(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

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Raabe GK, Collingwood KW, Wong O (1998) An updated mortality study of workers at a petroleum refinery in Beaumont, Texas. Am.J.Ind.Med. 33:61-81. Rappaport S, Kupper L, Lin Y (2005) On the importance of exposure variability to the doses of volatile organic compounds. Toxicological Sciences 83:224-236. Reddy, M.V., Bleicher, W.T., Blackburn, G.R., et al. 1990. DNA adduction by phenol, hydroquinone, or benzoquinone in vitro but not in vivo: nuclease P 1 -enhanced 32 P-postlabeling of adducts as labeled nuceloside bisphosphates, dinucleotides and nuceloside monophosphates. Carcinogensis 11: 1349-1357. Reddy, M.V., Schulz, S.C., Blackburn, G.R., et al. 1994. Lack of DNA adduct formation in mice treated with benzene. Mutat Res 325: 149-155. Reinhart, T. and Ottmar, R. 2000. Smoke Exposure at Western Wildfires. United States Department of Agriculture, Forest Service, Pacific Northwest Research Station. PNW-RP-525. Rickert DE, Baker TS, Bus JS, Barrow CS, Irons RD (1979) Benzene disposition in the rat after exposure by inhalation. Toxicol.Appl.Pharmacol. 49:417-423. Ries C, Loher F, Zang C, Ismair MG, Petrides PE. (1999). Matrix metalloproteinase production by bone marrow mononuclear cells from normal individuals and patients with acute and chronic myeloid leukemia or myelodysplastic syndromes. Clin Cancer Res. May;5(5):1115-24. Rinsky RA, Hornung RW, Silver SR, Tseng CY (2002) Benzene exposure and hematopoietic mortality: A long-term epidemiologic risk assessment. American Journal of Industrial Medicine 4:474-480. Rinsky, R. A., Smith, A. B., Hornung, R. W., Filloon, T. G., Young, R. J., Okun, A. H., and Landrigan, P. J. (1987). Benzene and leukemia: an epidemiologic risk assessment. N.Engl.J.Med. 316(17), 1044-1050. Rinsky, R. A., Young, R. J., and Smith, A. B. (1981). Leukemia in benzene workers. Am.J.Ind.Med. 2, 217-245. Robertson, M.L., Eastmond, D.A., and Smith, M.T. 1991. Two benzene metabolites, catechol and hydroquinone, produce a synergistic induction of micronuclei and toxicity in cultured human lymphocytes. Mutat Res 249: 201-209. Robinson, S.N., Shah, R., Wong, B.A., et al. 1997. Immunotoxicological effects of benzene inhalation in male Sprague Dawley rats. Toxicology 119: 227-237. Rosenthal G.J., and Snyder, C.A. 1985. Modulation of the immune response to Listeria monocytogenes by benzene inhalation. Toxicol Appl Pharmacol 80: 502-510. Rosenthal G.J., and Snyder, C.A. 1987. Inhaled benzene reduces aspects of cell-mediated tumor surveillance in mice. Toxicol Appl Pharmacol 88: 35-43. Benzene VCCEP Submission 225 March 2006
Ross D, Siegel D, Gibson NW, Pacheco D, Thomas DJ, Reasor M, Wierda D (1990) Activation and deactivation of quinones catalyzed by DT-diaphorase. Evidence for bioreductive activation of diaziquone (AZQ) in human tumor cells and detoxification of benzene metabolites in bone marrow stroma. Free Radic.Res.Commun. 8(4-6):373-381. Ross D, Siegel D, Schattenberg DG, Sun XMM, Moran JL (1996) Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: Identification of target cells and a potential role for modulation of apoptosis in benzene toxicity. Environ.Health Perspect. 104 Suppl. 6:1177-1182. Ross, D. 2000. The role of metabolism and specific metabolites in benzene-induced toxicity: Evidence and issues. J Toxicol Environ Health Part A 61: 357-372. Rothman, N., Haas, R., Hayes, R.B., et al. 1995. Benzene induces gene-duplication but not gene-inactivating mutations at the glycophorin A locus in exposed humans. Proc Natl Acad Sci USA 92: 4069-4073. Rothman N, Li G-L, Dosemeci M, Bechtold WE, Marti GE, Wang Y-Z, Linet M, Xi L, Lu W, Smith MT, Titenko-Holland N, Zhang L-P, Blot W, Yin S-N, Hayes RB (1996) Hematotoxicity among Chinese workers heavily exposed to benzene. Am.J.Ind.Med. 29:236-246. Rothman N, Smith MT, Hayes RB, Traver RD, Hoener BA, Campleman S, Li GL, Dosemeci M, Linet M, Zhang LP, Xi LQ, Wacholder S, Lu W, Meyer KB, Titenko-Holland N, Stewart JT, Yin SN, Ross D (1997) Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQ01 609 C-->T mutation and rapid fractional excretion of chlorzoxazone. Cancer Res. 57:2839-2842. Roudabush, R.I., Terhaar, C.J., Fassett, D.W., and Dzuba, S.P. 1965. Comparative acute effects of some chemicals on the skin of rabbits and guinea pigs. Toxicol Appl Pharmacol 7: 559-565. Rowley, J. D., Golomb, H. M., and Vardiman, J. W. (1981). Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. Blood 58, 759-767. Rowley, J. D., and Le Beau, M. M. (1989). Cytogenetic and molecular analysis of therapyrelated leukemia. Ann.N.Y.Acad.Sci. 567, 130-140. Roy A, Georgopoulos PG. (1998). Reconstructing week-long exposures to volatile organic compounds using physiologically based pharmacokinetic models. J. Expo. Anal. Environ. Epidemiol. 8(3):407-22. Rozen, M.G., Snyder, C.A. 1985. Protracted exposure of C57Bl/6 mice to 300ppm benzene depresses B- and T- lymphocyte numbers and mitogen responses: Evidence for thymic and bone marrow proliferation in response to the exposures. Toxicology 37: 13-26. Rozen, M.G., Snyder, C.A., and Albert, R.E. 1984. Depression in B- and T-lymphocyte mitogen induced blastogenesis in mice exposed to low concentrations of benzene. Tox Lett 20: 343- 349. Benzene VCCEP Submission 226 March 2006
