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

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1 with four to seven rings), which accounted <strong>for</strong> only 0.8% of the total weight ofDPM condensate,<br />

2 .produced the highest incidence of lung carcinomas following implantation into the rat lungs. A<br />

3 carcinoma incidence of 17.1% was observed following implantation of 0.21 mg lib/rat, whereas<br />

4 the nitro-PAH fraction (lid) at 0.18 mg/rat accounted <strong>for</strong> only a 2.8% carcinoma incidence.<br />

· 5 Hydrophilic fractions ofthe DPM extracts, vehicle (beeswax/trioctanoin) controls, and untreated<br />

6 controls failed to exhibit carcinoma <strong>for</strong>mation. Administration of all hydrophobic fractions (lia-<br />

7 d) produced a carcinoma incidence (20%) similar to the summed incidence of fraction lib<br />

8 (17.1 %) and lid (2.8%). The B[a]P positive controls (0.03, 0.1, 0.3 mg/rat) yielded a carcinoma<br />

9 incidence of 8.6%, 31.4%, and 77.1 %, respectively. The study showed that the tumorigenic<br />

10 agents were primarily four- to seven-ring P AHs and, to a lesser extent, nitroaromatics. However,<br />

11 these studies demonstrated that simultaneous administration of various P AH compounds resulted<br />

12 in a varying of the tumorigenic effect, thereby implying that the tumorigenic potency of P AH<br />

13 mixtures may not depend on ariy one individual P AH. This study did not provide any<br />

14 in<strong>for</strong>mation regarding the bioavailability of the particle-associated P AHs that might be<br />

15 responsible <strong>for</strong> carcinogenicitY.<br />

16 Kawabata et al. ( 1986) compared the effects of activated carbon and diesel exhaust on<br />

17 lung tumor <strong>for</strong>mation. One group of 59 F344 rats was intratracheally instilled with DPM 1<br />

18 mg/week <strong>for</strong> 10 weeks). A second group of 31 rats was instilled with the same dosing regime of<br />

19 activated carbon. Twenty-seven rats received oniy the. solvent (buffered saline with 0.05%<br />

20 Tween 80), and 53 rats were uninjected. Rats dying after 18 mo were autopsied. All animals<br />

21 .surviving 30 moor more postinstillation were sacrificed and evaluated <strong>for</strong> histopathology.<br />

22 Among 42 animals exposed to DPM surviving 18 mo or more, tumors were reported in 31,<br />

23 including 20 malignancies. In the subgroup surviving <strong>for</strong> 30 mo, tumors were detected in 19 of<br />

24 20 animals, including 1 0 malignancies. Among the rats exposed to activated carbon, the<br />

25 incidence of lung tumors equaled 11 of23 autopsied, with 7 cases of malignancy. Data <strong>for</strong> those<br />

26 ·dying between 18 and 30 mo and those sacrificed at 30 mo were not reported separately.<br />

27 Statistical analysis indicated that activated carbon induced a significant increase in lung tumor<br />

28 incidence compared with no tumors in 50 uninjected controls and 1 tumor in 23 solvent-injected<br />

29 controls. The tumor incidence increase was significant inthe DPM-instilled group and was<br />

30 significantly greater than the increase in the carbon-instilled group. This study provides evidence<br />

31 <strong>for</strong> the carcinogenicity of DPM. It also shows, as Heinrich et al. (1995) and Nikula et al. (1995)<br />

32 did, that particles lacking organic constituents also can induce tumors.<br />

33 Dasenbrock et al. (1996) conducted a study to determine the relative importance of the<br />

34 organi'c constituents of diesel particles and particle surface area in the induction of lung cancer in<br />

35 rats. Fifty-two female Wistar rats were intratracheally instilled with 16-17 doses of diesel<br />

2/1198 7-27 DRAFT--DO NOT CITE OR QUOTE

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