Visualization of Dust Generation in Outdoor Workplaces Using A Wearable Particle Monitor and Global Navigation Satellite System.

We manufactured a wearable particle monitor (WPM), which is a simple and low-cost dust monitor. We aimed to evaluate the usefulness of the device by using it and location information of a Global Navigation Satellite System (GNSS) to measure dust generation in outdoor workplaces. We used nine WPMs and a particle counter KC-52 to measure in parallel the dust concentration diffusing standard particles in a dust exposure apparatus to evaluate the measurability of the WPM, and visualized dust generation in outdoor workplaces to evaluate its usability. We obtained location information using a GNSS in parallel with measuring with the WPM. The measured values of the WPM followed the measured values of the KC-52, with a strong correlation of the values between the KC-52 and each WPM. The discrepancy among devices tended to increase, however, because the measured values of the WPMs increased. For outdoor measurements, we could create a heat map of the relative values of dust generation by combining two data of the WPM and the GNSS. The methods of using the WPM could overview the conditions needed to produce dust emissions in dust-generating workplaces.

Combining Indoor Positioning Using Wi-Fi Round Trip Time with Dust Measurement in the Field of Occupational Health.

Monitoring of personal exposure to hazardous substances has garnered increasing attention over the past few years. However, no straightforward and exact indoor positioning technique has been available until the recent discovery of Wi-Fi round trip time (Wi-Fi RTT). In this study, we investigated the possibility of using a combination of Wi-Fi RTT for indoor positioning and a wearable particle monitor (WPM) to observe dust concentration during walking in a simulated factory. Ultrasonic humidifiers were used to spray sodium chloride solution inside the factory. The measurements were recorded three times on different routes (Experiments A, B, and C). The error percentages, i.e., measurements that were outside the expected measurement area, were 7% (49 s/700 s) in Experiment A, 2.3% (15 s/660 s) in Experiment B, and 7.8% (50 s/645 s) in Experiment C. The dust measurements were also recorded without any obstruction. A heat map was created based on the results from both measured values. Wi-Fi RTT proved useful for computing the indoor position with high accuracy, suggesting the applicability of the proposed methodology for occupational health monitoring.

Changes over time in pulmonary inflammatory response in rat lungs after intratracheal instillation of nickel oxide nanoparticles.

OBJECTIVE: Nickel oxide nanoparticles (NiONPs) are representative metal oxide NPs and are categorized as an insoluble nickel compound. Our previous studies suggested that NiONPs have more pulmonary toxicity than micron-sized NiO because they may dissolve slowly and produce many more Ni ions. We confirmed the hypothesis that the slow dissolution of NiONPs induces a change in inflammatory response over time. METHOD: We reanalyzed our previous data on intratracheally instilled NiONP to rats and focused on Ni retention in the lungs and the lung weight ratio for each rat to the mean of control rat lungs. We also measured the solubility of NiONPs and micron-sized NiO samples by means of an artificial lysosomal fluid (ALF, pH 4.5). RESULTS: The in vivo test of instilled NiONPs resulted in the biomarkers reaching their peak values at 1 week or 1 month, and not at 3 days, after instillation. We found that as the NiO mass in the lung increased, the lung weight ratios tended to increase. The relationships shifted to more toxic at 3 days to 1 month (P < .01). Compared to the dissolution of NiONPs in the ALF that took roughly 1 week, the dissolution of NiONPs in vivo was take about 1 month or more. CONCLUSION: When intratracheally instilled NiONPs dissolve slowly in the phagolysosomes of alveolar macrophages (AM), the resulting Ni ions cause the AM to transform into foamy cells at 1 month, and the inflammatory response persists even at 3 months after instillation.

[Design and Evaluation of Miniature Cyclones for Dust Indicators].

