(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

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Paci E, Buiatti E, Costantini AS, Miligi L, Pucci N, Scarpelli A, Petrioli G, Simonato L, Winkelmann R, Kaldor JM (1989) Aplastic anemia, leukemia and other cancer mortality in a cohort of shoe workers exposed to benzene. Scand.J.Work.Environ.Health 15:313-318 Park, D. J., and Koeffler, H. P. (1996). Therapy-related myelodysplastic syndromes. Semin.Hematol. 33, 256-273. Parodi, S., Lutz, W.K., Colacci, A., et al. 1989. Results of animal studies suggest a nonlinear dose-response relationship for benzene effects. Environ Health Perspect 82: 171-176. Pathak, D. N., Lévay, G., and Bodell, W.J. 1995. DNA adduct formation in the bone marrow of B6C3 F1 mice treated with benzene. Carcinogenesis 16: 1803-1808. Paustenbach, D. J., Price, P. S., Ollison, W., Blank, C., Jernigan, J. D., Bass, R. D., and Peterson, H. D. (1992). Reevaluation of benzene exposure for the pliofilm (rubberworker) cohort (1936-1976). J.Toxicol.Environ.Health 36, 177-231. Paxton MB, Chinchilli VM, Brett SM, Rodricks JV (1994) Leukemia risk associated with benzene exposure in the Pliofilm cohort: I. mortality update and exposure distribution. Risk Anal. 14:147-154. Paxton MB, Chinchilli VM, Brett SM, Rodricks JV (1992) Reanalysis and update of the leukemogenic risk associated with occupational benzene exposure in the pliofilm cohort. (UnPub). Pedersen-Bjergaard, J., Larsen, S., Struck, J., Hansen, H., Specht, L., Ersboll, J., Hansen, M., and Nissen, N. (1987a). Risk of therapy related leukemia and preleukemia after Hodgkin's Disease: Relation to Age, Cumulative dose of Alkylating agents and Time from Chemotherapy. Lancet July 11, 83-89. Pedersen-Bjergaard J, Philip P (1987b) Chromosome characteristics of therapy-related acute non-lymphocytic leukemia and preleukemia: Possible implications for pathogenesis of the disease. Leuk.Res. 11:315-318. Pedersen-Bjergaard, J., Pedersen, M., Roulston, D., and Philip, P. (1995). Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood 86, 3542-3552. Pedersen-Bjergaard, J., Timshel, S., Andersen, M. K., Andersen, A. S., and Philip, P. (1998) Cytogenetically unrelated clones in therapy-related myelodysplasia and acute myeloid leukemia: experience from the Copenhagen series updated to 180 consecutive cases. Genes, Chromosomes & Cancer 23(4), 337-49. Pedersen-Bjergaard, J., Andersen, M. K., Christiansen, D. H., and Nerlov, C. Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. 2002. Blood. 99(6), 1909-12. Phillips, M.L., Esmen, N.A., Hall, T.A., and Lynch, R. 2004. Determinants of exposure to volatile organic compounds in four Oklahoma cities. Journal of Exposure Analysis and Environmental Epidemiology, 2004, (1-12. Benzene VCCEP Submission 223 March 2006
Picciani, D. 1979. Cytogenetic study of workers exposed to benzene. Environ Res 19: 33-38. Plappert, U., Barthel, E., Raddatz, K., et al. 1994. Early effects of benzene exposure in mice: Hematological versus genotoxic effects. Arch Toxicol 68: 284-290. Plappert U, Barthel E, Seidel HJ (1994) Reduction of benzene toxicity by toluene. Environ.Mol.Mutagen. 24:283-292 Pollini, G., and Columbi, R. (1964). Il danno cromosomico dei linfociti nel'emopatia benzenica. Med Lav 55, 653-654. Pope and Rall Eds. Case Studies in Environmental Medicine: Gasoline. Committee on Curriculum Development in Environmental Medicine, Institute of Medicine 992 pages. In: Environmental Medicine: Integrating a Missing Element into Medical Education, Washington DC: National Academy Press. Popp, W., Vahrenholz, C., Yaman, S., et al. 1992. Investigations of the frequency of DNA strand breakage and cross-linking in lymphocytes of female workers exposed to benzene and toluene. Carcinogenesis 13: 57-61. Powley MW and Carlson GP (1999). Species comparison of hepatic and pulmonary metabolism of benzene, Toxicology. 139: 207-217. Powley MW and Carlson GP (2000). Cytochromes P450 involved with benzene metabolism in hepatic and pulmonary microsomes. J Biochem Mol Toxicol. 14: 303-309. Powley MW and Carlson GP (2001). Hepatic and pulmonary microsomal benzene metabolism in CYP2E1 knockout mice. Toxicology. 169: 187-194. Pushkina, N.N., Gofmekler, V.A., and Klevtsova. 1968. Changes in content of ascorbic acid and nucleic acids produced by benzene and formaldehyde. Bull Exp Biol Med 66: 51-532. Pyatt D, Hays S, Cushing C. (2005). Do children have increased susceptibility for developing secondary acute myelogenous leukemia? Chemico-Biological Interactions 153-154:223-229. Pyatt D, Hays S. (2006 in press). Is age an independent risk factor for chemically induced acute myelogenous leukemia? Pyatt DW, Yang Y, Stillman W, Irons RD (2000) Hydroquinone inhibits PMA-induced activation of NF-kB in primary human CD19+ B lymphocytes. Cell Biology and Toxicology 16:41-51 Qu Q, Shore R, Li G, Jin X, Chen L, Cohen B, Melikian A, Eastmond D, Rappaport S, Yin S, Li H, Waidyanatha S, Li Y, Mu R, Zhang X, Li K (2002) Hematological changes among Chinese workers with a broad range of benzene exposures. American Journal of Industrial Medicine 42:275-285 Quitt M, Cassel A, Yoffe A, Anatol A, Froom P (2004) Autonomous growth of committed hematopoietic progenitors from peripheral blood of workers exposed to low levels of benzene. JOEM 46:27-29 Benzene VCCEP Submission 224 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
Page 179 and 180: NONCANCER HAZARD QUOTIENT 1.00 0.09
Page 181 and 182: Table 8.1. Derivation of noncancer
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Page 193 and 194: Table 8.9. Noncancer margins of saf
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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: Nedelcheva V, Gut I, Soucek P, Tich
Page 233 and 234: Ross D, Siegel D, Gibson NW, Pachec
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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