Health Assessment Document for Diesel Emissions - NSCEP | US ...
Health Assessment Document for Diesel Emissions - NSCEP | US ...
Health Assessment Document for Diesel Emissions - NSCEP | US ...
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1 DPM concentrations) that resulted in impairment of pulmonary function occurred at 2 mg/m 3 in<br />
2 cynomolgus monkeys (the only level tested), 1.5 and 3.5 mg/m 3 in rats, 4.24 and 6 mg/m 3 in<br />
3 hamsters, and 11.7 mg/m 3 in cats. Exposures in monkeys, cats, and rats (3.5 mg/m 3 ) were <strong>for</strong> 7<br />
4 to 8 hlday, 5 days/week <strong>for</strong> 104 to 130 weeks. While this duration is considered to constitute a<br />
5 lifetime study in rodents, it is a small part of the lifetime of a monkey or cat, so these effect levels<br />
6 are essentially comparing chronic rodent studies with a subchronic monkey study. Exposures in<br />
7 hamsters and rats (1.5 mg/m 3 ) varied in hours per day (8 to 20) and weeks of exposure (26 to<br />
8 130). In all species but the monkey, the testing results were consistent. with restrictive lung<br />
9 disease; alteration in expiratory flow rates indicated that 1.5 mg/m 3 DPM was a LOAEL <strong>for</strong> a<br />
10 chronic exposure (Gross, 1981 ). Monkeys demonstrated evidence of obstructive airway disease.<br />
11 The nature ofthe pulmonary impairment is dependent on the dose oftoxicants delivered to and<br />
12 retained in the lung, the site of deposition and effective clearance or repair, and the anatomy and·<br />
13 physiology of the affected species; these variables appear to be factors in the disparity of the<br />
14 airway disease in monkey versus the other species tested.<br />
15<br />
16 5.6.2.3. Histopathological and Histochemical Effects<br />
17 Histological studies have demonstrated that chronic exposure to diesel exhaust can result<br />
18 in effects on respiratory tract tissue (Table 5-6). Typical findings include alveolar histiocytosis,<br />
19 AM aggregation, tissue inflammation, increase in PMNs, hyperplasia of bronchiolar and alveolar<br />
20 Type II cells, thickened alveolar septa, edema, fibrosis, and emphysema. Lesions in the trachea<br />
21 and bronchi were observed in some studies. Associated with these histopathological findings<br />
22 were various histochemical changes in the lung, including increases in lung DNA, total protein,<br />
23 alkaline and acid phosphatase, glucose-6-phosphate dehydrogenase; increased synthesis of<br />
24 collagen; and release of inflammatory mediators such as leukotriene L TB and prostaglandin<br />
25 PGF2a- Although the overall laboratory evidence is that prolonged exposure to DPM results in<br />
26 histopathological and histochemical changes in the lungs of exposed animals, some studies have<br />
27 also demonstrated that there may be a threshold of exposure to DPM below which pathologic<br />
28 changes do not occur. These no-observed-adverse-effect levels <strong>for</strong> histopathological effects .were<br />
29 reported to be 2 mg/m 3 <strong>for</strong> cynomolgus monkeys (the only concentration tested), 0.11 to 0.35<br />
30 mg/m 3 <strong>for</strong> rats, and 0.25 mg/m 3 DPM <strong>for</strong> guinea pigs exposed <strong>for</strong> 7 to 20 hi day, 5 to· 5.5<br />
31 days/week <strong>for</strong> 104 to 130 weeks.<br />
32<br />
33 5.6.2.4. Effects on Defense Mechanisms<br />
34 The pathological effects of DPM appear to be strongly dependent on the relative rates of<br />
35 pulmonary deposition and clearance (Table 5-7). Clearance of particles from the alveolar region<br />
36 of the lungs is a multiphasic process involving phagoc)rtosis by AMs. Chronic exposure to DPM<br />
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