TECHNICAL REPORT DATA (fteue n*d Instructions on the revert* btfort compienngj 1 REPORT NO. EPA/600/5-88/040 3. RECIPIENT'S ACCESSION NO PB88-182860/AS 4. TITLE AND SUBTITLE Health Effects Assessment for Fluorenes 5. REPORT DATE «. PERFORMING ORGANIZATION CODE 7 AUTHOH(S) I. PERFORMING ORGANIZATION REPORT NO 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT NO. 11. CONTRACT/GRANT NO. 12. SPONSORING AGENCY NAME AND ADDRESS 13. TYPE OF REPORT AND PERIOD COVERED Environmental Criteria and Assessment Office Office of Research and Development U.S. Environmental Protection Agency Cincinnati. OH 45268 14. SPONSORING AGENCY CODE EPA/600/22 15. SUPPLEMENTARY NOTES 16. ABSTRACT This report summarizes and evaluates information relevant to a preliminary interim assessment of adverse health effects associated with specific chemicals or compounds. The Office of Emergency and Remedial Response (Superfund) uses these documents in preparing cost-benefit analyses under Executive Order 32991 for decision-making under CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in this document should be considered as preliminary and reflect limited resources allocated to this project. The intent in these assessments is to suggest acceptable exposure levels whenever sufficient data are available. The interim values presented reflect the ""elative degree of hazard associated with exposure or risk to the chemical(s) addressed. Whenever possible, two categories of values have been estimated for systemic toxicants (toxicants for which cancer is not the endpoint of concern). The first, RfDs or subchronic reference dose, is an estimate of an exposure level that would not be expected to cause adverse effects when exposure occurs during a limited time interval. The RfD is an estimate of an exposure level that would not be expected to cause adverse effects when exposure occurs for a significant portion of the lifespan. For compounds for which there is sufficient evidence of carcinogenicity, qi*s have been computed, if appropriate, based on oral and inhalation data if available. 7. KEY WORDS AND DOCUMENT ANALYSIS DESCRIPTORS b.lOENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group 18. DISTRIBUTION STATEMENT Public 1». SECURITY CLASS (This Report/ Unclassified 21. NO. Of PAGES 20. SECURITY CLASS (Tttiipagei Unclassified 22. PRICE EPA Form 2220.1 (Re*. 4-77) PREVIOUS COITION is OBSOLETE ------- EPA/600/8-88/040 May, 1987 HEALTH EFFECTS ASSESSMENT FOR FLUORENES ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT OFFICE OF RESEARCH AND DEVELOPMENT U.S. ENVIRONMENTAL PROTECTION AGENCY CINCINNATI, OH 45268 ------- DISCLAIMER This document has been reviewed In accordance with the U.S. Environmental Protection Agency's peer and administrative review policies and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. 11 ------- PREFACE This report summarizes and evaluates Information relevant to a prelimi- nary Interim assessment of adverse health effects associated with Fluorenes. Pertinent toxlcologlc and environmental data were located through online literature searches of the TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases. The basic literature searched supporting this document 1s current up to May 1986. Secondary sources of Information have also been relied upon In the preparation of this report and represent large-scale health assessment efforts that entail extens.lve peer and Agency review. The following Office of Health and Environmental Assessment (OHEA) sources have been extensively utilized: U.S. EPA. 1980a. Ambient Water Quality Criteria for Fluoranthene. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Water Regulations and Standards, Washington, DC. EPA 440/5-80-049. NTIS PB81-117608. U.S. EPA. 1980b. Ambient Water Quality Criteria for Polynuclear Aromatic Hydrocarbons. