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 In study by Wolff et al. (1990) described earlier in this chapter, levels of DNA adducts as<br />
2 determined by 32 P postlabeling were significantly higher <strong>for</strong> DE-exposed rats than <strong>for</strong> CB-<br />
3 exposed rats after 12 weeks of exposure to DPM concentrations of 10 mg/m 3 • The results of this<br />
4 study suggested that DNA adduct levels are influenced. by the organic content of the<br />
5 carbonaceousparticles and that the organic constituents may initiate carcinogenesis. It was<br />
6 hypothesized that the continued inflammatory and proliferative responses may then promote cell<br />
7 trans<strong>for</strong>mations. Although the DNA adduct <strong>for</strong>mation may have been the result of very small<br />
8 amounts of organics desorbed from the carbon particles, it is also poss.ible that these adducts are<br />
9 the result of oxygen radicals or other reactive agents released from neutrophils and macrophages.<br />
1 0 More recent reports have affirmed the latter contention. Randerath et al. (1992) and Williams et<br />
11 al. (1992) provided data showing DNA adduct levels to be increased following exposures to CB<br />
12 and that no organic fraction was involved.<br />
13 Gallagher et al. (1994) noted that DNA adduct-like compounds were <strong>for</strong>med in rat lungs<br />
14 following exposures to DE, Ti0 2,.or CB, but that the total adduct levels were not significantly<br />
15 elevated by DE exposure. Exposure to DE resulted in DNA adducts, possibly from' nitro-P AHs<br />
16 associated with the organic fraction of the DPM, but the overall significance of this mechanism<br />
17 in the carcinogenic response is uncertain. ·<br />
18 The uncertainty of the role of a genotoxic mechanism was further shown by Swaf<strong>for</strong>d et<br />
19 al. (1995), who detected no differences in mutational patterns in CB-induced or diesel exhaust-<br />
20 induced pulrn,onary carcinomas. It was, however, noted that inactivationofthe p53 may have a<br />
21 role in·neoplastic responses with a squamous-cell carcinoma component.<br />
22 Based on the assumption that DNA adduct <strong>for</strong>mation is a critical step in the initiation of<br />
23 carcinogenesis (Harris, 1985), increased residence time of P AHs in the lung would increase the<br />
24 opportunity <strong>for</strong> metabolism and subsequent adduct <strong>for</strong>mation. Some involvement of the organic<br />
25 components is suggested by data showing the <strong>for</strong>mation of DNA adducts in exposed animals and<br />
26 by the known carcinogenic and mutagenic potential of many of the compounds in diesel exhaust.<br />
27 Several studies affirm the bioavailability from inhaled diesel exhaust particles of compounds<br />
28 such as B[a]P and 1-NP, which are known to be carcinogenic or mutagenic. Furthermore, the<br />
29 fact that xenobiotics may undergo biotrans<strong>for</strong>mation to reactive intermediates following their<br />
30 entry into the body via inhalation ofDPM has been demonstrated <strong>for</strong> B[a]P and various<br />
31 nitroarenes. However, results from the metabolism/disposition studies using carbon particles to<br />
32 which organics have been experimentally adsorbed must be interpreted with caution. The<br />
33 concentration of organics on these particles is probably much greater than the monomolecular or<br />
34 bimolecular layer on actual DPM and, there<strong>for</strong>e, might facilitate desorption of the organics from<br />
35 these experimentally prepared particles.<br />
2/1198 10-21 DRAFT--DO NOT CITE OR QUOTE