Environmental Engineering Reference
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sources, ROFA has high concentrations of the transition metals Fe, Ni and V.
Consequently, the majority of studies reviewed in this section focus on the role of
these three metals in the infl ammatory and immune system effects produced by ROFA.
The studies discussed in this section were conducted by investigators affi liated
with NHEERL (Dreher et al. 1997 ; Ghio et al. 1998 ; Kadiiska et al. 1997 ; Kodavanti
et al. 1998 , 2001 ; Lambert et al. 2000 ; Nadadur and Kodavanti 2002 ), and used
samples of ROFA collected downstream of the cyclone of a Florida power plant, and
which burned low sulfur #6 residual oil as the source of particles. Another four stud-
ies (Antonini et al. 2004 ; Hamada et al. 2002 ; Lewis et al. 2003 ; and Roberts et al.
2004 ) were conducted by teams affi liated with the Harvard School of Public Health
and/or National Institute for Occupational Safety and Health (NIOSH). The concen-
trations of the target metals in the ROFA sources used in the following studies are
summarized in Table 8 , and are presented along with estimated ratios of experimen-
tal animal exposures to ambient human exposures that are based on average STN
metal concentrations (Table 1 ).
The fact that these studies were conducted by groups of affi liated researchers
using the same source(s) of ROFA leads to a similarity of experimental designs,
especially within laboratory groups. In most studies, suspensions of ROFA and
solutions of Fe, Ni and V were administered to rats by intratracheal instillation and
the responses of interest measured at two or more time periods after dosing (most
commonly 24 and 96 h). As with the majority of in vivo studies included in this
review, chemical and cellular indicators of infl ammation were evaluated in BALF. In
a number of studies, a chelating agent was used to bind the transition metals to con-
fi rm that the responses observed were largely (or at least partially) mediated by
divalent cations.
ROFA from a Florida Power Plant
In two early studies, researchers at NHEERL investigated the relative activity of
various soluble and insoluble formulations of ROFA on markers of acute lung injury
(Dreher et al. 1997 ) and production of free radical damage (Kadiiska et al. 1997 ) in
BALF from Sprague Dawley rats at 24 or 96 h post-treatment. Sulfate solutions of
Fe, Ni and V at doses equivalent to ROFA were administered to mimic the activity
of the ROFA. Dreher et al. ( 1997 ) also added a chelating agent to a soluble suspen-
sion of ROFA particles to confi rm the activity of the transition metals.
Dreher et al. ( 1997 ) found that ROFA preparations containing soluble metals
produced signifi cantly more injury as measured by increases in BALF parameters
than the non-soluble forms of ROFA. Although administration of equivalent doses
of the individual Fe, Ni or V sulfates (dose equivalent to 2.5 mg ROFA/rat; or 8.3 mg
ROFA/kg body wt) produced signifi cant injury compared to controls, the extent of
the injury was not as great as that produced by ROFA suspension. Neutralization to
a more physiologic range (pH 6.0) of the normally acidic ROFA suspension, ROFA
leachate, and V and Ni sulfates produced a fi ne precipitate. Rats dosed with the
neutralized ROFA and metal sulfates either died or exhibited severe respiratory dis-
tress. The addition of chelating agent to soluble ROFA enhanced rather than dimin-
ished the overall toxic response. In mixtures of individual metal sulfates, chelation
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