Science.gov

Sample records for nanoparticle pulmonary toxicity

  1. Nanoparticle-induced pulmonary toxicity.

    PubMed

    Li, Jasmine Jia'en; Muralikrishnan, Sindu; Ng, Cheng-Teng; Yung, Lin-Yue Lanry; Bay, Boon-Huat

    2010-09-01

    In recent decades, advances in nanotechnology engineering have given rise to the rapid development of many novel applications in the biomedical field. However, studies into the health and safety of these nanomaterials are still lacking. The main concerns are the adverse effects to health caused by acute or chronic exposure to nanoparticles (NPs), especially in the workplace environment. The lung is one of the main routes of entry for NPs into the body and, hence, a likely site for accumulation of NPs. Once NPs enter the interstitial air spaces and are quickly taken up by alveolar cells, they are likely to induce toxic effects. In this review, we highlight the different aspects of lung toxicity resulting from NP exposure, such as generation of oxidative stress, DNA damage and inflammation leading to fibrosis and pneumoconiosis, and the underlying mechanisms causing pulmonary toxicity.

  2. Pulmonary applications and toxicity of engineered nanoparticles.

    PubMed

    Card, Jeffrey W; Zeldin, Darryl C; Bonner, James C; Nestmann, Earle R

    2008-09-01

    Because of their unique physicochemical properties, engineered nanoparticles have the potential to significantly impact respiratory research and medicine by means of improving imaging capability and drug delivery, among other applications. These same properties, however, present potential safety concerns, and there is accumulating evidence to suggest that nanoparticles may exert adverse effects on pulmonary structure and function. The respiratory system is susceptible to injury resulting from inhalation of gases, aerosols, and particles, and also from systemic delivery of drugs, chemicals, and other compounds to the lungs via direct cardiac output to the pulmonary arteries. As such, it is a prime target for the possible toxic effects of engineered nanoparticles. The purpose of this article is to provide an overview of the potential usefulness of nanoparticles and nanotechnology in respiratory research and medicine and to highlight important issues and recent data pertaining to nanoparticle-related pulmonary toxicity.

  3. Pulmonary toxicity of manufactured nanoparticles

    NASA Astrophysics Data System (ADS)

    Peebles, Brian Christopher

    that carbon blacks contain free radical and other surface functionality as manufactured, and that exposure to ozone further functionalizes the surface. Samples of carbon black that have been exposed to ozone react with their ambient environment so that acid anhydride and cyclic ether functionality hydrolyze to form carboxylic acid functionality, observable by transmission Fourier transform infrared spectroscopy. Persistent free radical content, but not free radical content from ozone exposure, may mediate the toxic response of cells to carbon blacks in vitro. Results showed that macrophages exposed to carbon blacks that had been exposed to ozone were not less viable in vitro than macrophages exposed to carbon blacks as manufactured because the free radical content that resulted from ozone exposure was not persistent in an aqueous medium. Furthermore, concurrent exposure to ozonated carbon blacks and ozone was less lethal to macrophages than carbon black exposure alone, possibly because the ozone oxidatively preconditioned the macrophages to resist oxidative stress. The nature of redox-active iron species on the surface of iron-loaded synthetic carbon particles was explored. The particles had been shown in previous studies to provoke an inflammatory response involving the release of tumor necrosis factor (TNF)-alpha, which was correlated with their production of hydroxyl free radicals via the Fenton reaction in the presence of hydrogen peroxide. It was found that the source of bioavailable Fenton-active iron on the surfaces of the particles was fluoride species that were byproducts of a step in the synthetic process. Fluoride ligated the iron already on the surface, forming a complex that resisted precipitation in the biological medium and thus made the iron more bioavailable. The results of this thesis aim to clarify whether the size and surface chemistry of nanoparticles should be considered more closely as criteria with which to develop better environmental controls

  4. Pulmonary toxicity of ceria nanoparticles in mice after intratracheal instillation.

    PubMed

    Xue, Lingxi; He, Xiao; Li, Yuanyuan; Qu, Meihua; Zhang, Zhiyong

    2013-10-01

    Ceria nanoparticles (nano-ceria) are widely used for various applications such as catalytic converters for automobile exhaust, ultraviolet absorber, and electrolyte in fuel cells. Their potential impacts on the environment and human health have also drawn people's attention. The present study was designed to explore the pulmonary toxicity of nano-ceria in mice after an acute intratracheal instillation. CD-1 mice were exposed to 0.04, 0.4, 4 and 40 microg nano-ceria (corresponding to 10, 100, 1000 and 10000 times of the maximum exposure dose, respectively) and sacrificed at 1, 7, and 28 d post-exposure. Lung injury was assessed by bronchoalveolar ravage fluid (BALF) analysis, cell counts, biochemical analysis of lung homogenate, and histopathology. Cell differential analysis of the BALF show that the numbers of neutrophils and lymphocytes increased significantly in the mice exposed to 40 microg nano-ceria at 1 d after instillation, and returned to control levels by 7 d. The lactate dehydrogenate activity in the BALF from the 40 microg group increased significantly during the whole experimental period. Pathological changes were only found in the lung tissues from the mice of 40 microg nano-ceria group. The changes were most obvious by 7 d post-exposure, and returned to normal by 28 d. No other changes were found. The results of the present study suggest that exposure to nano-ceria at the current levels in the ambient air may not cause respiratory toxicity.

  5. Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity

    PubMed Central

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujishima, Kei; Yatera, Kazuhiro; Yamamoto, Kazuhiro

    2016-01-01

    Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation. PMID:26828483

  6. Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility.

    PubMed

    Kang, Gi Soo; Gillespie, Patricia A; Gunnison, Albert; Rengifo, Hernan; Koberstein, Jeffrey; Chen, Lung-Chi

    2011-02-01

    In this pilot study, we investigated which physicochemical properties of nickel hydroxide nanoparticles (nano-NH) were mainly responsible in inducing pulmonary toxicity. First, we studied the role of nickel ions solubilized from nano-NH by comparing the toxic effects of nano-NH to those of readily soluble nickel sulfate nanoparticles (nano-NS). Additionally, to test whether there was a non-specific stress response due to particle morphology, we compared the toxicity of nano-NH with that of carbon nanoparticles (nano-C) and titanium dioxide nanoparticles (nano-Ti), both of which had similar physical properties such as particle size and shape, to nano-NH. We exposed mice to each type of nanoparticles for 4?h via a whole-body inhalation system and examined oxidative stress and inflammatory responses in the lung. We also determined the lung burden and clearance of Ni following nano-NH and nano-NS exposures. The results showed that lung deposition of nano-NH was significantly greater than that of nano-NS and nano-NH appeared to have stronger inflammogenic potential than nano-NS even when lung Ni burden taken into consideration. This suggests that the toxicity of nano-NH is not driven solely by released Ni ions from deposited nano-NH particles. However, it is unlikely that the greater toxic potential of nano-NH is attributable to a generic stress response from any nanoparticle exposure, since nano-C and nano-Ti did not elicit toxic responses similar to those of nano-NH. These results indicate that the observed pulmonary toxicity by inhaled nano-NH were chemical-specific and deposited dose and solubility are key factors to understand toxicity induced by nano-NH.

  7. Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells.

    PubMed

    Sweeney, Sinbad; Leo, Bey Fen; Chen, Shu; Abraham-Thomas, Nisha; Thorley, Andrew J; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng Jim; Shaffer, Milo S P; Chung, Kian Fan; Ryan, Mary P; Porter, Alexandra E; Tetley, Teresa D

    2016-09-01

    Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P<0.01), 24h after treatment with 25μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf(®), this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag(+) ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

    NASA Astrophysics Data System (ADS)

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2015-11-01

    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO2) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO2 nanoparticles (2, 10 mg/m3, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

  9. Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

    NASA Astrophysics Data System (ADS)

    Yoshiura, Yukiko; Izumi, Hiroto; Oyabu, Takako; Hashiba, Masayoshi; Kambara, Tatsunori; Mizuguchi, Yohei; Lee, Byeong Woo; Okada, Takami; Tomonaga, Taisuke; Myojo, Toshihiko; Yamamoto, Kazuhiro; Kitajima, Shinichi; Horie, Masanori; Kuroda, Etsushi; Morimoto, Yasuo

    2015-06-01

    In order to investigate the pulmonary toxicity of titanium dioxide (TiO2) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO2 nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO2 nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO2 may not lead to chronic, irreversible legions in the lung, and that TiO2 nanoparticles may not have a high potential for lung disorder.

  10. Assessment of pulmonary toxicity of MgO nanoparticles in rats.

    PubMed

    Gelli, Kiranmai; Porika, Mahendar; Anreddy, Rama Narsimha Reddy

    2015-03-01

    In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post-exposure intervals. A dose-dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post-exposure periods (P <0.05), and a dose-dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post-exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose-dependent pulmonary toxicity in rats and was comparable with that of Quartz particles.

  11. Simple in vitro models can predict pulmonary toxicity of silver nanoparticles.

    PubMed

    Braakhuis, Hedwig M; Giannakou, Christina; Peijnenburg, Willie J G M; Vermeulen, Jolanda; van Loveren, Henk; Park, Margriet V D Z

    2016-08-01

    To study the effects of nanomaterials after inhalation, a large number of in vitro lung models have been reported in literature. Although the in vitro models contribute to the reduction of animal studies, insufficient data exists to determine the predictive value of these in vitro models for the in vivo situation. The aim of this study was to determine the correlation between in vitro and in vivo data by comparing the dose metrics of silver nanoparticles in an in vitro lung model of increasing complexity to our previously published in vivo inhalation study. In vivo, the previously published study showed that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation. The results of the present study show that particle surface area is a suitable dose metric to describe the effects of silver nanoparticles when using a simple monolayer of lung epithelial cells. The dose metric shifted from particle surface area to particle mass when adding an increasing number of macrophages. In addition, a co-culture of endothelial cells, epithelial cells and macrophages on a Transwell® insert correlated less well to the in vivo results compared to the epithelial monolayer. We conclude that for studying the acute pulmonary toxicity of nanoparticles simple in vitro models using an epithelial monolayer better predict the in vivo response compared to complex co-culture models.

  12. Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation

    PubMed Central

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Kawaguchi, Kenji; Sasaki, Takeshi

    2016-01-01

    We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity. PMID:27490535

  13. Pulmonary Toxicity in Rats Caused by Exposure to Intratracheal Instillation of SiO2 Nanoparticles.

    PubMed

    Yang, Hong; Wu, Qiu Yun; Li, Ming Yue; Lao, Can Shan; Zhang, Ying Jian

    2017-04-01

    The effect of the silica nanoparticles (SNs) on lungs injury in rats was investigated to evaluate the toxicity and possible mechanisms for SNs. Male Wistar rats were instilled intratracheally with 1 mL of saline containing 6.25, 12.5, and 25.0 mg of SNs or 25.0 mg of microscale SiO2 particles suspensions for 30 d, were then sacrificed. Histopathological and ultrastructural change in lungs, and chemical components in the urine excretions were investigated by light microscope, TEM and EDS. MDA, NO and hydroxyproline (Hyp) in lung homogenates were quantified by spectrophotometry. Contents of TNF-α, TGF-β1, IL-1β, and MMP-2 in lung tissue were determined by immunohistochemistry staining. There is massive excretion of Si substance in urine. The SNs lead pulmonary lesions of rise in lung/body coefficients, lung inflammation, damaged alveoli, granuloma nodules formation, and collagen metabolized perturbation, and lung tissue damage is milder than those of microscale SiO2 particles. The SNs also cause increase lipid peroxidation and high expression of cytokines. The SNs result into pulmonary fibrosis by means of increase lipid peroxidation and high expression of cytokines. Milder effect of the SNs on pulmonary fibrosis comparing to microscale SiO2 particles is contributed to its elimination from urine due to their ultrafine particle size. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  14. Pulmonary Toxicity of Instilled Silver Nanoparticles: Influence of Size, Coating and Rat Strain

    PubMed Central

    Seiffert, Joanna; Hussain, Farhana; Wiegman, Coen; Li, Feng; Bey, Leo; Baker, Warren; Porter, Alexandra; Ryan, Mary P.; Chang, Yan; Gow, Andrew; Zhang, Junfeng; Zhu, Jie; Tetley, Terry D.; Chung, Kian Fan

    2015-01-01

    Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP) respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20nm and 110nm; polyvinylpyrrolidone (PVP) and citrate-capped; 0.1 mg/Kg) in Brown-Norway (BN) and Sprague-Dawley (SD) rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL) in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma. PMID:25747867

  15. Pulmonary toxicity of instilled silver nanoparticles: influence of size, coating and rat strain.

    PubMed

    Seiffert, Joanna; Hussain, Farhana; Wiegman, Coen; Li, Feng; Bey, Leo; Baker, Warren; Porter, Alexandra; Ryan, Mary P; Chang, Yan; Gow, Andrew; Zhang, Junfeng; Zhu, Jie; Tetley, Terry D; Chung, Kian Fan

    2015-01-01

    Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP) respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20 nm and 110 nm; polyvinylpyrrolidone (PVP) and citrate-capped; 0.1 mg/Kg) in Brown-Norway (BN) and Sprague-Dawley (SD) rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20 nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL) in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20 nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20 nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma.

  16. Identification of the appropriate dose metric for pulmonary inflammation of silver nanoparticles in an inhalation toxicity study.

    PubMed

    Braakhuis, Hedwig M; Cassee, Flemming R; Fokkens, Paul H B; de la Fonteyne, Liset J J; Oomen, Agnes G; Krystek, Petra; de Jong, Wim H; van Loveren, Henk; Park, Margriet V D Z

    2016-01-01

    A number of studies have shown that induction of pulmonary toxicity by nanoparticles of the same chemical composition depends on particle size, which is likely in part due to differences in lung deposition. Particle size mostly determines whether nanoparticles reach the alveoli, and where they might induce toxicity. For the risk assessment of nanomaterials, there is need for a suitable dose metric that accounts for differences in effects between different sized nanoparticles of the same chemical composition. The aim of the present study is to determine the most suitable dose metric to describe the effects of silver nanoparticles after short-term inhalation. Rats were exposed to different concentrations (ranging from 41 to 1105 µg silver/m(3) air) of 18, 34, 60 and 160 nm silver particles for four consecutive days and sacrificed at 24 h and 7 days after exposure. We observed a concentration-dependent increase in pulmonary toxicity parameters like cell counts and pro-inflammatory cytokines in the bronchoalveolar lavage fluid. All results were analysed using the measured exposure concentrations in air, the measured internal dose in the lung and the estimated alveolar dose. In addition, we analysed the results based on mass, particle number and particle surface area. Our study indicates that using the particle surface area as a dose metric in the alveoli, the dose-response effects of the different silver particle sizes overlap for most pulmonary toxicity parameters. We conclude that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation.

  17. Pulmonary toxicity and kinetic study of Cy5.5-conjugated superparamagnetic iron oxide nanoparticles by optical imaging

    SciTech Connect

    Cho, Wan-Seob; Park, Sue Nie; Yu, Mi Kyung; Jon, Sangyong; Jeong, Jayoung

    2009-08-15

    Recent advances in the development of nanotechnology and devices now make it possible to accurately deliver drugs or genes to the lung. Magnetic nanoparticles can be used as contrast agents, thermal therapy for cancer, and be made to concentrate to target sites through an external magnetic field. However, these advantages may also become problematic when taking into account safety and toxicological factors. This study demonstrated the pulmonary toxicity and kinetic profile of anti-biofouling polymer coated, Cy5.5-conjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) by optical imaging. Negatively charged, 36 nm-sized, Cy5.5-conjugated TCL-SPION was prepared for optical imaging probe. Cy5.5-conjugated TCL-SPION was intratracheally instilled into the lung by a non-surgical method. Cy5.5-conjugated TCL-SPION slightly induced pulmonary inflammation. The instilled nanoparticles were distributed mainly in the lung and excreted in the urine via glomerular filtration. Urinary excretion was peaked at 3 h after instillation. No toxicity was found under the concentration of 1.8 mg/kg and the half-lives of nanoparticles in the lung and urine were estimated to be about 14.4 {+-} 0.54 h and 24.7 {+-} 1.02 h, respectively. Although further studies are required, our results showed that Cy5.5-conjugated TCL-SPION can be a good candidate for use in pulmonary delivery vehicles and diagnostic probes.

  18. Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories.

    PubMed

    Jacobsen, Nicklas Raun; Stoeger, Tobias; van den Brule, Sybille; Saber, Anne Thoustrup; Beyerle, Andrea; Vietti, Giulia; Mortensen, Alicja; Szarek, Józef; Budtz, Hans Christian; Kermanizadeh, Ali; Banerjee, Atrayee; Ercal, Nuran; Vogel, Ulla; Wallin, Håkan; Møller, Peter

    2015-11-01

    Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100 μg; ≥1.4 mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6 μg; ≥0.3 mg/kg) elicited acute toxicity in terms of reduced weight gain, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12.5 and 25 μg on a range of parameters. However, mice that survived a high dose (50 μg; 2.7 mg/kg) had an increased pulmonary collagen accumulation (fibrosis) at a similar level as a high bolus dose of crystalline silica. The recovery from these toxicological effects appeared dose-dependent. The results indicate that alveolar deposition of ZnO NP may cause significant adverse health effects. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Comparative Pulmonary Toxicity of Two Ceria Nanoparticles with the Same Primary Size

    PubMed Central

    Peng, Lu; He, Xiao; Zhang, Peng; Zhang, Jing; Li, Yuanyuan; Zhang, Junzhe; Ma, Yuhui; Ding, Yayun; Wu, Zhenqiang; Chai, Zhifang; Zhang, Zhiyong

    2014-01-01

    Ceria nanoparticles (nano-ceria) have recently gained a wide range of applications, which might pose unwanted risks to both the environment and human health. The greatest potential for the environmental discharge of nano-ceria appears to be in their use as a diesel fuel additive. The present study was designed to explore the pulmonary toxicity of nano-ceria in mice after a single exposure via intratracheal instillation. Two types of nano-ceria with the same distribution of a primary size (3–5 nm), but different redox activity, were used: Ceria-p, synthesized by a precipitation route, and Ceria-h, synthesized by a hydrothermal route. Both Ceria-p and Ceria-h induced oxidative stress, inflammatory responses and cytotoxicity in mice, but their toxicological profiles were quite different. The mean size of Ceria-p agglomerates was much smaller compared to Ceria-h, thereby causing a more potent acute inflammation, due to their higher number concentration of agglomerates and higher deposition rate in the deep lung. Ceria-h had a higher reactivity to catalyzing the generation of reactive oxygen species (ROS), and caused two waves of lung injury: bronchoalveolar lavage (BAL) inflammation and cytotoxicity in the early stage and redox-activity-evoked lipid peroxidation and pro-inflammation in the latter stage. Therefore, the size distribution of ceria-containing agglomerates in the exhaust, as well as their surface chemistry are essential characteristics to assess the potential risks of using nano-ceria as a fuel additive. PMID:24727375

  20. Comparative pulmonary toxicity of two ceria nanoparticles with the same primary size.

    PubMed

    Peng, Lu; He, Xiao; Zhang, Peng; Zhang, Jing; Li, Yuanyuan; Zhang, Junzhe; Ma, Yuhui; Ding, Yayun; Wu, Zhenqiang; Chai, Zhifang; Zhang, Zhiyong

    2014-04-10

    Ceria nanoparticles (nano-ceria) have recently gained a wide range of applications, which might pose unwanted risks to both the environment and human health. The greatest potential for the environmental discharge of nano-ceria appears to be in their use as a diesel fuel additive. The present study was designed to explore the pulmonary toxicity of nano-ceria in mice after a single exposure via intratracheal instillation. Two types of nano-ceria with the same distribution of a primary size (3-5 nm), but different redox activity, were used: Ceria-p, synthesized by a precipitation route, and Ceria-h, synthesized by a hydrothermal route. Both Ceria-p and Ceria-h induced oxidative stress, inflammatory responses and cytotoxicity in mice, but their toxicological profiles were quite different. The mean size of Ceria-p agglomerates was much smaller compared to Ceria-h, thereby causing a more potent acute inflammation, due to their higher number concentration of agglomerates and higher deposition rate in the deep lung. Ceria-h had a higher reactivity to catalyzing the generation of reactive oxygen species (ROS), and caused two waves of lung injury: bronchoalveolar lavage (BAL) inflammation and cytotoxicity in the early stage and redox-activity-evoked lipid peroxidation and pro-inflammation in the latter stage. Therefore, the size distribution of ceria-containing agglomerates in the exhaust, as well as their surface chemistry are essential characteristics to assess the potential risks of using nano-ceria as a fuel additive.

  1. Potential Toxicity and Underlying Mechanisms Associated with Pulmonary Exposure to Iron Oxide Nanoparticles: Conflicting Literature and Unclear Risk.

    PubMed

    Kornberg, Tiffany G; Stueckle, Todd A; Antonini, James A; Rojanasakul, Yon; Castranova, Vincent; Yang, Yong; Wang, Liying

    2017-10-06

    Fine/micron-sized iron oxide particulates are incidentally released from a number of industrial processes, including iron ore mining, steel processing, welding, and pyrite production. Some research suggests that occupational exposure to these particulates is linked to an increased risk of adverse respiratory outcomes, whereas other studies suggest that iron oxide is biologically benign. Iron oxide nanoparticles (IONPs), which are less than 100 nm in diameter, have recently surged in use as components of novel drug delivery systems, unique imaging protocols, as environmental catalysts, and for incorporation into thermoplastics. However, the adverse outcomes associated with occupational exposure to IONPs remain relatively unknown. Relevant in vivo studies suggest that pulmonary exposure to IONPs may induce inflammation, pulmonary fibrosis, genotoxicity, and extra-pulmonary effects. This correlates well with in vitro studies that utilize relevant dose, cell type(s), and meaningful end points. A majority of these adverse outcomes are attributed to increased oxidative stress, most likely caused by particle internalization, dissolution, release of free iron ions, and disruption of iron homeostasis. However, because the overall toxicity profile of IONPs is not well understood, it is difficult to set safe exposure limit recommendations that would be adequate for the protection of at-risk workers. This review article will focus on known risks following IONPs exposure supported by human, animal, and cell culture-based studies, the potential challenges intrinsic to IONPs toxicity assessment, and how these may contribute to the poorly characterized IONPs toxicity profile.

  2. The effect of zirconium doping of cerium dioxide nanoparticles on pulmonary and cardiovascular toxicity and biodistribution in mice after inhalation.

    PubMed

    Dekkers, Susan; Miller, Mark R; Schins, Roel P F; Römer, Isabella; Russ, Mike; Vandebriel, Rob J; Lynch, Iseult; Belinga-Desaunay, Marie-France; Valsami-Jones, Eugenia; Connell, Shea P; Smith, Ian P; Duffin, Rodger; Boere, John A F; Heusinkveld, Harm J; Albrecht, Catrin; de Jong, Wim H; Cassee, Flemming R

    2017-08-01

    Development and manufacture of nanomaterials is growing at an exponential rate, despite an incomplete understanding of how their physicochemical characteristics affect their potential toxicity. Redox activity has been suggested to be an important physicochemical property of nanomaterials to predict their biological activity. This study assessed the influence of redox activity by modification of cerium dioxide nanoparticles (CeO2 NPs) via zirconium (Zr) doping on the biodistribution, pulmonary and cardiovascular effects in mice following inhalation. Healthy mice (C57BL/6 J), mice prone to cardiovascular disease (ApoE(-/-), western-diet fed) and a mouse model of neurological disease (5 × FAD) were exposed via nose-only inhalation to CeO2 NPs with varying amounts of Zr-doping (0%, 27% or 78% Zr), or clean air, over a four-week period (4 mg/m(3) for 3 h/day, 5 days/week). Effects were assessed four weeks post-exposure. In all three mouse models CeO2 NP exposure had no major toxicological effects apart from some modest inflammatory histopathology in the lung, which was not related to the amount of Zr-doping. In ApoE(-/-) mice CeO2 did not change the size of atherosclerotic plaques, but there was a trend towards increased inflammatory cell content in relation to the Zr content of the CeO2 NPs. These findings show that subacute inhalation of CeO2 NPs causes minimal pulmonary and cardiovascular effect four weeks post-exposure and that Zr-doping of CeO2 NPs has limited effect on these responses. Further studies with nanomaterials with a higher inherent toxicity or a broader range of redox activities are needed to fully assess the influence of redox activity on the toxicity of nanomaterials.

  3. Assessing Nanoparticle Toxicity

    NASA Astrophysics Data System (ADS)

    Love, Sara A.; Maurer-Jones, Melissa A.; Thompson, John W.; Lin, Yu-Shen; Haynes, Christy L.

    2012-07-01

    Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

  4. COMPARATIVE IN VITRO PULMONARY TOXICITY OF ENGINEERED, MANUFACTURED, AND ENVIRONMENTAL NANOPARTICLES

    EPA Science Inventory

    Engineered nanomaterials display many unique physicochemical properties for a variety of applications and due to their novel propertiesapplications may have unique routes of exposure and toxicity. This study examines the: 1) ability of the MTT assay to generate false positives or...

  5. COMPARATIVE IN VITRO PULMONARY TOXICITY OF ENGINEERED, MANUFACTURED, AND ENVIRONMENTAL NANOPARTICLES

    EPA Science Inventory

    Engineered nanomaterials display many unique physicochemical properties for a variety of applications and due to their novel propertiesapplications may have unique routes of exposure and toxicity. This study examines the: 1) ability of the MTT assay to generate false positives or...

  6. Toxicity of therapeutic nanoparticles.

    PubMed

    Maurer-Jones, Melissa A; Bantz, Kyle C; Love, Sara A; Marquis, Bryce J; Haynes, Christy L

    2009-02-01

    A total of six nanotherapeutic formulations are already approved for medical use and more are in the approval pipeline currently. Despite the massive research effort in nanotherapeutic materials, there is relatively little information about the toxicity of these materials or the tools needed to assess this toxicity. Recently, the scientific community has begun to respond to the paucity of information by investing in the field of nanoparticle toxicology. This review is intended to provide an overview of the techniques needed to assess toxicity of these therapeutic nanoparticles and to summarize the current state of the field. We begin with background on the toxicological assessment techniques used currently as well as considerations in nanoparticle dosing. The toxicological research overview is divided into the most common applications of therapeutic nanoparticles: drug delivery, photodynamic therapy and bioimaging. We end with a perspective section discussing the current technological gaps and promising research aimed at addressing those gaps.

  7. Acute and subacute pulmonary toxicity caused by a single intratracheal instillation of colloidal silver nanoparticles in mice: pathobiological changes and metallothionein responses.

    PubMed

    Kaewamatawong, Theerayuth; Banlunara, Wijit; Maneewattanapinyo, Pattwat; Thammachareon, Chuchaat; Ekgasit, Sanong

    2014-01-01

    To study the acute and subacute pulmonary toxicity of colloidal silver nanoparticles (Ag-NPs), 0 or 100 ppm of Ag-NPs were instilled intratracheally in mice. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF) and histological alterations were determined 1, 3, 7, 15, and 30 days after instillation. Ag-NPs induced moderate pulmonary inflammation and injury on BALF indices during the acute period; however, these changes gradually regressed in a time-dependent manner. Concomitant histopathological and laminin immunohistochemical findings generally correlated to BALF data. Superoxide dismutase and metallothionein expression occurred in particle-laden macrophages and alveolar epithelial cells, which correlated to lung lesions in mice treated with Ag-NPs. These findings suggest that instillation of Ag-NPs causes transient moderate acute lung inflammation and tissue damage. Oxidative stress may underlie the induction of injury to lung tissue. Moreover, the expression of metallothionein in tissues indicated the protective response to exposure to Ag-NPs.

  8. Toxicity of nanoparticles.

    PubMed

    Zoroddu, Maria Antonietta; Medici, Serenella; Ledda, Alessia; Nurchi, Valeria Marina; Lachowicz, Joanna I; Peana, Massimiliano

    2014-01-01

    Nowadays more than thousands of different nanoparticles are known, though no well-defined guidelines to evaluate their potential toxicity and to control their exposure are fully provided. The way of entry of nanoparticles together with their specificities such as chemistry, chemical composition, size, shape or morphology, surface charge and area can influence their biological activities and effects. A specific property may give rise to either a safe particle or to a dangerous one. The small size allows nanoparticles to enter the body by crossing several barriers, to pass into the blood stream and lymphatic system from where they can reach organs and tissues and strictly interact with biological structures, thus damaging their normal functions in different ways. This review provides a summary of what is known on the toxicology related to the specificity of nanoparticles, both as technological tools or ambient pollutants. The aim is to highlight their potential hazard and to provide a balanced update on all the important questions and directions that should be focused in the near future.

  9. Role of engineered metal oxide nanoparticle agglomeration in reactive oxygen species generation and cathepsin B release in NLRP3 inflammasome activation and pulmonary toxicity.

    PubMed

    Sager, Tina M; Wolfarth, Michael; Leonard, Stephen S; Morris, Anna M; Porter, Dale W; Castranova, Vincent; Holian, Andrij

    2016-12-01

    Incomplete understanding of the contributions of dispersants and engineered nanoparticles/materials (ENM) agglomeration state to biological outcomes presents an obstacle for toxicological studies. Although reactive oxygen species (ROS) production is often regarded as the primary indicator of ENM bioactivity and toxicity, it remains unclear whether ENM produce ROS or whether ROS is an outcome of ENM-induced cell injury. Phagolysosomal disruption and cathepsin B release also promote bioactivity through inflammasome activation. Therefore, specific particle parameters, i.e. preexposure dispersion status and particle surface area, of two ENM (NiO and CeO2) were used to evaluate the role of ROS generation and cathepsin B release during ENM-induced toxicity. Male C57BL/6J mice were exposed to 0, 20, 40, or 80 μg of poorly or well-dispersed NiO-NP or CeO2-NP in four types of dispersion media. At 1- and 7-day postexposure, lung lavage fluid was collected to assess inflammation, cytotoxicity, and inflammasome activation. Results showed that preexposure dispersion status correlated with postexposure pulmonary bioactivity. The differences in bioactivity of NiO-NP and CeO2-NP are likely due to NiO-NP facilitating the release of cathepsin B and in turn inflammasome activation generating proinflammatory cytokines. Further, both metal oxides acted as free radical scavengers. Depending on the pH, CeO2-NP acted as a free radical scavenger in an acidic environment (an environment mimicking the lysosome) while the NiO-NP acted as a scavenger in a physiological pH (an environment that mimics the cytosol of the cell). Therefore, results from this study suggest that ENM-induced ROS is not likely a mechanism of inflammasome activation.

  10. Nanoparticle toxicity and cancer

    NASA Astrophysics Data System (ADS)

    Prevenslik, T.

    2011-07-01

    Nanoparticles (NPs) have provided significant advancements in cancer treatment. But as in any technology, there is a darkside. Experiments have shown NPs in body fluids pose a health risk by causing DNA damage that in of itself may lead to cancer. To avoid the dilemma that NPs are toxic to both cancer cells and DNA alike, the mechanism of NP toxicity must be understood so that the safe use of NPs may go forward. Reactive oxidative species (ROS) of peroxide and hydroxyl radicals damage the DNA by chemical reaction, but require NPs provide energies of about 5 eV not possible by surface effects. Only electromagnetic (EM) radiations beyond ultraviolet (UV) levels may explain the toxicity of NPs. Indeed, experiments show DNA damage from <100 nm NPs mimic the same reaction pathways of conventional sources of ionizing radiation, Hence, it is reasonable to hypothesize that NPs produce their own source of UV radiation, albeit at low intensity. Ionizing radiation from NPs at UV levels is consistent with the theory of QED induced EM radiation. QED stands for quantum electrodynamics. By this theory, fine < 100 nm NPs absorb low frequency thermal energy in the far infrared (FIR) from collisions with the water molecules in body fluids. Since quantum mechanics (QM) precludes NPs from having specific heat, absorbed EM collision energy cannot be conserved by an increase in temperature. But total internal reflection (TIR) momentarily confines the absorbed EM energy within the NP. Conservation proceeds by the creation of QED photons by frequency up-conversion of the absorbed EM energy to the TIR confinement frequency, typically beyond the UV. Subsequently, the QED photons upon scattering from atoms within the NP avoid TIR confinement and leak UV to the surroundings, thereby explaining the remarkable toxicity of NPs. But QED radiation need not be limited to natural or man-made NPs. Extensions suggest UV radiation is produced from biological NPs within the body, e.g., enzyme induced

  11. Pulmonary drug toxicity: radiologic and pathologic manifestations.

    PubMed

    Rossi, S E; Erasmus, J J; McAdams, H P; Sporn, T A; Goodman, P C

    2000-01-01

    Pulmonary drug toxicity is increasingly being diagnosed as a cause of acute and chronic lung disease. Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity. The clinical and radiologic manifestations of these drugs generally reflect the underlying histopathologic processes and include diffuse alveolar damage (DAD), nonspecific interstitial pneumonia (NSIP), bronchiolitis obliterans organizing pneumonia (BOOP), eosinophilic pneumonia, obliterative bronchiolitis, pulmonary hemorrhage, edema, hypertension, or veno-occlusive disease. DAD is a common manifestation of pulmonary drug toxicity and is frequently caused by cytotoxic drugs, especially cyclophosphamide, bleomycin, and carmustine. It manifests radiographically as bilateral hetero- or homogeneous opacities usually in the mid and lower lungs and on high-resolution computed tomographic (CT) scans as scattered or diffuse areas of ground-glass opacity. NSIP occurs most commonly as a manifestation of carmustine toxicity or of toxicity from noncytotoxic drugs such as amidarone. At radiography, it appears as diffuse areas of heterogeneous opacity, whereas early CT scans show diffuse ground-glass opacity and late CT scans show fibrosis in a basal distribution. BOOP, which is commonly caused by bleomycin and cyclophosphamide (as well as gold salts and methotrexate), appears on radiographs as hetero- and homogeneous peripheral opacities in both upper and lower lobes and on CT scans as poorly defined nodular consolidation, centrilobular nodules, and bronchial dilatation. Knowledge of these manifestations and of the drugs most frequently involved can facilitate diagnosis and institution of appropriate treatment.

  12. Nanoparticle Toxicity Mechanisms: Genotoxicity

    NASA Astrophysics Data System (ADS)

    Botta, Alain; Benameur, Laı̈la

    Despite the relatively small amount of convincing experimental data, the potentially genotoxic nature of certain nanoparticles seems plausible, owing in particular to the presence of reactive oxygen species (ROS) such as the superoxide anion O2 • - , the hydroxyl radical • OH, and singlet oxygen 1O2, and reactive nitrogen species (RNS) such as nitrogen monoxide NO, the peroxynitrite anion ONOO - , the peroxynitrite radical ONOO • , and dinitrogen trioxide N2O3, a powerful nitration agent.

  13. Nanoparticles: Is Toxicity a Concern?

    PubMed Central

    Rao, Pragna

    2011-01-01

    Nanotechnology involving manipulation of atoms and molecules at the nanoscale is one of the frontier areas of research in modern science. During the last few years, nanotechnology has witnessed breakthroughs in the fields of medicine, environment, therapeutics, drug development and biotechnology. This is due to the unique properties of nanomaterials (e.g. chemical, mechanical, optical, magnetic, and biological) which make them desirable for commercial and medical applications. Considering the theory and practice of using nanoparticles, nanotechnology has a great potential in improving treatment of various disorders and in vitro diagnostics. However, there is not much information available on the toxicity of nanoparticles in relation to human health. Toxic effect of nanomaterials on humans is the primary concern of the health industry. Nanomaterials are able to cross biological membranes and access cells, tissues and organs that larger-sized particles normally cannot. Nanomaterials can gain access to the blood stream via inhalation or ingestion. This may lead to both genotoxicity and biochemical toxicity. In this review we try to show which types, sizes and concentrations of nanoparticles are safe for human use and this will help in developing diagnostic, prognostic and therapeutic models using nanoparticles. PMID:27683397

  14. Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Nalabotu, Siva Krishna

    The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase

  15. TOXICITY OF SILVER NANOPARTICLES TO DAPHNIA MAGNA

    EPA Science Inventory

    Relatively little is known regarding toxicity of nanoparticles in the environment. It is widely assumed that the toxicity of nanoparticles will be less than that of their metallic ions. Also the effect of organics on metal toxicity is well established. Presented here are the resu...

  16. TOXICITY OF SILVER NANOPARTICLES TO DAPHNIA MAGNA

    EPA Science Inventory

    Relatively little is known regarding toxicity of nanoparticles in the environment. It is widely assumed that the toxicity of nanoparticles will be less than that of their metallic ions. Also the effect of organics on metal toxicity is well established. Presented here are the resu...

  17. Right or left: the role of nanoparticles in pulmonary diseases.

    PubMed

    Lu, Xuefei; Zhu, Tao; Chen, Chunying; Liu, Ying

    2014-09-29

    Due to the rapid development of the nanotechnology industry in the last decade, nanoparticles (NPs) are omnipresent in our everyday life today. Many nanomaterials have been engineered for medical purposes. These purposes include therapy for pulmonary diseases. On other hand, people are endeavoring to develop nanomaterials for improvement or replacement of traditional therapies. On the other hand, nanoparticles, as foreign material in human bodies, are reported to have potential adverse effects on the lung, including oxidase stress, inflammation, fibrosis and genotoxicity. Further, these damages could induce pulmonary diseases and even injuries in other tissues. It seems that nanoparticles may exert two-sided effects. Toxic effects of nanomaterials should be considered when their use is developed for therapies. Hence this review will attempt to summarize the two-side roles of nanoparticles in both therapies for pulmonary diseases and initiation of lung diseases and even secondary diseases caused by lung injuries. Determinants of these effects such as physicochemical properties of nanoparticles will also be discussed.

  18. Right or Left: The Role of Nanoparticles in Pulmonary Diseases

    PubMed Central

    Lu, Xuefei; Zhu, Tao; Chen, Chunying; Liu, Ying

    2014-01-01

    Due to the rapid development of the nanotechnology industry in the last decade, nanoparticles (NPs) are omnipresent in our everyday life today. Many nanomaterials have been engineered for medical purposes. These purposes include therapy for pulmonary diseases. On other hand, people are endeavoring to develop nanomaterials for improvement or replacement of traditional therapies. On the other hand, nanoparticles, as foreign material in human bodies, are reported to have potential adverse effects on the lung, including oxidase stress, inflammation, fibrosis and genotoxicity. Further, these damages could induce pulmonary diseases and even injuries in other tissues. It seems that nanoparticles may exert two-sided effects. Toxic effects of nanomaterials should be considered when their use is developed for therapies. Hence this review will attempt to summarize the two-side roles of nanoparticles in both therapies for pulmonary diseases and initiation of lung diseases and even secondary diseases caused by lung injuries. Determinants of these effects such as physicochemical properties of nanoparticles will also be discussed. PMID:25268624

  19. Novel Polymeric Nanoparticles for Pulmonary Gene Delivery

    NASA Astrophysics Data System (ADS)

    Fields, Rachel Jennifer

    The lung is an important target for gene and drug therapy of many diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), tubuerculosis (TB) and lung cancer. In fact, the pulmonary route has been employed as a means of delivering drugs for centuries, dating back 4000 years to India where inhaled vapors were used for medicinal purpose. Currently, pulmonary administration of small, hydrophobic drugs leads to rapid local and systemic absorption. However, delivery of large biomacromolecules, such as therapeutic genes, has not yet been accomplished. Here, I test the hypothesis that a rationally engineered nanoparticle (NP) vector can improve delivery of large biomacromolecules. . In this dissertation I tested this hypothesis using a hybrid NP delivery system consisting of a blend of poly(lactic-co-glycolic acid) (PLGA) and a poly(beta-amino ester) (PBAE), a cationic polymer that is particularly useful for delivery of nucleic acids.. PBAE/PLGA nanoparticles (15% PBAE) loaded with plasmid DNA were surface modified with cell-penetrating peptides (CPPs) via a PEGylated phospholipid linker. This optimized NP formulation was able to induce substantial intracellular uptake and transfect lung epithelial cells in vitro while imparting minimal cellular toxicity. In order to determine the most effective method to deliver these NPs to the lung I used fluorescently labeled particles to study the biodistribution of particles after administration to the lung of mice via various administration routes. I determined that the intranasal route was most effective. I further investigated this route and determined that an average of 37.1 +/- 15.1 % of lung cells had NP association after 4hrs. I also investigated the association of particles with different lung cell types like macrophages and alveolar epithelial cells and determined that our best particle formulations associated with approximately 80% of both of these cell types. To demonstrate the ability of the

  20. Polymeric nanoparticles in development for treatment of pulmonary infectious diseases.

    PubMed

    Lim, Young H; Tiemann, Kristin M; Hunstad, David A; Elsabahy, Mahmoud; Wooley, Karen L

    2016-11-01

    Serious lung infections, such as pneumonia, tuberculosis, and chronic obstructive cystic fibrosis-related bacterial diseases, are increasingly difficult to treat and can be life-threatening. Over the last decades, an array of therapeutics and/or diagnostics have been exploited for management of pulmonary infections, but the advent of drug-resistant bacteria and the adverse conditions experienced upon reaching the lung environment urge the development of more effective delivery vehicles. Nanotechnology is revolutionizing the approach to circumventing these barriers, enabling better management of pulmonary infectious diseases. In particular, polymeric nanoparticle-based therapeutics have emerged as promising candidates, allowing for programmed design of multi-functional nanodevices and, subsequently, improved pharmacokinetics and therapeutic efficiency, as compared to conventional routes of delivery. Direct delivery to the lungs of such nanoparticles, loaded with appropriate antimicrobials and equipped with 'smart' features to overcome various mucosal and cellular barriers, is a promising approach to localize and concentrate therapeutics at the site of infection while minimizing systemic exposure to the therapeutic agents. The present review focuses on recent progress (2005-2015) important for the rational design of nanostructures, particularly polymeric nanoparticles, for the treatment of pulmonary infections with highlights on the influences of size, shape, composition, and surface characteristics of antimicrobial-bearing polymeric nanoparticles on their biodistribution, therapeutic efficacy, and toxicity. WIREs Nanomed Nanobiotechnol 2016, 8:842-871. doi: 10.1002/wnan.1401 For further resources related to this article, please visit the WIREs website.

  1. Toxicity of Engineered Nanoparticles in the Environment

    PubMed Central

    Maurer-Jones, Melissa A.; Gunsolus, Ian L.; Murphy, Catherine J.; Haynes, Christy L.

    2014-01-01

    While nanoparticles occur naturally in the environment and have been intentionally used for centuries, the production and use of engineered nanoparticles has seen a recent spike, which makes environmental release almost certain. Therefore, recent efforts to characterize the toxicity of engineered nanoparticles have focused on the environmental implications, including exploration of toxicity to organisms from wide-ranging parts of the ecosystem food webs. Herein, we summarize the current understanding of toxicity of engineered nanoparticles to representatives of various trophic levels, including bacteria, plants, and multicellular aquatic/terrestrial organisms, to highlight important challenges within the field of econanotoxicity, challenges that analytical chemists are expertly poised to address. PMID:23427995

  2. Pulmonary Oxygen Toxicity: Investigation and Mentoring

    PubMed Central

    Hedley-Whyte, John

    2008-01-01

    SUMMARY At sea level oxygen is toxic to man when breathed for more than twenty-four hours at a percentage greater than about forty percent. Pulmonary pathology is the first manifestation in subjects with previously normal lungs. In patients with pre-existing lung disease the results are often additive. There is, however, great variation in response from subject to subject and between patients. Queen's Belfast and Harvard University Medical School have been the sites of seminal investigations. Mentoring at both universities is due to training at the University of Copenhagen. PMID:18269117

  3. Acute inhalation toxicity of silver nanoparticles.

    PubMed

    Sung, Jae Hyuck; Ji, Jun Ho; Song, Kyung Seuk; Lee, Ji Hyun; Choi, Kyung Hee; Lee, Sang Hee; Yu, Il Je

    2011-03-01

    The acute inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Seven-week-old rats, weighing approximately 218 g (males) and 153 g (females), were divided into four groups (five rats in each group): fresh-air control, low-dose (0.94 × 10(6) particle/cm(3), 76 µg/m(3)), middle-dose (1.64 × 10(6) particle/ cm(3), 135 µg/m( 3)), and high-dose (3.08 × 10(6) particle/cm(3), 750 µg/m(3)). The animals were then exposed to silver nanoparticles (average diameter 18-20 nm) for 4 hours in a whole-body inhalation chamber. The experiment was conducted following Organization Economic Cooperation and Development (OECD) test guideline 403 with the application of good laboratory practice (GLP). In addition to mortality and clinical observations, the body weights, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, and the organ weights measured. The lung function was also measured twice per week after the initial 4-hour exposure. No significant body weight changes or clinical changes were found during the 2-week observation period. The lung function tests also indicated no significant difference between the fresh air control and the exposed groups. Thus, LC50 silver nanoparticles are suggested for higher than 3.1 × 10(6) particles/cm(3) (750 µg/m(3)).

  4. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries.

    PubMed

    Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M

    2014-01-01

    Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud's phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.

  5. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

    PubMed Central

    Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M

    2014-01-01

    Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy. PMID:25045260

  6. Developmental Toxicity of Nanoparticles on the Brain.

    PubMed

    Umezawa, Masakazu; Onoda, Atsuto; Takeda, Ken

    2017-01-01

     The toxicity of nanoparticles (nanotoxicology) is being investigated to understand both the health impacts of atmospheric ultrafine particles-the size of which is a fraction (<0.1 μm aerodynamic diameter) of that of PM2.5 (<2.5 μm diameter)-and the safer use of engineered nanomaterials. Developmental toxicity of nanoparticles has been studied since their transfer from pregnant body to fetal circulation and offspring body was first reported. Here we reviewed the developmental toxicity of nanoparticles on the brain, one of the most important organs in maintenance of mental health and high quality of life. Recently the dose- and size-dependency of transplacental nanoparticle transfer to the fetus was reported. It is important to understand both the mechanism of direct effect of nanoparticles transferred to the fetus and offspring and the indirect effect mediated by induction of oxidative stress and inflammation in the pregnant body. Locomotor activity, learning and memory, motor coordination, and social behavior were reported as potential neurobehavioral targets of maternal nanoparticle exposure. Histopathologically, brain perivascular cells, including perivascular macrophages and surrounding astrocytes, have an important role in waste clearance from the brain parenchyma. They are potentially the most sensitive target of maternal exposure to low-dose nanoparticles. Further investigations will show the detailed mechanism of developmental toxicity of nanoparticles and preventive strategies against intended and unintended nanoparticle exposure. This knowledge will contribute to the safer design of nanoparticles through the development of sensitive and quantitative endpoints for prediction of their developmental toxicity.

  7. Nanoparticles, nanotechnology and pulmonary nanotoxicology.

    PubMed

    Ferreira, A J; Cemlyn-Jones, J; Robalo Cordeiro, C

    2013-01-01

    The recently emergent field of Nanotechnology involves the production and use of structures at the nanoscale. Research at atomic, molecular or macromolecular levels, has led to new materials, systems and structures on a scale consisting of particles less than 100 nm and showing unique and unusual physical, chemical and biological properties, which has enabled new applications in diverse fields, creating a multimillion-dollar high-tech industry. Nanotechnologies have a wide variety of uses from nanomedicine, consumer goods, electronics, communications and computing to environmental applications, efficient energy sources, agriculture, water purification, textiles, and aerospace industry, among many others. The different characteristics of nanoparticles such as size, shape, surface charge, chemical properties, solubility and degree of agglomeration will determine their effects on biological systems and human health, and the likelihood of respiratory hazards. There are a number of new studies about the potential occupational and environmental effects of nanoparticles and general precautionary measures are now fully justified. Adverse respiratory effects include multifocal granulomas, peribronchial inflammation, progressive interstitial fibrosis, chronic inflammatory responses, collagen deposition and oxidative stress. The authors present an overview of the most important studies about respiratory nanotoxicology and the effects of nanoparticles and engineered nanomaterials on the respiratory system. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  8. Anaerobic Toxicity of Cationic Silver Nanoparticles

    EPA Pesticide Factsheets

    Toxicity data for the impact of nano-silver on anaerobic degradation.This dataset is associated with the following publication:Gitipour, A., S. Thiel, K. Scheckel, and T. Tolaymat. Anaerobic Toxicity of Cationic Silver Nanoparticles. D. Barcelo Culleres, and J. Gan SCIENCE OF THE TOTAL ENVIRONMENT. Elsevier BV, AMSTERDAM, NETHERLANDS, 557: 363-368, (2016).

  9. Pulmonary toxicity of thioureas in the rat

    SciTech Connect

    Scott, A.M.; Powell, G.M.; Curtis, C.G. ); Upshall, D.G. )

    1990-04-01

    Administration of {alpha}-naphthylthiourea (ANTU) to rats causes damage to pulmonary endothelial cells and possibly mesothelial lining cells that together may account for the massive pleural effusion characteristic of thiourea toxicity. Using {sup 35}S-thiourea as a model compound, the extent of binding of {sup 35}S to lung proteins correlated well with the extent of edema, suggesting that the extent of binding of thiourea metabolites is a measure of lung toxicity. ANTU and phenylthiourea (PTU) compete for {sup 35}S binding to lung slices, suggesting that these toxins may act in a similar way. Binding of {sup 35}S in lung slices from resistant rats is much less than in controls, and resistance cannot be explained by differences in either whole body metabolism or redistribution of thiourea in vivo. Lung glutathione levels (in vitro and in vivo) in normal and resistant rats following thiourea administration were essentially the same. However, at doses of thiourea that cause pleural effusion, there was an increase in total lung glutathione.

  10. Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview)

    PubMed Central

    Katsnelson, Boris A; Privalova, Larisa I; Sutunkova, Marina P; Gurvich, Vladimir B; Loginova, Nadezhda V; Minigalieva, Ilzira A; Kireyeva, Ekaterina P; Shur, Vladimir Y; Shishkina, Ekaterina V; Beikin, Ya B; Makeyev, Oleg H; Valamina, Irene E

    2015-01-01

    The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs) in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 μm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other. Our data testify to the high activity of the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that safe levels of exposure to airborne NPs are possible in principle. However, there are no reliable foundations for establishing different permissible exposure levels for particles of different size within the nanometric range. For workroom air, such permissible exposure levels of metallic NP can be proposed at this stage, even if tentatively, based on a sufficiently conservative approach of decreasing approximately tenfold the exposure limits officially established for respective micro-scale industrial aerosols. It was shown that against the background of adequately composed combinations of some bioactive agents (comprising pectin, multivitamin-multimineral preparations, some amino acids, and omega-3 polyunsaturated fatty acid) the systemic toxicity and even genotoxicity of metallic NPs could be markedly attenuated. Therefore we believe that, along with decreasing NP-exposures, enhancing organisms’ resistance to their adverse action with the help

  11. Effects of silver and gold nanoparticles of different sizes in human pulmonary fibroblasts.

    PubMed

    Ávalos, Alicia; Haza, Ana Isabel; Mateo, Diego; Morales, Paloma

    2015-01-01

    Silver and gold nanoparticles (Ag-AuNPs) are currently some of the most manufactured nanomaterials. Accordingly, the hazards associated with human exposure to Ag-AuNPs should be investigated to facilitate the risk assessment process. In particular, because pulmonary exposure to Ag-AuNPs occurs during handling of these nanoparticles, it is necessary to evaluate the toxic response in pulmonary cells. The aim of this study was to evaluate the in vitro mechanisms of toxicity of different sizes of silver (4.7 and 42 nm) and gold nanoparticles (30, 50 and 90 nm) in human pulmonary fibroblasts (HPF). The toxicity was evaluated by observing cell viability and oxidative stress parameters. Data showed that AgNPs-induced cytotoxicity was size-dependent, whereas the AuNPs of the three sizes showed similar cytotoxicity. Silver nanoparticles of 4.7 nm were much more toxic than the large silver nanoparticles and the AuNPs. However, the pre-treatment with the antioxidant, N-acetyl-L-cysteine, protected HPF cells against treatment with Ag-AuNPs. The oxidative stress parameters revealed significant increase in reactive oxygen species levels, depletion of glutathione level and slight, but not statistically significant inactivation of superoxide dismutase, suggesting generation of oxidative stress. Hence, care has to be taken while processing and formulating the Ag-AuNPs till their final finished product.

  12. Physiologically important metal nanoparticles and their toxicity.

    PubMed

    Sengupta, Jayeeta; Ghosh, Sourav; Datta, Poulami; Gomes, Aparna; Gomes, Antony

    2014-01-01

    Nanotechnology has been setting benchmarks for the last two decades, but the origins of this technology reach back to ancient history. Today, nanoparticles of both metallic and non-metallic origin are under research and development for applications in various fields of biology/therapeutics. Physiologically important metals are of concern because they are compatible with the human system in terms of absorption, assimilation, excretion, and side effects. There are several physiologically inorganic metals that are present in the human body with a wide range of biological activities. Some of these metals are magnesium, chromium, manganese, iron, cobalt, copper, zinc, selenium and molybdenum. These metals are synthesized in the form of nanoparticles by different physical and chemical methods. Physiologically important nanoparticles are currently under investigation for their bio-medical applications as well as for therapeutics. Along with the applicative aspects of nanoparticles, another domain that is of great concern is the risk assessment of these nanoparticles to avoid unnecessary hazards. It has been seen that these nanoparticles have been shown to possess toxicity in biological systems. Conventional physical and chemical methods of metal nanoparticle synthesis may be one possible reason for nanoparticle toxicity that can be overcome by synthesis of nanoparticles from biological sources. This review is an attempt to establish metal nanoparticles of physiological importance to be the best candidates for future nanotechnological tools and medicines, owing to the acceptability and safety in the human body. This can only be successful if these particles are synthesized with a better biocompatibility and low or no toxicity.

  13. Fatal theophylline toxicity precipitated by in situ pulmonary artery thrombosis.

    PubMed Central

    Davies, R. J.; Hawkey, C. J.

    1989-01-01

    A 57 year old man developed theophylline toxicity in association with acute pulmonary artery thrombosis. The plasma half life of theophylline was prolonged suggesting impaired metabolism secondary to acute right heart failure. PMID:2780453

  14. Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

    PubMed Central

    Lanone, Sophie; Rogerieux, Françoise; Geys, Jorina; Dupont, Aurélie; Maillot-Marechal, Emmanuelle; Boczkowski, Jorge; Lacroix, Ghislaine; Hoet, Peter

    2009-01-01

    Background A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated. Results The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found. Conclusion Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity. PMID:19405955

  15. [Toxicity of nanoparticles on reproduction].

    PubMed

    Greco, F; Courbière, B; Rose, J; Orsière, T; Sari-Minodier, I; Bottero, J-Y; Auffan, M; Perrin, J

    2015-01-01

    Nanoparticles (NPs) are sized between 1 and 100nm. Their size allows new nanoscale properties of particular interest for industrial and scientific purpose. Over the past twenty years, nanotechnology conquered many areas of use (electronic, cosmetic, textile…). While, human is exposed to an increasing number of nanoparticles sources, health impacts and, particularly on reproductive function, remains poorly evaluated. Indeed, traceability of nanoparticles use is lacking and nanotoxicology follows different rules than classical toxicology. This review focuses on the impact of NPs on health and particularly on fertility and addresses potential risks of chronic exposure to NPs on human fertility. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Adverse biophysical effects of hydroxyapatite nanoparticles on natural pulmonary surfactant.

