Health Effects of Metals in Ambient Air Particulate Matter - Aerosols: Measurement, Dosimetry, and Health Effects - page 371

(Ni, V, Zn, Co, Mn, Cu), but not by any individual metal alone. Intraperitoneal pretreatment of
mice with the antioxidant dimethylthiourea abrogated ROFA-s-mediated AHR, conirming the
role of ROS in metal-induced inlammation. Interestingly, ROFA-s had no effect on AHR of 2
week old mice, in contrast to the AHR seen in 3 and 8 week old mice. This study also found
that ROFA treatment does not initiate neurogenic inlammation because ROFA-s-mediated AHR
was unchanged in neurokinin-1 receptor knockout mice and in mice treated with a neurokinin
antagonist. After either IT or inhalation, of ROFA, lung injury is evident within 24 h of exposure,
with a dose-dependent recruitment of PMNs, eosinophils, and monocytes into the airway. The peak
of this inlux occurs 18-24 h after exposure. The cellular inlux persisted 96 h later, and resolution
occurs slowly. Inlammatory lung injury after ROFA was accompanied by airway, an increase in
susceptibility to infections, and, at high concentration, noncardiogenic pulmonary edema.
AHR induced by ROFA and its soluble components has also been observed in mice that were
exposed to aerosolized ROFA-s. AHR to acetylcholine challenge occurred in a time- and dose-
dependent manner after exposure to ROFA-s with a peak at 48 h post-IH exposure. AHR was
accompanied by an earlier onset of BAL PMNs, (maximal at 12 h after exposure). The AHR caused
by ROFA-s was reproduced by a mixture of its major metal components (Ni, V, Zn, Co, Mn, Cu)
but not by any individual metal alone. Intraperitoneal pretreatment of mice with the antioxidant
dimethylthiourea abrogated ROFA-s-mediated AHR, conirming the role of ROS in metal-induced
inlammation. Interestingly, ROFA-s had no effect on AHR of 2 week old mice, in contrast to the
AHR seen in 3 and 8 week old mice. ROFA treatment did not initiate neurogenic inlammation,
because ROFA-s-mediated AHR was unchanged in neurokinin-1 receptor knockout mice and in
mice treated with a neurokinin antagonist.

14.3.5.4 Tire Dust
Gottipulo et al. (2008) instilled two kinds of tire dust into the lungs of male WKY rats. TP1 was made from
ground tires of recycled styrene butadiene rubber, while TP2 was from scrap tires. Elemental analyses
were available for both dusts. Tests were done with administered saline, TP1, and TP2. Additional tests
were done with soluble Zn or Cu, or both. For TP1 and TP2, there were increases in BAL luid markers
of inlammation and injury (TP2 > TP1) but no effects on cardiac enzymes. Instillation of Zn, Cu, and
Zn + Cu decreased the activity of cardiac aconitase, isocitrate dehydrogenase, succinate dehydrogenase,
cytochrome-c-oxidase, and superoxide dismutase as indicative of cardiac oxidative stress.

14.3.5.5 Metal Oxide Nanoparticles
Lu et al. (2009) compared in vitro assays of intrinsic free radical generation, oxidative activity
in an extracellular environment, cytotoxicity to A549 lung epithelial cells, hemolysis of healthy
human erythrocytes, and inlammation potency in WKY rat lungs. They used nanoparticles of
carbon black (CB), and metal oxide nanoparticles (2-30 nm) composed of NiO, CeO 2 , Co 3 O 4 ,
MgO, SiO 2 , anatase, rutile, and three kinds of alumina; ZnO as UFP (90-210 nm); and alumina as
0.3 μm microparticles. For assays using equivalent surface areas, only NiO and alumina #2 (7 nm)
caused signiicant lung inlammation, while four of the 13 metal oxides (NiO, CeO 2 , Co 3 O 4 , and
CB) caused signiicant free radical generation (of these, only NiO was inlammogenic), and 3 of 13
(NiO, CeO 2 , and alumina #2) were signiicantly hemolytic (of these, only NiO was inlammogenic).
Thus, in vitro assays cannot be relied on to predict lung inlammation.

14.4 SUMMARY OF UNRESOLVED ISSUES AND CONCLUSIONS

14.4.1 w Here d o PM M etal c oMPonents F it in tHe l arger
P icture oF PM-a ssociated H ealtH e FFects ?
There is clearly emerging evidence that the inhalation of some components of ambient air PM are
associated with adverse health effects at concentrations near or not much higher than current ambient