#ls ¦¦¦¦¦ifcSE United States ¦¦¦¦BiiiiH Environmental Protection 1=1 JF m Agency EPA/690/R-01/001F Final 11-30-2001 Provisional Peer Reviewed Toxicity Values for Benzo [k] fluoranthene (CASRN 207-08-9) Derivation of an Oral RfD Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ------- Acronyms and Abbreviations bw body weight cc cubic centimeters CD Caesarean Delivered CERCLA Comprehensive Environmental Response, Compensation and Liability Act of 1980 CNS central nervous system cu.m cubic meter DWEL Drinking Water Equivalent Level FEL frank-effect level FIFRA Federal Insecticide, Fungicide, and Rodenticide Act g grams GI gastrointestinal HEC human equivalent concentration Hgb hemoglobin i.m. intramuscular i.p. intraperitoneal IRIS Integrated Risk Information System IUR inhalation unit risk i.v. intravenous kg kilogram L liter LEL lowest-effect level LOAEL lowest-observed-adverse-effect level LOAEL(ADJ) LOAEL adjusted to continuous exposure duration LOAEL(HEC) LOAEL adjusted for dosimetric differences across species to a human m meter MCL maximum contaminant level MCLG maximum contaminant level goal MF modifying factor mg milligram mg/kg milligrams per kilogram mg/L milligrams per liter MRL minimal risk level MTD maximum tolerated dose MTL median threshold limit 1 ------- NAAQS National Ambient Air Quality Standards NOAEL no-observed-adverse-effect level NOAEL(ADJ) NOAEL adjusted to continuous exposure duration NOAEL(HEC) NOAEL adjusted for dosimetric differences across species to a human NOEL no-observed-effect level OSF oral slope factor p-IUR provisional inhalation unit risk p-OSF provisional oral slope factor p-RfC provisional inhalation reference concentration p-RfD provisional oral reference dose PBPK physiologically based pharmacokinetic PPb parts per billion ppm parts per million PPRTV Provisional Peer Reviewed Toxicity Value RBC red blood cell(s) RCRA Resource Conservation and Recovery Act RDDR Regional deposited dose ratio (for the indicated lung region) REL relative exposure level RfC inhalation reference concentration RfD oral reference dose RGDR Regional gas dose ratio (for the indicated lung region) s.c. subcutaneous SCE sister chromatid exchange SDWA Safe Drinking Water Act sq.cm. square centimeters TSCA Toxic Substances Control Act UF uncertainty factor microgram (.imol micromoles voc volatile organic compound 11 ------- 11-30-2001 PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR BENZO [k] FLUORANTHENE (CASRN 207-08-9) Derivation of an Oral RfD Background On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human health toxicity values for Superfund risk assessments, establishing the following three tiers as the new hierarchy: 1. EPA's Integrated Risk Information System (IRIS). 2. Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund Program. 3. Other (peer-reviewed) toxicity values, including: ~ Minimal Risk Levels produced by the Agency for Toxic Substances and Disease Registry (ATSDR), ~ California Environmental Protection Agency (CalEPA) values, and ~ EPA Health Effects Assessment Summary Table (HEAST) values. A PPRTV is defined as a toxicity value derived for use in the Superfund Program when such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are developed according to a Standard Operating Procedure (SOP) and are derived after a review of the relevant scientific literature using the same methods, sources of data, and Agency guidance for value derivation generally used by the EPA IRIS Program. All provisional toxicity values receive internal review by two EPA scientists and external peer review by three independently selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the multi-program consensus review provided for IRIS values. This is because IRIS values are generally intended to be used in all EPA programs, while PPRTVs are developed specifically for the Superfund Program. Because new information becomes available and scientific methods improve over time, PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS value for a specific chemical becomes available for Agency review, the analogous PPRTV for that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a PPRTV cannot be derived based on inadequate data. 1 ------- 11-30-2001 Disclaimers Users of this document should first check to see if any IRIS values exist for the chemical of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional Superfund and RCRA program offices are advised to carefully review the information provided in this document to ensure that the PPRTVs