    PubMed

    Fan, Qihui; Wang, Yi E; Zhao, Xinxin; Loo, Joachim S C; Zuo, Yi Y

    2011-08-23

    Inhaled nanoparticles (NPs) must first interact with the pulmonary surfactant (PS) lining layer that covers the entire internal surface of the respiratory tract and plays an important role in surface tension reduction and host defense. Interactions with the PS film determine the subsequent clearance, retention, and translocation of the inhaled NPs and hence their potential toxicity. To date, little is known how NPs interact with PS, and whether or not NPs have adverse effects on the biophysical function of PS. We found a time-dependent toxicological effect of hydroxyapatite NPs (HA-NPs) on a natural PS, Infasurf, and the time scale of surfactant inhibition after particle exposure was comparable to the turnover period of surfactant metabolism. Using a variety of in vitro biophysicochemical characterization techniques, we have determined the inhibition mechanism to be due to protein adsorption onto the HA-NPs. Consequently, depletion of surfactant proteins from phospholipid vesicles caused conversion of original large vesicles into much smaller vesicles with poor surface activity. These small vesicles, in turn, inhibited biophysical function of surfactant films after adsorption at the air-water interface. Cytotoxicity study found that the HA-NPs at the studied concentration were benign to human bronchial epithelial cells, thereby highlighting the importance of evaluating biophysical effect of NPs on PS. The NP-PS interaction mechanism revealed by this study may not only provide new insight into the toxicological study of nanoparticles but also shed light on the feasibility of NP-based pulmonary drug delivery.

  17. Polymeric Nanoparticles for Pulmonary Protein and DNA Delivery

    PubMed Central

    Menon, Jyothi U.; Ravikumar, Priya; Pise, Amruta; Gyawali, Dipendra; Hsia, Connie C.W.; Nguyen, Kytai T.

    2014-01-01

    Polymeric nanoparticles (NPs) are promising carriers of biological agents to lung due to advantages including biocompatibility, ease of surface modification, localized action and reduced systemic toxicity. However, there have been no studies extensively characterizing and comparing the behavior of polymeric NPs for pulmonary protein/DNA delivery both in vitro and in vivo. We screened six polymeric NPs: gelatin, chitosan, alginate, poly lactic-co-glycolic acid (PLGA), PLGA-chitosan, and PLGA-polyethylene glycol (PEG), for inhalational protein/ DNA delivery. All NPs except PLGA-PEG and alginate were <300 nm in size with bi-phasic core compound release profile. Gelatin, PLGA NPs and PLGA-PEG NPs remained stable in deionized water, serum, saline and simulated lung fluid (Gamble’s solution) over 5 days. PLGA-based NPs and natural polymer NPs exhibited highest cytocompatibility and dose-dependent in vitro uptake respectively by human alveolar type-1 epithelial cells. Based on these profiles, gelatin and PLGA NPs were used to encapsulate a) plasmid DNA encoding yellow fluorescent protein (YFP) or b) rhodamine-conjugated erythropoietin (EPO) for inhalational delivery to rats. Following a single inhalation, widespread pulmonary EPO distribution persisted for up to 10 days while increasing YFP expression was observed for at least 7 days for both NPs. The overall results support both PLGA and gelatin NPs as promising carriers for pulmonary protein/DNA delivery. PMID:24512977

  18. Anaerobic Toxicity of Cationic Silver Nanoparticles | Science ...

    EPA Pesticide Factsheets

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNps) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10-15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L-1, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L-1 as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag+. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L-1 as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. The current

  19. Anaerobic Toxicity of Cationic Silver Nanoparticles | Science ...

    EPA Pesticide Factsheets

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNps) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10-15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L-1, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L-1 as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag+. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L-1 as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. The current

  20. Anaerobic Toxicity of Cationic Silver Nanoparticles

    EPA Science Inventory

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged p...

  1. Anaerobic Toxicity of Cationic Silver Nanoparticles

    EPA Science Inventory

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged p...

  2. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    SciTech Connect

    Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  3. Nanomaterials and nanoparticles: sources and toxicity.

    PubMed

    Buzea, Cristina; Pacheco, Ivan I; Robbie, Kevin

    2007-12-01

    This review is presented as a common foundation for scientists interested in nanoparticles, their origin,activity, and biological toxicity. It is written with the goal of rationalizing and informing public health concerns related to this sometimes-strange new science of "nano," while raising awareness of nanomaterials' toxicity among scientists and manufacturers handling them.We show that humans have always been exposed to tiny particles via dust storms, volcanic ash, and other natural processes, and that our bodily systems are well adapted to protect us from these potentially harmful intruders. There ticuloendothelial system, in particular, actively neutralizes and eliminates foreign matter in the body,including viruses and nonbiological particles. Particles originating from human activities have existed for millennia, e.g., smoke from combustion and lint from garments, but the recent development of industry and combustion-based engine transportation has profoundly increased an thropogenic particulate pollution. Significantly, technological advancement has also changed the character of particulate pollution, increasing the proportion of nanometer-sized particles--"nanoparticles"--and expanding the variety of chemical compositions. Recent epidemiological studies have shown a strong correlation between particulate air pollution levels, respiratory and cardiovascular diseases, various cancers, and mortality. Adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape,agglomeration state, and electromagnetic properties. Animal and human studies show that inhaled nanoparticles are less efficiently removed than larger particles by the macrophage clearance mechanisms in the lungs, causing lung damage, and that nanoparticles can translocate through the circulatory, lymphatic, and nervous systems to many tissues and organs, including the brain. The key to

  4. Metal oxide nanoparticles with low toxicity.

    PubMed

    Ng, Alan Man Ching; Guo, Mu Yao; Leung, Yu Hang; Chan, Charis M N; Wong, Stella W Y; Yung, Mana M N; Ma, Angel P Y; Djurišić, Aleksandra B; Leung, Frederick C C; Leung, Kenneth M Y; Chan, Wai Kin; Lee, Hung Kay

    2015-10-01

    A number of different nanomaterials produced and incorporated into various products are rising. However, their environmental hazards are frequently unknown. Here we consider three different metal oxide compounds (SnO2, In2O3, and Al2O3), which have not been extensively studied and are expected to have low toxicity. This study aimed to comprehensively characterize the physicochemical properties of these nanomaterials and investigate their toxicity on bacteria (Escherichia coli) under UV illumination and in the dark, as well as on a marine diatom (Skeletonema costatum) under ambient illumination/dark (16-8h) cycles. The material properties responsible for their low toxicity have been identified based on comprehensive experimental characterizations and comparison to a metal oxide exhibiting significant toxicity under illumination (anatase TiO2). The metal oxide materials investigated exhibited significant difference in surface properties and interaction with the living organisms. In order for a material to exhibit significant toxicity, it needs to be able to both form a stable suspension in the culture medium and to interact with the cell walls of the test organism. Our results indicated that the observed low toxicities of the three nanomaterials could be attributed to the limited interaction between the nanoparticles and cell walls of the test organisms. This could occur either due to the lack of significant attachment between nanoparticles and cell walls, or due to their tendency to aggregate in solution. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Toxicity of silver nanoparticles in zebrafish models.

    PubMed

    Asharani, P V; Lian Wu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

    2008-06-25

    This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag(+) ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development.

  6. Toxicity of silver nanoparticles in zebrafish models

    NASA Astrophysics Data System (ADS)

    Asharani, P. V.; Lian Wu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

    2008-06-01

    This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag+ ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development.

  7. Responsive Hydrogel Nanoparticles for Pulmonary Delivery.

    PubMed

    Stocke, Nathanael A; Arnold, Susanne M; Hilt, J Zach

    2015-10-01

    Nanoparticles represent one of the most widely studied classes of advanced drug delivery platforms in recent years due to a wide range of unique properties and capabilities that can be utilized to improve upon traditional drug administration. Conversely, hydrogel nanoparticles (HNPs) - also called nanogels - represent a unique class of materials that combine the intrinsic advantages of nanotechnology with the inherent capabilities of hydrogels. Responsive hydrogels pose a particularly interesting class of materials that can sense and respond to external stimuli and previous reports of inhalable hydrogel particles have highlighted their potential in pulmonary delivery. Here, we synthesized two different pH-responsive HNPs, designated HNP120 and HNP270, by incorporating functional monomers with a common crosslinker and characterized their physicochemical properties. One of the HNP systems was selected for incorporation into a composite dry powder by spray drying, and the aerodynamic performance of the resulting powder was evaluated. The HNP120s displayed a hydrodynamic diameter of approximately 120 nm in their fully swollen state and a minimal diameter of around 80 nm while the HNP270s were approximately 270 nm and 115 nm, respectively. Electron microscopy confirmed particle size- and morphological uniformity of the HNPs. The HNP120s were spray dried into composite dry powders for inhalation and cascade impaction studies showed good aerosol performance with a mass median aerosol diameter (MMAD) of 4.82 ± 0.37 and a fine particle fraction > 30%. The HNPs released from the spray dried composites retained their responsive behavior thereby illustrating the potential for these materials as intelligent drug delivery systems that combine the advantages of nanotechnology, lung targeting through pulmonary delivery, and stimuli-responsive hydrogels.

  8. The significance of nanoparticles in particle-induced pulmonary fibrosis

    PubMed Central

    Byrne, James D; Baugh, John A

    2008-01-01

    Exposure to airborne nanoparticles contributes to many chronic pulmonary diseases. Nanoparticles, classified as anthropogenic and natural particles, and fibers of diameters less than 100 nm, have unrestricted access to most areas of the lung due to their size. Size relates to the deposition efficiency of the particle, with particles in the nano-range having the highest efficiencies. The deposition of nanoparticles in the lung can lead to chronic inflammation, epithelial injury, and further to pulmonary fibrosis. Cases of particle-induced pulmonary fibrosis, namely pneumoconiosis, are mostly occupationally influenced, and continue to be documented around the world. The tremendous growth of nanotechnology, however, has spurred fears of increased rates of pulmonary diseases, especially fibrosis. The severity of toxicological consequences warrants further examination of the effects of nanoparticles in humans, possible treatments and increased regulatory measures. PMID:18523535

  9. Low toxic maghemite nanoparticles for theranostic applications

    PubMed Central

    Zolotukhin, Peter V; Belanova, Anna A; Soldatov, Mikhail A; Lastovina, Tatiana A; Kubrin, Stanislav P; Nikolsky, Anatoliy V; Mirmikova, Lidia I

    2017-01-01

    Background Iron oxide nanoparticles have numerous and versatile biological properties, ranging from direct and immediate biochemical effects to prolonged influences on tissues. Most applications have strict requirements with respect to the chemical and physical properties of such agents. Therefore, developing rational design methods of synthesis of iron oxide nanoparticles remains of vital importance in nanobiomedicine. Methods Low toxic superparamagnetic iron oxide nanoparticles (SPIONs) for theranostic applications in oncology having spherical shape and maghemite structure were produced using the fast microwave synthesis technique and were fully characterized by several complementary methods (transmission electron microscopy [TEM], X-ray diffraction [XRD], dynamic light scattering [DLS], X-ray photoelectron spectroscopy [XPS], X-ray absorption near edge structure [XANES], Mossbauer spectroscopy, and HeLa cells toxicity testing). Results TEM showed that the majority of the obtained nanoparticles were almost spherical and did not exceed 20 nm in diameter. The averaged DLS hydrodynamic size was found to be ~33 nm, while that of nanocrystallites estimated by XRD waŝ16 nm. Both XRD and XPS studies evidenced the maghemite (γ-Fe2O3) atomic and electronic structure of the synthesized nanoparticles. The XANES data analysis demonstrated the structure of the nanoparticles being similar to that of macroscopic maghemite. The Mossbauer spectroscopy revealed the γ-Fe2O3 phase of the nanoparticles and vibration magnetometry study showed that reactive oxygen species in HeLa cells are generated both in the cytoplasm and the nucleus. Conclusion Quasispherical Fe3+ SPIONs having the maghemite structure with the average size of 16 nm obtained by using the fast microwave synthesis technique are expected to be of great value for theranostic applications in oncology and multimodal anticancer therapy. PMID:28919740

  10. Metal Oxide Nanoparticles: The Importance of Size, Shape, Chemical Composition, and Valence State in Determining Toxicity

    NASA Astrophysics Data System (ADS)

    Dunnick, Katherine

    , cerium oxide nanoparticles were chemically modified using a process known as doping, to alter their valence state. The size and shape of the cerium oxide nanoparticles remained constant. Overall, results indicated that cerium oxide was not toxic in both RLE-6TN and NR8383 pulmonary rat cells, however, chemically modifying the valence state of the nanomaterial did affect the antioxidant potential. To determine if this trend was measureable in vivo, rats were exposed to various cerium oxide nanoparticles via intratracheal instillation and damage, changes in pulmonary cell differentials, and phagocytic cell activity were assessed. Results implicate that chemically modifying the nanoparticles had an effect on the overall damage induced by the material but did not dramatically affect inflammatory potential or phagocytic cell activity. Overall the data from these studies imply that size, shape, chemical composition, and valence state of nanomaterials can be manipulated to alter their toxicity.

  11. Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles.

    PubMed

    Sun, Chuntang; Zhou, Le; Gou, Maling; Shi, Shuai; Li, Tao; Lang, Jinyi

    2016-06-01

    Doxorubicin (Dox) is a broad-spectrum antitumor drug used for the treatment of many types of malignant tumors. Although it possesses powerful antitumor activity, its clinical application is seriously encumbered by its unselective distribution and systemic toxicities, particularly myocardial toxicity. Thus, it is imperative to modify Dox to decrease its systemic toxicities and improve its therapeutic index. In the present study, we adopted a novel type of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles to encapsulate Dox to prepare Dox-loaded MPEG-PCL (Dox/MPEG-PCL) nanoparticles by a controllable self-assembly process. The cellular uptake efficiency and cell proliferation inhibition of the Dox/MPEG-PCL nanoparticles were examined. The antitumor activity of the Dox/MPEG-PCL nanoparticles was tested on a multiple pulmonary metastasis model of melanoma on C57BL/6 mice. Systemic toxicities and survival time were compared between the mice treated with the Dox/MPEG-PCL nanoparticles and free Dox. The potential myocardial toxicity of the Dox/MPEG-PCL nanoparticles was investigated using a prolonged observation period. Encapsulation of Dox in MPEG-PCL nanoparticles significantly improved the cellular uptake and cell proliferation inhibition of Dox in vivo. Intravenous injection of Dox/MPEG-PCL nanoparticles obtained significant inhibition of the growth and metastasis of melanoma in the lung and prolonged survival time compared with free Dox (P<0.05). The Dox/MPEG-PCL nanoparticles did not show obvious additional systemic toxicities compared with free Dox during the treatment time. During the prolonged observation period, obvious decreased cardiac toxicity was observed in the Dox/MPEG-PCL nanoparticle-treated mice compared with that observed in the free Dox-treated mice. These results indicated that encapsulating Dox with MPEG-PCL micelles could significantly promote its antitumor activity and reduce its toxicity to the myocardium.

  12. Nanoparticles in the environment: stability and toxicity.

    PubMed

    Kim, Hyun-A; Choi, Yoo Jin; Kim, Kyoung-Woong; Lee, Byung-Tae; Ranville, James F

    2012-09-10

    With the increasing use and application of engineered nanoparticles (ENPs) in a number industries, ENPs, through their unique properties, have made their way into the environment. However, the environmental fate and behavior of ENPs are largely unknown. Laboratory studies have shown that some ENPs have the potential for toxicity, suggesting they may affect organisms in the environment. To fully assess the risk of ENPs, a better estimation of exposure concentrations is needed. This requires an understanding of the stability and toxicity of nanoparticles (NPs) in the environment. This review presents a brief overview of the fate, behavior, and ecotoxicity of NPs in the environment. The fate and transport of NPs, which can be affected by various environmental conditions like light, pH, ionic strength, and type and concentration of cations, are important for the examination of the life cycle of NPs.

  13. Consideration Of The Toxicity of Manufactured Nanoparticles

    NASA Astrophysics Data System (ADS)

    Haasch, Mary L.; McClellan-Green, Patricia; Oberdörster, Eva

    2005-09-01

    Fullerene (C60 and single- and multi-wall carbon nanotubes, SWCNT and MWCNT, respectively) is engineered to be redox active and it is thought that the potential toxicity of fullerene exposure is related to the formation of reactive oxygen species. During manufacture, transport or during scientific investigation, there is a potential for human or environmental exposure to nanoparticles. Several studies regarding human exposure have indicated reasons for concern. There is a lack of studies addressing the toxicity of engineered nanoparticles in aquatic species but one study using the fish, largemouth bass, exposed to fullerene has shown increased (10-17-fold) lipid peroxidation (LPO) in the brain. It is likely that repair enzymes or anti-oxidants may have been induced in gill and liver tissues that had reduced LPO compared to control tissues (Oberdörster, 2004). In support of that hypothesis, suppressive subtractive hybridization was used with liver tissue and the biotransformation enzyme, cytochrome P450, specifically CYP2K4, and other oxidoreductases related to metabolism, along with repair enzymes, were increased while proteins related to normal physiological homeostasis were decreased in fullerene-exposed fish. In a new study involving the exposure of a toxicological model fish species, the fathead minnow (Pimephales promelas) to water-soluble fullerene (nC60), uptake and distribution indicated that nC60 elevated LPO in the brain and induced expression of CYP2 family isozymes in the liver. In an in vitro study, BSA-coated SWCNT interfered with biotransformation enzyme activity. These studies taken together provide support to the hypothesis that the toxicity of manufactured nanoparticles is related to oxidative stress and provide insight into possible mechanisms of toxicity as well as providing information for evaluating the risk to aquatic organisms exposed to manufactured nanoparticles.

  14. Biological Mechanism of Silver Nanoparticle Toxicity

    NASA Astrophysics Data System (ADS)

    Armstrong, Najealicka Nicole

    Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further

  15. Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles

    EPA Science Inventory

    The diversity of engineered-nanomaterials and their applications as well as potential unknown health effects of these novel materials are significant challenges to assessing the health risks of nanotechnology. An integrated multi-tier testing strategy (www.epa.gov/nanoscience/) ...

  16. Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles

    EPA Science Inventory

    The diversity of engineered-nanomaterials and their applications as well as potential unknown health effects of these novel materials are significant challenges to assessing the health risks of nanotechnology. An integrated multi-tier testing strategy (www.epa.gov/nanoscience/) ...

  17. Pulmonary toxicity of beryllium in albino rat

    SciTech Connect

    Goel, K.A.; Agrawal, V.P.; Garg, V.

    1980-01-01

    Arsenic compounds, if chronically exposed to human beings, significantly increase incidences of epidermoid carcinomas of the skin and lung. Nickel has been considered to be an important metallic carcinogen. Regarding beryllium, different opinions are held so far as its carcinogenic nature is concerned. While it is reported that there is an equivocal increase in the incidences of respiratory cancers in patients with chronic pulmonary berylliosis, investigation shows no increase in the incidence of respiratory cancer. Among experimental animals, intravenous injections of suspensions of beryllium salts to rabbits have been shown to induce osteogenic sarcomas. This abstract deals with the histopathological and enzymological study of lungs of albino rats after prolonged beryllium treatment.

  18. Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone-induced pulmonary toxicity.

    PubMed

    Rodríguez-García, J L.; García-Nieto, J C.; Ballesta, F; Prieto, E; Villanueva, M A.; Gallardo, J

    2001-07-01

    Amiodarone is an effective anti-arrhythmic agent. However, during long-term therapy, patients can develop severe adverse pulmonary reactions that are potentially life-threatening. A case of amiodarone-induced pulmonary toxicity is presented in a 78-year-old woman. She developed dyspnea and a pulmonary mass with associated multiple lung nodules mimicking a lung cancer following 5 years of treatment with amiodarone for atrial fibrillation. After drug withdrawal, and without any additional treatment, clinical and radiological improvement was observed, and radiological findings resolved completely within 6 months.

  19. Subchronic inhalation toxicity of gold nanoparticles.

    PubMed

    Sung, Jae Hyuck; Ji, Jun Ho; Park, Jung Duck; Song, Moon Yong; Song, Kyung Seuk; Ryu, Hyeon Ryol; Yoon, Jin Uk; Jeon, Ki Soo; Jeong, Jayoung; Han, Beom Seok; Chung, Yong Hyun; Chang, Hee Kyung; Lee, Ji Hyun; Kim, Dong Won; Kelman, Bruce J; Yu, Il Je

    2011-05-14

    Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold nanoparticles showed a dose

  20. Subchronic inhalation toxicity of gold nanoparticles

    PubMed Central

    2011-01-01

    Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME) of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males) and 145 g (females), were divided into 4 groups (10 rats in each group): fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3), middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3), and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3). The animals were exposed to gold nanoparticles (average diameter 4-5 nm) for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH), and total protein were also monitored in a cellular bronchoalveolar lavage (BAL) fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue distribution of gold

  1. Toxicity and Biokinetics of Colloidal Gold Nanoparticles

    PubMed Central

    Jo, Mi-Rae; Bae, Song-Hwa; Go, Mi-Ran; Kim, Hyun-Jin; Hwang, Yun-Gu; Choi, Soo-Jin

    2015-01-01

    Gold nanoparticles (Au-NPs) have promising potential for diverse biological application, but it has not been completely determined whether Au-NP has potential toxicity in vitro and in vivo. In the present study, toxicity of Au-NP was evaluated in human intestinal cells as well as in rats after 14-day repeated oral administration. Biokinetic study was also performed to assess oral absorption and tissue distribution. The results demonstrated that Au-NP did not cause cytotoxic effects on cells after 24 h exposure in terms of inhibition of cell proliferation, membrane damage, and oxidative stress. However, when a small number of cells were exposed to Au-NP for seven days, colony forming ability remarkably decreased by Au-NP treatment, suggesting its potential toxicity after long-term exposure at high concentration. Biokinetic study revealed that Au-NP slowly entered the blood stream and slightly accumulated only in kidney after oral administration to rats. Whereas, orally administered Au ions were rapidly absorbed, and then distributed in kidney, liver, lung, and spleen at high levels, suggesting that the biological fate of Au-NP is primarily in nanoparticulate form, not in ionic Au. Fourteen-day repeated oral toxicity evaluation showed that Au-NP did not cause severe toxicity in rats based on histopathological, hematological, and serum biochemical analysis.

  2. Amiodarone lung toxicity: role of pulmonary function tests.

    PubMed

    Foresti, V; Carini, L; Lovagnini-Scher, C A; Parisio, E; Scolari, N; Pozzi, G; Clini, V

    1987-01-01

    Forty-three patients treated with amiodarone hydrochloride with an average daily dose of 204.7 +/- 79.4 mg/day for a mean period of 37.1 +/- 25.3 months, were studied by clinical examination, chest roentgenograms, pulmonary function tests and blood gas analyses. The habits of cigarette smoking were also recorded and expressed as cigarette pack/years. Pulmonary function tests did not show any differences from control subjects and no correlation was found between exposure to drug and lung function. However, one patient developed abnormalities in the chest X-ray (interstitial type) and a reduction of carbon monoxide diffusion capacity as a possible manifestation of amiodarone lung toxicity. Nine patients (22%) had a 20% decrease from normal in carbon monoxide diffusion capacity and three (7%) had a 15% decrease in total lung capacity. More treated patients had interstitial abnormalities in the chest X-ray (14%) than controls (5.5%). Although pulmonary function test abnormalities could be detected in patients taking amiodarone, they were not usually severe enough to interfere with gas exchange. Our results confirm the rarity of amiodarone lung toxicity when a low dosage is used, and suggest the advisability of periodical monitoring, including clinical examination, chest X-ray and pulmonary function tests in order to detect the earliest signs of amiodarone lung toxicity.

  3. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-wing; James, John T.; Taylor, Larry

    2008-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. NASA established the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Because the toxicity of lunar dust is not known, LADTAG has recommended investigating its toxicity in the lungs of laboratory animals. After receiving this recommendation, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust in exposed rodents. The rodent pulmonary toxicity studies proposed here are the same as those proposed by the LADTAG. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal instillation (ITI). This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. We succeeded in completing an ITI study on JSC-1 lunar dust simulant in mice (Lam et al., Inhalation Toxicology 14:901-916, 2002, and Inhalation Toxicology 14: 917-928, 2002), and have conducted a pilot ITI study to examine the acute toxicity of an Apollo lunar (highland) dust sample. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies have been planned to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The ITI results will also be

  4. A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

    SciTech Connect

    Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

    2010-07-15

    Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

  5. Pulmonary toxicity of cytostatic drugs: cell kinetics

    SciTech Connect

    Witschi, H.; Godfrey, G.; Frome, E.; Lindenschmidt, R.C.

    1987-02-01

    Mice were treated with three cytostatic drugs: cyclophosphamide, busulfan, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The alveolar labeling index was measured following drug administration with a pulse of /sup 3/H-labeled thymidine and autoradiography. In cyclophosphamide-treated animals, peak alveolar cell proliferation was seen 5 days after injection of the drug. In animals treated with busulfan or BCNU, proliferation was even more delayed (occurring 2-3 weeks after administration). In contrast, with oleic acid, the highest alveolar cell labeling was found 2 days after intravenous administration. In animals exposed to a cytostatic drug, proliferation of type II alveolar cells was never a prominent feature whereas in animals treated with oleic acid there was an initial burst of type II cell proliferation. It is concluded that the patterns of pulmonary repair vary between chemicals designed to interfere with DNA replication as compared to agents which produce acute lung damage such as oleic acid.

  6. Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

    PubMed Central

    Cao, Zhengwang; Fang, Yiliang; Lu, Yonghui; Qian, Fenghua; Ma, Qinglong; He, Mingdi; Pi, Huifeng; Yu, Zhengping; Zhou, Zhou

    2016-01-01

    With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1β secretion in vivo. NiONP-induced IL-1β secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs. PMID:27524893

  7. Toxicity of silver nanoparticles - nanoparticle or silver ion?

    PubMed

    Beer, Christiane; Foldbjerg, Rasmus; Hayashi, Yuya; Sutherland, Duncan S; Autrup, Herman

    2012-02-05

    The toxicity of silver nanoparticles (AgNPs) has been shown in many publications. Here we investigated to which degree the silver ion fraction of AgNP suspensions, contribute to the toxicity of AgNPs in A549 lung cells. Cell viability assays revealed that AgNP suspensions were more toxic when the initial silver ion fraction was higher. At 1.5μg/ml total silver, A549 cells exposed to an AgNP suspension containing 39% silver ion fraction showed a cell viability of 92%, whereas cells exposed to an AgNP suspension containing 69% silver ion fraction had a cell viability of 54% as measured by the MTT assay. In addition, at initial silver ion fractions of 5.5% and above, AgNP-free supernatant had the same toxicity as AgNP suspensions. Flow-cytometric analyses of cell cycle and apoptosis confirmed that there is no significant difference between the treatment with AgNP suspension and AgNP supernatant. Only AgNP suspensions with silver ion fraction of 2.6% or less were significantly more toxic than their supernatant as measured by MTT assays. From our data we conclude that at high silver ion fractions (≥5.5%) the AgNPs did not add measurable additional toxicity to the AgNP suspension, whereas at low silver ion fractions (≤2.6%) AgNP suspensions are more toxic than their supernatant. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Gemcitabine-Induced Pulmonary Toxicity: A Case Report of Pulmonary Veno-Occlusive Disease.

    PubMed

    Turco, Célia; Jary, Marine; Kim, Stefano; Moltenis, Mélanie; Degano, Bruno; Manzoni, Philippe; Nguyen, Thierry; Genet, Bruno; Rabier, Marie-Blanche Valnet; Heyd, Bruno; Borg, Christophe

    2015-01-01

    Gemcitabine is a chemotherapeutic agent frequently used by for the treatment of several malignancies both in the adjuvant and metastatic setting. Although myelosuppression is the most adverse event of this therapy, gemcitabine might induce severe pulmonary toxicities. We describe a case of pulmonary veno-occlusive disease (PVOD) related to gemcitabine. The patient was an 83-year-old man with a metastatic pancreatic cancer who was treated by gemcitabine as first-line therapy. He was in good health and received no other chemotherapy. A dose of 1000 mg/m(2) of gemcitabine was administered over a 30-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. After a period of 6 months, a complete response was observed. Nevertheless, the patient developed a severe dyspnea, with arterial hypoxemia and very low lung diffusion for carbon monoxide. A CT scan showed diffuse ground glass opacities with septal lines, bilateral pleural effusion, and lymph node enlargement. On echocardiography, there was a suspicion of pulmonary hypertension with elevated systolic pulmonary artery pressure and normal left ventricular pressures. Right heart catheterization confirmed pulmonary hypertension and normal pulmonary artery occlusion pressure. Diagnosis of PVOD was made, and a gemcitabine-induced toxicity was suspected. A symptomatic treatment was started. At last follow-up, patient was in functional class I with near-normal of CT scan, arterial blood gases, and echocardiography. A gemcitabine-induced PVOD is the more likely diagnosis.

  9. Cationic Surface Modification of PLG Nanoparticles Offers Sustained Gene Delivery to Pulmonary Epithelial Cells

    PubMed Central

    BAOUM, ABDULGADER; DHILLON, NAVNEET; BUCH, SHILPA; BERKLAND, CORY

    2010-01-01

    Biodegradable polymeric nanoparticles are currently being explored as a nonviral gene delivery system; however, many obstacles impede the translation of these nanomaterials. For example, nanoparticles delivered systemically are inherently prone to adsorbing serum proteins and agglomerating as a result of their large surface/volume ratio. What is desired is a simple procedure to prepare nanoparticles that may be delivered locally and exhibit minimal toxicity while improving entry into cells for effectively delivering DNA. The objective of this study was to optimize the formulation of poly(D,L-lactide-co-glycolide) (PLG) nanoparticles for gene delivery performance to a model of the pulmonary epithelium. Using a simple solvent diffusion technique, the chemistry of the particle surface was varied by using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80–90%) and slowly released the same for 2 weeks. In A549 alveolar lung epithelial cells, high levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least 2 weeks. In contrast, PEI gene expression ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. PMID:19911425

  10. [Pulmonary toxicity associated with sirolimus therapy in liver transplantation].

    PubMed

    Jiménez Pérez, Miguel; Olmedo Martín, Raúl; Marín García, David; Lozano Rey, Juan Miguel; de la Cruz Lombardo, Jesús; Rodrigo López, Juan Miguel

    2006-12-01

    Sirolimus is a potent immunosuppressive drug that began to be used in the last few years. This drug was initially used in renal transplantation but its use in other solid organ transplantations such as liver, heart, lung and pancreas, has been increasing. Sirolimus is indicated in rescue therapies and to reduce the secondary toxic effects of calcineurin inhibitors. However, this drug has been associated with infrequent but severe pulmonary toxicity and cases of interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia, and alveolar proteinosis have been described. We present the case of a male liver transplant recipient who developed interstitial pneumonitis associated with sirolimus use.

  11. Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities.

    PubMed

    Mangal, Sharad; Gao, Wei; Li, Tonglei; Zhou, Qi Tony

    2017-06-01

    Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects. Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects, including cough and bronchospasm. Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy. Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers. However, the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs. Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles. This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers.

  12. Pulmonary toxicity in mice following exposure to cerium chloride.

    PubMed

    Hong, Jie; Yu, Xiaohong; Pan, Xiaoyu; Zhao, Xiaoyang; Sheng, Lei; Sang, Xuezi; Lin, Anan; Zhang, Chi; Zhao, Yue; Gui, Suxin; Sun, Qingqing; Wang, Ling; Hong, Fashui

    2014-06-01

    The widespread application of lanthanoids (Lns) in manufacturing industries has raised occupational and environmental health concerns about the possible increased health risks to humans exposed to Lns in their working and living environments. Numerous studies have shown that exposures to Ln cause pulmonary injury in animals, but very little is known about the molecular mechanisms of the pulmonary inflammation caused by cerium chloride (CeCl3) exposure. In this study, we evaluated the oxidative stress and molecular mechanism underlying with the pulmonary inflammation associated with chronic lung toxicity in mice treated with nasally instilled CeCl3 for 90 consecutive days. Our findings suggest that significant cerium accumulated in the lung, leading the obvious increase of the lung indices, significant increases in inflammatory cells and levels of lactate dehydrogenase, alkaline phosphate, and total protein, overproduction of reactive oxygen species and peroxidation of lipids, reduced antioxidant capacity, and pulmonary inflammation. CeCl3 exposure also activated nuclear factor κB, increased the expression of tumor necrosis factor α, cyclooxygenase-2, heme oxygenase 1, interleukin 2, interleukin 4, interleukin 6, interleukin 8, interleukin 10, interleukin 18, interleukin 1β, and CYP1A1. However, CeCl3 reduced the expression of nuclear factor κB (NF-κB)-inhibiting factor and heat shock protein 70. These findings suggest that the pulmonary inflammation caused by CeCl3 in mice is closely associated with oxidative stress and inflammatory cytokine expression.

  13. Pulmonary toxicity of printer toner following inhalation and intratracheal instillation.

    PubMed

    Morimoto, Yasuo; Oyabu, Takako; Horie, Masanori; Kambara, Tatsunori; Izumi, Hiroto; Kuroda, Etsushi; Creutzenberg, Otto; Bellmann, Bernd; Pohlmann, Gerhard; Schuchardt, Sven; Hansen, Tanja; Ernst, Heinrich

    2013-10-01

    The pulmonary effects of a finished toner were evaluated in intratracheal instillation and inhalation studies, using toners with external additives (titanium dioxide nanoparticles and amorphous silica nanoparticles). Rats received an intratracheal dose of 1 mg or 2 mg of toner and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months. The toner induced pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups and persistent neutrophil infiltration in the high-dose groups. There were increased concentrations of heme oxygenase-1 (HO-1) as a marker of oxidative stress in the bronchoalveolar lavage fluid (BALF) and the lung. In a 90-day inhalation study, rats were exposed to well-dispersed toner (mean of MMAD: 3.76 µm). The three mass concentrations of toner were 1, 4 and 16 mg/m(3) for 13 weeks, and the rats were sacrificed at 6 days and 91 days after the end of the exposure period. The low and medium concentrations did not induce neutrophil infiltration in the lung of statistical significance, but the high concentration did, and, in addition, upon histopathological examination not only showed findings of inflammation but also of fibrosis in the lung. Taken together, the results of our studies suggest that toners with external additives lead to pulmonary inflammation and fibrosis at lung burdens suggest beyond the overload. The changes observed in the pulmonary responses in this inhalation study indicate that the high concentration (16 mg/m(3)) is an LOAEL and that the medium concentration (4 mg/m(3)) is an NOAEL.

  14. Green synthesis of silver nanoparticles: an approach to overcome toxicity.

    PubMed

    Roy, Nidhija; Gaur, Archana; Jain, Aditi; Bhattacharya, Susinjan; Rani, Vibha

    2013-11-01

    Nanotechnology, with its advent, has made deep inroads into therapeutics. It has revolutionized conventional approaches in drug designing and delivery systems by creating a large array of nanoparticles that can pass even through relatively impermeable membranes such as blood brain barrier. Like the two sides of a coin, nanotechnology too has its own share of disadvantages which in this scenario is the toxicology of these nanoparticles. Numerous studies have discussed the toxicity of various nanoparticles and the recent advancements done in the field of nanotechnology is to make it less toxic. "Green synthesis" of nanoparticles is one such approach. The review summarizes the toxicity associated with the nanoparticles and the advancement of "green" nanomaterials to resolve the toxicity issues. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Pulmonary toxicity and fibrogenic response of carbon nanotubes

    PubMed Central

    Manke, Amruta; Wang, Liying; Rojanasakul, Yon

    2015-01-01

    Carbon nanotubes (CNTs) have been a subject of intensive research for a wide range of applications. However, because of their extremely small size and light weight, CNTs are readily inhaled into human lungs resulting in increased rates of pulmonary disorders, most notably fibrosis. Several studies have demonstrated the fibrogenic effects of CNTs given their ability to translocate into the surrounding areas in the lung causing granulomatous lesions and interstitial and sub-pleural fibrosis. However, the mechanisms underlying the disease process remain obscure due to the lack of understanding of the cellular interactions and molecular targets involved. Interestingly, certain physicochemical properties of CNTs have been shown to affect their respiratory toxicity, thereby becoming significant determinants of fibrogenesis. CNT-induced fibrosis involves a multitude of cell types and is characterized by the early onset of inflammation, oxidative stress and accumulation of extracellular matrix. Increased reactive oxygen species activate various cytokine/growth factor signaling cascades resulting in increased expression of inflammatory and fibrotic genes. Profibrotic growth factors and cytokines contribute directly to fibroblast proliferation and collagen production. Given the role of multiple players during the pathogenesis of CNT-induced fibrosis, the objective of this review is to summarize the key findings and discuss major cellular and molecular events governing pulmonary fibrosis. We also discuss the physicochemical properties of CNTs and their effects on pulmonary toxicities as well as various biological factors contributing to the development of fibrosis. PMID:23194015

  16. Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats

    PubMed Central

    Elshama, Said Said; EL-Kenawy, Ayman El-Meghawry; Osman, Hosam-Eldin Hussein

    2016-01-01

    Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose. PMID:26941796

  17. Pulmonary targeting with biodegradable salbutamol-loaded nanoparticles.

    PubMed

    Beck-Broichsitter, Moritz; Gauss, Julia; Gessler, Tobias; Seeger, Werner; Kissel, Thomas; Schmehl, Thomas

    2010-02-01

    Aerosol therapy using particulate drug carriers has become an increasingly attractive method to deliver therapeutic or diagnostic compounds to the lung. Polymeric nanoparticles are widely investigated carriers in nanomedicine. The targeted and controlled release of drugs from nanoparticles for pulmonary delivery, however, is a research field that has been so far rather unexploited. Therefore, the objective of this study was to compare the pulmonary absorption and distribution characteristics of salbutamol after aerosolization as solution or entrapped into novel polymeric nanoparticles in an isolated rabbit lung model (IPL). Physicochemical properties, morphology, encapsulation efficiency, in vitro drug release, stability of nanoparticles to nebulization, as well as pulmonary drug absorption and distribution after nebulization in the IPL were investigated. Salbutamol-loaded poly(D,L-lactide-co-glycolide) (PLGA) and poly(vinyl sulfonate-co-vinyl alcohol)-graft-poly(D,L-lactide-co-glycolide) (VS(72)-10) nanoparticles were prepared by a modified solvent displacement technique with a mean particle size of approximately 120 nm and a polydispersity index below 0.150. VS(72)-10 nanoparticles showed a more negative zeta-potential of -54.2 +/- 3.3 mV compared to PLGA nanoparticles (-36.5 +/- 2.6 mV). Salbutamol encapsulation efficiency was 25.2 +/- 4.9% and 63.4 +/- 3.5% for PLGA and VS(72)-10 nanoparticles, respectively. After nebulization utilizing the MicroSprayer physicochemical properties of salbutamol-loaded VS(72)-10 nanoparticles were virtually unchanged, whereas nebulized salbutamol-loaded PLGA nanoparticles showed a significant increase in mean particle size and polydispersity. In vitro release studies demonstrated a sustained release of the encapsulated salbutamol from VS(72)-10 nanoparticles. In parallel, a sustained salbutamol release profile was observed after aerosol delivery of these particles to the IPL as reflected by a lower salbutamol recovery in the

  18. Release, transport and toxicity of engineered nanoparticles.

    PubMed

    Soni, Deepika; Naoghare, Pravin K; Saravanadevi, Sivanesan; Pandey, Ram Avatar

    2015-01-01

    Recent developments in nanotechnology have facilitated the synthesis of novel engineered nanoparticles (ENPs) that possess new and different physicochemical properties. These ENPs have been ex tensive ly used in various commercial sectors to achieve both social and economic benefits. However. the increasing production and consumption of ENPs by many different industries has raised concerns about their possible release and accumulation in the environment. Released EN Ps may either remain suspended in the atmosphere for several years or may accumulate and eventually be modified int o other substances. Settled nanoparticles can he easily washed away during ra in s. and therefore may easily enter the food chain via water and so il. Thus. EN Ps can contaminate air. water and soil and can subsequently pose adverse risks to the health of different organisms. Studies to date indicate that ENP transport to and within the ecosystem depend on their chemical and physical properties (viz .. size. shape and solubility) . Therefore. the EN Ps display variable behavior in the environment because of their individual properties th at affect their tendency for adsorption, absorption, diffusional and colloidal interaction. The transport of EN Ps also influences their fate and chemical transformation in ecosystems. The adsorption, absorption and colloidal interaction of ENPs affect their capacity to be degraded or transformed, whereas the tendency of ENPs to agglomerate fosters their sedimentation. How widely ENPs are transported and their environmental fate influence how tox ic they may become to environmental organisms. One barrier to fully understanding how EN Ps are transformed in the environment and how best to characterize their toxicity, is related to the nature of their ultrafine structure. Experiments with different animals, pl ants, and cell lines have revealed that ENPs induce toxicity via several cellular pathways that is linked to the size. shape. surface area

  19. Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells.

    PubMed

    Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L'azou, Béatrice

    2012-09-28

    Silica nanoparticles (nano-SiO(2)) are one of the most popular nanomaterials used in industrial manufacturing, synthesis, engineering and medicine. While inhalation of nanoparticles causes pulmonary damage, nano-SiO(2) can be transported into the blood and deposit in target organs where they exert potential toxic effects. Kidney is considered as such a secondary target organ. However, toxicological information of their effect on renal cells and the mechanisms involved remain sparse. In the present study, the cytotoxicity of nano-SiO(2) of different sizes was investigated on two renal proximal tubular cell lines (human HK-2 and porcine LLC-PK(1)). The molecular pathways involved were studied with a focus on the involvement of oxidative stress. Nanoparticle characterization was performed (primary nanoparticle size, surface area, dispersion) in order to investigate a potential relationship between their physical properties and their toxic effects. Firstly, evidence of particle internalization was obtained by transmission electron microscopy and conventional flux cytometry techniques. The use of specific inhibitors of endocytosis pathways showed an internalization process by macropinocytosis and clathrin-mediated endocytosis for 100 nm nano-SiO(2) nanoparticles. These nanoparticles were localized in vesicles. Toxicity was size- and time-dependent (24h, 48 h, 72 h). Indeed, it increased as nanoparticles became smaller. Secondly, analysis of oxidative stress based on the assessment of ROS (reactive oxygen species) production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde) clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm nano-SiO(2). The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin reductase) could explain their lesser toxicity with 100 nm nano-SiO(2).

  20. Toxicity of food-relevant nanoparticles in intestinal epithelial models

    NASA Astrophysics Data System (ADS)

    McCracken, Christie

    Nanoparticles are increasingly being incorporated into common consumer products, including in foods and food packaging, for their unique properties at the nanoscale. Food-grade silica and titania are used as anti-caking and whitening agents, respectively, and these particle size distributions are composed of approximately one-third nanoparticles. Zinc oxide and silver nanoparticles can be used for their antimicrobial properties. However, little is known about the interactions of nanoparticles in the body upon ingestion. This study was performed to investigate the role of nanoparticle characteristics including surface chemistry, dissolution, and material type on toxicity to the intestinal epithelium. Only mild acute toxicity of zinc oxide nanoparticles was observed after 24-hour treatment of intestinal epithelial C2BBe1 cells based on the results of toxicity assays measuring necrosis, apoptosis, membrane damage, and mitochondrial activity. Silica and titanium dioxide nanoparticles were not observed to be toxic although all nanoparticles were internalized by cells. In vitro digestion of nanoparticles in solutions representing the stomach and intestines prior to treatment of cells did not alter nanoparticle toxicity. Long-term repeated treatment of cells weekly for 24 hours with nanoparticles did not change nanoparticle cytotoxicity or the growth rate of the treated cell populations. Thus, silica, titanium dioxide, and zinc oxide nanoparticles were found to induce little toxicity in intestinal epithelial cells. Fluorescent silica nanoparticles were synthesized as a model for silica used in foods that could be tracked in vitro and in vivo. To maintain an exterior of pure silica, a silica shell was hydrolyzed around a core particle of quantum dots or a fluorescent dye electrostatically associated with a commercial silica particle. The quantum dots used were optimized from a previously reported microwave quantum dot synthesis to a quantum yield of 40%. Characterization

  1. Assessing the pulmonary toxicity of single-walled carbon nanohorns

    SciTech Connect

    Lynch, Rachel M; Voy, Brynn H; Glass-Mattie, Dana F; Mahurin, Shannon Mark; Saxton, Arnold; Donnel, Robert L.; Cheng, Mengdawn

    2007-01-01

    Previous studies have suggested that single-walled carbon nanotubes (SWCNTs) may pose a pulmonary hazard. We investigated the pulmonary toxicity of single-walled carbon nanohorns (SWCNHs), a relatively new carbon-based nanomaterial that is structurally similar to SWCNTs. Mice were exposed to 30 {micro}g of surfactant-suspended SWCNHs or an equal volume of vehicle control by pharyngeal aspiration and sacrificed 24 hours or 7 days post-exposure. Total and differential cell counts and cytokine analysis of bronchoalveolar lavage fluid demonstrated a mild inflammatory response which was mitigated by day 7 post-exposure. Whole lung microarray analysis demonstrated that SWCNH-exposure did not lead to robust changes in gene expression. Finally, histological analysis showed no evidence of granuloma formation or fibrosis following SWCNH aspiration. These combined results suggest that SWCNH is a relatively innocuous nanomaterial when delivered to mice in vivo using aspiration as a delivery mechanism.

  2. Assessing the pulmonary toxicity of single-walled carbon nanohorns

    SciTech Connect

    Lynch, Rachel M; Voy, Brynn H; Glass-Mattie, Dana F; Mahurin, Shannon Mark; Saxton, Arnold; Donnel, Robert L.; Cheng, Mengdawn

    2007-01-01

    Previous studies have suggested that single-walled carbon nanotubes (SWCNTs) may be pose a pulmonary hazard. We investigated the pulmonary toxicity of single-walled carbon nanohorns (SWCNHs), a relatively new carbon-based nanomaterial that is structurally similar to SWCNTs. Mice were exposed to 30 g of surfactant-suspended SWCNHs by pharyngeal aspiration and sacrificed 24 hours or 7 days post exposure. Total and differential cell counts and cytokine analysis of bronchoalveolar lavage fluid demonstrated a mild inflammatory response which was mitigated by day 7 post exposure. Whole lung microarray analysis demonstrated that SWCNH-exposure did not lead to robust changes in gene expression. Finally, histological analysis showed no evidence of granuloma formation or fibrosis following SWCNH aspiration. These combined results suggest that SWCNH is a relatively innocuous nanomaterial when delivered to mice in vivo using aspiration as a delivery mechanism.

  3. Acute toxicity of nickel nanoparticles in rats after intravenous injection

    PubMed Central

    Magaye, Ruth R; Yue, Xia; Zou, Baobo; Shi, Hongbo; Yu, Hongsheng; Liu, Kui; Lin, Xialu; Xu, Jin; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2014-01-01

    This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine. PMID:24648736

  4. Biodistribution of Amikacin Solid Lipid Nanoparticles after Pulmonary Delivery

    PubMed Central

    Varshosaz, J.; Ghaffari, S.; Mirshojaei, S. F.; Jafarian, A.; Atyabi, F.; Kobarfard, F.; Azarmi, S.

    2013-01-01

    The main purpose of the present work was studying the biodistribution of amikacin solid lipid nanoparticles (SLNs) after pulmonary delivery to increase its concentration in the lungs for treatment of cystic fibrosis lung infections and also providing a new method for clinical application of amikacin. To achieve this aim, 99mTc labelled amikacin was loaded in cholesterol SLNs and after in vitro optimization, the desired SLNs and free drug were administered through pulmonary and i.v. routes to male rats and qualitative and biodistribution studies were done. Results showed that pulmonary delivery of SLNs of amikacin by microsprayer caused higher drug concentration in lungs than kidneys while i.v. administration of free drug caused reverse conditions. It seems that pulmonary delivery of SLNs may improve patients' compliance due to reduction of drug side effects in kidneys and elongation of drug dosing intervals due to the sustained drug release from SLNs. PMID:23984315

  5. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-wing; James, John T.

    2009-01-01

    NASA will build an outpost on the lunar surface for long-duration human habitation and research. The surface of the Moon is covered by a layer of fine, reactive dust, and the living quarters in the lunar outpost are expected to be contaminated by lunar dust. Because the toxicity of lunar dust is not known, NASA has tasked its toxicology laboratory to evaluate the risk of exposure to the dust and to establish safe exposure limits for astronauts working in the lunar habitat. Studies of the pulmonary toxicity of a dust are generally done first in rodents by intratracheal/intrapharyngeal instillation. This toxicity screening test is then followed by an inhalation study, which requires much more of the test dust and is labor intensive. Preliminary results obtained by examining lung lavage fluid from dust-treated mice show that lunar dust was somewhat toxic (more toxic than TiO2, but less than quartz dust). More extensive studies are in progress to further examine lung lavage fluid for biomarkers of toxicity and lung tissues for histopathological lesions in rodents exposed to aged and activated (ground) lunar dust samples. In these studies, reference dusts (TiO2 and quartz) of known toxicities and have industrial exposure limits will be studied in parallel so the relative toxicity of lunar dust can be determined. The results from the instillation studies will be useful for choosing exposure concentrations for the animal inhalation study. The animal inhalation exposure will be conducted with lunar dust simulant prior to the study with the lunar dust. The experiment with the simulate will ensure that the study techniques used with actual lunar dust will be successful. The results of instillation and inhalation studies will reveal the toxicological risk of exposures and are essential for setting exposure limits on lunar dust for astronauts living in the lunar habitat.

  6. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: a review of the state of the art.

    PubMed

    Weber, S; Zimmer, A; Pardeike, J

    2014-01-01

    Drug delivery by inhalation is a noninvasive means of administration that has following advantages for local treatment for airway diseases: reaching the epithelium directly, circumventing first pass metabolism and avoiding systemic toxicity. Moreover, from the physiological point of view, the lung provides advantages for systemic delivery of drugs including its large surface area, a thin alveolar epithelium and extensive vasculature which allow rapid and effective drug absorption. Therefore, pulmonary application is considered frequently for both, the local and the systemic delivery of drugs. Lipid nanoparticles - Solid Lipid Nanoparticles and Nanostructured Lipid Carriers - are nanosized carrier systems in which solid particles consisting of a lipid matrix are stabilized by surfactants in an aqueous phase. Advantages of lipid nanoparticles for the pulmonary application are the possibility of a deep lung deposition as they can be incorporated into respirables carriers due to their small size, prolonged release and low toxicity. This paper will give an overview of the existing literature about lipid nanoparticles for pulmonary application. Moreover, it will provide the reader with some background information for pulmonary drug delivery, i.e., anatomy and physiology of the respiratory system, formulation requirements, application forms, clearance from the lung, pharmacological benefits and nanotoxicity.

  7. Vectorization by nanoparticles decreases the overall toxicity of airborne pollutants

    PubMed Central

    Maiz-Gregores, Helena; Nesslany, Fabrice; Betbeder, Didier

    2017-01-01

    Atmospheric pollution is mainly composed of volatile pollutants and particulate matter that strongly interact. However, their specific roles in the induction of cellular toxicity, in particular the impact of the vectorization of atmospheric pollutants by ultrafine particles, remains to be fully elucidated. For this purpose, non-toxic poly-lactic co-glycolic acid (PLGA) nanoparticles were synthesized and three pollutants (benzo(a)pyrene, naphthalene and di-ethyl-hexyl-phthalate) were adsorbed on the surface of the nanoparticles in order to evaluate the toxicity (cytotoxicity, genotoxicity and ROS induction) of these complexes to a human airway epithelial cell line. The adsorption of the pollutants onto the nanoparticles was confirmed by HPLC analysis. Interestingly, the cytotoxicity assays (MTT, LDH and CellTox Green) clearly demonstrated that the vectorization by nanoparticles decreases the toxicity of the adsorbed pollutants. Genotoxicity was assessed by the micronucleus test and the comet assay and showed no increase in primary DNA damage or in chromosomal aberrations of nanoparticle vectorized pollutants. Neither cytotoxicity nor genotoxicity was correlated with ROS induction. To conclude, our results indicate that the vectorization of pollutants by nanoparticles does not potentiate the toxicity of the pollutants studied and that, on the contrary, adsorption onto nanoparticles could protect cells against pollutants’ toxicity. PMID:28813539

  8. Predicting Pulmonary O2 Toxicity: A New Look at the Unit Pulmonary Toxicity Dose

    DTIC Science & Technology

    1985-05-01

    must be carefully balanced agoinst its potential hazards, the nature of which depend on the partial pressure of 02 (P0 ). At dry ambient pressures ...greater than approximately 3 ATA, exposure to 100% 02 produces a variety of central nervous system symptoms; exposure to lover pressures facilitates a...of studies have documented the pathogenesis of pulmonary injury in normal men exposed to 02 for 6 to 74 h at pressures ranging from 0.83 to 2.0 ATA

  9. Toxicity of Silver Nanoparticles at the Air-Liquid Interface

    PubMed Central

    Holder, Amara L.; Marr, Linsey C.

    2013-01-01

    Silver nanoparticles are one of the most prevalent nanomaterials in consumer products. Some of these products are likely to be aerosolized, making silver nanoparticles a high priority for inhalation toxicity assessment. To study the inhalation toxicity of silver nanoparticles, we have exposed cultured lung cells to them at the air-liquid interface. Cells were exposed to suspensions of silver or nickel oxide (positive control) nanoparticles at concentrations of 2.6, 6.6, and 13.2 μg cm−2 (volume concentrations of 10, 25, and 50 μg ml−1) and to 0.7 μg cm−2 silver or 2.1 μg cm−2 nickel oxide aerosol at the air-liquid interface. Unlike a number of in vitro studies employing suspensions of silver nanoparticles, which have shown strong toxic effects, both suspensions and aerosolized nanoparticles caused negligible cytotoxicity and only a mild inflammatory response, in agreement with animal exposures. Additionally, we have developed a novel method using a differential mobility analyzer to select aerosolized nanoparticles of a single diameter to assess the size-dependent toxicity of silver nanoparticles. PMID:23484109

  10. Sulfidation of Silver Nanoparticles: Natural antidote to their toxicity

    PubMed Central

    Levard, Clément; Hotze, Ernest M.; Colman, Benjamin P.; Truong, Lisa; Yang, X. Y.; Bone, Audrey; Brown, Gordon E.; Tanguay, Robert L.; Di Giulio, Richard T.; Bernhardt, Emily S.; Meyer, Joel N.; Wiesner, Mark R.; Lowry, Gregory V.

    2014-01-01

    Nanomaterials are highly dynamic in biological and environmental media. A critical need for advancing environmental health and safety research for nanomaterials is to identify commonly occurring physical and chemical transformations affecting nanomaterial properties and toxicity. Silver nanoparticles, one of the most ecotoxic and well-studied nanomaterials, readily sulfidize in the environment. Here, we show that very low degrees of sulfidation (0.019 S/Ag mass ratio) universally and significantly decreases the toxicity of silver nanoparticles to four diverse types of aquatic and terrestrial eukaryotic organisms. Toxicity reduction is primarily associated with a decrease in Ag+ availability after sulfidation due to the lower solubility of Ag2S relative to elemental Ag (Ag(0)). We also show that chloride in exposure media determines silver nanoparticle toxicity by controlling the speciation of Ag. These results highlight the need to consider environmental transformation of NPs in assessing their toxicity to accurately portray their potential environmental risks. PMID:24180218

  11. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages

    SciTech Connect

    Skornik, W.A.; Brain, J.D.