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Voluntary Children’s Chemical Eva
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6.1.2 Types of Adverse Health Effec
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Glossary of Terms μg Microgram AA
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STEL Short-Term Exposure Limit TEAM
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enzene induced pancytopenias can pr
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A fertility study in female rats ex
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estimate is very conservative both
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2.0 BASIS FOR INCLUSION OF BENZENE
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2.5 Air Monitoring Data Several of
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Table 3.1: Proposed Benzene AEGL Va
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4.0 Regulatory Overview This sectio
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passenger vehicles operated at cold
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Benzene has been designated a hazar
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products had ceased” [46 Fed. Reg
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5.0 CHEMICAL OVERVIEW This section
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Table 5.3: Environmental Fate and T
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general, the production rate is abo
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gasoline. Aromatic hydrocarbons, su
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The EPA Office of Air Quality Plann
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Benzene VCCEP Submission March 2006
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Table 5.11: Benzene Releases for Al
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6.1.2.2 Chronic Toxicity Toxicity a
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6.1.2.2e Other Hematopoietic Malign
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that transient, high peak exposures
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absorption compared to inhalation,
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increased risk of disease. It shoul
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The National Cancer Institute (NCI)
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exposure. This was also supported b
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follow-up of this same cohort, Wong
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development of MDS)and/or AML. It i
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quantification of benzene air conce
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4.0, 95% CI = 1.8-9.3) but not ALL
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6.2 Benzene Toxicology—Animal Haz
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eakage and loss was comparable whet
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Table 6.2: In Vivo Genotoxicity of
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Table 6.2 Continued: In Vivo Genoto
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6.2.2.3 Transplacental Genotoxicity
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induce solid tumors in animals in t
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mice in the 300-ppm group had bilat
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decreases in maternal weight gain,
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increased resorptions. The effects
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proposed that transplacental effect
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glycerol lysis time, and incidence
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6.2.5.2 Chronic Toxicity Repeat-dos
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LOAELs for carcinogenic effects in
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the measurements of doses are suspe
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intracellular pathogen, Listeria mo
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2. Evidence indicates that myelotox
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7.0 Exposure Assessments This secti
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throughout childhood, see Table 7.1
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7.2 Sources of Benzene Exposure Chi