Dust indicators based on light scattering photometers are widely used to measure aerosol concentrations in work environments. These concentrations at workplaces in Japan are measured by these dust indicators and calibrated by mass concentration in order to control workers' exposure to dust. The mass concentration in a specific point in a workplace is measured simultaneously with a dust indicator. The mass concentration of the respirable fraction of dust particles should be determined by the gravimetric method with low volume air samplers or other devices, but some dust indicators are not equipped with a size separator for respirable fraction, and we used to get unstable results at the calibration. In this study, we designed miniature cyclones for a dust indicator and evaluated their performances of respirable fraction and PM2.5 fraction.

Inhalation of titanium dioxide (P25) nanoparticles to rats and changes in surfactant protein (SP-D) levels in bronchoalveolar lavage fluid and serum.

Titanium dioxide (TiO2) nanoparticles are typical and widely used nanomaterials, and there are many studies on the inflammatory responses induced by their inhalation. In this study, we conducted a 4-week inhalation exposure study of aerosolized TiO2> nanoparticles (P25) to male Wistar rats. The mean aerosol concentration measured at each day was 4.1 mg/m3 by dry powder dispersion of TiO2 nanoparticles. Control and exposure groups of rats were killed at 3 and 30 days after the termination of exposure, and bronchoalveolar lavage fluid (BALF) and serum were collected for analysis of total cell count, neutrophil count, and surfactant protein (SP-D) in BALF and SP-D in serum, as well as other serum biomarkers. SP-D is a component of lung surfactants produced in type II alveolar epithelial cells and Clara cells and secreted into the alveolar space and blood. The neutrophil count in the BALF was significantly elevated at 3 and 30 days. The levels of SP-D in the BALF were also elevated at 3 and 30 days, while the serum SP-D levels were elevated at 3 days only. We determined the amounts of TiO2 in the rat lungs in the exposure group at 3, 30, and 73 days to analyze the lung deposition fraction (10.2%) and the biological half-life time (72.4 days) of inhaled TiO2 nanoparticles. Histopathological analysis revealed mild pulmonary inflammation in lung tissue at 3 days. Serum SP-D was found to be a potential biomarker for exposure to TiO2 nanoparticles in this study.

Health Effects of Toner Exposure Among Japanese Toner-Handling Workers: A 10-Year Prospective Cohort Study.

The main objective of this study was to evaluate the risk of the respiratory diseases, i.e. pneumoconiosis, lung fibrosis, granulomatous pneumonitis, lung cancer and bronchial asthma, which have been reported as related to toner exposure. The second main objective was to clarify the association between toner exposure and parameters related with toner-handling worker's health. We conducted a 10-year prospective cohort study from 2004 to 2013 in 296 Japanese toner-handling workers. The evaluation of toner exposure and medical health check were performed once a year. There was no obvious evidence of occurrence of lung diseases. We also investigated several health parameters to recognize the change of respiratory health before onset of pneumoconiosis, lung fibrosis, lung cancer and bronchial asthma. However there were some sporadic statistically significant findings, to bring all health parameters, we did not find obvious evidence that toner exposure would cause adverse health effects as a whole. We concluded that the possibility that toner exposure would cause adverse health effects was quite low.

Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials.

