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

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Table 11-4. Incidence of lung tumors in Fischer 344 rats (males and females combined) exposed to diesel engine exhaust Dose metric Exposure Lung particle concentration Weekly exposure burden (mg/cm 2 Lung tumor (mg/m 3 ) (mg/m3 X h)a lung surface)b incidencec 0 0 0 4/250 0.7 56 3.5 X 10 4 2.2 176 4.2 x w- 3 6.6 248 1.3 x w- 2 •Exposures were 16 hours/day, 5 days/week. bCalculated using mathematical models listed in Appendix C.
Table 11-5. Unit risk estimates per 1-1g/m 3 of diesel exhaust based on the Yu et al. (1991) dosimetry model Lung burden/lung surface area Lung burden/body weight';. Mauderly et al., 1987 3.4 X I o- 5 9_9 X J0-5 lshinishi et al., 1986 1.6 X J0- 5 4_6 X J0-5 Brightwell et al., 1989 7_1 X J0-5 2_J X J0-5 Geometric mean of three studies 3.4 X J0-5 9_9 X J0-5 1 The potency estimates derived using the LMS model are an improvement over most of 2 the earlier estimates because of improved methods for extrapolating dose from experimental 3 animals to humans. These assessments as wel_l as earlier ones, however, are based on the premise 4 that carcinogenic effects are a function of the whole particle concentration. Moreover, risk 5 estimates are calculated using the default assumption that responses vary linearly with particle 6 concentration even at ambient exposure concentrations. As noted in Chapter 10, however, while 7 particle effects may be dominant at large lung burdens, other components such as polycyclic 8 aromatic compounds, nitroaromatics, and surface-associated reactive oxygen species are likely to 9 play a more important role as exposure concentrations approach those found in the ambient air. 1 0 In an attempt to account for the effects of particles as well as particle-associated 11 components of DE, a biologically based two-stage model with piecewise constant parameters 12 was developed. This model assumes that both the carbon and the organic fraction have initiating 13 properties and that the carbon fraction also has effects on the proliferation, conversion and 14 progression steps of carcinogenesis. In addition, it accounts for the tumor initiating and 15 promoting effects at high exposure concentrations. A description of this model has been 16 published by Chen and Oberdorster (1996).· (See Appendix B for details.) The resultant two- 17 stage model is then used to predict tumor responses under various exposure scenarios and to 18 investigate the impacts of different biological assumptions on risk projection. 19 The parameters for the two-stage model were statistically estimated initially, using tumor 20 response data from animals exposed to high concentrations of DE and assuming particles 21 continue to exert effects at low concentrations (i.e., nonthreshold for particle effects). When the 22 two:.stage biologically based dose-response model (BBDr) was compared with results derived 23 with the LMS model, using malignant tumor data from the Mauderly et al. (1987) study, the 24 results were nearly identical (Table 11-6). The maximum likelihood estimate (MLE) of cancer 25 risk for the BBDr model at an exposure concentration of 1 J..lg/m 3 was calculated to be 8.2 x 10- 6 2/1198 11-15 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
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1 Heinrich et al. ( 1986a; see also
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1 thoracic area at subsequent times
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1 with matched controls for the num
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----- N \0 00 VI I 0'1 N tJ § I I
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1 In related studies, Navarro et al
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1 Mauderly et al. (1987b) evaluated
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1 pattern of adverse effects on res
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1 DPM concentrations) that resulted
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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1 Klosterkotter, W; Blinemann, G. (
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1 Misiorowski, RL; Strom, KA; Vosta
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1 Wright, ES. (1986) Effects of sho
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1 Studies showing these effects are
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1 exposure level. In the 0.3 5 mg/m
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1 to derive the RfC. The discussion
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1 The BMC values are the lower 95%
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Table 6-5. Results of benchmark con
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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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Page 391 and 392: 1 9.5. REFERENCES 2 3 "Barfknecht,
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Page 399: 1 inconsequential in rats relative
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Page 432: 1 The potency of the other diesel e
Page 439: Table 11-2. Incidence of lung tumor
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Page 449: 1 to reflect the potency of several
Page 452: 1 Huisingh. J; Bradow, R; Jungers,
Page 462: 1 particles are fine and ultrafine
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Page 477 and 478: 1 For example, in a recent meta-ana
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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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