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

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1 serum enzymes in the control versus the exposed female rats appear to be a random event among<br />

2 these aged subjects. The incidence of age-related disease, such as mononuclear cell leukemia,<br />

3 can markedly affect such enzyme levels, seriously compromising the usefulness of a comparison<br />

4 to historical controls. The serum sodium values of 144 versus 148 mmol/L in control and<br />

5 exposed rats, respectively, although statistically different, would have no biological import.<br />

6 The increased serum enzyme activities, aJkaline phosphatase, SGOT, SGPT, garnma-<br />

7 glutamyl transpeptidase, and decreased cholinesterase activity suggest an impaired liver;<br />

8 however, such an impairment was not established histopathologically (Heinrich et al., 1982;<br />

9 Research Committee <strong>for</strong> HERP Studies, 1988; Brightwell et al., 1986). The increased urea<br />

10 nitrogen, electrolyte levels, and gamma globulin concentration and reduction in total blood<br />

11 proteins are indicative of impaired kidney function. Again there was no histopathological con:fir-<br />

12 mation of impaired kidneys in these studies.<br />

13 Clinical chemistry studies suggest impairment of both liver and kidney functions in rats<br />

14 and hamsters chronically exposed to high concentrations of diesel exhaust. The absence of<br />

15 histopathological confirmation, the appearance of such effects near the end of the lifespan of the<br />

16 laboratory animal, and the failure to find such biochemical changes in cats exposed to a higher<br />

17 dose, however, tend to discredit the probability of hepatic and renal hazards to humans exposed<br />

18 at atmospheric levels of diesel exhaust.<br />

19<br />

20 5.1.2.3.9. Effects on microsomal enzymes.· Several studies have examined the effects of diesel<br />

21 exhaust exposure on microsomal enzymes associated with the metabolism and possible<br />

22 activation of xenobiotics, especially polynuclear aromatic hydrocarbons. These studies are<br />

23 summarized in Table 5-12. Lee et al. ( 1980) measured the activities' of aryl hydrocarbon<br />

24 hydroxylase (AHH) and epoxide hydrase (EH) in liver, lung, testis, and prostate gland of adult<br />

25 male rats exposed to 6.32 mg/m 3 DPM 20 h/day <strong>for</strong> 42 days, Maximal significant AHH activities<br />

26 (pmol/min/mg microsomal protein)occurred at different times during the exposure period, and<br />

27 differences between controls and exposed rats, respectively, were as follows: prostate<br />

28 0.29 versus 1.31, lung 3.67 versus 5.11, and liver 113.9 versus 164.0. There was no difference in<br />

29 AHH activity in the testis between exposed and control rats. Epoxide hydrase activity was not<br />

30 significantly different from control values <strong>for</strong> any of the organs tested.<br />

31 Pepelko and Peirano (1983) found no statistical differences in liver microsomal<br />

32 cytochrome P448-450 levels and liver microsomal AHH between coritrol and diesel-exposed<br />

33 mice either at 6 and 8 mo of exposure. Small differences were noted in the lung microsomal<br />

34 AHH activities, but these were believed to be artifactual differences, due to increases in<br />

2/1198 5-63 DRAFT --DO NOT CITE OR QUOTE

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