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

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1 radicals present on the particle surface, which are potent oxidizing agents for bio-organic 2 substrates. 3 The observation that some of the DE-induced rat tumors are different pathologically from 4 what one would expect in humans and that some are similar may also support the thought that 5 multiple MOAs may be present. 6 Given the information at hand, dual modes of action are more likely than a single mode. 7 One would be driven by particles and one by the organic/inorganic components, with a shifting 8 influence as the exposure/dose varies from high to low. The role of contributory toxicity from ·9 other constituents, such as N0 2 or oxygen free radicals, among others, is uncertain. 10 It would be ideal if the MOA were informative about whether all humans were equally 11 susceptible or whether some population subgroups were more or less susceptible. The human 12 evidence, i.e., occupational and population-derived studies, does not provide any particular insight 13 about variations in susceptibility, nor do the animal studies. Neither female versus male nor adult 14 versus children's susceptibility differences are specifically indicated: the former may have been 15 discemable given the nature of the studies, but there is no study basis to address possible 16 children's risk issues. Later, in this section, a·qualitative discussion about susceptibility is 17 included that acknowledges that toxicological wisdom suggests that background respiratory 18 system conditions could make some in the population more susceptible to chronic effects of DE 19 exposure. Similarly, infants and children could have greater susceptibility simply because their 20 developing organs and defense systems may be less effective at dealing with insults from DE 21 exposure. These suggestions are not unique to DE exposure, though. 22 23 12.2.3. Carcinogenic Hazard Assessment 24 For inhalation exposure, both human studies and animal bioassays are available to assess 25 the chronic exposure carcinogenic potential for DE. In fact, both the human and the animal 26 studies provide evidence that exposure to DE has potential to be carcinogenic to humans under 27 some condition of exposure. Chapters 7 and 8 review these data in detail. A finding· about the 28 hazard potential does not specify the magnitude of the impact, information on which is discussed 29 30 in Chapter 11, the carcinogenicity dose-response evaluation section. 31 12.2.3.1. Human Evidence 32 A total of 26 key epidemiologic studies have been evaluated to examine the association 33 between exposure to DE and increased cancer response. The positive human evidence consists of 34 observed increases in lung cancer mortality .in a number of occupational exposure studies and 35 some suggestion of other possible cancer sites. Cohort, .case control, and population-based studies 2/1/98 12-9 DRAFT--DO NOT CITE OR QUOTE
1 are available. Exposure is most often defined indirectly by occupation or job title in the industry- 2 r_elated studies and is self-reported in population-based studies. The lack of direct exposure 3 measurements, a condition common to retrospective epidemiology studies, is an overall limitation 4 in the database. An excess risk (e.g. elevated standardized mortality ratios, relative risks, or odds 5 ratios> 1.0) for lung cancer was observed in 5 of 9 cohort studies and 8 of 10 case-control studies .. 6 Of these studies, three cohort and three case-control studies observed a dose-response relationship 7 by using duration of employment as a surrogate for dose. 8 The most convincing evidence that exposure to DE can induce lung cancer in humans 9 comes from case-control and cohort studies among U.S. railroad workers and truck drivers. The 10 study of railroad workers, a well-conducted and well-analyzed study, is evaluated and published 11 as both a cohort and case-control study with varied controlling for confounders. The case-control 12. study is the best for control of confounders, especially the question of smoking and its possible 13 role as a confounder for the reported lung cancer increase. Statistically significant higher risks of 14 41% to 43% for lung cancer were found in the case-control study for 20 or more years of 15 exposure, and these risks were not confounded by smoking or asbestos exposure, adjustments for 16 which were rigorously accounted for in the study methodology. In the retrospective cohort study 17 of these same railroad workers, the risks varied from 20% to 72% higher than the general 18 population, all statistically significant depending on the duration of exposure. Although 19 adjustments for possible asbestos exposure were accounted for, there was no adjustment for the 20 possible role of smoking. However, recognition was given to the rigorous smoking adjustments 21 in the case-control study, which showed no effect on risks. Though the overall risks were 22 increased in the railroad worker cohort study, the identification of a dose-response relationship is 23 a subject of debate. A case-control §tudy oftruck drivers showed statistically significant 24 increased risks of 80% to 240%, depending on data stratification and duration of exposure after 25 adjustment for smoking. 26 There is a notable consistency in finding elevated, although not always statistically 27 significant, increases in lung cancer among workers exposed to DE in several industries. There 28 are industry-specific findings of elevated lung cancer risk from truck drivers, professional drivers, 29 and railroad workers, with some of the studies having adjusted for smoking. When the possible 30 role of smoking as a confounder was accounted for, the increased risks prevailed. 31 A very recent meta-analysis (Bhatia et al., 1998) shows the consistency of elevated risks 32 in the epidemiology database and lends clear support to a causal association between increased 33 risks for lung cancer and exposure to DE. Using 29 epidemiology studies, 23 of which met 34 inclusion criteria, statistically significant relative risks (RR) for all studies were 1.33 (95% CI = 35 1.24-1.44). A subanalysis of case-control studies showed a RR of 1.33 (95% CI = 1.18-1.51); for 2/1198 12-10 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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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
Page 413: 1 response. cell injury, or cell pr
Page 418: 1 Caution must be exercised in extr
Page 424: 1 Rister, M: Baehner, RL. ( 1977) E
Page 432: 1 The potency of the other diesel e
Page 439 and 440: Table 11-2. Incidence of lung tumor
Page 441: Table 11-5. Unit risk estimates per
Page 444: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
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
Page 473: 1 · some of which can be informed
Page 477 and 478: 1 For example, in a recent meta-ana
Page 479 and 480: 1 nonthreshold-mutagen driven MOA.
Page 484: 1 that their developing pulmonary a
Page 491: 1 impacts. Use of these measures re
Page 495: 2/1198 Appendix A Experimental Prot
Page 504 and 505: APPENDIX A. EXPERIMENTAL PROTOCOL A
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Page 511 and 512: 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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