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

1 radicals present on the particle surface, which are potent oxidizing agents for bio-organic
2 substrates.
3 The observation that some of the DE-induced rat tumors are different pathologically from
4 what one would expect in humans and that some are similar may also support the thought that
5 multiple MOAs may be present.
6 Given the information at hand, dual modes of action are more likely than a single mode.
7 One would be driven by particles and one by the organic/inorganic components, with a shifting
8 influence as the exposure/dose varies from high to low. The role of contributory toxicity from
·9 other constituents, such as N0 2 or oxygen free radicals, among others, is uncertain.
10 It would be ideal if the MOA were informative about whether all humans were equally
11 susceptible or whether some population subgroups were more or less susceptible. The human
12 evidence, i.e., occupational and population-derived studies, does not provide any particular insight
13 about variations in susceptibility, nor do the animal studies. Neither female versus male nor adult
14 versus children's susceptibility differences are specifically indicated: the former may have been
15 discemable given the nature of the studies, but there is no study basis to address possible
16 children's risk issues. Later, in this section, a·qualitative discussion about susceptibility is
17 included that acknowledges that toxicological wisdom suggests that background respiratory
18 system conditions could make some in the population more susceptible to chronic effects of DE
19 exposure. Similarly, infants and children could have greater susceptibility simply because their
20 developing organs and defense systems may be less effective at dealing with insults from DE
21 exposure. These suggestions are not unique to DE exposure, though.
22
23 12.2.3. Carcinogenic Hazard Assessment
24 For inhalation exposure, both human studies and animal bioassays are available to assess
25 the chronic exposure carcinogenic potential for DE. In fact, both the human and the animal
26 studies provide evidence that exposure to DE has potential to be carcinogenic to humans under
27 some condition of exposure. Chapters 7 and 8 review these data in detail. A finding· about the
28 hazard potential does not specify the magnitude of the impact, information on which is discussed
29
30
in Chapter 11, the carcinogenicity dose-response evaluation section.
31 12.2.3.1. Human Evidence
32 A total of 26 key epidemiologic studies have been evaluated to examine the association
33 between exposure to DE and increased cancer response. The positive human evidence consists of
34 observed increases in lung cancer mortality .in a number of occupational exposure studies and
35 some suggestion of other possible cancer sites. Cohort, .case control, and population-based studies
2/1/98 12-9 DRAFT--DO NOT CITE OR QUOTE