Fly Ash Inhalation Research Articles

Subacute inhalation toxicity assessment of fly ash from industrial waste incinerators

Fly ash from industrial waste incinerators has been a significant concern because of their constituent toxic heavy metals and organic compounds. The objective of this study was to identify the subacute inhalation toxicity of fly ash from industrial waste incinerators, using whole body inhalation exposure chambers. Male and female groups of Sprague-Dawley rats were exposed to fly ash by inhalation of concentrations of 0, 50, 100, 200 mg/m3, for 6 h/day, 5 days/week for 4 weeks. There was no significant difference in body weight, and relative organ weight to body weight, between the exposure groups and the control group. Hematological examinations revealed a significant increase of monocyte counts in fly ash exposed rats and brown pigment laden macrophage was found in the lungs of rats exposed to high concentration of fly ash. A decrease of blood glucose levels and an increase in glutamate oxaloacetate transaminase activity were observed in fly ash treated rats. There was also a significant increase of lactate dehydrogenase levels in rat blood exposed fly ash. A significant dose-dependent increase of DNA damage was found in lymphocytes, spleen, bronchoalveolar lavage, liver, lung, and thymus of rats exposed to fly ash. In addition, the level of lipid peroxidation was increased in the plasma of rats exposed to a high concentration of fly ash. These results suggest that inhalation of fly ash from industrial waste incinerators can induce histopathologic, hematological, and serum biochemical changes and oxidative damage.

Increased Nonconducted P-Wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

Increased Nonconducted P-Wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

Increased Nonconducted P-Wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

BackgroundExposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that are reflected in the electrocardiogram (ECG), including altered cardiac rhythm, myocardial ischemia, and reduced heart rate variability (HRV). The sensitivity and reliability of ECG-derived parameters as indicators of the cardiovascular toxicity of PM in rats are unclear.ObjectiveWe hypothesized that spontaneously hypertensive (SH) rats are more susceptible to the development of PM-induced arrhythmia, altered ECG morphology, and reduced HRV than are Wistar Kyoto (WKY) rats, a related strain with normal blood pressure.MethodsWe exposed rats once by nose-only inhalation for 4 hr to residual oil fly ash (ROFA), an emission source particle rich in transition metals, or to air and then sacrificed them 1 or 48 hr later.ResultsROFA-exposed SH rats developed nonconducted P-wave arrhythmias but no changes in ECG morphology or HRV. We found no ECG effects in ROFA-exposed WKY rats. ROFA-exposed SH rats also had greater pulmonary injury, neutrophil infiltration, and serum C-reactive protein than did ROFA-exposed WKY rats.ConclusionsThese results suggest that cardiac arrhythmias may be an early sensitive indicator of the propensity for PM inhalation to modify cardiovascular function.

Systemic oxidative stress induced by Diabetes and Residual Oil Fly Ash Inhalation

The importance of evaluating the systemic effects of diabetic subjects exposed to air pollution is notorious, specially to the relevance that both factors have in the world socio‐economic scenario. The aim of the present study is to evaluate the effects of diabetes and chronic exposure to “residual oil fly ash” (ROFA) in the rat systemic oxidative stress. The animals were divided into four groups: diabetic: treated with ROFA (DM POL) − 50μg of ROFA/10μL of saline, intranasal instillation (i.n.); diabetic (DM NPOL) ‐ 10μL of saline, i.n; non‐diabetic treated with ROFA (ND POL) − 50μg of ROFA/10μL of saline, i.n. and non‐diabetic (ND NPOL) ‐ 10μL of saline, i.n., for 60 days. The diabetes was induced by 60mg/kg, i.p. streptozotocin administration. Blood sample was collected on the 30º and 60° days of treatment to evaluate SOD and catalase activity and the lipid peroxidation (through the concentration of malondialdeyde ‐MDA‐). After 30 days, we observed that ND POL animals showed higher levels of SOD comparing to the other groups (p<0.05) while catalase and MDA concentration did not show difference among the groups. After 60 days, the diabetic groups (DM POL and DM NPOL) showed increased levels of MDA. SOD activity was not statistically different among the groups (p> 0.05) while catalase showed statistically increased in the DM POL, DM NPOL and ND POL groups as compared to the control group ND NPOL (p<0.05). The global mortality rate of the DM POL group was 46% while in the other groups this rate was 0%. All deaths occurred after the 30° day of treatment with ROFA. The present study suggests that diabetic condition increases the susceptibility of health adverse effects induced by ROFA instillation and that oxidants could be involved in these effects.Support: FFFCMPA

Effect of fly ash inhalation on biochemical and histomorphological changes in rat liver

