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

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CONTENTS (continued) 2.5.1. Volatile Organic Compounds Attributable to Traffic .................. 2-47 2.5.2. Polycyclic Aromatic Hydrocarbons ..... ·.· ........................ 2-47 2.5.3. Nitroarene Concentrations in Ambient Air .......................... 2-51 2.6. EXPOSURE PERSPECTIVE .......................................... 2-56 2.7. SUMMARY ....................................................... 2-58 2.8. REFERENCES ................................................... · .. 2-59 4. DOSIMETRIC FACTORS .................................................. 4·1 4.1. INTRODUCTION ........ ' ....................... : . .................. 4-1 4.2. REGIONAL DEPOSITION OF INHALED PARTICLES .................... 4-2 4.2.1. Physical Processes, Physiological/ Anatomical Considerations, and Particle Characteristics ....................................... 4-2 4.2.2. Species Variability in Regional Dose ............................... 4-4 4.3. RESPIRATORY TRACT CLEARANCE RATES .......................... 4-6 4.3.1. Tracheobronchial Clearance ...................................... 4-6 4.3.2. Clearance From the Alveolar Region ............................... 4·9 4.3.2.1. Alveolar Clearance in Humans ............................. 4-9 4.3.2.2. Alveolar Clearance in Animals ............................ 4-10 4.3.2.3. Lung .. Burden and Pulmonary Overload Resulting in· Impaired Clearance ..................................... 4-13 4.3.3. Role of AMs in the Clearance of Particulate Matter ................... 4·16 4.3.3.1. AM-Mediated Clearance of Particulate Matter ................ 4-16 4.3.3.2. Translocations ofParticles to Extraalveolar Macrophage Compartment Sites ............... .' ........... 4-18. 4.3.3.3. Potential Mecharusms for an AM Sequestration Compartmentfor Particles During. Particle Overload ........... 4-20 4.3.3.4. Physiologically Based Models for Pulmonary Retention and Clearance oflnsoluble Particles ................ 4-21 4.4. BIOA V AILABILITY OF ORGANIC CONSTITUENTS PRESENT ON DIESEL EXHAUST PARTICLES ............................... : .. 4-22 4A.l. Laboratory Animal Studies ...................................... 4-23 4..4.2. Extraction of Diesel Particle-Associated Organics in Biological Fluids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.:25 4.4.3. Extraction of Diesel Particle-Associated Organics by Alveolar Lung Cells and Other Cell Types ................ : ......... · 4-27 4.4.4. Bioavailability of Adsorbed Compounds as a Function of Particle Clearance Rates and Extraction Rates of Adsorbed Compounds .. : ...... 4·28 4.5. CONSIDERATIONS FOR DOSIMETRY MODELING .................... 4-30 4.6. SUMMARY ........................................................ 4-31 4.7. REFERENCES ...................................................... 4·33 5. NONCANCER HEALTH EFFECTS OF DIESEL EXHAUST . . . . . . . . . . . . . . . . . . . . 5-1 5 .1. HEALTH EFFECTS OF WHOLE EXHAUST . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1 · 211/9.8 lV DRAFT--DO NOT CITE OR QUOTE
CONTENTS (continued) 5.1.1. Human Data ................................................. 5-1 5.1.1.1. Short-Term Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1 5.1.1.2. Long-Term Exposures ...................... :............ 5-7 5.1.2. Laboratory Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-17 5.1.2.1. Acute Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-17 • 5.1.2.2. Short-Term and Subchronic Exposures..................... 5-19 5.1.2.3. Chronic Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-24 5.2. COMPARISON OF HEALTH EFFECTS OF FILTERED AND UNFILTERED DIESEL EXHAUST .................. ·. . . . . . . . . . . . . . . . . 5-71 5.3. INTERACTIVE EFFECTS OF DIESEL EXHAUST ...................... 5-75 5.4. COMPARATIVE RESPONSIVENESS AMONG SPECIES TO THE PULMONARY EFFECTS OF DIESEL EXHAUST . . . . . . . . . . . . . . . . . . . . . . 5-77 5.5. DOSE-RATE AND PARTICULATE CAUSATIVE ISSUES . . . . . . . . . . . . . . . 5-78 5.6. SUMMARY AND DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-81 5.6.1. Effects of Diesel Exhaust on Humans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-81 5.6.2. Effects of Diesel Exhaust on Laboratory Animals . . . . . . . . . . . . . . . . . . . 5-83 5.6.2.1. Effects on Survival and Growth . . . . . . . . . . . . . . . . . . . . . . . . . . 5-83 5.6.2.2. Effects on Pulmonary Function . . . . . . . . . . . . . . . . . . . . . . . . . . 5-83 5.6.2.3. Histopathological and Histochemical Effects . . . . . . . . . . . . . . . . 5-84 5.6.2.4. Effects on Defense Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . 5-84 5.6.2.5. Neurological and Behavioral Effects . . . . . . . . . . . . . . . . . . . . . . 5-85 5.6.2.6. Other Noncancerous Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . 5-86 5.6.3. Comparison of Filtered and Unfiltered Diesel Exhaust .. ; ............ ; 5-86 5.6.4. Interactive Effects of Diesel Exhaust .................... :. . . . . . . . . 5-86 5.6.5. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . 5-86 5.7. REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-87 ·6. QUALITATIVE AND QUANTITATIVE ASSESSMENT OF NONCANCER HEALTH EFFECTS-DERIVATION OF THE INHALATION REFERENCE CONCENTRATION .......................................... 6-1 6.1. INTROnUCTION ....................... .' ........................... 6-1 6.2. DETERMINATION OF CRITICAL TARGET SITE ..................... : . . 6-2 6.3. APPROACH FOR DERIVATION OF THE INHALATION REFERENCE CONCENTRATION ...................................... 6-3 6.4. THE PRINCIPAL STUDIES FOR INHALATION REFERENCE CONCENTRATION DERIVATION ..................................... 6-5 6.5. SUPPORTING STUDIES FOR INHALATION REFERENCE CONCENTRATION DERIVATION ..................................... 6-8 6.5 .1. Respiratory Tract Effects in Species Other Than the .Rat ............... 6-12 6.6. DERIVATION OF THE INHALATION REFERENCE CONCENTRATION ......................................... : ....... 6-14 6.6.1. Application of the Benchmark Dose Approach to 2/1198 v DRAFT--DO NOT CITE OR QUOTE
Page 1 and 2: DRAFT DO NOT CITE OR QUOTE Health A
Page 9 and 10: CONTENTS (continued) 11.2.1. H.fl.Z
Page 12: LIST OF TABLES (continued) 2-14. Me
Page 17 and 18: PREFACE This draft health assessmen
Page 20 and 21: AUTHORS, REVIEWERS, AND CONTRIBUTOR
Page 22: l. INTRODUCTION 1 Diesel engines ar
Page 42 and 43: 1 achieved by using specific solven
Page 45 and 46: Nitro-PAH• Table 2-10. Concentrat
Page 50: 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
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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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Page 511 and 512:
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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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