used are appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically updated; therefore, users should ensure that the values contained in the PPRTV are current at the time of use. It is important to remember that a provisional value alone tells very little about the adverse effects of a chemical or the quality of evidence on which the value is based. Therefore, users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of Research and Development's National Center for Environmental Assessment, Superfund Health Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may choose of their own initiative to use these PPRTVs are advised that Superfund resources will not generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund Program. Questions Regarding PPRTVs Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed to the EPA Office of Research and Development's National Center for Environmental Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI. INTRODUCTION An RfD for benzo[k]fluoranthene (B[k]F) is not available on IRIS (U.S. EPA, 2001), in the HEAST (U.S. EPA, 1997), or in the Drinking Water Regulations and Health Advisory list (U.S. EPA, 2000), and the chemical was never reviewed by the RfD/RfC Work Group (U.S. EPA, 1995). A HEEP for Benzo[k]fluoranthene (U.S. EPA, 1987), a HEA for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1984), a Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1991a), and a Multimedia Document for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1992) did not derive an RfD for B[k]F. No other pertinent EPA documents were located in the CARA lists (U.S. EPA, 1991b, 1994). The ATSDR (1995) Toxicological Profile for Polycyclic Aromatic Hydrocarbons declined to derive oral MRLs for B[k]F due to lack of suitable data. The NTP (2001) Management Status Report, WHO (1997), the IARC monograph series (IARC,1973, 1983, 1987), and Patty's Toxicology (Warshawsky, 2001) were searched for relevant information. Literature searches of the following databases were conducted from 1989 to April 2001 for relevant studies: TOXLINE, MEDLINE, TSCATS, 2 ------- 11-30-2001 GENETOX, HSDB, CANCERLIT, CCRIS, EMIC/EMICBACK, DART/ETICBACK, and RTECS. REVIEW OF THE PERTINENT LITERATURE Human Studies The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984, 1991a, 1992; WHO, 1997) found no available human data regarding the toxicity of B[k]F following oral exposure. The literature search identified no new studies regarding the toxicity of B[k]F in humans following oral exposure. Animal Studies The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984, 1991a, 1992; WHO, 1997) found no available animal data that could be used as the basis for derivation of an RfD for B[k]F. B[k]F suppressed the antibody response in a dose-related manner in an acute study in which male C57BL/6J mice (2/group) were administered B[k]F in corn oil as a single oral gavage at 0.1, 1.0, 10 or 100 mg/kg (Silkworth et al., 1995). Twelve hours after treatment, the mice were immunized i.v. with sheep erythrocytes. The splenic primary direct (IgM) antibody response was evaluated 5 days after immunization using a plaque assay. At the highest dose, B[k]F suppressed the immune response by approximately 94% of control. However, this study is of inadequate duration for derivation of an RfD. FEASIBILITY OF DERIVING A PROVISIONAL RfD FOR BENZO [k] FLUORANTHENE A provisional RfD for B[k]F cannot be derived because of the lack of human and adequate animal oral data. REFERENCES ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for Polycyclic Aromatic Hydrocarbons (PAH). U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA. IARC (International Agency for Research on Cancer). 1973. IARC Monographs on the Evaluation of Carcinogenic Risk of the Chemical to Man. Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic Compounds. Vol. 3, p. 45-68. 3 ------- 11-30-2001 IARC (International Agency for Research on Cancer). 1983. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Polynuclear Aromatic Compounds. Part 1. Chemical, Environmental and Experimental Data. Vol. 32, p. 135. IARC (International Agency for Research on Cancer). 1987. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Suppl. 7. p. 58. NTP (National Toxicology Program). 2001. Management Status Report. Examined April 9, 2001. Online, http://ntp-server.niehs.nih.gov/main pages/NTP ALL STDY PG.html Silkworth, J.B., T. Lipinskas and C.R. Stoner. 