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (/sup 198/Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC/sub 50/) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m/sup 3/), zinc sulfate (greater than or equal to 3.1 mg/m/sup 3/), ferric sulfate (greater than or equal to 7.8 mg/m/sup 3/), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m/sup 3/), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m/sup 3/ cupric sulfate or 9.8 mg/m/sup 3/ ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC/sub 50/ values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  12. Relative toxicity of inhaled metal sulfate salts for pulmonary macrophages.

    PubMed

    Skornik, W A; Brain, J D

    1983-08-01

    The effects of metal sulfate aerosols on respiratory defense mechanisms in hamsters were studied. Pulmonary macrophage phagocytic rates were measured by determining the in vivo uptake of radioactive colloidal gold (198Au) 1, 24, or 48 h after a single 4-h exposure. The concentrations of sulfate aerosols causing a 50% inhibition in pulmonary macrophage endocytosis (EC50) were determined. When hamsters were exposed for 4 h to cupric sulfate (greater than or equal to 4.8 mg/m3), zinc sulfate (greater than or equal to 3.1 mg/m3), ferric sulfate (greater than or equal to 7.8 mg/m3), or zinc ammonium sulfate (greater than or equal to 10.0 mg/m3), macrophage endocytosis was significantly reduced 1 h after exposure compared with that in unexposed control animals. Although the response was variable, 24 h after exposures to the higher sulfate concentrations the percent of gold ingested by pulmonary macrophages remained depressed. By 48 h, the rate of macrophage endocytosis in hamsters had returned to normal control values except in hamsters exposed to 4.8 mg/m3 cupric sulfate or 9.8 mg/m3 ferric sulfate. These hamsters showed significant increases in phagocytosis. The EC50 values in milligrams of sulfate per cubic meter for cupric sulfate, zinc sulfate, ferric sulfate, and zinc ammonium sulfate were 2.7, 4.5, 7.5, and 17.9, respectively. These results are negatively correlated with the ranking of sulfates using the criteria of relative irritant potency, as measured by increases in pulmonary flow resistance. Thus, rankings of related chemical structures are not absolute. Their relative toxicities vary depending on the end point selected.

  13. Amiodarone-Induced Pulmonary Toxicity – A Frequently Missed Complication

    PubMed Central

    Sweidan, Alexander J.; Singh, Navneet K.; Dang, Natasha; Lam, Vinh; Datta, Jyoti

    2016-01-01

    INTRODUCTION Amiodarone is often used in the suppression of tachyarrhythmias. One of the more serious adverse effects includes amiodarone pulmonary toxicity (APT). Several pulmonary diseases can manifest including interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary nodules or masses, and pleural effusion. Incidence of APT varies from 5–15% and is correlated to dosage, age of the patient, and preexisting lung disease. DESCRIPTION A 56-year-old male with a past medical history of coronary artery disease and chronic obstructive pulmonary disease was admitted for a coronary artery bypass graft. Post-operatively, the patient was admitted to the ICU for ventilator management and continued to receive his home dose of amiodarone 400 mg orally twice daily, which he had been taking for the past 3 months. The patient was found to be hypoxemic with a PaO2 52 mmHg and bilateral infiltrates on chest x-ray. Patient also complained of new onset dyspnea. Physical exam found bilateral rhonchi with bibasilar crackles and subcutaneous emphysema along the left anterior chest wall. Daily chest x-rays showed worsening of bilateral interstitial infiltrates and pleural effusions. A chest high-resolution computed tomography on post-operative day 3 showed extensive and severe bilateral ground glass opacities. APT was suspected and amiodarone was discontinued. A course of oral prednisone without antibiotics was initiated, and after one week of treatment the chest film cleared, the PaO2 value normalized and dyspnea resolved. DISCUSSION APT occurs via cytotoxic T cells and indirectly by immunological reaction. Typically the lungs manifest a diffuse interstitial pneumonitis with varying degrees of fibrosis. Infiltrates with a ‘ground-glass’ appearance appreciated on HRCT are more definitive than chest x-ray. Pulmonary nodules can be seen, frequently in the upper lobes. These are postulated to be accumulations of

  14. Bosutinib induced pleural effusions: Case report and review of tyrosine kinase inhibitors induced pulmonary toxicity.

    PubMed

    Moguillansky, Natalia I; Fakih, Hafiz Abdul Moiz; Wingard, John R

    2017-01-01

    Tyrosine kinase inhibitors are known to cause pulmonary complications. We report a case of bosutinib related bilateral pleural effusions in a patient with chronic myeloid leukemia. Characteristics of the pleural fluid are presented. We also discuss other tyrosine kinase inhibitors induced pulmonary toxicities, including pulmonary hypertension and interstitial lung disease.

  15. Toxicity and bio-accumulation of inhaled cerium oxide nanoparticles in CD1 mice.

    PubMed

    Aalapati, Srinivas; Ganapathy, Selvam; Manapuram, Saikumar; Anumolu, Goparaju; Prakya, Balakrishna Murthy

    2014-11-01

    Male CD1 mice were subjected to nose-inhalation exposure of CeO2 nanoparticles (NPs) for 0, 7, 14 or 28 days with 14 or 28 days of recovery time at an aerosol concentration of 2 mg/m(3). Markers of lung injury and pro-inflammatory cytokines (interleukin-1beta, tumour necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid (BALF), oxidative stress in lungs, bio-accumulation, and histopathology of pulmonary and extrapulmonary tissues were assessed. BALF analysis revealed the induction of pulmonary inflammation, as evident by an increase in the influx of neutrophils with a significant secretion of pro-inflammatory cytokines that lead to generation of oxidative stress and cytotoxicity, as is evident by induction of lipid peroxidation, depletion of glutathione and increased BALF lactate dehydrogenase and protein. The histopathological examination revealed that these inhaled CeO2 NPs were located all over the pulmonary parenchyma, inducing a severe, chronic, active inflammatory response characterised by necrosis, proteinosis, fibrosis and well-formed discrete granulomas in the pulmonary tissue and tubular degeneration leading to coagulative necrosis in kidneys. Inductively coupled plasma optical emission spectrometer results showed a significant bio-accumulation of these particles in the pulmonary and extrapulmonary tissues, even after one month of post-inhalation exposure. Together, these findings suggest that inhalation exposure of CeO2 NPs can induce pulmonary and extrapulmonary toxicity.

  16. Toxicity, Bioaccumulation and Biotransformation of Silver Nanoparticles in Marine Organisms.

    EPA Science Inventory

    The toxicity, bioaccumulation and biotransformation of citrate and polyvinylpyrrolidone (PVP) coated silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) in marine organisms via marine sediment exposure was investigated. Results from 7-d sediment toxicity tests indicate that Ag...

  17. Toxicity, Bioaccumulation and Biotransformation of Silver Nanoparticles in Marine Organisms.

    EPA Science Inventory

    The toxicity, bioaccumulation and biotransformation of citrate and polyvinylpyrrolidone (PVP) coated silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) in marine organisms via marine sediment exposure was investigated. Results from 7-d sediment toxicity tests indicate that Ag...

  18. In vitro toxicity of zinc oxide nanoparticles: a review

    NASA Astrophysics Data System (ADS)

    Pandurangan, Muthuraman; Kim, Doo Hwan

    2015-03-01

    The toxic effect of ZnO nanoparticles is due to their solubility. ZnO nanoparticles dissolve in the extracellular region, which in turn increases the intracellular [Zn2+] level. The mechanism for increased intracellular [Zn2+] level and ZnO nanoparticles dissolution in the medium is still unclear. Cytotoxicity, increased oxidative stress, increased intracellular [Ca2+] level, decreased mitochondrial membrane potential, and interleukin-8 productions occur in the BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells following the exposure of ZnO nanoparticles. Confluent C2C12 cells are more resistant to ZnO nanoparticles compared to the sparse monolayer. Loss of 3T3-L1 cell viability, membrane leakage, and morphological changes occurs due to exposure of ZnO nanoparticles. ZnO nanoparticle induces cytotoxicity and mitochondrial dysfunction in RKO colon carcinoma cells. The occurrence of apoptosis, increased ROS level, reduced mitochondrial activity and formation of tubular intracellular structures are reported following exposure of ZnO nanoparticles in skin cells. Macrophages, monocytes, and dendritic cells are affected by ZnO nanoparticles. In addition, genotoxicity is also induced. The present review summarizes the literature on in vitro toxicity of ZnO nanoparticles (10-100 nm) on various cell lines.

  19. Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

    SciTech Connect

    Kelsey, Chris R.; Horwitz, Mitchell E.; Chino, Junzo P.; Craciunescu, Oana; Steffey, Beverly; Folz, Rodney J.; Chao, Nelson J.; Rizzieri, David A.; Marks, Lawrence B.

    2011-11-01

    Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meier method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.

  20. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, C.-W.; James, J. T.; Taylor, L.; Zeidler-Erdely, P. C.; Castranova, V.

    2009-01-01

    NASA will build an outpost on the Moon for prolonged human habitation and research. The lunar surface is covered by a layer of fine, reactive dust. Astronauts on the Moon will go in and out of the base for various activities, and will inevitably bring some dust into the living quarters. Depressurizing the airlock so that astronauts can exit for outdoor activities could also bring dust inside the airlock to the habitable area. Concerned about the potential health effects on astronauts exposed to airborne lunar dust, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust. The toxicity data also will be needed by toxicologists to establish safe exposure limits for astronauts residing in the lunar habitat and by environmental engineers to design an appropriate dust mitigation strategy. We conducted a study to examine biomarkers of toxicity (inflammation and cytotoxicity) in lung lavage fluids from mice intrapharyngeally instilled with lunar dust samples; we also collected lung tissue from the mice for histopathological examination 3 months after the dust instillation. Reference dusts (TiO2 and quartz) having known toxicities and industrial exposure limits were studied in parallel with lunar dust so that the relative toxicity of lunar dust can be determined. A 6-month histopathology study has been planned. These instillation experiments will be followed by inhalation studies, which are more labor intensive and technologically difficult. The animal inhalation studies will be conducted first with an appropriate lunar dust simulant to ensure that the exposure techniques to be used with actual lunar dust will be successful. The results of these studies collectively will reveal the toxicological risk of exposures and enable us to establish exposure limits on lunar dust for astronauts living in the lunar habitat.

  1. Pulmonary Toxicity Studies of Lunar Dusts in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, C.-W.; James, J. T.; Taylor, L.; Zeidler-Erdely, P. C.; Castranova, V.

    2009-01-01

    NASA will build an outpost on the Moon for prolonged human habitation and research. The lunar surface is covered by a layer of fine, reactive dust. Astronauts on the Moon will go in and out of the base for various activities, and will inevitably bring some dust into the living quarters. Depressurizing the airlock so that astronauts can exit for outdoor activities could also bring dust inside the airlock to the habitable area. Concerned about the potential health effects on astronauts exposed to airborne lunar dust, NASA directed the JSC Toxicology Laboratory to determine the pulmonary toxicity of lunar dust. The toxicity data also will be needed by toxicologists to establish safe exposure limits for astronauts residing in the lunar habitat and by environmental engineers to design an appropriate dust mitigation strategy. We conducted a study to examine biomarkers of toxicity (inflammation and cytotoxicity) in lung lavage fluids from mice intrapharyngeally instilled with lunar dust samples; we also collected lung tissue from the mice for histopathological examination 3 months after the dust instillation. Reference dusts (TiO2 and quartz) having known toxicities and industrial exposure limits were studied in parallel with lunar dust so that the relative toxicity of lunar dust can be determined. A 6-month histopathology study has been planned. These instillation experiments will be followed by inhalation studies, which are more labor intensive and technologically difficult. The animal inhalation studies will be conducted first with an appropriate lunar dust simulant to ensure that the exposure techniques to be used with actual lunar dust will be successful. The results of these studies collectively will reveal the toxicological risk of exposures and enable us to establish exposure limits on lunar dust for astronauts living in the lunar habitat.

  2. Sulfidation of silver nanoparticle reduces its toxicity in zebrafish.

    PubMed

    Devi, G Prathinkra; Ahmed, Khan Behlol Ayaz; Varsha, M K N Sai; Shrijha, B S; Lal, K K Subin; Anbazhagan, Veerappan; Thiagarajan, R

    2015-01-01

    Chemical transformations of metal nanoparticles can be an important way to mitigate nanoparticle toxicity. Sulfidation of silver nanoparticle (AgNPs) is a natural process shown to occur in environment. Very few studies, employing microbes and embryonic stages of zebrafish, have shown reduction in AgNPs toxicity as a direct result of sulfidation. However the feasibility of reducing nanoparticle toxicity by sulfidation of AgNPs has never been studied in adult vertebrates. In this study, we have used adult zebrafish as a model to study the efficacy of sulfidation of AgNPs in reducing nanoparticle toxicity by employing a battery of biomarkers in liver and brain. While AgNPs enhanced liver oxidative stress, altered detoxification enzymes and affected brain acetylcholinesterase activity, sulfidation of AgNPs resulted in significant alleviation of changes in these parameters. Histopathological analyses of liver and sulphydryl levels also support the significance of sulfidated AgNPs in controlling the toxicity of AgNPs. Our study provides the first biochemical data on the importance of sulfidation of AgNPs in reducing biological toxicity in adult vertebrates. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Toxicity and bioactivity of cobalt nanoparticles on the monocytes.

    PubMed

    Liu, Ya-ke; Ye, Jun; Han, Qing-lin; Tao, Ran; Liu, Fan; Wang, Wei

    2015-05-01

    To explore the toxicity and biological activity of cobalt nanoparticles on the osteoclasts. Analyze the relationship between cobalt nanoparticles and osteolysis. Monocyte-macrophages (RAW 264.7) was cultured in vitro, osteoclast-like cells were induced by lipopolysaccharides (LPS). After RAW 264.7 was induced for 24 h, Methyl Thiazolium Tetrazolium (MTT) biological toxicity test of osteoclast-like cell was preceded using Cobalt nanoparticles (set 4 concentrations: 10, 20, 50, 100 μM) and cobalt chloride (set 4 concentrations: 10, 20, 50, 100 μM) at 2, 4, 8, 24 and 48 h respectively. The relative expression of mRNA of CA II and Cat K after RAW 264.7 induction was determined by Q-PCR. mRNA relative expression of CA II, Cat K were reduced at multiple concentrations both cobalt nanoparticles and cobalt chloride, and was time and concentration dependent, cobalt nanoparticles are more significant than cobalt chloride group. But when the cobalt nanoparticles concentration is in 10-50 μM, the mRNA relative expression of CA II, Cat K increased. Cobalt nanoparticles have biological toxicity. At multiple concentrations, the differentiation and proliferation of osteoclasts was inhibited, but when the concentration of cobalt nanoparticles is in 10-50 μM, it has been strengthened. © 2015 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

  4. Assessment of toxicity of nanoparticles using insects as biological models.

    PubMed

    Zhou, Yan; Rocha, Aracely; Sanchez, Carlos J; Liang, Hong

    2012-01-01

    Nanomaterials have become increasingly important in medicine, manufacturing, and consumer products. The fundamental understanding in effects of nanoparticles (NPs) on and their interactions with biomolecules and organismal systems have yet to be achieved. In this chapter, we firstly provide a brief review of the interactions between nanoparticles and biological systems. We will then provide an example by describing a novel method to assess the effects of NPs on biological systems, using insects as a model. Nanoparticles were injected into the central nervous system of the discoid cockroach (Blaberus discoidalis). It was found that insects became hyperactive compared to negative control (water injections). Our method could provide a generic method of assessing nanoparticles toxicity.

  5. Budesonide-loaded solid lipid nanoparticles for pulmonary delivery: preparation, optimization, and aerodynamic behavior.

    PubMed

    Esmaeili, Maryam; Aghajani, Mahdi; Abbasalipourkabir, Roghayeh; Amani, Amir

    2016-12-01

    Advantages of lipid nanoparticles for pulmonary applications are possibility of deep lung deposition with prolonged release and low toxicity. This study aimed to evaluate the effects of formulation and processing parameters on particle size of prepared SLNs. Budesonide-loaded solid lipid nanoparticles (BUD-SLNs) were prepared with different values of drug content, ultrasonication amplitude, and homogenization time and the data were modeled using artificial neural networks (ANNs). Optimal conditions for fabrication of small-sized particles of 170-200 nm were found to be low drug content with high-amplitude and high-homogenization time. In vitro aerosolization performance of BUD-SLNs was then compared to that of commercial budesonide which indicated enhancement in fine particle fraction value.

  6. Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles.

    PubMed

    Sayes, Christie M; Reed, Kenneth L; Glover, Kyle P; Swain, Keith A; Ostraat, Michele L; Donner, E Maria; Warheit, David B

    2010-03-01

    Inhalation toxicity and exposure assessment studies for nonfibrous particulates have traditionally been conducted using particle mass measurements as the preferred dose metric (i.e., mg or microg/m(3)). However, currently there is a debate regarding the appropriate dose metric for nanoparticle exposure assessment studies in the workplace. The objectives of this study were to characterize aerosol exposures and toxicity in rats of freshly generated amorphous silica (AS) nanoparticles using particle number dose metrics (3.7 x 10(7) or 1.8 x 10(8) particles/cm(3)) for 1- or 3-day exposures. In addition, the role of particle size (d(50) = 37 or 83 nm) on pulmonary toxicity and genotoxicity endpoints was assessed at several postexposure time points. A nanoparticle reactor capable of producing, de novo synthesized, aerosolized amorphous silica nanoparticles for inhalation toxicity studies was developed for this study. SiO(2) aerosol nanoparticle synthesis occurred via thermal decomposition of tetraethylorthosilicate (TEOS). The reactor was designed to produce aerosolized nanoparticles at two different particle size ranges, namely d(50) = approximately 30 nm and d(50) = approximately 80 nm; at particle concentrations ranging from 10(7) to 10(8) particles/cm(3). AS particle aerosol concentrations were consistently generated by the reactor. One- or 3-day aerosol exposures produced no significant pulmonary inflammatory, genotoxic, or adverse lung histopathological effects in rats exposed to very high particle numbers corresponding to a range of mass concentrations (1.8 or 86 mg/m(3)). Although the present study was a short-term effort, the methodology described herein can be utilized for longer-term inhalation toxicity studies in rats such as 28-day or 90-day studies. The expansion of the concept to subchronic studies is practical, due, in part, to the consistency of the nanoparticle generation method.

  7. A Mechanistic Study on the Amiodarone-Induced Pulmonary Toxicity

    PubMed Central

    Al-Shammari, Bader; Khalifa, Mohamed; Bakheet, Saleh A.; Yasser, Moustafa

    2016-01-01

    Amiodarone- (AM-) induced pulmonary toxicity (AIPT) is still a matter of research and is poorly understood. In attempting to resolve this issue, we treated Sprague-Dawley rats with AM doses of 80 mg/kg/day/i.p. for one, two, three, and four weeks. The rats were weighed at days 7, 14, 21, and 28 and bronchoalveolar lavages (BAL) were obtained to determine total leukocyte count (TLC). For each group, lung weighing, histopathology, and homogenization were performed. Fresh homogenates were used for determination of ATP content, lipid peroxides, GSH, catalase, SOD, GPx, GR activities, NO, and hydroxyproline levels. The results showed a significant decrease in body weight and GSH depletion together with an increase in both lung weight and lung/body weight coefficient in the first week. Considerable increases in lung hydroxyproline level with some histopathological alterations were apparent. Treatment for two weeks produced a significant increase in BAL fluid, TLC, GR activity, and NO level in lung homogenate. The loss of cellular ATP and inhibition of most antioxidative protective enzymatic system appeared along with alteration in SOD activity following daily treatment for three weeks, while, in rats treated with AM for four weeks, more severe toxicity was apparent. Histopathological diagnosis was mostly granulomatous inflammation and interstitial pneumonitis in rats treated for three and four weeks, respectively. As shown, it is obvious that slow oedema formation is the only initiating factor of AIPT; all other mechanisms may occur as a consequence. PMID:26933474

  8. Toxicity of CeO2 nanoparticles - the effect of nanoparticle properties.

    PubMed

    Leung, Yu Hang; Yung, Mana M N; Ng, Alan M C; Ma, Angel P Y; Wong, Stella W Y; Chan, Charis M N; Ng, Yip Hang; Djurišić, Aleksandra B; Guo, Muyao; Wong, Mabel Ting; Leung, Frederick C C; Chan, Wai Kin; Leung, Kenneth M Y; Lee, Hung Kay

    2015-04-01

    Conflicting reports on the toxicity of CeO2 nanomaterials have been published in recent years, with some studies finding CeO2 nanoparticles to be toxic, while others found it to have protective effects against oxidative stress. To investigate the possible reasons for this, we have performed a comprehensive study on the physical and chemical properties of nanosized CeO2 from three different suppliers as well as CeO2 synthesized by us, and tested their toxicity. For toxicity tests, we have studied the effects of CeO2 nanoparticles on a Gram-negative bacterium Escherichia coli in the dark, under ambient and UV illuminations. We have also performed toxicity tests on the marine diatom Skeletonema costatum under ambient and UV illuminations. We found that the CeO2 nanoparticle samples exhibited significantly different toxicity, which could likely be attributed to the differences in interactions with cells, and possibly to differences in nanoparticle compositions. Our results also suggest that toxicity tests on bacteria may not be suitable for predicting the ecotoxicity of nanomaterials. The relationship between the toxicity and physicochemical properties of the nanoparticles is explicitly discussed in the light of the current results.

  9. Computational nanotoxicology: Predicting toxicity of nanoparticles

    NASA Astrophysics Data System (ADS)

    Burello, Enrico; Worth, Andrew

    2011-03-01

    A statistical model based on a quantitative structure-activity relationship accurately predicts the cytotoxicity of various metal oxide nanoparticles, thus offering a way to rapidly screen nanomaterials and prioritize testing.

  10. Toxicity of silver nanoparticles against bacteria, yeast, and algae

    NASA Astrophysics Data System (ADS)

    Dorobantu, Loredana S.; Fallone, Clara; Noble, Adam J.; Veinot, Jonathan; Ma, Guibin; Goss, Greg G.; Burrell, Robert E.

    2015-04-01

    The toxicity mechanism employed by silver nanoparticles against microorganisms has captivated scientists for nearly a decade and remains a debatable issue. The question most frequently asked is whether silver nanoparticles exert specific effects on microorganisms beyond the well-documented antimicrobial activity of Ag+. Here, we study the effects of citrate- (d = 17.5 ± 9.4 nm) and 11-mercaptoundecanoic acid (d = 38.8 ± 3.6 nm)-capped silver nanoparticles on microorganisms belonging to various genera. The antimicrobial effect of Ag+ was distinguished from that of nanosilver by monitoring microbial growth in the presence and absence of nanoparticles and by careful comparison of the responses of equimolar silver nitrate solution. The results show that when using equimolar silver solutions, silver nitrate has higher toxic potential on all microorganisms than both nanoparticles tested. Furthermore, some microorganisms are more susceptible to silver than others and the choice of capping agent is relevant in the toxicity. Atomic force microscopy disclosed that AgNO3 had a destructive effect on algae. The antimicrobial activity of nanosilver could be exploited to prevent microbial colonization of medical devices and to determine the fate of nanoparticles in the environment.

  11. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma

    PubMed Central

    Sabet, Yasmin; Ramirez, Saul; Rosell Cespedes, Elizabeth; Rensoli Velasquez, Marimer; Porres-Muñoz, Mateo; Gaur, Sumit; Figueroa-Casas, Juan B.; Porres-Aguilar, Mateo

    2016-01-01

    Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID:27190667

  12. Curcumin nanoparticles attenuate cardiac remodeling due to pulmonary arterial hypertension.

    PubMed

    Rice, Kevin M; Manne, Nandini D P K; Kolli, Madhukar B; Wehner, Paulette S; Dornon, Lucy; Arvapalli, Ravikumar; Selvaraj, Vellaisamy; Kumar, Arun; Blough, Eric R

    2016-12-01

    Herein, we investigate whether curcumin nanoparticles (Cur NPs) are effective for the treatment of monocrotaline (MCT)-induced pulmonary arterial hypertension in Sprague Dawley rat. Echocardiography was performed at the start of the study and 28 days after MCT injection. Compared to MCT only animals, Cur NP administration was associated with reduced right ventricular (RV) wall thickness and a decreased right ventricle weight/body weight ratio. Cur NPs also attenuated MCT induced increase in RV mRNA expression of TNF-α and IL-1β. These changes were also associated with decreased RV expression of nitrotyrosine, fibronectin and myosin heavy chain-β.

  13. Ceramic nanoparticles: Recompense, cellular uptake and toxicity concerns.

    PubMed

    Singh, Deependra; Singh, Satpal; Sahu, Jageshwari; Srivastava, Shikha; Singh, Manju Rawat

    2016-01-01

    Over the past few years, nanoparticles and their role in drug delivery have been the centre of attraction as new drug delivery systems. Various forms of nanosystems have been designed, such as nanoclays, scaffolds and nanotubes, having numerous applications in areas such as drug loading, target cell uptake, bioassay and imaging. The present study discusses various types of nanoparticles, with special emphasis on ceramic nanocarriers. Ceramic materials have high mechanical strength, good body response and low or non-existing biodegradability. In this article, the various aspects concerning ceramic nanoparticles, such as their advantages over other systems, their cellular uptake and toxicity concerns are discussed in detail.

  14. Gold Nanoparticles in Cancer Therapy: Efficacy, Biodistribution, and Toxicity.

    PubMed

    Zhao, Jun; Lee, Patrick; Wallace, Michael J; Melancon, Marites P

    2015-01-01

    Gold-based nanoparticles are utilized for cancer therapeutics as a system for drug delivery, or as a mediator for thermal therapy, whether ablation or hyperthermia. This review discusses how the design of the physicochemical properties of the different types of gold-based nanoparticles affects their treatment efficacy. The basic principles and mechanism at which it mediates heating and delivers drugs efficiently in vivo is also summarized. We will also review the in vivo preclinical data on the biodistribution, intratumoral distribution, cell internalization, and its associated toxicity. Lastly, an updated list of the clinical trials based on nanoparticles and future perspectives are provided.

  15. TOXICITY OF AMORPHOUS SILICA NANOPARTICLES IN MOUSE KERATINOCYTES

    SciTech Connect

    Yu, Kyung; Wang, Wei; Gu, Baohua; Hussain, Saber

    2009-01-01

    The present study was designed to examine the uptake, localization and the cytotoxic effects of well-dispersed amorphous silica nanoparticles in mouse keratinocytes (HEL-30). Mouse keratinocytes were exposed for 24h to various concentrations of amorphous silica nanoparticles in homogeneous suspensions of average size distribution (30, 48, 118 and 535 nm SiO2) then assessed for uptake and biochemical changes. Results of transmission electron microscopy revealed all sizes of silica were taken up into the cells and localized into the cytoplasm. The lactate dehydrogenase (LDH) assay shows LDH leakage was dose- and size-dependent with exposure to 30 and 48 nm nanoparticles. However, no LDH leakage was observed for either 118 or 535 nm nanoparticles. The mitochondrial viability assay (MTT) showed significant toxicity for 30 and 48 nm at high concentrations (100 g/mL) compare to the 118 and 535 nm particles. Further studies were carried out to investigate if cellular reduced GSH and mitochondria membrane potential are involved in the mechanism of SiO2 toxicity. The redox potential of cells (GSH) was reduced significantly at concentrations of 50, 100 and 200 g/mL at 30 nm nanoparticle exposures. However, silica nanoparticles larger than 30 nm showed no changes in GSH levels. Reactive oxygen species (ROS) formation did not show any significant change between controls and the exposed cells. In summary, amorphous silica nanoparticles below 100 nm induced cytotoxicity suggest size-of the particles is critical to produce biological effects.

  16. Original Research: Evaluation of pulmonary response to inhaled tungsten (IV) oxide nanoparticles in golden Syrian hamsters

    PubMed Central

    Prajapati, Milankumar V; Adebolu, Olujoba O; Morrow, Benjamin M

    2016-01-01

    Extensive industrial and military uses of tungsten have raised the possibilities of human occupational and environmental exposure to nanoparticles of this metal, with concomitant health concerns. The goal of this study was to investigate the potential mechanism of pulmonary toxicity associated with inhaled tungsten (IV) oxide nanoparticles (WO3 NPs) in Golden Syrian Hamsters. Animals exposed to WO3 NPs via inhalation were divided into three groups — control and two treatment groups exposed to either 5 or 10 mg/m3 of aerosolized WO3 NPs for 4 h/day for four days. A long-term exposure study (4 h/day for eight days) was also carried out using an additional three groups. Pulmonary toxicity assessed by examining changes in cell numbers, lactate dehydrogenase activity, alkaline phosphatase activity, total protein content, TNF-α, and HMGB1 levels in bronchoalveolar lavage fluids showed a significant difference when compared to control (P < 0.05). The molecular mechanism was established by assessing protein expression of cathepsin B, TXNIP, NLRP3, ASC, IL-1β and caspase-1. Western blot analysis indicated a 1.5 and 1.7 fold changes in NLRP3 in treatment groups (5 mg/m3, P < 0.05 and 10 mg/m3, P < 0.01, respectively), whereas levels of cathepsin B were 1.3 fold higher in lung tissue exposed to WO3 NPs suggesting activation of inflammasome pathway. Morphological changes studied using light and electron microscopy showed localization of nanoparticles and subsequent perturbation in airway epithelia, macrophages, and interstitial areas of alveolar structures. Results from the current study indicate that inhalation exposure to WO3 NPs may induce cytotoxicity, morphological changes, and lung injury via pyroptotic cell death pathway caused by activation of caspase-1. PMID:27534980

  17. Lipid nanoparticle delivery of a microRNA-145 inhibitor improves experimental pulmonary hypertension.

    PubMed

    McLendon, Jared M; Joshi, Sachindra R; Sparks, Jeff; Matar, Majed; Fewell, Jason G; Abe, Kohtaro; Oka, Masahiko; McMurtry, Ivan F; Gerthoffer, William T

    2015-07-28

    pathology, and histopathology and did not detect significant off-target effects. AntimiR-145 reduced the degree of pulmonary arteriopathy, reduced the severity of pulmonary hypertension, and reduced the degree of cardiac dysfunction. The results establish effective and low toxicity of lung delivery of a miRNA-145 inhibitor using functionalized cationic lipopolyamine nanoparticles to repair pulmonary arteriopathy and improve cardiac function in rats with severe PAH.

  18. Reducing Environmental Toxicity of Silver Nanoparticles through Shape Control.

    PubMed

    Gorka, Danielle E; Osterberg, Joshua S; Gwin, Carley A; Colman, Benjamin P; Meyer, Joel N; Bernhardt, Emily S; Gunsch, Claudia K; DiGulio, Richard T; Liu, Jie

    2015-08-18

    The use of antibacterial silver nanomaterials in consumer products ranging from textiles to toys has given rise to concerns over their environmental toxicity. These materials, primarily nanoparticles, have been shown to be toxic to a wide range of organisms; thus methods and materials that reduce their environmental toxicity while retaining their useful antibacterial properties can potentially solve this problem. Here we demonstrate that silver nanocubes display a lower toxicity toward the model plant species Lolium multiflorum while showing similar toxicity toward other environmentally relevant and model organisms (Danio rerio and Caenorhabditis elegans) and bacterial species (Esherichia coli, Bacillus cereus, and Pseudomonas aeruginosa) compared to quasi-spherical silver nanoparticles and silver nanowires. More specifically, in the L. multiflorum experiments, the roots of silver nanocube treated plants were 5.3% shorter than the control, while silver nanoparticle treated plant roots were 39.6% shorter than the control. The findings here could assist in the future development of new antibacterial products that cause less environmental toxicity after their intended use.

  19. Metal Nanoparticle Pollutants Interfere with Pulmonary Surfactant Function In Vitro☆

    PubMed Central

    Bakshi, Mandeep Singh; Zhao, Lin; Smith, Ronald; Possmayer, Fred; Petersen, Nils O.

    2008-01-01

    Abstract Reported associations between air pollution and pulmonary and cardiovascular diseases prompted studies on the effects of gold nanoparticles (Au NP) on pulmonary surfactant function. Low levels (3.7 mol % Au/lipid, 0.98% wt/wt) markedly inhibited adsorption of a semisynthetic pulmonary surfactant (dipalmitoyl-phosphatidylcholine (DPPC)/palmitoyl-oleoyl-phosphatidylglycerol/surfactant protein B (SP-B); 70:30:1 wt %). Au NP also impeded the surfactant's ability to reduce surface tension (γ) to low levels during film compression and to respread during film expansion. Transmission electron microscopy showed that Au NP generated by a seed-growth method were spherical with diameters of ∼15 nm. Including palmitoyl-oleoyl-phosphatidylglycerol appeared to coat the NP with at least one lipid bilayer but did not affect NP shape or size. Similar overall observations occurred with dimyristoyl phosphatidylglycerol. Dipalmitoyl-phosphatidylglycerol was less effective in NP capping, although similar sized NP were formed. Including SP-B (1% wt/wt) appears to induce the formation of elongated strands of interacting threads with the fluid phosphatidylglycerols (PG). Including DPPC resulted in formation of aggregated, less spherical NP with a larger size distribution. With DPPC, strand formation due to SP-B was not observed. Agarose gel electrophoresis studies demonstrated that the aggregation induced by SP-B blocked migration of PG-coated NP. Migration was also influenced by the fluidity of the PGs. It is concluded that Au NP can interact with and sequester pulmonary surfactant phospholipids and, if inhaled from the atmosphere, could impede pulmonary surfactant function in the lung. PMID:17890383

  20. Physicochemical properties of nanoparticles regulate translocation across pulmonary surfactant monolayer and formation of lipoprotein corona.

    PubMed

    Hu, Guoqing; Jiao, Bao; Shi, Xinghua; Valle, Russell P; Fan, Qihui; Zuo, Yi Y

    2013-12-23

    Interaction with the pulmonary surfactant film, being the first line of host defense, represents the initial bio-nano interaction in the lungs. Such interaction determines the fate of the inhaled nanoparticles and their potential therapeutic or toxicological effect. Despite considerable progress in optimizing physicochemical properties of nanoparticles for improved delivery and targeting, the mechanisms by which inhaled nanoparticles interact with the pulmonary surfactant film are still largely unknown. Here, using combined in vitro and in silico methods, we show how hydrophobicity and surface charge of nanoparticles differentially regulate the translocation and interaction with the pulmonary surfactant film. While hydrophilic nanoparticles generally translocate quickly across the pulmonary surfactant film, a significant portion of hydrophobic nanoparticles are trapped by the surfactant film and encapsulated in lipid protrusions upon film compression. Our results support a novel model of pulmonary surfactant lipoprotein corona associated with inhaled nanoparticles of different physicochemical properties. Our data suggest that the study of pulmonary nanotoxicology and nanoparticle-based pulmonary drug delivery should consider this lipoprotein corona.

  1. [Health effects of nanoparticles and nanomaterials (III). Toxicity and health effects of nanoparticles].

    PubMed

    Hirose, Akihiko; Hirano, Seishiro

    2008-07-01

    As described before in the first Frontier Report of this series, there are two types of nanoparticles to be considered in hygiene science; One is the environmental nanoparticle emitted from automobiles and the other is the manufactured nanoparticle. In general nanoparticles (less than 100 nm) are reported to be permeable through cell membrane and tissues and their large surface area is responsible for the greater toxicity compared to larger particles. However, there are contradictory reports on the health effects of nanoparticles. Recent reports suggest that carbon nanotubes, fiber-shaped biopersistent nanoparticles, resemble asbestos in the pathogenesis of granuloma and mesothelioma. As such we summarize health effects of environmental and manufactured nanoparticles in the literature so far including our studies, in this report.

  2. Toxic effects of gold nanoparticles on Salmonella typhimurium bacteria

    PubMed Central

    Wang, Shuguang; Lawson, Rasheeda; Ray, Paresh C; Yu, Hongtao

    2013-01-01

    Nanometer-sized gold, due to its beautiful and bountiful color and unique optical properties, is a versatile material for many industrial and societal applications. We have studied the effect of gold nanoparticles on Salmonella typhimurium strain TA 102. The gold nanoparticles in solution prepared using the citrate reduction method is found not to be toxic or mutagenic but photomutagenic to the bacteria; however, careful control experiments indicate that the photomutagenicity is due to the co-existing citrate and Au3+ ions, not due to the gold nanoparticle itself. Au3+ is also found to be photomutagenic to the bacteria at concentrations lower than 1 µM, but toxic at higher concentrations. The toxicity of Au3+ is enhanced by light irradiation. The photomutagenicity of both citrate and Au3+ is likely due to the formation of free radicals, as a result of light-induced citrate decarboxylation or Au3+ oxidation of co-existing molecules. Both processes can generate free radicals that may cause DNA damage and mutation. Studies of the interaction of gold nanoparticles with the bacteria indicate that gold nanoparticles can be absorbed onto the bacteria surface but not able to penetrate the bacteria wall to enter the bacteria. PMID:21415096

  3. Pulmonary Toxicity Studies of Lunar Dust in Rodents

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.

    2012-01-01

    NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological

  4. Nanoparticle-Mediated Pulmonary Drug Delivery: A Review

    PubMed Central

    Paranjpe, Mukta; Müller-Goymann, Christel C.

    2014-01-01

    Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed. PMID:24717409

  5. Toxicity, Bioaccumulation and Biotransformation of Silver Nanoparticles in Marine Organisms

    EPA Science Inventory

    The toxicity, bioaccumulation and biotransformation of citrate and polyvinylpyrrolidone (PVP) capped silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) and titanium dioxide (TiO2) NPs in marine organisms via marine sediment exposure were investigated. Results from 7-d sedimen...

  6. Toxicity, Bioaccumulation and Biotransformation of Silver Nanoparticles in Marine Organisms

    EPA Science Inventory

    The toxicity, bioaccumulation and biotransformation of citrate and polyvinylpyrrolidone (PVP) capped silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) and titanium dioxide (TiO2) NPs in marine organisms via marine sediment exposure were investigated. Results from 7-d sedimen...

  7. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

    PubMed Central

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

    2014-01-01

    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. PMID:25407529

  8. A Review of Molecular Mechanisms Involved in Toxicity of Nanoparticles

    PubMed Central

    Khalili Fard, Javad; Jafari, Samira; Eghbal, Mohammad Ali

    2015-01-01

    In recent decades, the use of nanomaterials has received much attention in industrial and medical fields. However, some reports have mentioned adverse effects of these materials on the biological systems and cellular components. There are several major mechanisms for cytotoxicity of nanoparticles (NPs) such as physicochemical properties, contamination with toxic element, fibrous structure, high surface charge and radical species generation. In this review, a brief key mechanisms involved in toxic effect of NPs are given, followed by the in vitro toxicity assays of NPs and prooxidant effects of several NPs such as carbon nanotubes, titanium dioxide NPs, quantum dots, gold NPs and silver NPs. PMID:26819915

  9. Relationship between chemical composition and pulmonary toxicity of source-specific ambient particulate matter

    EPA Science Inventory

    Epidemiological studies have reported incidence of cardio-pulmonary disease associated with increase in particulate matter (PM) exposure. In this study, the pulmonary toxicity potential of combustion and ambient PM were investigated using data from animal studies at the US EPA....

  10. Relationship between chemical composition and pulmonary toxicity of source-specific ambient particulate matter

    EPA Science Inventory

    Epidemiological studies have reported incidence of cardio-pulmonary disease associated with increase in particulate matter (PM) exposure. In this study, the pulmonary toxicity potential of combustion and ambient PM were investigated using data from animal studies at the US EPA....

  11. Applications and toxicity of silver nanoparticles: a recent review.

    PubMed

    Marin, Stefania; Vlasceanu, George Mihail; Tiplea, Roxana Elena; Bucur, Ioana Raluca; Lemnaru, Madalina; Marin, Maria Minodora; Grumezescu, Alexandru Mihai

    2015-01-01

    Silver nanoparticles (AgNPs) exhibit a consistent amount of flexible properties which endorse them for a larger spectrum of applications in biomedicine and related fields. Over the years, silver nanoparticles have been subjected to numerous in vitro and in vivo tests to provide information about their toxic behavior towards living tissues and organisms. Researchers showed that AgNPs have high antimicrobial efficacy against many bacteria species including Escherichia coli, Neisseria gonorrhea, Chlamydia trachomatis and also viruses. Due to their novel properties, the incorporation of silver nanoparticles into different materials like textile fibers and wound dressings can extend their utility on the biomedical field while inhibiting infections and biofilm development. Among the noble metal nanoparticles, AgNPs present a series of features like simple synthesis routes, adequate and tunable morphology, and high surface to volume ratio, intracellular delivery system, a large plasmon field area recommending them as ideal biosensors, catalysts or photo-controlled delivery systems. In bioengineering, silver nanoparticles are considered potentially ideal gene delivery systems for tissue regeneration. The remote triggered detection and release of bioactive compounds of silver nanoparticles has proved their relevance also in forensic sciences. The authors report an up to date review related to the toxicity of AgNPs and their applications in antimicrobial activity and biosensors for gene therapy.

  12. Comparative Metal Oxide Nanoparticle Toxicity Using Embryonic Zebrafish

    PubMed Central

    Wehmas, Leah C.; Anders, Catherine; Chess, Jordan; Punnoose, Alex; Pereira, Cliff B.; Greenwood, Juliet A.; Tanguay, Robert L.

    2015-01-01

    Engineered metal oxide nanoparticles (MO NPs) are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO), titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration = 3.5–9.1 mg/L). This toxicity was life stage dependent. The 24 h toxicity increased greatly (~22.7 fold) when zebrafish exposures started at the larval life stage compared to the 24 hour toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40–89% of total sample) were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity. PMID:26029632

  13. Toxicity of combined mixtures of nanoparticles to plants.

    PubMed

    Jośko, Izabela; Oleszczuk, Patryk; Skwarek, Ewa

    2017-06-05

    An increasing production and using of nanoproducts results in releasing and dispersing nanoparticles (NPs) in the environment. Being released into various environment components, NPs may interact with numerous pollutants, including other NPs. This research aimed at assessing toxicity of combined binary mixtures of NPs. The study focused on assessing mixtures of NPs believed to be toxic (nano-ZnO+nano-CuO) and nano-ZnO/nano-CuO with the ones that are insignificantly toxic or non-toxic NPs (nano-TiO2/nano-Cr2O3/nano-Fe2O3). Toxicity of combined mixtures proved comparable to toxicity of individual mixtures of NPs (the sum of effects triggered by individual types of NPs comprising respective mixtures). Toxicity evaluation was based on two parameters: seed germination and inhibition of root growth with respect to four plant species: Lepidium sativum, Linum utisassimmum, Cucumis sativus and Triticum aestivum. The findings showed combined mixtures of NPs to be significantly less toxic in comparison to individual mixtures, irrespective of their components. Within the scope of concentrations used, greatest differences between the toxicity of mixtures were reported at the 100mgL(-1) concentration. Toxicity levels of combined and individual mixtures might have been determined by a lower total concentration of Zn and Cu metals and a greater aggregation of particles in combined mixtures than in individual mixtures.

  14. Pulmonary administration of integrin-nanoparticles regenerates collapsed alveoli.

    PubMed

    Horiguchi, Michiko; Kojima, Hisako; Sakai, Hitomi; Kubo, Hiroshi; Yamashita, Chikamasa

    2014-08-10

    Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causes widespread and irreversible alveoli collapse. In search of a treatment target molecule, which is able to regenerate collapsed alveoli, we sought to identify a factor that induces differentiation in human alveolar epithelial stem cells using all-trans retinoic acid (ATRA), whose alveolar repair capacity has been reported in animal experiments. When human alveolar epithelial stem cells were exposed to ATRA at a concentration of 10μM for over seven days, approximately 20% of the cells differentiated into each of the type-I and type-II alveolar epithelial cells that constitute the alveoli. In a microarray analysis, integrin-α1 and integrin-β3 showed the largest variation in the ATRA-treated group compared with the controls. Furthermore, the effect of the induction of differentiation in human alveolar epithelial stem cells using ATRA was suppressed by approximately one-fourth by siRNA treatments with integrin α1 and integrin β3. These results suggested that integrin α1 and β3 are factors responsible for the induction of differentiation in human alveolar epithelial stem cells. We accordingly investigated whether integrin nanoparticles also had a regenerative effect in vivo. Elastase-induced COPD model mouse was produced, and the alveolar repair effect of pulmonary administration using nanoparticles of integrin protein was evaluated by X-ray CT scanning. Improvement in the CT value in comparison with an untreated group indicated that there was an alveolar repair effect. In this study, it was shown that the differentiation-inducing effect on human alveolar epithelial stem cells by ATRA was induced by increased expression of integrin, and that the induced integrin enhanced phosphorylation signaling of AKT, resulting in inducing differentiations. Furthermore, the study demonstrated that lung administration of nanoparticles with increased solubility and stability of integrin

  15. Sulfidation of silver nanoparticles: natural antidote to their toxicity.

    PubMed

    Levard, Clement; Hotze, Ernest M; Colman, Benjamin P; Dale, Amy L; Truong, Lisa; Yang, X Y; Bone, Audrey J; Brown, Gordon E; Tanguay, Robert L; Di Giulio, Richard T; Bernhardt, Emily S; Meyer, Joel N; Wiesner, Mark R; Lowry, Gregory V

    2013-01-01

    Nanomaterials are highly dynamic in biological and environmental media. A critical need for advancing environmental health and safety research for nanomaterials is to identify physical and chemical transformations that affect the nanomaterial properties and their toxicity. Silver nanoparticles, one of the most toxic and well-studied nanomaterials, readily react with sulfide to form Ag(0)/Ag2S core-shell particles. Here, we show that sulfidation decreased silver nanoparticle toxicity to four diverse types of aquatic and terrestrial eukaryotic organisms (Danio rerio (zebrafish), Fundulus heteroclitus (killifish), Caenorhabditis elegans (nematode worm), and the aquatic plant Lemna minuta (least duckweed)). Toxicity reduction, which was dramatic in killifish and duckweed even for low extents of sulfidation (about 2 mol % S), is primarily associated with a decrease in Ag(+) concentration after sulfidation due to the lower solubility of Ag2S relative to elemental Ag (Ag(0)). These results suggest that even partial sulfidation of AgNP will decrease the toxicity of AgNPs relative to their pristine counterparts. We also show that, for a given organism, the presence of chloride in the exposure media strongly affects the toxicity results by affecting Ag speciation. These results highlight the need to consider environmental transformations of NPs in assessing their toxicity to accurately portray their potential environmental risks.

  16. An Evaluation of Coating Material Dependent Toxicity of Silver Nanoparticles

    NASA Astrophysics Data System (ADS)

    Silva, Thilini Upekshika

    Silver nanoparticles (AgNPs) synthesized using numerous types of coating materials may exhibit different toxicity effects. The study evaluated coating material dependent toxicity by selecting 3 types of AgNP synthesis methods with different coating materials (citrate, polyvinyl pyrrolidone, and branched polyethyleneimine, coated AgNPs as citrate-AgNPs, PVP-AgNPs, and BPEI-AgNPs respectively). Two acute aquatic toxicity tests were performed; 48hr D. magna and MetPLATE E. coli toxicity tests. Significantly different toxicity effects were observed in D. magna test exhibiting lethal median concentrations (LC50) for citrate-AgNPs, PVP-AgNPs, and BPEI AgNPs respectively as, 2.7, 11.2, and 0.57microg/L. Median inhibitory concentrations (EC50) for MetPLATE tests were 1.27, 1.73, and 0.31mg/L respectively with significant different toxicity effects. Silver ion fractions were detected in the range of 2.4-19.2% in tested NP suspensions. Study suggests the toxicity effects are due to the cumulative action of ionic and nanoparticle fractions in the suspensions.

  17. Novel lipid hybrid albumin nanoparticle greatly lowered toxicity of pirarubicin.

    PubMed

    Zhou, Jing; Zhang, Xuanmiao; Li, Mei; Wu, Wenqi; Sun, Xun; Zhang, Ling; Gong, Tao

    2013-10-07

    Pirarubicin (THP) is an effective anthracycline for the treatment of solid tumor. However, its potential side effects are prominent and clinical use is restricted. We aimed to develop a novel pirarubicin-oleic acid complex albumin nanoparticle (THP-OA-AN) in order to reduce the toxicity of THP. Oleic acid, human serum albumin (HSA), and egg yolk lecithin E80 was used to prepare THP-OA-AN. Prepared THP-OA-AN was characterized and animal experiments were conducted to assess its tumor suppression effect, distribution, and toxicity. Comparison between THP and THP-OA-AN showed that, with retained antitumor efficiency, the toxicity of THP-OA-AN is significantly reduced regarding bone marrow suppression, cardiotoxicity, renal toxicity, and gastrointestinal toxicity. This study developed a safe and effective formulation of THP, which has greater potential for clinic use in the tumor therapy.

  18. Silver nanoparticles in cancer: therapeutic efficacy and toxicity.

    PubMed

    Ong, C; Lim, J Z Z; Ng, C-T; Li, J J; Yung, L-Y L; Bay, B-H

    2013-02-01

    In recent years, there has been escalating interest in the biomedical applications of nanoparticles (NPs). In particular, silver nanoparticles (AgNPs) are increasingly being investigated as tools for novel cancer therapeutics, capitalizing on their unique properties to enhance potential therapeutic efficacy. However, questions as to are we able to contain or control the toxicity effects of AgNPs, and how much do we know about the toxicological profile of AgNPs which are commonly used in emerging nanotechnology-based applications, still remain. Hence, serious considerations have to be given to the hazards and risks of toxicity associated with the use of AgNPs. This review focuses on the current applications of AgNPs, their known effects and toxicity, as well as the potential of harnessing them for use in cancer therapy.

  19. Nanoparticle Toxicity Mechanisms: Oxidative Stress and Inflammation

    NASA Astrophysics Data System (ADS)

    L'Azou, Béatrice; Marano, Francelyne

    Toxicology plays a key role in understanding the potentially harmful biological effects of nanoparticles, since epidemiological studies are still difficult to implement given the lack of data concerning exposure. For this reason, in 2005, Günter Oberdörster coined the term `nanotoxicology' to specify the emerging discipline that dealt with ultrafine particles (UFP). It involves in vivo or in vitro studies under controlled conditions to establish the dose-response relationship, so difficult to expose by epidemiological studies. It also aims to determine the thresholds below which biological effects are no longer observed. It is concerned with the role played by properties specific to nanoparticles in the biological response: size, surface reactivity, chemical composition, solubility, etc.

  20. Silver nanoparticle protein corona and toxicity: a mini-review.

    PubMed

    Durán, Nelson; Silveira, Camila P; Durán, Marcela; Martinez, Diego Stéfani T

    2015-09-04

    Silver nanoparticles are one of the most important materials in the nanotechnology industry. Additionally, the protein corona is emerging as a key entity at the nanobiointerface; thus, a comprehensive understanding of the interactions between proteins and silver nanoparticles is imperative. Therefore, literature reporting studies involving both single molecule protein coronas (i.e., bovine and human serum albumin, tubulin, ubiquitin and hyaluronic-binding protein) and complex protein coronas (i.e., fetal bovine serum and yeast extract proteins) were selected to demonstrate the effects of protein coronas on silver nanoparticle cytotoxicity and antimicrobial activity. There is evidence that distinct and differential protein components may yield a "protein corona signature" that is related to the size and/or surface curvature of the silver nanoparticles. Therefore, the formation of silver nanoparticle protein coronas together with the biological response to these coronas (i.e., oxidative stress, inflammation and cytotoxicity) as well as other cellular biophysicochemical mechanisms (i.e., endocytosis, biotransformation and biodistribution) will be important for nanomedicine and nanotoxicology. Researchers may benefit from the information contained herein to improve biotechnological applications of silver nanoparticles and to address related safety concerns. In summary, the main aim of this mini-review is to highlight the relationship between the formation of silver nanoparticle protein coronas and toxicity.

  1. Pulmonary toxicity of carbon nanotubes and asbestos - similarities and differences.

    PubMed

    Donaldson, Ken; Poland, Craig A; Murphy, Fiona A; MacFarlane, Marion; Chernova, Tatyana; Schinwald, Anja

    2013-12-01

    Carbon nanotubes are a valuable industrial product but there is potential for human pulmonary exposure during production and their fibrous shape raises the possibility that they may have effects like asbestos, which caused a worldwide pandemic of disease in the20th century that continues into present. CNT may exist as fibres or as more compact particles and the asbestos-type hazard only pertains to the fibrous forms of CNT. Exposure to asbestos causes asbestosis, bronchogenic carcinoma, mesothelioma, pleural fibrosis and pleural plaques indicating that both the lungs and the pleura are targets. The fibre pathogenicity paradigm was developed in the 1970s-80s and has a robust structure/toxicity relationship that enables the prediction of the pathogenicity of fibres depending on their length, thickness and biopersistence. Fibres that are sufficiently long and biopersistent and that deposit in the lungs can cause oxidative stress and inflammation. They may also translocate to the pleura where they can be retained depending on their length, and where they cause inflammation and oxidative stress in the pleural tissues. These pathobiological processes culminate in pathologic change - fibroplasia and neoplasia in the lungs and the pleura. There may also be direct genotoxic effects of fibres on epithelial cells and mesothelium, contributing to neoplasia. CNT show some of the properties of asbestos and other types of fibre in producing these types of effects and more research is needed. In terms of the molecular pathways involved in the interaction of long biopersistent fibres with target tissue the events leading to mesothelioma have been a particular area of interest. A variety of kinase pathways important in proliferation are activated by asbestos leading to pre-malignant states and investigations are under way to determine whether fibrous CNT also affects these molecular pathways. Current research suggests that fibrous CNT can elicit effects similar to asbestos but more

  2. Pulmonary vascular lesions in the toxic oil syndrome in Spain.

    PubMed Central

    Fernández-Segoviano, P; Esteban, A; Martínez-Cabruja, R

    1983-01-01

    A histological study was made of pulmonary arteries at the necropsies of nine patients who died after the ingestion of denatured rapeseed oil during the epidemic which occurred in Spain in May 1981. Lesions found in the elastic pulmonary arteries were characterised by pronounced intimal proliferation of an oedematous nature, accumulation of large vacuolated cells within the media, and loss of vascular smooth muscle. In muscular pulmonary arteries there was pronounced medial hypertrophy and intimal proliferation, which was so severe in one case that it completely occluded the arterial lumen. Foamy cells were found in the intima. Muscularisation was seen in the walls of pulmonary arterioles. Images PMID:6648850

  3. Toxicity of Cerium Oxide Nanoparticles in Human Lung Cancer Cells

    SciTech Connect

    Weisheng, Lin; Huang, Yue-wern; Zhou, Xiao Dong; Ma, Yinfa

    2006-12-31

    With the fast development of nanotechnology, the nanomaterials start to cause people's attention for potential toxic effect. In this paper, the cytotoxicity and oxidative stress caused by 20-nm cerium oxide (CeO2) nanoparticles in cultured human lung cancer cells was investigated. The sulforhodamine B method was employed to assess cell viability after exposure to 3.5, 10.5, and 23.3 μg/ml of CeO2 nanoparticles for 24, 48, and 72 h. Cell viability decreased significantly as a function of nanoparticle dose and exposure time. Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species, glutathione, malondialdehyde, α-tocopherol, and lactate dehydrogenase, were quantitatively assessed. It is concluded from the results that free radicals generated by exposure to 3.5 to 23.3 μg/ml CeO2 nanoparticles produce significant oxidative stress in the cells, as reflected by reduced glutathione and α-tocopherol levels; the toxic effects of CeO2 nanoparticles are dose dependent and time dependent; elevated oxidative stress increases the production of malondialdehyde and lactate dehydrogenase, which are indicators of lipid peroxidation and cell membrane damage, respectively.

