[Show abstract][Hide abstract] ABSTRACT: 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.
Preview · Article · Jan 2016 · The Journal of Toxicological Sciences
[Show abstract][Hide abstract] ABSTRACT: Talc is a mineral that is widely used in cosmetic products, antiseptics, paints, and rubber manufacturing. Although the toxicological effects of talc have been studied extensively, until now no detailed inhalation study of talc focusing on oxidative stress has been done. This repeated 4 weeks whole-body inhalation toxicity study of talc involved Sprague-Dawley rats. Male and female groups of rats were exposed to inhaled talc at 0, 5, 50, and 100 mg/m(3) for 6 hours daily, 5 days/week for 4 weeks. The objective was to identify the 4-week inhalation toxicity of talc and investigate antioxidant activity after exposure to talc. There were no treatment-related symptoms or mortality in rats treated with talc. Glucose (GLU) was decreased significantly in male rats exposed to 50 and 100 mg/m(3) of talc. Histopathological examination revealed infiltration of macrophages on the alveolar walls and spaces near the terminal and respiratory bronchioles. In male and female rats exposed to 100 mg/m(3) talc, expression of superoxide dismutase 2, a typical biological indicator of oxidative damage, was significantly increased. Thus, inhalation of talc induces macrophage aggregations and oxidative damage in the lung.
Full-text · Article · Oct 2015 · International Journal of Toxicology
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Jan 2015 · Regulatory Toxicology and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Metal-based nanoparticles (NPs) such as silver (Ag) and titanium dioxide (TiO2) are widely used in industrial and household applications. Because of the increasing use of such manufactured NPs and their release into the natural environment, NPs are likely to have a widespread geographic distribution. Concerns over discharge of considerable amounts of these NPs into the environment are increasing. Although recent studies have raised concerns about the health risks and environmental impacts of NPs, little is known about their environmental fate and behavior, particularly in aquatic ecosystems, which is the final destination of NPs due to precipitation and runoff. In this review, we discuss possible routes of environmental exposure as well as the occurrence, behavior, and bioaccumulation of Ag-NPs and TiO2-NPs in the environment.
Full-text · Article · Mar 2014 · Molecular and Cellular Toxicology
[Show abstract][Hide abstract] ABSTRACT: Increase in the use of manufactured nanomaterials (NMs) has led to concerns about the environmental impacts. Especially, hazard of metal-based NMs is more severe due to ions released from surface by water quality parameters and physicochemical properties after entering into the water environment. However, little is known about the effects of ionization on the toxicity of metal-based NMs in the water environment. To address this question, we prepared the suspensions of silver nanoparticles (AgNP) at 25 μg L(-1) containing different concentrations of Ag(+) (5, 10, 20, 45, and 75% Ag(+) to total Ag), and evaluated their toxicity to Japanese medaka (Oryzias latipes) embryos. Higher Ag(+) ratios in the AgNP suspension, suggesting the lower number of particles, led to the higher adverse effects on embryos and sac-fries. In addition, histopathology analysis revealed that AgNPs penetrated through chorion of eggs and skin membrane, and were distributed into the tissues. The results imply that the ionization could decrease the toxicity of metal-based NMs in the water environment.
Full-text · Article · Feb 2014 · Journal of Environmental Science and Health Part A Toxic/Hazardous Substances & Environmental Engineering
[Show abstract][Hide abstract] ABSTRACT: Combined repeated-dose toxicity study of citrate-capped silver nanoparticles (7.9 ± 0.95 nm) with reproduction/developmental toxicity was investigated in rats orally treated with 62.5, 125 and 250 mg/kg, once a day for 42 days for males and up to 52 days for females. The test was performed based on the Organization for Economic Cooperation and Development test guideline 422 and Good Laboratory Practice principles. No death was observed in any of the groups. Alopecia, salivation and yellow discolouration of the lung were observed in a few rats but the symptoms were not dose-dependent. Haematology, serum biochemical investigation and histopathological analysis revealed no statistically significant differences between control group and the treated groups. Toxicity endpoints of reproduction/developmental screening test including mating, fertility, implantation, delivery and foetus were measured. There was no evidence of toxicity.
[Show abstract][Hide abstract] ABSTRACT: Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m(3) for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m(3) in male rats and 0.9 mg/m(3) in female rats under the present experimental condition.
