(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

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Kinney, P.L., Chillrud, S.N., Ramstrom, S., Ross, J., and Spengler, J.D. 2002. Exposures to multiple air toxics in New York City. Environmental Health Perspectives, 110(4): 539-546. Kipen HM, Cody RP, Crump KS, Allen BC, Goldstein BD (1988) Hematologic effects of benzene: a thirty-five year longitudinal study of rubber workers. Toxicol Ind Health 4(4):411-430 Kjeldsberg C, Elenitoba K, Foucar K, Hussong J, McKenna R, Perkins S, Peterson L, Perterson P, Rodgers G (2000) Pratical diagnosis of hematologic disorders. American Society of Clinical Pathologists, Chicago, IL Kline, S.A., Xiang, Q., Goldstein, B.D., et al. 1993. Reaction of (E,E)-muconaldehyde and its aldehyde metabolites, (E,E)-6-oxohexadienoic acid and (E,E)-6-hydroxyhexz-2,4-dienal, with glutathione. Chem Res Toxicol 6:578-583. Kolachana, P., Subrahmanyam, V.V., Meyer, K.B., et al. 1993. Benzene and its phenolic metabolites produce oxidative DNA damage in HL60 cells in vitro and in the bone marrow in vivo. Cancer Res 53:1023-1026. Kraut, A., Lilis, R., Marcus, M., et al. 1988. Neurotoxic effects of solvent exposure on sewage treatment workers. Arch Environ Health 43: 263-268. Krewski, D. Snyder, R., Beatty, P., Granville, G., Meck, M., and Sonawane, B. 2000. Assessing the health risks of benzene: a report on the Benzene State-of-the-Science Workshop. J. Toxicol. Environ. Health A61: 307-338. Krishnan K, Haddad S, Beliveau M, Tardif R. (2002). Physiological modeling and extrapolation of pharmacokinetic interactions from binary to more complex chemical mixtures. Environ. Health Perspect. 110 Suppl 6:989-94. Kuna, R.A., Nicolich, M.J., Schroeder, R. E., and Rusch, G.M. 1992. A female rat fertility study with inhaled benzene. J Am Coll Toxicol 11: 275-282. Kuna, R.A. and Kapp, R.W. 1981. The embryotoxic/teratogenic potential of benzene vapor in rats. Toxicol Appl Pharmacol 57:1-7. Kuttesch JF Jr, Wexler LH, Marcus RB, Fairclough D, Weaver-McClure L, White M, Mao L, Delaney TF, Pratt CB, Horowitz ME, Kun LE. (1996). Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas. J Clin Oncol. Oct;14(10):2818-25. Lagorio S, Forastiere F, Iavarone I, Rapiti E, Vanacore N, Perucci CA, Carere A (1994) Mortality of filling station attendants. Scand.J.Work.Environ.Health 20:331-338 Lamm SH, Walters AS, Wilson R, Byrd DM, Grunwald H (1989) Consistencies and inconsistencies underlying the quantitative assessment of leukemia risk from benzene exposure. Environ.Health Perspect. 82:289-297 Lan Q, Zhang L, Li G, Vermeulen R, Weinberg R, Dosemeci M, Rappaport S, Shen M, Alter B, Wu Y, Kopp W, Waidyanatha S, Rabkin C, Guo W, Chanock S, Hayes R, Linet M, Kim S, Yin S, Rothman N, Smith M (2004) Hematotoxicity in workers exposed to low levels of benzene. Science 306:1774-1776 Benzene VCCEP Submission 215 March 2006
Lange, A., Smolik, R., Zatonski, W., et al. 1973. Leukocyte agglutinins in workers exposed to benzene, toluene, and xylene. Int Arch Arbeitsmed 31: 45-50 [in ATSDR 1993, 1997]. Larson R (2000) Myeloid leukemia after cytotoxic therapy and other hematotoxins. Journal of Toxicology and Environmental Health PartA 61:381-386 Larson RA, Wang YX, Banerjee M, Wiemels J, Hartford C, Le Beau MM, Smith MT (1999) Prevalence of the inactivating 609 C-->T polymorphism in the NAD(P)H:quinone oxidoreductase (NQO1) gene in patients with primary and therapy-related myeloid leukemia. Blood 94:803-807 Lawryk, N. J., Lioy, P. J., and Weisel, C. P. 1995. Exposure to volatile organic compounds in the passenger compartment of automobiles during periods of normal and malfunctioning operation. Journal of Exposure Analysis and Environmental Epidemiology. 5(4):511-531. Lawryk, N.J. and Weisel, C.P. 1996. Concentrations of volatile organic compounds in the passenger compartments of automobiles. Environmental Science and Technology, 30, 810- 816. Le Beau, M. M., Albain, K. S., Larson, R. A., Vardiman, J. W., Davis, E. M., Blough, R. R., Golomb, H. M., and Rowley, J. D. (1986a). Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7. J.Clin.Oncol. 4(3), 325- 345. Le Beau, M. M., Westbrook, C. A., Diaz, M. O., Larson, R. A., Rowley, J. D., Gasson, J. C., Golde, D. W., and Sherr, C. J. 1986b. Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. Science. 231(4741), 984-7. Le Noire C (1897) Sur un cas de purapura attribue a l'intoxication par le benzene. Bull. Mem. Soc. Med. Hop. Paris 14:1251-1260 Leibowitz, H. Brusick, D., Matheson, D.R., et al. 1979. Commonly used fuels and solvents evaluated in a battery of short-term bioassays. Environ Mutagen 1: 172-173. Lemasters, G.K., Livingston, G.K., Lockey, J.E., Olsen, D.M., Shukla, R., New, G., Selevan, S.G., and Yiin, J.H. 1997. Genotoxic changes after low-level solvent and fuel exposure on aircraft maintenance personnel. Mutagenesis, 12(4): 237-243. Lemasters, G.K., Olsen, D.M., Yiin, J.H., Lockey, J.E., Shukla, R., Selevan, S. G., Schrader, S.M., Toth, G.P., Evenson, D.P., and Huszar, G.B. 1999. Male reproductive effects of solvent and fuel exposure during aircraft maintenance. Reproductive Toxicology, 13(3):155-166. Leone, G., Mele, L., Pulsoni, A., Equitani, F., and Pagano, L. (1999). The incidence of secondary leukemias. Haematologica 84, 937-945. Lévay, G., Ross, D., and Bodell, W.J. 1993. Peroxidase activation of hydroquinone results in the formation of DNA adducts inHL-60 cells, mouse bone marrow macrophages and human bone marrow. Carcinogenesis 14: 2329-2334. Benzene VCCEP Submission 216 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
Page 171 and 172: information associated with benzene
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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 and 220: Hsieh, G.C., Parker, R.D., and Shar
Page 221: Jo, W.K. and Park, K.H. 1998. Expos
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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