Health Effects of Metals in Ambient Air Particulate Matter - Aerosols: Measurement, Dosimetry, and Health Effects - page 359

While no studies involving inhalation exposures of laboratory animals in vivo or of cells in vitro
to pure chemicals and their compounds, at doses with environmental relevance, have produced
adverse health effects, some toxicological studies using high PM mass exposures of diluted tailpipe
emissions, especially whole diesel engine exhaust (WDE) or to source-related PM mixtures con-
taining multiple metals, such as residual oil ly ash (ROFA), coal ly ash (CFA), and concentrated
ambient particles (CAPs), have produced effects that appear to be related to their relatively low
contents of metals and carbonaceous material. However, it has been dificult to determine the roles
played by the individual components in the effects observed. Also, many laboratory-based studies
have used resuspended dusts at relatively high mass concentrations, and the relevance of the effects
observed to human ambient air exposures at much lower PM mass levels is, therefore, uncertain.
While effects found in high-dose laboratory in vitro exposures have occasionally been suggested to
also occur with exposures near to ambient concentrations (e.g., inlammatory indicators in the CAPs
study of Maciejczyk and Chen [2005] and Maciejczyk et al. [2010]), more often those effects have
not been found (e.g., no abnormal levels of cytokines in human volunteers in the CAPs exposure
study of Ghio et al. [2000]).
Studies of the effects of relatively low concentrations of airborne PM components in humans have
all involved complex mixtures. These include those short-term inhalation exposures to (1) CAPs in
healthy human volunteers, and (2) diluted WDE, and (3) natural exposures to ambient PM, where
data from simultaneous daily and/or seasonal or annual average PM compositional analyses were
available for time-series and cross-sectional studies of effects in large human populations. Due to the
limitations of statistical power in such natural population studies, the epidemiological analyses have
focused more on identifying the contributions to the effects of factors or source-related mixtures
than of individual components within the mixtures. Additional information comes from laboratory
studies that have involved instillation of particle suspensions into human lungs and subsequent anal-
yses of bronchoalveolar lavage luid (BALF) samples for particle retention and biomarkers of effects.
Studies of the effects of relatively low concentrations of airborne PM components in laboratory
animals that involve complex mixtures include: (1) short-term inhalation exposures to CAPs in
mice, rats, and dogs; (2) subchronic inhalation exposures of CAPs to mice and rats; and (3) inhala-
tion and intratracheal (IT) lung instillation of components and source-related mixtures.
A major objective of this chapter is to combine the analyses of the experimental studies with
CAPs and other ambient air PM components in humans and other animals with the associations
between ambient air concentrations of PM and its components to determine the nature and extent
of the effects of ambient air PM and its components of major organ systems and their cross-species
consistency, and to identify, as possible, the more potent PM components. Mauderly and Chow
(2008) have reviewed the health effects on carbonaceous compounds in ambient air, and Chen and
Lippmann (2009) have reviewed the health effects of metals in ambient air. The emphasis in this
chapter will be on the metal content of the PM on the basis that they appear to be more potent, at
typical ambient air concentrations, than those of EC and OC.
It is important to remember that all three particle size ranges are chemically nonspeciic pollutant
classes, and may originate from, or been derived from, various emission source types. Thus, PM
toxicity may well vary, depending on its size distribution, source, and chemical composition. If the
PM toxicity could be associated with speciic source signatures, then health effects research could
be better focused on speciic PM components that come from those sources and speciic biological
mechanisms could be postulated for further consideration by toxicological studies. PM health
effects research is, therefore, now being increasingly focused on source apportionment of PM using
chemical speciation data, and this review of the CAPs literature emphasizes those CAPs studies
that used PM compositional data to identify associations of exposures to PM source categories or to
individual PM components that have been associated with health-related effects.
In addition to this introduction, this chapter contains sections discussing studies in humans
(Section 14.2), studies in laboratory animals and in vitro (Section 14.3), and unresolved issues and
conclusions (Section 14.4).