The effect of fly ash inhalation (4 h daily, 5 days a week) for 28 days on the deposition of metal ions and histopathological changes in the liver and serum clinical enzymes has been studied. The results showed an increase in the concentration of metals such as cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), and lead (Pb) in the tissues of exposed rats. The level of metals varied from metal to metal and from organ to organ. Level of serum enzymes such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, and alkaline phosphatase were increased in fly ash exposed rats using whole body inhalation exposure as compared to sham controls. Histopathological studies of rat liver exposed to fly ash revealed infiltration of mononuclear cells in and around the portal triads, which seems to be laden with fly ash particles. Hepatocytes showed necrotic changes such as pyknotic nuclei, karyorrhexis, and karyolytic. These changes were more towards the centrolobular areas than the midzonal and periportal areas. These findings demonstrate that the toxic metals of inhaled fly ash in rats may get translocated into extrapulmonary organs, become deposited and hence may manifest their toxic effects on different tissues.

Residual oil fly ash inhalation in guinea pigs: influence of absorbate and glutathione depletion.

Inhaled urban particulate matter (PM) often contains metals that appear to contribute to its toxicity. These particles first make contact with a thin layer of epithelial lining fluid in the respiratory tract. Antioxidants present in this fluid and in cells might be important susceptibility factors in PM toxicity. We investigated the role of ascorbic acid (C) and glutathione (GSH) as determinants of susceptibility to inhaled residual oil fly ash (ROFA) in guinea pigs (male, Hartley). Guinea pigs were divided into four groups, +C+GSH, +C-GSH, -C+GSH, and -C-GSH, and exposed to clean air or ROFA (< 2.5 micron diameter, 19--25 mg/m(3) nose-only for 2.0 h). C and/or GSH were lowered by either feeding C-depleted diet (1 microg C/kg diet, 2 weeks) and/or by ip injection of a mixture of buthionine-S,R-sulfoximine (2.7 mmol/kg body weight) and diethylmaleate (1.2 mmol/kg, 2 h prior). Nasal lavage (NL) and bronchoalveolar lavage (BAL) fluid and cells were examined at 0 h and 24 h postexposure to ROFA. The C-deficient diet lowered C concentrations in BAL fluid and cells and in NL fluid by 90%, and the GSH-depletion regimen lowered both GSH and C in the BAL fluid and cells by 50%. ROFA deposition was calculated at time 0 from lung Ni levels to be 46 microg/g wet lung. In unexposed animals, the combined deficiency of C and GSH modified the cellular composition of cells recovered in lavage fluid, i.e., the increased number of eosinophils and macrophages in BAL fluid. ROFA inhalation increased lung injury in the -C-GSH group only (evidenced by increased BAL protein, LDH and neutrophils, and decreased BAL macrophages). ROFA exposure decreased C in BAL and NL at 0 h, and increased BAL C and GSH (2- to 4-fold above normal) at 24 h in nondepleted guinea pigs, but had no effect on C and GSH in depleted guinea pigs. Combined deficiency of C and GSH resulted in the highest macrophage and eosinophil counts of any group. GSH depletion was associated with increased BAL protein and LDH, increased numbers of BAL macrophages and eosinophils, and decreased rectal body temperatures. We conclude that combined deficiency of C and GSH increased susceptibility to inhaled ROFA; caused unusual BAL cellular changes; resulted in lower antioxidant concentrations in BAL than were observed with single deficiencies. Antioxidant deficiency may explain increased susceptibility to PM in elderly or diseased populations and may have important implications for extrapolating animal toxicity data to humans.

97/04190 Inflammation, chemokine expression, and death in monocrotaline-treated rats following fuel oil fly ash inhalation

97/04190 Inflammation, chemokine expression, and death in monocrotaline-treated rats following fuel oil fly ash inhalation

Elevation of rat pulmonary, hepatic and lung surfactant lipids by fly ash inhalation

Fly ash contains many polycyclic aromatic hydrocarbons and genotoxic trace elements. In rats, fly ash exposure profoundly affects lung and liver histology. In the present study, the effect of fly ash inhalation on lung and liver lipids of rats was examined. Male Wistar strain rats were exposed daily to fly ash (0.27 ± 0.01 mg/L air) in an inhalation chamber, 6 hr daily over a period of 15 days, and were killed on various days, i.e. 16, 30, 60, and 120. Fly ash inhalation significantly (P < 0.05) increased total phospholipids (PL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in lungs. PC and dipalmitoylphosphatidylcholine (DPPC) contents in microsomes and lung surfactant also were significantly (P < 0.05) higher in rats exposed to fly ash compared to control group animals. Radiolabeled precursor incorporation studies indicated that fly ash induced the synthesis of PC and DPPC by both CDP-choline pathway and N-methylation of PE in lung microsomes and enhanced their secretion into lung surfactant. In liver, PC and PE contents were elevated significantly (P < 0.05) by fly ash exposure on days 16 and 30 respectively. A similar elevation of PC was observed in hepatic microsomes; this increase was due to its increased synthesis. However, the increased synthesis of PC in liver occurred to a greater extent by the N-methylation pathway than by the CDP-choline pathway.

