Health Assessment Document for Diesel Emissions - NSCEP | US ...
Health Assessment Document for Diesel Emissions - NSCEP | US ...
Health Assessment Document for Diesel Emissions - NSCEP | US ...
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1 B.l. INTRODUCTION<br />
2 As previously discussed in Chapter 11, the most appropriate method to assess cancer risk·<br />
3 of diesel exhaust is to take into account effects of both particles (carbon core) and organics<br />
4 because evidence exists that both agents are involved in carcinogenic process. The reasons <strong>for</strong><br />
5 this conclusion are based on the following observations: (1) organics include a variety of<br />
6 polycyclic aromatic hydrocarbons (P AHs) and nitroaromatics, many of which are known to be<br />
7 carcinogenic; (2) the results of recent studies on inert particles and carbon black in rats strongly<br />
8 support the hypothesis that the carbon core of the diesel particle may b,e the primary component<br />
9 responsible <strong>for</strong> the induction of lung cancer; (3) PAHs are unlikely responsible <strong>for</strong> all observed<br />
10 tumors because they account <strong>for</strong> less than 0.1 J.lglmg particulate matter (Tong and Karasek,<br />
11 1984); and (4) the observation of disproportionate high tumor incidence in high exposure animals<br />
1 2 coincides with disproportionate increase of cumulative lung burden of diesel particle as exposure<br />
1 3 concentration increases.<br />
14 A workshop on Research Needs <strong>for</strong> Risk <strong>Assessment</strong> of Inhaled Particulate Matter was<br />
15 organized and sponsored by the U.S. Environmental Protection Agency (EPA) in March, 1992.<br />
1 6 The purpose of the workshop was to determine the extent of in<strong>for</strong>mation that can be used <strong>for</strong><br />
1 7 quantitative risk assessment and to discuss mechanisms of particle-induced lung tumors to serve<br />
18 as a guidance <strong>for</strong> future research needs. Two major, among several other, conclusions that are<br />
19 relevant to quantitative risk assessment were reached by the Workshop:<br />
20.<br />
21<br />
22<br />
23<br />
24<br />
25<br />
26<br />
27<br />
( 1) particle overloading of the lung tissue may induce both initiation (by P AH specific<br />
adducts and adducts through oxygen radicals) and cell proliferation steps in tumor<br />
<strong>for</strong>mation, and<br />
(2) more research is needed to improve the risk assessment of particle-induced lung<br />
cancers.<br />
28 Although there are not enough data available to construct a biologically based<br />
29 dose-response model, it is desirable to investigate implications of the hypothetical mechanisms<br />
30 ·proposed by the workshop. The purpose of the alternative modeling presented in this report is to<br />
31 do just that. Briefly, the biological issues and their implications to quantitative risk assessment<br />
32<br />
33<br />
that we would like to consider are the following.<br />
34 1. Particles deposited in lung are phagocytized by a,lveolar macrophages. Because the<br />
3 5 phagocytizing macro phages in animals from high-dose group may be more likely to be<br />
36 activated to release mediators including reactive oxygen species, cytokines, and growth<br />
3 7 factors_, it is of interest to determine whether or not the available tumor response data are<br />
211/98 B-2 . DRAFT--DO NOT CITE OR QUOTE