Health Assessment Document for Diesel Emissions - NSCEP | US ...

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1 5.6.2.6. Other Noncancerous Effects 2 Essentially no effects (based on the weight of evidence of a number of studies) were 3 noted for reproductive and teratogenic effects in mice, rats, rabbits, and monkeys; clinical 4 chemistry and hematology in the rat, cat, hamster, and monkeys; and enzyme induction in the rat · 5 and mouse (Tables 5-10 through 5-12 and 5-14). 6 7 5.6.3. Comparison of Filtered and Unfiltered Diesel Exhaust 8 The compariso!l of the toxic responses in laboratory animals exposed to whole diesel 9 exhaust or filtered exhaust containing no particles demonstrates across laboratories that diesel 1 0 particles are the principaf etiologic agent of noncancerous health effects in laboratory animals 11 exposed to diesel exhaust (Table 5-15). Whether the particles act additively or synergistically 12 with the gases cannot be determined from the designs of the studies. Under equivalent exposure 13 regimens, hamsters have lower levels of retained DPM in their lungs than rats and mice do and 14 consequently less pulmonary function impairment and·pulmonary pathology. These differences 15 may result from a lower intake rate ofDPM, lower deposition rate and/or more rapid clearance 16 rate, or lung tissue that is less susceptible to the cytotoxicity of DPM. Observations of a 17 decreased respiration in hamsters when exposed by inhalation favor lower intake and deposition 18 rates. 19 20 5.6.4. Interactive Effects of Diesel Exhaust 21 . There is no direct evidence that diesel exhaust interacts with other substances in an 22 exposure environment, other than an impaired resistance to respiratory tract infections. Young 23 animals were not more susceptible. In several ways, animals with laboratory-induced 24 emphysema were more resistant. There is experimental evidence that both inorganic and organic 25 compounds can be adsorbed onto carbonaceous particles. When such substances become 26 affiliated with particles, these substances can be carried deeper into the lungs where they might 27 have a more direct and potent effect on epithelial cells or on AM ingesting the particles. Few 28 specific studies to test interactive effects of diesel exhaust with atmospheric contaminants, other 29 than coal dust, have been conducted. Coal dust and DPM had an additive effect only. 30 31 5.6.5. Summary 32 The principal noncancerous health hazard to humans from exposure to diesel exhaust is a 33 structural, functional, or biochemical injury to the lung. Current knowledge indicates that the 34 carb_onaceous core of the diesel particle is the prime c;ausative agent of lung injury. The limg 35 injury appears to be mediated by a progressive impairment of AMs. Because noncancerous 36 pulmonary effects occur at lower doses than those inducing tumors in rats and appear to be 211/98 5-86 DRAFT--DO NOT CITE OR QUOTE
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 '26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 cofactors in the etiology of diesel exhaust-induced tumors in rats, noncancerous pulmonary effects are relevant factors in the development of risk assessments. 5. 7. REFERENCES Ames, RG; Attfield, MD; Hankinson, JL; Hearl, FJ; Reger, RB. (1982) Acute respiratory effects of exposure to diesel emissions in coal miners. Am Rev Respir Dis 125:39-42. Ames, RG; Reger, RB; Hall, DS. (1984)Chronic respiratory effects of exposure to diesel emissions in coal mines. Arch Environ Health 39:389-394. Attfield, MD. (1978) The effect of exposure to silica and diesel exhaust in underground metal and nonmetal miners. In: Kelley, WD, ed. Industrial hygiene for mining and tunneling: proceedings of an American Conference of Governmental Industrial Hygienists topical symposium; November 1978; Denver, CO; pp. 129-135. Attfield, MD; Trabant, GD; Wheeler, RW. (1982) Exposure to diesel fumes and dust at six potash mines. Ann Occup Hyg 26:817-831. Barnes, DG; Daston, GP; Evans, JS; Jarabek, AM; Kavlock, RJ; Kimmel, CA; Park, C; Spitzer, HL. (1995) Benchmark Dose Workshop: criteria for use of a benchmark dose to estimate a reference dose. Reg Toxicol Pharmacol 21:296-306. Barnhart, MI; Chen, S-T; Salley, SO; Puro, H. (1981) Ultrastructure and morphometry of the alveolar lung of guinea pigs chronically exposed to diesel engine exhaust: six month's experience. J Appl Toxicol1:88-103. Barnhart, MI; Salley, SO; Chen, S-T; Puro, H. (1982) Morphometric ultrastructural analysis of alveolar lungs of guinea pigs chronically exposed by inhalation to diesel exhaust (DE). In: Lewtas, J, ed. Toxicological effects of emissions from diesel engines: proceedings of the Environmental Protection Agency diesel emissions symposium; October 1981; Raleigh, NC. 183-200. (Developments in toxicology and environmental science: v. 1 0). New York: Elsevier Biomedical; pp. BatJigelli, MC. (1965) Effects of diesel exhaust. Arch Environ Health 10:165-167. Battigelli, MC; Mannella, RJ; Hatch, TF. (1964) Environmental and clinical investigation of workmen exposed to diesel exhaust in railroad engine houses. Ind Med Surg 33:121-124. Battigelli, MC; Hengstenberg, F; Mannela, RJ; Thomas, AP. (1966) Mucociliary activity. Arch Environ Health 12:460-466. . Bhatnagar, RS. (1980.) Collagen and prolyl hydroxylase levels in lungs in dogs exposed to automobile exhaust and other noxious gas mixtures. In: Stara, JF; Dungworth, DL; Orthoefer, JG; Tyler, WS, eds. Long-term effects of air ·pollutants in canine species. Cincinnati, OH: U.S. Environmental Protection Agency, Environmental Criteria and Assessment Office; report no. EPA-600/8-80-014; pp. 71-87. Bhatnagar, RS; Hussain, MZ; Sorensen, KR; Von Dohlen, FM; Danner, RM; McMillan, L; Lee, SD. (1980) Biochemical alterations in lung connective tissue in rats and mice exposed to diesel emissions. In: Pepelko, WE; Danner, RM; Clarke, NA, eds. Health effects of diesel engine emissions: proceedings of an international symposium, v. 1; December 1979; Cincinnati, OH. Cincinnati, OH: U.S. Environmental Protection Agency, Health Effects Research Laboratory; pp. 557-570; EPA report no. EPA-600/9-80-057a. Available from: NTIS, Springfield, VA; PB81-173809. - Bice, DE; Mimderly, JL; Jones, RK; McClellan, RO. ( 1985) Effects of inhaled diesel exhaust on immune responses afterlung immunization. Fundam Appl Toxicol5:1075-1086. 2/1/98 5-87 DRAFT --DO NOT CITE OR QUOTE
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DRAFT DO NOT CITE OR QUOTE Health A
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CONTENTS (continued) 2.5.1. Volatil
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CONTENTS (continued) 11.2.1. H.fl.Z
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LIST OF TABLES (continued) 2-14. Me
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PREFACE This draft health assessmen
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AUTHORS, REVIEWERS, AND CONTRIBUTOR
