)

Robertson, I.G.C. and B. Jernström. 1986. The enzymatic conjugation of glutathione with bay-region diol-epoxides of benzo[a]pyrene, benz[a]anthracene, and chrysene. Carcinogenesis 7: 1633-1636.

Schlede, E., R. Kuntzman, S. Haber, and A.H. Conney. 1970. Effect of enzyme induction on the metabolism and tissue distribution of benzo[a]pyrene. Cancer Res. 30: 2898-2904.

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Wenzel-Hartung, R., H. Brune, G. Grimmer, P. Germann, J. Timm, and W. Wosniok. 1990. Evaluation of the carcinogenic potency of 4 environmental polycyclic aromatic compounds following intrapulmonary application in rats. Exp. Pathol. (Jena) 40: 221-227.

Weston, A., R.M. Hodgson, A.J. Hewer, R. Kuroda, and P.L. Grover. 1985. Comparative studies of the metabolic activation of chrysene in rodent and human skin. Chem. Biol. Interact. 54: 223-242.

White, K.L., H.H. Lysy, and M.P. Holsapple. 1985. Immunosuppression by polycyclic aromatic hydrocarbons: A structure-activity relationship in B6C3F₁ and DBA/2 mice. Immunopharmacology 9: 155-164.

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.

Wood, A.W., W. Levin, D. Ryan, et al. 1977. High mutagenicity of metabolically activated chrysene 1,2-dihydrodiol: Evidence for bay region activation of chrysene. Biochem. Biophys. Res. Commun. 78: 847-854.

Wood, A.W., W. Levin, R.L. Chang, et al. 1979. Mutagenicity and tumorigenicity of phenanthrene and chrysene epoxides and diol epoxides. Cancer Res. 39: 4069-4077.

Wood, A.W., R.L. Chang, W. Levin, 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. Hoffmann. 1959. A study of tobacco carcinogenesis. VII. The role of higher polycyclic hydrocarbons. Cancer 12: 1079-1086. Retrieve Toxicity Profiles Condensed Version

Last Updated 8/29/97