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Water Regulations and Standards, Washington, DC. €PA 440/5-80-069. NITS PB81-117806. U.S. EPA. 1980c. Hazard Profile for Polynuclear Aromatic Hydro- carbons (PAH). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington, DC. U.S. EPA. 1983a. Reportable Quantity Document for Fluorene. 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. 1983b. Reportable Quantity Document for Fluoranthene. 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. 111 ------- ABSTRACT Oral and Inhalation toxldty data were not sufficient to derive risk assessment values for fluorene or benzo( j ,k)fluorene. Short-term test data Indicate that benzofluorene has the potential to be carcinogenic In humans. The available short-term data for fluorene, however 1s Insufficient to address Us carcinogenic potential. 1v ------- ACKNOWLEDGEMENTS The Initial draft of this report was prepared by Syracuse Research Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen Blackburn were the Technical Project Monitors and John Helms (Office of Toxic Substances) was the Project Officer. The final documents In this series were prepared for the Office of Emergency and Remedial Response, Washington, DC. Scientists from the following U.S. EPA offices provided review comments for this document series: Environmental Criteria and Assessment Office, Cincinnati, OH Carcinogen Assessment Group Office of A1r Quality Planning and Standards Office of Solid Waste Office of Toxic Substances Office of Drinking Water Editorial review for the document series was provided by the following: Judith Olsen and Erma Durden Environmental Criteria and Assessment Office Cincinnati, OH Technical support services for the document series was provided by the following: Bette Zwayer, Jacky Bohanon and K1m Davidson Environmental Criteria and Assessment Office Cincinnati, OH ------- TABLE OF CONTENTS 1 ? T 4 s ft 7. ENVIRONMENTAL CHEMISTRY AND FATE ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . . TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS CARCINOGENICITY 4.1. OTHER RELEVANT DATA 4.2. WEIGHT OF EVIDENCE REGULATORY STANDARDS AND CRITERIA RECOMMENDATIONS REFERENCES Page . . 1 5 . . . 6 . . 7 . . . 7 . . . 10 . . . 11 . . . 12 . . . 14 ------- LIST OF ABBREVIATIONS CHO Chinese hamster ovary DMSO Dimethyl sulfoxlde DNA Deoxyr1bonucle1c add HGPRT Hypoxanth1ne-guan1ne phosphorbosyl transferase RfD Reference dose RfD§ Subchronlc reference dose SCE Sister chromatld exchange ------- 1. ENVIRONMENTAL CHEMISTRY AND FATE Selected physical and chemical properties and environmental fate of selected fluorenes are presented In Tables 1-1 and 1-2. In both air and water, fluorene and benzo(J,k)fluorene are largely asso- ciated with participate matter. When adsorbed to participate matter, the fluorenes could potentially be transported long distances before ultimately being removed by chemical reaction or wet and dry deposition (HSOB, 1986). Vapor-phase fluoranthene has an estimated photodegradatlon half-life of 4-5 days (HSDB, 1986) and fluorene may have a similarly short reaction half- life. In water, the fluorenes should rapidly adsorb onto sediments and partlculate matter In the water column and bloconcentrate 1n aquatic organ- Isms. Physical properties Indicate that adsorption and bloconcentratlon of benzo(j,k)fluorene should be greater than that of fluorene. The fluorenes are apparently stable In sediments for .decades or more (BJoerseth et al., 1979). In the unadsorbed state 1n water, benzo(j,k)fluorene Is predicted to photodegrade (half-life days to weeks); unadsorbed fluorene may also photo- chemlcally degrade (HSDB, 1986; Sadtler, n.d.). The fluorenes are expected to adsorb strongly to soil and to blodegrade 1n the presence of acclimated microorganisms. Fluorene should degrade faster than benzo(j,k)fluorene (HSDB, 1986). 