Health Effects of Metals in Ambient Air Particulate Matter - Aerosols: Measurement, Dosimetry, and Health Effects - page 368

of oxide and sulfate forms of transition metals (Mn, Ni, V, Fe, Cu oxides, and Ni and V sulfates)
at concentrations of 0.05 mg/m 3 . Such concentrations are 2-4 orders of magnitude higher than
for typical ambient U.S. levels (usually 0.1-1.0 μg/m 3 for such metals). No signiicant effects of
exposure to the transition metal aerosols were observed. The discrepancy between the results of
Muggenburg et al. (2003) and those of Clarke et al. (2000) leave open major questions about PM
effects on the cardiovascular system of the dog. The use of ROFA samples from different sources
may have accounted for the differences in response that were reported.
Kodavanti et al. (2003) exposed male SD, WKY, and SH male rats to Boston ROFA, which
contained bioavailable Zn at doses of 2, 5, or 10 mg/m 3 for 6 h/day for four consecutive days.
A second exposure paradigm used exposure to 10 mg/m 3 ROFA for 6 h/day, 1 day/week, for 4 or
16 consecutive weeks. Cardiovascular effects were not seen in SD and SH rats with the acute or
chronic exposure, but WKY rats from the 16 week exposure group had cardiac lesions consisting of
chronic-active inlammation, multifocal myocardial degeneration, ibrosis, and decreased numbers
of granulated mast cells. These results suggest that myocardial injury in sensitive rats can be caused
by long-term inhalation of high concentrations of ROFA.
14.3.5 l ung i nstillation s tudies witH PM c oMPonents
Besides using CAPs inhalation study, which can be expensive and time consuming, studies using
collected urban PM for intratracheal instillation/aspiration (IT/IA) to healthy and compromised
animals have also produced interesting information concerning inluential PM components and
their health-related effects. Although there are many issues such as extrapolation and dosimetry
that need to be addressed when IT is used in a toxicological study, the results of IT of ambient
PM collected from different geographical areas can be used to support the hypothesis that PM
composition is one of the most relevant parameters affecting ambient PM-associated health effects.
Similarly, IT delivery of well-deined components of ambient air PM, in studies of comparative
toxicity, can also be informative for the identiication of particularly inluential components.
14.3.5.1 Ambient Air PM
Instillation in rats of Ottawa PM extracts at 2.5 mg induced pronounced biphasic hypothermia, a
severe drop in HR, and increased arrhythmias (Watkinson et al., 2000a,b) that were not seen with a
comparable instilled dose of Mt. St. Helens volcanic ash. The results of this study showed that urban
sites with high contributions from vehicles and industry were most toxic. This study also showed
that the biological effects differ as a function of site and season. The analysis based on chemical
class indicated that PM containing metal oxides, transition metals (Pb, Mn, Cu, Se, Zn, and As),
EC, OC, and hopanes/steranes were the most important predictors of cytotoxic and inlammatory
responses. The analysis also indicated that SO 4 = , secondary organic aerosols, meat cooking, and
vegetative detritus were not correlated with the biological responses. On the other hand, analysis
based on the source apportionment, the most toxic samples were from the sites during seasons
with the largest contributions of diesel and gasoline emissions, whereas wood burning was only
weakly correlated with toxicity endpoints. The analysis also indicated that SO 4 = , secondary organic
aerosols, meat cooking, and vegetative detritus were not correlated with the biological responses.
This study supports the concept that speciic constituents and/or sources of PM affect its toxicity.
Adamson et al. (2000) sought to determine which component(s) of the urban air PM from Toronto
could account for its pulmonary toxicity. They did an aqueous extraction of the whole dust and
instilled the extract and equivalent concentrations of the soluble metals within it into the lungs
of mice. Three days later, in comparison to IT saline, only the whole extract and the Zn solution
produced signiicant increases in inlammatory cells and protein in BALF. With 28 days of exposure,
the Zn produced focal necrosis of Type 1 alveolar cells, and focal ibrosis was seen at 4 weeks.
Gerlofs-Nijland et al. (2007) collected PM 2.5 and PM 10-2.5 CAPs from six European cities
with contrasting trafic proiles, PM composition, and in vitro analyses, and exposed SH rats