Environmental Engineering Reference
In-Depth Information
numbers of replicates, lower cost and shorter timelines, and minimize the need to
sacrifi ce animals. In general, the in vitro studies support the fi ndings of the in vivo
investigations in that they provide evidence that high exposures to PM metal extracts
and the dominant transition metals can produce ROS and may also alter gene
expression involved in cell-signaling pathways and metal-homeostasis. However, as
noted previously, the exposure levels used in the majority of the in vivo studies are
extremely high and of dubious relevance to actual human exposures. It is also very
diffi cult to extrapolate exposures in cell cultures to either laboratory animal studies
or human exposures to ambient PM. Therefore, although the reviewed studies
inform the possibility of a hazard, they are of limited usefulness in evaluating the
risk that metals in PM pose.
4
Summary
In this review, we critically evaluated the epidemiological and toxicological evidence
for the role of specifi c transition metals (As, Cr, Cu, Fe, Mn, Ni, Se, Ti, V and Zn) in
causing or contributing to the respiratory and cardiovascular health effects associ-
ated with ambient PM. Although the epidemiologic studies are suggestive, and both
the in vivo and in vitro laboratory studies document the toxicity of specifi c metals
(Fe, Ni, V and Zn), the overall weight of evidence does not convincingly implicate
metals as major contributors to health effects. None of the epidemiology studies that
we reviewed conclusively implicated specifi c transition metals as having caused the
respiratory and cardiovascular effects associated with ambient levels of PM. However,
the studies reviewed tended to be internally consistent in identifying some metals
(Fe, Ni, V and Zn) more frequently than others (As, Cu, Mn and Se) as having posi-
tive associations with health effects. The major problem with which the epidemio-
logical studies were faced was classifying and quantifying exposure. Community
and population exposures to metals or other components of ambient PM were
inferred from centrally-located samplers that may not accurately represent individual
level exposures. Only a few authors reported fi ndings that did not support the stated
premise of the study; indeed, statistically signifi cant associations are not necessarily
biologically signifi cant. It is likely that “negative studies” are under-represented in
the published literature, making it a challenge to achieve a balanced evaluation of the
role of metals in causing health effects associated with ambient PM.
Both the in vivo and in vitro study results demonstrated that individual metals
(Cu, Fe, Ni, V and Zn) and extracts of metals from ambient PM sources can produce
acute infl ammatory responses. However, the doses administered to laboratory ani-
mals were many orders of magnitude greater than what humans experience from
breathing ambient air. The studies that used intratracheal instillation have the advan-
tage of delivering a known dose to a specifi c anatomical location, but are not
analogous to an inhaled dose that is distributed over the surface area of the respira-
tory tract. Studies, in which laboratory animals or human volunteers inhaled CAPs
best represent exposures to the general human population.
 
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