0068h -1- 07/31/86 ------- TABLE 1-1 Selected Physical and Chemical Properties and Half-Lives for Fluorene (CAS 86-73-7) Property Value Reference Chemical class: Molecular weight: Vapor pressure at 25°C: Log octanol/water partition coefficient: Bloconcentratlon factor: Soil adsorption coefficient: Half-lives In Air: Water: Soil: polynuclear aromatic hydrocarbon 166.22 6.6xlO"4 mm Hg, estimated Water solubility at 25°C: 1.90 mg/l 4.18 1290 (blueglll sunflsh) 3070 NR NR years (adsorbed to sediments) NR Mackay and Shul, 1981 Mackay and Shul, 1981 Hansch and Leo, 1985 Velth et al., 1979 Lyn»n et al., 1982 Bjoerseth et al., 1979 NR = Not reported 0068h -2- 10/07/86 ------- TABLE 1-2 Selected Physical and Chemical Properties and Half-Lives for Benzo(j ,k)fluorene Property Value Reference Compound: CAS number: Chemical class: Molecular weight: Vapor pressure at 25°C: Water solubility at 25°C: Log octanol/water partition coefficient: B1oconcentrat1on factor: Soil adsorption coefflcent: Half-lives In Air: Water: Soil: benzo(j,k)fluorene 206-44-0 polynuclear aromatic hydrocarbon 202.26 1.91xlO~3 mm Hg, estimated 0.26 mg/j. 5.20 380 (rainbow trout) 3981 (fathead minnow) 9160 4-5 days (vapor phase) days to weeks (unadsorbed state) years (adsorbed to sediments) NR Hackay and Shu1, 1981 Hackay and Shu1, 1981 Hansch and Leo, 1985 NLM, 1986 Lyman et al., 1982 NLM, 1986 NLM, 1986 Bjoerseth et al., 1979 NR = Not reported 0068h -3- 10/07/86 ------- Because fluorene and benzo(J ,k)fluorene have been found 1n ambient air and water, exposure by Inhalation and 1ngest1on are of concern. Estimates of total dally human exposure to benzo(J,k)fluorene are as follows (U.S.EPA, 1980a): Source Estimated Exposure (mq/day) Water 0.017 Food 1.6-16 Air 0.040-0.080 These data Indicate that food Is the greatest source of benzo(j,k)fluorene. Pertinent exposure data for fluorene could not be located In the available literature. 0068h -4- 07/31/86 ------- 2. ABSORPTION FACTORS IN HUMAN AND EXPERIMENTAL ANIMALS Pertinent data regarding the absorption of fluorene or benzo(j.k)- fluorene following oral or Inhalation exposure could not be located In the available literature. The relatively high llpld solubility of both compounds Indicates that they are likely to be absorbed following oral or Inhalation exposure. 0068h -5- 07/31/86 ------- 3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS Pertinent data regarding subchronlc, chronic, teratogenlc or other reproductive effects of fluorene or benzo(j,k)fluorene following oral or Inhalation exposure could not be located In the available literature. Mixtures of polynuclear aromatic hydrocarbons, Including benzo(j.k)- fluorene, have been tested for their Interactive toxic effects In mice by subcutaneous exposure (Pfelffer, 1973, 1977) and by dermal application (Schmahl et al., 1977). No synerglstlc or antagonistic effects were noted by either exposure method. 0068h -6- 10/07/86 ------- 4. CARCINOGENICITY • Pertinent data regarding the carcinogenic potential of fluorene or benzo(j,k)fluorene 1n humans or laboratory animals by either the oral or Inhalation routes of exposure could not be located In the available literature. 4.1. OTHER RELEVANT DATA Morton and Christian (1974) made bi-weekly applications of benzo(j.k)- fluorene 1n decalln or In a 1:1 mixture (by volume) of decalln and the cocarclnogen n-dodecane to the Interscapular skin of 15-20 two-month-old C3H male mice. The mice received 50/mg application and were treated for 82 weeks. No skin tumors were observed 1n mice treated with benzo(j,k)fluorene In either decalln or the decal1n-n-dodecane mixture. Van Ouurren and Goldschmldt (1976) tested benzo(j,k)fluorene for Us tumor promoting and cocardnogenlc activity. In the tumor promoting study, benzo(a)pyrene (150 mg) was applied to the skin of 50 female