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

1 five daily doses of2,000 f...lg. One week later, 2 f...lg of the tumor promoter tetradecanoylphorbol
2 acetate (TPA) was applied topically twice weekly. The tumor-promotion experiments used mice
3 treated with 50.5 f...lg ofB[a]P followed by weekly (twice weekly for high dose) topical
4 applications (at the aforementioned doses) of the extracts. For the complete carcinogenesis
5 experiments, the test extracts were applied weekly (twice weekly for the high doses) for 50 to 52
6 weeks. Only extracts from the Nissan, Oldsmobile, and Caterpillar engines were used in the.
7 complete carcinogenesis experiments. ·
8 In the tumor-initiation studies, both B[a]P alone and the Nissan.engine DPM extract
9 followed by TP A treatment produced a significant increase in tumor (dermal papillomas)
1 0 incidence at 7 to 8 weeks postapplication. By 15 weeks, the tumor incidence was greater than
11 · 90% for both groups. No significant carcinoma formation was noted for mice in the tumor-
12 initiation experiments following exposure to DPM extracts of the other diesel engines, although
13 the Oldsmobile engine DPM extract at 2.0 mg/mouse did produce a 40 percent papilloma
14 incidence in male mice at 6 mo. This effect, however, was not dose dependent.
15 B[a]P (50.5 f...lg/week), coke oven extract (at 1.0, 2.0, or 4.0 mg/week), and the highest
16 dose of roofing tar extract (4.0 mg/week) all tested positive for complete carcinogenesis activity.
17 DPM extracts from only the Nissan, Oldsmobile, and Caterpillar engines were tested for
18 complete carcinogenic potential, and all three proved to be negative using the Sencar mouse
19 assay.
20 The results of the dermal application experiments by N esnow et aL (1982) are presented
21 in Table. 7-5. The tumor initiation-promotion assay was considered positive if a dose-dependent
22 response was obtained and if at least two doses provided a papilloma-per-mouse value that was
23 three times or greater than that of the background value. Based on these criteria, only emissions
24 from the Nissan were considered positive. Tumor initiation and complete carcinogenesis assays
25 required that at least one dose produce a tumor incidence of at least 20%. None of the DPM
26 samples yielded positive results based on this criterion.
27 Kunitake et al. (1986, 1988) evaluated the effects of a dichloromethane extract ofDPM
28 obtained from a 1983 MMC M-6D22P 11-L V-6 engine. An acetone solution was applied in 10
29 doses every other day, followed by promotion with 2.5 f...lg ofTPA three times weekly for 25
30 weeks. Exposure groups received a total dose of 0.5, 5, 15, or 45 mg of extract. Papillomas
31 were reported in 2 of 50 animals examined in the 45 mg exposure group and in 1 of 48 in the 15
32 mg group compared with. 0 of 50 among controls. Differences, however, were not statistically
33 significant.
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