  4. Toxicity assessment of zero valent iron nanoparticles on Artemia salina.

    PubMed

    Kumar, Deepak; Roy, Rajdeep; Parashar, Abhinav; Raichur, Ashok M; Chandrasekaran, Natarajan; Mukherjee, Anita; Mukherjee, Amitava

    2017-05-01

    The present study deals with the toxicity assessment of two differently synthesized zero valent iron nanoparticles (nZVI, chemical and biological) as well as Fe(2+) ions on Artemia salina at three different initial concentrations of 1, 10, and 100 mg/L of these particles. The assessment was done till 96 h at time intervals of 24 h. EC50 value was calculated to evaluate the 50% mortality of Artemia salina at all exposure time durations. Between chemically and biologically synthesized nZVI nanoparticles, insignificant differences in the level of mortality were demonstrated. At even 24 h, Fe(2+) ion imparted complete lethality at the highest exposure concentration (100 mg/L). To understand intracellular oxidative stress because of zero valent iron nanoparticles, ROS estimation, SOD activity, GSH activity, and catalase activity was performed which demonstrated that ionic form of iron is quite lethal at high concentrations as compared with the same concentration of nZVI exposure. Lower concentrations of nZVI were more toxic as compared with the ionic form and was in order of CS-nZVI > BS-nZVI > Fe(2+) . Cell membrane damage and bio-uptake of nanoparticles were also evaluated for all three concentrations of BS-nZVI, CS-nZVI, and Fe(2+) using adult Artemia salina in marine water; both of which supported the observations made in toxicity assessment. This study can be further explored to exploit Artemia salina as a model organism and a biomarker in an nZVI prone aquatic system to detect toxic levels of these nanoparticles. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1617-1627, 2017. © 2017 Wiley Periodicals, Inc.

  5. Molecular Mechanisms of Toxicity of Silver Nanoparticles in Zebrafish Embryos

    PubMed Central

    2013-01-01

    Silver nanoparticles cause toxicity in exposed organisms and are an environmental health concern. The mechanisms of silver nanoparticle toxicity, however, remain unclear. We examined the effects of exposure to silver in nano-, bulk-, and ionic forms on zebrafish embryos (Danio rerio) using a Next Generation Sequencing approach in an Illumina platform (High-Throughput SuperSAGE). Significant alterations in gene expression were found for all treatments and many of the gene pathways affected, most notably those associated with oxidative phosphorylation and protein synthesis, overlapped strongly between the three treatments indicating similar mechanisms of toxicity for the three forms of silver studied. Changes in oxidative phosphorylation indicated a down-regulation of this pathway at 24 h of exposure, but with a recovery at 48 h. This finding was consistent with a dose-dependent decrease in oxygen consumption at 24 h, but not at 48 h, following exposure to silver ions. Overall, our data provide support for the hypothesis that the toxicity caused by silver nanoparticles is principally associated with bioavailable silver ions in exposed zebrafish embryos. These findings are important in the evaluation of the risk that silver particles may pose to exposed vertebrate organisms. PMID:23758687

  6. Molecular mechanisms of toxicity of silver nanoparticles in zebrafish embryos.

    PubMed

    van Aerle, Ronny; Lange, Anke; Moorhouse, Alex; Paszkiewicz, Konrad; Ball, Katie; Johnston, Blair D; de-Bastos, Eliane; Booth, Timothy; Tyler, Charles R; Santos, Eduarda M

    2013-07-16

    Silver nanoparticles cause toxicity in exposed organisms and are an environmental health concern. The mechanisms of silver nanoparticle toxicity, however, remain unclear. We examined the effects of exposure to silver in nano-, bulk-, and ionic forms on zebrafish embryos (Danio rerio) using a Next Generation Sequencing approach in an Illumina platform (High-Throughput SuperSAGE). Significant alterations in gene expression were found for all treatments and many of the gene pathways affected, most notably those associated with oxidative phosphorylation and protein synthesis, overlapped strongly between the three treatments indicating similar mechanisms of toxicity for the three forms of silver studied. Changes in oxidative phosphorylation indicated a down-regulation of this pathway at 24 h of exposure, but with a recovery at 48 h. This finding was consistent with a dose-dependent decrease in oxygen consumption at 24 h, but not at 48 h, following exposure to silver ions. Overall, our data provide support for the hypothesis that the toxicity caused by silver nanoparticles is principally associated with bioavailable silver ions in exposed zebrafish embryos. These findings are important in the evaluation of the risk that silver particles may pose to exposed vertebrate organisms.

  7. Assessment of the In Vivo Toxicity of Gold Nanoparticles

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Shiun; Hung, Yao-Ching; Liau, Ian; Huang, G. Steve

    2009-08-01

    The environmental impact of nanoparticles is evident; however, their toxicity due to their nanosize is rarely discussed. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. GNPs of 3, 5, 50, and 100 nm did not show harmful effects; however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. The majority of mice in these groups died within 21 days. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles.

  8. Interference of engineered nanoparticles with in vitro toxicity assays.

    PubMed

    Kroll, Alexandra; Pillukat, Mike Hendrik; Hahn, Daniela; Schnekenburger, Jürgen

    2012-07-01

    Accurate in vitro assessment of nanoparticle cytotoxicity requires a careful selection of the test systems. Due to high adsorption capacity and optical activity, engineered nanoparticles are highly potential in influencing classical cytotoxicity assays. Here, four common in vitro assays for oxidative stress, cell viability, cell death and inflammatory cytokine production (DCF, MTT, LDH and IL-8 ELISA) were assessed for validity using 24 well-characterized engineered nanoparticles. For all nanoparticles, the possible interference with the optical detection methods, the ability to convert the substrates, the influence on enzymatic activity and the potential to bind proinflammatory cytokines were analyzed in detail. Results varied considerably depending on the assay system used. All nanoparticles tested were found to interfere with the optical measurement at concentrations of 50 μg cm⁻² and above when DCF, MTT and LDH assays were performed. Except for Carbon Black, particle interference could be prevented by altering assay protocols and lowering particle concentrations to 10 μg cm⁻². Carbon Black was also found to oxidize H₂DCF-DA in a cell-free system, whereas only ZnO nanoparticles significantly decreased LDH activity. A dramatic loss of immunoreactive IL-8 was observed for only one of the three TiO₂ particle types tested. Our results demonstrate that engineered nanoparticles interfere with classic cytotoxicity assays in a highly concentration-, particle- and assay-specific manner. These findings strongly suggest that each in vitro test system has to be evaluated for each single nanoparticle type to accurately assess the nanoparticle toxicity.

  9. Inhaled Diesel Emissions Generated with Cerium Oxide Nanoparticle Fuel Additive Induce Adverse Pulmonary and Systemic Effects

    PubMed Central

    Snow, Samantha J.; McGee, John; Miller, Desinia B.; Bass, Virginia; Schladweiler, Mette C.; Thomas, Ronald F.; Krantz, Todd; King, Charly; Ledbetter, Allen D.; Richards, Judy; Weinstein, Jason P.; Conner, Teri; Willis, Robert; Linak, William P.; Nash, David; Wood, Charles E.; Elmore, Susan A.; Morrison, James P.; Johnson, Crystal L.; Gilmour, Matthew Ian; Kodavanti, Urmila P.

    2014-01-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe. PMID:25239632

  10. Inhaled diesel emissions generated with cerium oxide nanoparticle fuel additive induce adverse pulmonary and systemic effects.

    PubMed

    Snow, Samantha J; McGee, John; Miller, Desinia B; Bass, Virginia; Schladweiler, Mette C; Thomas, Ronald F; Krantz, Todd; King, Charly; Ledbetter, Allen D; Richards, Judy; Weinstein, Jason P; Conner, Teri; Willis, Robert; Linak, William P; Nash, David; Wood, Charles E; Elmore, Susan A; Morrison, James P; Johnson, Crystal L; Gilmour, Matthew Ian; Kodavanti, Urmila P

    2014-12-01

    Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe.

  11. Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.

    PubMed

    Lee, Jinsoo; Yu, Wook-Joon; Song, Jeongah; Sung, Changhyun; Jeong, Eun Ju; Han, Ji-Seok; Kim, Pilje; Jo, Eunhye; Eom, Ikchun; Kim, Hyun-Mi; Kwon, Jung-Taek; Choi, Kyunghee; Choi, Jonghye; Kim, Heyjin; Lee, Handule; Park, Juyoung; Jin, Seon Mi; Park, Kwangsik

    2016-12-01

    Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.

  12. Toxicity of silver and gold nanoparticles on marine microalgae.

    PubMed

    Moreno-Garrido, Ignacio; Pérez, Sara; Blasco, Julián

    2015-10-01

    The increased use of nanomaterials in several novel industrial applications during the last decade has led to a rise in concerns about the potential toxic effects of released engineered nanoparticles (NPs) into the environment, as their potential toxicity to aquatic organisms is just beginning to be recognised. Toxicity of metallic nanoparticles to aquatic organisms, including microalgae, seems to be related to their physical and chemical properties, as well as their behaviour in the aquatic media where processes of dissolution, aggregation and agglomeration can occur. Although the production of these particles has increased considerably in recent years, data on their toxicity on microalgae, especially those belonging to marine or estuarine environments remain scarce and scattered. The literature shows a wide variation of results on toxicity, mainly due to the different methodology used in bioassays involving microalgae. These can range for up to EC50 data, in the case of AgNPs, representing five orders of magnitude. The importance of initial cellular density is also addressed in the text, as well as the need for keeping test conditions as close as possible to environmental conditions, in order to increase their environmental relevance. This review focuses on the fate and toxicity of silver, gold, and gold-silver alloy nanoparticles on microalgae, as key organisms in aquatic ecosystems. It is prompted by their increased production and use, and taking into account that oceans and estuaries are the final sink for those NPs. The design of bioassays and further research in the field of microalgae nanoecotoxicology is discussed, with a brief survey on newly developed technology of green (algae mediated) production of Ag, Au and Ag-Au bimetallic NPs, as well as some final considerations about future research on this field. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Species-specific toxicity of ceria nanoparticles to Lactuca plants.

    PubMed

    Zhang, Peng; Ma, Yuhui; Zhang, Zhiyong; He, Xiao; Li, Yuanyuan; Zhang, Jing; Zheng, Lirong; Zhao, Yuliang

    2015-02-01

    Species-specific differences in the toxicity of manufactured nanoparticles (MNPs) have been reported, but the underlying mechanisms are unknown. We previously found that CeO2 NPs inhibited root elongation of head lettuce, whereas no toxic effect was observed on other plants (such as wheat, cucumber and radish). In this study, interactions between Lactuca plants and three types of CeO2 NPs (lab-synthesized 7 and 25 nm CeO2 NPs, and a commercial CeO2 NPs) were investigated. It was found that CeO2 NPs were toxic to three kinds of Lactuca genus plants and different CeO2 NPs showed different degrees of toxicity. The results of X-ray absorption near edge fine structure indicate that small parts of CeO2 NPs were transformed from Ce(IV) to Ce(III) in roots of the plants that were treated with CeO2 NPs during the seed germination stage. But the high sensitivity of Lactuca plants to the released Ce(3+) ions caused the species-specific phytotoxicity of CeO2 NPs. Differences in sizes and zeta potentials among three types of CeO2 NPs resulted in their different degrees of biotransformation which accounted for the discrepancy in the toxicity to Lactuca plants. This study is among the few, and may indeed the first, that addresses the relation between the physicochemical properties of nanoparticles and its species-specific phytotoxicity.

  14. Size-dependent toxicity of silver nanoparticles to Glyptotendipes tokunagai

    PubMed Central

    Choi, Seona; Kim, Soyoun; Bae, Yeon-Jae; Park, June-Woo; Jung, Jinho

    2015-01-01

    Objectives This study aims to evaluate the size-dependent toxicity of spherical silver nanoparticles (Ag NPs) to an endemic benthic organism, Glyptotendipes tokunagai. Methods Ag nanoparticles of three nominal sizes (50, 100, and 150 nm) capped with polyvinyl pyrrolidone (PVP-Ag NPs) were used. Their physicochemical properties, acute toxicity (48 hours), and bioaccumulation were measured using third instar larvae of G. tokunagai. Results The aggregation and dissolution of PVP-Ag NPs increased with exposure time and concentration, respectively, particularly for 50 nm PVP-Ag NPs. However, the dissolved concentration of Ag ions was not significant compared with the median lethal concentration value for AgNO3 (3.51 mg/L). The acute toxicity of PVP-Ag NPs was highest for the smallest particles (50 nm), whereas bioaccumulation was greatest for the largest particles (150 nm). However, larger PVP-Ag NPs were absorbed and excreted rapidly, resulting in shorter stays in G. tokunagai than the smaller ones. Conclusions The size of PVP-Ag NPs significantly affects their acute toxicity to G. tokunagai. In particular, smaller PVP-Ag NPs have a higher solubility and stay longer in the body of G. tokunagai, resulting in higher toxicity than larger PVP-Ag NPs. PMID:26184045

  15. Central nervous system toxicity of metallic nanoparticles

    PubMed Central

    Feng, Xiaoli; Chen, Aijie; Zhang, Yanli; Wang, Jianfeng; Shao, Longquan; Wei, Limin

    2015-01-01

    Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed. PMID:26170667

  16. Silver nanoparticle toxicity in sea urchin Paracentrotus lividus.

    PubMed

    Siller, Lidija; Lemloh, Marie-Louise; Piticharoenphun, Sunthon; Mendis, Budhika G; Horrocks, Benjamin R; Brümmer, Franz; Medaković, Davorin

    2013-07-01

    Silver nanoparticles (AgNPS) are an important model system for studying potential environmental risks posed by the use of nanomaterials. So far there is no consensus as to whether toxicity is due to AgNPs themselves or Ag(+) ions leaching from their surfaces. In sea urchin Paracentrotus lividus, AgNPs cause dose dependent developmental defects such as delayed development, bodily asymmetry and shortened or irregular arms, as well as behavioural changes, particularly in swimming patterns, at concentration ∼0.3 mg/L AgNPs. It has been observed that AgNPs are more toxic than their equivalent Ag(+) ion dose.

  17. Nanoparticles in medicine: Current challenges facing inorganic nanoparticle toxicity assessments and standardizations.

    PubMed

    Hofmann-Amtenbrink, Margarethe; Grainger, David W; Hofmann, Heinrich

    2015-10-01

    Although nanoparticles research is ongoing since more than 30years, the development of methods and standard protocols required for their safety and efficacy testing for human use is still in development. The review covers questions on toxicity, safety, risk and legal issues over the lifecycle of inorganic nanoparticles for medical applications. The following topics were covered: (i) In vitro tests may give only a very first indication of possible toxicity as in the actual methods interactions at systemic level are mainly neglected; (ii) the science-driven and the regulation-driven approaches do not really fit for decisive strategies whether or not a nanoparticle should be further developed and may receive a kind of "safety label". (iii) Cost and time of development are the limiting factors for the drug pipeline. Knowing which property of a nanoparticle makes it toxic it may be feasible to re-engineer the particle for higher safety (safety by design). Testing the safety and efficacy of nanoparticles for human use is still in need of standardization. In this concise review, the author described and discussed the current unresolved issues over the application of inorganic nanoparticles for medical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Pulmonary drug delivery: a role for polymeric nanoparticles?

    PubMed

    d'Angelo, Ivana; Conte, Claudia; Miro, Agnese; Quaglia, Fabiana; Ungaro, Francesca

    2015-01-01

    Pulmonary drug delivery represents the best way of treating lung diseases, since it allows direct delivery of the drug to the site of action, with few systemic effects. Meanwhile, the lungs may be used as a portal of entry to the body, allowing systemic delivery of drugs via the airway surfaces into the bloodstream. In both cases, the therapeutic effect of the inhaled drug can be optimized by embedding it in appropriately engineered inhalable carriers, which can protect the drug against lung defense mechanisms and promote drug transport across the extracellular and cellular barriers. To this purpose, the attention has been very recently focused on polymeric nanoparticles (NPs). The aim of this review is to offer an overview on the recent advances in NPs for pulmonary drug delivery. After a description of the main challenges encountered in developing novel inhaled products, the design rules to engineer polymeric NPs for inhalation, and in so doing to overcome barriers imposed by the lungs anatomy and physiology, are described. Then, the state-of-art on inhalable biocompatible polymeric NPs based on enzymatically-degradable natural polymers and biodegradable poly(ester)s is presented, with a special focus on NP-based dry powders for inhalation. Finally, the in vitro/in vivo models useful to address the never-ending toxicological debate related to the use of NPs for inhalation are described.

  19. Silver nanoparticle toxicity in Drosophila: size does matter.

    PubMed

    Gorth, Deborah J; Rand, David M; Webster, Thomas J

    2011-01-01

    Consumer nanotechnology is a growing industry. Silver nanoparticles are the most common nanomaterial added to commercially available products, so understanding the influence that size has on toxicity is integral to the safe use of these new products. This study examined the influence of silver particle size on Drosophila egg development by comparing the toxicity of both nanoscale and conventional-sized silver particles. The toxicity assays were conducted by exposing Drosophila eggs to particle concentrations ranging from 10 ppm to 100 ppm of silver. Size, chemistry, and agglomeration of the silver particles were evaluated using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering. This analysis confirmed individual silver particle sizes in the ranges of 20-30 nm, 100 nm, and 500-1200 nm, with similar chemistry. Dynamic light scattering and transmission electron microscope data also indicated agglomeration in water, with the transmission electron microscopic images showing individual particles in the correct size range, but the dynamic light scattering z-average sizes of the silver nanoparticles were 782 ± 379 nm for the 20-30 nm silver nanoparticles, 693 ± 114 nm for the 100 nm silver nanoparticles, and 508 ± 32 nm for the 500-1200 nm silver particles. Most importantly, here we show significantly more Drosophila egg toxicity when exposed to larger, nonnanometer silver particles. Upon exposure to silver nanoparticles sized 20-30 nm, Drosophila eggs did not exhibit a statistically significant (P < 0.05) decrease in their likelihood to pupate, but eggs exposed to larger silver particles (500-1200 nm) were 91% ± 18% less likely to pupate. Exposure to silver nanoparticles reduced the percentage of pupae able to emerge as adults. At 10 ppm of silver particle exposure, only 57% ± 48% of the pupae exposed to 20-30 nm silver particles became adults, whereas 89% ± 25% of the control group became adults, and 94% ± 52% and 91

  20. Silver nanoparticle toxicity in Drosophila: size does matter

    PubMed Central

    Gorth, Deborah J; Rand, David M; Webster, Thomas J

    2011-01-01

    Background: Consumer nanotechnology is a growing industry. Silver nanoparticles are the most common nanomaterial added to commercially available products, so understanding the influence that size has on toxicity is integral to the safe use of these new products. This study examined the influence of silver particle size on Drosophila egg development by comparing the toxicity of both nanoscale and conventional-sized silver particles. Methods: The toxicity assays were conducted by exposing Drosophila eggs to particle concentrations ranging from 10 ppm to 100 ppm of silver. Size, chemistry, and agglomeration of the silver particles were evaluated using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering. Results: This analysis confirmed individual silver particle sizes in the ranges of 20–30 nm, 100 nm, and 500–1200 nm, with similar chemistry. Dynamic light scattering and transmission electron microscope data also indicated agglomeration in water, with the transmission electron microscopic images showing individual particles in the correct size range, but the dynamic light scattering z-average sizes of the silver nanoparticles were 782 ± 379 nm for the 20–30 nm silver nanoparticles, 693 ± 114 nm for the 100 nm silver nanoparticles, and 508 ± 32 nm for the 500–1200 nm silver particles. Most importantly, here we show significantly more Drosophila egg toxicity when exposed to larger, nonnanometer silver particles. Upon exposure to silver nanoparticles sized 20–30 nm, Drosophila eggs did not exhibit a statistically significant (P < 0.05) decrease in their likelihood to pupate, but eggs exposed to larger silver particles (500–1200 nm) were 91% ± 18% less likely to pupate. Exposure to silver nanoparticles reduced the percentage of pupae able to emerge as adults. At 10 ppm of silver particle exposure, only 57% ± 48% of the pupae exposed to 20–30 nm silver particles became adults, whereas 89% ± 25% of the control

  1. ECMO for pulmonary rescue in an adult with amiodarone-induced toxicity.

    PubMed

    Benassi, Filippo; Molardi, Alberto; Righi, Elena; Santangelo, Rosaria; Meli, Marco

    2015-05-01

    Amiodarone is a highly effective antiarrhythmic agent. Unfortunately amiodarone-induced pulmonary toxicity is described for medium-long term therapy. We describe a case of a 65-year-old man admitted to our department for breathlessness and with a history of recurrent episodes of atrial fibrillation for which he had been receiving amiodarone (200 mg/day) since 2008. Despite diuretic therapy, along with aspirin, statins and antibiotics the patient continued to complain of severe dyspnea and had a moderate fever. Thus, diagnostic hypotheses different from acute cardiac failure were considered, in particular non-cardiogenic causes of pulmonary infiltrates. Following suspicion of amiodarone-induced pulmonary toxicity, the drug was discontinued and corticosteroid therapy was initiated. Due to the deterioration of the clinical picture, we proceeded to intubation. After few hours from intubation we were forced to institute a veno-venous extracorporeal membrane oxygenation due to the worsening of pulmonary function. The patient's clinical condition improved which allowed us to remove the ECMO after 15 days of treatment. Indications for use of ECMO have expanded considerably. To our knowledge this is the first successful, reported article of a veno-venous ECMO used to treat amiodarone-induced toxicity in an adult. In patients with severe but potentially reversible pulmonary toxicity caused by amiodarone, extracorporeal life support can maintain pulmonary function and vital organ perfusion at the expense of low morbidity, while allowing time for drug clearance.

  2. Nanoparticles: Their potential toxicity, waste and environmental management

    SciTech Connect

    Bystrzejewska-Piotrowska, Grazyna Golimowski, Jerzy; Urban, Pawel L.

    2009-09-15

    This literature review discusses specific issues related to handling of waste containing nanomaterials. The aims are (1) to highlight problems related to uncontrolled release of nanoparticles to the environment through waste disposal, and (2) to introduce the topics of nanowaste and nanotoxicology to the waste management community. Many nanoparticles used by industry contain heavy metals, thus toxicity and bioaccumulation of heavy metals contained in nanoparticles may become important environmental issues. Although bioavailability of heavy metals contained in nanoparticles can be lower than those present in soluble form, the toxicity resulting from their intrinsic nature (e.g. their size, shape or density) may be significant. An approach to the treatment of nanowaste requires understanding of all its properties - not only chemical, but also physical and biological. Progress in nanowaste management also requires studies of the environmental impact of the new materials. The authors believe Amara's law is applicable to the impact of nanotechnologies, and society might overestimate the short-term effects of these technologies, while underestimating the long-term effects. It is necessary to have basic information from companies about the level and nature of nanomaterials produced or emitted and about the expectation of the life cycle time of nanoproducts as a basis to estimate the level of nanowaste in the future. Without knowing how companies plan to use and store recycled and nonrecycled nanomaterials, development of regulations is difficult. Tagging of nanoproducts is proposed as a means to facilitate separation and recovery of nanomaterials.

  3. Role of Physicochemical Properties in Nanoparticle Toxicity

    PubMed Central

    Shin, Seung Won; Song, In Hyun; Um, Soong Ho

    2015-01-01

    With the recent rapid growth of technological comprehension in nanoscience, researchers have aimed to adapt this knowledge to various research fields within engineering and applied science. Dramatic advances in nanomaterials marked a new epoch in biomedical engineering with the expectation that they would have huge contributions to healthcare. However, several questions regarding their safety and toxicity have arisen due to numerous novel properties. Here, recent studies of nanomaterial toxicology will be reviewed from several physiochemical perspectives. A variety of physiochemical properties such as size distribution, electrostatics, surface area, general morphology and aggregation may significantly affect physiological interactions between nanomaterials and target biological areas. Accordingly, it is very important to finely tune these properties in order to safely fulfill a bio-user’s purpose. PMID:28347068

  4. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension

    PubMed Central

    Phan, Carole; Seferian, Andrei; Huertas, Alice; Thuillet, Raphaël; Sattler, Caroline; Le Hiress, Morane; Tamura, Yuichi; Jutant, Etienne-Marie; Chaumais, Marie-Camille; Bouchet, Stéphane; Manéglier, Benjamin; Molimard, Mathieu; Rousselot, Philippe; Sitbon, Olivier; Simonneau, Gérald; Montani, David; Humbert, Marc

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease that can be induced by dasatinib, a dual Src and BCR-ABL tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). Today, key questions remain regarding the mechanisms involved in the long-term development of dasatinib-induced PAH. Here, we demonstrated that chronic dasatinib therapy causes pulmonary endothelial damage in humans and rodents. We found that dasatinib treatment attenuated hypoxic pulmonary vasoconstriction responses and increased susceptibility to experimental pulmonary hypertension (PH) in rats, but these effects were absent in rats treated with imatinib, another BCR-ABL tyrosine kinase inhibitor. Furthermore, dasatinib treatment induced pulmonary endothelial cell apoptosis in a dose-dependent manner, while imatinib did not. Dasatinib treatment mediated endothelial cell dysfunction via increased production of ROS that was independent of Src family kinases. Consistent with these findings, we observed elevations in markers of endothelial dysfunction and vascular damage in the serum of CML patients who were treated with dasatinib, compared with CML patients treated with imatinib. Taken together, our findings indicate that dasatinib causes pulmonary vascular damage, induction of ER stress, and mitochondrial ROS production, which leads to increased susceptibility to PH development. PMID:27482885

  5. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    PubMed Central

    Jacobsen, Nicklas Raun; Møller, Peter; Jensen, Keld Alstrup; Vogel, Ulla; Ladefoged, Ole; Loft, Steffen; Wallin, Håkan

    2009-01-01

    Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-). We studied the effects instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles. PMID:19138394

  6. Interaction of engineered nanoparticles with toxic and essential elements

    NASA Astrophysics Data System (ADS)

    Shumakova, A. A.; Gmoshinski, I. V.; Khotimchenko, S. A.; Trushina, E. N.

    2015-11-01

    Interaction of engineered nanoparticles with toxic and essential trace elements must be taken into consideration when estimating risks of NPs presented in the natural environment. The purpose of this work was to study the possible influence of silica, titanium dioxide (rutile) and fullerenol NPs on the toxicity of cadmium and to research the status of some trace elements and related indices of immune function in experiments on laboratory animals. Young male Wistar rats received cadmium salt (1 mg/kg b.w. Cd) orally for 28 days separately or in conjunction with the said kinds of NPs in different doses. A number of effects was observed as a result of combined action of Cd together with NPs, increase in bioaccumulation of this toxic trace element in the liver was most evident. The observed effects didn't show simple dose- dependence in respect to nanomaterials that should be taken into consideration when assessing the possible risks of joint action of nanoparticles and toxic elements existing in the environment in extremely low doses. Violation of microelement homeostasis caused by the combined action of Cd and NPs can have various adverse effects, such as inhibition of T-cell immunity induced by co-administration of Cd with rutile NPs.

  7. Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps.

    PubMed

    Bergin, Ingrid L; Witzmann, Frank A

    2013-01-01

    The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures.

  8. Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps

    PubMed Central

    Bergin, Ingrid L.; Witzmann, Frank A.

    2013-01-01

    The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures. PMID:24228068

  9. Toxicity and biodistribution of orally administered casein nanoparticles.

    PubMed

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  10. Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles

    PubMed Central

    Varshosaz, J.; Minaiyan, M.; Forghanian, M.

    2014-01-01

    The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1), iv solution of sCT (5 μg·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly. PMID:24701588

  11. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles.

    PubMed

    Bakand, Shahnaz; Hayes, Amanda

    2016-06-14

    Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood-brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

  12. Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles

    PubMed Central

    Bakand, Shahnaz; Hayes, Amanda

    2016-01-01

    Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood–brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture. PMID:27314324

  13. Biodistribution and toxicity of spherical aluminum oxide nanoparticles.

    PubMed

    Park, Eun-Jung; Lee, Gwang-Hee; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun; Cho, Myung-Haing; Kim, Dong-Wan

    2016-03-01

    With the rapid development of the nano-industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ-aluminum oxide hydroxide nanoparticles (γ-AlOHNPs), γ- and α-AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ-AlONPs, followed by the α-AlONPs and γ-AlOHNPs. In mice, γ-AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were observed in the blood of mice dosed with γ-AlOHNPs (10 mg kg(-1)). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS-2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The results showed γ-AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ-AlOHNPs, but not γ-AlONPs or α-AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ-AlOHNPs compared with γ-AlONPs and α-AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs.

  14. Chemical and physical characteristics of cellulose insulation particulates, and evaluation of potential acute pulmonary toxicity.

    PubMed

    Morgan, Daniel L; Su, Yin-Fong; Dill, Jeffrey A; Turnier, John C; Westerberg, R Bruce; Smith, Cynthia S

    2004-12-01

    During installation of cellulose insulation (CI) in new and older houses, significant quantities of airborne material are generated. This study characterized the chemical and physical properties, and potential acute pulmonary toxicity of CI. CI from four manufacturers was analyzed for inorganic additives and trace element impurities. Aerosols were generated and size fractionated. The number and size of fibrous and nonfibrous particles in the respirable fractions were determined. Respirable CI particulates were intratracheally instilled in rats (5 mg/kg) to evaluate potential pulmonary toxicity. CI samples were similar in composition with small differences due primarily to fire retardants. Less than 0.1% of CI was respirable and contained few fibers. Acute exposure to CI caused transient inflammation in the lungs and increased 4-hydroxyproline. Microscopic evaluation revealed a minimal to mild, non-progressing granulomatous pneumonitis. Low concentrations of respirable particles were found in CI aerosols. Particles consisted primarily of fire retardants with few fibers, and caused mild pulmonary toxicity in rats.

  15. Natural inorganic nanoparticles – formation, fate, and toxicity in the environment.

    EPA Science Inventory

    The synthesis, stability, and toxicity of engineered metal nanoparticles (ENPs) have been extensively studied during the past two decades. In contrast, research on the formation, fate and ecological effects of naturally occurring nanoparticles (NNPs) has become a focus of attent...

  16. Natural inorganic nanoparticles – formation, fate, and toxicity in the environment.

    EPA Science Inventory

    The synthesis, stability, and toxicity of engineered metal nanoparticles (ENPs) have been extensively studied during the past two decades. In contrast, research on the formation, fate and ecological effects of naturally occurring nanoparticles (NNPs) has become a focus of attent...

  17. Involvement of serotonin mechanism in methamphetamine-induced chronic pulmonary toxicity in rats.

    PubMed

    Wang, Y; Liu, M; Wang, H M; Bai, Y; Zhang, X H; Sun, Y X; Wang, H L

    2013-07-01

    The widest distribution and the highest uptake of methamphetamine (MA) in the human body occurred in the lungs, so that more and more attention should be paid to MA-induced pulmonary toxicity. MA induces the release of serotonin, which is an important mediator in pulmonary disease. The purpose of this study is to investigate the chronic response of the lung to MA and its potential mechanism in rats. Models of the chronic toxicity of MA were established with MA of 5 mg/kg and 10 mg/kg (intraperitoneally, twice per day) for 5 weeks. It was found that the high dose of MA induced rat pulmonary toxicity: crowded lung parenchyma, thickened septum, reduced number of alveolar sacs, inflammatory cell infiltration, and pulmonary arteriolar remodeling. In addition, MA resulted in a significant increase in the lung serotonin concentration and the marked upregulation of tryptophan hydroxylase 1, vesicular monoamine transporter 2, serotonin transporter, and downregulation of monoamine oxidase-A. These findings suggest that MA induced chronic pulmonary toxicity, which is concerned with the elevated serotonin concentration in rat lungs by increased synthesis, reduced metabolism, augmented accumulation, and promoted release of serotonin.

  18. Induction of pulmonary fibrosis by cerium oxide nanoparticles

    PubMed Central

    Ma, Jane Y.; Mercer, Robert R.; Barger, Mark; Schwegler-Berry, Diane; Scabilloni, James; Ma, Joseph K.; Castranova, Vincent

    2015-01-01

    Cerium compounds have been used as a diesel engine catalyst to lower the mass of diesel exhaust particles, but are emitted as cerium oxide (CeO2) nanoparticles in the diesel exhaust. In a previous study, we have demonstrated a wide range of CeO2-induced lung responses including sustained pulmonary inflammation and cellular signaling that could lead to pulmonary fibrosis. In this study, we investigated the fibrogenic responses induced by CeO2 in a rat model at various time points up to 84 days post-exposure. Male Sprague Dawley rats were exposed to CeO2 by a single intratracheal instillation. Alveolar macrophages (AM) were isolated by bronchial alveolar lavage (BAL). AM-mediated cellular responses, osteopontin (OPN) and transform growth factor (TGF)-β1 in the fibrotic process were investigated. The results showed that CeO2 exposure significantly increased fibrotic cytokine TGF-β1 and OPN production by AM above controls. The collagen degradation enzymes, matrix metalloproteinase (MMP)-2 and -9 and the tissue inhibitor of MMP were markedly increased in the BAL fluid at 1 day- and subsequently declined at 28 days after exposure, but remained much higher than the controls. CeO2 induced elevated phospholipids in BAL fluid and increased hydroxyproline content in lung tissue in a dose- and time-dependent manner. Immunohistochemical analysis showed MMP-2, MMP-9 and MMP-10 expressions in fibrotic regions. Morphological analysis noted increased collagen fibers in the lungs exposed to a single dose of 3.5 mg/kg CeO2 and euthanized at 28 days post-exposure. Collectively, our studies show that CeO2 induced fibrotic lung injury in rats, suggesting it may cause potential health effects. PMID:22613087

  19. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles.

    PubMed

    Larsen, Søren T; Jackson, Petra; Poulsen, Steen S; Levin, Marcus; Jensen, Keld A; Wallin, Håkan; Nielsen, Gunnar D; Koponen, Ismo K

    2016-11-01

    Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay.

  20. Airway irritation, inflammation, and toxicity in mice following inhalation of metal oxide nanoparticles

    PubMed Central

    Larsen, Søren T.; Jackson, Petra; Poulsen, Steen S.; Levin, Marcus; Jensen, Keld A.; Wallin, Håkan; Nielsen, Gunnar D.; Koponen, Ismo K.

    2016-01-01

    Abstract Metal oxide nanoparticles are used in a broad range of industrial processes and workers may be exposed to aerosols of the particles both during production and handling. Despite the widespread use of these particles, relatively few studies have been performed to investigate the toxicological effects in the airways following inhalation. In the present study, the acute (24 h) and persistent (13 weeks) effects in the airways after a single exposure to metal oxide nanoparticles were studied using a murine inhalation model. Mice were exposed 60 min to aerosols of either ZnO, TiO2, Al2O3 or CeO2 and the deposited doses in the upper and lower respiratory tracts were calculated. Endpoints were acute airway irritation, pulmonary inflammation based on analyses of bronchoalveolar lavage (BAL) cell composition, DNA damage assessed by the comet assay and pulmonary toxicity assessed by protein level in BAL fluid and histology. All studied particles reduced the tidal volume in a concentration-dependent manner accompanied with an increase in the respiratory rate. In addition, ZnO and TiO2 induced nasal irritation. BAL cell analyses revealed both neutrophilic and lymphocytic inflammation 24-h post-exposure to all particles except TiO2. The ranking of potency regarding induction of acute lung inflammation was Al2O3 = TiO2 < CeO2 ≪ ZnO. Exposure to CeO2 gave rise to a more persistent inflammation; both neutrophilic and lymphocytic inflammation was seen 13 weeks after exposure. As the only particles, ZnO caused a significant toxic effect in the airways while TiO2 gave rise to DNA-strand break as shown by the comet assay. PMID:27323801

  1. Toxicity effect of silver nanoparticles in brine shrimp Artemia.

    PubMed

    Arulvasu, Chinnasamy; Jennifer, Samou Michael; Prabhu, Durai; Chandhirasekar, Devakumar

    2014-01-01

    The present study revealed the toxic effect of silver nanoparticles (AgNPs) in Artemia nauplii and evaluated the mortality rate, hatching percentage, and genotoxic effect in Artemia nauplii/cysts. The AgNPs were commercially purchased and characterized using field emission scanning electron microscope with energy dispersive X-ray spectroscopy. Nanoparticles were spherical in nature and with size range of 30-40 nm. Artemia cysts were collected from salt pan, processed, and hatched in sea water. Artemia nauplii (II instar) were treated using silver nanoparticles of various nanomolar concentrations and LC50 value (10 nM) and mortality rate (24 and 48 hours) was evaluated. Hatching percentage of decapsulated cysts treated with AgNPs was examined. Aggregation of AgNPs in the gut region of nauplii was studied using phase contrast microscope and apoptotic cells in nauplii stained with acridine orange were observed using fluorescence microscope. DNA damage of single cell of nauplii was determined by comet assay. This study showed that as the concentration of AgNPs increased, the mortality rate, aggregation in gut region, apoptotic cells, and DNA damage increased in nauplii, whereas the percentage of hatching in Artemia cysts decreased. Thus this study revealed that the nanomolar concentrations of AgNPs have toxic effect on both Artemia nauplii and cysts.

  2. Toxicity Effect of Silver Nanoparticles in Brine Shrimp Artemia

    PubMed Central

    Arulvasu, Chinnasamy; Jennifer, Samou Michael; Prabhu, Durai; Chandhirasekar, Devakumar

    2014-01-01

    The present study revealed the toxic effect of silver nanoparticles (AgNPs) in Artemia nauplii and evaluated the mortality rate, hatching percentage, and genotoxic effect in Artemia nauplii/cysts. The AgNPs were commercially purchased and characterized using field emission scanning electron microscope with energy dispersive X-ray spectroscopy. Nanoparticles were spherical in nature and with size range of 30–40 nm. Artemia cysts were collected from salt pan, processed, and hatched in sea water. Artemia nauplii (II instar) were treated using silver nanoparticles of various nanomolar concentrations and LC50 value (10 nM) and mortality rate (24 and 48 hours) was evaluated. Hatching percentage of decapsulated cysts treated with AgNPs was examined. Aggregation of AgNPs in the gut region of nauplii was studied using phase contrast microscope and apoptotic cells in nauplii stained with acridine orange were observed using fluorescence microscope. DNA damage of single cell of nauplii was determined by comet assay. This study showed that as the concentration of AgNPs increased, the mortality rate, aggregation in gut region, apoptotic cells, and DNA damage increased in nauplii, whereas the percentage of hatching in Artemia cysts decreased. Thus this study revealed that the nanomolar concentrations of AgNPs have toxic effect on both Artemia nauplii and cysts. PMID:24516361

  3. Edible lipid nanoparticles: digestion, absorption, and potential toxicity.

    PubMed

    McClements, David Julian

    2013-10-01

    Food-grade nanoemulsions are being increasingly used in the food and beverage industry to encapsulate, protect, and deliver hydrophobic functional components, such as oil-soluble flavors, colors, preservatives, vitamins, and nutraceuticals. These nanoemulsions contain lipid nanoparticles (radius <100 nm) whose physicochemical characteristics (e.g., composition, dimensions, structure, charge, and physical state) can be controlled by selection of appropriate ingredients and fabrication techniques. Nanoemulsions have a number of potential advantages over conventional emulsions for applications within the food industry: higher stability to particle aggregation and gravitational separation; higher optical transparency; and, increased bioavailability of encapsulated components. On the other hand, there are also some risks associated with consumption of lipid nanoparticles that should be considered before they are widely utilized, such as their ability to alter the fate of bioactive components within the gastrointestinal tract and the potential toxicity of some of the components used in their fabrication (e.g., surfactants and organic solvents). This article provides an overview of the current status of the biological fate and potential toxicity of food-grade lipid nanoparticles suitable for utilization within the food and beverage industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Biophysical inhibition of synthetic vs. naturally-derived pulmonary surfactant preparations by polymeric nanoparticles.

    PubMed

    Beck-Broichsitter, Moritz; Ruppert, Clemens; Schmehl, Thomas; Günther, Andreas; Seeger, Werner

    2014-01-01

    Reasonable suspicion has accumulated that inhaled nano-scale particulate matter influences the biophysical function of the pulmonary surfactant system. Hence, it is evident to provide novel insights into the extent and mechanisms of nanoparticle-surfactant interactions in order to facilitate the fabrication of safe nanomedicines suitable for pulmonary applications. Negatively- and positively-charged poly(styrene) nanoparticles (diameters of ~100nm) served as model carriers. Nanoparticles were incubated with several synthetic and naturally-derived pulmonary surfactants to characterize the sensitivity of each preparation to biophysical inactivation. Changes in surface properties (i.e. adsorption and dynamic surface tension behavior) were monitored in a pulsating bubble surfactometer. Both nanoparticle formulations revealed a dose-dependent influence on the biophysical behavior of all investigated pulmonary surfactants. However, the surfactant sensitivity towards inhibition depended on both the carrier type, where negatively-charged nanoparticles showed increased inactivation potency compared to their positively-charged counterparts, and surfactant composition. Among the surfactants tested, synthetic mixtures (i.e. phospholipids, phospholipids supplemented with surfactant protein B, and Venticute®) were more susceptible to surface-activity inhibition as the more complex naturally-derived preparations (i.e. Alveofact® and large surfactant aggregates isolated from rabbit bronchoalveolar lavage fluid). Overall, nanoparticle characteristics and surfactant constitution both influence the extent of biophysical inhibition of pulmonary surfactants. © 2013.

  5. Deglycosylated bleomycin has the antitumor activity of bleomycin without pulmonary toxicity.

    PubMed

    Burgy, Olivier; Wettstein, Guillaume; Bellaye, Pierre S; Decologne, Nathalie; Racoeur, Cindy; Goirand, Françoise; Beltramo, Guillaume; Hernandez, Jean-François; Kenani, Abderraouf; Camus, Philippe; Bettaieb, Ali; Garrido, Carmen; Bonniaud, Philippe

    2016-02-17

    Bleomycin (BLM) is a potent anticancer drug used to treat different malignancies, mainly lymphomas, germ cell tumors, and melanomas. Unfortunately, BLM has major, dose-dependent, pulmonary toxicity that affects 20% of treated individuals. The most severe form of BLM-induced pulmonary toxicity is lung fibrosis. Deglyco-BLM is a molecule derived from BLM in which the sugar residue d-mannosyl-l-glucose disaccharide has been deleted. The objective of this study was to assess the anticancer activity and lung toxicity of deglyco-BLM. We compared the antitumor activity and pulmonary toxicity of intraperitoneally administrated deglyco-BLM and BLM in three rodent models. Pulmonary toxicity was examined in depth after intratracheal administration of both chemotherapeutic agents. The effect of both drugs was further studied in epithelial alveolar cells in vitro. We demonstrated in rodent cancer models, including a human Hodgkin's lymphoma xenograft and a syngeneic melanoma model, that intraperitoneal deglyco-BLM is as effective as BLM in inducing tumor regression. Whereas the antitumor effect of BLM was accompanied by a loss of body weight and the development of pulmonary toxicity, deglyco-BLM did not affect body weight and did not engender lung injury. Both molecules induced lung epithelial cell apoptosis after intratracheal administration, but deglyco-BLM lost the ability to induce caspase-1 activation and the production of ROS (reactive oxygen species), transforming growth factor-β1, and other profibrotic and inflammatory cytokines in the lungs of mice and in vitro. Deglyco-BLM should be considered for clinical testing as a less toxic alternative to BLM in cancer therapy. Copyright © 2016, American Association for the Advancement of Science.

  6. Polymeric nanoparticle-aptamer bioconjugates can diminish the toxicity of mercury in vivo.

    PubMed

    Hu, Xiangang; Tulsieram, Kurt Lomas; Zhou, Qixing; Mu, Li; Wen, Jianping

    2012-01-05

    Targeted delivery drugs by nanoparticles and aptamers is a hot issue; however, the application to ameliorate toxicity of toxicants is unknown, and the information about nanoparticle-aptamer toxicology and pharmacology is limited. In this work, nanoparticle-aptamer was synthesized and then its toxicological and pharmacological information was studied. Mercury was selected as a model toxicant and the antidote was entrapped by nanoparticle-aptamer. The nanoparticle-aptamer with a suitable size of 120 nm avoided aptamer biodegradation and achieved an effective release of antidote. Rats were orally administered mercury-contaminated rice and then nanoparticle-aptamer was intravenously injected. The nanoparticle-aptamer markedly reduced the quantity of mercury in both the brain and kidney, and enhanced the excretion of urinary mercury. Water Maze and Open Field tests showed that nanoparticle-aptamer ameliorated the neurotoxicity and improved the learning and memory of rats. The pharmacology of nanoparticle-aptamer involved slow antidote release, antidote-toxicant antagonism, enhancement of crucial enzymes activity and decreased lipid peroxidation. Toxicology of nanoparticle-aptamer was also studied by hematologic tests (creatinine, urea, red and white blood cell), and exhibited little toxicity. Nanoparticle-aptamer can diminish the toxicity of mercury in vivo with few adverse effects, and is a potential tool in reducing the hazards of toxicants to human health.

  7. Lipid nanoparticles protect from edelfosine toxicity in vivo.

    PubMed

    Lasa-Saracíbar, Beatriz; Aznar, María Ángela; Lana, Hugo; Aizpún, Ismael; Gil, Ana Gloria; Blanco-Prieto, Maria J

    2014-10-20

    Edelfosine, an alkyl-lysophospholipid antitumor drug with severe side-effects, has previously been encapsulated into lipid nanoparticles (LN) with the purpose of improving their toxicity profile. LN are made of lipids recognized as safe by the Food and Drug Administration (FDA) and, therefore, these systems are generally considered as nontoxic vehicles. However, toxicity studies regarding the use of LN as vehicles for drug administration are limited. In the present study, we investigated the in vivo toxicity of free edelfosine, and the protection conferred by LN. The free drug, non-loaded LN and edelfosine-loaded LN were orally administered to mice. Our results show that the oral administration of the free drug at 4 times higher than the therapeutic dose caused the death of the animals within 72h. Moreover, histopathology revealed gastrointestinal toxicity and an immunosuppressive effect. In contrast, LN showed a protective effect against edelfosine toxicity even at the higher dose and were completely safe. LN are, therefore, a safe vehicle for the administration of edelfosine by the oral route. The nanosystems developed could be further used for the administration of other drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Toxicity of Nanoparticles and an Overview of Current Experimental Models

    PubMed Central

    Bahadar, Haji; Maqbool, Faheem; Niaz, Kamal; Abdollahi, Mohammad

    2016-01-01

    Nanotechnology is a rapidly growing field having potential applications in many areas. Nanoparticles (NPs) have been studied for cell toxicity, immunotoxicity, and genotoxicity. Tetrazolium-based assays such as MTT, MTS, and WST-1 are used to determine cell viability. Cell inflammatory response induced by NPs is checked by measuring inflammatory biomarkers, such as IL-8, IL-6, and tumor necrosis factor, using ELISA. Lactate dehydrogenase (LDH) assay is used for cell membrane integrity. Different types of cell cultures, including cancer cell lines have been employed as in vitro toxicity models. It has been generally agreed that NPs interfere with either assay materials or with detection systems. So far, toxicity data generated by employing such models are conflicting and inconsistent. Therefore, on the basis of available experimental models, it may be difficult to judge and list some of the more valuable NPs as more toxic to biological systems and vice versa. Considering the potential applications of NPs in many fields and the growing apprehensions of FDA about the toxic potential of nanoproducts, it is the need of the hour to look for new internationally agreed free of bias toxicological models by focusing more on in vivo studies. PMID:26286636

  9. Toxicity of Nanoparticles and an Overview of Current Experimental Models.

    PubMed

    Bahadar, Haji; Maqbool, Faheem; Niaz, Kamal; Abdollahi, Mohammad

    2016-01-01

    Nanotechnology is a rapidly growing field having potential applications in many areas. Nanoparticles (NPs) have been studied for cell toxicity, immunotoxicity, and genotoxicity. Tetrazolium-based assays such as MTT, MTS, and WST-1 are used to determine cell viability. Cell inflammatory response induced by NPs is checked by measuring inflammatory biomarkers, such as IL-8, IL-6, and tumor necrosis factor, using ELISA. Lactate dehydrogenase (LDH) assay is used for cell membrane integrity. Different types of cell cultures, including cancer cell lines have been employed as in vitro toxicity models. It has been generally agreed that NPs interfere with either assay materials or with detection systems. So far, toxicity data generated by employing such models are conflicting and inconsistent. Therefore, on the basis of available experimental models, it may be difficult to judge and list some of the more valuable NPs as more toxic to biological systems and vice versa. Considering the potential applications of NPs in many fields and the growing apprehensions of FDA about the toxic potential of nanoproducts, it is the need of the hour to look for new internationally agreed free of bias toxicological models by focusing more on in vivo studies.

  10. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

    PubMed Central

    2012-01-01

    , but the polymer with a ratio of 75:25 had a continuous and longer release profile. Cytotoxicity studies showed that nanoparticles do not affect cell growth and were not toxic to cells. Conclusion In summary, α1AT-loaded nanoparticles may be considered as a novel formulation for efficient treatment of many pulmonary diseases. PMID:22607686

  11. Silver nanoparticles: therapeutical uses, toxicity, and safety issues.

    PubMed

    dos Santos, Carolina Alves; Seckler, Marcelo Martins; Ingle, Avinash P; Gupta, Indarchand; Galdiero, Stefania; Galdiero, Massimiliano; Gade, Aniket; Rai, Mahendra

    2014-07-01

    The promises of nanotechnology have been realized to deliver the greatest scientific and technological advances in several areas. The biocidal activity of Metal nanoparticles in general and silver nanoparticles (AgNPs) depends on several morphological and physicochemical characteristics of the particles. Many of the interactions of the AgNPs with the human body are still poorly understood; consequently, the most desirable characteristics for the AgNPs are not yet well established. Therefore, the development of nanoparticles with well-controlled morphological and physicochemical features for application in human body is still an active area of interdisciplinary research. Effects of the development of technology of nanostructured compounds seem to be so large and comprehensive that probably it will impact on all fields of science and technology. However, mechanisms of safety control in application, utilization, responsiveness, and disposal accumulation still need to be further studied in-depth to ensure that the advances provided by nanotechnology are real and liable to provide solid and consistent progress. This review aims to discuss AgNPs applied in biomedicine and as promising field for insertion and development of new compounds related to medical and pharmacy technology. The review also addresses drug delivery, toxicity issues, and the safety rules concerning biomedical applications of silver nanoparticles. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  12. Toxicity of Calcium Hydroxide Nanoparticles on Murine Fibroblast Cell Line

    PubMed Central

    Dianat, Omid; Azadnia, Sina; Mozayeni, Mohammad Ali

    2015-01-01

    Introduction: One of the major contributing factors, which may cause failure of endodontic treatment, is the presence of residual microorganisms in the root canal system. For years, most dentists have been using calcium hydroxide (CH) as the intracanal medicament between treatment sessions to eliminate remnant microorganisms. Reducing the size of CH particles into nanoparticles enhances the penetration of this medicament into dentinal tubules and increases their antimicrobial efficacy. This in vitro study aimed to compare the cytotoxicity of CH nanoparticles and conventional CH on fibroblast cell line using the Mosmann’s Tetrazolium Toxicity (MTT) assay. Methods and Materials: This study was conducted on L929 murine fibroblast cell line by cell culture and evaluation of the direct effect of materials on the cultured cells. Materials were evaluated in two groups of 10 samples each at 24, 48 and 72 h. At each time point, 10 samples along with 5 positive and 5 negative controls were evaluated. The samples were transferred into tubes and exposed to fibroblast cells. The viability of cells was then evaluated. The Two-way ANOVA was used for statistical analysis and the level of significance was set at 0.05. Results: Cytotoxicity of both materials decreased over time and for conventional CH was lower than that of nanoparticles. However, this difference was not statistically significant (P>0.05). Conclusion: The cytotoxicity of CH nanoparticles was similar to that of conventional CH. PMID:25598810

  13. A Review on the Respiratory System Toxicity of Carbon Nanoparticles.

    PubMed

    Pacurari, Maricica; Lowe, Kristine; Tchounwou, Paul B; Kafoury, Ramzi

    2016-03-15

    The respiratory system represents the main gateway for nanoparticles' entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles' interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products.

  14. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

    PubMed

    Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

    2013-01-01

    Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

  15. Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION)

    PubMed Central

    Singh, Neenu; Jenkins, Gareth J.S.; Asadi, Romisa; Doak, Shareen H.

    2010-01-01

    Superparamagnetic iron oxide nanoparticles (SPION) are being widely used for various biomedical applications, for example, magnetic resonance imaging, targeted delivery of drugs or genes, and in hyperthermia. Although, the potential benefits of SPION are considerable, there is a distinct need to identify any potential cellular damage associated with these nanoparticles. Besides focussing on cytotoxicity, the most commonly used determinant of toxicity as a result of exposure to SPION, this review also mentions the importance of studying the subtle cellular alterations in the form of DNA damage and oxidative stress. We review current studies and discuss how SPION, with or without different surface coating, may cause cellular perturbations including modulation of actin cytoskeleton, alteration in gene expression profiles, disturbance in iron homeostasis and altered cellular responses such as activation of signalling pathways and impairment of cell cycle regulation. The importance of protein-SPION interaction and various safety considerations relating to SPION exposure are also addressed. PMID:22110864

  16. Influence of silver nanoparticles on metabolism and toxicity of moulds.

    PubMed

    Pietrzak, Katarzyna; Twarużek, Magdalena; Czyżowska, Agata; Kosicki, Robert; Gutarowska, Beata

    2015-01-01

    The unique antimicrobial features of silver nanoparticles (AgNPs) are commonly applied in innumerable products. The lack of published studies on the mechanisms of AgNPs action on fungi resulted in identification of the aim of this study, which was: the determination of the influence of AgNPs on the mould cytotoxicity for swine kidney cells (MTT test) and the production of selected mycotoxins, organic acids, extracellular enzymes by moulds. The conducted study had shown that silver nanoparticles can change the metabolism and toxicity of moulds. AgNPs decrease the mycotoxin production of Aspergillus sp. (81-96%) and reduce mould cytotoxicity (50-75%). AgNPs influence the organic acid production of A. niger and P. chrysogenum by decreasing their concentration (especially of the oxalic and citric acid). Also, a change in the extracellular enzyme profile of A. niger and P. chrysogenum was observed, however, the total enzymatic activity was increased.

  17. The immune toxicity of titanium dioxide on primary pulmonary alveolar macrophages relies on their surface area and crystal structure.