ZCR/Ha Swiss mice (6-8 weeks of age). Fourteen days after the benzo(a)pyrene applica- tion, benzo(j,k)fluorene 1n acetone at 40 mg was applied 3 times/week for the duration of the study (440 days). In this system, benzo(j,k)fluorene showed no tumor-promoting activity. In the cocardnogenldty study (Van Ouuren and Goldschmldt, 1976), benzo(a)pyrene (5 mg) was applied to the skin of mice simultaneously with benzo(j,k)fluorene (50 mg) In acetone. The compounds were applied 3 times/ week over a test period of 440 days. The number of mice with paplllomas and carcinomas more than doubled with benzo(j,k)fluorene as compared with benzo- (a)pyrene controls (16/50 benzo(a)pyrene; 39/50 benzo(a)pyrene + benzo(j.k)- fluorene). Benzo(j,k)fluorene also Increased the number of tumors per mouse 0068h -7- 10/07/86 ------- and decreased the days to the appearance of the first tumor as compared with the benzo(a)pyrene controls (210 days to first tumor, benzo(a)pyrene; 99 days, benzo(a)pyrene * benzo(j,k)fluorene). R1ce et al. (1984) applied [3H]-benzo(a)pyrene (15-22 nmol=3.8-5.5 yg) In acetone or a mixture of [3H]-benzo(a)pyrene (3.8-5.5 yg) and benzo(j,k)fluorene (37 yg) In acetone to the skin of 5-10 female CD-I mice. After 24 hours, the mice were killed and the treated skin removed and analyzed for DNA adducts, evidence of DNA disruption. Co-application of benzo(j,k)fluorene with [3H]-benzo(a)pyrene resulted In an average Increase of DNA adduct formation of 66% as compared with [3H]-benzo{a)- pyrene treatment alone. A study by Busby et al. (1984) provides evidence that benzo(J,k)fluorene has activity as a complete carcinogen. In the mouse lung adenoma bloassay, at least 50 Swiss-Webster BLU:Ha newborn male and female mice were Injected IntraperHoneally with 1/7 of the dose on day 1, 2/7 of the dose on day 8 and the remaining 4/7 of the dose on day 15. Vehicle control mice received DMSO; positive control mice received benzo(a)pyrene; and the benzo(j.k)- fluorene-treated mice received a total dose of 700 yg (163 yg/kg) or 3.5 mg (815 mg/kg). At 24 weeks of age, treated mice were sacrificed, gross observations were recorded and lungs were fixed for hlstopathologlcal examination. The results showed that the 3.5 mg dose of benzo(j,k)fluorene Induced a significant Increase In the total Incidence (58%, p<0.0001) and number of lung tumors (1.08 tumors/mouse, p<0.001) as compared with vehicle controls (9%, 0.09 tumors/mouse). About 20% of the mice with lung tumors 1n the high dose benzo(j,k)fluorene group had lesions diagnosed as adenocarclnomas. No 0068h -8- 10/07/86 ------- significant " tumor response was observed 1n mice receiving the low benzo- (j ,k)f luorene dose (20%, 0.24 tumors/mouse). None of the lung tumors In this group were diagnosed as adenocardnomas. Positive controls responded appropriately. Benzo(j,k)fluorene has been shown to be weakly mutagenlc In Salmonella typhlmurlum strains TA100 (K1nae et al., 1981) and TA98 (Epler et al., 1978) with S-9 metabolic activation. Benzo(j,k)fluorene was found to be mutagenlc 1n S. typhlmurlum strain TM677 with S-9 metabolic activation (Kaden et al., 1979). K1nae et al. (1981) observed negative results with benzo(j,k)- fluorene In S. typhlmurlum strains TA98 and TA1535 with or without metabolic activation and In the Bacillus subt111s rec assay. Benzo(j,k)fluorene was negative for unscheduled DNA synthesis 1n the hepatocyte primary culture/DNA repair test (McQueen and Williams, 1980). The compound was also negative for gene mutation In the human lymphoblast line AHH-1, which Is competent for xenoblotlc metabolism (Crespl and Thllly, 1984). L1 (1984) determined benzo(j,k)fluorene to be weakly mutagenlc 1n the CHO cell HGPRT assay with S-9 metabolic activation. The number of mutants was found to Increase with the amount of S-9 added to the culture, although cell survival was reduced at higher S-9 concentrations. Benzo(j,k)fluorene was also mutagenlc In repair-deficient CHO cells 1n the presence of rat mlcrosomes at 0.5-0.7 mg/mi (Hoy et al., 1984). Pertinent data regarding the carcinogenic potential of fluorene 1n laboratory animals by any route could not be located In the available literature. Fluorene has tested negative In mutation assays with S-9 metabolic activation using S. typhlmurlum strains TA98, TA100, TA1535 and TA1537 (Sakal et al., 1985; Epler et al., 1978; McCann et al., 1975). 