BACKGROUND: In order to examine whether myeloperoxidase (MPO) can be a useful marker for evaluating the pulmonary toxicity of nanomaterials, we analyzed MPO protein in bronchoalveolar lavage fluid (BALF) samples obtained from previous examinations of a rat model. In those examinations we performed intratracheal instillation exposures (dose: 0.2-1.0 mg) and inhalation exposures (exposure concentration: 0.32-10.4 mg/m3) using 9 and 4 nanomaterials with different toxicities, respectively. Based on those previous studies, we set Nickel oxide nanoparticles (NiO), cerium dioxide nanoparticles (CeO2), multi wall carbon nanotubes with short or long length (MWCNT (S) and MWCNT (L)), and single wall carbon nanotube (SWCNT) as chemicals with high toxicity; and titanium dioxide nanoparticles (TiO2 (P90) and TiO2 (Rutile)), zinc oxide nanoparticles (ZnO), and toner with external additives including nanoparticles as chemicals with low toxicity. We measured the concentration of MPO in BALF samples from rats from 3 days to 6 months following a single intratracheal instillation, and from 3 days to 3 months after the end of inhalation exposure. RESULTS: Intratracheal instillation of high toxicity NiO, CeO2, MWCNT (S), MWCNT (L), and SWCNT persistently increased the concentration of MPO, and inhalation of NiO and CeO2 increased the MPO in BALF. By contrast, intratracheal instillation of low toxicity TiO2 (P90), TiO2 (Rutile), ZnO, and toner increased the concentration of MPO in BALF only transiently, and inhalation of TiO2 (Rutile) and ZnO induced almost no increase of the MPO. The concentration of MPO correlated with the number of total cells and neutrophils, the concentration of chemokines for neutrophils (cytokine-induced neutrophil chemoattractant (CINC)-1 and heme oxygenase (HO)-1), and the activity of released lactate dehydrogenase (LDH) in BALF. The results from the receiver operating characteristics (ROC) for the toxicity of chemicals by the concentration of MPO proteins in the intratracheal instillation and inhalation exposures showed that the largest areas under the curves (AUC) s in both examinations occurred at 1 month after exposure. CONCLUSION: These data suggest that MPO can be a useful biomarker for the ranking of the pulmonary toxicity of nanomaterials, especially at 1 month after exposure, in both intratracheal instillation and inhalation exposure.

Biopersistence of NiO and TiO2 Nanoparticles Following Intratracheal Instillation and Inhalation.

The hazards of various types of nanoparticles with high functionality have not been fully assessed. We investigated the usefulness of biopersistence as a hazard indicator of nanoparticles by performing inhalation and intratracheal instillation studies and comparing the biopersistence of two nanoparticles with different toxicities: NiO and TiO2 nanoparticles with high and low toxicity among nanoparticles, respectively. In the 4-week inhalation studies, the average exposure concentrations were 0.32 and 1.65 mg/m³ for NiO, and 0.50 and 1.84 mg/m³ for TiO2. In the instillation studies, 0.2 and 1.0 mg of NiO nanoparticles and 0.2, 0.36, and 1.0 mg of TiO2 were dispersed in 0.4 mL water and instilled to rats. After the exposure, the lung burden in each of five rats was determined by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES) from 3 days to 3 months for inhalation studies and to 6 months for instillation studies. In both the inhalation and instillation studies, NiO nanoparticles persisted for longer in the lung compared with TiO2 nanoparticles, and the calculated biological half times (BHTs) of the NiO nanoparticles was longer than that of the TiO2 nanoparticles. Biopersistence also correlated with histopathological changes, inflammatory response, and other biomarkers in bronchoalveolar lavage fluid (BALF) after the exposure to nanoparticles. These results suggested that the biopersistence is a good indicator of the hazards of nanoparticles.

The Effectiveness of Specific Risk Mitigation Techniques Used in the Production and Handling of Manufactured Nanomaterials: A Systematic Review.

Many kinds of manufactured nanomaterials (MNMs) have been developed and used as basic materials of industrial products, and they may pose health risks for workers in not only developed countries but also in developing countries. Few studies have looked at the evidence for effects of controls that mitigate the risk of exposure to MNMs. Therefore, we systematically searched the literature from the year 2000 to 2015. We included studies that compared the use of an exposure control to the situation without such a technique and those that measured the exposure to MNMs as the outcome. In order to evaluate the effectiveness of these controls, we used their "protection factor", defined as the ratio between concentrations without and with the control. We located 1,131 references in PubMed and other lists, and out of these references, 41 studies fulfilled our inclusion criteria. We categorized them as engineering controls such as enclosure, local exhaust ventilation or process automation, and as personal protective equipment (PPE). For enclosure systems we found a protection factor beyond 100. For other engineering controls, the better controls scored 10 to 20, but many cases of local exhaust ventilation had a protection factor of less than 10 and some cases even increased exposure. PPE such as N95 or equivalent filtering respirators had a protection factor of approximately 10 tested with nano-sized aerosols. We conclude that there is low quality evidence that specific engineering controls can reduce exposure to MNMs but that enclosure is considerably more effective. For respiratory protection the evidence is of very low quality due to the lack of field studies. This information can be used to decide about controls when exposure to MNMs exceeds proposed occupational exposure limits or when no toxicological information is available for a MNM.

Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives.

We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 µm) at three mass concentrations of 1, 4, and 16 mg/m3 for 22.5 months, and the rats were sacrificed after 6 months, 12 months, and 22.5 months of exposure. The low and medium concentrations did not induce statistically significant pulmonary inflammation, but the high concentration did, and, in addition, a histopathological examination showed fibrosis in the lung. Although lung tumor was observed in one sample of high exposure for 22.5 months, the cause was not statistically significant. On the other hand, a persistent increase in 8-OHdG was observed in the high exposure group, indicating that DNA damage by oxidative stress with persistent inflammation leads to the formation of tumorigenesis. The results of our studies show that toners with external additives lead to pulmonary inflammation, oxidative stress, and fibrosis only at lung burdens beyond overload. These data suggest that toners with external additives may have low toxicity in the lung.

Pulmonary responses in rat lungs after intratracheal instillation of 4 crystal forms of titanium dioxide nanoparticles.

OBJECTIVE: Titanium dioxide nanoparticles are widely used as UV filters in cosmetics and as a photocatalyst. We evaluated pulmonary responses to different crystal forms of TiO2 nanoparticles. METHODS: We used 4 different TiO2 samples with similar specific surface areas (anatase, rutile, amorphous, and P25). Each sample was suspended in distilled water and intratracheally instilled to male Wister rats at the dose of 1 mg per rat. Five rats per group were sacrificed at 3 days, 1 month, and 6 months after instillation, and bronchoalveolar lavage fluid was collected from the right lung to determine the total cell count and polymorphonuclear cell (PMN) counts. The left lung tissues were stained with hematoxylin and eosin for the evaluation of inflammation and with elastica van Gieson for the evaluation of collagen deposition. RESULTS: The total cell counts and PMN counts of the amorphous and P25 of four samples showed a significant increase compared with the control group at 3 days after instillation. The inflammation rate of P25 also showed a significant increase compared with controls at 3 days. The collagen deposition rate in the alveolar duct of P25 increased significantly compared with controls from 3 days to 6 months. The other samples showed a mild response after instillation. CONCLUSION: Although the TiO2 nanoparticles used in this study had similar specific surface areas, there were different inflammatory responses in the rat lungs. Other factors, such as different production processes or the surface activities of particles, may have been responsible for the different responses.

Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation.

We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m³) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

Comparison of the Pulmonary Oxidative Stress Caused by Intratracheal Instillation and Inhalation of NiO Nanoparticles when Equivalent Amounts of NiO Are Retained in the Lung.

NiO nanoparticles were administered to rat lungs via intratracheal instillation or inhalation. During pulmonary toxicity caused by NiO nanoparticles, the induction of oxidative stress is a major factor. Both intratracheal instillation and inhalation of NiO nanoparticles induced pulmonary oxidative stress. The oxidative stress response protein, heme oxygenase-1 (HO-1), was induced by the administration of NiO nanoparticles at both the protein and gene expression level. Additionally, certain oxidative-stress markers in the lung, such as 8-iso-prostaglandin F2α, thioredoxin, and inducible nitric oxide synthase were increased. Furthermore, the concentration of myeloperoxidase (MPO) in the lung was also increased by the administration of NiO nanoparticles. When the amount of NiO in the lung is similar, the responses against pulmonary oxidative stress of intratracheal instillation and inhalation are also similar. However, the state of pulmonary oxidative stress in the early phase was different between intratracheal instillation and inhalation, even if the amount of NiO in the lung was similar. Inhalation causes milder oxidative stress than that caused by intratracheal instillation. On evaluation of the nanoparticle-induced pulmonary oxidative stress in the early phase, we should understand the different states of oxidative stress induced by intratracheal instillation and inhalation.

