Respiratory and Cardiovascular Effects of Metals in Ambient Particulate Matter: A Critical Review - Reviews of Environmental Contamination and Toxicology - page 179

study. Instillation of ROFA fractions from the precipitator produced signifi cant
increases in infl ammatory markers, ROS (no p value given), and signifi cantly
decreased bacterial clearance compared to air heater ROFA and saline controls.
Critical Comments on In Vivo Studies with ROFA
It should be noted that the metal concentrations used in the ROFA studies discussed
here (see Table 8 ) were extremely high and do not refl ect actual ambient exposures.
For PM 2.5 metals, ambient concentrations of metals in the ROFA extracts gleaned
from STN and IMPROVE (Table 1 ), and ambient concentrations reported for the
epidemiological studies (see Table 4 ), were up to three million times higher than
those found in ambient air. Fe levels reported in the ROFA extracts were up to
120,000 times higher than ambient levels, while ROFA levels of Zn were up to
27,000 times higher. Concentrations of Ni and V in the ROFA extracts were even
higher, i.e., respectively up to 1.9 million and 3.1 million times higher than recorded
ambient levels. These extreme differences between ROFA and ambient levels of
metals should be considered when interpreting the signifi cance of the ROFA study
results. It should also be noted that on a mass basis, ROFA contains a higher propor-
tion of Ni and V than ambient PM.
In Vivo Exposures to Individual Metals
The metals most frequently detected in ambient PM in the U.S. are Cu, Fe and Zn,
with Ni, V; other metals are detected less frequently. The studies described below
investigated the toxicity of individual metals found in specifi c-source particulates.
The doses of individual metals tested in these studies are summarized in Table 9 . No
Observed Adverse Effect Levels (NOAEL) and Lowest Observed Adverse Effect
Levels (LOAEL) are also presented in this table where suffi cient dose-response
information was available.
Using the Canadian atmospheric dust sample, EHC-93 (Environmental Health
Center-93), Adamson et al. ( 2000 ) conducted a series of studies to determine which
of the metal constituents in this PM was associated with toxicity. The concentra-
tions of the target metals in the EHC-93 PM are presented in Table 6 . Swiss mice
were intratracheally instilled with the soluble EHC-93 concentration of Al ammo-
nium nitrate, Cu sulfate, Fe sulfate, Pb nitrate, Mg chloride, Ni chloride, Zn chloride
or saline controls. Since the concentration of Zn appeared to have the greatest effect
on infl ammatory markers in BALFs, additional studies were conducted with Zn
chloride and Zn sulfate at one and ten times the concentration of soluble Zn in the
EHC-93 sample. The mice developed a strong infl ammatory response and lung
injury over the 2-week post-instillation period, and after 4 weeks the animals treated
with Zn sulfate at ten times the EHC-93 concentration had also developed fi brosis.
The authors point out that the doses used were roughly four times ambient levels
and that the method of administration was not analogous to ambient human PM