1995. Immunosuppressive potential of several polycyclic aromatic hydrocarbons (PAH) found at a superfund site: New model used to evaluate additive interactions between benzo[a]pyrene and TCDD. Toxicology. 105: 375-386. U.S. EPA. 1984. Health Effects Assessment for Polycyclic Aromatic Hydrocarbons (PAH). 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. EPA/540/1-86/013. U.S. EPA. 1987. Health and Environmental Effects Profile for Benzo[k]fluoranthene. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1991a. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAH). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. U.S. EPA. 1991b. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. April 1991. U.S. EPA. 1992. Multimedia Document for Polycyclic Aromatic Hydrocarbons. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH. August. U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. December 1994. U.S. EPA. 1995. Monthly Status Report of RfD/RfC and CRAVE Work Groups (as of 09/01/95). Office of Research and Development, National Center for Environmental Assessment, Washington, DC. 4 ------- 11-30-2001 U.S. EPA. 1997. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update. Prepared by the Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. July 1997. EPA-540-R-97-036. NTIS PB97-921199. U.S. EPA. 2000. Drinking Water Regulations and Health Advisories. Summer 2000. Office of Water, Washington, DC. Examined April 9, 2001. Online. http://www.epa. gov/ ost/drinking/ standards/ U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and Development, National Center for Environmental Assessment, Washington, DC. Examined April 9, 2001. Online, http://www.epa.gov/iris/ Warshawsky, D. 2001. Polycyclic and heterocyclic aromatic hydrocarbons. In: Patty's Toxicology, 5th ed., E. Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley and Sons, New York. p. 303-382. WHO (World Health Organization). 1997. Environmental Health Criteria. 202: Selected Non-heterocyclic Polycyclic Aromatic Hydrocarbons. International Programme on Chemical Safety, Geneva, Switzerland. 5 ------- 11-30-2001 Provisional Peer Reviewed Toxicity Values for Benzo [k] fluoranthene (CASRN 207-08-9) Derivation of an Oral Slope Factor Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ------- Acronyms and Abbreviations bw body weight cc cubic centimeters CD Caesarean Delivered CERCLA Comprehensive Environmental Response, Compensation and Liability Act of 1980 CNS central nervous system cu.m cubic meter DWEL Drinking Water Equivalent Level FEL frank-effect level FIFRA Federal Insecticide, Fungicide, and Rodenticide Act g grams GI gastrointestinal HEC human equivalent concentration Hgb hemoglobin i.m. intramuscular i.p. intraperitoneal IRIS Integrated Risk Information System IUR inhalation unit risk i.v. intravenous kg kilogram L liter LEL lowest-effect level LOAEL lowest-observed-adverse-effect level LOAEL(ADJ) LOAEL adjusted to continuous exposure duration LOAEL(HEC) LOAEL adjusted for dosimetric differences across species to a human m meter MCL maximum contaminant level MCLG maximum contaminant level goal MF modifying factor mg milligram mg/kg milligrams per kilogram mg/L milligrams per liter MRL minimal risk level MTD maximum tolerated dose MTL median threshold limit 1 ------- NAAQS National Ambient Air Quality Standards NOAEL no-observed-adverse-effect level NOAEL(ADJ) NOAEL adjusted to continuous exposure duration NOAEL(HEC) NOAEL adjusted for dosimetric differences across species to a human NOEL no-observed-effect level OSF oral slope factor p-IUR provisional inhalation unit risk p-OSF provisional oral slope factor p-RfC provisional inhalation reference concentration p-RfD provisional oral reference dose PBPK physiologically based pharmacokinetic PPb parts per billion ppm parts per million PPRTV Provisional Peer Reviewed Toxicity Value RBC red blood cell(s) RCRA Resource Conservation and Recovery Act RDDR Regional deposited dose ratio (for the indicated lung region) REL relative exposure level RfC inhalation reference concentration RfD oral reference dose RGDR Regional gas dose ratio (for the indicated lung region) s.c. subcutaneous SCE sister chromatid exchange SDWA Safe Drinking Water Act sq.cm. square centimeters TSCA Toxic Substances Control Act UF uncertainty factor microgram (.imol micromoles voc volatile organic compound 11 ------- 11-30-2001 PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR BENZO [k] FLUORANTHENE (CASRN 207-08-9) Derivation of an Oral Slope Factor Background On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human health toxicity values for Superfund risk assessments, establishing the following three tiers as the new hierarchy: 1. EPA's Integrated Risk Information System (IRIS). 2. Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund Program. 3. Other (peer-reviewed) toxicity values, including: ~ Minimal Risk Levels produced by the Agency for Toxic Substances and Disease Registry (ATSDR), ~ California Environmental Protection Agency (CalEPA) values, and ~ EPA Health Effects Assessment Summary Table (HEAST) values. A PPRTV is defined as a toxicity value derived for use in the Superfund Program when such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are developed according to a Standard Operating Procedure (SOP) and are derived after a review of the relevant scientific literature using the same methods, sources of data, and Agency guidance for value derivation generally used by the EPA IRIS Program. All provisional toxicity values receive internal review by two EPA scientists and external peer review by three independently selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the multi-program consensus review provided for IRIS values. This is because IRIS values are generally intended to be used in all EPA programs, while PPRTVs are developed specifically for the Superfund Program. Because new information becomes available and scientific methods improve over time, PPRTVs are reviewed on a five-year basis and updated into the active database. Once an IRIS value for a specific chemical becomes available for Agency review, the analogous PPRTV for that same chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a PPRTV cannot be derived based on inadequate data. 1 ------- 11-30-2001 Disclaimers Users of this document should first check to see if any IRIS values exist for the chemical of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional Superfund and RCRA program offices are advised to carefully review the information provided in this document to ensure that the PPRTVs used are appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically updated; therefore, users should ensure that the values contained in the PPRTV are current at the time of use. It is important to remember that a provisional value alone tells very little about the adverse effects of a chemical or the quality of evidence on which the value is based. Therefore, users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of Research and Development's National Center for Environmental Assessment, Superfund Health Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may choose of their own initiative to use these PPRTVs are advised that Superfund resources will not generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund Program. Questions Regarding PPRTVs Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed to the EPA Office of Research and Development's National Center for Environmental Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI. INTRODUCTION A carcinogenicity assessment for benzo[k]fluoranthene (B[k]F) is available on IRIS (U.S. EPA, 2001). This assessment, verified 02/07/1990, was based on a Carcinogen Assessment of Coke Oven Emissions (U.S. EPA, 1984a), a HEEP for Benzo[k]fluoranthene (U.S. EPA, 1987), and a Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAH) (U.S. EPA, 1991a). B[k]F was assigned to weight-of-evidence Group B2, probable human carcinogen, based on increased incidences of epidermoid carcinomas in a lung implantation study in rats (Deutsch-Wenzel et al., 1983) and skin tumors in dermal application studies in mice (Amin et al., 1985; LaVoie et al., 1982; Van Duuren et al., 1966). Supporting data from genotoxicity tests included positive results for mutations in bacteria (Hermann et al., 1980; LaVoie et al., 1980). It was noted that B[k]F is a component of mixtures that are known to produce cancer in humans, although there are no human data that specifically link B[k]F with human cancers. However, due to the lack of adequate oral data for B[k]F, an oral slope factor was not included on IRIS (U.S. EPA, 2001). 