0068h -9- 10/07/86 ------- Fluorene also was negative In the Escherlchla coll WP2/WP100 rec assay (Mamber et al., 1983). The compound was found to be weakly mutagenlc when tested with S. typhlmurlum strain TA97 with S-9 metabolic activation (Sakal et al., 1985). Fluorene has also been tested In L517847K ~ mouse lymphoma cells for forward mutation (Oberly et al., 1984^, In Chinese hamster cells for SCE In bone marrow (Neal and Probst, 1983), 1n negative primary culture/DNA repair assays using mouse and hamster hepatocytes (McQueen et al., 1983) and 1n the CHO/HGPRT assay (Hs1e et al., 1979). In all the above tests, fluorene was negative. 4.2. HEIGHT OF EVIDENCE Benzo(j,k)fluorene has been shown to have a potential to be a complete carcinogen In a newborn mouse lung adenoma bloassay (Busby et al., 1984). This evidence 1s sufficient to classify benzo(j,k)fluorene as an IARC Group 3 chemical and place It 1n EPA Group C, "possible human carcinogen" (U.S. EPA, 1986). Because of the lack of studies concerning the carcinogenic potential of fluorene, It can be classified as an IARC Group 3 chemical and a EPA Group 0 chemical, "not classified" (U.S. EPA, 1986). 0068h -10- 12/29/86 ------- 5. REGULATORY STANDARDS AND CRITERIA * An ambient water quality criterion of 42 yg/l has been calculated for benzo(j,k)fluorene (U.S. EPA, 1980a). This value was derived from a study by Hoffmann et al. (1972) 1n which 50 V9. of 1.0% benzo(j ,k)fluorene applied to the skin of Swiss albino mice 3 times/week for 12 months caused no Increase In mortality. Other parameters of toxldty were not evaluated. It 1s uncertain whether this value protects against the carcinogenic potential of benzo(J,k)fluorene. No standards or criteria are available for fluorene. 0068h -11- 07/31/86 ------- 6. RECOMMENDATIONS Because of the lack of data for the cardnogenlcHy and threshold toxlclty of benzo(],k)fluorene and fluorene by relevant routes of exposure, risk assessment values for these compounds have not been derived 1n past health assessment activities. An ambient water quality criterion of 42 vg/l was developed for benzo(j,k)fluorene (U.S. EPA, 1980a), based on the lack of Increased evidence of mortality In mice dermally exposed 3 times/week for 12 months (Hoffmann et a!., 1972). This study Is Insuffi- cient for derivations of RfD/RfO- values because the parameters of toxldty evaluated were not sufficient for estimation of a threshold for noncarclnogenlc toxldty. The primary Issue requiring resolution 1s the cardnogenlcHy of fluo- rene and benzo(j,k)fluorene by oral or Inhalation exposure. According to exposure data provided by the U.S. EPA (1980a), both routes of exposure may be Important, at least for benzo(J ,k)fluorene. Human data could not be located regarding the cardnogenlcHy of fluorene or benzo(j,k)fluorene and no animal data were located on fluorene. Fluorene was negative 1n mutagen- • 1dty tests In microorganisms (Mamber et al., 1983; Sakal et al., 1985) and 1n mutagenldty and clastogenldty tests 1n mammalian systems (Oberly et al., 1984; Neal and Probst, 1983; McQueen et al., 1983; Hs1e et al., 1979). Benzo(j,k)fluorene, on the other hand, has been shown to be a cocardnogen with benzo(a)pyrene 1n a dermal test In mice (Van Duuren and Goldschmldt, 1976), a complete carcinogen In the newborn mouse lung adenoma assay (Busby et al., 1984) and weakly mutagenlc In prokaryotlc (K1nae et al., 1981; Kaden et al., 1979) and mammalian (LI, 1984; Hoy et al., 1984) test systems. 