(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

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Irons, R.D. 2001. Analysis of the underlying biological basis for using neonatal hematology measurements in risk assessments of the developmental toxicity of benzene. CONCAWE, Brussels, Belgium: unpublished Irons RD (1997) Leukemogenesis as a toxic response. In: Comprehensive Toxicology, edited by Sipes IG, McQueen CA, Gandolfi AJ, Bloom JC. Elsevier Science Ltd., New York, pp 175-199 Irons RD, Dent JG, Edgar TS, Rickert DE (1978) Benzene is metabolized and covalently bound in bone marrow In Vivo. Irons RD, Moore BJ (1980) Effect of short term benzene administration on circulating lymphocyte subpoulations in the rabbit: evidence of a selective b-lymphocyte sensitivity. Res.Commun.Chem.Pathol.Pharmacol. 27(1):147-155 Irons, R.D., and Stillman, W.S. 1996. Impact of benzene metabolites on differentiation of bone marrow progenitor cells. Environ Health Perspect suppl 6: 1239-1246. Irons RD, and Stillman WS (1993). Cell proliferation and differentiation in chemical leukemogenesis. Stem Cells 11:235-242. Irons RD, Stillman WS, Colagiovanni DB, Henry VA (1992). Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colonystimulating factor in vitro. Proc.Natl.Acad.Sci.USA 89:3691-3695. Isbell, M. 1999. Use of biomarkers in an indoor air study: lack of correlation between aromatic VOCs with respective urinary biomarkers. The Science of the Total Environment, 241: 151-159. Jacobs A, Geary C, Osman J (1993). Hematological disorders and occupational hazards: a British Society for Haematology/Health and Safety executive study. Br.J.Haematol. 84:555-557. Jacobs, G.A. 1992. Acute Toxicity Data 1: 188-189. Jakobsson R, Ahlbon A, Bellander T, Lundberg I (1993) Acute myeloid leukemia among petrol station attendants. Achives of Environmental Health 48:255-259 Jandl JH (1997) Blood, Textbook of Hematology. Little, Brown & Company, Boston Jarvisalo J, Tola S, Korkala M-L, Jarvinen E (1984). A cancer register-based case study of occupations of patients with acute myeloid leukemia. Cancer 54:785-790. Jo, W.K. and Yu, C.H, 2001. Public bus and taxicab drivers’ exposure to aromatic work-time volatile organic compounds. Environmental Research Section A, 86, 6-72. Jo, W.K. and Park, K.H. 1999a. Commuter exposure to volatile organic compounds under different driving conditions. Atmospheric Environment, 33:409-417. Jo, W.K. and Park, K.H. 1999b. Concentrations of volatile organic compounds in the passenger side and the back seat of automobiles. Journal of Exposure Analysis and Environmental Epidemiology, 8:217-227. Benzene VCCEP Submission 213 March 2006
Jo, W.K. and Park, K.H. 1998. Exposure to carbon monoxide, methyl-tertiary butyl ether (MTBE), and benzene levels inside vehicles traveling on an urban area in Korea. Journal of Exposure Analysis and Environmental Epidemiology, 8:159-171. Jo, W.K. and Choi, S.J. 1996. Vehicle occupants' exposure to aromatic volatile organic compounds while commuting on an urban-suburban route in Korea. Journal of Air and Waste Management Association, 46: 749-754. Johansson, B., Mertens, F., Heim, S., Kristoffersson, U., and Mitelman, F. (1991). Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocytic leukemia (sANLL). Eur.J.Haematol. 47, 17-27. Johnson, T.R., Capel, J., Paul, R., and Wijnberg, L. 1999. Estimation of Carbon Monoxide Exposures and Associated Carboxyhemoglobin Levels in Denver Residents Using pNEM/CO (Version 2.0). Prepared for EPA Office of Air Quality Planning and Standards. Draft. March 15, 1999. Kaatsch, P., Kaletsch, U., Meinert, R. et al. 1998. German case control study on childhood leukemia – basic considerations, methodology, and summary of the results. Klin Padiatr. 210: 185-191. Kaden, D.A., Hites, R.A., and Thilly, W.G. 1979. Mutagenicity of soot and associated polycyclic aromatic hydrocarbons to Salmonella typhimurium. Cancer Res 39: 4152-4159. Kahn, H., and Muzyka, V. 1973. The chronic effect of benzene on porphyrin metabolism. Work Environ Health 10: 140-143. Kaldor, J., Day, N., Clarke, E., and et al (1990). Leukemia following Hodgkin's Disease. NEJM 322, 7-12. Kalf, G., Rushmore, T., and Snyder, R. 1982. Benzene inhibits RNA synthesis in mitochondria from liver and bone marrow. Chem Biol Interact 42: 353-370. Keller, K.A., and Snyder, C.A. 1986. Mice exposed in utero to low concentrations of benzene exhibit enduring changes in their colony forming hematopoietic cells. Toxicology 42: 171-181. Keller, K.A., and Snyder, C.A. 1988. Mice exposed in utero to 20ppm benzene exhibit altered numbers of recognizable hematopoietic cells up to seven weeks after exposure. Fundam Appl Toxicol 10: 224-232. Kelsey KT, Ross D, Traver RD, Christiani DC, Zuo Z-F, Spitz MR, Wang M, Xu X, Lee B-K, Schwartz BS, Wiencke JK (1997) Ethnic variation in the prevalence of a common NAD(P)H quinone oxidoreductase polymorphism and its implications for anti-cancer chemotherapy. Br.J.Cancer 76:852-854 Kenyon EM, Kraichely RE, Hudson KT, Medinsky MA. (1996). Differences in rates of benzene metabolism correlate with observed genotoxicity. Toxicol. Appl. Pharmacol. 136(1):49-56. Kezic, S., Monster, A.C., van de Gevel, I.A., Kruse, J., Opdam, J.J., and Verberk, M.M. 2001. Dermal absorption of neat liquid solvents on brief exposures in volunteers. American Industrial Hygiene Association Journal, 62(1): 12-18. Benzene VCCEP Submission 214 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
Page 169 and 170: These findings illustrate examples
Page 171 and 172: information associated with benzene
Page 173 and 174: species are more sensitive than oth
Page 175 and 176: 8.2.3.1 Point of Departure for Non-
Page 177 and 178: 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
Page 183 and 184: Table 8.3. Points of departure for
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: Hsieh, G.C., Parker, R.D., and Shar
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 and 232: Picciani, D. 1979. Cytogenetic stud
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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