    PubMed

    Liu, Ran; Yin, Li-hong; Pu, Yue-pu; Li, Yun-hui; Zhang, Xiao-qiang; Liang, Ge-yu; Li, Xiao-bo; Zhang, Juan; Li, Yan-fen; Zhang, Xue-yan

    2010-12-01

    Surface properties are critical to assess effects of titanium dioxide (TiO2) primary nanoparticles on the immune function of pulmonary alveolar macrophage (PAMs). In this study the immune toxicity of TiO2 primary nanoparticles on PAMs relies on their surface area and crystal structure were determined. The primary PAMs of rats exposed to different sizes and crystal structure of TiO2 particles at different dosages for 24 hrs were evaluated for cytokines, phagocytosis, chemotaxis and surface molecules expression. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) level of PAMs significantly increased when exposed to TiO2 primary particles and there were significant association with the exposure total surface area and crystal structure of TiO2 particles in the former. TiO2 particles showed significant inhibiting effects on phagocytotic ability, chemotactic ability, Fc receptors and MHC-II molecular expression of macrophages compared with control. Exposure dosage and crystal structure of TiO2 particles play effects on phagocytotic ability and chemotactic ability of PAMs. These results suggested that TiO2 nanoparticles could induce the release of inflammatory mediators, initiate the inflammation development and inhibit the immune function of PAMs associated with non-specific immunity and specific immunity relies on surface area and crystal structure. NO activity might be a candidate marker indicating the TiO2 exposure burden and cell damage in PAMs.

  18. Porous mannitol carrier for pulmonary delivery of cyclosporine A nanoparticles.

    PubMed

    Leung, Sharon Shui Yee; Wong, Jennifer; Guerra, Heloisa Victorino; Samnick, Kevin; Prud'homme, Robert K; Chan, Hak-Kim

    2017-03-01

    This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a D-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported. Formulations stabilized by TPGS provided a much better dose uniformity, suggesting that TPGS is a better anchoring agent compared with lecithin. The effects of mannitol carrier density and CsA loading (4.9-27%) on aerosol performance and dissolution profiles were assessed. The fine particle fraction (FPF) increased from 44 to 63% as the mannitol concentration decreased from 1 to 5%. All formulations achieved full dissolution within an hour without significant influence from the mannitol content and CsA loading. The initial dissolution rates of the present formulations were almost double than that of the spray-dried counterpart, with 90% of the drug dissolved in 10 min. Overall, the CsA NPs were successfully incorporated into the porous mannitol which demonstrated good aerosol performance and enhanced dissolution profiles. These spray-freeze-drying (SFD) powders were stable after 2-year storage under desiccation at 20 ± 3°C.

  19. Inhalation of Carbon Black Nanoparticles Aggravates Pulmonary Inflammation in Mice

    PubMed Central

    Saputra, Devina; Yoon, Jin-ha; Park, Hyunju; Heo, Yongju; Yang, Hyoseon; Lee, Eun Ji; Lee, Sangjin; Song, Chang-Woo; Lee, Kyuhong

    2014-01-01

    An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel aerosolization process, and the mice were exposed to the aerosol for 4 hours. We found that CBNP inhalation exacerbated lung inflammation, as evidenced by histopathology analysis and by the expression levels of interleukin-6 protein, fibronectin, and interferon-γ mRNAs in lung tissues. Notably, fibronectin mRNA expression showed a statistically significant increase in expression after CBNP exposure. These data suggest that the concentration of CBNPs delivered (calculated to be 12.5 μg/m3) can aggravate lung inflammation in mice. Our results also suggest that the inhalation of ultrafine particles like PM 2.5 is an impactful environmental risk factor for humans, particularly in susceptible populations with predisposing lung conditions. PMID:25071917

  20. Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics.

    PubMed

    Warheit, David B; Webb, Thomas R; Colvin, Vicki L; Reed, Kenneth L; Sayes, Christie M

    2007-01-01

    Pulmonary toxicology studies in rats demonstrate that nanoparticles are more toxic than fine-sized particles of similar chemistry. This study, however, provides evidence to contradict this theory. The aims of the study were (1) to compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min-U-Sil quartz ( approximately 500 nm); the toxicity of synthetic 12 nm nanoquartz II particles versus (mined) Min-U-Sil ( approximately 500 nm) versus (synthetic) fine-quartz particles (300 nm); and (2) to evaluate the surface activities among the samples as they relate to toxicity. Well-characterized samples were tested for surface activity and hemolytic potential. In addition, groups of rats were instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various alpha-quartz particle types in phosphate-buffered saline solution and subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postexposure. Exposures to the various alpha-quartz particles produced differential degrees of pulmonary inflammation and cytotoxicity, which were not always consistent with particle size but correlated with surface activity, particularly hemolytic potential. Lung tissue evaluations of three of the quartz samples demonstrated "typical" quartz-related effects--dose-dependent lung inflammatory macrophage accumulation responses concomitant with early development of pulmonary fibrosis. The various alpha-quartz-related effects were similar qualitatively but with different potencies. The range of particle-related toxicities and histopathological effects in descending order were nanoscale quartz II = Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles. The results demonstrate that the pulmonary toxicities of alpha-quartz particles appear to correlate better with surface activity than particle size and surface area.

  1. Toxicity study of cerium oxide nanoparticles in human neuroblastoma cells.

    PubMed

    Kumari, Monika; Singh, Shailendra Pratap; Chinde, Srinivas; Rahman, Mohammed Fazlur; Mahboob, Mohammed; Grover, Paramjit

    2014-01-01

    The present study consisted of cytotoxic, genotoxic, and oxidative stress responses of human neuroblastoma cell line (IMR32) following exposure to different doses of cerium oxide nanoparticles (CeO2 NPs; nanoceria) and its microparticles (MPs) for 24 hours. Cytotoxicity was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays whereas genotoxicity was assessed using the cytokinesis-block micronucleus and comet assays. A battery of assays including lipid peroxidation, reactive oxygen species (ROS), hydrogen peroxide, reduced glutathione, nitric oxide, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, and glutathione S-transferase were performed to test the hypothesis that ROS was responsible for the toxicity of nanoceria. The results showed that nanosized CeO2 was more toxic than cerium oxide MPs. Hence, further study on safety evaluation of CeO2 NPs on other models is recommended.

  2. Methods for nanoparticle labeling of ricin and effect on toxicity

    NASA Astrophysics Data System (ADS)

    Wark, Alastair W.; Yu, Jun; Lindsay, Christopher D.; Nativo, Paola; Graham, Duncan

    2009-09-01

    The unique optical properties associated with nanostructured materials that support the excitation of surface plasmons offer many new opportunities for the enhanced optical investigation of biological materials that pose a security threat. In particular, ricin is considered a significant bioterrorism risk due to its high toxicity combined with its ready availability as a byproduct in castor oil production. Therefore, the development of optical techniques capable of rapid on-site toxin detection with high molecular specificity and sensitivity continues to be of significant importance. Furthermore, understanding of the ricin cell entry and intracellular pathways remains poor due to a lack of suitable bioanalytical techniques. Initial work aimed at simultaneously tackling both these issues is described where different approaches for the nanoparticle labeling of ricin are investigated along with changes in ricin toxicity associated with the labeling process.

  3. Pulmonary toxicity of cyclophosphamide: a 1-year study

    SciTech Connect

    Morse, C.C.; Sigler, C.; Lock, S.; Hakkinen, P.J.; Haschek, W.M.; Witschi, H.P.

    1985-01-01

    The development of cyclophosphamide-induced pulmonary lesions over a 1-year period was studied in mice. Male BALB/c mice received a single intraperitoneal injection of 100 mg/kg of cyclophosphamide. Within 3 weeks there were scattered foci of intraalveolar foamy macrophages. With time, these foci increased in size and, 1 year later, occupied large areas in all lung lobes. There was also diffuse interstitial fibrosis. Chemical determination done 3, 12, 24, and 52 weeks after cyclophosphamide showed that lungs of animals treated with cyclophosphamide had significantly more hydroxyproline per lung than controls. One year after cyclophosphamide pressure - volume curves measured in vivo were shifted down and to the right and total lung volumes were decreased. A single injection of cyclophosphamide produced an irreversible and progressive pulmonary lesion. 16 references, 5 figures, 3 tables.

  4. Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles after repeated oral administration to rats.

    PubMed

    Yun, Jun-Won; Kim, Seung-Hyun; You, Ji-Ran; Kim, Woo Ho; Jang, Ja-June; Min, Seung-Kee; Kim, Hee Chan; Chung, Doo Hyun; Jeong, Jayoung; Kang, Byeong-Cheol; Che, Jeong-Hwan

    2015-06-01

    Although silicon dioxide (SiO2), silver (Ag) and iron oxide (Fe2O3) nanoparticles are widely used in diverse applications from food to biomedicine, in vivo toxicities of these nanoparticles exposed via the oral route remain highly controversial. To examine the systemic toxicity of these nanoparticles, well-dispersed nanoparticles were orally administered to Sprague-Dawley rats daily over a 13-week period. Based on the results of an acute toxicity and a 14-day repeated toxicity study, 975.9, 1030.5 and 1000 mg kg(-1) were selected as the highest dose of the SiO2 , Ag and Fe2O3 nanoparticles, respectively, for the 13-week repeated oral toxicity study. The SiO2 and Fe2O3 nanoparticles did not induce dose-related changes in a number of parameters associated with the systemic toxicity up to 975.9 and 1000 mg kg(-1) , respectively, whereas the Ag nanoparticles resulted in increases in serum alkaline phosphatase and calcium as well as lymphocyte infiltration in liver and kidney, raising the possibility of liver and kidney toxicity induced by the Ag nanoparticles. Compared with the SiO2 and Fe2O3 nanoparticles showing no systemic distribution in all tissues tested, the Ag concentration in sampled blood and organs in the Ag nanoparticle-treated group significantly increased with a positive and/or dose-related trend, meaning that the systemic toxicity of the Ag nanoparticles, including liver and kidney toxicity, might be explained by extensive systemic distribution of Ag originating from the Ag nanoparticles. Our current results suggest that further study is required to identify that Ag detected outside the gastrointestinal tract were indeed a nanoparticle form or ionized form. Copyright © 2015 John Wiley & Sons, Ltd.

  5. COMPARATIVE TOXICITY OF DIFFERENT EMISSION PARTICLES IN MURINE PULMONARY EPITHELIAL CELLS AND MACROPHAGES

    EPA Science Inventory

    Comparative Toxicity of Different Emission Particles in Murine Pulmonary Epithelial Cells and Macrophages. T Stevens1, M Daniels2, P Singh2, M I Gilmour2. 1 UNC, Chapel Hill 27599 2Experimental Toxicology Division, NHEERL, RTP, NC 27711

    Epidemiological studies have shown ...

  6. COMPARATIVE TOXICITY OF DIFFERENT EMISSION PARTICLES IN MURINE PULMONARY EPITHELIAL CELLS AND MACROPHAGES

    EPA Science Inventory

    Comparative Toxicity of Different Emission Particles in Murine Pulmonary Epithelial Cells and Macrophages. T Stevens1, M Daniels2, P Singh2, M I Gilmour2. 1 UNC, Chapel Hill 27599 2Experimental Toxicology Division, NHEERL, RTP, NC 27711

    Epidemiological studies have shown ...

  7. Molecular dynamics simulation study of a pulmonary surfactant film interacting with a carbonaceous nanoparticle.

    PubMed

    Choe, Seungho; Chang, Rakwoo; Jeon, Jonggu; Violi, Angela

    2008-11-01

    This article reports an all-atom molecular dynamics simulation to study a model pulmonary surfactant film interacting with a carbonaceous nanoparticle. The pulmonary surfactant is modeled as a dipalmitoylphosphatidylcholine monolayer with a peptide consisting of the first 25 residues from surfactant protein B. The nanoparticle model with a chemical formula C188H53 was generated using a computational code for combustion conditions. The nanoparticle has a carbon cage structure reminiscent of the buckyballs with open ends. A series of molecular-scale structural and dynamical properties of the surfactant film in the absence and presence of nanoparticle are analyzed, including radial distribution functions, mean-square displacements of lipids and nanoparticle, chain tilt angle, and the surfactant protein B peptide helix tilt angle. The results show that the nanoparticle affects the structure and packing of the lipids and peptide in the film, and it appears that the nanoparticle and peptide repel each other. The ability of the nanoparticle to translocate the surfactant film is one of the most important predictions of this study. The potential of mean force for dragging the particle through the film provides such information. The reported potential of mean force suggests that the nanoparticle can easily penetrate the monolayer but further translocation to the water phase is energetically prohibitive. The implication is that nanoparticles can interact with the lung surfactant, as supported by recent experimental data by Bakshi et al.

  8. Compared in vivo toxicity in mice of lung delivered biodegradable and non-biodegradable nanoparticles.

    PubMed

    Aragao-Santiago, Letícia; Hillaireau, Hervé; Grabowski, Nadège; Mura, Simona; Nascimento, Thais L; Dufort, Sandrine; Coll, Jean-Luc; Tsapis, Nicolas; Fattal, Elias

    2016-01-01

    To design nanoparticle (NP)-based drug delivery systems for pulmonary administration, biodegradable materials are considered safe, but their potential toxicity is poorly explored. We here explore the lung toxicity in mice of biodegradable nanoparticles (NPs) and compare it to the toxicity of non-biodegradable ones. NP formulations of poly(d,l-lactide-co-glycolide) (PLGA) coated with chitosan (CS), poloxamer 188 (PF68) or poly(vinyl alcohol) (PVA), which renders 200 nm NPs of positive, negative or neutral surface charge respectively, were analyzed for their biodistribution by in vivo fluorescence imaging and their inflammatory potential after single lung nebulization in mice. After exposure, analysis of bronchoalveolar lavage (BAL) cell population, protein secretion and cytokine release as well as lung histology were carried out. The inflammatory response was compared to the one induced by non-biodegradable counterparts, namely, TiO2 of rutile and anatase crystal form and polystyrene (PS). PLGA NPs were mostly present in mice lungs, with little passage to other organs. An increase in neutrophil recruitment was observed in mice exposed to PS NPs 24 h after nebulization, which declined at 48 h. This result was supported by an increase in interleukin (IL)-6 and tumor necrosis factor α (TNFα) in BAL supernatant at 24 h. TiO2 anatase NPs were still present in lung cells 48 h after nebulization and induced the expression of pro-inflammatory cytokines and the recruitment of polymorphonuclear cells to BAL. In contrast, regardless of their surface charge, PLGA NPs did not induce significant changes in the inflammation markers analyzed. In conclusion, these results point out to a safe use of PLGA NPs regardless of their surface coating compared to non-biodegradable ones.

  9. Induction of pulmonary fibrosis by cerium oxide nanoparticles

    SciTech Connect

    Ma, Jane Y.; Mercer, Robert R.; Barger, Mark; Schwegler-Berry, Diane; Scabilloni, James; Ma, Joseph K.; Castranova, Vincent

    2012-08-01

    Cerium compounds have been used as a diesel engine catalyst to lower the mass of diesel exhaust particles, but are emitted as cerium oxide (CeO{sub 2}) nanoparticles in the diesel exhaust. In a previous study, we have demonstrated a wide range of CeO{sub 2}-induced lung responses including sustained pulmonary inflammation and cellular signaling that could lead to pulmonary fibrosis. In this study, we investigated the fibrogenic responses induced by CeO{sub 2} in a rat model at various time points up to 84 days post-exposure. Male Sprague Dawley rats were exposed to CeO{sub 2} by a single intratracheal instillation. Alveolar macrophages (AM) were isolated by bronchial alveolar lavage (BAL). AM-mediated cellular responses, osteopontin (OPN) and transform growth factor (TGF)-β1 in the fibrotic process were investigated. The results showed that CeO{sub 2} exposure significantly increased fibrotic cytokine TGF-β1 and OPN production by AM above controls. The collagen degradation enzymes, matrix metalloproteinase (MMP)-2 and -9 and the tissue inhibitor of MMP were markedly increased in the BAL fluid at 1 day- and subsequently declined at 28 days after exposure, but remained much higher than the controls. CeO{sub 2} induced elevated phospholipids in BAL fluid and increased hydroxyproline content in lung tissue in a dose- and time-dependent manner. Immunohistochemical analysis showed MMP-2, MMP-9 and MMP-10 expressions in fibrotic regions. Morphological analysis noted increased collagen fibers in the lungs exposed to a single dose of 3.5 mg/kg CeO{sub 2} and euthanized at 28 days post-exposure. Collectively, our studies show that CeO{sub 2} induced fibrotic lung injury in rats, suggesting it may cause potential health effects. -- Highlights: ► Cerium oxide exposure significantly affected the following parameters in the lung. ► Induced fibrotic cytokine OPN and TGF-β1 production and phospholipidosis. ► Caused imbalance of the MMP-9/ TIMP-1 ratio that favors fibrosis

  10. Comparative toxicity study of Ag, Au, and Ag-Au bimetallic nanoparticles on Daphnia magna.

    PubMed

    Li, Ting; Albee, Brian; Alemayehu, Matti; Diaz, Rocio; Ingham, Leigha; Kamal, Shawn; Rodriguez, Maritza; Bishnoi, Sandra Whaley

    2010-09-01

    A comparative assessment of the 48-h acute toxicity of aqueous nanoparticles synthesized using the same methodology, including Au, Ag, and Ag-Au bimetallic nanoparticles, was conducted to determine their ecological effect in freshwater environments through the use of Daphnia magna, using their mortality as a toxicological endpoint. D. magna are one of the standard organisms used for ecotoxicity studies due to their sensitivity to chemical toxicants. Particle suspensions used in toxicity testing were well-characterized through a combination of absorbance measurements, atomic force or electron microscopy, flame atomic absorption spectrometry, and dynamic light scattering to determine composition, aggregation state, and particle size. The toxicity of all nanoparticles tested was found to be dose and composition dependent. The concentration of Au nanoparticles that killed 50% of the test organisms (LC(50)) ranged from 65-75 mg/L. In addition, three different sized Ag nanoparticles (diameters = 36, 52, and 66 nm) were studied to analyze the toxicological effects of particle size on D. magna; however, it was found that toxicity was not a function of size and ranged from 3-4 μg/L for all three sets of Ag nanoparticles tested. This was possibly due to the large degree of aggregation when these nanoparticles were suspended in standard synthetic freshwater. Moreover, the LC(50) values for Ag-Au bimetallic nanoparticles were found to be between that of Ag and Au but much closer to that of Ag. The bimetallic particles containing 80% Ag and 20% Au were found to have a significantly lower toxicity to Daphnia (LC(50) of 15 μg/L) compared to Ag nanoparticles, while the toxicity of the nanoparticles containing 20% Ag and 80% Au was greater than expected at 12 μg/L. The comparison results confirm that Ag nanoparticles were much more toxic than Au nanoparticles, and that the introduction of gold into silver nanoparticles may lower their environmental impact by lowering the amount

  11. Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant polymer nanoparticles.

    PubMed

    Cochran, David B; Wattamwar, Paritosh P; Wydra, Robert; Hilt, J Zach; Anderson, Kimberly W; Eitel, Richard E; Dziubla, Thomas D

    2013-12-01

    The biomedical use of superparamagnetic iron oxide nanoparticles has been of continued interest in the literature and clinic. Their ability to be used as contrast agents for imaging and/or responsive agents for remote actuation makes them exciting materials for a wide range of clinical applications. Recently, however, concern has arisen regarding the potential health effects of these particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro models, with oxidative stress being implicated as playing a key role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here, we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems.

  12. Death by bleomycin pulmonary toxicity in ovarian dysgerminoma with pathologic complete response to chemotherapy. A case report.

    PubMed

    Calzas Rodríguez, Julia; Carmen Juarez Morales, María Del; Casero, Miguel Angel Racionero

    2016-01-01

    With cisplatin-based chemotherapy, most patients with ovarian dysgerminoma will survive long-term. Bleomycin is an important part of ovarian germ cell tumors (OGCT) treatment, and its dose-limiting toxicity is the development of pulmonary toxicity and it is increased in patients older than 40 years. We report the case of an elderly patient with an unresectable ovarian dysgerminoma who received neoadjuvant chemotherapy and who developed fatal bleomycin pulmonary toxicity (BPT) after surgery. A monitoring of pulmonary function is not routinely recommended for detecting BPT, although together with carefully assessment for symptoms or signs suggestive of pulmonary toxicity is the best way to reduce the risk of BPT. The frequency of pulmonary events in older patients makes us to think about the possibility of either reduce the dose of bleomycin or removing it from the BEP in ovarian GCT.

  13. In Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles

    EPA Science Inventory

    Nanomaterials (NMs) encompass a diversity of materials with unique physicochemical characteristics which raise concerns about their potential risk to human health. Rapid predictive testing methods are needed to characterize NMs health effects as well as to screen and prioritize N...

  14. In Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles

    EPA Science Inventory

    Nanomaterials (NMs) encompass a diversity of materials with unique physicochemical characteristics which raise concerns about their potential risk to human health. Rapid predictive testing methods are needed to characterize NMs health effects as well as to screen and prioritize N...

  15. Role of oxidative stress in thuringiensin-induced pulmonary toxicity

    SciTech Connect

    Tsai, S.-F. . E-mail: sftsai@tactri.gov.tw; Yang Chi; Liu, B.-L.; Hwang, J.-S.; Ho, S.-P. . E-mail: spho@dragon.nchu.edu.tw

    2006-10-15

    To understand the effect of thuringiensin on the lungs tissues, male Sprague-Dawley rats were administrated with thuringiensin by intratracheal instillation at doses 0.8, 1.6 and 3.2 mg/kg of body weight, respectively. The rats were sacrificed 4 h after treatment, and lungs were isolated and examined. Subsequently, an effective dose of 1.6 mg/kg was selected for the time course study (4, 8, 12, and 24 h). Intratracheal instillation of thuringiensin resulted in lung damage, as evidenced by increase in lung weight and decrease in alkaline phosphatase (10-54%), an enzyme localized primarily in pulmonary alveolar type II epithelial cells. Furthermore, the administration of thuringiensin caused increases in lipid peroxidation (21-105%), the indices of lung injury. In addition, the superoxide dismutase (SOD) and glutathione (GSH) activities of lung tissue extracts were measured to evaluate the effect of thuringiensin on antioxidant defense system. The SOD activity and GSH content in lung showed significant decreases in a dose-related manner with 11-21% and 15-37%, respectively. Those were further supported by the release of proinflammatory cytokines, as indicated by increases in IL-1{beta} (229-1017%) and TNF-{alpha} (234%) levels. Therefore, the results demonstrated that changes in the pulmonary oxidative-antioxidative status might play an important role in the thuringiensin-induced lung injury.

  16. Variable silver nanoparticle toxicity to Daphnia in boreal lakes.

    PubMed

    Conine, Andrea L; Rearick, Daniel C; Xenopoulos, Marguerite A; Frost, Paul C

    2017-09-06

    Variable sensitivity of organisms to silver nanoparticles (AgNPs) caused by changes in physico-chemical variables in aquatic ecosystems is receiving increasing attention. Variables such as dissolved organic carbon, pH, light, the presence of algae and bacteria, dissolved oxygen and different ions have all been studied individually, but it is still unclear how these variables in combination alter AgNP toxicity in natural ecosystems. Here we examined AgNP toxicity on survival of wild-caught Daphnia using AgNP suspensions placed in water from several different lakes at the IISD-Experimental Lakes Area, which span a gradient of water quality parameters. The partitioning of AgNPs between particulate and dissolved organic matter fractions was also assessed due to the potential for algal sequestration and detoxification of AgNPs. We found that toxicity varied between lakes with LC50 values ranging between 34 and 292μg AgL(-1). Time of year in terms of days since ice-off and carbon to nitrogen ratios of particulate matter were the major predictors of toxicity between ecosystems. Total dissolved phosphorus, dissolved organic carbon, and particulate carbon to phosphorus ratios also played minor roles in influencing survival of Daphnia between water types. We found variable partitioning of silver into the particulate fraction within lakes and no significant differences between lakes. Silver associated with particulate organic matter increased with increasing concentrations of AgNPs in the ecosystem. Overall, we found strong evidence that AgNP toxicity is highly context dependent in natural lake ecosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. An evaluation of acute toxicity of colloidal silver nanoparticles.

    PubMed

    Maneewattanapinyo, Pattwat; Banlunara, Wijit; Thammacharoen, Chuchaat; Ekgasit, Sanong; Kaewamatawong, Theerayuth

    2011-11-01

    Tests for acute oral toxicity, eye irritation, corrosion and dermal toxicity of colloidal silver nanoparticles (AgNPs) were conducted in laboratory animals following OECD guidelines. Oral administration of AgNPs at a limited dose of 5,000 mg/kg produced neither mortality nor acute toxic signs throughout the observation period. Percentage of body weight gain of the mice showed no significant difference between control and treatment groups. In the hematological analysis, there was no significant difference between mice treated with AgNPs and controls. Blood chemistry analysis also showed no differences in any of the parameter examined. There was neither any gross lesion nor histopathological change observed in various organs. The results indicated that the LD(50) of colloidal AgNPs is greater than 5,000 mg/kg body weight. In acute eye irritation and corrosion study, no mortality and toxic signs were observed when various doses of colloidal AgNPs were instilled in guinea pig eyes during 72 hr observation period. However, the instillation of AgNPs at 5,000 ppm produced transient eye irritation during early 24 hr observation time. No any gross abnormality was noted in the skins of the guinea pigs exposed to various doses of colloidal AgNPs. In addition, no significant AgNPs exposure relating to dermal tissue changes was observed microscopically. In summary, these findings of all toxicity tests in this study suggest that colloidal AgNPs could be relatively safe when administered to oral, eye and skin of the animal models for short periods of time.

  18. Toxicity of polymeric nanoparticles in vivo and in vitro

    NASA Astrophysics Data System (ADS)

    Voigt, Nadine; Henrich-Noack, Petra; Kockentiedt, Sarah; Hintz, Werner; Tomas, Jürgen; Sabel, Bernhard A.

    2014-06-01

    Polybutylcyanoacrylate nanoparticles (PBCA NPs) are candidates for a drug delivery system, which can cross the blood-brain barrier (BBB). Because little is known about their toxicity, we exposed cells to PBCA NPs in vitro and in vivo and monitored their life and death assays. PBCA NPs were fabricated with different surfactants according to the mini-emulsion technique. Viabilities of HeLa and HEK293 cells after NP incubation were quantified by analysing cellular metabolic activity (MTT-test). We then repetitively injected i.v. rhodamine-labelled PBCA NP variations into rats and monitored the survival and morphology of retrogradely labelled neurons by in vivo confocal neuroimaging (ICON) for five weeks. To test for carrier-efficacy and safety, PBCA NPs loaded with Kyotorphin were injected in rats, and a hot plate test was used to quantify analgesic effects. In vitro, we found dose-dependent cell death which was, however, only detectable at very high doses and mainly seen in the cultures incubated with NPs fabricated with the tensids SDS and Tween. However, the in vivo experiments did not show any NP-induced neuronal death, even with particles which were toxic at high dose in vitro, i.e. NPs with Tween and SDS. The increased pain threshold at the hot plate test demonstrated that PBCA NPs are able to cross the BBB and thus comprise a useful tool for drug delivery into the central nervous system (CNS). Our findings showing that different nanoparticle formulations are non-toxic have important implications for the value of NP engineering approaches in medicine.

  19. Toxicity of polymeric nanoparticles in vivo and in vitro

    PubMed Central

    Voigt, Nadine; Henrich-Noack, Petra; Kockentiedt, Sarah; Hintz, Werner; Tomas, Jürgen

    2015-01-01

    Polybutylcyanoacrylate nanoparticles (PBCA NPs) are candidates for a drug delivery system, which can cross the blood–brain barrier (BBB). Because little is known about their toxicity, we exposed cells to PBCA NPs in vitro and in vivo and monitored their life and death assays. PBCA NPs were fabricated with different surfactants according to the mini-emulsion technique. Viabilities of HeLa and HEK293 cells after NP incubation were quantified by analysing cellular metabolic activity (MTT-test). We then repetitively injected i.v. rhodamine-labelled PBCA NP variations into rats and monitored the survival and morphology of retrogradely labelled neurons by in vivo confocal neuroimaging (ICON) for five weeks. To test for carrier-efficacy and safety, PBCA NPs loaded with Kyotorphin were injected in rats, and a hot plate test was used to quantify analgesic effects. In vitro, we found dose-dependent cell death which was, however, only detectable at very high doses and mainly seen in the cultures incubated with NPs fabricated with the tensids SDS and Tween. However, the in vivo experiments did not show any NP-induced neuronal death, even with particles which were toxic at high dose in vitro, i.e. NPs with Tween and SDS. The increased pain threshold at the hot plate test demonstrated that PBCA NPs are able to cross the BBB and thus comprise a useful tool for drug delivery into the central nervous system (CNS). Our findings showing that different nanoparticle formulations are non-toxic have important implications for the value of NP engineering approaches in medicine. PMID:26420981

  20. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model

    PubMed Central

    Hu, Yu-Lan; Qi, Wang; Han, Feng; Shao, Jian-Zhong; Gao, Jian-Qing

    2011-01-01

    Background Although there are a number of reports regarding the toxicity evaluation of inorganic nanoparticles, knowledge on biodegradable nanomaterials, which have always been considered safe, is still limited. For example, the toxicity of chitosan nanoparticles, one of the most widely used drug/gene delivery vehicles, is largely unknown. In the present study, the zebrafish model was used for a safety evaluation of this nanocarrier. Methods Chitosan nanoparticles with two particle sizes were prepared by ionic cross-linking of chitosan with sodium tripolyphosphate. Chitosan nanoparticles of different concentrations were incubated with zebrafish embryos, and ZnO nanoparticles were used as the positive control. Results Embryo exposure to chitosan nanoparticles and ZnO nanoparticles resulted in a decreased hatching rate and increased mortality, which was concentration-dependent. Chitosan nanoparticles at a size of 200 nm caused malformations, including a bent spine, pericardial edema, and an opaque yolk in zebrafish embryos. Furthermore, embryos exposed to chitosan nanoparticles showed an increased rate of cell death, high expression of reactive oxygen species, as well as overexpression of heat shock protein 70, indicating that chitosan nanoparticles can cause physiological stress in zebrafish. The results also suggest that the toxicity of biodegradable nanocarriers such as chitosan nanoparticles must be addressed, especially considering the in vivo distribution of these nanoscaled particles. Conclusion Our results add new insights into the potential toxicity of nanoparticles produced by biodegradable materials, and may help us to understand better the nanotoxicity of drug delivery carriers. PMID:22267920

  1. Understanding the toxicity of aggregated zero valent copper nanoparticles against Escherichia coli.

    PubMed

    Rispoli, Fred; Angelov, Angel; Badia, Daniel; Kumar, Amit; Seal, Sudipta; Shah, Vishal

    2010-08-15

    Copper nanoparticles are used in wide variety of applications and in the current study we report the antimicrobial activity of these particles. Influence of pH, temperature, aeration rate, concentration of nanoparticles and concentration of bacteria on the toxicity of copper nanoparticles against Escherichia coli have been studied using a centroid mixture design of experiment. The linear and quadratic regression model shows that the toxicity of copper nanoparticles not only depends on the primary effect of the parameters tested (pH, temperature, aeration, concentration of E. coli and concentration of nanoparticles), but also on the interactive effect of these parameters.

  2. Pulmonary extraction of propranolol in normal and oxygen-toxic sheep

    SciTech Connect

    Howell, R.E.; Lanken, P.N.; Hansen-Flaschen, J.H.; Haselton, F.R.; Albelda, S.M.; Fishman, A.P.

    1989-07-01

    To help define the mechanisms involved in the handling of propranolol by normal and injured lungs, we studied the pulmonary extraction of (/sup 3/H)propranolol in 23 unanesthetized sheep. Extraction of propranolol by normal lungs during a single circulation was characterized by (1) subsequent back-diffusion and pulmonary retention of the drug, (2) no evidence of saturable uptake or binding, (3) no effect of isoproterenol or imipramine, and (4) no effect of increasing cardiac output by treadmill exercise. In lungs damaged by oxygen toxicity, (/sup 3/H)propranolol extraction decreased progressively to 63% of base line, paralleling progressive arterial hypoxemia and hypercapnia. In contrast, (/sup 14/C)serotonin extraction remained unchanged from base line. Our results suggest that in normal unanesthetized sheep, pulmonary extraction of propranolol occurs primarily by passive diffusion that is flow-limited. Also, lung injury induced by oxygen toxicity in sheep reduces the pulmonary extraction of propranolol. Indeed, in oxygen toxicity, the depressed extraction of propranolol is a more sensitive marker of lung injury than is serotonin extraction.

  3. In Vivo Toxicity of Intravenously Administered Silica and Silicon Nanoparticles

    PubMed Central

    Ivanov, Sergey; Zhuravsky, Sergey; Yukina, Galina; Tomson, Vladimir; Korolev, Dmitry; Galagudza, Michael

    2012-01-01

    Both silicon and silica nanoparticles (SiNPs and SiO2NPs, respectively) are currently considered to be promising carriers for targeted drug delivery. However, the available data on their in vivo toxicity are limited. The present study was aimed at investigation of SiNP and SiO2NP (mean diameter 10 and 13 nm, respectively) toxicity using both morphological and functional criteria. Hematological and biochemical parameters were assessed in Sprague-Dawley rats 5, 21 and 60 days after administration of NPs. Inner ear function was determined using otoacoustic emission testing at 21 and 60 days after infusion of NPs. Furthermore, the histological structure of liver, spleen and kidney samples was analyzed. Intravenous infusion of SiNPs or SiO2NPs (7 mg/kg) was not associated with significant changes in hemodynamic parameters. Hearing function remained unchanged over the entire observation period. Both inter- and intragroup changes in blood counts and biochemical markers were non-significant. Histological findings included the appearance of foreign body-type granulomas in the liver and spleen as well as microgranulation in the liver after administration of NPs. The number of granulomas was significantly lower after administration of SiNPs compared with SiO2NPs. In conclusion, both tested types of NPs are relatively biocompatible nanomaterials, at least when considering acute toxicity.

  4. Toxicity of copper oxide nanoparticle suspensions to aquatic biota.

    PubMed

    Manusadžianas, Levonas; Caillet, Celine; Fachetti, Louis; Gylytė, Brigita; Grigutytė, Reda; Jurkonienė, Sigita; Karitonas, Rolandas; Sadauskas, Kazys; Thomas, Fabien; Vitkus, Rimantas; Férard, Jean-François

    2012-01-01

    Toxicity effects induced by nanosuspensions of CuO (<50 nm; Sigma-Aldrich) on macrophytic algae cells of Nitellopsis obtusa (96-h median lethal concentration [LC50]), microphytic algae Chlorella (30-min median inhibitory concentration [IC50]), shrimp Thamnocephalus platyurus (24-h LC50), and rotifer Brachionus calyciflorus (24-h LC50) were investigated. No substantial differences between the effects of nonsonicated and sonicated nCuO suspensions were observed. The particle size distribution analysis accomplished by the laser diffraction technique at suspension concentration from 3 to 100 mg/L revealed rapid (within 5 min) reagglomeration of the particles after the sonication. The observed adverse effects on N. obtusa cells may be attributed to nanoparticles per se, but not to ionic Cu, because neither chemical analysis nor biological testing (algae survival in the supernatants of suspensions) confirmed the presence of cupric ions in toxic amounts. Contrary to ionic Cu form, nCuO delayed the initial phase of N. obtusa cell membrane depolarization. Lethality tests with rewash demonstrated that the least used 5-min exposure in 100 mg/L nCuO sonicated suspension induced 70% mortality in charophyte cells after 8 d, whereas the rewash after a short exposure to a noticeably toxic concentration of Cu(2+) prevented cell mortality. The obtained data suggested the possible influence of a thick charophyte cell wall on the dynamics of nanotoxicity effects.

  5. Toxicity of mycotoxins for the rat pulmonary macrophage in vitro.

    PubMed Central

    Sorenson, W G; Gerberick, G F; Lewis, D M; Castranova, V

    1986-01-01

    The presence of mycotoxins in grains is well documented. Workers in grain handling occupations are commonly exposed to grain dust aerosols. Work in our laboratory has shown that T-2 toxin is highly toxic to rat alveolar macrophages in vitro, causing loss of viability, release of radiolabeled chromium, inhibition of macromolecular synthesis, inhibition of phagocytosis, and inhibition of macrophage activation. Similarly, patulin caused a significant release of radiolabeled chromium, decrease in ATP levels, significant inhibition of protein and RNA synthesis, and inhibition of phagocytosis. The data show that both T-2 toxin and patulin are highly toxic to rat alveolar macrophages in vitro. The data further suggest that the presence of these mycotoxins in airborne respirable dust might present a hazard to exposed workers. PMID:2423320

  6. Toxicity of mycotoxins for the rat pulmonary macrophage in vitro

    SciTech Connect

    Sorenson, W.G.; Gerberick, G.F.; Lewis, D.M.; Castranova, V.

    1986-04-01

    The presence of mycotoxins in grains is well documented. Workers in grain handling occupations are commonly exposed to grain dust aerosols. Work in our laboratory has shown that T-2 toxin is highly toxic to rat alveolar macrophages in vitro, causing loss of viability, release of radiolabeled chromium, inhibition of macromolecular synthesis, inhibition of phagocytosis, and inhibition of macrophage activation. Similarly, patulin caused a significant release of radiolabeled chromium, decrease in ATP levels, significant inhibition of protein and RNA synthesis, and inhibition of phagocytosis. The data show that both T-2 toxin and patulin are highly toxic to rat alveolar macrophages in vitro. The data further suggest that the presence of these mycotoxins in airborne respirable dust might present a hazard to exposed workers.

  7. Acute fibrinous organising pneumonia: a manifestation of trimethoprim-sulfamethoxazole pulmonary toxicity.

    PubMed

    Jamous, Fady; Ayaz, Syed Zain; Choate, Jacquelyn

    2014-10-29

    A 50-year-old man was treated with trimethoprim-sulfamethoxazole (TMP-SMX) for acute arthritis of his right big toe. Within a few days, he developed dyspnoea, hypoxaemia and diffuse pulmonary infiltrates. Symptoms improved with discontinuation of the antibiotic but worsened again with its reintroduction. An open lung biopsy was performed. We describe the workup performed and the factors that pointed to a final diagnosis of TMP-SMX-related pulmonary toxicity in the form of acute fibrinous organising pneumonia. 2014 BMJ Publishing Group Ltd.

  8. Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

    PubMed Central

    Wang, Wen; Jin, Minghua; Du, Zhongjun; Li, Yanbo; Duan, Junchao; Yu, Yongbo; Sun, Zhiwei

    2013-01-01

    This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process. PMID:23593469

  9. Estimation of the toxicity of silver nanoparticles by using planarian flatworms.

    PubMed

    Kustov, Leonid; Tiras, Kharlampii; Al-Abed, Souhail; Golovina, Natalia; Ananyan, Mikhail

    2014-03-01

    The regeneration of planarian flatworms - specifically, changes to the area of the regeneration bud (blastema) after surgical dissection - was proposed for use as a robust tool for estimating the toxicity of silver nanoparticles. The use of Planaria species, due to their unique regenerative capacity, could result in a reduction in the use of more-traditional laboratory animals for toxicity testing. With our novel approach, silver nanoparticles were found to be moderately toxic to the planarian, Girardia tigrina. 2014 FRAME.

  10. Size-dependent study of pulmonary responses to nano-sized iron and copper oxide nanoparticles.

    PubMed

    Kumar, Rajiv; Nagesha, Dattatri K

    2013-01-01

    The application of nanotechnology in various fields has resulted in a tremendous increase in the synthesis of variety of engineered nanoparticles (NPs). These applications are possible only due to the small size and large surface area of the NPs which imparts them unique properties. Inorganic oxide NPs as iron and copper oxide NPs are widely used in several biomedical and synthetic applications. The beneficial aspects of these NPs are concurrently associated with several drastic and deleterious effects as well. Size of the NPs plays a critical role in systemic clearance from the body. Initial studies have confirmed inflammatory responses in mice associated with non-biodegradable oxide NPs. The associated oxidative stress varied from mild effects to reactive oxygen species generation which can potentiate DNA damage or even induced carcinogenesis. Copper oxide NPs, in particular, induced acute toxicity and inflict neutrophil infiltration. This chapter focuses on the applicability of various in vivo techniques for studying the effect of these NPs, especially on the pulmonary system. These in vivo techniques would certainly provide a better understanding and insight into the mechanistic pathways by which these NPs interact with various organ systems in human body.

  11. Transport and Toxicity of Silver Nanoparticles in HepaRG Cell Spheroids.

    PubMed

    Senyavina, N V; Gerasimenko, T N; Pulkova, N V; Maltseva, D V

    2016-04-01

    We studied the effects of silver nanoparticles (10 nm) on HepaRG cell spheroids simulating liver tissue. The mathematical model was proposed that describes nanoparticle diffusion in a spheroid consisting of 5000 cells depending on the external nanoparticle concentration. It was demonstrated that cells in the 3D model were less sensitive to the toxic effects of nanoparticles in comparison with 2D cultures. Impaired integrity of the cell membrane did not deteriorate cell viability (according to MTT test).

  12. Toxicity of nanoparticle surface coating agents: Structure-cytotoxicity relationship.

    PubMed

    Zhang, Ying; Li, Xiaoping; Yu, Hongtao

    2016-07-02

    Surface coating agents for metal nanoparticles, cationic alkyl ammonium bromides, and anionic alkyl sulfates were tested against human skin keratinocytes (HaCaT) and blood T lymphocytes (TIB-152). The surfactants of short chain (C8) are not cytotoxic, but as chain length increases, their cytotoxicity increases and levels off at C12 for cationic surfactants against both cell lines and for anionic surfactants against the TIB-152, but C14 for anionic surfactants against HaCaT. The cationic surfactants are more toxic than the anionic surfactants for HaCaT; while with similar cytotoxicity for TIB-152 cells. di- and tetra-Alkyl ammonium salts are more cytotoxic than the mono-substituted.

  13. Pulmonary toxicity of Mount St. Helens volcanic ash

    SciTech Connect

    Sanders, C.L.; Conklin, A.W.; Gelman, R.A.; Adee, R.R.; Rhoads, K.

    1982-02-01

    The effects of Mount St. Helens volcanic ash, a sandy loam soil, and quartz particles on the lung and mediastinal lymph nodes of Fischer rats were studied at time intervals of up to 109 days after in tratracheal instillation of 40 mg ash, soil, or quartz in a single dose or after multiple doses of ash instilled in seven consecutive weekly doses for a total deposition of 77 mg. Quartz caused early granuloma formation, later fibrosis was also seen in lymph nodes. Volcanic ash caused an ill-defined inflammatory reaction with a few rats showing granuloma formulation, a very limited linear fibrosis, and a moderate lipoproteinosis, and lymph nodes were enlarged with numerous microgranulomas but without reticulin and collagen formation. Pulmonary reactions to soil particles were less intense but similar to those in ash- exposed animals; lymph nodes were not enlarged. No significant clearance of ash was found at 3 months after instillation. Volcanic ash produced a simple pneumoconiosis similar to what has been described for animals and humans living for prolonged periods of time in dusty desert areas of the United States.

  14. A Review on the Respiratory System Toxicity of Carbon Nanoparticles

    PubMed Central

    Pacurari, Maricica; Lowe, Kristine; Tchounwou, Paul B.; Kafoury, Ramzi

    2016-01-01

    The respiratory system represents the main gateway for nanoparticles’ entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles’ interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products. PMID:26999172

  15. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    PubMed Central

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  16. Nanoparticle toxicity assessment using an in vitro 3-D kidney organoid culture model.

    PubMed

    Astashkina, Anna I; Jones, Clint F; Thiagarajan, Giridhar; Kurtzeborn, Kristen; Ghandehari, Hamid; Brooks, Benjamin D; Grainger, David W

    2014-08-01

    Nanocarriers and nanoparticles remain an intense pharmaceutical and medical imaging technology interest. Their entry into clinical use is hampered by the lack of reliable in vitro models that accurately predict in vivo toxicity. This study evaluates a 3-D kidney organoid proximal tubule culture to assess in vitro toxicity of the hydroxylated generation-5 PAMAM dendrimer (G5-OH) compared to previously published preclinical in vivo rodent nephrotoxicity data. 3-D kidney proximal tubule cultures were created using isolated murine proximal tubule fractions suspended in a biomedical grade hyaluronic acid-based hydrogel. Toxicity in these cultures to neutral G5-OH dendrimer nanoparticles and gold nanoparticles in vitro was assessed using clinical biomarker generation. Neutral PAMAM nanoparticle dendrimers elicit in vivo-relevant kidney biomarkers and cell viability in a 3-D kidney organoid culture that closely reflect toxicity markers reported in vivo in rodent nephrotoxicity models exposed to this same nanoparticle.

  17. Pulmonary toxicity of endotoxins: comparison of lipopolysaccharides from various bacterial species.

    PubMed Central

    Helander, I; Saxén, H; Salkinoja-Salonen, M; Rylander, R

    1982-01-01

    Lipopolysaccharides from three gram-negative bacteria isolated from bale cotton and piggery air were analyzed for their chemical composition, and their pulmonary toxicity for guinea pigs, lethal toxicity for mice, and pyrogenicity for rabbits were measured. Lipopolysaccharides from Enterobacter agglomerans and Citrobacter freundii had closely related chemical compositions; both were pyrogenic for rabbits and caused a dose-dependent influx of polymorphonuclear leukocytes into the airways of guinea pigs. The lethal toxicities of these lipopolysaccharides in mice were comparable to that of Salmonella typhimurium lipopolysaccharide, which was used as a reference. Lipopolysaccharide from Agrobacterium sp. was chemically different from those of E. agglomerans and C. freundii, did not induce any influx of polymorphonuclear leukocytes, and was only weakly toxic or pyrogenic. The low biological activity of the agrobacterial lipopolysaccharide may be due to its different chemical composition. PMID:7056574

  18. Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats.

    PubMed

    Schwotzer, Daniela; Ernst, Heinrich; Schaudien, Dirk; Kock, Heiko; Pohlmann, Gerhard; Dasenbrock, Clemens; Creutzenberg, Otto

    2017-07-12

    Nanomaterials like cerium oxide and barium sulfate are frequently processed in industrial and consumer products and exposure of humans and other organisms is likely. Generally less information is given on health effects and toxicity, especially regarding long-term exposure to low nanoparticle doses. Since inhalation is still the major route of uptake the present study focused on pulmonary effects of CeO2NM-212 (0.1, 0.3, 1.0, 3.0 mg/m(3)) and BaSO4NM-220 nanoparticles (50.0 mg/m(3)) in a 90-day exposure setup. To define particle-related effects and potential mechanisms of action, observations in histopathology, bronchoalveolar lavage and immunohistochemistry were linked to pulmonary deposition and clearance rates. This further allows evaluation of potential overload related effects. Lung burden values increased with increasing nanoparticle dose levels and ongoing exposure. At higher doses, cerium clearance was impaired, suggesting lung overload. Barium elimination was extremely rapid and without any signs of overload. Bronchoalveolar lavage fluid analysis and histopathology revealed lung tissue inflammation with increasing severity and post-exposure persistency for CeO2. Also, marker levels for genotoxicity and cell proliferation were significantly increased. BaSO4 showed less inflammation or persistency of effects and particularly affected the nasal cavity. CeO2 nanoparticles penetrate the alveolar space and affect the respiratory tract after inhalation mainly in terms of inflammation. Effects at low dose levels and post-exposure persistency suggest potential long-term effects and a notable relevance for human health. The generated data might be useful to improve nanoparticle risk assessment and threshold value generation. Mechanistic investigations at conditions of non-overload and absent inflammation should be further investigated in future studies.

  19. Pulmonary toxicity of components of textile paint linked to the Ardystil syndrome: intratracheal administration in hamsters.

    PubMed Central

    Clottens, F L; Verbeken, E K; Demedts, M; Nemery, B

    1997-01-01

    OBJECTIVES: It was hypothesised from an epidemiological investigation that a formula change from Acramin FWR (a polyurea) to Acramin FWN (a polyamide-amine) had led to severe pulmonary disease in textile printing sprayers in SPAIN AND ALGERIA. To verify this, the pulmonary toxicity of the components of the paint systems involved was assessed in experimental animals. METHODS: Individual components and relevant mixtures, diluted in phosphate buttered saline, were given by intratracheal instillation of 2 ml/kg to hamsters. Pulmonary toxicity was assessed on days 3, 7, 14, 28, and 92 after a single intratracheal instillation, by histology and by measuring wet and dry lung weight, protein concentration, the activities of lactate dehydrogenase, alkaline phosphatase, beta-N-acetyl-glucosaminidase, and gamma-glutamyltransferase, inflammatory cell number and distribution in bronchoalveolar lavage fluid (BALF), and hydroxyproline content in dried lung tissue. RESULTS: Based on the doses that killed 50% of the animals (LD50s), the various components were found to be 10 to 1250 times more toxic when given intratracheally than when given orally (according to reported oral LD50s in rats). Acramin FWN, Acramin FWR, Acrafix FHN, or their mixtures caused lung damage. Protein concentration, enzyme activities, total cell number, and percentage of polymorphonuclear neutrophils were increased in BALF during the first week after intratracheal instillation. Lung weights remained high for at least a month. Histology showed inflammatory cell infiltration and subsequent fibrosis with collagen deposition. This finding was confirmed by an increased hydroxyproline content in dried lung tissue. Acramoll W did not show toxic effects. CONCLUSIONS: The study suggests that there is no major difference, in hamsters, between the acute intratracheal toxicity of Acramin FWR and that of Acramin FWN. Consequently, there is no simple toxicological explanation for the epidemiological hypothesis. However

  20. Comparative Particle Surface Reactivity and Pulmonary Toxicity of Lunar and Terrestrial Dusts in Exposed Rats

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-wing; Zeidler-Erdely, Patti C.; Wallace, William; Scully, Robert R.; Meyers, Valerie; Hunter, Robert; Renne, Roger; McCluskey, Richard; Castranova, Vincent; Barger, Mark; hide

    2015-01-01

    Humans will set foot on the moon again. The lunar surface has been bombarded for 4 billion years by micrometeoroids and cosmic radiation, creating a layer of fine dust having a potentially reactive particle surface. Whether or not the surface reactivity (SR) of a dust contributes substantially to oxidative stress (OS) leading to pulmonary toxicity remains unsettled. To investigate the impact of SR on the toxicity of particles, and in particular, lunar dust, We ground two aliquots of an Apollo-14 lunar soil (aged) by two methods to restore or increase their SR, measured as the ability to generate hydroxyl radicals, and compared their toxicities with those of unground lunar dust, aged quartz and titanium dioxide. Intratracheally instilled at 0, 1, 2.5, or 7.5 mg/rat, all of these respirable dusts caused dose-dependent increases in pulmonary lesions, and toxicity biomarkers assessed in bronchoalveolar lavage fluids. Lunar dust (which mineralogically resembles an Arizona volcanic ash) was moderately toxic. These three respirable-size lunar dusts that had identical mineral properties but 14-fold difference in SR were equally toxic; quartz had the lowest SR but was most toxic. Our results, show that the toxicity of mineral dusts is dependent on mineral properties and not on the SR of the particles, and support the contention that OS induced by particle exposure must come predominately from endogenous sources. We postulate that the dust-elicited neutrophils are the persistent source of OS; this assertion is the subject of further investigation and review in our companion paper (Lam et al. 2015).

  1. Toxic behavior of silver and zinc oxide nanoparticles on environmental microorganisms.

    PubMed

    Dhas, Sindhu Priya; Shiny, Punalur John; Khan, Sudheer; Mukherjee, Amitava; Chandrasekaran, Natrajan

    2014-09-01

    Silver and zinc oxide nanoparticles (Ag and ZnO NPs) are widely used as antimicrobial agents. However, their potential toxicological impact on environmental microorganisms is largely unexplored. The aim of this work was to investigate the sensitivity and adaptability of five bacterial species isolated from sewage towards Ag and ZnO NPs. The bacterial species were exposed to increasing concentration of nanoparticles and the growth inhibitory effect, exopolysaccharides (EPSs) and extracellular proteins (ECPs) productions were determined. The involvement of surface charge in nanoparticles toxicity was also determined. The bacterial species were constantly exposed to nanoparticles to determine the adaptation behavior toward nanoparticles. The nanoparticles exhibited remarkable growth inhibitory effect on tested bacterial species. The toxicity of nanoparticles was found to be strongly dependent on surface charge effects. Though, these organisms are highly sensitive to Ag and ZnO NPs, the continuous exposure to these nanoparticles leads to moderate adaptation of bacterial species and the adapted bacterial species convert the highly toxic nano form to less toxic microform. Finally we predict that the continuing applications of nanoparticles in consumer products may lead to the development of nanoparticles resistant bacterial strains in future.

  2. Pulmonary surfactant augments cytotoxicity of silica nanoparticles: Studies on an in vitro air-blood barrier model.

    PubMed

    Kasper, Jennifer Y; Feiden, Lisa; Hermanns, Maria I; Bantz, Christoph; Maskos, Michael; Unger, Ronald E; Kirkpatrick, C James

    2015-01-01

    The air-blood barrier is a very thin membrane of about 2.2 µm thickness and therefore represents an ideal portal of entry for nanoparticles to be used therapeutically in a regenerative medicine strategy. Until now, numerous studies using cellular airway models have been conducted in vitro in order to investigate the potential hazard of NPs. However, in most in vitro studies a crucial alveolar component has been neglected. Before aspirated NPs encounter the cellular air-blood barrier, they impinge on the alveolar surfactant layer (10-20 nm in thickness) that lines the entire alveolar surface. Thus, a prior interaction of NPs with pulmonary surfactant components will occur. In the present study we explored the impact of pulmonary surfactant on the cytotoxic potential of amorphous silica nanoparticles (aSNPs) using in vitro mono- and complex coculture models of the air-blood barrier. Furthermore, different surface functionalisations (plain-unmodified, amino, carboxylate) of the aSNPs were compared in order to study the impact of chemical surface properties on aSNP cytotoxicity in combination with lung surfactant. The alveolar epithelial cell line A549 was used in mono- and in coculture with the microvascular cell line ISO-HAS-1 in the form of different cytotoxicity assays (viability, membrane integrity, inflammatory responses such as IL-8 release). At a distinct concentration (100 µg/mL) aSNP-plain displayed the highest cytotoxicity and IL-8 release in monocultures of A549. aSNP-NH2 caused a slight toxic effect, whereas aSNP-COOH did not exhibit any cytotoxicity. In combination with lung surfactant, aSNP-plain revealed an increased cytotoxicity in monocultures of A549, aSNP-NH2 caused a slightly augmented toxic effect, whereas aSNP-COOH did not show any toxic alterations. A549 in coculture did not show any decreased toxicity (membrane integrity) for aSNP-plain in combination with lung surfactant. However, a significant augmented IL-8 release was observed, but no

  3. Pulmonary Toxicity and Modifications in Iron Homeostasis Following Libby Amphibole Asbestos Exposure in Rat Models of Cardiovascular Disease

    EPA Science Inventory

    Rationale: Individuals suffering from cardiovascular disease (CVD) develop iron dysregulation which may influence pulmonary toxicity and injury upon exposure to asbestos. We hypothesized spontaneously hypertensive (SH) and spontaneously hypertensive heart failure (SHHF) rats woul...

  4. Pulmonary Toxicity and Modifications in Iron Homeostasis Following Libby Amphibole Asbestos Exposure in Rat Models of Cardiovascular Disease

    EPA Science Inventory

    Rationale: Individuals suffering from cardiovascular disease (CVD) develop iron dysregulation which may influence pulmonary toxicity and injury upon exposure to asbestos. We hypothesized spontaneously hypertensive (SH) and spontaneously hypertensive heart failure (SHHF) rats woul...

