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

1 response. cell injury, or cell proliferation, all of which accompany long-term exposures to inhaled
2 insoluble particles (Morrow, 1986). Such responses are generally greater after prolonged
3 exposure than in the current 12-week exposure. These responses might be factors in progression
4 to tumors in long-term inhalation exposures of rodents, when large lung burdens of particles
5 accumulate (Morrow, 1986), and in the increased incidence in tumors when B[a]P is merely
6 mixed with Fe 20 3 particles versus adsorbed onto the particle (Saffiotti et al., 1965).
7 Studies have also been conducted to evaluate DNA adduct formation in the lungs of
8 animals exposed both to DE and to particles that are nearly devoid of 9rganics (e.g., CB) or that
9 completely lack organic fractions (e.g., Ti0 2 ).
1 0 DNA adduct formation in the lungs of animals subjected to long-term exposure to whole
11 DE has been described by Wong et al. ( 1986). Using tissues from animals of the Mauderly et al.
12 ( 1987) study, these investigators reported an increase in DNA adduct formation in male and
13 female F344 rats exposed to whole DE (7.1 mg of particles/m 3 ) for 7 h/day, 5 days/week for up to ·
14 30 mo. 32 P postlabeling was applied to DNA that was extracted from six control and six exhaust-
15 exposed rats (males and females). Characterization of the adducts and identification of the
16 exhaust components responsible for their formation were not within the scope of the study. The
17 lungs of exhaust-exposed rats were darkly pigmented and contained diesel particle-laden
18 macrophages. Aggregates of these rnacrophages were frequently associated with alveolar wall
19 fibrosis, bronchiolar metaplasia and, occasionally, squamous metaplasia. Lungs from control rats
I
20 were not darkly pigmented and had relatively unaltered airways and structures. Autoradiographic
21 analysis revealed elevated levels of DNA adducts in the exhaust-exposed rats. The authors
22 indicated that quantitative and qualitative data regarding DNA adducts resulting from diesel
23 exhaust exposure may be useful for extrapolation to potential effects in humans.
24 A study by Bond etal. (1989) addressed several key topics regarding the role of DNA
25 adducts in the pulmonary carcinogenicity of DE. Using groups ofrats exposed to whole DE at
26 particle concentrations ofO, 0.35, 3.5, 7.0, or 10.0 mg/m 3 for 12 weeks, the relationship between
27 DNA adduct levels and exposure concentration was examined. The. data for the exposure levels
28 employed indicated that DNA adduct formation (about 14 adducts per 10 9 bases) was similar
29 across all exposure concentrations and was approximately twice that of the sham-exposed group.
30 The fact that DNA adduct formation was independent of exposure concentration may be
31 explained, in part, by previously reported data (Bond and Mauderly, 1984) showing that
32 metabolism of organics associated with diesel exhaust by the isolated perfused rat lung could be
33 saturated at high concentrations, thereby limiting the production of metabolites required for the
34 · formation of DNA adducts.
35 The time course for DNA adduct formation was also examined by Bond et al. (1989).
36 Over a 12-week period of exposure to diesel exhaust (7 mg/m 3 DPM), lung DNA adducts. were
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