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

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