  5. Nebulized solid lipid nanoparticles for the potential treatment of pulmonary hypertension via targeted delivery of phosphodiesterase-5-inhibitor.

    PubMed

    Makled, Shaimaa; Nafee, Noha; Boraie, Nabila

    2017-01-30

    Phosphodiesterase type 5 (PDE-5) inhibitors - among which sildenafil citrate (SC) - play a primary role in the treatment of pulmonary hypertension (PH). Yet, SC can be only administered orally or parenterally with lot of risks. Targeted delivery of SC to the lungs via inhalation/nebulization is mandatory. In this study, solid lipid nanoparticles (SLNs) loaded with SC were prepared and characterized in terms of colloidal, morphological and thermal properties. The amount of drug loaded and its release behavior were estimated as a function of formulation variables. The potential of lipid nanocarriers to retain their properties following nebulization and autoclaving was investigated. In addition, toxicity aspects of plain and loaded SLNs on A549 cells were studied with respect to concentration. Spherical SLNs in the size range (100-250nm) were obtained. Particles ensured high encapsulation efficiency (88-100%) and sustained release of the payload over 24h. Cell-based viability experiments revealed a concentration-dependant toxicity for both plain and loaded SLNs recording an IC50 of 516 and 384μg/mL, respectively. Nebulization with jet nebulizer and sterilization via autoclaving affected neither the colloidal stability of SLNs nor the drug entrapment, proving their potential as pulmonary delivery system. Interaction of SLNs with mucin was a function of the emulsifier coating layer. Results yet seeking clinical evidence - might give promises of new therapy for PH of higher safety, better performance and higher patient compliance. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Pulmonary toxicity of indium-tin oxide production facility particles in rats

    PubMed Central

    Badding, Melissa A.; Fix, Natalie R.; Orandle, Marlene S.; Barger, Mark W.; Dunnick, Katherine M.; Cummings, Kristin J.; Leonard, Stephen S.

    2016-01-01

    Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Occupational exposures to potentially toxic particles generated during ITO production have increased in recent years as the demand for consumer electronics continues to rise. Previous studies have demonstrated cytotoxicity in vitro and animal models have shown pulmonary inflammation and injury in response to various indium-containing particles. In humans, pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which indium materials or specific processes in the workplace may be the most toxic to workers is unknown. Here we examined the pulmonary toxicity of three different particle samples that represent real-life worker exposures, as they were collected at various production stages throughout an ITO facility. Indium oxide (In2O3), sintered ITO (SITO) and ventilation dust (VD) particles each caused pulmonary inflammation and damage in rats over a time course (1, 7 and 90 days post-intratracheal instillation), but SITO and VD appeared to induce greater toxicity in rat lungs than In2O3 at a dose of 1 mg per rat. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days after treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of an emerging occupational health issue. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID:26472246

  7. Pulmonary toxicity of indium-tin oxide production facility particles in rats.

    PubMed

    Badding, Melissa A; Fix, Natalie R; Orandle, Marlene S; Barger, Mark W; Dunnick, Katherine M; Cummings, Kristin J; Leonard, Stephen S

    2016-04-01

    Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Occupational exposures to potentially toxic particles generated during ITO production have increased in recent years as the demand for consumer electronics continues to rise. Previous studies have demonstrated cytotoxicity in vitro and animal models have shown pulmonary inflammation and injury in response to various indium-containing particles. In humans, pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which indium materials or specific processes in the workplace may be the most toxic to workers is unknown. Here we examined the pulmonary toxicity of three different particle samples that represent real-life worker exposures, as they were collected at various production stages throughout an ITO facility. Indium oxide (In2O3), sintered ITO (SITO) and ventilation dust (VD) particles each caused pulmonary inflammation and damage in rats over a time course (1, 7 and 90 days post-intratracheal instillation), but SITO and VD appeared to induce greater toxicity in rat lungs than In2O3 at a dose of 1 mg per rat. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days after treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of an emerging occupational health issue. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  8. ELEMENTAL ANALYSIS OF RESPIRABLE TIRE PARTICLES AND ASSESSMENT OF CARDIO-PULMONARY TOXICITY IN RATS

    EPA Science Inventory

    Elemental Analysis of Respirable Tire Particles and Assessment of Cardio-pulmonary Toxicity in Rats

    R.R. Gottipolu, PhD1, E. Landa, PhD2, J.K. McGee, MS1, M.C. Schladweiler, BS1, J.G. Wallenborn, MS3, A.D. Ledbetter, BS1, J.E. Richards, MS1 and U.P. Kodavanti, PhD1. 1NHEER...

  9. Pulmonary toxicity and metabolic activation of dauricine in CD-1 mice.

    PubMed

    Jin, Hua; Dai, Jieyu; Chen, Xiaoyan; Liu, Jia; Zhong, Dafang; Gu, Yansong; Zheng, Jiang

    2010-03-01

    Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C. and has shown promising pharmacological activities with a great potential for clinic use. However, the adverse effects and toxicity of the alkaloid are unfortunately ignored. The objective of the current study was to evaluate the toxicity of dauricine in vitro and in vivo. Mice (CD-1) were treated intraperitoneally with dauricine at various doses, and sera and lung lavage fluids were collected after 24 h of treatment. No changes in serum aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen were noticed, whereas a dose-dependent increase in lactate dehydrogenase activity was observed in lung lavage fluids. Ethidium-based staining studies showed that remarkable cells lost membrane integrity in the lungs of the animals treated with dauricine at 150 mg/kg. Histopathological evaluation of lungs of mice showed that dauricine at the same dose caused significant alveolar edema and hemorrhage. Exposure to dauricine at 40 muM for 24 h resulted in up to 60% cell death in human lung cell lines BEAS-2B, WI-38, and A549. Ketoconazole showed protective effect on the pulmonary injury in mice given dauricine. A quinone methide metabolite of dauricine was identified in mouse lung microsomal incubations, and the presence of ketoconazole in the microsomal incubations suppressed the formation of the quinone methide metabolite. In conclusion, dauricine produced pulmonary injury in CD-1 mice. The pulmonary toxicity appears to depend on the metabolism of dauricine mediated by CYP3A. The electrophilic quinone methide metabolite probably plays an important role in the pulmonary toxicity induced by dauricine.

  10. ELEMENTAL ANALYSIS OF RESPIRABLE TIRE PARTICLES AND ASSESSMENT OF CARDIO-PULMONARY TOXICITY IN RATS

    EPA Science Inventory

    Elemental Analysis of Respirable Tire Particles and Assessment of Cardio-pulmonary Toxicity in Rats

    R.R. Gottipolu, PhD1, E. Landa, PhD2, J.K. McGee, MS1, M.C. Schladweiler, BS1, J.G. Wallenborn, MS3, A.D. Ledbetter, BS1, J.E. Richards, MS1 and U.P. Kodavanti, PhD1. 1NHEER...

  11. Aquatic Toxicity Comparison of Silver Nanoparticles and Silver Nanowires.

    PubMed

    Sohn, Eun Kyung; Johari, Seyed Ali; Kim, Tae Gyu; Kim, Jin Kwon; Kim, Ellen; Lee, Ji Hyun; Chung, Young Shin; Yu, Il Je

    2015-01-01

    To better understand the potential ecotoxicological impact of silver nanoparticles (AgNPs) and silver nanowires (AgNWs) released into freshwater environments, the toxicities of these nanomaterials were assessed and compared using Organization for Economic Cooperation and Development (OECD) test guidelines, including a "Daphnia sp., acute immobilization test," "Fish, acute toxicity test," and "freshwater alga and cyanobacteria, growth inhibition test." Based on the estimated median lethal/effective concentrations of AgNPs and AgNWs, the susceptibility to the nanomaterials was different among test organisms (daphnia > algae > fish), suggesting that the AgNPs are classified as "category acute 1" for Daphnia magna, "category acute 2" for Oryzias latipes, and "category acute 1" for Raphidocelis subcapitata, while the AgNWs are classified as "category acute 1" for Daphnia magna, "category acute 2" for Oryzias latipes, and "category acute 2" for Raphidocelis subcapitata, according to the GHS (Globally Harmonized System of Classification and Labelling of Chemicals). In conclusion, the present results suggest that more attention should be paid to prevent the accidental or intentional release of silver nanomaterials into freshwater aquatic environments.

  12. Toxicity, distribution, and accumulation of silver nanoparticles in Wistar rats

    NASA Astrophysics Data System (ADS)

    Espinosa-Cristobal, L. F.; Martinez-Castañon, G. A.; Loyola-Rodriguez, J. P.; Patiño-Marin, N.; Reyes-Macías, J. F.; Vargas-Morales, J. M.; Ruiz, Facundo

    2013-06-01

    The bactericidal effect of silver nanoparticles (SNP) has lead to their application in several products mainly in the medicine field. This study analyzed the distribution, accumulation, and toxicity in principal organs of Wistar rats exposed to SNP suspensions by oral administration. Two sizes of washed SNP (14 and 36 nm) were prepared, characterized, and redispersed in deionized water. Each suspension was administrated to Wistar rats by oral way for 55 days; after finishing this treatment time, rats were sacrificed by anesthesia overdose. Organs were collected, processed, and prepared; then, accumulation and concentrations of SNP were obtained using inductively coupled plasma mass spectrometry (ICP-MS). Toxicity was determined by clinical chemistry and hematology from blood samples in three different periods; light microscopy (LM) and scanning electron microscopy (SEM) were applied to evaluate histopathology in tissues. Silver concentrations were higher in small intestine, followed by kidney, liver, and brain. Clinical chemistry and hematology showed altered values in blood urea nitrogen, total proteins, and mean corpuscular hemoglobin, concentration values had statistical difference in both groups (14 and 36 nm) ( p < 0.05). LM, SEM, ICP-MS, clinical chemistry, and hematology tests suggest that the administration way, concentration, shape, size, presentation, administration time of SNP used in this study, do not change significantly these values.

  13. Mechanisms of Nanoparticle-Induced Oxidative Stress and Toxicity

    PubMed Central

    Wang, Liying

    2013-01-01

    The rapidly emerging field of nanotechnology has offered innovative discoveries in the medical, industrial, and consumer sectors. The unique physicochemical and electrical properties of engineered nanoparticles (NP) make them highly desirable in a variety of applications. However, these novel properties of NP are fraught with concerns for environmental and occupational exposure. Changes in structural and physicochemical properties of NP can lead to changes in biological activities including ROS generation, one of the most frequently reported NP-associated toxicities. Oxidative stress induced by engineered NP is due to acellular factors such as particle surface, size, composition, and presence of metals, while cellular responses such as mitochondrial respiration, NP-cell interaction, and immune cell activation are responsible for ROS-mediated damage. NP-induced oxidative stress responses are torch bearers for further pathophysiological effects including genotoxicity, inflammation, and fibrosis as demonstrated by activation of associated cell signaling pathways. Since oxidative stress is a key determinant of NP-induced injury, it is necessary to characterize the ROS response resulting from NP. Through physicochemical characterization and understanding of the multiple signaling cascades activated by NP-induced ROS, a systemic toxicity screen with oxidative stress as a predictive model for NP-induced injury can be developed. PMID:24027766

  14. Toxic Effects of Silica Nanoparticles on Zebrafish Embryos and Larvae

    PubMed Central

    Shi, Huiqin; Tian, Linwei; Guo, Caixia; Huang, Peili; Zhou, Xianqing; Peng, Shuangqing; Sun, Zhiwei

    2013-01-01

    Silica nanoparticles (SiNPs) have been widely used in biomedical and biotechnological applications. Environmental exposure to nanomaterials is inevitable as they become part of our daily life. Therefore, it is necessary to investigate the possible toxic effects of SiNPs exposure. In this study, zebrafish embryos were treated with SiNPs (25, 50, 100, 200 µg/mL) during 4–96 hours post fertilization (hpf). Mortality, hatching rate, malformation and whole-embryo cellular death were detected. We also measured the larval behavior to analyze whether SiNPs had adverse effects on larvae locomotor activity. The results showed that as the exposure dosages increasing, the hatching rate of zebrafish embryos was decreased while the mortality and cell death were increased. Exposure to SiNPs caused embryonic malformations, including pericardial edema, yolk sac edema, tail and head malformation. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lower dose (25 and 50 µg/mL SiNPs) produced substantial hyperactivity while the higher doses (100 and 200 µg/mL SiNPs) elicited remarkably hypoactivity in dark periods. In summary, our data indicated that SiNPs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior. PMID:24058598

  15. Validation of an LDH assay for assessing nanoparticle toxicity.

    PubMed

    Han, Xianglu; Gelein, Robert; Corson, Nancy; Wade-Mercer, Pamela; Jiang, Jingkun; Biswas, Pratim; Finkelstein, Jacob N; Elder, Alison; Oberdörster, Günter

    2011-09-05

    Studies showed that certain cytotoxicity assays were not suitable for assessing nanoparticle (NP) toxicity. We evaluated a lactate dehydrogenase (LDH) assay for assessing copper (Cu-40, 40nm), silver (Ag-35, 35nm; Ag-40, 40nm), and titanium dioxide (TiO(2)-25, 25nm) NPs by examining their potential to inactivate LDH and interference with β-nicotinamide adenine dinucleotide (NADH), a substrate for the assay. We also performed a dissolution assay for some of the NPs. We found that the copper NPs, because of their high dissolution rate, could interfere with the LDH assay by inactivating LDH. Ag-35 could also inactivate LDH probably because of the carbon matrix used to cage the particles during synthesis. TiO(2)-25 NPs were found to adsorb LDH molecules. In conclusion, NP interference with the LDH assay depends on the type of NPs and the suitability of the assay for assessing NP toxicity should be examined case by case. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Aquatic Toxicity Comparison of Silver Nanoparticles and Silver Nanowires

    PubMed Central

    Kim, Tae Gyu; Kim, Jin Kwon; Kim, Ellen; Lee, Ji Hyun; Chung, Young Shin

    2015-01-01

    To better understand the potential ecotoxicological impact of silver nanoparticles (AgNPs) and silver nanowires (AgNWs) released into freshwater environments, the toxicities of these nanomaterials were assessed and compared using Organization for Economic Cooperation and Development (OECD) test guidelines, including a “Daphnia sp., acute immobilization test,” “Fish, acute toxicity test,” and “freshwater alga and cyanobacteria, growth inhibition test.” Based on the estimated median lethal/effective concentrations of AgNPs and AgNWs, the susceptibility to the nanomaterials was different among test organisms (daphnia > algae > fish), suggesting that the AgNPs are classified as “category acute 1” for Daphnia magna, “category acute 2” for Oryzias latipes, and “category acute 1” for Raphidocelis subcapitata, while the AgNWs are classified as “category acute 1” for Daphnia magna, “category acute 2” for Oryzias latipes, and “category acute 2” for Raphidocelis subcapitata, according to the GHS (Globally Harmonized System of Classification and Labelling of Chemicals). In conclusion, the present results suggest that more attention should be paid to prevent the accidental or intentional release of silver nanomaterials into freshwater aquatic environments. PMID:26125025

  17. Validation of an LDH Assay for Assessing Nanoparticle Toxicity

    PubMed Central

    Han, Xianglu; Gelein, Robert; Corson, Nancy; Wade-Mercer, Pamela; Jiang, Jingkun; Biswas, Pratim; Finkelstein, Jacob N.; Elder, Alison; Oberdörster, Günter

    2014-01-01

    Studies showed that certain cytotoxicity assays were not suitable for assessing nanoparticle (NP) toxicity. We evaluated a lactate dehydrogenase (LDH) assay for assessing copper (Cu-40, 40 nm), silver (Ag-35, 35 nm; Ag-40, 40 nm), and titanium dioxide (TiO2-25, 25 nm) NPs by examining their potential to inactivate LDH and interference with β-nicotinamide adenine dinucleotide (NADH), a substrate for the assay. We also performed a dissolution assay for some of the NPs. We found that the copper NPs, because of their high dissolution rate, could interfere with the LDH assay by inactivating LDH. Ag-35 could also inactivate LDH probably because of the carbon matrix used to cage the particles during synthesis. TiO2-25 NPs were found to adsorb LDH molecules. In conclusion, NP interference with the LDH assay depends on the type of NPs and the suitability of the assay for assessing NP toxicity should be examined case by case. PMID:21722700

  18. Research of nickel nanoparticles toxicity with use of Aquatic Organisms

    NASA Astrophysics Data System (ADS)

    Morgaleva, T.; Morgalev, Yu; Gosteva, I.; Morgalev, S.

    2015-11-01

    The effect of nanoparticles with the particle size Δ50=5 nm on the test function of aquatic organisms was analyzed by means of biotesting methods with the use of a complex of test-organisms representing general trophic levels. The dependence of an infusoria Paramecium caudatum chemoattractant-elicited response, unicellular algae Chlorella vulgaris Beijer growth rate, Daphnia magna Straus mortality and trophic activity and Danio rerio fish kill due to nNi disperse system concentration, is estimated. It is determined that the release of chlorella into cultivated environment including nNi as a feed for daphnias raises the death rate of entomostracans. The minimal concentration, whereby an organism response to the effect of nNi is registered, depends on the type of test organism and the analysed test function. L(E)C20 is determined for all the organisms used in bioassays. L(E)C50 is estimated for Paramecium caudatum (L(E)C50 = 0.0049 mg/l), for Chlorella vulgaris Beijer (L(E)C50 = 0.529 mg/l), for Daphnia m. S (L(E)C50 > 100 mg/l) and for fish Danio rerio (L(E)C50 > 100 mg/l). According to the Globally Harmonized System hazard substance evaluation criteria and Commission Directive 93/67/EEC, nNi belongs to the “acute toxicity 1” category of toxic substances.

  19. Environmental transformations of silver nanoparticles: impact on stability and toxicity.

    PubMed

    Levard, Clément; Hotze, E Matt; Lowry, Gregory V; Brown, Gordon E

    2012-07-03

    Silver nanoparticles (Ag-NPs) readily transform in the environment, which modifies their properties and alters their transport, fate, and toxicity. It is essential to consider such transformations when assessing the potential environmental impact of Ag-NPs. This review discusses the major transformation processes of Ag-NPs in various aqueous environments, particularly transformations of the metallic Ag cores caused by reactions with (in)organic ligands, and the effects of such transformations on physical and chemical stability and toxicity. Thermodynamic arguments are used to predict what forms of oxidized silver will predominate in various environmental scenarios. Silver binds strongly to sulfur (both organic and inorganic) in natural systems (fresh and sea waters) as well as in wastewater treatment plants, where most Ag-NPs are expected to be concentrated and then released. Sulfidation of Ag-NPs results in a significant decrease in their toxicity due to the lower solubility of silver sulfide, potentially limiting their short-term environmental impact. This review also discusses some of the major unanswered questions about Ag-NPs, which, when answered, will improve predictions about their potential environmental impacts. Research needed to address these questions includes fundamental molecular-level studies of Ag-NPs and their transformation products, particularly Ag(2)S-NPs, in simplified model systems containing common (in)organic ligands, as well as under more realistic environmental conditions using microcosm/mesocosm-type experiments. Toxicology studies of Ag-NP transformation products, including different states of aggregation and sulfidation, are also required. In addition, there is the need to characterize the surface structures, compositions, and morphologies of Ag-NPs and Ag(2)S-NPs to the extent possible because they control properties such as solubility and reactivity.

  20. Toxic pulmonary effects of photodynamic therapy (PDT) in a mouse model

    NASA Astrophysics Data System (ADS)

    Luketich, James D.; Perry, Yaron; Wong, Hsien; Epperly, Michael W.

    2002-06-01

    A major limitation of PDT for Barrett's esophagus is the development of esophageal strictures. This report summarizes the effects of PDT delivered to mouse esophagus. Sixty-two C3H/Nsd mice were injected with Photofrin (2-10mg/Kg) intraperitoneally. Forty-eight hours later a 1 cm laser probe was passed orally to the mid-esophagus. Light energy (630nm) ranged from 0 to 400 Joules/cm (J). Animals were sacrificed if death was imminent, otherwise at 6 weeks and 3 months. Gross and microscopic exams were performed on paraffin embedded esophagus and lung specimens. Exposure to 400J as a single fraction, 125 X 3 or 150 X 3 fractions resulted in a lethal pulmonary injury in 90% of mice within 48 hours. There was no esophageal mucosal damage at this early time point. Lower doses caused minor pulmonary injury allowing long-term survival but no change in the esophageal endothelium and no stricture. In the mouse, this histopathologic study demonstrates that pulmonary toxicity is the limiting factor following esophageal PDT. At lower PDT doses, minimal pulmonary damage occurred but no effect was observed on the esophagus. We believe the 5 mm depth of PDT injury leads to lethal pulmonary damage preventing subsequent study of the effects on the esophagus.

  1. Thioridazine in PLGA nanoparticles reduces toxicity and improves rifampicin therapy against mycobacterial infection in zebrafish.

    PubMed

    Vibe, Carina Beatrice; Fenaroli, Federico; Pires, David; Wilson, Steven Ray; Bogoeva, Vanya; Kalluru, Raja; Speth, Martin; Anes, Elsa; Griffiths, Gareth; Hildahl, Jon

    2016-08-01

    Encapsulating antibiotics such as rifampicin in biodegradable nanoparticles provides several advantages compared to free drug administration, including reduced dosing due to localized targeting and sustained release. Consequently, these characteristics reduce systemic drug toxicity. However, new nanoformulations need to be tested in complex biological systems to fully characterize their potential for improved drug therapy. Tuberculosis, caused by infection with the bacterium Mycobacterium tuberculosis, requires lengthy and expensive treatment, and incomplete therapy contributes to an increasing incidence of drug resistance. Recent evidence suggests that standard therapy may be improved by combining antibiotics with bacterial efflux pump inhibitors, such as thioridazine. However, this drug is difficult to use clinically due to its toxicity. Here, we encapsulated thioridazine in poly(lactic-co-glycolic) acid nanoparticles and tested them alone and in combination with rifampicin nanoparticles, or free rifampicin in macrophages and in a zebrafish model of tuberculosis. Whereas free thioridazine was highly toxic in both cells and zebrafish embryos, after encapsulation in nanoparticles no toxicity was detected. When combined with rifampicin nanoparticles, the nanoparticles loaded with thioridazine gave a modest increase in killing of both Mycobacterium bovis BCG and M. tuberculosis in macrophages. In the zebrafish, the thioridazine nanoparticles showed a significant therapeutic effect in combination with rifampicin by enhancing embryo survival and reducing mycobacterial infection. Our results show that the zebrafish embryo is a highly sensitive indicator of drug toxicity and that thioridazine nanoparticle therapy can improve the antibacterial effect of rifampicin in vivo.

  2. Acute pulmonary toxicity of urban particulate matter and ozone.

    PubMed Central

    Vincent, R.; Bjarnason, S. G.; Adamson, I. Y.; Hedgecock, C.; Kumarathasan, P.; Guénette, J.; Potvin, M.; Goegan, P.; Bouthillier, L.

    1997-01-01

    We have investigated the acute lung toxicity of urban particulate matter in interaction with ozone. Rats were exposed for 4 hours to clean air, ozone (0.8 ppm), the urban dust EHC-93 (5 mg/m3 or 50 mg/m3), or ozone in combination with urban dust. The animals were returned to clean air for 32 hours and then injected (intraperitoneally) with [3H]thymidine to label proliferating cells and killed after 90 minutes. The lungs were fixed by inflation, embedded in glycol methacrylate, and processed for light microscopy autoradiography. Cell labeling was low in bronchioles (0.14 +/- 0.04%) and parenchyma (0.13 +/- 0.02%) of air control animals. Inhalation of EHC-93 alone did not induce cell labeling. Ozone alone increased (P < 0.05) cell labeling (bronchioles, 0.42 +/- 0.16%; parenchyma, 0.57 +/- 0.21%), in line with an acute reparative cell proliferation. The effects of ozone were clearly potentiated by co-exposure with either the low (3.31 +/- 0.31%; 0.99 +/- 0.18%) or the high (4.45 +/- 0.51%; 1.47 +/- 0.18%) concentrations of urban dust (ozone X EHC-93, P < 0.05). Cellular changes were most notable in the epithelia of terminal bronchioles and alveolar ducts and did not distribute to the distal parenchyma. Enhanced DNA synthesis indicates that particulate matter from ambient air can exacerbate epithelial lesions in the lungs. This may extend beyond air pollutant interactions, such as to effects of inhaled particles in the lungs of compromised individuals. Images Figure 1 PMID:9403707

  3. Pulmonary toxicity of dust generated during weaving of carpets.

    PubMed

    Ameen, M; Ahmad, I; Rahman, Q

    2002-12-01

    The dust generated during weaving (carpet dust) tibbati, knotted and tuffted carpets in carpet industry was studied for its toxicity in vitro and in vivo. Carpet dust (0.5, 1.0, 2.5 and 5.0 mg/1 x 10(6) cells) caused in vitro cytotoxicity in rat alveolar macrophages (AM) in a concentration-dependent manner. The cytotoxic, inflammatory and oxidative responses were observed in bronchoalveolar lavage fluid (BALF) of rats at 1, 4, 8 and 16 days after exposure. Rats were intratracheally exposed at 5 mg/rat individually to all three types of carpet dust. All types of carpet dusts produced increased AM, lymphocytes (PMN) population in BALF suggesting their inflammatory reactions. Cytotoxic nature of carpet dust was shown by the increased activities of lactate dehydrogenase (LDH) and acid phosphatase (AP) in BALF. Increased AM population and in vitro cytotoxicity due to carpet dusts have shown some correlation with the levels of LDH and AP activities in BALF. The gradual enhanced profile of hydrogen peroxide (H2O2) and nitric oxide (NO) along with depletion of reduced glutathione (GSH) in AM due to these carpet dusts are suggestive of their oxidant nature. The enzyme activities of both glutathione peroxidase (GPx) and glutathione reductase (GR) in AM were marginally reduced in exposed rats. In conclusion, the data suggest the cytotoxic, inflammatory and oxidant nature of carpet dusts. It is extrapolated that health effects on carpet weavers would be associated with the concentration and nature of airborne dust generated during weaving of carpets.

  4. Toxicity of various silver nanoparticles compared to silver ions in Daphnia magna

    PubMed Central

    2012-01-01

    Background To better understand the potential ecotoxicological impacts of silver nanoparticles released into freshwater environments, the Daphnia magna 48-hour immobilization test was used. Methods The toxicities of silver nitrate, two types of colloidal silver nanoparticles, and a suspension of silver nanoparticles were assessed and compared using standard OECD guidelines. Also, the swimming behavior and visible uptake of the nanoparticles by Daphnia were investigated and compared. The particle suspension and colloids used in the toxicity tests were well-characterized. Results The results obtained from the exposure studies showed that the toxicity of all the silver species tested was dose and composition dependent. Plus, the silver nanoparticle powders subsequently suspended in the exposure water were much less toxic than the previously prepared silver nanoparticle colloids, whereas the colloidal silver nanoparticles and AgNO3 were almost similar in terms of mortality. The silver nanoparticles were ingested by the Daphnia and accumulated under the carapace, on the external body surface, and connected to the appendages. All the silver species in this study caused abnormal swimming by the D. magna. Conclusion According to the present results, silver nanoparticles should be classified according to GHS (Globally Harmonized System of classification and labeling of chemicals) as "category acute 1" to Daphnia neonates, suggesting that the release of nanosilver into the environment should be carefully considered. PMID:22472056

  5. Toxicity of various silver nanoparticles compared to silver ions in Daphnia magna.

    PubMed

    Asghari, Saba; Johari, Seyed Ali; Lee, Ji Hyun; Kim, Yong Seok; Jeon, Yong Bae; Choi, Hyun Jung; Moon, Min Chaul; Yu, Il Je

    2012-04-02

    To better understand the potential ecotoxicological impacts of silver nanoparticles released into freshwater environments, the Daphnia magna 48-hour immobilization test was used. The toxicities of silver nitrate, two types of colloidal silver nanoparticles, and a suspension of silver nanoparticles were assessed and compared using standard OECD guidelines. Also, the swimming behavior and visible uptake of the nanoparticles by Daphnia were investigated and compared. The particle suspension and colloids used in the toxicity tests were well-characterized. The results obtained from the exposure studies showed that the toxicity of all the silver species tested was dose and composition dependent. Plus, the silver nanoparticle powders subsequently suspended in the exposure water were much less toxic than the previously prepared silver nanoparticle colloids, whereas the colloidal silver nanoparticles and AgNO(3) were almost similar in terms of mortality. The silver nanoparticles were ingested by the Daphnia and accumulated under the carapace, on the external body surface, and connected to the appendages. All the silver species in this study caused abnormal swimming by the D. magna. According to the present results, silver nanoparticles should be classified according to GHS (Globally Harmonized System of classification and labeling of chemicals) as "category acute 1" to Daphnia neonates, suggesting that the release of nanosilver into the environment should be carefully considered.

  6. Comparison of toxicity of uncoated and coated silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Nguyen, K. C.; Seligy, V. L.; Massarsky, A.; Moon, T. W.; Rippstein, P.; Tan, J.; Tayabali, A. F.

    2013-04-01

    This study compares toxic effects of uncoated (20, 40, 60 and 80 nm) and OECD (Organization for Economic Co-operation and Development) standard citrate- and polyvinylpyrrolidone (PVP)-coated (10, 50, and 75 nm) silver nanoparticles (Ag-NPs) in J774A. 1 macrophage and HT29 epithelial cells. The cells were exposed to different concentrations (silver content) of Ag-NPs for 24 h. Analysis showed that uncoated Ag-NPs, at a concentration of 1 μg/ml, decreased cell viability by 20-40% and that 20 and 40 nm particles were 10% more cytotoxic than the 60 and 80 nm particles. In exposures to coated Ag-NPs, cell viability dropped at 25 μg/ml or higher concentrations, and the effects were also size-dependent. PVP-coated particles induced greater cytotoxicity than citrate-coated particles. Changes in sub-cellular architecture were observed in J774A. 1 cells upon exposure to test Ag-NPs. Furthermore, uncoated Ag-NPs (1 μg/mL) decreased the expression of selected cytokines including TNF-α, IL-1β, and IL-12 (p70) in J774A. 1 and IL-8 in HT29 cells. In contrast, both citrate- and PVP-coated Ag-NPs increased the expression of these cytokines at higher concentrations (25 μg/ml), and PVP-coated particles elevated cytokine levels the most. Moreover, while uncoated Ag-NPs resulted in decreased glutathione (GSH) content and increased superoxide dismutase (SOD) activity in test cells in a size-dependent manner at 1 μg/ml, coated Ag-NPs caused non-significant changes in GSH and SOD, even at the highest test concentrations. Lastly, uncoated (20 and 40 nm) at 1 μg/ml and coated Ag-NPs (10 nm PVP) at 50 μg/ml slightly increased the production of reactive oxygen species (ROS). Our data showed that uncoated Ag-NPs are more toxic than coated Ag-NPs. While uncoated Ag-NPs appear to suppress inflammatory responses and enhance oxidative stress in the test cells, coated Ag-NPs induce toxic effects through up-regulation of cytokines. Our findings support the toxicity of Ag-NPs as being size

  7. Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).

    PubMed

    Gao, Jiejun; Mahapatra, Cecon T; Mapes, Christopher D; Khlebnikova, Maria; Wei, Alexander; Sepúlveda, Marisol S

    2016-11-01

    Nanoparticles (NPs, 1-100 nm) can enter the environment and result in exposure to humans and other organisms leading to potential adverse health effects. The aim of the present study is to evaluate the effects of early life exposure to polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs, 50 nm), particularly with respect to vascular toxicity on zebrafish embryos and larvae (Danio rerio). Previously published data has suggested that PVP-AgNP exposure can inhibit the expression of genes within the vascular endothelial growth factor (VEGF) signaling pathway, leading to delayed and abnormal vascular development. Here, we show that early acute exposure (0-12 h post-fertilization, hpf) of embryos to PVP-AgNPs at 1 mg/L or higher results in a transient, dose-dependent induction in VEGF-related gene expression that returns to baseline levels at hatching (72 hpf). Hatching results in normoxia, negating the effects of AgNPs on vascular development. Interestingly, increased gene transcription was not followed by the production of associated proteins within the VEGF pathway, which we attribute to NP-induced stress in the endoplasmic reticulum (ER). The impaired translation may be responsible for the observed delays in vascular development at later stages, and for smaller larvae size at hatching. Silver ion (Ag(+)) concentrations were < 0.001 mg/L at all times, with no significant effects on the VEGF pathway. We propose that PVP-AgNPs temporarily delay embryonic vascular development by interfering with oxygen diffusion into the egg, leading to hypoxic conditions and ER stress.

  8. Prenatal development toxicity study of zinc oxide nanoparticles in rats

    PubMed Central

    Hong, Jeong-Sup; Park, Myeong-Kyu; Kim, Min-Seok; Lim, Jeong-Hyeon; Park, Gil-Jong; Maeng, Eun-Ho; Shin, Jae-Ho; Kim, Meyoung-Kon; Jeong, Jayoung; Park, Jin-A; Kim, Jong-Choon; Shin, Ho-Chul

    2014-01-01

    This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. PMID:25565834

  9. Surface coating mediates the toxicity of polymeric nanoparticles towards human-like macrophages.

    PubMed

    Grabowski, Nadège; Hillaireau, Hervé; Vergnaud, Juliette; Tsapis, Nicolas; Pallardy, Marc; Kerdine-Römer, Saadia; Fattal, Elias

    2015-03-30

    The purpose of this study was to investigate the toxicity of a series of poly(lactide-co-glycolic) (PLGA) nanoparticles on human-like THP-1 macrophages. Positively-, negatively-charged and neutral nanoparticles (200 nm) were prepared using chitosan (CS), poloxamer 188 (PF68) and poly(vinyl alcohol) (PVA) as stabilizer. Stabilizer-free PLGA nanoparticles were obtained as well. When used at therapeutically relevant concentrations (up to 0.1 mg/mL in vitro), all tested nanoparticles showed no or scarce signs of toxicity, as assessed by cell mitochondrial activity, induction of apoptosis and necrosis, production of intracellular reactive oxygen species (ROS) and secretion of pro-inflammatory cytokines. At high concentrations (above 1mg/mL), cytotoxicity was found to be induced by the presence of stabilizers, whatever the toxicological pattern of the stabilizer itself. While stabilizer-free PLGA nanoparticles exerted no cytotoxicity, the slightly cytotoxic CS polymer conferred PLGA nanoparticles significant cytotoxicity when used as nanoparticle stabilizer; more surprisingly, the otherwise innocuous PVA and PF68 polymers also conferred a significant cytotoxicity to PLGA nanoparticles. These results unveiled the critical toxicological contribution played by stabilizers used for the formulation of PLGA nanoparticles when used at high concentrations, which may have implications for local toxicities of PLGA-based nanomedicine, and provided additional insight in cytotoxic effects of internalized nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

    PubMed

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

  11. Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

    PubMed Central

    Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

    2017-01-01

    In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

  12. Toxicity of nanoparticles embedded in paints compared to pristine nanoparticles, in vitro study.

    PubMed

    Smulders, Stijn; Luyts, Katrien; Brabants, Gert; Golanski, Luana; Martens, Johan; Vanoirbeek, Jeroen; Hoet, Peter H M

    2015-01-22

    The unique physicochemical properties of nanomaterials has led to an increased use in the paint and coating industry. In this study, the in vitro toxicity of three pristine ENPs (TiO2, Ag and SiO₂), three aged paints containing ENPs (TiO₂, Ag and SiO₂) and control paints without ENPs were compared. In a first experiment, cytotoxicity was assessed using a biculture consisting of human bronchial epithelial (16HBE14o-) cells and human monocytic cells (THP-1) to determine subtoxic concentrations. In a second experiment, a new coculture model of the lung-blood barrier consisting of 16HBE14o- cells, THP-1 and human lung microvascular endothelial cells (HLMVEC) was used to study pulmonary and extrapulmonary toxicity. The results show that the pristine TiO₂ and Ag ENPs have some cytotoxic effects at relative high dose, while pristine SiO₂ ENPs and all aged paints with ENPs and control paints do not. In the complex triculture model of the lung-blood barrier, no considerable changes were observed after exposure to subtoxic concentration of the different pristine ENPs and paint particles. In conclusion, we demonstrated that although pristine ENPs show some toxic effects, no significant toxicological effects were observed when they were embedded in a complex paint matrix. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.

    PubMed

    Nair, Harikrishnan A; Snima, K S; Kamath, Ravindranath C; Nair, Shantikumar V; Lakshmanan, Vinoth-Kumar

    2015-01-01

    Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

  14. Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells

    PubMed Central

    Mura, Simona; Hillaireau, Herve; Nicolas, Julien; Le Droumaguet, Benjamin; Gueutin, Claire; Zanna, Sandrine; Tsapis, Nicolas; Fattal, Elias

    2011-01-01

    Background Because of the described hazards related to inhalation of manufactured nanoparticles, we investigated the lung toxicity of biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles displaying various surface properties on human bronchial Calu-3 cells. Methods Positively and negatively charged as well as neutral nanoparticles were tailored by coating their surface with chitosan, Poloxamer, or poly (vinyl alcohol), respectively. Nanoparticles were characterized in terms of size, zeta potential, and surface chemical composition, confirming modifications provided by hydrophilic polymers. Results Although nanoparticle internalization by lung cells was clearly demonstrated, the cytotoxicity of the nanoparticles was very limited, with an absence of inflammatory response, regardless of the surface properties of the PLGA nanoparticles. Conclusion These in vitro results highlight the safety of biodegradable PLGA nanoparticles in the bronchial epithelium and provide initial data on their potential effects and the risks associated with their use as nanomedicines. PMID:22114491

  15. Triglyceride-coated nanoparticles: skin toxicity and effect of UV/IR irradiation on them.

    PubMed

    Jebali, Ali; Kazemi, Bahram

    2013-09-01

    Triglyceride (TG) is an important compound on the skin, produced by sebaceous glands, and may change cytotoxicity of different nanoparticles. To date, there is no report about toxicity of nanoparticles coated with TG. On the other hand, the use of ultraviolet (UV) and infrared (IR) with nanoparticles changes nanoparticle cytotoxicity. The combination of nanoparticles with UV or IR is applicable, because it may be used for treatment or detection of local cancers, surface microbial infections and other skin diseases. In this study, different nanoparticles including titanium dioxide, zinc oxide, magnesium oxide, silver, gold, and TG-coated form of these nanoparticles, were added to suspensions of Balb/c skin cells, and then incubated for 24h at 37°C. Additionally, TG-coated nanoparticles were treated with UV and IR irradiation for 1h. Different methods were applied for evaluation of cytotoxicity, including 5-diphenyl-tetrazolium bromide assay, lactate dehydrogenase (LDH) assay, cell metabolic assay, ATP assay, and reactive oxygen species (ROS) generation assay. This research showed that TG-coated nanoparticles had less LDH release and ROS generation with higher cell viability, cell metabolic activity, and ATP level, compared with pristine nanoparticles. In contrast, the combination of UV and IR with TG-coated nanoparticles led to higher LDH release and ROS generation with less cell viability, cell metabolic activity, and ATP level, in comparison with pristine nanoparticles. Overall, pristine metal nanoparticles without irradiation had higher cytotoxicity than metal oxide nanoparticles. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Toxicity of zero-valent iron nanoparticles to a trichloroethylene-degrading groundwater microbial community.

    PubMed

    Zabetakis, Kara M; Niño de Guzmán, Gabriela T; Torrents, Alba; Yarwood, Stephanie

    2015-01-01

    The microbiological impact of zero-valent iron used in the remediation of groundwater was investigated by exposing a trichloroethylene-degrading anaerobic microbial community to two types of iron nanoparticles. Changes in total bacterial and archaeal population numbers were analyzed using qPCR and were compared to results from a blank and negative control to assess for microbial toxicity. Additionally, the results were compared to those of samples exposed to silver nanoparticles and iron filings in an attempt to discern the source of toxicity. Statistical analysis revealed that the three different iron treatments were equally toxic to the total bacteria and archaea populations, as compared with the controls. Conversely, the silver nanoparticles had a limited statistical impact when compared to the controls and increased the microbial populations in some instances. Therefore, the findings suggest that zero-valent iron toxicity does not result from a unique nanoparticle-based effect.

  17. Surface charge of gold nanoparticles mediates mechanism of toxicity

    NASA Astrophysics Data System (ADS)

    Schaeublin, Nicole M.; Braydich-Stolle, Laura K.; Schrand, Amanda M.; Miller, John M.; Hutchison, Jim; Schlager, John J.; Hussain, Saber M.

    2011-02-01

    Recently gold nanoparticles (Au NPs) have shown promising biological and military applications due to their unique electronic and optical properties. However, little is known about their biocompatibility in the event that they come into contact with a biological system. In the present study, we have investigated whether modulating the surface charge of 1.5 nm Au NPs induced changes in cellular morphology, mitochondrial function, mitochondrial membrane potential (MMP), intracellular calcium levels, DNA damage-related gene expression, and of p53 and caspase-3 expression levels after exposure in a human keratinocyte cell line (HaCaT). The evaluation of three different Au NPs (positively charged, neutral, and negatively charged) showed that cell morphology was disrupted by all three NPs and that they demonstrated a dose-dependent toxicity; the charged Au NPs displayed toxicity as low as 10 µg ml-1 and the neutral at 25 µg ml-1. Furthermore, there was significant mitochondrial stress (decreases in MMP and intracellular Ca2+ levels) following exposure to the charged Au NPs, but not the neutral Au NPs. In addition to the differences observed in the MMP and Ca2+ levels, up or down regulation of DNA damage related gene expression suggested a differential cell death mechanism based on whether or not the Au NPs were charged or neutral. Additionally, increased nuclear localization of p53 and caspase-3 expression was observed in cells exposed to the charged Au NPs, while the neutral Au NPs caused an increase in both nuclear and cytoplasmic p53 expression. In conclusion, these results indicate that surface charge is a major determinant of how Au NPs impact cellular processes, with the charged NPs inducing cell death through apoptosis and neutral NPs leading to necrosis.Recently gold nanoparticles (Au NPs) have shown promising biological and military applications due to their unique electronic and optical properties. However, little is known about their biocompatibility in the

  18. Dose-Dependent Pulmonary Toxicity After Postoperative Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

    SciTech Connect

    Rice, David C. Smythe, W. Roy; Liao Zhongxing; Guerrero, Thomas; Chang, Joe Y.; McAleer, Mary F.; Jeter, Melenda D.; Correa, Arlene Ph.D.; Vaporciyan, Ara A.; Liu, H. Helen; Komaki, Ritsuko; Forster, Kenneth M.; Stevens, Craig W.

    2007-10-01

    Purpose: To determine the incidence of fatal pulmonary events after extrapleural pneumonectomy and hemithoracic intensity-modulated radiotherapy (IMRT) for malignant pleural mesothelioma. Methods and Materials: We retrospectively reviewed the records of 63 consecutive patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy and IMRT at University of Texas M. D. Anderson Cancer Center. The endpoints studied were pulmonary-related death (PRD) and non-cancer-related death within 6 months of IMRT. Results: Of the 63 patients, 23 (37%) had died within 6 months of IMRT (10 of recurrent cancer, 6 of pulmonary causes [pneumonia in 4 and pneumonitis in 2], and 7 of other noncancer causes [pulmonary embolus in 2, sepsis after bronchopleural fistula in 1, and cause unknown but without pulmonary symptoms or recurrent disease in 4]). On univariate analysis, the factors that predicted for PRD were a lower preoperative ejection fraction (p = 0.021), absolute volume of lung spared at 10 Gy (p = 0.025), percentage of lung volume receiving {>=}20 Gy (V{sub 20}; p 0.002), and mean lung dose (p = 0.013). On multivariate analysis, only V{sub 20} was predictive of PRD (p = 0.017; odds ratio, 1.50; 95% confidence interval, 1.08-2.08) or non-cancer-related death (p = 0.033; odds ratio, 1.21; 95% confidence interval, 1.02-1.45). Conclusion: The results of our study have shown that fatal pulmonary toxicities were associated with radiation to the contralateral lung. V{sub 20} was the only independent determinant for risk of PRD or non-cancer-related death. The mean V{sub 20} of the non-PRD patients was considerably lower than that accepted during standard thoracic radiotherapy, implying that the V{sub 20} should be kept as low as possible after extrapleural pneumonectomy.

  19. ROC curves and evaluation of radiation-induced pulmonary toxicity in breast cancer

    SciTech Connect

    Lind, Pehr A. . E-mail: Pehr.Lind@Karolinska.se; Wennberg, Berit M.Sc.; Gagliardi, Giovanna; Rosfors, Stefan; Blom-Goldman, Ulla; Lidestahl, Anders; Svane, Gunilla

    2006-03-01

    Purpose: To study clinical, radiologic, and physiologic pulmonary toxicity in 128 women after adjuvant radiotherapy (RT) for breast cancer in relation to dosimetric factors. Methods and Material: The patients underwent pulmonary function testing before and 5 months post-RT. Similarly, computer tomography of the chest was repeated 4 months post-RT and changes were scored with a semiquantitative system. Clinical symptoms were registered and scored according to Common Toxicity Criteria. All patients underwent three-dimensional dose planning, and the ipsilateral lung volume receiving {>=}13 Gy (V13), V20, and V30 were calculated. Multiple logistic or regression analyses were used for multivariate modeling. The relation between the dosimetric factors and side effects was also analyzed with receiver operating characteristic (ROC) curves. Results: V20 was, according to multivariate modeling, the most important variable for the occurrence of the three studied side effects (p < 0.01). Age was also related to symptomatic and radiologic pneumonitis. Reduced pre-RT functional level was more common in patients developing symptomatic toxicity. The ROC areas for symptomatic pneumonitis in relation to V13, V20, and V30 were 0.69, 0.69, and 0.67, and for radiologic pneumonitis 0.85, 0.85, and 0.81. Conclusions: Our results support the use of three-dimensional planning aimed at minimizing the percent of incidentally irradiated lung volume to reduce pulmonary toxicity. Age was also correlated with post-RT side effects. According to ROC analysis, V20 could well predict the risk for radiologic pneumonitis for the studied semiquantitative model.

  20. Anti-angiogenic effect of bare titanium dioxide nanoparticles on pathologic neovascularization without unbearable toxicity.

    PubMed

    Jo, Dong Hyun; Kim, Jin Hyoung; Son, Jin Gyeong; Song, Nam Woong; Kim, Yong-Il; Yu, Young Suk; Lee, Tae Geol; Kim, Jeong Hun

    2014-07-01

    Local application requires fewer nanoparticles than systemic delivery to achieve effective concentration. In this study, we investigated the potential toxicity and efficacy of bare titanium dioxide (TiO2) nanoparticles by local administration into the eye. Mono-disperse, 20nm-size TiO2 nanoparticles did not affect the viability of retinal constituent cells within certain range of concentrations (~1.30μg/mL). Furthermore, local delivery of TiO2 nanoparticles did not induce any significant toxicity at the level of gene expression and histologic integrity in the retina of C57BL/6 mice. Interestingly, at the low concentration (130ng/mL) without definite toxicity, these nanoparticles suppressed in vitro angiogenesis processes and in vivo retinal neovascularization in oxygen-induced retinopathy mice when they are administered intravitreally. Taken together, our results demonstrate that even TiO2 nanoparticles can be safely utilized for the treatment of retinal diseases at the adequate concentration levels, especially through local administration. In this paper the local application of titanium dioxide is described as a local treatment for retinal diseases associated with neovascularization. While these nanoparticles have known systemic toxicity, this work demonstrates that when applied locally in a mouse model, they can be used without observable toxicity even in their native forms. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio

    NASA Astrophysics Data System (ADS)

    Zhang, Weicheng; Liu, Xiawei; Bao, Shaopan; Xiao, Bangding; Fang, Tao

    2016-12-01

    For safety and environmental risk assessments of nanomaterials (NMs) and to provide essential toxicity data, nano-specific toxicities, or excess toxicities, of ZnO, CuO, and Ag nanoparticles (NPs) (20, 20, and 30 nm, respectively) to Escherichia coli and Saccharomyces cerevisiae in short-term (6 h) and long-term (48 h) bioassays were quantified based on a toxic ratio. ZnO NPs exhibited no nano-specific toxicities, reflecting similar toxicities as ZnO bulk particles (BPs) (as well as zinc salt). However, CuO and Ag NPs yielded distinctly nano-specific toxicities when compared with their BPs. According to their nano-specific toxicities, the capability of these NPs in eliciting hazardous effects on humans and the environment was as follows: CuO > Ag > ZnO NPs. Moreover, long-term bioassays were more sensitive to nano-specific toxicity than short-term bioassays. Overall, nano-specific toxicity is a meaningful measurement to evaluate the environmental risk of NPs. The log T e particle value is a useful parameter for quantifying NP nano-specific toxicity and enabling comparisons of international toxicological data. Furthermore, this value could be used to determine the environmental risk of NPs.

  2. Development of a biopolymer nanoparticle-based method of oral toxicity testing in aquatic invertebrates.

    PubMed

    Gott, Ryan C; Luo, Yangchao; Wang, Qin; Lamp, William O

    2014-06-01

    Aquatic toxicity testing generally focuses on the water absorption/dermal route of exposure to potential toxic chemicals, while much less work has been done on the oral route of exposure. This is due in part to the difficulties of applying traditional oral toxicity testing to aquatic environments, including the tendency for test chemicals to dissolve into water. The use of biopolymer nanoparticles to encapsulate test chemicals onto food to prevent dissolution is one solution presented herein. The biopolymers zein and chitosan were explored for their previously known nanoparticle-forming abilities. Nanoparticles containing the test chemical rhodamine B were formed, applied as films to coat food, and then fed to the test organism, the freshwater amphipod Hyalella azteca. In feeding trials both zein and chitosan nanoparticles showed a significantly lower release rate of rhodamine B into water than food dyed with rhodamine B without biopolymer nanoparticles. Zein nanoparticles also showed better retention ability than chitosan nanoparticles. Both kinds of nanoparticles showed no significant effect on the survival, growth, or feeding behavior of H. azteca. Thus these biopolymers may be an effective system to encapsulate and deliver chemicals to aquatic invertebrates without interfering with common toxicity assessment endpoints like survival and growth. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes

    EPA Science Inventory

    Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes Nanoparticle uptake in cells may be an important determinant of their potential cytotoxic and inflammatory effects. Six commercial TiO2 NP (A=Alfa Aesar,10nm, A*=Alfa Aesar 32nm, B=P25 27...

  4. Enhanced resistance to nanoparticle toxicity is conferred by overproduction of extracellular polymeric substances.

    PubMed

    Joshi, Nimisha; Ngwenya, Bryne T; French, Christopher E

    2012-11-30

    The increasing production and use of engineered nanoparticles, coupled with their demonstrated toxicity to different organisms, demands the development of a systematic understanding of how nanoparticle toxicity depends on important environmental parameters as well as surface properties of both cells and nanomaterials. We demonstrate that production of the extracellular polymeric substance (EPS), colanic acid by engineered Escherichia coli protects the bacteria against silver nanoparticle toxicity. Moreover, exogenous addition of EPS to a control strain results in an increase in cell viability, as does the addition of commercial EPS polymer analogue xanthan. Furthermore, we have found that an EPS producing strain of Sinorhizobium meliloti shows higher survival upon exposure to silver nanoparticles than the parent strain. Transmission electron microscopy (TEM) observations showed that EPS traps the nanoparticles outside the cells and reduces the exposed surface area of cells to incoming nanoparticles by inducing cell aggregation. Nanoparticle size characterization in the presence of EPS and xanthan indicated a marked tendency towards aggregation. Both are likely effective mechanisms for reducing nanoparticle toxicity in the natural environment. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes

    EPA Science Inventory

    Toxicity Assessment of Six Titanium Dioxide Nanoparticles in Human Epidermal Keratinocytes Nanoparticle uptake in cells may be an important determinant of their potential cytotoxic and inflammatory effects. Six commercial TiO2 NP (A=Alfa Aesar,10nm, A*=Alfa Aesar 32nm, B=P25 27...

  6. Ultrastructural hepatocytic alterations induced by silver nanoparticle toxicity.

    PubMed

    Almansour, Mansour; Sajti, Laszlo; Melhim, Walid; Jarrar, Bashir M

    2016-01-01

    Silver nanoparticles (SNPs) are widely used in nanomedicine and consuming products with potential risk to human health. While considerable work was carried out on the molecular, biochemical, and physiological alterations induced by these particles, little is known of the ultrastructural pathological alterations that might be induced by nanosilver materials. The aim of the present work is to investigate the hepatocyte ultrastructural alterations that might be induced by SNP exposure. Male rats were subjected to a daily single dose (2 mg/kg) of SNPs (15-35 nm diameter) for 21 days. Liver biopsies from all rats under study were processed for transmission electron microscopy examination. The following hepatic ultrastructural alterations were demonstrated: mitochondria swelling and crystolysis, endoplasmic reticulum disruption, cytoplasmic vacuolization, lipid droplets accumulation, glycogen depletion, karyopyknosis, apoptosis, sinusoidal dilatation, Kupffer cells activation, and myelin figures formation. The current findings may indicate that SNPs can induce hepatocyte organelles alteration, leading to cellular damage that may affect the function of the liver. These findings might indicate that SNPs potentially trigger heptocyte ultrastructural alterations that may affect the function of the liver with potential risk on human health in relation to numerous applications of these particles. More work is needed to elucidate probable ultrastructural alterations in the vital organs that might result from nanosilver toxicity.

  7. Synthesis of fluorapatite-hydroxyapatite nanoparticles and toxicity investigations.

    PubMed

    Montazeri, N; Jahandideh, R; Biazar, Esmaeil

    2011-01-01

    In this study, calcium phosphate nanoparticles with two phases, fluorapatite (FA; Ca(10)(PO(4))(6)F(2)) and hydroxyapatite (HA; Ca(10)(PO(4))(6)(OH)(2)), were prepared using the solgel method. Ethyl phosphate, hydrated calcium nitrate, and ammonium fluoride were used, respectively, as P, Ca, and F precursors with a Ca:P ratio of 1:72. Powders obtained from the sol-gel process were studied after they were dried at 80°C and heat treated at 550°C. The degree of crystallinity, particle and crystallite size, powder morphology, chemical structure, and phase analysis were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Zetasizer experiments. The results of XRD analysis and FTIR showed the presence of hydroxyapatite and fluorapatite phases. The sizes of the crystallites estimated from XRD patterns using the Scherrer equation and the crystallinity of the hydroxyapatite phase were about 20 nm and 70%, respectively. Transmission electron microscope and SEM images and Zetasizer experiments showed an average size of 100 nm. The in vitro behavior of powder was investigated with mouse fibroblast cells. The results of these experiments indicated that the powders were biocompatible and would not cause toxic reactions. These compounds could be applied for hard-tissue engineering.

