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

1 In related studies, Navarro et al. ( 1981) evaluated the effect of exposure to diesel exhaust
2 on rat hepatic and pulmonary microsomal enzyme activities. The same exposure regimen was
3 employed (20 h/day, 5.5 days/week, for up to 1 year), and the exhaust was diluted to achieve
4 concentrations of0.25 and 1.5 mg/m 3 DPM (a few studies were also conducted at 0.75 mg/m 3 ).
5 After 8 weeks of exposure, there was no evidence for the induction of cytochrome P450,
6 cytochrome P448, or NADPH-dependent cytochrome c reductase in rat liver microsomes. One
7 year of exposure had little, if any, effect on the hepatic metabolism ofB[a]P. However, 1 year of
8 exposure to 0.25 and 1.5 mg/m 3 significantly impaired the ability of lll\lg microsomes to
9 metabolize B[a]P (0.15 and 0.02 nmole/30 min/mg protein, respectively, versus 0.32 nmole/30
10 min/mg protein for the controls).
11 There are conflicting results regarding the induction of microsomal AHH activities in the
12 lungs and liver of rodents exposed to diesel exhaust. One study reported induced AHH activity
13 in the lungs, liver, and prostate of rats exposed to diesel exhaust containing 6.32 mg/m 3 DPM for
14 20 h/day for 42 days; however, no induction of AHH was observed in the lungs ofrats and mice
15 exposed to 6 mg/m 3 DPM for 8 h/day, 7 days/week for up to 8 moor to 0.25 to 2 mg/m 3 for
16 periods up to 2 years. Exposure to diesel exhaust has not been shown to produce adverse effects
17 on microsomal cytochrome P450 in the lungs or liver of rats or mice. The weight of evidence
18 suggests that the absence of enzyme induction in the rodent lung exposed to diesel exhaust is
19 caused either by the unavailability of the adsorbed hydrocarbons or by their presence in
20 insufficient quantities for enzyme induction.
21
22 5.1.2.3.10. Effects on behavior and neurophysiology. Studies on the effects of exposure to
23 diesel exhaust on the behavior and neurophysiology of laboratory animals are summarized in
24 Table 5-13. Laurie et al. (1978) and Laurie et al. (1980) examined behavioral alterations in adult
25 and neonatal rats exposed to diesel exhaust. Exposure for 20 h/day, 7 days/week, for 6 weeks to
26 exhaust containing 6 mg/m 3 DPM produced a significant reduction in adult spontaneous ioco-
27 motor activity (SLA) and in neonatal pivoting (Laurie et al., 1978). In a follow-up study, Laurie
28 et al. (1980) found that shorter exposure (8 h/day) to 6 Iilg/m 3 DPM also resulted in a reduction
29 of SLA in adult rats. Laurie et al. (1980) conducted additional behavioral tests on adult rats
30 exposed during their neonatal period. For two of three exposure situations (20 h/day for 17 days
31 postparturition, or 8 h/day for the first 28 or 42 days postparturition), significantly lower SLA
32 was observed in the majority of the tests conducted on the adults after week 5 of measurement.
33 When compared with control rats, adult 15-month-old rats that had been exposed as neonates (20
34 h/day for 17 days) also exhibited a significantly slower rate of acquisition of a bar-pressing task
35 · to obtain food. The investigators noted that the evidence was insufficient to determine whether
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