Subchronic inhalation toxicity of gold nanoparticles.

BACKGROUND: Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. RESULTS: The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 µg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 µg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 µg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold nanoparticles showed a dose-dependent accumulation of gold in only lungs and kidneys with a gender-related difference in gold nanoparticles content in kidneys. CONCLUSIONS: Lungs were the only organ in which there were dose-related changes in both male and female rats. Changes observed in lung histopathology and function in high-dose animals indicate that the highest concentration (20 µg/m3) is a LOAEL and the middle concentration (0.38 µg/m3) is a NOAEL for this study.

Exposure assessment of carbon nanotube manufacturing workplaces.

Seven CNT (carbon nanotube) handling workplaces were investigated for exposure assessment. Personal sampling, area sampling, and real-time monitoring using an SMPS (scanning mobility particle sizer), dust monitor, and aethalometer were performed to characterize the mass exposure, particle size distribution, and particle number exposure. No workplace was found to exceed the current ACGIH (American Conference of Governmental Industrial Hygienists) TLVs (threshold limit values) and OELs (occupational exposure levels) set by the Korean Ministry of Labor for carbon black (3.5 mg/m(3)), PNOS (particles not otherwise specified; 3 mg/m(3)), and asbestos (0.1 fiber/cc). Nanoparticles and fine particles were most frequently released after opening the CVD (chemical vapor deposition) cover, followed by catalyst preparation. Other work processes that prompted nanoparticle release included spraying, CNT preparation, ultrasonic dispersion, wafer heating, and opening the water bath cover. All these operation processes could be effectively controlled with the implementation of exposure mitigation, such as engineering control, except at one workplace where only natural ventilation was used.

Subchronic inhalation toxicity of silver nanoparticles.

The subchronic inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Eight-week-old rats, weighing approximately 253.2 g (males) and 162.6 g (females), were divided into four groups (10 rats in each group): fresh-air control, low dose (0.6 x 10(6) particle/cm(3), 49 microg/m(3)), middle dose (1.4 x 10(6) particle/cm(3), 133 microg/m(3)), and high dose (3.0 x 10(6) particle/cm(3), 515 microg/m(3)). The animals were exposed to silver nanoparticles (average diameter 18-19 nm) for 6 h/day, 5 days/week, for 13 weeks in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and the organ weights were measured. Bile-duct hyperplasia in the liver increased dose dependently in both the male and female rats. Histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, including mixed inflammatory cell infiltrate, chronic alveolar inflammation, and small granulomatous lesions. Target organs for silver nanoparticles were considered to be the lungs and liver in the male and female rats. No observable adverse effect level of 100 microg/m(3) is suggested from the experiments.

Lung function changes in Sprague-Dawley rats after prolonged inhalation exposure to silver nanoparticles.

The antimicrobial activity of silver nanoparticles has resulted in their widespread use in many consumer products. However, despite the continuing increase in the population exposed to silver nanoparticles, the effects of prolonged exposure to silver nanoparticles have not been thoroughly determined. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during 90 days of inhalation exposure to silver nanoparticles. The rats were exposed to silver nanoparticles (18 nm diameter) at concentrations of 0.7 x 10(6) particles/cm(3) (low dose), 1.4 x 10(6) particles /cm(3) (middle dose), and 2.9 x 10(6) particles /cm(3) (high dose) for 6 h/day in an inhalation chamber for 90 days. The lung function was measured every week after the daily exposure, and the animals sacrificed after the 90-day exposure period. Cellular differential counts and inflammatory measurements, such as albumin, lactate dehydrogenase (LDH), and total protein, were also monitored in the acellular bronchoalveolar lavage (BAL) fluid of the rats exposed to the silver nanoparticles for 90 days. Among the lung function test measurements, the tidal volume and minute volume showed a statistically significant decrease during the 90 days of silver nanoparticle exposure. Although no statistically significant differences were found in the cellular differential counts, the inflammation measurements increased in the high-dose female rats. Meanwhile, histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, such as infiltrate mixed cell and chronic alveolar inflammation, including thickened alveolar walls and small granulomatous lesions. Therefore, when taken together, the decreases in the tidal volume and minute volume and other inflammatory responses after prolonged exposure to silver nanoparticles would seem to indicate that nanosized particle inhalation exposure can induce lung function changes, along with inflammation, at much lower mass dose concentrations when compared to submicrometer particles.

Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats.

The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. Thus, the exposed population continues to increase as the applications expand. Although previous studies on silver dust, fumes, and silver compounds have revealed some insights, little is yet known about the toxicity of nano-sized silver particles, where the size and surface area are recognized as important determinants for toxicity. Thus, the inhalation toxicity of silver nanoparticles is of particular concern to ensure the health of workers and consumers. However, the dispersion of inhalable ambient nano-sized particles has been an obstacle in evaluating the effect of the inhalation of nano-sized particles on the respiratory system. Accordingly, the present study used a device that generates silver nanoparticles by evaporation/condensation using a small ceramic heater. As such, the generator was able to distribute the desired concentrations of silver nanoparticles to chambers containing experimental animals. The concentrations and distribution of the nanoparticles with respect to size were also measured directly using a differential mobility analyzer and ultrafine condensation particle counter. Therefore, the inhalation toxicity of silver nanoparticles was tested over a period of 28 days. Eight-week-old rats, weighing about 283 g for the males and 192 g for the females, were divided into 4 groups (10 rats in each group): a fresh-air control, a low-dose group (1.73 x 10(4)/cm3), a middle-dose group (1.27 x 10(5)/cm3), and a high-dose group (1.32 x 10(6) particles/cm3, 61 microg/m3). The animals were exposed to the silver nanoparticles for 6 h/day, 5 days/wk, for a total of 4 wk. The male and female rats did not show any significant changes in body weight relative to the concentration of silver nanoparticles during the 28-day experiment. Plus, there were no significant changes in the hematology and blood biochemical values in either the male or female rats. Therefore, the initial results indicated that exposure to silver nanoparticles at a concentration near the current American Conference of Governmental Industrial Hygienists (ACGIH) silver dust limit (100 microg/m3) did not appear to have any significant health effects.