0068h -12- 05/14/87 ------- These data, coupled with the fact that other polycycllc aromatic hydro- carbons are known carcinogens, emphasize the need to ascertain the cardno- genlclty of fluorene and benzolj,k)fluorene by oral and Inhalation routes of exposure. If adequate testing determines that these compounds are not carcino- genic, efforts should be made to determine thresholds for noncarclnogenlc toxlclty. Data are needed to determine the target organ(s) or system(s) most likely to be Injured by exposure to these compounds. Oral exposure to determine subchronlc, developmental and reproductive toxldty would also be necessary. Inhalation toxldty would be more difficult to ascertain because these compounds have relatively low vapor pressures (Mackay and Shu1, 1981) and occur In the atmosphere largely associated with partlculate matter. 0068h -13- 12/29/86 ------- 7. REFERENCES Bjoerseth, A., J. Knutzen and J. Ske1. 1979. Determination of polycycllc aromatic hydrocarbons In sediments and mussels from Saudafjord, VI. Norway, by glass capillary gas chromatography. Sc1. Toxlcol. Environ. 13: 71-86. Busby, H.F., Jr.,, M.E. Goldman, P.M. Newberne and G.N. Wogan. 1984. Tumor1gen1dty of fluoranthene 1n a newborn mouse lung adenoma bloassay. Cardnogenesls. 5(10): 1311-1316. Crespl, C.L. and W.G. ThUly. 1984. Assay for gene mutation 1n a human lymphoblast line, AHH-1, competent for xenoblotlc metabolism. Mutat. Res. 128: 221-230. Epler, 3.L., F.W. Larimer, T.K. Rao, C..E. Nix and T. Ho. 1978. Energy- related po.llutants In the environment: Use of short-term tests for mutagen- Iclty 1n the Isolation and Identification of blohazards. Environ. Health Perspect. 27: 11-20. Hansch, C. and A.J. Leo. 1985. Medchem Project. Issue #26. Pomona College, Claremont, CA. Hoffmann, 0., G. Rathkamp, S. Nesnow and E.L. Hynder. 1972. Fluoranthenes: Quantitative determination 1n cigarette smoke, promotion by pyrolysls, and tumor Initiating activity. J. Natl. Cancer Inst. 49(4): 1165. 0068h -14- . 07/31/86 ------- Horton, A.W. and G.M. Christian. 1974. Cocarclnogenlc versus Incomplete carcinogenic activity among aromatic hydrocarbons. Contrast between chrysene and benzo(b)tr1phenylene. J. Nat"!. Cancer Inst. 53(4): 1017-1020. Hoy, C.A., E.P. Salazar and L.H. Thompson. 1984. Rapid detection of DNA-damag1ng agents using repair-deficient CHO cells. Mutat. Res. 130(5): 321-322. HSOB (Hazardous Substance Data Bank). 1986. No. 5486. On-Hne Hs1e, A.H., J. O'Neill, J.R. San Sebastian, O.B. Couch and P.A. BMmer. 1979. Quantitative mammalian cell genetic toxicology: Study of the cyto- toxldty and mutagenlcHy of seventy Individual environmental agents related to energy technologies and three subfractlons of a crude synthetic oil In the CHO/HGPRT system. Environ. Scl. Res. 15: 291-315. Kaden, D.A., R.A. H1tes and U.G. ThUly. 1979. MutagenlcHy of soot and associated polycycllc aromatic hydrocarbons to Salmonella typhlmurlum. Cancer Res. 39(10): 4152-4159. K1nae, N, T. Hashlzume, T. Maklta, I. TomHa, I. Klmura and H. KanamoM. 1981. The toxlclty of pulp and paper mill effluents: 1. MutagenlcHy of the sediment samples derived from kraft paper mills. Water Res. 15(1): 17-24. L1, A.P. 1984. Use of Aroclor !254-1nduced rat liver homogenate In the assaying of promutagens 1n Chinese hamster ovary cells. Environ. Mutagen. 6(4): 539-544. 0068h -15- 07/31/86 ------- Lyman, W.J., W.F. Reehe and O.H. Rosenblatt. 