  8. Bivalve molluscs as a unique target group for nanoparticle toxicity.

    PubMed

    Canesi, Laura; Ciacci, Caterina; Fabbri, Rita; Marcomini, Antonio; Pojana, Giulio; Gallo, Gabriella

    2012-05-01

    Due to the continuous development and production of manufactured nanomaterials or nanoparticles (NPs), their uptake and effects in the aquatic biota represent a major concern. Estuarine and coastal environments are expected to represent the ultimate sink for NPs, where their chemical behavior (aggregation/agglomeration) and consequent fate may be critical in determining the biological impact. Bivalve mollusks are abundant from freshwater to marine ecosystems, where they are widely utilized in biomonitoring of environmental perturbations. As suspension-feeders, they have highly developed processes for cellular internalization of nano- and micro-scale particles (endo- and phagocytosis), integral to key physiological functions such as intra-cellular digestion and cellular immunity. Here we will summarise available information on the effects of different types of NPs in different bivalve species, in particular Mytilus spp. Data on the effects and modes of action of different NPs on mussel hemocytes in vitro demonstrate that cell-mediated immunity represents a significant target for NPs. Moreover, in vivo exposure to NPs indicates that, due to the physiological mechanisms involved in the feeding process, NP agglomerates/aggregates taken up by the gills are directed to the digestive gland, where intra-cellular uptake of nanosized materials induces lysosomal perturbations and oxidative stress. Overall, bivalves represent a particularly suitable model for investigating the effects and mechanisms of action underlying the potential toxicity of NPs in marine invertebrates.

  9. EVALUATION OF THE PULMONARY TOXICITY OF AMBIENT PARTICULATE MATTER FROM CAMP VICTORY, IRAQ

    PubMed Central

    Porter, K. L.; Green, F. H. Y.; Harley, R. A.; Vallyathan, V.; Castranova, V.; Waldron, N. R.; Leonard, S. S.; Nelson, D. E.; Lewis, J. A.; Jackson, D. A.

    2016-01-01

    Anecdotal reports in the press and epidemiological studies suggest that deployment to Iraq and Afghanistan may be associated with respiratory diseases and symptoms in U.S. military personnel and veterans. Exposures during military operations were complex, but virtually all service members were exposed to high levels of respirable, geogenic dust. Inhalation of other dusts has been shown to be associated with adverse health effects, but the pulmonary toxicity of ambient dust from Iraq has not been previously studied. The relative toxicity of Camp Victory dust was evaluated by comparing it to particulate matter from northern Kuwait, a standard U.S. urban dust, and crystalline silica using a single intratracheal instillation in rats. Lung histology, protein levels, and cell counts were evaluated in the bronchoalveolar lavage fluid 1–150 d later. The Iraq dust provoked an early significant, acute inflammatory response. However, the level of inflammation in response to the Iraq dust, U.S. urban dust, and Kuwait dust rapidly declined and was nearly at control levels by the end of the study At later times, animals exposed to the Iraq, U.S. urban, or Kuwait dusts showed increased small airway remodeling and emphysema compared to silica-exposed and control animals without evidence of fibrosis or premalignant changes. The severity and persistence of pulmonary toxicity of these three dusts from the Middle East resemble those of a U.S. urban dust and are less than those of silica. Therefore, Iraq dust exposure is not highly toxic, but similar to other poorly soluble low-toxicity dusts. PMID:26594896

  10. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles

    SciTech Connect

    Roedel, Erik Q.; Cafasso, Danielle E.; Lee, Karen W.M.; Pierce, Lisa M.

    2012-02-15

    Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24 h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals. -- Highlights: ► Intratracheal instillation of W–Ni–Co and W–Ni–Fe induces lung inflammation in rats. ► W–Ni–Co and W–Ni–Fe alter expression of oxidative stress and toxicity genes. ► W

  11. Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary toxicity

    PubMed Central

    Fujita, Katsuhide; Fukuda, Makiko; Endoh, Shigehisa; Maru, Junko; Kato, Haruhisa; Nakamura, Ayako; Shinohara, Naohide; Uchino, Kanako; Honda, Kazumasa

    2015-01-01

    Abstract To elucidate the effect of size on the pulmonary toxicity of single-wall carbon nanotubes (SWCNTs), we prepared two types of dispersed SWCNTs, namely relatively thin bundles with short linear shapes (CNT-1) and thick bundles with long linear shapes (CNT-2), and conducted rat intratracheal instillation tests and in vitro cell-based assays using NR8383 rat alveolar macrophages. Total protein levels, MIP-1α expression, cell counts in BALF, and histopathological examinations revealed that CNT-1 caused pulmonary inflammation and slower recovery and that CNT-2 elicited acute lung inflammation shortly after their instillation. Comprehensive gene expression analysis confirmed that CNT-1-induced genes were strongly associated with inflammatory responses, cell proliferation, and immune system processes at 7 or 30 d post-instillation. Numerous genes were significantly upregulated or downregulated by CNT-2 at 1 d post-instillation. In vitro assays demonstrated that CNT-1 and CNT-2 SWCNTs were phagocytized by NR8383 cells. CNT-2 treatment induced cell growth inhibition, reactive oxygen species production, MIP-1α expression, and several genes involved in response to stimulus, whereas CNT-1 treatment did not exert a significant impact in these regards. These results suggest that SWCNTs formed as relatively thin bundles with short linear shapes elicited delayed pulmonary inflammation with slower recovery. In contrast, SWCNTs with a relatively thick bundle and long linear shapes sensitively induced cellular responses in alveolar macrophages and elicited acute lung inflammation shortly after inhalation. We conclude that the pulmonary toxicity of SWCNTs is closely associated with the size of the bundles. These physical parameters are useful for risk assessment and management of SWCNTs. PMID:25865113

  12. Size effects of single-walled carbon nanotubes on in vivo and in vitro pulmonary toxicity.

    PubMed

    Fujita, Katsuhide; Fukuda, Makiko; Endoh, Shigehisa; Maru, Junko; Kato, Haruhisa; Nakamura, Ayako; Shinohara, Naohide; Uchino, Kanako; Honda, Kazumasa

    2015-03-01

    To elucidate the effect of size on the pulmonary toxicity of single-wall carbon nanotubes (SWCNTs), we prepared two types of dispersed SWCNTs, namely relatively thin bundles with short linear shapes (CNT-1) and thick bundles with long linear shapes (CNT-2), and conducted rat intratracheal instillation tests and in vitro cell-based assays using NR8383 rat alveolar macrophages. Total protein levels, MIP-1α expression, cell counts in BALF, and histopathological examinations revealed that CNT-1 caused pulmonary inflammation and slower recovery and that CNT-2 elicited acute lung inflammation shortly after their instillation. Comprehensive gene expression analysis confirmed that CNT-1-induced genes were strongly associated with inflammatory responses, cell proliferation, and immune system processes at 7 or 30 d post-instillation. Numerous genes were significantly upregulated or downregulated by CNT-2 at 1 d post-instillation. In vitro assays demonstrated that CNT-1 and CNT-2 SWCNTs were phagocytized by NR8383 cells. CNT-2 treatment induced cell growth inhibition, reactive oxygen species production, MIP-1α expression, and several genes involved in response to stimulus, whereas CNT-1 treatment did not exert a significant impact in these regards. These results suggest that SWCNTs formed as relatively thin bundles with short linear shapes elicited delayed pulmonary inflammation with slower recovery. In contrast, SWCNTs with a relatively thick bundle and long linear shapes sensitively induced cellular responses in alveolar macrophages and elicited acute lung inflammation shortly after inhalation. We conclude that the pulmonary toxicity of SWCNTs is closely associated with the size of the bundles. These physical parameters are useful for risk assessment and management of SWCNTs.

  13. Toxicity of tungsten carbide and cobalt-doped tungsten carbide nanoparticles in mammalian cells in vitro.

    PubMed

    Bastian, Susanne; Busch, Wibke; Kühnel, Dana; Springer, Armin; Meissner, Tobias; Holke, Roland; Scholz, Stefan; Iwe, Maria; Pompe, Wolfgang; Gelinsky, Michael; Potthoff, Annegret; Richter, Volkmar; Ikonomidou, Chrysanthy; Schirmer, Kristin

    2009-04-01

    Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. We aimed to assess the toxicity of well-characterized tungsten carbide (WC) and cobalt-doped tungsten carbide (WC-Co) nanoparticle suspensions in an array of mammalian cells. We examined acute toxicity of WC and of WC-Co (10% weight content Co) nanoparticles in different human cell lines (lung, skin, and colon) as well as in rat neuronal and glial cells (i.e., primary neuronal and astroglial cultures and the oligodendrocyte precursor cell line OLN-93). Furthermore, using electron microscopy, we assessed whether nanoparticles can be taken up by living cells. We chose these in vitro systems in order to evaluate for potential toxicity of the nanoparticles in different mammalian organs (i.e., lung, skin, intestine, and brain). Chemical-physical characterization confirmed that WC as well as WC-Co nanoparticles with a mean particle size of 145 nm form stable suspensions in serum-containing cell culture media. WC nanoparticles were not acutely toxic to the studied cell lines. However, cytotoxicity became apparent when particles were doped with Co. The most sensitive were astrocytes and colon epithelial cells. Cytotoxicity of WC-Co nanoparticles was higher than expected based on the ionic Co content of the particles. Analysis by electron microscopy demonstrated presence of WC nanoparticles within mammalian cells. Our findings demonstrate that doping of WC nanoparticles with Co markedly increases their cytotoxic effect and that the presence of WC-Co in particulate form is essential to elicit this combinatorial effect.

  14. Toxicity of Tungsten Carbide and Cobalt-Doped Tungsten Carbide Nanoparticles in Mammalian Cells in Vitro

    PubMed Central

    Bastian, Susanne; Busch, Wibke; Kühnel, Dana; Springer, Armin; Meißner, Tobias; Holke, Roland; Scholz, Stefan; Iwe, Maria; Pompe, Wolfgang; Gelinsky, Michael; Potthoff, Annegret; Richter, Volkmar; Ikonomidou, Chrysanthy; Schirmer, Kristin

    2009-01-01

    Background Tungsten carbide nanoparticles are being explored for their use in the manufacture of hard metals. To develop nanoparticles for broad applications, potential risks to human health and the environment should be evaluated and taken into consideration. Objective We aimed to assess the toxicity of well-characterized tungsten carbide (WC) and cobaltdoped tungsten carbide (WC-Co) nanoparticle suspensions in an array of mammalian cells. Methods We examined acute toxicity of WC and of WC-Co (10% weight content Co) nanoparticles in different human cell lines (lung, skin, and colon) as well as in rat neuronal and glial cells (i.e., primary neuronal and astroglial cultures and the oligodendro cyte precursor cell line OLN-93). Furthermore, using electron microscopy, we assessed whether nanoparticles can be taken up by living cells. We chose these in vitro systems in order to evaluate for potential toxicity of the nanoparticles in different mammalian organs (i.e., lung, skin, intestine, and brain). Results Chemical–physical characterization confirmed that WC as well as WC-Co nanoparticles with a mean particle size of 145 nm form stable suspensions in serum-containing cell culture media. WC nanoparticles were not acutely toxic to the studied cell lines. However, cytotoxicity became apparent when particles were doped with Co. The most sensitive were astrocytes and colon epithelial cells. Cytotoxicity of WC-Co nanoparticles was higher than expected based on the ionic Co content of the particles. Analysis by electron microscopy demonstrated presence of WC nanoparticles within mammalian cells. Conclusions Our findings demonstrate that doping of WC nanoparticles with Co markedly increases their cytotoxic effect and that the presence of WC-Co in particulate form is essential to elicit this combinatorial effect. PMID:19440490

  15. Inhalation toxicity and lung toxicokinetics of C60 fullerene nanoparticles and microparticles.

    PubMed

    Baker, Gregory L; Gupta, Amit; Clark, Mark L; Valenzuela, Blandina R; Staska, Lauren M; Harbo, Sam J; Pierce, Judy T; Dill, Jeffery A

    2008-01-01

    While several recent reports have described the toxicity of water-soluble C60 fullerene nanoparticles, none have reported the toxicity resulting from the inhalation exposures to C60 fullerene nanoparticles or microparticles. To address this knowledge gap, we exposed male rats to C60 fullerene nanoparticles (2.22 mg/m3, 55 nm diameter) and microparticles (2.35 mg/m3, 0.93 microm diameter) for 3 h a day, for 10 consecutive days using a nose-only exposure system. Nanoparticles were created utilizing an aerosol vaporization and condensation process. Nanoparticles and microparticles were subjected to high-pressure liquid chromatography (HPLC), XRD, and scanning laser Raman spectroscopy, which cumulatively indicated no chemical modification of the C60 fullerenes occurred during the aerosol generation. At necropsy, no gross or microscopic lesions were observed in either group of C60 fullerene exposures rats. Hematology and serum chemistry results found statistically significant differences, although small in magnitude, in both exposure groups. Comparisons of bronchoalveolar (BAL) lavage fluid parameters identified a significant increase in protein concentration in rats exposed to C60 fullerene nanoparticles. BAL fluid macrophages from both exposure groups contained brown pigments, consistent with C60 fullerenes. C60 lung particle burdens were greater in nanoparticle-exposed rats than in microparticle-exposed rats. The calculated lung deposition rate and deposition fraction were 41 and 50% greater, respectively, in C60 fullerene nanoparticle-exposed group than the C60 fullerene microparticle-exposed group. Lung half-lives for C60 fullerene nanoparticles and microparticles were 26 and 29 days, respectively. In summary, this first in vivo assessment of the toxicity resulting from inhalation exposures to C60 fullerene nanoparticles and microparticles found minimal changes in the toxicological endpoints examined. Additional toxicological assessments involving longer duration

  16. Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

    PubMed Central

    Singh, Pramila; DeMarini, David M; Dick, Colin A J; Tabor, Dennis G; Ryan, Jeff V; Linak, William P; Kobayashi, Takahiro; Gilmour, M Ian

    2004-01-01

    Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975. PMID:15175167

  17. Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

    PubMed

    Singh, Pramila; DeMarini, David M; Dick, Colin A J; Tabor, Dennis G; Ryan, Jeff V; Linak, William P; Kobayashi, Takahiro; Gilmour, M Ian

    2004-06-01

    Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975.

  18. Silver nanoparticle toxicity to Daphnia magna is a function of dissolved silver concentration.

    PubMed

    Newton, Kim M; Puppala, Hema L; Kitchens, Christopher L; Colvin, Vicki L; Klaine, Stephen J

    2013-10-01

    The most persistent question regarding the toxicity of silver nanoparticles (AgNPs) is whether this toxicity is due to the nanoparticles themselves or the silver ions (Ag(+)) they release. The present study investigates the role of surface coating and the presence of dissolved organic carbon on the toxicity of AgNPs to Daphnia magna and tests the hypothesis that the acute toxicity of AgNPs is a function of dissolved Ag produced by nanoparticle dissolution. Toxicity of silver nitrate (AgNO3) and AgNPs with surface coatings-gum arabic (AgGA), polyethylene glycol (AgPEG), and polyvinylpyrrolidone (AgPVP)-at 48 h was assessed in US Environmental Protection Agency moderately hard reconstituted water alone and augmented with Suwannee River dissolved organic carbon (DOC). As expected, AgNO3 was the most toxic to D. magna and AgPVPs were the least toxic. In general, Suwannee River DOC presence reduced the toxicity of AgNO3, AgGAs, and AgPEG, while the toxicity of AgPVPs was unaffected. The measured dissolved Ag concentrations for all AgNPs and AgNO3 at the 48-h median lethal concentration in moderately hard reconstituted water were similar. The presence of Suwannee River DOC decreased the ratio of measured dissolved Ag to measured total Ag concentration. These results support the hypothesis that toxicity of AgNPs to D. magna is a function of dissolved Ag concentration from these particles.

  19. Use of Metal Oxide Nanoparticle Band Gap to Develop a Predictive Paradigm for Oxidative Stress and Acute Pulmonary Inflammation

    PubMed Central

    Zhang, Haiyuan; Ji, Zhaoxia; Xia, Tian; Meng, Huan; Low-Kam, Cecile; Liu, Rong; Pokhrel, Suman; Lin, Sijie; Wang, Xiang; Liao, Yu-Pei; Wang, Meiying; Li, Linjiang; Rallo, Robert; Damoiseaux, Robert; Telesca, Donatello; Mädler, Lutz; Cohen, Yoram; Zink, Jeffrey I.; Nel, Andre E.

    2014-01-01

    We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (Ec) levels with the cellular redox potential (−4.12 to −4.84 eV) was strongly correlated to the ability of Co3O4, Cr2O3, Ni2O3, Mn2O3 and CoO nanoparticles to induce oxygen radicals, oxidative stress and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of CB57 Bl/6 mice. Co3O4, Ni2O3, Mn2O3 and CoO nanoparticles could also oxidize cytochrome c as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute pulmonary inflammation that is not predicted by Ec levels, the adverse biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. Taken together, these results demonstrate, for the first time, that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated in vitro/in vivo hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure-activity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials. PMID:22502734

  20. Development of screening assays for nanoparticle toxicity assessment in human blood: preliminary studies with charged Au nanoparticles.

    PubMed

    Love, Sara A; Thompson, John W; Haynes, Christy L

    2012-09-01

    As nanoparticles have found increased use in both consumer and medical applications, corresponding increases in possible exposure to humans necessitate studies examining the impacts of these nanomaterials in biological systems. This article examines the effects of approximately 30-nm-diameter gold nanoparticles, with positively and negatively charged surface coatings in human blood. Here, we study the exposure effects, with up to 72 h of exposure to 5, 15, 25 and 50 µg/ml nanoparticles on hemolysis, reactive oxygen species (ROS) generation and platelet aggregation in subsets of cells from human blood. Assessing viability with hemolysis, results show significant changes in a concentration-dependent fashion. Rates of ROS generation were investigated using the dichlorofluorscein diacetate-based assay as ROS generation is a commonly suspected mechanism of nanoparticle toxicity; herein, ROS was not a significant factor. Optical monitoring of platelet aggregation revealed that none of the examined nanoparticles induced aggregation upon short-term exposure.

  1. Photoinduced toxicity of PrF3 and LaF3 nanoparticles

    NASA Astrophysics Data System (ADS)

    Pudovkin, M. S.; Zelenikhin, P. V.; Krasheninnikova, A. O.; Korableva, S. L.; Nizamutdinov, A. S.; Alakshin, E. M.; Semashko, V. V.; Safiullin, R. A.; Kadirov, M. K.

    2016-10-01

    PrF3 and LaF3 nanoparticles were synthesized by the hydrothermal method. The size distribution of these nanoparticles in the colloidal solution produced was studied by photon correlation spectroscopy. The mean diameter of the nanoparticles was 42 ± 1 nm. During the study of the toxicity of the nanoparticles, the mixture of a colloidal solution of the nanoparticles with cells to be studied was irradiated by 30-mW continuous lasers at wavelengths of 532 and 473 nm. The concentration of salmonella cells in normal saline was 106 cell/mL, while that of nanoparticles was 0.1 g/L. The cell survival percentage was 39, 34, and 20% for the irradiation times of 5, 10, and 15 min, respectively, at an optimal laser radiation power density of 0.4 W/cm at a wavelength of 532 nm. It was ascertained that LaF3 nanoparticles do not possess the property of photoinduced toxicity and the apoptosing effect. Moreover, the property of photoinduced toxicity is not shared by microparticles, in contrast to nanoparticles.

  2. Developmental toxicity and DNA damaging properties of silver nanoparticles in the catfish (Clarias gariepinus).

    PubMed

    Sayed, Alaa El-Din H; Soliman, Hamdy A M

    2017-10-01

    Although, silver nanoparticles (AgNPs) are used in many different products, little information is known about their toxicity in tropical fish embryos. Therefore, this study evaluated the developmental toxicity of waterborne silver nanoparticles in embryos of Clarias gariepinus. Embryos were treated with (0, 25, 50, 75ng/L silver nanoparticles) in water up to 144h postfertilization stage (PFS). Results revealed various morphological malformations including notochord curvature and edema. The mortality rate, malformations, and DNA fragmentation in embryos exposed to silver nanoparticles increased in a dose- and embryonic stage-dependent manner. The total antioxidant capacity and the activity of catalase in embryos exposed to 25ng/L silver nanoparticles were decreased significantly while the total antioxidant capacity and the activity of catalase were insignificantly increased with increasing concentrations in the embryos from 24 to 144 h-PFS exposed to 50 and 75ng/L silver nanoparticles. Lipid peroxidation values showed fluctuations with doses of silver nanoparticles. Histopathological lesions including severely distorted and wrinkled notochord were observed. The current data propose that the toxicity of silver nanoparticles in C. gariepinus embryos is caused by oxidative stress and genotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles

    SciTech Connect

    Cho, Wan-Seob; Cho, Minjung; Jeong, Jinyoung; Choi, Mina; Cho, Hea-Young; Han, Beom Seok; Kim, Sheen Hee; Kim, Hyoung Ook; Lim, Yong Taik; Chung, Bong Hyun Jeong, Jayoung

    2009-04-01

    In general, gold nanoparticles are recognized as being as nontoxic. Still, there have been some reports on their toxicity, which has been shown to depend on the physical dimension, surface chemistry, and shape of the nanoparticles. In this study, we carry out an in vivo toxicity study using 13 nm-sized gold nanoparticles coated with PEG (MW 5000). In our findings the 13 nm sized PEG-coated gold nanoparticles were seen to induce acute inflammation and apoptosis in the liver. These nanoparticles were found to accumulate in the liver and spleen for up to 7 days after injection and to have long blood circulation times. In addition, transmission electron microscopy showed that numerous cytoplasmic vesicles and lysosomes of liver Kupffer cells and spleen macrophages contained the PEG-coated gold nanoparticles. These findings of toxicity and kinetics of PEG-coated gold nanoparticles may have important clinical implications regarding the safety issue as PEG-coated gold nanoparticles are widely used in biomedical applications.

  4. Understanding the mutual impact of interaction between hydrophobic nanoparticles and pulmonary surfactant monolayer.

    PubMed

    Sachan, Amit K; Galla, Hans-Joachim

    2014-03-26

    Interaction between hydrophobic nanoparticles (NPs) and a pulmonary surfactant (PS) film leads to a shift in molecular packing of surfactant molecules in the PS film around the interacting NPs. The resultant structural arrangement of surfactants around the NPs may be a potential structural factor responsible for their high retention ability within the film. Moreover, during this interaction, surfactant molecules coat the NPs and change their surface properties.

  5. Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos.

    PubMed

    Asharani, P V; Lianwu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

    2011-03-01

    Nanoparticles have diverse applications in electronics, medical devices, therapeutic agents and cosmetics. While the commercialization of nanoparticles is rapidly expanding, their health and environmental impact is not well understood. Toxicity assays of silver, gold, and platinum nanoparticles, using zebrafish embryos to study their developmental effects were carried out. Gold (Au-NP, 15-35 nm), silver (Ag-NP, 5-35 nm) and platinum nanoparticles (Pt-NP, 3-10 nm) were synthesized using polyvinyl alcohol (PVA) as a capping agent. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. The addition of Ag-NP resulted in a concentration-dependant increase in mortality rate. Both Ag-NP and Pt-NP induced hatching delays, as well as a concentration dependant drop in heart rate, touch response and axis curvatures. Ag-NP also induced other significant phenotypic changes including pericardial effusion, abnormal cardiac morphology, circulatory defects and absence or malformation of the eyes. In contrast, Au-NP did not show any indication of toxicity. Uptake and accumulation of nanoparticles in embryos was confirmed by inductively coupled plasma optical emission spectroscopy (ICP-OES), which revealed detectable levels in embryos within 72 hpf. Ag-NP and Au-NP were taken up by the embryos in relatively equal amounts whereas lower Pt concentrations were observed in embryos exposed to Pt-NP. This was probably due to the small size of the Pt nanoparticles compared to Ag-NP and Au-NP, thus resulting in fewer metal atoms being retained in the embryos. Among the nanoparticles studied, Ag-NPs were found to be the most toxic and Au-NPs the non-toxic. The toxic effects exhibited by the zebrafish embryos as a consequence of nanoparticle exposure, accompanied by the accumulation of metals inside the body calls for urgent further investigations in this field.

  6. Fate and toxicity of metallic and metal-containing nanoparticles for biomedical applications.

    PubMed

    Li, Yu-Feng; Chen, Chunying

    2011-11-04

    It is important to obtain a better understanding of the uptake, trafficking, pharmacokinetics, clearance, and role of nanomaterials in biological systems, so that their possible undesirable effects can be avoided. A number of metallic or metal-containing nanomaterials, such as gold nanoparticles and nanorods, quantum dots, iron oxides nanoparticles, and endohedral metallofullerenes, have already been or will soon become very promising for biomedical applications. This review presents a summary of currently available data on the fate and toxicity of these metallic or metal-containing nanoparticles based on animal studies. Several issues regarding the nanotoxicity assessment and future directions on the study of the fate of these nanoparticles are also proposed.

  7. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles.

    PubMed

    Roedel, Erik Q; Cafasso, Danielle E; Lee, Karen W M; Pierce, Lisa M

    2012-02-15

    Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals.

  8. Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives

    PubMed Central

    Yoshiura, Yukiko; Myojo, Toshihiko; Oyabu, Takako; Lee, Byeong-Woo; Okada, Takami; Li, Yunshan; Higashi, Toshiaki

    2017-01-01

    We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 μm) at three mass concentrations of 1, 4, and 16 mg/m3 for 22.5 months, and the rats were sacrificed after 6 months, 12 months, and 22.5 months of exposure. The low and medium concentrations did not induce statistically significant pulmonary inflammation, but the high concentration did, and, in addition, a histopathological examination showed fibrosis in the lung. Although lung tumor was observed in one sample of high exposure for 22.5 months, the cause was not statistically significant. On the other hand, a persistent increase in 8-OHdG was observed in the high exposure group, indicating that DNA damage by oxidative stress with persistent inflammation leads to the formation of tumorigenesis. The results of our studies show that toners with external additives lead to pulmonary inflammation, oxidative stress, and fibrosis only at lung burdens beyond overload. These data suggest that toners with external additives may have low toxicity in the lung. PMID:28191462

  9. Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives.

    PubMed

    Tomonaga, Taisuke; Izumi, Hiroto; Yoshiura, Yukiko; Myojo, Toshihiko; Oyabu, Takako; Lee, Byeong-Woo; Okada, Takami; Li, Yunshan; Kawai, Kazuaki; Higashi, Toshiaki; Morimoto, Yasuo

    2017-01-01

    We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 μm) at three mass concentrations of 1, 4, and 16 mg/m(3) for 22.5 months, and the rats were sacrificed after 6 months, 12 months, and 22.5 months of exposure. The low and medium concentrations did not induce statistically significant pulmonary inflammation, but the high concentration did, and, in addition, a histopathological examination showed fibrosis in the lung. Although lung tumor was observed in one sample of high exposure for 22.5 months, the cause was not statistically significant. On the other hand, a persistent increase in 8-OHdG was observed in the high exposure group, indicating that DNA damage by oxidative stress with persistent inflammation leads to the formation of tumorigenesis. The results of our studies show that toners with external additives lead to pulmonary inflammation, oxidative stress, and fibrosis only at lung burdens beyond overload. These data suggest that toners with external additives may have low toxicity in the lung.

  10. Acute pulmonary hemorrhage during isoflurane anesthesia in two cats exposed to toxic black mold (Stachybotrys chartarum).

    PubMed

    Mader, Douglas R; Yike, Iwona; Distler, Anne M; Dearborn, Dorr G

    2007-09-01

    Acute pulmonary hemorrhage developed during isoflurane anesthesia in 2 Himalayan cats undergoing routine dental cleaning and prophylaxis. The cats were siblings and lived together. In both cats, results of pre-operative physical examinations and laboratory testing were unremarkable. Blood pressure and oxygen saturation were within reference ranges throughout the dental procedure. Approximately 15 to 20 minutes after administration of isoflurane was begun, frothy blood was noticed within the endotracheal tube. Blood was suctioned from the endotracheal tube, and the cats were allowed to recover from anesthesia. 1 cat initially responded to supportive care but developed a second episode of spontaneous pulmonary hemorrhage approximately 30 hours later and died. The other cat responded to supportive care and was discharged after 4 days, but its condition deteriorated, and the cat died 10 days later. Subsequently, it was discovered that the home was severely contaminated with mold as a result of storm damage that had occurred approximately 7 months previously. Retrospective analysis of banked serum from the cats revealed satratoxin G, a biomarker for Stachybotrys chartarum, commonly referred to as "toxic black mold." Findings highlight the potential risk of acute pulmonary hemorrhage in animals living in an environment contaminated with mold following flood damage.

  11. Silver nanoparticles: mechanism of antimicrobial action, synthesis, medical applications, and toxicity effects

    NASA Astrophysics Data System (ADS)

    Prabhu, Sukumaran; Poulose, Eldho K.

    2012-10-01

    Silver nanoparticles are nanoparticles of silver which are in the range of 1 and 100 nm in size. Silver nanoparticles have unique properties which help in molecular diagnostics, in therapies, as well as in devices that are used in several medical procedures. The major methods used for silver nanoparticle synthesis are the physical and chemical methods. The problem with the chemical and physical methods is that the synthesis is expensive and can also have toxic substances absorbed onto them. To overcome this, the biological method provides a feasible alternative. The major biological systems involved in this are bacteria, fungi, and plant extracts. The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications. In most of the therapeutic applications, it is the antimicrobial property that is being majorly explored, though the anti-inflammatory property has its fair share of applications. Though silver nanoparticles are rampantly used in many medical procedures and devices as well as in various biological fields, they have their drawbacks due to nanotoxicity. This review provides a comprehensive view on the mechanism of action, production, applications in the medical field, and the health and environmental concerns that are allegedly caused due to these nanoparticles. The focus is on effective and efficient synthesis of silver nanoparticles while exploring their various prospective applications besides trying to understand the current scenario in the debates on the toxicity concerns these nanoparticles pose.

  12. Acute pulmonary edema in a storehouse of moldy oranges: a severe case of the organic dust toxic syndrome.

    PubMed

    Yoshida, K; Ando, M; Araki, S

    1989-01-01

    A woman who was 41 y of age developed pulmonary edema after massive fungal inhalation at an orange storehouse. A provocation test by exposure in the work-place was positive. Neither immunological studies with fungi isolated nor other clinical and histological examinations showed any evidence of hypersensitivity pneumonitis. This is the first report of a subject with organic dust toxic syndrome who developed pulmonary edema associated with the handling of moldy oranges.

  13. Pulmonary Toxicity, Distribution, and Clearance of Intratracheally Instilled Silicon Nanowires in Rats.

    PubMed

    Roberts, Jenny R; Mercer, Robert R; Chapman, Rebecca S; Cohen, Guy M; Bangsaruntip, Sarunya; Schwegler-Berry, Diane; Scabilloni, James F; Castranova, Vincent; Antonini, James M; Leonard, Stephen S

    Silicon nanowires (Si NWs) are being manufactured for use as sensors and transistors for circuit applications. The goal was to assess pulmonary toxicity and fate of Si NW using an in vivo experimental model. Male Sprague-Dawley rats were intratracheally instilled with 10, 25, 50, 100, or 250 μg of Si NW (~20-30 nm diameter; ~2-15 μm length). Lung damage and the pulmonary distribution and clearance of Si NW were assessed at 1, 3, 7, 28, and 91 days after-treatment. Si NW treatment resulted in dose-dependent increases in lung injury and inflammation that resolved over time. At day 91 after treatment with the highest doses, lung collagen was increased. Approximately 70% of deposited Si NW was cleared by 28 days with most of the Si NW localized exclusively in macrophages. In conclusion, Si NW induced transient lung toxicity which may be associated with an early rapid particle clearance; however, persistence of Si NW over time related to dose or wire length may lead to increased collagen deposition in the lung.

  14. Toxicity of nanoparticles embedded in paints compared with pristine nanoparticles in mice.

    PubMed

    Smulders, Stijn; Luyts, Katrien; Brabants, Gert; Landuyt, Kirsten Van; Kirschhock, Christine; Smolders, Erik; Golanski, Luana; Vanoirbeek, Jeroen; Hoet, Peter H M

    2014-09-01

    The unique physical and chemical properties of nanomaterials have led to their increased use in many industrial applications, including as a paint additive. For example, titanium dioxide (TiO2) engineered nanoparticles (ENPs) have well-established anti-UV, self-cleaning, and air purification effects. Silver (Ag) ENPs are renowned for their anti-microbial capabilities and silicon dioxide (SiO2) ENPs are used as fire retardants and anti-scratch coatings. In this study, the toxic effects and biodistribution of three pristine ENPs (TiO2, Ag, and SiO2), three aged paints containing ENPs (TiO2, Ag, and SiO2) along with control paints without ENPs were compared. BALB/c mice were oropharyngeally aspirated with ENPs or paint particles (20 μg/aspiration) once a week for 5 weeks and sacrificed either 2 or 28 days post final aspiration treatment. A bronchoalveolar lavage was performed and systemic blood toxicity was evaluated to ascertain cell counts, induction of inflammatory cytokines, and key blood parameters. In addition, the lung, liver, kidney, spleen, and heart were harvested and metal concentrations were determined. Exposure to pristine ENPs caused subtle effects in the lungs and negligible alterations in the blood. The most pronounced toxic effects were observed after Ag ENPs exposure; an increased neutrophil count and a twofold increase in pro-inflammatory cytokine secretion (keratinocyte chemoattractant (KC) and interleukin-1ß (IL-1ß)) were identified. The paint containing TiO2 ENPs did not modify macrophage and neutrophil counts, but mildly induced KC and IL-1ß. The paints containing Ag or SiO2 did not show significant toxicity. Biodistribution experiments showed distribution of Ag and Si outside the lung after aspiration to respectively pristine Ag or SiO2 ENPs. In conclusion, we demonstrated that even though direct exposure to ENPs induced some toxic effects, once they were embedded in a complex paint matrix little to no adverse toxicological effects were

  15. Toxicity of Nanoparticles Embedded in Paints Compared with Pristine Nanoparticles in Mice

    PubMed Central

    Smulders, Stijn; Luyts, Katrien; Brabants, Gert; Landuyt, Kirsten Van; Kirschhock, Christine; Smolders, Erik; Golanski, Luana; Vanoirbeek, Jeroen; Hoet, Peter HM

    2014-01-01

    The unique physical and chemical properties of nanomaterials have led to their increased use in many industrial applications, including as a paint additive. For example, titanium dioxide (TiO2) engineered nanoparticles (ENPs) have well-established anti-UV, self-cleaning, and air purification effects. Silver (Ag) ENPs are renowned for their anti-microbial capabilities and silicon dioxide (SiO2) ENPs are used as fire retardants and anti-scratch coatings. In this study, the toxic effects and biodistribution of three pristine ENPs (TiO2, Ag, and SiO2), three aged paints containing ENPs (TiO2, Ag, and SiO2) along with control paints without ENPs were compared. BALB/c mice were oropharyngeally aspirated with ENPs or paint particles (20 μg/aspiration) once a week for 5 weeks and sacrificed either 2 or 28 days post final aspiration treatment. A bronchoalveolar lavage was performed and systemic blood toxicity was evaluated to ascertain cell counts, induction of inflammatory cytokines, and key blood parameters. In addition, the lung, liver, kidney, spleen, and heart were harvested and metal concentrations were determined. Exposure to pristine ENPs caused subtle effects in the lungs and negligible alterations in the blood. The most pronounced toxic effects were observed after Ag ENPs exposure; an increased neutrophil count and a twofold increase in pro-inflammatory cytokine secretion (keratinocyte chemoattractant (KC) and interleukin-1ß (IL-1ß)) were identified. The paint containing TiO2 ENPs did not modify macrophage and neutrophil counts, but mildly induced KC and IL-1ß. The paints containing Ag or SiO2 did not show significant toxicity. Biodistribution experiments showed distribution of Ag and Si outside the lung after aspiration to respectively pristine Ag or SiO2 ENPs. In conclusion, we demonstrated that even though direct exposure to ENPs induced some toxic effects, once they were embedded in a complex paint matrix little to no adverse toxicological effects were

  16. Local delivery of siRNA-loaded calcium phosphate nanoparticles abates pulmonary inflammation.

    PubMed

    Frede, Annika; Neuhaus, Bernhard; Knuschke, Torben; Wadwa, Munisch; Kollenda, Sebastian; Klopfleisch, Robert; Hansen, Wiebke; Buer, Jan; Bruder, Dunja; Epple, Matthias; Westendorf, Astrid M

    2017-08-08

    The local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach to dampen inflammation during pulmonary diseases. For the local therapeutic treatment of pulmonary inflammation, we produced multi-shell nanoparticles consisting of a calcium phosphate core, coated with siRNAs directed against pro-inflammatory mediators, encapsulated into poly(lactic-co-glycolic acid), and coated with a final outer layer of polyethylenimine. Nasal instillation of nanoparticles loaded with a mixture of siRNAs directed against different cytokines to mice suffering from TH1 cell-mediated lung inflammation, or of siRNA directed against NS-1 in an influenza infection model led to a significant reduction of target gene expression which was accompanied by distinct amelioration of lung inflammation in both models. Thus, this study provides strong evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of inflammatory disorders of the lung. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Pulmonary oxygen toxicity in rats treated with cytochrome P-450 inducers

    SciTech Connect

    Ebel, R.E.; Barlow, R.L.; Gregory, E.M.

    1987-05-01

    Pulmonary oxygen toxicity is assumed to result from damage caused by superoxide (O/sub 2//sup -/) hydrogen peroxide (H/sub 2/O/sub 2/) and/or hydroxyl radical (OH) produced by the partial reduction of molecular oxygen (O/sub 2/). The microsomal cytochrome P-450 (P-450) monooxygenase system is known to produce O/sub 2//sup -/ and H/sub 2/O/sub 2/. They have studied the influence of monooxygenase induction using phenobarbital (PB) and ..beta..-naphthoflavone (..beta..-NF) on O/sub 2/ toxicity in the rat. PB- or ..beta..-NF induce hepatic P-450 but only ..beta..-NF induces pulmonary P-450. Pulmonary microsomes produced O/sub 2//sup -/ and H/sub 2/O/sub 2/ at rates (expressed per mg microsomal protein) which did not vary as a function of pretreatment. Rats were exposed to 100% O/sub 2/ for up to 3 days. After 3 days of O/sub 2/, lung weights were about 50% above controls regardless of pretreatment. The microsomal monooxygenase enzymes (P-450, b/sub 5/ and NADPH P-450 reductase) were quantified in liver and lung. Lung microsomal P-450 was reduced after 3 days of O/sub 2/ exposure regardless of pretreatment. The protective enzymes (catalase, superoxide dismutase (SOD) and glutathione (GSH) peroxidase) and non-protein sulfhydryl groups (NPSH) were also quantified in lung and liver samples. Lung NPSH and GSH peroxidase were increased after 3 days of O/sub 2/ exposure regardless of pretreatment while SOD was increased in controls and PB- but not ..beta..-NF-treated rats. Three of 14 ..beta..-NF-treated rats died during O/sub 2/ exposure while no animals in the control or PB-treated groups died.

  18. Subacute pulmonary toxicity of copper indium gallium diselenide following intratracheal instillations into the lungs of rats.

    PubMed

    Tanaka, Akiyo; Hirata, Miyuki; Shiratani, Masaharu; Koga, Kazunori; Kiyohara, Yutaka

    2012-01-01

    The aim of this study was to clarify the pulmonary toxicity of copper indium gallium diselenide (CIGS) solar cells on 62 8-wk-old rats. Male Wistar rats were given 0.5, 5 or 50 mg/kg of CIGS particles, intratracheally, 3 times for a week. Control rats were given vehicle, distilled water, only. These rats were euthanized 0, 1 or 3 wk after the final instillation serially, and toxicological effects were determined. None of the CIGS-treated groups exhibited suppression of body weight gain compared with the control group. The relative lung weight in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups were significantly increased compared with that in the control group throughout the observation period. Although serum copper (Cu) and selenium (Se) concentrations were not affected by instillations of CIGS particles, the indium (In) levels increased with the passage of time in the CIGS 5 mg/kg-treated and 50 mg/kg-treated groups. However, the serum gallium (Ga) levels decreased in the CIGS 50 mg/kg-treated group from 0 to 3 wk. The content of each metal in the lung increased depending on the dose instilled and was constant during observation periods. Histopathologically, foci of slight to severe pulmonary inflammatory response and exudation were present among all the CIGS-treated groups, and the severity of these lesions worsened with the passage of time. The present results clearly demonstrate that CIGS particles caused subacute pulmonary toxicity and that dissolution of CIGS particles in the lung was considerably slow when repeated intratracheal instillations were given to rats.

  19. Ecotoxicity of engineered nanoparticles to aquatic invertebrates: a brief review and recommendations for future toxicity testing.

    PubMed

    Baun, A; Hartmann, N B; Grieger, K; Kusk, K O

    2008-07-01

    Based on a literature review and an overview of toxic effects of engineered nanoparticles in aquatic invertebrates, this paper proposes a number of recommendations for the developing field of nanoecotoxicology by highlighting the importance of invertebrates as sensitive and relevant test organisms. Results show that there is a pronounced lack of data in this field (less than 20 peer-reviewed papers are published so far), and the most frequently tested engineered nanoparticles in invertebrate tests are C(60), carbon nanotubes, and titanium dioxide. In addition, the majority of the studies have used Daphnia magna as the test organism. To date, the limited number of studies has indicated acute toxicity in the low mg l(-1) range and higher of engineered nanoparticles to aquatic invertebrates, although some indications of chronic toxicity and behavioral changes have also been described at concentrations in the high microg l(-1) range. Nanoparticles have also been found to act as contaminant carriers of co-existing contaminants and this interaction has altered the toxicity of specific chemicals towards D. magna. We recommend that invertebrate testing is used to advance the level of knowledge in nanoecotoxicology through standardized short-term (lethality) tests with invertebrates as a basis for investigating behaviour and bioavailability of engineered nanoparticles in the aquatic environment. Based on this literature review, we further recommend that research is directed towards invertebrate tests employing long-term low exposure with chronic endpoints along with more research in bioaccumulation of engineered nanoparticles in aquatic invertebrates.

  20. A comprehensive toxicity study of zinc oxide nanoparticles versus their bulk in Wistar rats: Toxicity study of zinc oxide nanoparticles.

    PubMed

    Srivastav, Anurag Kumar; Kumar, Mahadeo; Ansari, Nasreen Ghazi; Jain, Abhishek Kumar; Shankar, Jai; Arjaria, Nidhi; Jagdale, Pankaj; Singh, Dhirendra

    2016-12-01

    The purpose of this study was to characterize the zinc oxide nanoparticles (ZnO-NPs) and their bulk counterpart in suspensions and to access the impact of their acute oral toxicity at doses of 300 and 2000 mg/kg in healthy female Wistar rats. The hematological, biochemical, and urine parameters were accessed at 24 and 48 h and 14 days posttreatment. The histopathological evaluations of tissues were also performed. The distribution of zinc content in liver, kidney, spleen, plasma, and excretory materials (feces and urine) at 24 and 48 h and 14 days posttreatment were accessed after a single exposure at dose of 2000 mg/kg body weight. The elevated level of alanine amino transferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were observed in ZnO-NPs at a dose of 2000 mg/kg at all time points. There was a decrease in iron levels in all the treated groups at 24 h posttreatment as compared to control groups but returned to their normal level at 14 days posttreatment. The hematological parameters red blood cells, hemoglobin, hematocrit, platelets, and haptoglobin were reduced at 48 h posttreatment at a dose of 2000 mg/kg ZnO-NPs and showed hemolytic condition. All the treated groups were comparable to control group at the end of 14 days posttreatment. The zinc concentration in the kidney, liver, plasma, feces, and urine showed a significant increase in both groups as compared to control. This study explained that ZnO-NPs produced more toxicological effect as compared to their bulk particles as evidenced through alteration in some hemato-biochemical parameters and with few histopathological lesions in liver and kidney tissues. © The Author(s) 2016.

  1. Biogenic silver nanoparticles based on trichoderma harzianum: synthesis, characterization, toxicity evaluation and biological activity

    NASA Astrophysics Data System (ADS)

    Guilger, Mariana; Pasquoto-Stigliani, Tatiane; Bilesky-Jose, Natália; Grillo, Renato; Abhilash, P. C.; Fraceto, Leonardo Fernandes; Lima, Renata De

    2017-03-01

    White mold is an agricultural disease caused by the fungus Sclerotinia sclerotiorum, which affects important crops. There are different ways of controlling this organism, but none provides inhibition of its resistance structures (sclerotia). Nanotechnology offers promising applications in agricultural area. Here, silver nanoparticles were biogenically synthesized using the fungus Trichoderma harzianum and characterized. Cytotoxicity and genotoxicity were evaluated, and the nanoparticles were initially tested against white mold sclerotia. Their effects on soybean were also investigated with no effects observed. The nanoparticles showed potential against S. sclerotiorum, inhibiting sclerotia germination and mycelial growth. Nanoparticle characterization data indicated spherical morphology, satisfactory polydispersity and size distribution. Cytotoxicity and genotoxicity assays showed that the nanoparticles caused both the effects, although, the most toxic concentrations were above those applied for white mold control. Given the potential of the nanoparticles against S. sclerotiorum, we conclude that this study presents a first step for a new alternative in white mold control.

  2. Biogenic silver nanoparticles based on trichoderma harzianum: synthesis, characterization, toxicity evaluation and biological activity

    PubMed Central

    Guilger, Mariana; Pasquoto-Stigliani, Tatiane; Bilesky-Jose, Natália; Grillo, Renato; Abhilash, P. C.; Fraceto, Leonardo Fernandes; Lima, Renata de

    2017-01-01

    White mold is an agricultural disease caused by the fungus Sclerotinia sclerotiorum, which affects important crops. There are different ways of controlling this organism, but none provides inhibition of its resistance structures (sclerotia). Nanotechnology offers promising applications in agricultural area. Here, silver nanoparticles were biogenically synthesized using the fungus Trichoderma harzianum and characterized. Cytotoxicity and genotoxicity were evaluated, and the nanoparticles were initially tested against white mold sclerotia. Their effects on soybean were also investigated with no effects observed. The nanoparticles showed potential against S. sclerotiorum, inhibiting sclerotia germination and mycelial growth. Nanoparticle characterization data indicated spherical morphology, satisfactory polydispersity and size distribution. Cytotoxicity and genotoxicity assays showed that the nanoparticles caused both the effects, although, the most toxic concentrations were above those applied for white mold control. Given the potential of the nanoparticles against S. sclerotiorum, we conclude that this study presents a first step for a new alternative in white mold control. PMID:28300141

  3. Toxicity and developmental defects of different sizes and shape nickel nanoparticles in zebrafish

    PubMed Central

    Ispas, Cristina; Andreescu, Daniel; Patel, Avni; Goia, Dan V.; Andreescu, Silvana; Wallace, Kenneth N.

    2009-01-01

    Metallic nanoparticles such as nickel are used in catalytic, sensing and electronic applications, but health and environmental affects have not been fully investigated. While some metal nanoparticles result in toxicity, it is also important to determine whether nanoparticles of the same metal but of different size and shape changes toxicity. Three different size nickel nanoparticle (Ni NPs) of 30, 60, and 100 nm and larger particle clusters of aggregated 60 nm entities with a dendritic structure were synthesized and exposed to zebrafish embryos assessing mortality and developmental defects. Ni NPs exposure was compared to soluble nickel salts. All three 30, 60, and 100 nm Ni NPs are equal to or less toxic than soluble nickel while dendritic clusters were more toxic. With each Ni NP exposure, thinning of the intestinal epithelium first occurs around the LD10 continuing into the LD50. LD50 exposure also results in skeletal muscle fiber separation. Exposure to soluble nickel does not cause intestinal defects while skeletal muscle separation occurs at concentrations well over LD50. These results suggest that configuration of nanoparticles may affect toxicity more than size and defects from Ni NPs exposure occur by different biological mechanisms than soluble nickel. PMID:19746736

  4. Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery.

    PubMed

    Häfeli, Urs O; Riffle, Judy S; Harris-Shekhawat, Linda; Carmichael-Baranauskas, Anita; Mark, Framin; Dailey, James P; Bardenstein, David

    2009-01-01

    Magnetic targeting is useful for intravascular or intracavitary drug delivery, including tumor chemotherapy or intraocular antiangiogenic therapy. For all such in vivo applications, the magnetic drug carrier must be biocompatible and nontoxic. In this work, we investigated the toxic properties of magnetic nanoparticles coated with polyethylenoxide (PEO) triblock copolymers. Such coatings prevent the aggregation of magnetic nanoparticles and guarantee consistent magnetic and nonmagnetic flow properties. It was found that the PEO tail block length inversely correlates with toxicity. The nanoparticles with the shortest 0.75 kDa PEO tails were the most toxic, while particles coated with the 15 kDa PEO tail block copolymers were the least toxic. Toxicity responses of the tested prostate cancer cell lines (PC3 and C4-2), human umbilical vein endothelial cells (HUVECs), and human retinal pigment epithelial cells (HRPEs) were similar. Furthermore, all cell types took up the coated magnetic nanoparticles. It is concluded that magnetite nanoparticles coated with triblock copolymers containing PEO tail lengths of above 2 kDa are biocompatible and appropriate for in vivo application.

  5. Impact of cerium oxide nanoparticles shape on their in vitro cellular toxicity.

    PubMed

    Forest, Valérie; Leclerc, Lara; Hochepied, Jean-François; Trouvé, Adeline; Sarry, Gwendoline; Pourchez, Jérémie

    2017-02-01

    Cerium oxides (CeO2) nanoparticles, also referred to as nanoceria, are extensively used with a wide range of applications. However, their impact on human health and on the environment is not fully elucidated. The aim of this study was to investigate the influence of the CeO2 nanoparticles morphology on their in vitro toxicity. CeO2 nanoparticles of similar chemical composition and crystallinity were synthesized, only the shape varied (rods or octahedrons/cubes). Macrophages from the RAW264.7 cell line were exposed to these different samples and the toxicity was evaluated in terms of lactate dehydrogenase (LDH) release, Tumor Necrosis Factor alpha (TNF-α) production and reactive oxygen species (ROS) generation. Results showed no ROS production, whatever the nanoparticle shape. The LDH release and the TNF-α production were significantly and dose-dependently enhanced by rod-like nanoparticles, whereas they did not vary with cubic/octahedral nanoparticles. In conclusion, a strong impact of CeO2 nanoparticle morphology on their in vitro toxicity was clearly demonstrated, underscoring that nanoceria shape should be carefully taken in consideration, especially in a "safer by design" context. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Toxicity Assessment of Iron Oxide Nanoparticles in Zebrafish (Danio rerio) Early Life Stages

    PubMed Central

    Zhu, Xiaoshan; Tian, Shengyan; Cai, Zhonghua

    2012-01-01

    Iron oxide nanoparticles have been explored recently for their beneficial applications in many biomedical areas, in environmental remediation, and in various industrial applications. However, potential risks have also been identified with the release of nanoparticles into the environment. To study the ecological effects of iron oxide nanoparticles on aquatic organisms, we used early life stages of the zebrafish (Danio rerio) to examine such effects on embryonic development in this species. The results showed that ≥10 mg/L of iron oxide nanoparticles instigated developmental toxicity in these embryos, causing mortality, hatching delay, and malformation. Moreover, an early life stage test using zebrafish embryos/larvae is also discussed and recommended in this study as an effective protocol for assessing the potential toxicity of nanoparticles. This study is one of the first on developmental toxicity in fish caused by iron oxide nanoparticles in aquatic environments. The results will contribute to the current understanding of the potential ecotoxicological effects of nanoparticles and support the sustainable development of nanotechnology. PMID:23029464

  7. Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.

    PubMed

    Peng, Xinqi; Perkins, Michael W; Simons, Jannitt; Witriol, Alicia M; Rodriguez, Ashley M; Benjamin, Brittany M; Devorak, Jennifer; Sciuto, Alfred M

    2014-06-01

    This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

  8. Intracellular calcium levels as screening tool for nanoparticle toxicity

    PubMed Central

    Meindl, Claudia; Kueznik, Tatjana; Bösch, Martina; Roblegg, Eva; Fröhlich, Eleonore

    2015-01-01

    The use of engineered nano-sized materials led to revolutionary developments in many industrial applications and in the medical field. These materials, however, also may cause cytotoxicity. In addition to size, surface properties and shape were identified as relevant parameters for cell damage. Cell damage may occur as disruption of membrane integrity, induction of apoptosis and by organelle damage. Generation of oxidative stress may serve as an indicator for cytotoxicity. Effects occurring upon short contact of particles with cells, for instance in the systemic blood circulation, could be identified according to increases of intracellular [Ca2+] levels, which are caused by variety of toxic stimuli. Negatively charged, neutral and positively charged polystyrene particles of different sizes were used to study the role of size and surface properties on viability, membrane disruption, apoptosis, lysosome function, intracellular [Ca2+] levels and generation of oxidative stress. Silica particles served to test this hypothesis. Twenty nm polystyrene particles as well as 12 nm and 40 nm silica particles caused membrane damage and apoptosis with no preference of the surface charge. Only 20 nm plain and amine functionalized polystyrene particles cause oxidative stress and only the plain particles lysosomal damage. A potential role of surface charge was identified for 200 nm polystyrene particles, where only the amidine particles caused lysosomal damage. Increases in intracellular [Ca2+] levels and cytotoxicity after 24 h was often linked but determination of intracellular [Ca2+] levels could serve to characterize further the type of membrane damage. © 2015 The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd. Nano-sized materials may cause cytotoxicity. Negatively charged, neutral and positively charged polystyrene particles of different sizes and silica nanoparticles were used to study the role of size and surface properties on viability, membrane

  9. Carbon black and titanium dioxide nanoparticles induce distinct molecular mechanisms of toxicity.

    PubMed

    Boland, Sonja; Hussain, Salik; Baeza-Squiban, Armelle

    2014-01-01

    Increasing evidence link nanomaterials with adverse biological outcomes and due to the variety of applications and potential human exposures to nanoparticles, it is thus important to evaluate their toxicity for the risk assessment of workers and consumers. It is crucial to understand the underlying mechanisms of their toxicity as observation of similar effects after different nanomaterial exposures does not reflect similar intracellular processing and organelle interactions. A thorough understanding of mechanisms is needed not only for accurate prediction of potential toxicological impacts but also for the development of safer nanoapplications by modulating the physicochemical characteristics. Furthermore biomedical applications may also take advantage of an in depth knowledge about the mode of action of nanotoxicity to design new nanoparticle-derived drugs. In the present manuscript we discuss the similarities and differences in molecular pathways of toxicity after carbon black (CB) and titanium dioxide (TiO₂) nanoparticle exposures and identify the main toxicity mechanisms induced by these two nanoparticles which may also be indicative for the mode of action of other insoluble nanomaterials. We address the translocation, cell death induction, genotoxicity, and inflammation induced by TiO₂ and CB nanoparticles which depend on their internalization, reactive oxygen species (ROS) production capacities and/or protein interactions. We summarize their distinct cellular mechanisms of toxicity and the crucial steps which may be targeted to avoid adverse effects or to induce them for nanomedical purposes. Several physicochemical characteristics could influence these general toxicity pathways depicted here and the identification of common toxicity pathways could support the grouping of nanomaterials in terms of toxicity. © 2014 Wiley Periodicals, Inc.