Comparison of pulmonary inflammatory responses following intratracheal instillation and inhalation of nanoparticles.

In order to examine whether intratracheal instillation studies can be useful for determining the harmful effect of nanoparticles, we performed inhalation and intratracheal instillation studies using samples of the same nanoparticles. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In the intratracheal instillation study, rats were exposed to 0.2 or 1 mg of NiO or TiO2. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the single intratracheal instillation. In the inhalation study, rats were exposed to inhaled NiO or TiO2 (1.65, 1.84 mg/m(3), respectively) for 4 weeks. The same endpoints were examined from 3 days to 3 months after the end of exposure. Inhalation of NiO induced an increase in the number of neutrophils in BALF and concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and heme oxygenase (HO)-1. Intratracheal instillation of NiO induced persistent inflammation and upregulation of these cytokines was observed in the rats. However, inhalation of TiO2 did not induce pulmonary inflammation, and intratracheal instillation of TiO2 transiently induced an increase in the number of neutrophils in BALF and the concentrations of CINC-1, CINC-2 and HO-1. Taken together, a difference in pulmonary inflammation was observed between the high and low toxicity nanomaterials in the intratracheal instillation studies, as in the inhalation studies, suggesting that intratracheal instillation studies may be useful for ranking the harmful effects of nanoparticles.

Long-term retention of pristine multi-walled carbon nanotubes in rat lungs after intratracheal instillation.

As a result of the growing potential industrial and medical applications of multi-walled carbon nanotubes (MWCNTs), people working in or residing near facilities that manufacture them may be exposed to airborne MWCNTs in the future. Because of concerns regarding their toxicity, quantitative data on the long-term clearance of pristine MWCNTs from the lungs are required. We administered pristine MWCNTs well dispersed in 0.5 mg ml(-1) Triton-X solution to rats at doses of 0.20 or 0.55 mg via intratracheal instillation and investigated clearance over a 12-month observation period. The pristine MWCNTs pulmonary burden was determined 1, 3, 7, 28, 91, 175 and 364 days after instillation using a method involving combustive oxidation and infrared analysis, combined with acid digestion and heat pretreatment. As 0.15- and 0.38-mg MWCNTs were detected 1 day after administration of 0.20 and 0.55 mg MWCNTs, respectively, approximately 30% of administrated MWCNTs may have been cleared by bronchial ciliary motion within 24 h of administration. After that, the pulmonary MWCNT burden did not decrease significantly over time for up to 364 days after instillation, suggesting that MWCNTs were not readily cleared from the lung. Transmission electron microscopy (TEM) showed that alveolar macrophages internalized the MWCNTs and retained in the lung for at least 364 days after instillation. MWCNTs were not detected in the liver or brain within the 364-day study period (<0.04 mg per liver, < 0.006 mg per brain).

Comparison between whole-body inhalation and nose-only inhalation on the deposition and health effects of nanoparticles.

OBJECTIVES: We performed the two inhalation exposures, whole-body inhalation and nose-only inhalation, to investigate the pulmonary deposition and health effects of the two inhalation methods. METHODS: In both methods, we exposed rats to the same TiO2 nanoparticles at almost the same exposure concentration for 6 h and compared the deposited amounts of nanoparticles and histopathological changes in the lungs. Rats were exposed to rutile-type TiO2 nanoparticles generated by the spray-dry method for 6 h. The exposure concentration in the whole-body chamber was 4.10 ± 1.07 mg/m(3), and that in nose-only chamber was 4.01 ± 1.11 mg/m(3). The particle sizes were 230 and 180 nm, respectively. A control group was exposed to fresh air. RESULTS: The amounts of TiO2 deposited in the lungs as measured by ICP-AES after acid digestion just after the exposure were: 42.6 ± 3.5 µg in the whole-body exposure and 46.0 ± 7.7 µg in the nose-only exposure groups. The histopathological evaluation was the same in both exposure groups: no infiltration of inflammatory cells in the alveolar space and interstitium, and no fibrosis. CONCLUSION: The two inhalation methods using the same material under the same exposure conditions resulted in the same particle deposition and histopathology in the lung.