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Table 7.3: Outdoor Ambient Air Benz
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Table 7.5: County-Wide 24-hour Ambi
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Age-specific benzene intakes are pr
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Table 7.9: Total ADDs for Exposure
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Table 7.10 (cont.) Study Location a
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Table 7.11: Summary of Benzene Meas
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factor change attributable to benze
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where: ADD = average daily dose (mg
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Table 7.16: Total ADDS from In-Home
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Table 7.18: Summary of Age-Specific
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Table 7.20: Summary Statistics for
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In-Vehicle Exposures In-vehicle exp
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Table 7.30: Average of Mean In-Vehi
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e similar to those in other U.S. st
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vehicle); the total amount of time
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use of small non-road engine equipm
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Children may be exposed to benzene
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Table 7.36: Typical School Year Wee
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An addition of less than 1 µg/m 3
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In the mid-1990s, the American Petr
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Table 7.44: Dermal Benzene Absorpti
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Table 7.47: Product Names and Manuf
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Table 7.49: Summary of Age-Specific
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For children and non-smoking adults
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Benzene Exposure (mg/kg-day) Figure
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ackground pathways of exposure, inc
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8.1.3 EPA Default Risk Assessment N
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8.2.1 Potential for Increased Sensi
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These findings illustrate examples
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information associated with benzene
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species are more sensitive than oth
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8.2.3.1 Point of Departure for Non-
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Cancer risks were calculated using
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NONCANCER HAZARD QUOTIENT 1.00 0.09
Page 181 and 182: Table 8.1. Derivation of noncancer
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Page 185 and 186: Table 8.4. (cont.) Noncancer Hazard
Page 187 and 188: Table 8.5. Noncancer hazard quotien
Page 189 and 190: Table 8.6. Cancer risk estimates as
Page 191 and 192: Table 8.7. Indoor air comparison (i
Page 193 and 194: Table 8.9. Noncancer margins of saf
Page 195 and 196: Table 8.10. Noncancer margins of sa
Page 197 and 198: Table 8.11. Indoor air comparison (
Page 199 and 200: Table 8.13. (cont.) Notes: Cancer M
Page 201 and 202: the continental U.S. for each leuke
Page 203 and 204: in significant reductions in benzen
Page 205 and 206: Aksoy M (1977) Leukemia in workers
Page 207 and 208: Austin, C.C., Wang, D., Ecobichon,
Page 209 and 210: Buckley, J.D., Ribison, L.L., Swoti
Page 211 and 212: CONCAWE. 1996. Scientific basis for
Page 213 and 214: Ding, X-J, Li, Y., Ding, Y. el al.
Page 215 and 216: Forni, A. 1994. Comparison of chrom
Page 217 and 218: Goldwater LJ (1941) Disturbances in
Page 219 and 220: Hsieh, G.C., Parker, R.D., and Shar
Page 221 and 222: Jo, W.K. and Park, K.H. 1998. Expos
Page 223 and 224: Lange, A., Smolik, R., Zatonski, W.
Page 225 and 226: Lynge E, Andersen A, Nilsson R, Bar
Page 227 and 228: Meadows, A., Obringer, A. M. O., Ba
Page 229 and 230: Nedelcheva V, Gut I, Soucek P, Tich
Page 231: Picciani, D. 1979. Cytogenetic stud
Page 235 and 236: Sathiakumar, N., Delzell, E., Cole,
Page 237 and 238: Smith, M. T., Zhang, L. P., Wang, Y
Page 239 and 240: Thomas, K.W., Pellizzari, E.D., Cla
Page 241 and 242: United States Environmental Protect
Page 243 and 244: URS. 2002. Air Quality Trend in the
Page 245 and 246: Weisel, C.P. 2002. Assessing exposu
Page 247 and 248: Xing, S.G., Shi, X., Wu, Z.L., Chen
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(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

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