Full-text · Article · Nov 2013 · The Journal of Toxicological Sciences
[Show abstract][Hide abstract] ABSTRACT: Aluminum nanoparticles (Al-NPs) are one of the most widely used nanomaterial in cosmetics and medical materials. For this reason, Al-NP exposure is very likely to occur via inhalation in the environment and the workplace. Nevertheless, little is known about the mechanism of Al-NP neurotoxicity via inhalation exposure. In this study, we investigated the effect AL-NPs on the brain. Rats were exposed to Al-NPs by nasal instillation at 1 mg/kg body weight (low exposure group), 20 mg/kg body weight (moderate exposure group), and 40 mg/kg body weight (high exposure group), for a total of 3 times, with a 24-hr interval after each exposure. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that the presence of aluminum was increased in a dose-dependent manner in the olfactory bulb (OFB) and the brain. In microarray analysis, the regulation of mitogen-activated protein kinases (MAPK) activity (GO: 0043405), including Ptprc, P2rx7, Map2k4, Trib3, Trib1, and Fgd4 was significantly over-expressed in the treated mice than in the controls (p = 0.0027). Moreover, Al-NPs induced the activation of ERK1 and p38 MAPK protein expression in the brain, but did not alter the protein expression of JNK, when compared to the control. These data demonstrate that the nasal exposure of Al-NPs can permeate the brain via the olfactory bulb and modulate the gene and protein expression of MAPK and its activity.
Full-text · Article · Sep 2013 · Toxicological Research
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.
[Show abstract][Hide abstract] ABSTRACT: Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage. Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/uteh.
No preview · Article · Aug 2013 · Toxicology Letters
[Show abstract][Hide abstract] ABSTRACT: The developmental toxicity of silver nanoparticles (AgNPs) was investigated following exposure of Oryzias latipes (medaka) embryos to 0.1-1 mg/L of homogeneously dispersed AgNPs for 14 days. During this period, developmental endpoints, including lethality, heart rate, and hatching rate, were evaluated by microscopy for different stages of medaka embryonic development. To compare toxic sensitivity, acute adult toxicity was assessed. There was no difference in acute lethal toxicity between embryo and adult medaka. Interestingly, we found that the increase in stepwise toxicity was dependent on the developmental stage of the embryo. Lethal embryonic toxicity increased from exposure days 1 to 3 and exposure days 5 to 8, whereas there was no change from exposure days 3 to 5. In addition, 7 d exposure to 0.8 mg/L AgNPs resulted in significant heart beat retardation in medaka embryos. AgNPs also caused a dose-dependent decrease in the hatching rate and body length of larvae. These results indicate that AgNP exposure causes severe developmental toxicity to medaka embryos and that toxicity levels are enhanced at certain developmental stages, which should be taken into consideration in assessments of metallic NPs toxicity to embryos.
[Show abstract][Hide abstract] ABSTRACT: Triclosan (TCS) is a chemical compound used in household products as biocide. However, their pulmonary toxicity has been unclear. Thus, the purpose of this study was to investigate the possibility of injury to the lung by inhalation of TCS. Rats were exposed to TCS by single intratracheal instillation of 10 µg/B.W. kg for the low-dose group and 1,000 µg/B.W. kg for the high-dose group, respectively. TCS induced increase in the level of total cell (TC) count, polymorphonuclear leukocytes (PMNs), total protein (TP), lactate acid dehydrogenase (LDH), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) at 1 day after instillation. However, most pulmonary toxicity marker levels except TP in BALF were restored 14 days after instillation. In addition, TCS led to reduction of cell viability with morphological change in lung eptiehelial cells (L2 cell). Therefore, TCS may affect responses of acute inflammation and permeability in the lung.
No preview · Article · Jun 2013 · The Journal of Toxicological Sciences
[Show abstract][Hide abstract] ABSTRACT: In this study, physico-chemical properties and environmental fate were investigated and ecotoxicity tests using fish, daphnia and algae were conducted for an initial ecological risk assessment of 1,2-Benzisothiazol-3-one. Due to low volatility of the test substance under environmental conditions, it is likely to distributed in soil and water environment. The compound has low adsorption in the soil, with low bioconcentration potential. Acute toxicity results showed that 96 h- for Oryzias laties was 4.7 mg/L (measured) and 48h- for Daphnia magna was 3.3 mg/L (measured). In a growth inhibition test with Pseudokirchneriella subcapitata, 72 h- was 0.456 mg/L (growth rate, nominal) and 0.262 mg/L (yield, nominal). Using the acute toxicity value of algae, predicted no-effect concentration (PNEC) in the aquatic environment was determined to be 2.62 using an factor of 100. According to globally harmonized system (GHS), the compound was categorized as aquatic acute 1 for algae, while it was categorized as aquatic acute 2 for fish and daphnia. This screening assessment suggests that the test substance may pose ecological risks in the aquatic environment.
[Show abstract][Hide abstract] ABSTRACT: 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.
Full-text · Article · Mar 2013 · Molecular and Cellular Toxicology