Ambient particulate matter 2.5 (PM2.5) and total suspended particles (TSPs) are common airborne pollutants that cause respiratory and cardiovascular diseases. We investigated the differences of cytotoxicity and mechanism between PM2.5 and TSP activity in human alveolar epithelial A549 cells. Atmospheric samples from the central district of Seoul were collected and their chemical compositions were analyzed by inductively-coupled plasma mass spectrometry and ion chromatography. PM2.5 and TSP contained high concentrations of heavy metals (Cu, Fe, Zn, and Pb). The most abundant ions in PM2.5 were SO₄²⁻, NH₄⁺, and NO₃⁻. A549 cells were exposed to PM2.5 and TSP (25–200 µg/mL) for 24 h. TSP was more cytotoxic than PM2.5 per unit mass. PM2.5 induced oxidative stress, as evidenced by increased levels of a glutamate-cysteine ligase modifier, whereas low-concentration TSP increased hemeoxygenase-1 levels. PM2.5 and TSP did not affect c-Jun N-terminal kinase expression. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in PM2.5- and TSP-treated cells decreased significantly in the cytosol and increased in the nucleus. Thus, Nrf2 may be a key transcription factor for detoxifying environmental airborne particles in A549 cells. TSP and PM2.5 could activate the protective Kelch-like ECH-associated protein 1/Nrf2 pathway in A549 cells.

The toxicity profiles of the widely used guanidine-based chemicals have not been fully elucidated. Herein, we evaluated the in vitro and in vivo toxicity of eight guanidine-based chemicals, focusing on inhalation toxicity. Among the eight chemicals, dodecylguanidine hydrochloride (DGH) was found to be the most cytotoxic (IC₅₀: 0.39 μg/mL), as determined by the water soluble tetrazolium salts (WST) assay. An acute inhalation study for DGH was conducted using Sprague-Dawley rats at 8.6 ± 0.41, 21.3 ± 0.83, 68.0 ± 3.46 mg/m³ for low, middle, and high exposure groups, respectively. The levels of lactate dehydrogenase, polymorphonuclear leukocytes, and cytokines (MIP-2, TGF-β1, IL-1β, TNF-α, and IL-6) in the bronchoalveolar lavage fluid increased in a concentration-dependent manner. Histopathological examination revealed acute inflammation with necrosis in the nasal cavity and inflammation around terminal bronchioles and alveolar ducts in the lungs after DGH inhalation. The LC₅₀ of DGH in rats after exposure for 4 h was estimated to be >68 mg/m³. Results from the inhalation studies showed that DGH was more toxic in male rats than in female rats. Overall, DGH was found to be the most cytotoxic chemical among guanidine-based chemicals. Exposure to aerosols of DGH could induce harmful pulmonary effects on human health.

Background/Aim: The use of glycolic acid is present in a variety of consumer products, including medicines, cleaners, cosmetics, and paint strippers. It has recently led to concerns about toxicity from inhalation exposure. Herein, the pulmonary toxicity of glycolic acid was investigated in rats. Materials and Methods: We conducted acute (~458 mg/m³) and sub-acute (~49.5 mg/m³) inhalation tests to identify the potential toxicities of glycolic acid. Results: Inhalation exposure to glycolic acid in the acute and subacute inhalation tests did not cause any specific changes in clinical examinations, including body weight, organ weight, hematology, serum biochemistry, and histopathology. The polymorphonuclear neutrophils (PMNs) and inflammatory cytokines in Bronchoalveolar lavage fluid (BALF) increased in rats exposed to single and repeated inhalations. In the sub-acute test, the changes induced by glycolic acid were minor or returned to normal during the recovery period. Conclusion: The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m³ at the end of a 28-day inhalation test in male rats.

In order to investigate the effects of metallic nanoparticles (NPs) on the performance of in vitro bioassay, zinc oxide NP (ZnO NP), aluminum oxide NP (Al₂O₃ NP), bare silver NP (Ag NP), and Ag NP capped with citrate (Ag^cit NP) were evaluated with yeast (Saccharomyces cerevisiae Y190) two-hybrid system (YES assay), carrying Japanese medaka estrogen receptors (mERs) in the presence of 17β-estradiol (E2, 10⁻⁶ M), a reference chemical for estrogenic activity. The distribution of NPs in the yeast was also examined by field-emission transmission electron microscopy (FE-TEM). The results show that TEM analysis revealed that NPs were present inside the yeast and accumulated deep inside the cell organelles, suggesting that cell death was caused by NPs. However, despite no significant change of mortality, the E2 estrogenic activities in yeast exposed to ZnO NP and Al₂O₃ NP were dose-dependently reduced. For Ag NP and Ag^cit NP, such phenomenon observed in the exposure of ZnO NP and Al₂O₃ NP did not occur. From the observations, we found that ZnO NP and Al₂O₃ NP in the environmental media could result in underestimated estrogenicity of endocrine-disrupting compounds when evaluated by YES assay.