1982. Handbook of Chemical Property Estimation Methods Environmental Behavior of Organic Compounds. McGraw-Hill Book Co.. New York. p. 4-9. Mackay, 0. and W.Y. Shlu. 1981. A critical review of Henry's Law Constants for chemicals of environmental Interest. J. Phys. Chem. Ref. Data. 19: 1175-1199. Mamber S.W., V. Bryson and S.E. Katz. 1983. The Escher1ch1a coll HP2/WP100 rec assay for detection of potential chemical carcinogens. Mutat. Res. 119(1): 135-144. McCann, J., E. Choi, E. Yamasakl and' B.N. Ames. 1975. Detection of carcinogens as mutagens In the Salmonella/mlcrosome test. Assay of 300 chemicals. Proc. Natl. Acad. Sc1. U.S.A. 72: 5135-5139. McQueen, C.A. and G.M. Williams. 1980. Verification of unscheduled DNA synthesis as DNA repair In the hepatocyte primary culture/DNA repair test. Ann. N.Y. Acad. Sc1. 5: 349-404. McQueen, C.A., D.M. Krelser and G.M. Williams. 1983. The hepatocyte primary culture/DNA assay using mouse or hamster hepatocytes. Environ. Mutagen. 5: 1-8. Neal, S.B. and G.S. Probst. 1983. Chemically-Induced slster-chromatld exchange Vn vivo In bone marrow of Chinese hamsters. An evaluation of 24 compounds. Mutat. Res. 113: 33-43. 0068h -16- 10/07/86 ------- NLM (National Library of Medicine). 1986. Hazardous Substance Data Base. Online. Oberly, T.J., 8.J. Bewsey and G.S. Probst. 1984. An evaluation of the L-5178Y TK+/-mouse lymphoma forward mutation assay using 42 chemicals. Mutat. Res. 125(2): 291-306. Pfelffer, E.H. 1973. Investigations on the carcinogenic burden by air pollution 1n man. VII. Studies on the oncogenlc Interaction of polycycllc aromatic hydrocarbons. Zbl. Bakt. Hyg. 1 Abt. Or1g. B., 15869. (Cited In U.S. EPA, 1980a) Pfelffer, E.H. 1977. Oncogenlc Interaction of carcinogenic and noncarclno- genlc polycycllc aromatic hydrocarbons In mice. In: Air Pollution and Cancer In Man, V. Mohr et al., Ed. IARC Scl. Publ. No. 16. p. 69. (Cited In U.S. EPA, 1980a) R1ce, J.E., T.O. Hosted, Jr. and E.J. Lavole. 1984. Fluoranthene and pyrene enhance benzo[a]pyrene-ONA adduct formation jji vivo 1n mouse skin. Cancer Lett. 24(3): 327-333. Sabljlc, A. 1984. Prediction of the nature and strength of soil sorptlon of organic pollutants by molecular topology. J. Agrlc. Food Chem. 32: 243-246. Sadtler. n.d. Sadtler Standard UV Spectra No. 2114. Sadtler Research Laboratory, Philadelphia, PA. 0068h -17- 10/07/86 ------- Sakal, M., 0. Yoshlda and S. M1zujak1. 1985. MutagenlcHy of polycycllc aromatic hydrocarbons and qulnones on Salmonella typhlmuMum TA97. Mutat. Res. 156: 61-67. Schmahl, 0., et al. 1977. Syncardnogenlc action of polycycllc hydro- carbons In automobile exhaust gas condensates. 1^: Air Pollution and Cancer In Man, V. Mohr, et al., Ed. IARC Sc1. Publ. No. 16. p. 53. (Cited \n U.S. EPA, 1980a) U.S. EPA. 1980a. Ambient Water Quality Criteria for Fluoranthene. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Water Regulations and Standards, Washington, DC. EPA 440/5-80-049. NTIS PB81-117608. U.S. EPA. 1980b, Ambient Water Quality Criteria for Polynuclear Aromatic Hydrocarbons. Prepared by the Office of Health and Environmental Assess- ment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Water Regulations and Standards, Washington, DC. EPA 440/5-80-069. NTIS PB81-117806. U.S. EPA. 1980c. Hazard Profile for Polynuclear Aromatic Hydrocarbons (PAH). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington, DC. 0068h . -18- 02/05/87 ------- U.S. EPA. 1983a. Reportable Quantity Document for Fluorene. 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. 1983b. Reportable Quantity Document for Fluoranthene. 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. 1986. Guidelines for Carcinogenic Risk Assessment. Federal Register. 51(185): 33992-34003. Van Duuren, B.L. and .8.M. Goldschmldt. 1976. Cocarclnogenlc and tumor- promoting agents In tobacco cardnogenesls. J. Natl. Cancer Inst. 56: 1237-1242. VeHh, G.D., D.L. Delore and B.V. Bergstedt. 1979. Measuring and estimat- ing the bloconcentratlon factor of chemicals In fish. J. Fish Res. Board Can. 36: 1040-1048. 0068h -19- 02/05/87 ------- |