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l. INTRODUCTION 1 Diesel engines ar
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1 achieved by using specific solven
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Nitro-PAH• Table 2-10. Concentrat
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1 pollutants depends on the amount
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1 For the simplest alkoxy radicals,
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1 2 3 4 5 6 7 8 9 10 11 12 13 H ON0
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1 conditions (Pitts et al., 1985c )
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Table 2-14. Mean particle, gas, and
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1 sample collection. There was no b
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1 of downtown Los Angeles (Arey et
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1 exposures. This is a complex ques
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1 Dunstan, TDJ; Mauldin, RF; Jinxia
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1 Lipkea, WH; DeJoode, AD; Christen
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1 Pitts, JN, Jr; Sweetman, JA; Ziel
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1 NOTE TO READERS CHAPTER3 2 Becaus
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1 volume basis (Table 4-1 ). This i
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1 Pritchard (1989), utilizing data
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1 4.3.3.3. Potential Mechanisms for
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1 not accurately reflect the actual
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1 Lee, PS; Chan, TL; Hering, WE. (1
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1 one-half units up to 3, strong (O
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Study Ulfvarson et a!. (1987) Batti
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N -,_. -\0 00 VI N ,_. 0 § I I 0 0
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1 control]). Heinrich et al. (1986a
Page 174: 1 Heinrich et al. ( 1986a; see also
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Page 189: 1 with matched controls for the num
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Page 201: 1 In related studies, Navarro et al
Page 210: 1 Mauderly et al. (1987b) evaluated
Page 216 and 217: 1 pattern of adverse effects on res
Page 218: 1 DPM concentrations) that resulted
Page 226 and 227: 1 Klosterkotter, W; Blinemann, G. (
Page 228 and 229: 1 Misiorowski, RL; Strom, KA; Vosta
Page 232: 1 Wright, ES. (1986) Effects of sho
Page 235: 1 Studies showing these effects are
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Page 251 and 252: 1 to derive the RfC. The discussion
Page 253 and 254: 1 The BMC values are the lower 95%
Page 255: Table 6-5. Results of benchmark con
Page 262: 1 U.S. Environmental Protection Age
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1 the latter, 16 were classified as
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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1 burdens of the NMRI mice after 12
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1 with four to seven rings), which
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1 five daily doses of2,000 f...lg.
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1 occupations. The observed absence
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1 occupations). Analysis was conduc
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1 the confined space of a truck cab
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1 The corresponding odds ratios for
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1 Approximately 20,000 miners are e
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1 bladder cancer was found in Canad
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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1 Kaplan, I. (1959) Relationship of
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9. MUTAGENICITY 1 Since 1978, more
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1 the presence of heritable translo
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1 9.5. REFERENCES 2 3 "Barfknecht,
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1 U.S. Environmental Protection Age
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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1 inconsequential in rats relative
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1 response. cell injury, or cell pr
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1 Caution must be exercised in extr
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1 Rister, M: Baehner, RL. ( 1977) E
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1 The potency of the other diesel e
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Table 11-2. Incidence of lung tumor
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Table 11-5. Unit risk estimates per
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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1 to reflect the potency of several
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1 Huisingh. J; Bradow, R; Jungers,
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1 particles are fine and ultrafine
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1 are available. Exposure is most o
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1 · some of which can be informed
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1 For example, in a recent meta-ana
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1 nonthreshold-mutagen driven MOA.
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1 that their developing pulmonary a
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1 impacts. Use of these measures re
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2/1198 Appendix A Experimental Prot
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APPENDIX A. EXPERIMENTAL PROTOCOL A
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2/1198 Appendix B Alternative Model
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1 d: Dose of organics, mg/cm 2 of l
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Table B-4. Comparison of observed t
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1 uncertainties below). Based on th
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1 B.lO. RFERENCES 2 3 Bohning D., A
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1 and 2 m.(t) = (y2i - YI/exp[Ap)a/
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1 C.l. INTRODUCTION 2 As discussed
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1 For mouth breathing: 2 (DF)H . =
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TABLE C-1. LUNG MODEL FOR RATS AT T
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TABLE C-3. RATIO OF PULMONARY SURFA
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