Environmental Engineering Reference
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with saline or 8.33 mg/mL HP-12 suspension, sacrifi ced 4 or 24 h post-instillation,
and samples of blood, lung, heart and liver collected and analyzed for transition met-
als. Signifi cantly higher levels of V and Ni were found in the lung, plasma, heart and
liver of animals instilled with HP-12 as compared to saline controls (p
0.05), sug-
gesting that the soluble metals are cleared and presumably enter the systemic circula-
tion, while insoluble metals remained in the lungs. However, higher baseline levels of
Zn and Mn were found in the tissues of control animals, making it more challenging
to detect changes related to instillation of these same metals in HP-12. Of particular
relevance to the purpose of this study is the observation that there were no signifi cant
differences in the amount of Zn (4 and 24 h) or Mn (24 h) in the heart of HP-12-treated
animals, compared to controls.
Hamada et al. ( 2002 ) investigated the effects of ROFA from the precipitator of a
Boston area power plant on airway hyper-responsiveness in 7-8-week-old, and
2-and 3-week-old BALB/c mice exposed by inhalation for 30 min to nebulized
aerosols of ROFA at 0 (controls), 10, 50 and 100 mg/mL; the fi nal pH of the ROFA
suspension was acidic (viz., 5.5). To determine the effect of pH, mice were also
exposed to aerosols adjusted to a pH of 7.2. Airway responsiveness was measured
by exposing control and ROFA-exposed mice to increasing concentrations of
methacholine aerosol at periods up to 120 h post-ROFA. The potential role of ROS
in the response of ROFA-exposed mice to methacholine challenge was explored by
pre-treating groups of mice with the antioxidant dimethythiourea (DMTU) at doses
of 5, 10, 50 or 100 mg/kg 30 min prior to exposure to 50 mg/mL ROFA aerosol.
Infl ammatory markers were evaluated in BALF from 8-week-old mice exposed to
50 mg/mL ROFA at 6, 12, 24 and 48 h post-exposure. As a side study to determine
if age and maturation determine airway responsiveness, mice aged 2, 3, and
7-8 weeks old were exposed to 50 mg/mL ROFA and examined 6 and 12 h later for
infl ammatory response in BALF. Exposure to 50 or 100 mg/mL ROFA, but not to
10 mg/mL, signifi cantly amplifi ed the airway hyper-responsiveness to all challenge
concentrations of methacholine at 12, 24 and 48 h after exposure. A mixture con-
taining the individual metals, but not the individual metals alone, produced approxi-
mately the same level of signifi cant response as the complete ROFA suspension.
ROFA suspensions adjusted to pH 7.2 or 5.5 both produced signifi cantly higher
airway responsiveness than saline; moreover, fi ltered ROFA produced signifi cantly
greater responsiveness than saline. The authors did not indicate if adjusting the
acidic ROFA suspension to physiologic pH resulted in the formation of a fi ne pre-
cipitate as observed by Dreher ( 1997 ).
Treatment with DMTU prior to inhaling ROFA decreased the magnitude of
response to subsequent methacholine challenge. Maturation of the respiratory and
immune system was relevant to the response to methacholine in the following order:
very young 2-week <3- <7-8-week-old mice. Although this series of experiments
was conducted with high, non-ambient doses of ROFA and constituent metals, the
fi ndings suggest that some type of interactions of the constituent metals in the
ROFA are involved in provoking the infl ammatory response and that oxidative
mechanisms may be at least partially responsible for the injury. This is also one of
the few in vivo studies, in which animals were exposed to PM by inhalation.
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