Health Effects of Metals in Ambient Air Particulate Matter - Aerosols: Measurement, Dosimetry, and Health Effects - page 366

been related to vehicular emissions. Plasma ibrinogen levels in SH rats were better correlated with
the levels of water-soluble metals, particularly Zn, than mass and other components of the CAPs
(Kodavanti et al., 2005). This study demonstrated that strain-speciic systemic effects were not
linked to high mass but appear to be dependent on CAP chemical composition.
14.3.3 l onger -t erM caP s i nHalation s tudies
A series of longer-term PM 2.5 CAPs inhalation studies were conducted at NYU's laboratory in
Sterling Forest. Because these studies collected both long-term ECG data as well as simultaneous
data on PM 2.5 composition, such studies can have more power to identify possible causal
components of ambient PM 2.5 . These NYU subchronic CAPs inhalation studies involved a series
of experiments that were used to study both the acute and cumulative effects of daily inhalation
exposures to PM 2.5 CAPs in a mouse model of atherosclerosis. The results of the irst of these studies,
involving 5-6 months of warm-season daily exposures (5 day/week, 6 h/day to an average CAPs
concentration = 110 μg/m 3 ) were described n a special issue of Inhalation Toxicology (Chen and
Hwang, 2005; Chen and Nadziejko, 2005; Gunnison and Chen, 2005; Hwang et al., 2005; Lippmann
et al., 2005a,b; Maciejczyk and Chen, 2005; Veronesi et al., 2005). These papers documented CAPs
exposure-associated acute and chronic effects on cardiac function, increased amounts of, and more
invasive, aortic plaque, and changes in brain cell distribution and in gene expression markers, as
well as data on the effects of daily CAPs exposures in vitro on Nf k B activation.
The biological plausibility of ambient air PM contributing to changes in brain cell distribution
was enhanced by a follow-up study by Sama et al. (2007) in which they conducted in vitro assays of
the cellular and genomic responses of immortalized microglia cells (BV2) to CAPs collected during
the same study described in the special issue of Inhalation Toxicology . Two composite samples
were applied to the microglia cells; one composed of CAPs from days with high potency (HP) in
their stimulation of NF k B release in human bronchial epithelial cells and the other from CAPs
collected on days with low potency (LP). The LP composites reduced intracellular ATP at doses
>250 μg/mL, and depolarized mitochondrial membranes (>6 μg/mL) within 15 min. HP and LP
CAPs (>25 μg/mL) differentially affected the endogenous scavengers, glutathione and nonprotein
sulfhydryl, after 1.5 h. Both HP and LP CAPs stimulated the release of proinlammatory cytokines
TNF a and IL-6 after 6 h of exposure. Microarray analysis of both HP and LP exposed microglia
(75 μg/mL) identiied 3200 (HP) and 160 (LP) differentially expressed (up- and downregulated)
genes relative to the media controls. The results implicate Ni and/or V in the production of these
effects in that these two metals were much higher in concentration in the HP than the LP CAPs. The
biological plausibility for ine and ultraine PM in ambient air to be translocated, from the lungs to
the brain, and to have neurological effects, is supported in a review paper by Peters et al. (2006).
To investigate the contributions of PM 2.5 components to cardiovascular effects, Lippmann et al.
(2005b) used the 5 months of daily 6-h source apportionments of Maciejczyk and Chen (2005),
the continuous HR data for exposure days (weekdays only) used in Hwang et al. (2005), and the
corresponding HRV data used in Chen and Hwang (2005) to determine the source-related PM 2.5
components' associations with HR and HRV. They used HR and HRV data collected on normal
(C57) mice and a murine model for atherosclerotic disease (ApoE −/− ) (Chen and Hwang, 2005;
Hwang et al., 2005). Daily 6 h PM 2.5 air samples were also collected and analyzed by XRF,
permitting attribution to major PM 2.5 source categories (secondary SO 4 = , suspended soil, residual
oil combustion, and a remainder category, which was largely due to long-range transported motor
vehicle trafic). Lippmann et al. (2005c) examined associations between these PM 2.5 components
and both HR and HRV for three different daily time periods: (1) during exposure, (2) the afternoon
following exposure, and (3) late at night. For HR, there were signiicant transient associations
(p = <0.01) for secondary sulfate during exposure, and for residual oil combustion (predominantly
V and Ni) in the afternoon. For HRV, there were comparable associations with suspended soil
(predominantly Si, Al, Ca) in the afternoon and for both residual oil combustion and trafic (Br, Fe,