Jung-Taek Kwon

Evaluation of toxicity to triclosan in rats following 28 days of exposure to aerosol inhalation

The present study was conducted to investigate the potential subchronic toxicity of triclosan (TCS) in rats following 28 days of exposure by repeated inhalation. Four groups of six rats of each sex were exposed to TCS-containing aerosols by nose-only inhalation of 0, 0.04, 0.13, or 0.40 mg/L for 6 h/day, 5 days/week over a 28-day period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. At 0.40 mg/L, rats of both sexes exhibited an increase in the incidence of postdosing salivation and a decrease in body weight. Histopathological alterations were found in the nasal septum and larynx. There were no treatment-related effects in rats of either sex at ⩽0.13 mg/L. Under the present experimental conditions, the target organs in rats were determined to be the nasal cavity and larynx. The no-observed-adverse-effect concentration in rats was determined to be 0.13 mg/L.

Ethylene glycol potentiated didecyldimethylammonium chloride toxicity in human bronchial epithelial cells

Didecyldimethylammonium chloride (DDAC) is an antimicrobial agent used as a preservative in household products. DDAC is toxic in human lung cells and in mouse lung. Aerosol products that contain DDAC often include ethylene glycol (EG) as a solvent; no safety information is available for respiratory toxicity of this combination (DDAC and EG). Human bronchial epithelial cells (BEAS-2B) were exposed (24 h) to DDAC and EG, separately or together. DDAC showed concentration-dependent cytotoxicity. EG did not affect cell viability. Compared to DDAC alone, EG and DDAC together enhanced mitochondrial damage and cell membrane disruption. Increased reactive oxygen species and decreased glutathione levels were seen in cells treated with the combination. Intracellular DDAC concentrations were elevated in the presence of EG. EG potentiated DDAC toxicity in lung cells by inducing oxidative stress through enhanced cellular uptake of DDAC. The use of these chemicals together in spray-type products should be carefully considered.

Didecyldimethylammonium chloride induces oxidative stress and inhibits cell growth in lung epithelial cells

Didecyldimethylammonium chloride (DDAC) is a commonly used biocide that can cause lung inflammation and fibrosis. However, the mechanism of this pulmonary toxicity is unclear. Thus, we examined the mechanism for the DDAC-induced pulmonary toxicity at the cellular level by using lung epithelial cells. DDAC induced cell damage, including injury of mitochondria and lysosomes with the release of lactate dehydrogenase (LDH), as well as caused cell morphological changes and necrotic reactions. In a clonogenic assay, treatment with a low concentration of DDAC (5 μM) for 10 days reduced both the number and size of the colonies, which are indexes of cell growth. In addition, DDAC increased intracellular reactive oxygen species (ROS) production while it decreased glutathione (GSH) activity. Therefore, our results suggest that exposure to even a low concentration of DDAC may inhibit cell growth and cause oxidative stress in lung epithelial cells.

Evaluation of comparative cytotoxicity of spray-type chemicals used in household products

Chemicals are widely used in our daily lives for various purposes such as disinfectant, air fresher, paints and hair spray. However, their pulmonary toxicity has less studied compared with oral and dermal toxicity. Therefore, the purpose of this study was to examine comparative cytotoxicity of triclosan (TCS), benzisothiazolinone (BIT), dichlorophene (DCP) and citral (CTR) major using spray-type chemicals used in household products (CHPs) in Korea. TCS, DCP and BIT induced more severe mitochondria injury and cell membrane damage than CTR in lung epithelial cell during 24 hrs exposure. Furthermore, the result of clonogenic assay revealed that exposure of CHPs significantly decreased colony size and that BIT reduced cell growth at most compared with TCS, DCP and CTR. In summary, results of comparative cytotoxicity demonstrated that inhalation of TCS, DCP and BIT may cause pulmonary toxicity. Therefore, our results suggest that TCS, BIT and DCP are requiring inhalation toxicity assessment for maintaining a high quality of life.

Spatial–Temporal Dispersion of Aerosolized Nanoparticles During the Use of Consumer Spray Products and Estimates of Inhalation Exposure

We evaluated the spatial-temporal dispersion of airborne nanomaterials during the use of spray consumer products and estimated the level of consumer inhalation exposure. A total of eight spray products including five propellant and three pump types were selected to evaluate the dispersion of airborne nanoparticles across time and space in a cleanroom which could control the background particles. Four products were advertised to contain silver and one contained titanium nanoparticles, while three products were specified no ENM but as being manufactured through the use of nanotechnology. We used direct-reading instruments with a thermodesorber unit to measure the particles (number, mass, surface area), as well as filter sampling to examine physicochemical characteristics. Sampling was conducted simultaneously at each location (1 m, near-field; 2, 3 m, far-field) by distance from the source. We estimated the inhaled doses at the breathing zone, and the doses deposited in each part of the respiratory tract using the experimental data and mathematical models. Nanoparticles released from the propellant sprays persisted in the air and dispersed over a large distance due to their small size (1466-5565 particles/cm3). Conversely, the pump sprays produced larger droplets that settled out of the air relatively close to the source, so the concentration was similar to background level (<200 particles/cm3). The estimates of inhalation exposure also suggested that exposure to nanoparticles was greater with propellant sprays (1.2 × 108 ± 4.0 × 107 particles/kgbw/day) than pump sprays (2.7 × 107 ± 6.5 × 106 particles/kgbw/day). We concluded that the propellant sprays create a higher risk of exposure than the pump sprays.

Acute pulmonary toxicity and inflammation induced by combined exposure to didecyldimethylammonium chloride and ethylene glycol in rats

Didecyldimethylammonium chloride (DDAC), an antimicrobial agent, has been reported to induce pulmonary toxicity in animal studies. DDAC is frequently used in spray-form household products in combination with ethylene glycol (EG). The purpose of this study was to evaluate the toxic interaction between DDAC and EG in the lung. DDAC at a sub-toxic dose (100 μg/kg body weight) was mixed with a non-toxic dose of EG (100 or 200 μg/kg body weight), and was administrated to rats via intratracheal instillation. Lactate dehydrogenase activity and total protein content in the bronchoalveolar lavage fluid (BALF) were not changed by singly treated DDAC or EG, but significantly enhanced at 1 d after treatment with the mixture, with the effect dependent on the dose of EG. Total cell count in BALF was largely increased and polymorphonuclear leukocytes were predominantly recruited to the lung in rats administrated with the mixture. Inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6 also appeared to be increased by the mixture of DDAC and EG (200 μg/kg body weight) at 1 d post-exposure, which might be associated with the increase in inflammatory cells in lung. BALF protein content and inflammatory cell recruitment in the lung still remained elevated at 7 d after the administration of DDAC with the higher dose of EG. These results suggest that the combination of DDAC and EG can synergistically induce pulmonary cytotoxicity and inflammation, and EG appears to amplify the harmful effects of DDAC on the lung. Therefore pulmonary exposure to these two chemicals commonly found in commercial products can be a potential hazard to human health.

Pulmonary Toxicity Assessment of Aluminum Oxide Nanoparticles via Nasal Instillation Exposure

Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.

P155 Removal efficiencies of solvents by thermodesorber during nanoparticles monitoring of spraying products

This abstract was published in error and withdrawn at the author’s request.