2 ------- 11-30-2001 U.S. EPA (1991a) explored the use of a relative potency factor approach to derive slope factors for B[k]F and other PAHs from the existing slope factor for benzo[a]pyrene. However, the CRAVE Work Group decided not to include relative potency information for PAHs on IRIS because the methodology was not sufficiently developed, the underlying database had not been sufficiently reviewed, and surrounding issues (e.g., route-to-route extrapolation) had not received sufficient peer review (U.S. EPA, 1994a). The HEAST (U.S. EPA, 1997) reports the availability of the weight-of-evidence assessment on IRIS, but contains no additional information. The Drinking Water Standards and Health Advisories list (U.S. EPA, 2000) includes the cancer group B2 designation for B[k]F, but does not include additional cancer risk information. A Health Effects Assessment for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1984b) was located, but no relevant documents specific to B[k]F were found in the CARA lists (U.S. EPA, 1991b, 1994b). The International Agency for Research on Cancer (IARC, 1973, 1983, 1987) evaluated B[k]F for carcinogenicity and placed the chemical in Group 2B (possible human carcinogen), finding that there is sufficient evidence that B[k]F is carcinogenic to experimental animals and that the chemical was mutagenic to Salmonella typhimurium in the presence of an exogenous metabolic system. CalEPA derived an oral slope factor for B[k]F, but it is based on a relative potency factor approach (CalEPA, 1999). ACGIH (2000) has not assessed the carcinogenicity of B[k]F. The NTP (2001) Management Status Report, Patty's Toxicology (Warshawsky, 2001), WHO (1997), the ATSDR (1995) Toxicological Profile for Polycyclic Aromatic Hydrocarbons, and a Multimedia Document for Polycyclic Aromatic Hydrocarbons (U.S. EPA, 1992) were searched for relevant information. Literature searches of the following databases were conducted from 1989 to April 2001 for relevant studies: TOXLINE, MEDLINE, TSCATS, GENETOX, HSDB, CANCERLIT, CCRIS, EMIC/EMICBACK, DART/ETICBACK, and RTECS. REVIEW OF THE PERTINENT LITERATURE Human Studies The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984b, 1987, 1991a, 1992; WHO, 1997) found no available human data regarding the carcinogenic potential of B[k]F. The literature search identified no new studies regarding carcinogenicity of B[k]F in humans. Animal Studies The most recent reviews (ATSDR, 1995; IARC, 1983, 1987; U.S. EPA, 1984b, 1987, 1991a, 1992; WHO, 1997) found no available animal oral data regarding the carcinogenic potential of B[k]F. The literature search identified no new studies regarding carcinogenicity of B[k]F in animals. 3 ------- 11-30-2001 Other Studies The literature search identified the following relevant data for carcinogenicity of B[k]F not included on IRIS. No statistically significant increase in sister chromatid exchange or micronucleus induction was observed in mice orally gavaged with B[k]F suspended in sunflower oil (100 mg/kg), whereas the number of SCEs/metaphase (but not micronucleus induction) was statistically significantly increased in animals given a single intraperitoneal injection of B[k]F (100 mg/kg) (Bryant et al., 1993). B[k]F formed DNA adducts in vitro in rat hepatocytes (Topinka et al., 1998). B[k]F suspended in corn oil, administered to male C57BL/6J mice as a single oral gavage at 0.1, 1.0, 10 or 100 mg/kg, suppressed the antibody response to sheep erythrocyte immunization in a dose-related manner; at the highest dose, suppression was approximately 94% of control response (Silkworth et al., 1995). FEASIBILITY OF DERIVING A PROVISIONAL ORAL SLOPE FACTOR FOR BENZO [k] FLUORANTHENE A provisional oral slope factor for B[k]F cannot be derived because human and animal oral cancer data are lacking. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 2000. TLVs® and BEIs®: Threshold Limit Values for Chemical Substances and Physical Agents, Biological Exposure Indices. Cincinnati, OH. Amin, S., N. Hussain, G. Balanikas, K. Huie and S.S. Hecht. 1985. Mutagenicity and tumor initiating activity of methylated benzo[k]fluoranthenes. Cancer Lett. 26: 343-347. ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for Polycyclic Aromatic Hydrocarbons (PAH). U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA. Bryant, M.F., P. Kwanyuen, G.L. Erexson and A.D. Kligerman. 1993. Analyses of cytogenetic damage in mouse peripheral blood lymphocytes after either intraperitoneal or gavage exposure to five polycyclic aromatic hydrocarbons. Environ. Mol. Mutagen. 21: 9. [Abstract] CalEPA (California Environmental Protection Agency). 1999. Air Toxics Hot Spots Program Risk Assessment Guidelines. Part II: Technical Support Document for Describing Available Cancer Potency Factors. April 1999. Office of Environmental Health Hazard Assessment. Online, http://www.oehha.ca.gov/air/cancer guide/hsca2.html 4 ------- 11-30-2001 Deutsch-Wenzel, R., H. Brune, G. Grimmer et al. 1983. Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons. J. Natl. Cancer Inst. 71: 539-544. (Cited in ATSDR, 1995) Hermann, M., J.P. Durand, J.M. Charpentier et al. 1980. Correlations of mutagenic activity with polynuclear aromatic hydrocarbon content of various mineral oils. In: Polynuclear Aromatic Hydrocarbons: Chemical Analysis and Biological Fate, M. Cooke and A.J. Dennis, Ed. Battelle Press, Columbus, OH. p. 899-916. (Cited in WHO, 1997) IARC (International Agency for Research on Cancer). 1973. IARC Monographs on the Evaluation of Carcinogenic Risk of the Chemical to Man. Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic Compounds. Vol. 3, p. 69. IARC (International Agency for Research on Cancer). 1983. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Polynuclear Aromatic Compounds. Parti. Chemical, Environmental and Experimental Data. Vol.32, p. 147. IARC (International Agency for Research on Cancer). 1987. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Suppl. 7. p. 58. LaVoie, E.J., L. Tulley, V. Bedenko and D. Hoffmann. 1980. Mutagenicity, tumor initiating activity, and metabolism of tricyclic polynuclear aromatic hydrocarbons. In: Polynuclear Aromatic Hydrocarbons: Chemistry and Biological Effects, A. Bjorseth and A.J. Dennis, Ed. Battelle Press, Columbus, OH. p. 1041-1057. (Cited in WHO, 1997) LaVoie, E.J., S. Amin., S.S. Hecht et al. 1982. Tumor initiating activity of dihydrodiols of benzo[b]fluoranthene, benzo[j]fluoranthene and benzo[k]fluoranthene. Carcinogenesis. 3: 49-52. (Cited in WHO, 1997) NTP (National Toxicology Program). 2001. Management Status Report. Examined April 9, 2001. Online, http://ntp-server.niehs.nih.gov/main pages/NTP ALL STDY PG.html Silkworth, J.B., T. Lipinskas and C.R. Stoner. 1995. Immunosuppressive potential of several polycyclic aromatic hydrocarbons (PAH) found at a superfund site: New model used to evaluate additive interactions between benzo[a]pyrene and TCDD. Toxicology. 105: 375-386. Topinka, J., L.R. Schwarz, F. Kiefer et al. 1998. DNA adduct formation in mammalian cell cultures by polycyclic aromatic hydrocarbons (PAH) and nitro-PAH in coke oven emission extract. Mutat. Res. 419: 91-105. 5 ------- 11-30-2001 U.S. EPA. 1984a. Carcinogen Assessment of Coke Oven Emissions. Office of Health and Environmental Assessment, Washington, DC. U.S. EPA. 1984b. Health Effects Assessment for Polycyclic Aromatic Hydrocarbons (PAH). 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. EPA/540/1-86/013. U.S. EPA. 1987. Health and Environmental Effects Profile for Benzo[k]fluoranthene. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1991a. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAH). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Drinking Water, Washington, DC. U.S. EPA. 1991b. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. April 1991. U.S. EPA. 1992. Multimedia Document for Polycyclic Aromatic Hydrocarbons. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH. August. U.S. EPA. 1994a. CRAVE meeting notes (February 1994) on polycyclic aromatic hydrocarbons. Reported May 11, 1994. Available from National Center for Environmental Assessment, Washington, DC. U.S. EPA. 1994b. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. December 1994. U.S. EPA. 1997. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update. Prepared by the Office of Research and Development, National Center for Environmental Assessment, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. July 1997. EPA/540/R-97/036. NTIS PB97-921199. U.S. EPA. 2000. Drinking Water Regulations and Health Advisories. Summer 2000. Office of Water, Washington, DC. Examined April 9, 2001. Online. http://www.epa. gov/ ost/drinking/ standards/ 6 ------- 11-30-2001 U.S. EPA. 2001. Integrated Risk Information System (IRIS). Office of Research and Development, National Center for Environmental Assessment, Washington, DC. Examined April 9, 2001. Online, http://www.epa.gov/iris/ Van Duuren, B.L., A. Sivak, A. Segal, L. Orris and L. Langseth. 1966. The tumor-promoting agents of tobacco leaf and tobacco smoke condensate. J. Natl. Cancer Inst. 37:519-526. (Cited in WHO, 1997) Warshawsky, D. 2001. Polycyclic and heterocyclic aromatic hydrocarbons. In: Patty's Toxicology, 5th ed., E. Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley and Sons, New York. p. 303-382. WHO (World Health Organization). 1997. Environmental Health Criteria. 202: Selected Non-heterocyclic Polycyclic Aromatic Hydrocarbons. International Programme on Chemical Safety, Geneva, Switzerland. 7 ------- |