Health Effects of Metals in Ambient Air Particulate Matter - Aerosols: Measurement, Dosimetry, and Health Effects - page 370

metal sulfate mixtures, providing direct evidence for soluble transition metals to produce pulmonary
injury, at least for exposures at relatively high doses of ROFA. To further demonstrate how ROFA
with differing V and Ni may differ in terms of their ability to cause in vivo acute pulmonary injury,
male SD rats were exposed IT with either saline or saline suspension of 10 ROFA samples collected
at various sites within a power plant (Kodavanti et al., 1998). After 24 h, ROFA containing the
highest concentrations of water-leachable Fe, V, and Ni or V and Ni caused the largest increase in
these biochemical indices of lung injury, while ROFA containing primarily soluble V caused more
dramatic PMN inlux. It appears that while V was responsible for the recruitment of PMNs, Ni was
responsible for increase pulmonary permeability, suggesting that the potency and the mechanism of
pulmonary injury differ between V and Ni.
BAL inlammatory markers in normotensive WKY and SH rats were examined after a single
IT to either saline or ROFA. BAL lung injury markers were measured at 24 and 96 h post-IT
(Kodavanti et al., 2001). Rats were also IT instilled with either VSO 4 or NiSO 4 ·6H 2 O in saline and
assessed at 6 and 24 h post-IT. ROFA-induced increases in BALF markers of inlammation were
generally greater in SH rats than in WKY rats and had resolved by 96 h post-IT in both strains. In
response to a single-metal IT exposure, both the onset and duration of the inlammatory response,
were metal and strain dependent. V-induced increases in BALF protein and LDH peaked at 6 h
post-IT in WKY rats. In SH rats, BALF protein and LDH were not affected by V. Ni increased
BALF protein in both strains. The Ni-induced increase in LDH activity was progressive over 24 h
(WKY > SH). The number of macrophages decreased following V and Ni exposure at 6 h, and this
decrease was reversed by 24 h in both strains. V caused BALF PMNs to increase only in WKY rats.
The Ni-induced increase in BALF PMNs was more dramatic and progressive than that of V, but
was similar in both strains. Lung histology similarly revealed more severe and persistent edema,
perivascular and peribronchiolar inlammation, and hemorrhage in Ni- than in V-exposed rats.
This effect of Ni appeared slightly more severe in SH than in WKY rats. This study showed that
inlammatory response to metallic constituents of ROFA is both strain and dose dependent, and that
V caused pulmonary injury only in WKY rats, whereas Ni was toxic to both strains. In subsequent
studies (Kodavanti et al., 2001; Wu et al., 2003), however, Zn was found to be the responsible
component in a batch of different oil combustion emission particles.
Some, or perhaps most, of the differences in biological responses to the metals in the ROFA
could be explained by aqueous solubility, and the effects of solubility on translocation. Wallenborn
et al. (2007) measured the elemental content of lungs, plasma, heart, and liver of male WKY rats
after IT administration of either saline or 8.3 mg/kg of ROFA from a Boston power plant, and
measured tissue concentrations 4 and 24 h after the instillation. Water-soluble metals (V, Ni, Zn, and
Mn) were detected at both time points, while Al and Si were not.
The effects of two ROFA samples of equivalent diameters, but having different metal and
SO 4 = content, on pulmonary responses in SD rats were studied (Gavett et al., 1997). One sample
had higher saline-leachable SO 4 = , Ni, V, and Fe, whereas the other sample had higher Zn. At a
dose of 2.5 mg, 4 of 24 rats exposed to high-Zn ROFA suspension or supernatant had died 4 days
post-IT, while none had in high-Ni, V, and Fe groups. Pathological indices, such as alveolitis,
early ibrotic changes, and perivascular edema, were greater in both high-Zn suspension and
supernatant-exposed groups than the other ROFA. In surviving rats, exposures to high-Zn ROFA
also worsened the baseline pulmonary function parameters and AHR to acetylcholine as well
as BAL PMNs. This study conirmed the inding of an earlier study in guinea pigs that soluble
forms of Zn are capable of producing a greater pulmonary response than other sulfated metals in
combustion generated particles (Amdur et al., 1978).
AHR induced by ROFA and its soluble components was also observed in mice exposed to an
aerosolized soluble leachate of ROFA (ROFA-s). AHR to acetylcholine challenge occurred in a
time- and dose-dependent manner after exposure to ROFA-s with peak at 48 h post-IH exposure.
AHR was accompanied by an earlier onset of BAL PMNs, which was maximal at 12 h after
exposure. The AHR caused by ROFA-s was reproduced by a mixture of its major metal components