Analysis of pulmonary surfactant in rat lungs after inhalation of nanomaterials: Fullerenes, nickel oxide and multi-walled carbon nanotubes.

The health risks of inhalation exposure to engineered nanomaterials in the workplace are a major concern in recent years, and hazard assessments of these materials are being conducted. The pulmonary surfactant of lung alveoli is the first biological entity to have contact with airborne nanomaterials in inhaled air. In this study, we retrospectively evaluated the pulmonary surfactant components of rat lungs after a 4-week inhalation exposure to three different nanomaterials: fullerenes, nickel oxide (NiO) nanoparticles and multi-walled carbon nanotubes (MWCNT), with similar levels of average aerosol concentration (0.13-0.37 mg/m(3)). Bronchoalveolar lavage fluid (BALF) of the rat lungs stored after previous inhalation studies was analyzed, focusing on total protein and the surfactant components, such as phospholipids and surfactant-specific SP-D (surfactant protein D) and the BALF surface tension, which is affected by SP-B and SP-C. Compared with a control group, significant changes in the BALF surface tension and the concentrations of phospholipids, total protein and SP-D were observed in rats exposed to NiO nanoparticles, but not in those exposed to fullerenes. Surface tension and the levels of surfactant phospholipids and proteins were also significantly different in rats exposed to MWCNTs. The concentrations of phospholipids, total protein and SP-D and BALF surface tension were correlated significantly with the polymorphonuclear neutrophil counts in the BALF. These results suggest that pulmonary surfactant components can be used as measures of lung inflammation.

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation.

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO2) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO2 nanoparticles (2, 10 mg/m3, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation.

In order to investigate the pulmonary toxicity of titanium dioxide (TiO2) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO2 nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO2 nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO2 may not lead to chronic, irreversible legions in the lung, and that TiO2 nanoparticles may not have a high potential for lung disorder.

Expression of cytokine-induced neutrophil chemoattractant in rat lungs following an intratracheal instillation of micron-sized nickel oxide nanoparticle agglomerates.

OBJECTIVE: In our previous study, we reported that the micron-sized nickel oxide nanoparticle agglomerates induced neutrophil infiltration and the gene expression of the cytokine-induced neutrophil chemoattractant (CINC)-2αß in a rat lung. In this study, we examined the expression of the CINCs family in the lung using the same rat model exposed to micron-sized nickel oxide nanoparticle agglomerates. METHODS: The count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 µm (primary diameter: 8.41 nm). Male Wistar rats received an intratracheal instillation of 1 mg (3.3 mg/kg) of nickel oxide nanoparticles and were dissected at 3 days, 1 week, 1 month, 3 months, and 6 months after the instillation. The negative control group received an instillation of saline. The concentration of CINC-1 in the lung and the bronchoalveolar lavage fluid (BALF), CINC-2αß in the BALF, and CINC-3 in the lung and the BALF was examined. RESULTS: The concentration of CINC-1 was elevated at 3 days, 3 months, and 6 months in the lung tissue and from 3 days to 6 months in the BALF. The concentration of CINC-2αß was elevated from 3 days to 3 months in the BALF. The concentration of CINC-3 was also elevated at 3 days, 1 week, 3 months, and 6 months in the lung tissue. Infiltration of neutrophil and alveolar macrophage was observed mainly in the alveoli during the observed time period. CONCLUSION: These results suggest that CINC-1 to -3 were totally involved in the lung injury caused by micron-sized nickel oxide nanoparticle agglomerates.