Health Effects of Metals in Ambient Air Particulate Matter - Aerosols: Measurement, Dosimetry, and Health Effects - page 369

intratracheally with 3 or 10 mg PM/kg. They assessed changes in biochemical markers, cell
differentials, and histopathological changes in the lungs and blood 24 h later. They reported dose-
related adverse effects with both PM 2.5 and PM 10-2.5 CAPs that were mainly related to cytotoxicity,
inlammation, and blood viscosity. There was a trend toward greater toxicity with increasing
trafic levels. They selected component markers for trafic-related PM sources, that is, polynuclear
aromatic hydrocarbons (PAHs), Zn, Cu, Ba, and K. There was no correlation of any of the effect
markers with combustion-exhaust-related PAHs except for an increase of lymphocytes associated
with PM 2.5 CAPs (p = 0.04). There was a signiicant correlation between PM 2.5 Zn and BALF protein
(p = 0.01) and LDH (p = 0.03), and PM 2.5 K with total BALF cells and PMNs. In pathological assays,
there were signiicant associations of PM 2.5 K with alveolar inlammatory foci, and ascorbate with
PM 2.5 Cu (p = 0.02) and Ba (p = 0.01). For the PM 10-2.5 CAPs, there were signiicant correlations of
BALF protein with Cu (p = 0.02) and with Ba (p = 0.05), and for alveolitis with Cu (p = 0.04). They
concluded that the effects were attributable to components derived from brake wear (Cu and Ba),
tire wear (Zn), and wood smoke (K).
14.3.5.2 Utah Valley Dust
Some of the most convincing evidence to demonstrate that the lung dose of bioavailable transition
metals, not just instilled PM mass, was the primary determinant of the acute inlammatory response
was derived from a series of studies using ambient PM 10 collected in the Utah valley (Frampton
et al., 1999; Dye et al., 2001; Ghio and Devlin, 2001). Frampton et al. (1999) showed that the extract
of PM 10 collected during the strike (having the lowest metal content, speciically soluble Fe, Cu,
Pb, and Zn), showed no apparent cytotoxicity, minimal induction of cytokines, and lowest oxidant
generation ability compared to extracts from PM 10 (collected before and after the strike) having
higher metal content. These experiments indicate: (1) that instillation of ambient air particles, albeit
at a very high concentration, can produce cardiovascular effects; and (2) that exposures of equal mass
dose to particle mixtures of differing composition did not produce the same cardiovascular effects,
suggesting that PM composition rather than just mass was responsible for the observed effects.
To investigate the dose, time course, and the roles of speciic metals, Dye et al. (2001) exposed SD
rats, by IT, with equivalent masses of aqueous extracts of the same Utah ambient PM 10 , described
earlier, at 0, 0.83, 3.3, 8.3, or 16 mg extract/kg body weight in 0.3 mL saline (Dreher et al., 1997).
Twenty-four hours after IT, rats exposed to extracts of PM 10 collected when the plant was open
developed signiicant pulmonary injury and PMN inlammation. Additionally, 50% of rats exposed
to these extracts had increased airway responsiveness to acetylcholine, compared to 17% and 25%
of rats exposed to saline or to the extracts of PM 10 collected when the plant was closed. By 96 h,
these effects were largely resolved, except for increases in lung lavage luid PMNs and lymphocytes
in rats exposed to PM 10 extracts from prior to the plant closing. Analogous effects were observed
with lung histologic assessment. Chemical analysis of extract solutions demonstrated that extracts
of PM 10 collected when the plant was open contained more SO 4 = , cationic salts (e.g., Ca, K, Mg),
and certain metals (e.g., Cu, Zn, Fe, Pb, As, Mn, Ni). The strong qualitative coherence among
these human epidemiological, clinical, and animal toxicological studies clearly showed that soluble
metals could be the most important components related to PM exposure-related health outcomes.
14.3.5.3 Residual Oil Fly Ash
SD rats were exposed IT to ROFA suspension, leachate, washed, neutralized suspension, neutralized
leachate, neutralized leachate supernate, and suspension + deferoxamine (2.5 mg ROFA/rat). The
leachate produced similar lung injury to that induced by the suspension, implicating the soluble
components for the effects. The inlammatory effects were abrogated by depletion of metals from
the ROFA leachate. A mixture of transition metal sulfate containing Fe, V, and Ni largely reproduced
the lung injury induced by ROFA. Neutralization of ROFA, soluble Ni, and transition metal sulfate
mixtures produced ine precipitates in the solutions, leading to the production of a more progressive
acute lung injury for ROFA particles, and enhanced morbidity/mortality for Ni and the transition