Reduction in pulmonary and hepatic respiratory cytochrome contents by fly ash inhalation in rats

Exposure of rats to fly ash for 15 days, 6 hours daily, inhibited pulmonary and hepatic NADH-oxidase activity. The content of cytochrome b and cytochromes a + a 3 was significantly lower in the lungs of the fly-ash-exposed group. However, in liver, fly ash exposure reduced the cytochrome a + a 3 level without affecting the cytochrome b content, indicating a tissue-specific effect. Mitochondrial protein content in both organs was the same in both groups.

Induction of pulmonary and hepatic cytochrome P-450 species by coal fly ash inhalation in rats

The effect of fly ash inhalation on xenobiotic metabolizing enzymes and heme metabolism in lung and liver has been studied in rats. Fly ash inhalation induced pulmonary and hepatic cytochrome P-450 content, aryl hydrocarbon hydroxylase and glutathione S-transferase activity. Induction of cytochrome P-450 was accompanied by induction of δ-amino levulinic acid synthetase in lung and inhibition of heme oxygenase in both lung and liver. Fly ash inhalation induced those species of cytochrome P-450 which closely resembled cytochrome P-448 in spectral properties and electrophoretic mobility.

Comparative lung immunotoxicity of inhaled quartz and coal combustion fly ash

Some inhaled particles that are deposited in the terminal airways and alveoli clear to the lung-associated lymph nodes, and insoluble particles have a long half-life in these tissues. Because the lung-associated lymph nodes are essential in the induction of immunity after lung immunization, the accumulation of inhaled particles in these tissues could alter immune responses that develop after lung immunization. This study evaluated the effects of inhaled insoluble fly ash particles or alpha quartz on the immune functions of lung-associated lymph nodes. F344 rats were exposed for 20 days by inhalation of fly ash from a fluidized bed combustor (FBC) or a pulverized coal combustor (PCC). Rats were similarly exposed to quartz particles (Min-U-Sil). Control rats were exposed to filtered air. Groups of ten exposed and ten control rats from each group were immunized by intratracheal instillation of 10(8) sheep red blood cells at 4, 6, 40, and 52 weeks after the start of exposures. The cellularity of the lung-associated lymph nodes and antibody-mediated immunity were evaluated at 7 days after immunization. Tissues from lung and lung-associated lymph nodes were taken for histopathology. The inhalation of FBC fly ash, PCC fly ash, and quartz particles all significantly increased the number of lymphoid cells in the lung-associated lymph nodes at each of the sacrifice times. However, FBC fly ash had no significant effect on antibody immunity, while both PCC fly ash and quartz caused suppression of antibody responses at 52 weeks after the start of exposure. Histopathology data showed that exposure to quartz and PCC fly ash caused significant cellular changes in lungs and lung-associated lymph nodes, while FBC fly ash had less effect. These data indicate that an acute exposure (20 days) to relatively insoluble particles significantly increased the cellularity of the lung-associated lymph nodes for up to 52 weeks after the start of the exposure, but the pulmonary toxicity of the particles inhaled appeared to influence the effects of the exposure on antibody immune responses.

Cytotoxicity of inhaled coal fly ash in rats

The effect of inhalation of coal fly ash for 6 hr daily for 15 days has been studied on the hematology, blood chemistry, and histopathology of lungs and liver of rats up to 4 months from the first day of exposure. Fly ash inhalation significantly reduced WBC, RBC, and hemoglobin contents at earlier periods after exposure but tended to return to normal values at later periods. Fly ash inhalation reduced lymphocytes and increased polymorphonuclears up to 60 days after exposure and after that the alterations were reversible. Blood glucose increased and blood urea and acid phosphatase decreased at early periods after inhalation, but at later periods returned to control group values. Fly ash inhalation profoundly affected the histological structure of lungs and liver at early periods after inhalation. Numerous fly ash-laden macrophages, thickening of alveolar septa, and alveolar dilatation were noted. In the liver, periportal necrosis was also observed. These changes, however, were reversible.

Effect of inhalation of coal fly ash on vitamin A distribution in organs of the rat.

