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East Asia leads the global chemical industry, but environmental chemical risk in these countries is an emerging concern. Despite this, only a few native species that are representative of East Asian environments are listed as test species in international guidelines compared with those native to Europe and America. This review suggests that Zacco platypus, Misgurnus anguillicaudatus, Hydrilla verticillata, Neocaridina denticulata spp., and Scenedesmus obliquus, all resident to East Asia, are promising test species for ecotoxicity tests. The utility of these five species in environmental risk assessment (ERA) varies depending on their individual traits and the state of ecotoxicity research, indicating a need for different applications of each species according to ERA objectives. Furthermore, the traits of these five species can complement each other when assessing chemical effects under diverse exposure scenarios, suggesting they can form a versatile battery for ERA. This review also analyzes recent trends in ecotoxicity studies and proposes emerging research issues, such as the application of alternative test methods, comparative studies using model species, the identification of specific markers for test species, and performance of toxicity tests under environmentally relevant conditions. The information provided on the utility of the five species and alternative issues in toxicity tests could assist in selecting test species suited to study objectives for more effective ERA. [ABSTRACT FROM AUTHOR]

Recent research on in vitro systems has focused on mimicking the in vivo situation of cells within the respiratory system. However, few studies have predicted inhalation toxicity using conventional and simple submerged two‐dimensional (2D) cell culture models. We investigated the conventional submerged 2‐D cell culture model as a method for the prediction of acute inhalation toxicity. Median lethal concentration (LC50) (rat, inhalation, 4 h) and half maximal inhibitory concentration (IC50) (lung or bronchial cell, 24 h) data for 59 substances were obtained from the literature and by experiments. Cytotoxicity assays were performed on 44 substances with reported LC50, but without IC50, data to obtain the IC50 values. A weak correlation was observed between the IC50 and LC50 of all substances. Semi‐volatile organic compounds (SVOCs) and non‐VOCs (NVOCs) (16 substances) with a water solubility of ≥1 g/L were strongly correlated between 24‐h IC50 and 4‐h LC50, and this had an excellent predictive ability to distinguish between Categories 1–3 and 4 (Globally Harmonized System classification for acute inhalation toxicity). Our results suggest that the submerged 2‐D cell culture model may be used to predict in vivo acute inhalation toxicity for substances with a water solubility of ≥1 g/L in SVOCs and NVOCs. We investigated the submerged 2‐D cell culture model as a method to predict acute inhalation toxicity. LC50 and IC50 data for 59 substances were obtained from the literature and by experiments. We observed a strong correlation and predictive ability between IC50 and LC50 in substances with high water solubility and low vapor pressure. This suggests that simple submerged 2‐D cell culture models may be used as an indicator of in vivo acute inhalation toxicity for these types of substances. [ABSTRACT FROM AUTHOR]

Cetylpyridinium chloride (CPC), a quaternary ammonium compound and cationic surfactant, is used in personal hygiene products such as toothpaste, mouthwash, and nasal spray. Although public exposure to CPC is frequent, its pulmonary toxicity has yet to be fully characterized. Due to high risks of CPC inhalation, we aimed to comprehensively elucidate the in vitro and in vivo toxicity of CPC. The results demonstrated that CPC is highly cytotoxic against the A549 cells with a half‐maximal inhibitory concentration (IC50) of 5.79 μg/ml. Following CPC exposure, via intratracheal instillation (ITI), leakage of lactate dehydrogenase, a biomarker of cell injury, was significantly increased in all exposure groups. Further, repeated exposure of rats to CPC for 28 days caused a decrease in body weight of the high‐exposure group and the relative weights of the lungs and kidneys of the high recovery group, but no changes were evident in the histological and serum chemical analyses. The bronchoalveolar lavage fluid (BALF) analysis showed a significant increase in proinflammatory cytokines interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α levels. ITI of CPC induced focal inflammation of the pulmonary parenchyma in rats' lungs. Our study demonstrated that TNF‐α was the most commonly secreted proinflammatory cytokine during CPC exposure in both in vitro and in vivo models. Polymorphonuclear leukocytes in the BALF, which are indicators of pulmonary inflammation, significantly increased in a concentration‐dependent manner in all in vivo studies including the ITI, acute, and subacute inhalation assays, demonstrating that PMNs are the most sensitive parameters of pulmonary toxicity. We performed an in vitro toxicity test and pulmonary toxicity studies using human lung epithelial cells and Sprague–Dawley (SD) rats to evaluate the toxicity of cetylpyridinium chloride (CPC), one of quaternary ammonium compounds (QACs). The results demonstrated that CPC is highly cytotoxic. Intratracheal instillation of CPC induced multifocal inflammation of the pulmonary parenchyma, with corresponding increases in several inflammatory‐related cytokines and polymorphonuclear leukocyte (PMN) levels. These results suggested that CPC could induce inflammation, which leads to fibrosis of the pulmonary system. [ABSTRACT FROM AUTHOR]

Silver is commonly used as a disinfectant, and chronic exposure to silver may cause argyria, resulting in a gray-blue discoloration of human skin. However, the mechanism for cellular toxicity of silver has not been well explained. We studied the mode of cell death, the ratio of glutathione disulfide/glutathione, induction of metallothionein and activation of mitogen-activated protein kinases in J774.1 cells together with activation of antioxidant responsive element and nuclear factor-κB in CHO cells following exposure to silver ion (Ag+) to investigate the mechanism by which Ag+ causes lethal effects. Ag+ increased phosphorylation levels of extracellular signal-regulated, c-Jun N-terminal and p38 mitogen-activated protein kinases and remarkably increased the ratio of glutathione disulfide/glutathione in both a time- and concentration-dependent manner. Luciferase reporter gene assays revealed that antioxidant responsive element and nuclear factor-κB were activated following exposure to Ag+. In addition, exposure to Ag+ increased the mRNA and protein levels of metallothionein. We investigated whether or not Ag+ killed J774.1 cells by inducing apoptosis. Ag+ increased the activity of caspase-3/7 which was abrogated by caspase 3 and pan-caspase inhibitors. However, these inhibitors did not ameliorate the cytotoxic effects of Ag+, suggesting that Ag+ causes oxidative stress, which leads to necrotic rather than apoptotic cell death in J774.1 cells by decreasing functional sulfhydryl groups including glutathione in the cells. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

East Asia leads the global chemical industry, but environmental chemical risk in these countries is an emerging concern. Despite this, only a few native species that are representative of East Asian environments are listed as test species in international guidelines compared with those native to Europe and America. This review suggests that Zacco platypus , Misgurnus anguillicaudatus , Hydrilla verticillata , Neocaridina denticulata spp., and Scenedesmus obliquus , all resident to East Asia, are promising test species for ecotoxicity tests. The utility of these five species in environmental risk assessment (ERA) varies depending on their individual traits and the state of ecotoxicity research, indicating a need for different applications of each species according to ERA objectives. Furthermore, the traits of these five species can complement each other when assessing chemical effects under diverse exposure scenarios, suggesting they can form a versatile battery for ERA. This review also analyzes recent trends in ecotoxicity studies and proposes emerging research issues, such as the application of alternative test methods, comparative studies using model species, the identification of specific markers for test species, and performance of toxicity tests under environmentally relevant conditions. The information provided on the utility of the five species and alternative issues in toxicity tests could assist in selecting test species suited to study objectives for more effective ERA.