Pulmonary toxicity screening of triclosan in rats after intratracheal instillation

Kwon, Jung-Taek; Yang, Yong; Kang, Min-Sung; Seo, Gyun-Baek; Lee, Dong Hun; Yang, Ming; Shim, Ilseob; Kim, Hyun-Mi; Kim, Pilje; Choi, Kyunghee; Lee, Kyuhong

doi:10.2131/jts.38.471

Cited by 21 publications

(13 citation statements)

References 9 publications

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“…IL-6 is predominantly produced by macrophages and monocytes, and plays important roles in recruitment of inflammatory cells, including PMNs, into the lung (Yu et al, 2002;Gabay, 2006;Jones et al, 2006). Therefore, the concentrations of TNF-α and IL-6 in BALF are usually analyzed to determine the acute pulmonary inflammation (Sayes et al, 2007;Kwon et al, 2013). In the current study, the BALF levels of TNF-α were not changed by singly treated DDAC or EG, but those in mixture-treated rats seemed to be slightly increased even though there were no statistical differences (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

Kwon

Kim

et al. 2016

J. Toxicol. Sci.

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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.

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Section: Resultsmentioning

confidence: 99%

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

Kwon

Kim

et al. 2016

J. Toxicol. Sci.

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“…Clonogenic assay is an in vitro technique for evaluating the effect of a certain agent on cell survival and proliferation via observation of the number and size of cell colonies after exposure of single cells to the agent . This assay can be used in cancer research to estimate the anti‐tumorigenic activities of drug candidates and also in toxicological research to identify the adverse effects of chemicals . In the present study, TEG itself did not affect the colony formation, but remarkably inhibited A549 cell survival and proliferation in combination with BAC (Figure ).…”

Section: Discussionmentioning

confidence: 54%

Evaluation of pulmonary toxicity of benzalkonium chloride and triethylene glycol mixtures using in vitro and in vivo systems

Kwon

Lim

Kwon

et al. 2019

Environmental Toxicology

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Benzalkonium chloride (BAC) is a widely used disinfectant/preservative, and respiratory exposure to this compound has been reported to be highly toxic. Spray‐form household products have been known to contain BAC together with triethylene glycol (TEG) in their solutions. The purpose of this study was to estimate the toxicity of BAC and TEG mixtures to pulmonary organs using in vitro and in vivo experiments. Human alveolar epithelial (A549) cells incubated with BAC (1‐10 μg/mL) for 24 hours showed significant cytotoxicity, while TEG (up to 1000 μg/mL) did not affect cell viability. However, TEG in combination with BAC aggravated cell damage and inhibited colony formation as compared to BAC alone. TEG also exacerbated BAC‐promoted production of reactive oxygen species (ROS) and reduction of glutathione (GSH) level in A549 cells. However, pretreatment of the cells with N‐acetylcysteine (NAC) alleviated the cytotoxicity, indicating oxidative stress could be a mechanism of the toxicity. Quantification of intracellular BAC by LC/MS/MS showed that cellular distribution/absorption of BAC was enhanced in A549 cells when it was exposed together with TEG. Intratracheal instillation of BAC (400 μg/kg) in rats was toxic to the pulmonary tissues while that of TEG (up to 1000 μg/kg) did not show any harmful effect. A combination of nontoxic doses of BAC (200 μg/kg) and TEG (1000 μg/kg) promoted significant lung injury in rats, as shown by increased protein content and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluids (BALF). Moreover, BAC/TEG mixture recruited inflammatory cells, polymorphonuclear leukocytes (PMNs), in terminal bronchioles and elevated cytokine levels, tumor necrosis factor α (TNF‐α), and interleukin 6 (IL‐6) in BALF. These results suggest that TEG can potentiate BAC‐induced pulmonary toxicity and inflammation, and thus respiratory exposure to the air mist from spray‐form products containing this chemical combination is potentially harmful to humans.

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“…A report from Leutkemeier et al (1974) also showed that 3 weeks of exposure to TCS vapor by repeated inhalation caused acute inflammation with focal ulcerations in the nasal cavity and trachea at 0.30 mg/L. Recently, we have demonstrated that a single intratracheal instillation of TCS to rats results in acute pulmonary toxicity, including acute inflammation and lung dysfunction (Kwon et al, 2013). The other histopathological changes observed in the treatment groups were not considered to be treatment-related effects, because they did not show a dose-response relationship and these findings are well Table 8 Incidence and severity of histopathological findings in male and female rats exposed to TCS for 28 days.…”

Section: Tablementioning

confidence: 61%

“…This chemical is effective against certain types of fungi and various types of bacteria by blocking the active site of the enoyl-acyl carrier protein reductase (ENR), which is an essential enzyme for fatty acid biosynthesis in fungi and bacteria (McMurry et al, 1998;Heath et al, 2000). Because humans do not possess this ENR and TCS has low acute toxicity, the use of TCS has not been highly regulated, and it is accepted as well tolerated and safe (Bhargava and Leonard, 1996;Kwon et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…More than 50% of the rats died after a single 2 h exposure to 1.3 mg/L; the LC 50 value for rats was <1.3 mg/L for either sex (Leutkemeier et al, 1974). In addition, TCS has toxic effects, including causing a decrease in cell viability with morphological changes in L2 rat epithelial lung cells, and acute inflammatory and permeability effects in the lung after a single intratracheal instillation of 1 mg/kg (Kwon et al, 2013). Despite the widespread use of TCS, there is a lack of information regarding its repeated-dose toxicity after inhalation.…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Kwon

Shim

et al. 2015

Regulatory Toxicology and Pharmacology

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Pulmonary toxicity screening of triclosan in rats after intratracheal instillation

Cited by 21 publications

References 9 publications

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

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

Evaluation of pulmonary toxicity of benzalkonium chloride and triethylene glycol mixtures using in vitro and in vivo systems

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

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