Fly ash contains several polycyclic aromatic hydrocarbons. The effect of inhalation of coal fly ash on vitamin A distribution in various organs of rat has been studied. Inhalation of fly ash for 6 h daily, for 15 d, decreased vitamin A content in liver. The absorption of orally given [3H]retinyl acetate was decreased and so was its localization in liver of rats inhaling coal fly ash.

Cytokinetic and morphological changes in the lungs and lung-associated lymph nodes of rats after inhalation of fly ash

Fischer-344 rats (male and female) were exposed to 36 mg/m 3 of fluidized bed coal combustion fly ash or sham-exposed for 7 hr/day, 5 days/week for 4 weeks, and sacrificed after 2 or 4 weeks of exposure and at 2, 22, and 42 weeks after the end of exposure. Animals were injected with tritiated thymidine 2 hr before sacrifice and autoradiographs prepared from 1-μm sections of lung and lymph node tissue embedded in glycol methacrylate plastic. Differences in labeling indices of pulmonary epithelial cells, alveolar macrophages, airway epithelial cells, and cells of the lung-associated lymph nodes between the exposed and control animals were maximal after 2 and 4 weeks of exposure. Labeling indices for lung epithelial cells were about the same in control and exposed animals at 2, 22, and 42 weeks after the end of exposure. However, these values were elevated relative to earlier control levels. In contrast, morphological changes in the fly ash-exposed animals were most prominent after the end of the exposure. These changes included thickening of the alveolar walls, clusters of particle-filled macrophages in the alveolar region, and perivascular inflammation. Additionally, there were small granulomas in the alveolar region at 42 weeks after the end of exposure. Granulomas were also formed in the lung-associated lymph nodes and bronchus-associated lymphoid tissue. We conclude that the inhalation of fly ash alone had little detrimental effect upon the rat lung. However, the increases in proliferation indicate the potential for fly ash combined with a carcinogen to enhance the carcinogen's effect.

Effects of fly ash inhalation on murine immune function: Changes in macrophage-mediated activities

Mice were exposed to fly ash particles (<2.1 μm diameter) by inhalation for variable amounts of time at concentrations ranging from 535 to 2221 μg/m 3. This fine fraction was approximately 32% by weight of the total dust generated. The effects of these exposures were assessed on macrophage-mediated functions. Phagocytosis of bacterial cells by the alveolar macrophages was depressed in the fly ash-exposed animals as was the ability to enhance T-cell mitogenesis. Fly ash exposure failed to produce a significant change in the cellular immune response (delayed-type hypersensitivity reaction) to antigenic challenge in the lungs of sensitized animals.

Effects of fly ash inhalation on murine immune function: Effects on systemic response

Mice were exposed to fly ash at levels ranging from 728–2221 μg/m 3 respirable for varying periods of time, and several immunological parameters were measured. Little change was noted in splenic response to mitogens or cytolytic ability. Splenic lymphocytes from fly ash-exposed mice incorporated significantly more thymidine following subcutaneous sensitization with BCG, although no differences were noted in response of these lymphocytes to PPD. Fly ash exposure of greater than 1 week caused a suppression of antibody response to aerosols of Escherichia coli in the spleen, but not in the mediastinal lymph nodes. Following 3–4 weeks of fly ash exposure, no changes in splenic antibody responses were noted following intravenous injections of LPS or intratracheal injections of DNP-Ficoll. However, after 9 months exposure at higher concentrations of fly ash, splenic plaque-forming responses were significantly suppressed after both aerosol and intratracheal exposure to antigen.

STUDIES OF THE CHRONIC INHALATION OF COAL FLY ASH BY RATS

Abstract Respiratory disease-free rats were exposed in two experiments to respirable (mass median aerodynamic diameter MMAD about 2 μ) aerosols of size-classified power plant fly ash at average concentrations of up to 4.2 mg m-3 for 8 h per day for up to 180 consecutive days. The aerosols were characterized with respect to both physical and chemical properties. Immediately after exposure, the animals were evaluated biochemically, morphologically and with other sensitive biological tests to detect effects associated with fly ash inhalation when compared with unexposed controls. Lung burdens of up to 4 mg of ash were found. Macrophages lavaged from lungs of exposed rats were more numerous and yielded more progenitor cell colonies in culture (at the 10% confidence level based on the Mann-Whitney rank-sum test) than from controls. Tracheal mucous glycoprotein secretion was decreased at 7,50 and 90 days of exposure and increased at 180 days. Clumping of fly ash in cells in the lungs was observed. There were no apparent untoward health effects from inhaled fly ash, since the observed differences between exposed and control rats did not constitute an adverse response.