  10. Carbon Black and Titanium Dioxide Nanoparticles Induce Distinct Molecular Mechanisms of Toxicity

    PubMed Central

    Boland, Sonja; Hussain, Salik; Baeza-Squiban, Armelle

    2014-01-01

    Increasing evidence link nanomaterials with adverse biological outcomes and due to the variety of applications and potential human exposures to nanoparticles it is thus important to evaluate their toxicity for the risk assessment of workers and consumers. It is crucial to understand the underlying mechanisms of their toxicity as observation of similar effects after different nanomaterial exposures does not reflect similar intracellular processing and organelle interactions. A thorough understanding of mechanisms is not only needed for accurate prediction of potential toxicological impacts but also for the development of safer nanoapplications by modulating the physico-chemical characteristics. Furthermore biomedical applications may also take advantage of an in depth knowledge about the mode of action of nanotoxicity to design new nanoparticle-derived drugs. In the present manuscript we discuss the similarities and differences in molecular pathways of toxicity after carbon black and TiO2 nanoparticle exposures and identify the main toxicity mechanisms induced by these two nanoparticles which may also be indicative for the mode of action of other insoluble nanomaterials. We address the translocation, cell death induction, genotoxicity and inflammation induced by titanium dioxide and carbon black nanoparticles which depend on their internalisation, ROS production capacities and/or protein interactions. We summarise their distinct cellular mechanisms of toxicity and the crucial steps which may be targeted to avoid adverse effects or to induce them for nanomedical purposes. Several physico-chemical characteristics could influence these general toxicity pathways depicted here and the identification of common toxicity pathways could support the grouping of nanomaterials in terms of toxicity. PMID:25266826

  11. Apoptosis-mediated in vivo toxicity of hydroxylated fullerene nanoparticles in soil nematode Caenorhabditis elegans.

    PubMed

    Cha, Yun Jeong; Lee, Jaesang; Choi, Shin Sik

    2012-03-01

    Although a number of manufactured nanoparticles are applied for the medical and clinical purposes, the understanding of interaction between nanomaterials and biological systems are still insufficient. Using nematode Caenorhabditis elegans model organism, we here investigated the in vivo toxicity or safety of hydroxylated fullerene nanoparticles known to detoxify anti-cancer drug-induced oxidative damages in mammals. The survival ratio of C. elegans rapidly decreased by the uptake of nanoparticles from their L4 larval stage with resulting in shortened lifespan (20 d). Both reproduction rate and body size of C. elegans were also reduced after exposure to 100 μg mL(-1) of fullerol. We found ectopic cell corpses caused by apoptotic cell death in the adult worms grown with fullerol nanoparticles. By the mutation of core pro-apoptotic regulator genes, ced-3 and ced-4, these nanoparticle-induced cell death were significantly suppressed, and the viability of animals consequently increased despite of nanoparticle uptake. The apoptosis-mediated toxicity of nanoparticles particularly led to the disorder of digestion system in the animals containing a large number of undigested foods in their intestine. These results demonstrated that the water-soluble fullerol nanoparticles widely used in medicinal applications have a potential for inducing apoptotic cell death in multicellular organisms despite of their antioxidative detoxifying property. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Pulmonary toxicity screening studies in male rats with M5 respirable fibers and particulates.

    PubMed

    Warheit, David B; Webb, Thomas R; Reed, Kenneth L

    2007-09-01

    M5 fiber is a high-strength, high-performance organic fiber type that is a rigid rod material and composed of heterocyclic polymer fibers of type PIPD. The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled M5 respirable fibers and particulates in rats. Using a pulmonary bioassay and bridging methodology, the acute lung toxicity of intratracheally instilled M5 particulates and that of its fibers were compared with a positive control particle type, quartz, as well as a negative control particle type, carbonyl iron particles. Moreover, the results of these instillation studies were bridged with data previously generated from inhalation studies with quartz and carbonyl iron particles, using the quartz and iron particles as the inhalation/instillation bridge material. For the bioassay experimental design, in the bronchoalveolar lavage studies, the lungs of rats were intratracheally instilled with 0.5 or 0.75 mg/kg of M5 particulate or 1 or 5 mg/kg of the following control or particle types: (1) M5 long fiber preparation, (2) silica-quartz particles, and (3) carbonyl iron particles. Phosphate-buffered saline (PBS)-instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, cell proliferation methods, and histopathological evaluation of lung tissue at 24 h, 1 wk, 1 mo and 3 mo post instillation exposure. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to M5 particulate and M5 long fiber preparation produced transient inflammatory and cell injury effects at 24 h postexposure (pe) as well as at 24 h and 1 wk pe, respectively, but these effects were not sustained when compared to quartz-silica effects. Exposures to

  13. Interaction of silver nanoparticles with biological objects: antimicrobial properties and toxicity for the other living organisms

    NASA Astrophysics Data System (ADS)

    Egorova, E. M.

    2011-04-01

    This paper presents several examples of the biological effects of small-sized silver nanoparticles (10.5±3.5nm) observed in experiments on bacteria, slim mold, unicellular alga and plant seeds. The nanoparticles were prepared by the biochemical synthesis, based on the reduction of metal ions in reverse vicelles by biological reductants - natural plant pigments (flavonoids). It is found that, except for the plant seeds, silver nanoparticles (SNP) act as a strong toxic agent, both in water solution and as part of liquid-phase material. It is shown also that the biological action of silver nanoparticles can not be reduced to the toxic action of silver ions in equivalent concentrations or to that of the surfactant (the SNP stabilizer) present in the SNP water solution. Possible SNP applications are suggested.

  14. A general mechanism for intracellular toxicity of metal-containing nanoparticles

    NASA Astrophysics Data System (ADS)

    Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M.; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo

    2014-05-01

    The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a ``lysosome-enhanced Trojan horse effect'' since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments.The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where

  15. Assessing toxicity of nanoparticles using Brachionus manjavacas (Rotifera).

    PubMed

    Snell, Terry W; Hicks, Daniel G

    2011-04-01

    Rotifers are major components of zooplankton in freshwater and coastal marine ecosystems throughout the world and could be useful indicator species, providing valuable insight into the effects of nanoparticles on microinvertebrate grazers. Here we report initial efforts to characterize the immediate and longer-term effects of nanoparticle exposure on the reproduction of the coastal marine and salt lake rotifer Brachionus manjavacas. We used chemically unreactive fluorescent nanoparticles to probe how size and concentration affects the mode of uptake, distribution within the rotifer body, reproductive rate, feeding behavior, and offspring fitness. Population growth rate (r) was depressed 50% in rotifer populations exposed to 0.30 μg mL(-1) of 37-nm particles, and 89% in populations exposed to 1.1 μg mL(-1). Larger particles of identical chemical composition, but with diameters up to 3000 nm, caused no reduction in population growth rate. These larger particles remain confined in the gut, implicating nanoparticle size as a critical factor in the ability to penetrate the gut wall and enter tissues. Transfer of the F1 offspring from nanoparticle exposed maternal females into nanoparticle-free media demonstrated that nanoparticles are rapidly cleared from the animals with no significant residual adverse effects. Copyright © 2009 Wiley Periodicals, Inc.

  16. Physicochemical characteristics of nanomaterials that affect pulmonary inflammation

    PubMed Central

    2014-01-01

    The increasing manufacture and use of products based on nanotechnology raises concerns for both workers and consumers. Various studies report induction of pulmonary inflammation after inhalation exposure to nanoparticles, which can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Each of these aspects can affect their toxicity, although it is largely unknown to what extent. The aim of the current review is to analyse published data on inhalation of nanoparticles to identify and evaluate the contribution of their physicochemical characteristics to the onset and development of pulmonary inflammation. Many physicochemical characteristics of nanoparticles affect their lung deposition, clearance, and pulmonary response that, in combination, ultimately determine whether pulmonary inflammation will occur and to what extent. Lung deposition is mainly determined by the physical properties of the aerosol (size, density, shape, hygroscopicity) in relation to airflow and the anatomy of the respiratory system, whereas clearance and translocation of nanoparticles are mainly determined by their geometry and surface characteristics. Besides size and chemical composition, other physicochemical characteristics influence the induction of pulmonary inflammation after inhalation. As some nanoparticles dissolve, they can release toxic ions that can damage the lung tissue, making dissolution rate an important characteristic that affects lung inflammation. Fibre-shaped materials are more toxic to the lungs compared to spherical shaped nanoparticles of the same chemical composition. In general, cationic nanoparticles are more cytotoxic than neutral or anionic nanoparticles. Finally, surface reactivity correlates well with observed pulmonary inflammation. With all these characteristics affecting different stages of the events leading to pulmonary inflammation, no unifying dose metric could be identified to describe pulmonary

  17. Investigation of the toxicity of bismuth oxide nanoparticles in various cell lines.

    PubMed

    Abudayyak, Mahmoud; Öztaş, Ezgi; Arici, Merve; Özhan, Gül

    2017-02-01

    Nanoparticles have been drawn attention in various fields ranging from medicine to industry because of their physicochemical properties and functions, which lead to extensive human exposure to nanoparticles. Bismuth (Bi)-based compounds have been commonly used in the industrial, cosmetic and medical applications. Although the toxicity of Bi-based compounds was studied for years, there is a serious lack of information concerning their toxicity and effects in the nanoscale on human health and environment. Therefore, we aimed to investigate the toxic effects of Bi (III) oxide (Bi2O3) nanoparticles in liver (HepG2 hepatocarcinoma cell), kidney (NRK-52E kidney epithelial cell), intestine (Caco-2 colorectal adenocarcinoma cell), and lung (A549 lung carcinoma cell) cell cultures. Bi2O3 nanoparticles (∼149.1 nm) were easily taken by all cells and showed cyto- and genotoxic effects. It was observed that the main cell death pathways were apoptosis in HepG2 and NRK-52E cells and necrosis in A549 and Caco-2 cells exposed to Bi2O3 nanoparticles. Also, the glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy deoxyguanine (8-OHdG) levels were significantly changed in HepG2, NRK-52E, and Caco-2 cells, except A549 cell. The present study is the first to evaluate the toxicity of Bi2O3 nanoparticles in mammalian cells. Bi2O3 nanoparticles should be thoroughly assessed for their potential hazardous effects to human health and the results should be supported with in vivo studies to fully understand the mechanism of their toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with adjuvant radiotherapy for breast cancer.

    PubMed

    Meattini, Icro; Guenzi, Marina; Fozza, Alessandra; Vidali, Cristiana; Rovea, Paolo; Meacci, Fiammetta; Livi, Lorenzo

    2017-01-01

    Conservative management of breast cancer represents the standard treatment for early disease. Breast conserving surgery associated with radiotherapy for stage I-II has been proven to be as equally effective as mastectomy in term of local control, distant disease, and overall survival. The growing minimal invasive surgical approach on the axillary region, and the new breast reconstructive techniques, will probably lead to a significant decrease of the rate of side-effects related to mastectomy. Therefore, the adverse events caused by adjuvant radiation still remain a challenge. Cutaneous, pulmonary and cardiac toxicity represent the main toxicities of adjuvant radiotherapy for breast cancer. Safety profile of radiation is strongly dependent on the multidisciplinary management of the single case (systemic treatment, endocrine therapy, surgery), individual characteristics (i.e., co-morbidities, age, habits), and radiation-related aspects. Radiation techniques development, and facilities implementation concerning organs-at-risk sparing systems (i.e., image-guided radiotherapy, tracking systems, respiratory gating), represent brand new tools for the clinical oncologist, that would certainly minimize toxicity profile in the next future. However, data reported from published literature will greatly help physicians, to give to the patients appropriate counseling regarding the efficacy and potential adverse events of treatments, thus optimizing the informed decision-making process.

  19. Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles

    PubMed Central

    2012-01-01

    Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. PMID:22303956

  20. Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat

    PubMed Central

    PRABHU, BADANAVALU M.; ALI, SYED F.; MURDOCK, RICHARD C.; HUSSAIN, SABER M.; SRIVATSAN, MALATHI

    2010-01-01

    Metal nanoparticles, due to their unique properties and important applications in optical, magnetic, thermal, electrical, sensor devices and cosmetics, are beginning to be widely manufactured and used. This new and rapidly growing field of technology warrants a thorough examination of the material’s bio-compatibility and safety. Ultra-small particles may adversely affect living cells and organisms since they can easily penetrate the body through skin contact, inhalation and ingestion. Retrograde transport of copper nanoparticles from nerve endings on the skin can reach the somatosensory neurons in dorsal root ganglion (DRG). Since copper nanoparticles have industrial and healthcare applications, we determined the concentration and size-dependant effects of their exposure on survival of DRG neurons of rat in cell culture. The neurons were exposed to copper nanoparticles of increasing concentrations (10–100 μM) and sizes (40, 60 and 80 nm) for 24 h. Light microscopy, histochemical staining for copper, lactate dehydrogenase (LDH) assay for cell death, and MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay for cell viability were performed to measure the resultant toxicity and cell survival. DRG neurons exposed to copper nanoparticles displayed vacuoles and detachment of some neurons from the substratum. Neurons also exhibited disrupted neurite network. LDH and MTS assays revealed that exposure to copper nanoparticles had significant toxic effect with all the sizes tested when compared to unexposed control cultures. Further analysis of the results showed that copper nanoparticles of smaller size and higher concentration exerted the maximum toxic effects. Rubeanic acid staining showed intracellular deposition of copper. These results demonstrate that copper nanoparticles are toxic in a size- and concentration-dependent manner to DRG neurons. PMID:20543894

  1. Toxicity Testing of Pristine and Aged Silver Nanoparticles in Real Wastewaters Using Bioluminescent Pseudomonas putida

    PubMed Central

    Mallevre, Florian; Alba, Camille; Milne, Craig; Gillespie, Simon; Fernandes, Teresa F.; Aspray, Thomas J.

    2016-01-01

    Impact of aging on nanoparticle toxicity in real matrices is scarcely investigated due to a lack of suitable methodologies. Herein, the toxicity of pristine and aged silver nanoparticles (Ag NPs) to a bioluminescent Pseudomonas putida bioreporter was measured in spiked crude and final wastewater samples (CWs and FWs, respectively) collected from four wastewater treatment plants (WWTPs). Results showed lower toxicity of pristine Ag NPs in CWs than in FWs. The effect of the matrix on the eventual Ag NP toxicity was related to multiple physico-chemical parameters (biological oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS) pH, ammonia, sulfide and chloride) based on a multivariate analysis. However, no collection site effect was concluded. Aged Ag NPs (up to eight weeks) were found less toxic than pristine Ag NPs in CWs; evident increased aggregation and decreased dissolution were associated with aging. However, Ag NPs exhibited consistent toxicity in FWs despite aging; comparable results were obtained in artificial wastewater (AW) simulating effluent. The study demonstrates the potency of performing nanoparticle acute toxicity testing in real and complex matrices such as wastewaters using relevant bacterial bioreporters. PMID:28344306

  2. Toxicity Testing of Pristine and Aged Silver Nanoparticles in Real Wastewaters Using Bioluminescent Pseudomonas putida.

    PubMed

    Mallevre, Florian; Alba, Camille; Milne, Craig; Gillespie, Simon; Fernandes, Teresa F; Aspray, Thomas J

    2016-03-11

    Impact of aging on nanoparticle toxicity in real matrices is scarcely investigated due to a lack of suitable methodologies. Herein, the toxicity of pristine and aged silver nanoparticles (Ag NPs) to a bioluminescent Pseudomonas putida bioreporter was measured in spiked crude and final wastewater samples (CWs and FWs, respectively) collected from four wastewater treatment plants (WWTPs). Results showed lower toxicity of pristine Ag NPs in CWs than in FWs. The effect of the matrix on the eventual Ag NP toxicity was related to multiple physico-chemical parameters (biological oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS) pH, ammonia, sulfide and chloride) based on a multivariate analysis. However, no collection site effect was concluded. Aged Ag NPs (up to eight weeks) were found less toxic than pristine Ag NPs in CWs; evident increased aggregation and decreased dissolution were associated with aging. However, Ag NPs exhibited consistent toxicity in FWs despite aging; comparable results were obtained in artificial wastewater (AW) simulating effluent. The study demonstrates the potency of performing nanoparticle acute toxicity testing in real and complex matrices such as wastewaters using relevant bacterial bioreporters.

  3. Effects of airborne toxicants on pulmonary function and mitochondrial DNA damage in rodent lungs.

    PubMed

    Rumsey, William L; Bolognese, Brian; Davis, Alicia B; Flamberg, Pearl L; Foley, Joseph P; Katchur, Steven R; Kotzer, Charles J; Osborn, Ruth R; Podolin, Patricia L

    2017-05-01

    Inhalation of airborne toxicants such as cigarette smoke and ozone is a shared health risk among the world's populations. The use of toxic herbicides like paraquat (PQ) is restricted by many countries, yet in the developing world PQ has demonstrable ill effects. The present study examined changes in pulmonary function, mitochondrial DNA (mtDNA) integrity and markers of DNA repair induced by acute or repeated exposure of PQ to rats. Similar to cigarette smoke and ozone, PQ promotes oxidative stress, and the impact of PQ on mtDNA was compared with that obtained with these agents. Tracheal instillation (i.t.) of PQ (0.01-0.075 mg/kg) dose dependently increased Penh (dyspnoea) by 48 h while body weight and temperature declined. Lung wet weight and the wet/dry weight ratio rose; for the latter, by as much as 52%. At low doses (0.02 and 0.03 mg/kg), PQ increased Penh by about 7.5-fold at 72 h. It quickly waned to near baseline levels. The lung wet/dry weight ratio remained elevated 7 days after administration coincident with marked inflammatory cell infiltrate. Repeated administration of PQ (1 per week for 8 weeks) resulted in a similar rise in Penh on the first instillation, but the magnitude of this response was markedly attenuated upon subsequent exposures. Pulmonary [lactate] and catalase activity, [8-oxodG] and histone fragmentation (cell death) were significantly increased. Repeated PQ instillation downregulated the expression of the mitochondrial-encoded genes, mtATP8, mtNd2 and mtcyB and nuclear ones for the DNA glycosylases, Ogg1, Neil1, Neil2 and Neil3. Ogg1 protein content decreased after acute and repeated PQ administration. mtDNA damage or changes in mtDNA copy number were evident in lungs of PQ-, cigarette smoke- and ozone-exposed animals. Taken together, these data indicate that loss of pulmonary function and inflammation are coupled to the loss of mtDNA integrity and DNA repair capability following exposure to airborne toxicants. © The Author 2016

  4. In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

    SciTech Connect

    Hanns-Rudolf, Paur; Cassee, Flemming R.; Teeguarden, Justin G.; Fissan, Heinz; Diabate, Silvia; Aufderheide, M.; Kreyling, Wolfgang G.; Hanninen, Otto; Kasper, G.; Riediker, Michael; Rothen-Rutishauser, Barbara; Schmid, Otmar

    2011-10-01

    The rapid introduction of engineered nanostructured materials into numerous industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of consumer products. The dynamic development of new nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety. In this consensus document from a workshop on in-vitro cell systems for nanotoxicity testing an overview is given of the main issues concerning inhalation exposure to nanoparticles, lung physiology, nanoparticle-related biological mechanisms, in-vitro cell exposure systems for nanoparticles and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanotoxicity. For the investigation of pulmonary nanotoxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

  5. Effect of toxicity of Ag nanoparticles on SERS spectral variance of bacteria

    NASA Astrophysics Data System (ADS)

    Cui, Li; Chen, Shaode; Zhang, Kaisong

    2015-02-01

    Ag nanoparticles (NPs) have been extensively utilized in surface-enhanced Raman scattering (SERS) spectroscopy for bacterial identification. However, Ag NPs are toxic to bacteria. Whether such toxicity can affect SERS features of bacteria and interfere with bacterial identification is still unknown and needed to explore. Here, by carrying out a comparative study on non-toxic Au NPs with that on toxic Ag NPs, we investigated the influence of nanoparticle concentration and incubation time on bacterial SERS spectral variance, both of which were demonstrated to be closely related to the toxicity of Ag NPs. Sensitive spectral alterations were observed on Ag NPs with increase of NPs concentration or incubation time, accompanied with an obvious decrease in number of viable bacteria. In contrast, SERS spectra and viable bacterial number on Au NPs were rather constant under the same conditions. A further analysis on spectral changes demonstrated that it was cell response (i.e. metabolic activity or death) to the toxicity of Ag NPs causing spectral variance. However, biochemical responses to the toxicity of Ag were very different in different bacteria, indicating the complex toxic mechanism of Ag NPs. Ag NPs are toxic to a great variety of organisms, including bacteria, fungi, algae, protozoa etc., therefore, this work will be helpful in guiding the future application of SERS technique in various complex biological systems.

  6. In Vitro Vascular Toxicity of Metal Oxide Nanoparticles

    EPA Science Inventory

    Engineered nanoparticles (NPs) are designed to possess unique physicochemical properties, but may also produce atypical and unforeseen exposure scenarios with adverse health effects. The ability ofNPs to translocate into systemic circulation following either inhalation or ingesti...

  7. In Vitro Vascular Toxicity of Metal Oxide Nanoparticles

    EPA Science Inventory

    Engineered nanoparticles (NPs) are designed to possess unique physicochemical properties, but may also produce atypical and unforeseen exposure scenarios with adverse health effects. The ability ofNPs to translocate into systemic circulation following either inhalation or ingesti...

  8. Chitosan coating of copper nanoparticles reduces in vitro toxicity and increases inflammation in the lung

    NASA Astrophysics Data System (ADS)

    Worthington, Kristan L. S.; Adamcakova-Dodd, Andrea; Wongrakpanich, Amaraporn; Mudunkotuwa, Imali A.; Mapuskar, Kranti A.; Joshi, Vijaya B.; Guymon, C. Allan; Spitz, Douglas R.; Grassian, Vicki H.; Thorne, Peter S.; Salem, Aliasger K.

    2013-10-01

    Despite their potential for a variety of applications, copper nanoparticles induce very strong inflammatory responses and cellular toxicity following aerosolized delivery. Coating metallic nanoparticles with polysaccharides, such as biocompatible and antimicrobial chitosan, has the potential to reduce this toxicity. In this study, copper nanoparticles were coated with chitosan using a newly developed and facile method. The presence of coating was confirmed using x-ray photoelectron spectroscopy, rhodamine tagging of chitosan followed by confocal fluorescence imaging of coated particles and observed increases in particle size and zeta potential. Further physical and chemical characteristics were evaluated using dissolution and x-ray diffraction studies. The chitosan coating was shown to significantly reduce the toxicity of copper nanoparticles after 24 and 52 h and the generation of reactive oxygen species as assayed by DHE oxidation after 24 h in vitro. Conversely, inflammatory response, measured using the number of white blood cells, total protein, and cytokines/chemokines in the bronchoalveolar fluid of mice exposed to chitosan coated versus uncoated copper nanoparticles, was shown to increase, as was the concentration of copper ions. These results suggest that coating metal nanoparticles with mucoadhesive polysaccharides (e.g. chitosan) could increase their potential for use in controlled release of copper ions to cells, but will result in a higher inflammatory response if administered via the lung.

  9. Toxicity mechanisms in Escherichia coli vary for silver nanoparticles and differ from ionic silver.

    PubMed

    Ivask, Angela; Elbadawy, Amro; Kaweeteerawat, Chitrada; Boren, David; Fischer, Heidi; Ji, Zhaoxia; Chang, Chong Hyun; Liu, Rong; Tolaymat, Thabet; Telesca, Donatello; Zink, Jeffrey I; Cohen, Yoram; Holden, Patricia Ann; Godwin, Hilary A

    2014-01-28

    Silver nanoparticles (Ag NPs) are commonly added to various consumer products and materials to impair bacterial growth. Recent studies suggested that the primary mechanism of antibacterial action of silver nanoparticles is release of silver ion (Ag(+)) and that particle-specific activity of silver nanoparticles is negligible. Here, we used a genome-wide library of Escherichia coli consisting of ∼4000 single gene deletion mutants to elucidate which physiological pathways are involved in how E. coli responds to different Ag NPs. The nanoparticles studied herein varied in both size and surface charge. AgNO3 was used as a control for soluble silver ions. Within a series of differently sized citrate-coated Ag NPs, smaller size resulted in higher Ag ion dissolution and toxicity. Nanoparticles functionalized with cationic, branched polyethylene imine (BPEI) exhibited equal toxicity with AgNO3. When we used a genome-wide approach to investigate the pathways involved in the response of E. coli to different toxicants, we found that only one of the particles (Ag-cit10) exhibited a pattern of response that was statistically similar to that of silver ion. By contrast, the pathways involved in E. coli response to Ag-BPEI particles were more similar to those observed for another cationic nanoparticle that did not contain Ag. Overall, we found that the pathways involved in bacterial responses to Ag nanoparticles are highly dependent on physicochemical properties of the nanoparticles, particularly the surface characteristics. These results have important implications for the regulation and testing of silver nanoparticles.

  10. Preparation and characterization of spray-dried tobramycin powders containing nanoparticles for pulmonary delivery.

    PubMed

    Pilcer, Gabrielle; Vanderbist, Francis; Amighi, Karim

    2009-01-05

    Using high-pressure homogenization and spray-drying techniques, novel formulations were developed for manufacturing dry powder for inhalation, composed of a mixture of micro- and nanoparticles in order to enhance lung deposition. Particle size analysis was performed by laser diffraction. Spray-drying was applied in order to retrieve nanoparticles in dried-powder state from tobramycin nanosuspensions. The aerolization properties of the different formulations were evaluated by a multi-stage liquid impinger. Suspensions of nanoparticles of tobramycin containing Na glycocholate at 2% (w/w) relative to tobramycin content and presenting a mean particle size about 200 nm were produced. The results from the spray-dried powders showed that the presence of nanoparticles in the formulations improved particle dispersion properties during inhalation. The fine particle fraction (percentage of particles below 5 microm) increased from 36% for the raw micronized tobramycin material to about 61% for the most effective formulation. These new nanoparticle-containing tobramycin DPI formulations, based on the use of very low level of excipient and presenting high lung deposition properties, offer very important perspectives for improving the delivery of drugs to the pulmonary tract.

  11. Size-dependent in vivo toxicity of PEG-coated gold nanoparticles

    PubMed Central

    Zhang, Xiao-Dong; Wu, Di; Shen, Xiu; Liu, Pei-Xun; Yang, Na; Zhao, Bin; Zhang, Hao; Sun, Yuan-Ming; Zhang, Liang-An; Fan, Fei-Yue

    2011-01-01

    Background Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice. Methods Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 μg/kg over 28 days. Results The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver. Conclusion The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future. PMID:21976982

  12. The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae.

    PubMed

    Zhang, Weicheng; Bao, Shaopan; Fang, Tao

    2016-04-20

    Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te ((particle)) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs' nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te ((particle)) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te ((ion)) efficiently determined the NPs toxicity associated with released ions.

  13. The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae

    PubMed Central

    Zhang, Weicheng; Bao, Shaopan; Fang, Tao

    2016-01-01

    Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te (particle) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs’ nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te (particle) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te (ion) efficiently determined the NPs toxicity associated with released ions. PMID:27094203

  14. The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae

    NASA Astrophysics Data System (ADS)

    Zhang, Weicheng; Bao, Shaopan; Fang, Tao

    2016-04-01

    Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te (particle) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs’ nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te (particle) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te (ion) efficiently determined the NPs toxicity associated with released ions.

  15. Effects from Filtration, Capping Agents, and Presence/Absence of Food on the Toxicity of Silver Nanoparticles to Daphnia Magna

    EPA Science Inventory

    Relatively little is known regarding the behavior and toxicity of nanoparticles in the environment. The objectives of the work presented here include establishing the toxicity of a variety of silver nanoparticles (AgNPs) to Daphnia magna neonates, assessing the applicability of ...

  16. Effects from Filtration, Capping Agents, and Presence/Absence of Food on the Toxicity of Silver Nanoparticles to Daphnia Magna

    EPA Science Inventory

    Relatively little is known regarding the behavior and toxicity of nanoparticles in the environment. The objectives of the work presented here include establishing the toxicity of a variety of silver nanoparticles (AgNPs) to Daphnia magna neonates, assessing the applicability of ...

  17. Encapsulation of Aconitine in Self-Assembled Licorice Protein Nanoparticles Reduces the Toxicity In Vivo

    NASA Astrophysics Data System (ADS)

    Ke, Li-jing; Gao, Guan-zhen; Shen, Yong; Zhou, Jian-wu; Rao, Ping-fan

    2015-11-01

    Many herbal medicines and compositions are clinically effective but challenged by its safety risks, i.e., aconitine (AC) from aconite species. The combined use of Radix glycyrrhizae (licorice) with Radix aconite L. effectively eliminates toxicity of the later while increasing efficacy. In this study, a boiling-stable 31-kDa protein (namely GP) was purified from licorice and self-assembled into nanoparticles (206.2 ± 2.0 nm) at pH 5.0, 25 °C. The aconitine-encapsulated GP nanoparticles (238.2 ± 1.2 nm) were prepared following the same procedure and tested for its toxicity by intraperitoneal injection on ICR mouse ( n = 8). Injection of GP-AC nanoparticles and the mixed licorice-aconite decoction, respectively, caused mild recoverable toxic effects and no death, while the aconitine, particle-free GP-AC mixture and aconite decoction induced sever toxic effects and 100 % death. Encapsulation of poisonous alkaloids into self-assembled herbal protein nanoparticles contributes to toxicity attenuation of combined use of herbs, implying a prototype nanostructure and a universal principle for the safer clinical applications of herbal medicines.

  18. Amphiphilic poly-N-vynilpyrrolidone nanoparticles: Cytotoxicity and acute toxicity study.

    PubMed

    Kuskov, A N; Kulikov, P P; Shtilman, M I; Rakitskii, V N; Tsatsakis, A M

    2016-10-01

    The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Encapsulation of Aconitine in Self-Assembled Licorice Protein Nanoparticles Reduces the Toxicity In Vivo.

    PubMed

    Ke, Li-Jing; Gao, Guan-Zhen; Shen, Yong; Zhou, Jian-Wu; Rao, Ping-Fan

    2015-12-01

    Many herbal medicines and compositions are clinically effective but challenged by its safety risks, i.e., aconitine (AC) from aconite species. The combined use of Radix glycyrrhizae (licorice) with Radix aconite L. effectively eliminates toxicity of the later while increasing efficacy. In this study, a boiling-stable 31-kDa protein (namely GP) was purified from licorice and self-assembled into nanoparticles (206.2 ± 2.0 nm) at pH 5.0, 25 °C. The aconitine-encapsulated GP nanoparticles (238.2 ± 1.2 nm) were prepared following the same procedure and tested for its toxicity by intraperitoneal injection on ICR mouse (n = 8). Injection of GP-AC nanoparticles and the mixed licorice-aconite decoction, respectively, caused mild recoverable toxic effects and no death, while the aconitine, particle-free GP-AC mixture and aconite decoction induced sever toxic effects and 100 % death. Encapsulation of poisonous alkaloids into self-assembled herbal protein nanoparticles contributes to toxicity attenuation of combined use of herbs, implying a prototype nanostructure and a universal principle for the safer clinical applications of herbal medicines.

  20. In vivo toxicity of enoxaparin encapsulated in mucoadhesive nanoparticles: Topical application in a wound healing model

    NASA Astrophysics Data System (ADS)

    Huber, S. C.; Marcato, P. D.; Barbosa, R. M.; Duran, N.; Annichino-Bizzacchi, J. M.

    2013-04-01

    Wound healing comprises four distinct phases and involves many cell events and biologic markers. The use of nanoparticles for topical application has gaining attention due to its deeper penetration in the skin and the retention capacity of the drug in the site of application. In this study the effect and toxicity of mucoadhesive polymeric nanoparticles loaded with enoxaparin was evaluated in in vivo model of skin ulcer. Our results showed an interesting formulation based on mucoadhesive nanoparticles with enoxaparin that improved wound healing without cytotoxicity in vitro in all endpoint evaluated. Then, this semi-solid formulation is a promising option for skin ulcer treatment.

  1. Analysis of copper nanoparticles toxicity based on a stress-responsive bacterial biosensor array

    NASA Astrophysics Data System (ADS)

    Li, Fenfang; Lei, Chunyang; Shen, Qinpeng; Li, Lijun; Wang, Ming; Guo, Manli; Huang, Yan; Nie, Zhou; Yao, Shouzhuo

    2012-12-01

    The rapid development in nanoparticle production and application during the past decade requires an easy, rapid, and predictive screening method for nanoparticles toxicity assay. In this study, the toxicological effects and the source of toxicity of copper nanoparticles (CuNPs) are investigated based on a stress-responsive bacterial biosensor array. According to the responses of the biosensing strains, it is found that CuNPs induce not only oxidative stress in E. coli, but also protein damage, DNA damage, and cell membrane damage, and ultimately cause cell growth inhibition. Through enzyme detoxification analysis, the toxicological effects of CuNPs are traced to H2O2 generation from CuNPs. Rapid copper release from CuNPs and Cu(i) production are observed. The oxidation of the released Cu(i) has a close relation to H2O2 production, as tris-(hydroxypropyltriazolylmethyl) amine, the specific Cu(i) chelator, can largely protect the cells from the toxicity of CuNPs. In addition, the TEM study shows that CuNPs can be adsorbed and incepted fast by the cells. Comparatively, copper microparticles are relatively stable in the system and practically non-toxic, which indicates the importance of toxic estimation of materials at the nanoscale. In addition, the Cu(ii) ion can induce protein damage, membrane damage, and slight DNA damage only at a relatively high concentration. The current study reveals the preliminary mechanism of toxicity of CuNPs, and suggests that the stress-responsive bacterial biosensor array can be used as a simple and promising tool for rapid screening in vitro toxicity of nanoparticles and studying the primary mechanism of the toxicity.The rapid development in nanoparticle production and application during the past decade requires an easy, rapid, and predictive screening method for nanoparticles toxicity assay. In this study, the toxicological effects and the source of toxicity of copper nanoparticles (CuNPs) are investigated based on a stress

  2. Oxidative Dissolution of Silver Nanoparticles by Chlorine: Implications to Silver Nanoparticle Fate and Toxicity.

    PubMed

    Garg, Shikha; Rong, Hongyan; Miller, Christopher J; Waite, T David

    2016-04-05

    The kinetics of oxidative dissolution of silver nanoparticles (AgNPs) by chlorine is investigated in this work, with results showing that AgNPs are oxidized in the presence of chlorine at a much faster rate than observed in the presence of dioxygen and/or hydrogen peroxide. The oxidation of AgNPs by chlorine occurs in air-saturated solution in stoichiometric amounts with 2 mol of AgNPs oxidized for each mole of chlorine added. Dioxygen plays an important role in OCl(-)-mediated AgNP oxidation, especially at lower OCl(-) concentrations, with the mechanism shifting from stoichiometric oxidation of AgNPs by OCl(-) in the presence of dioxygen to catalytic removal of OCl(-) by AgNPs in the absence of dioxygen. These results suggest that the presence of chlorine will mitigate AgNP toxicity by forming less-reactive AgCl(s) following AgNP oxidation, although the disinfection efficiency of OCl(-) may not be significantly impacted by the presence of AgNPs because a chlorine-containing species is formed on OCl(-) decay that has significant oxidizing capacity. Our results further suggest that the antibacterial efficacy of nanosilver particles embedded on fabrics may be negated when treated with detergents containing strong oxidants, such as chlorine.

  3. Gold nanoparticles: Distribution, bioaccumulation and toxicity. In vitro and in vivo studies.

    PubMed

    Lopez-Chaves, Carlos; Soto-Alvaredo, Juan; Montes-Bayon, Maria; Bettmer, Jörg; Llopis, Juan; Sanchez-Gonzalez, Cristina

    2017-09-04

    Concerns about the bioaccumulation and toxicity of gold nanoparticles inside humans have recently risen. HT-29 and HepG2 cell lines and Wistar rats were exposed to 10, 30 or 60 nm gold nanoparticles to determine their tissue distribution, subcellular location and deleterious effects. Cell viability, ROS production and DNA damage were evaluated in vitro. Lipid peroxidation and protein carbonylation were determined in liver. ICP-MS measurements showed the presence of gold in intestine, kidney, liver, spleen, feces and urine. Subcellular locations of gold nanoparticles were observed in colon cells and liver samples by transmission electron microscopy. Inflammatory markers in liver and biochemical parameters in plasma were measured to assess the inflammatory status and presence of tissue damage. The size of the nanoparticles determined differences in the biodistribution and the excretion route. The smallest nanoparticles showed more deleterious effects, confirmed by their location inside the cell nucleus and the higher DNA damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Relationship of pulmonary toxicity and carcinogenicity of fine and ultrafine granular dusts in a rat bioassay

    PubMed Central

    Kolling, Angelika; Ernst, Heinrich; Rittinghausen, Susanne; Heinrich, Uwe

    2011-01-01

    The current carcinogenicity study with female rats focused on the toxicity and carcinogenicity of intratracheally instilled fine and ultrafine granular dusts. The positive control, crystalline silica, elicited the greatest magnitude and progression of pulmonary inflammatory reactions, fibrosis and the highest incidence of primary lung tumors (39.6%). Addition of poly-2-vinylpyridine-N-oxide decreased inflammatory responses, fibrosis, and the incidence of pulmonary tumors induced by crystalline quartz to 21.4%. After repeated instillation of soluble, ultrafine amorphous silica (15 mg) a statistically significant tumor response (9.4%) was observed, although, the inflammatory response in the lung was not as persistently severe as in rats treated with carbon black. Instillation of ultrafine carbon black (5 mg) caused a lung tumor incidence of 15%. In contrast to a preceding study using a dose of 66 mg coal dust, lung tumors were not detected after exposure to the same coal dust at a dose of 10 mg in this study. Pulmonary inflammatory responses to coal dust were very low indicating a mechanistic threshold for the development of lung tumors connected with particle related chronic inflammation. The animals treated with ultrafine carbon black and ultrafine amorphous silica showed significantly more severe lesions in non-cancerous endpoints when compared to animals treated with fine coal dust. Furthermore, carbon black treated rats showed more severe non-cancerous lung lesions than amorphous silica treated rats. Our data show a relationship between tumor frequencies and increasing scores when using a qualitative scoring system for specific non-cancerous endpoints such as inflammation, fibrosis, epithelial hyperplasia, and squamous metaplasia. PMID:21819261

  5. Reduction of Pulmonary Toxicity of Stachybotrys chartarum Spores by Methanol Extraction of Mycotoxins

    PubMed Central

    Rao, Carol Y.; Brain, Joseph D.; Burge, Harriet A.

    2000-01-01

    The fungus Stachybotrys chartarum has been implicated in cases of nonspecific indoor air quality complaints in adults and in cases of pulmonary hemorrhaging in infants. The effects that have been described have been attributed to mycotoxins. Previous dose-effect studies focused on exposure to a single mycotoxin in a solvent, a strategy which is unlikely to accurately characterize the effects of inhaled spores. In this study we examined the role of mycotoxins in the pulmonary effects caused by S. chartarum spores and the dose dependency of these effects. S. chartarum spores were extracted in methanol to reduce the mycotoxin content of the spores. Then either untreated (toxin-containing) or methanol-extracted S. chartarum spores were intratracheally instilled into male 10-week-old Charles River-Dawley rats. After 24 h, the lungs were lavaged, and the bronchoalveolar lavage fluid was analyzed to determine differences in lactic dehydrogenase, albumin, hemoglobin, myeloperoxidase, and leukocyte differential counts. Weight change was also monitored. Our data show that methanol extraction dramatically reduced the toxicity of S. chartarum spores. No statistically significant effects were observed in the bronchoalveolar lavage fluids of the animals that were treated with methanol-extracted spores at any dose. Conversely, dose-dependent effects of the toxin-containing spores were observed when we examined the lactic dehydrogenase, albumin, and hemoglobin concentrations, the polymorphonuclear leukocyte counts, and weight loss. Our findings show that a single, intense exposure to toxin-containing S. chartarum spores results in pulmonary inflammation and injury in a dose-dependent manner. Importantly, the effects are related to methanol-soluble toxins in the spores. PMID:10877773

  6. A meta-analysis of carbon nanotube pulmonary toxicity studies--how physical dimensions and impurities affect the toxicity of carbon nanotubes.

    PubMed

    Gernand, Jeremy M; Casman, Elizabeth A

    2014-03-01

    This article presents a regression-tree-based meta-analysis of rodent pulmonary toxicity studies of uncoated, nonfunctionalized carbon nanotube (CNT) exposure. The resulting analysis provides quantitative estimates of the contribution of CNT attributes (impurities, physical dimensions, and aggregation) to pulmonary toxicity indicators in bronchoalveolar lavage fluid: neutrophil and macrophage count, and lactate dehydrogenase and total protein concentrations. The method employs classification and regression tree (CART) models, techniques that are relatively insensitive to data defects that impair other types of regression analysis: high dimensionality, nonlinearity, correlated variables, and significant quantities of missing values. Three types of analysis are presented: the RT, the random forest (RF), and a random-forest-based dose-response model. The RT shows the best single model supported by all the data and typically contains a small number of variables. The RF shows how much variance reduction is associated with every variable in the data set. The dose-response model is used to isolate the effects of CNT attributes from the CNT dose, showing the shift in the dose-response caused by the attribute across the measured range of CNT doses. It was found that the CNT attributes that contribute the most to pulmonary toxicity were metallic impurities (cobalt significantly increased observed toxicity, while other impurities had mixed effects), CNT length (negatively correlated with most toxicity indicators), CNT diameter (significantly positively associated with toxicity), and aggregate size (negatively correlated with cell damage indicators and positively correlated with immune response indicators). Increasing CNT N2 -BET-specific surface area decreased toxicity indicators.

  7. Successful treatment of severe amiodarone pulmonary toxicity with polymyxin B-immobilized fiber column direct hemoperfusion.

    PubMed

    Sato, Nahoko; Kojima, Keisuke; Horio, Yuko; Goto, Eisuke; Masunaga, Aiko; Ichiyasu, Hidenori; Kohrogi, Hirotsugu

    2013-04-01

    Amiodarone pulmonary toxicity (APT) is the most serious side effect of amiodarone. Although severe APT, such as ARDS, is rare, mortality of severe APT is high. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is a medical device that reduces blood endotoxin levels in sepsis. Recent reports have shown that PMX-DHP improves oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis and drug-induced severe interstitial pneumonia. Here, we present a case study of a patient with severe APT treated with PMX-DHP with complete recovery. The patient rapidly developed respiratory failure and required mechanical ventilation. Despite corticosteroid pulse therapy, no clinical improvement was noted. PMX-DHP was then started, and severe respiratory failure improved with reduction of serum levels of amiodarone and its metabolite monodesethylamiodarone. The patient was weaned from mechanical ventilation and has done well without recurrence. To our knowledge, this is the first reported case of PMX-DHP therapy for severe APT. We speculate that PMX-DHP could be a new treatment strategy for severe APT.

  8. Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.

    PubMed

    Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng

    2017-11-01

    Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.

  9. Transport of nanoparticles across pulmonary surfactant monolayer: a molecular dynamics study.

    PubMed

    Xu, Yan; Deng, Li; Ren, Hao; Zhang, Xianren; Huang, Fang; Yue, Tongtao

    2017-07-21

    Pulmonary nanodrug delivery is an emerging concept, especially for targeted lung cancer therapy. Once inhaled, the nanoparticles (NPs) acting as drug carriers need to efficiently cross the pulmonary surfactant monolayer (PSM) of lung alveoli, which act as the first barrier for external particles entering the lung. Herein, by performing molecular dynamics simulations, we study how inhaled NPs interact with the PSM, particularly focusing on the transport of NPs with different properties across the PSM. While hydrophilic NPs translocate directly across the PSM, transport of hydrophobic NPs is achieved as the PSM wraps them. Intriguingly, when hydrophilic NPs are decorated with lipid molecules (LCNPs), they are wrapped by the PSM efficiently with mild PSM perturbation. Moreover, the structure formed is like a vesicle, which will likely fuse with cell membranes to accomplish the transport of hydrophilic NPs into secondary organs. This behavior makes the LCNP a prospective candidate for pulmonary nanodrug delivery. Herein, the effects of the physical properties of LCNPs on their transport are investigated. Increasing the LCNP size promotes its wrapping by reducing the PSM bending energy. The binding energy that drives transport can be strengthened by increasing the lipid coating density and the lipid tail length, both of which also reduce the risk of PSM rupture during transport. These results should help researchers understand how to better use surface decorations to achieve efficient pulmonary entry, which may provide useful guidance for the design of nano-based platforms for inhaled drug delivery.

  10. Analysis of copper nanoparticles toxicity based on a stress-responsive bacterial biosensor array.

    PubMed

    Li, Fenfang; Lei, Chunyang; Shen, Qinpeng; Li, Lijun; Wang, Ming; Guo, Manli; Huang, Yan; Nie, Zhou; Yao, Shouzhuo

    2013-01-21

    The rapid development in nanoparticle production and application during the past decade requires an easy, rapid, and predictive screening method for nanoparticles toxicity assay. In this study, the toxicological effects and the source of toxicity of copper nanoparticles (CuNPs) are investigated based on a stress-responsive bacterial biosensor array. According to the responses of the biosensing strains, it is found that CuNPs induce not only oxidative stress in E. coli, but also protein damage, DNA damage, and cell membrane damage, and ultimately cause cell growth inhibition. Through enzyme detoxification analysis, the toxicological effects of CuNPs are traced to H(2)O(2) generation from CuNPs. Rapid copper release from CuNPs and Cu(I) production are observed. The oxidation of the released Cu(I) has a close relation to H(2)O(2) production, as tris-(hydroxypropyltriazolylmethyl) amine, the specific Cu(I) chelator, can largely protect the cells from the toxicity of CuNPs. In addition, the TEM study shows that CuNPs can be adsorbed and incepted fast by the cells. Comparatively, copper microparticles are relatively stable in the system and practically non-toxic, which indicates the importance of toxic estimation of materials at the nanoscale. In addition, the Cu(II) ion can induce protein damage, membrane damage, and slight DNA damage only at a relatively high concentration. The current study reveals the preliminary mechanism of toxicity of CuNPs, and suggests that the stress-responsive bacterial biosensor array can be used as a simple and promising tool for rapid screening in vitro toxicity of nanoparticles and studying the primary mechanism of the toxicity.

  11. The pulmonary toxicity of talc and granite dust as estimated from an in vivo hamster bioassay.

    PubMed

    Beck, B D; Feldman, H A; Brain, J D; Smith, T J; Hallock, M; Gerson, B

    1987-02-01

    A short-term animal bioassay was used to assess the toxicity of occupational dusts. We quantified pulmonary responses in hamsters exposed to granite (12% quartz) and talc (quartz and asbestos-free) dust collected from worksites. Personal samples collected on workers showed similar quartz content and particle-size distributions to the high-volume samples collected for bioassays, thus demonstrating that the particulates were representative of worker exposure. We measured biochemical and cellular indicators of injury in bronchoalveolar lavage fluid (BAL) of animals exposed to dust suspensions by intra-tracheal instillation. The assays measured release of cytoplasmic and lysosomal enzymes into the cell-free supernatant of BAL; levels of albumin and red blood cells; changes in macrophage and polymorphonuclear neutrophil cell numbers; and in situ macrophage phagocytosis. Dose-response (0.15, 0.75, and 3.75 mg/100 g body wt) and time-course (1-14 days postexposure) studies were performed. One day after exposure, both talc and granite dust resulted in elevated enzyme levels, pulmonary edema, and increased cell numbers in BAL. Macrophage phagocytosis was also inhibited. Based on earlier studies, response levels were either intermediate between nontoxic iron oxide and toxic alpha-quartz or comparable with alpha-quartz. The response to granite dust diminished fairly rapidly over time. By contrast, after talc exposure, there was a more persistent elevation in enzyme levels, and macrophage phagocytosis remained depressed. These results indicate that, when a similar mass was deposited in the lungs, talc caused more lung injury than did granite. Better estimates of exposure-dose relationships in talc and granite workers as well as longer-term animal studies are required to evaluate the harmfulness of these work environments at present-day exposure levels.

  12. Biotic and abiotic interactions in aquatic microcosms determine fate and toxicity of Ag nanoparticles: part 2-toxicity and Ag speciation.

    PubMed

    Bone, Audrey J; Colman, Benjamin P; Gondikas, Andreas P; Newton, Kim M; Harrold, Katherine H; Cory, Rose M; Unrine, Jason M; Klaine, Stephen J; Matson, Cole W; Di Giulio, Richard T

    2012-07-03

    To study the effects of complex environmental media on silver nanoparticle (AgNP) toxicity, AgNPs were added to microcosms with freshwater sediments and two species of aquatic plants (Potamogeton diversifolius and Egeria densa), followed by toxicity testing with microcosm surface water. Microcosms were designed with four environmental matrices in order to determine the contribution of each environmental compartment to changes in toxicity: water only (W), water + sediment (WS), water + plants (WP), and water + plants + sediment (WPS). Silver treatments included AgNPs with two different coatings, gum arabic (GA-AgNPs) or polyvinylpyrollidone (PVP-AgNPs), as well as AgNO(3). Water samples taken from the microcosms at 24 h postdosing were used in acute toxicity tests with two standard model organisms, early life stage zebrafish (Danio rerio) and Daphnia magna. Speciation of Ag in these samples was analyzed using Ag L3-edge X-ray absorption near edge spectroscopy (XANES). Silver speciation patterns for the nanoparticle treatments varied significantly by coating type. While PVP-AgNPs were quite stable and resisted transformation across all matrices (>92.4% Ag(0)), GA-AgNP speciation patterns suggest significantly higher transformation rates, especially in treatments with plants (<69.2% and <58.8% Ag(0) in WP and WPS, respectively) and moderately increased transformation with sediments (<85.6% Ag(0)). Additionally, the presence of plants in the microcosms (with and without sediments) reduced both the concentration of Ag in the water column and toxicity for all Ag treatments. Reductions in toxicity may have been related to decreased water column concentrations as well as changes in the surface chemistry of the particles induced by organic substances released from the plants.

  13. Reduced in vivo toxicity of doxorubicin by encapsulation in cholesterol-containing self-assembled nanoparticles.

    PubMed

    Gonzalez-Fajardo, Laura; Mahajan, Lalit H; Ndaya, Dennis; Hargrove, Derek; Manautou, José E; Liang, Bruce T; Chen, Ming-Hui; Kasi, Rajeswari M; Lu, Xiuling

    2016-05-01

    We previously reported the development of an amphiphilic brush-like block copolymer composed of polynorbornene-cholesterol/polyethylene glycol (P(NBCh9-b-NBPEG)) that self-assembles in aqueous media to form long circulating nanostructures capable of encapsulating doxorubicin (DOX-NPs). Biodistribution studies showed that this formulation preferentially accumulates in tumor tissue with markedly reduced accumulation in the heart and other major organs. The aim of the current study was to evaluate the in vivo efficacy and toxicity of DOX containing self-assembled polymer nanoparticles in a mouse xenograft tumor model and compare its effects with the hydrochloride non-encapsulated form (free DOX). DOX-NPs significantly reduced the growth of tumors without inducing any apparent toxicity. Conversely, mice treated with free DOX exhibited significant weight loss, early toxic cardiomyopathy, acute toxic hepatopathy, reduced hematopoiesis and fatal toxicity. The improved safety profile of the polymeric DOX-NPs can be explained by the low circulating concentration of non-nanoparticle-associated drug as well as the reduced accumulation of DOX in non-target organs. These findings support the use of P(NBCh9-b-NBPEG) nanoparticles as delivery platforms for hydrophobic anticancer drugs intended to reduce the toxicity of conventional treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Impact of water chemistry on the particle-specific toxicity of copper nanoparticles to Daphnia magna.

    PubMed

    Xiao, Yinlong; Peijnenburg, Willie J G M; Chen, Guangchao; Vijver, Martina G

    2018-01-01

    Toxicity of metallic nanoparticle suspensions (NP(total)) is generally assumed to result from the combined effect of the particles present in suspensions (NP(particle)) and their released ions (NP(ion)). Evaluation and consideration of how water chemistry affects the particle-specific toxicity of NP(total) are critical for environmental risk assessment of nanoparticles. In this study, it was found that the toxicity of Cu NP(particle) to Daphnia magna, in line with the trends in toxicity for Cu NP(ion), decreased with increasing pH and with increasing concentrations of divalent cations and dissolved organic carbon (DOC). Without the addition of DOC, the toxicity of Cu NP(total) to D. magna at the LC50 was driven mainly by Cu NP(ion) (accounting for ≥53% of the observed toxicity). However, toxicity of Cu NP(total) in the presence of DOC at a concentration ranging from 5 to 50mg C/L largely resulted from the NP(particle) (57%-85%), which could be attributable to the large reduction of the concentration of Cu NP(ion) and the enhancement of the stability of Cu NP(particle) when DOC was added. Our results indicate that water chemistry needs to be explicitly taken into consideration when evaluating the role of NP(particle) and NP(ion) in the observed toxicity of NP(total). Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Silver nanoparticle toxicity is related to coating materials and disruption of sodium concentration regulation.

    PubMed

    Kwok, Kevin W H; Dong, Wu; Marinakos, Stella M; Liu, Jie; Chilkoti, Ashutosh; Wiesner, Mark R; Chernick, Melissa; Hinton, David E

    2016-11-01

    Silver nanoparticles (AgNPs) have been increasingly commercialized and their release into the environment is imminent. Toxicity of AgNP has been studied with a wide spectrum of organisms, yet the mechanism of toxicity remains largely unknown. This study systematically compared toxicity of 10 AgNPs of different particle diameters and coatings to Japanese medaka (Oryzias latipes) larvae to understand how characteristics of AgNP relate to toxicity. Dissolution of AgNPs was largely dependent on particle size, but their aggregation behavior and toxicity were more dependent on coating materials. 96 h lethal concentration 50% (LC50) values correlated with AgNP aggregate size rather than size of individual nanoparticles. Of the AgNPs studied, the dissolved Ag concentration in the test suspensions did not account for all of the observed toxicity, indicating the role of NP-specific characteristics in resultant toxicity. Exposure to AgNP led to decrease of sodium concentration in the tissue and increased expression of Na(+)/K(+ )ATPase. Gene expression patterns also suggested that toxicity was related to disruption of sodium regulation and not to oxidative stress.

  16. Drug Delivery Nanoparticles with Locally Tunable Toxicity Made Entirely from a Light-Activatable Prodrug of Doxorubicin.

    PubMed

    Schutt, Carolyn; Ibsen, Stuart; Zahavy, Eran; Aryal, Santosh; Kuo, Stacey; Esener, Selin; Berns, Michael; Esener, Sadik

    2017-08-08

    A major challenge facing nanoparticle-based delivery of chemotherapy agents is the natural and unavoidable accumulation of these particles in healthy tissue resulting in local toxicity and dose-limiting side effects. To address this issue, we have designed and characterized a new prodrug nanoparticle with controllable toxicity allowing a locally-delivered light trigger to convert the payload of the particle from a low to a high toxicity state. The nanoparticles are created entirely from light-activatable prodrug molecules using a nanoprecipitation process. The prodrug is a conjugate of doxorubicin and photocleavable biotin (DOX-PCB). These DOX-PCB nanoparticles are 30 times less toxic to cells than doxorubicin, but can be activated to release pure therapeutic doxorubicin when exposed to 365 nm light. These nanoparticles have an average diameter of around 100 nm and achieve the maximum possible prodrug loading capacity since no support structure or coating is required to prevent loss of prodrug from the nanoparticle. These light activatable nanoparticles demonstrate tunable toxicity and can be used to facilitate future therapy development whereby light delivered specifically to the tumor tissue would locally convert the nanoparticles to doxorubicin while leaving nanoparticles accumulated in healthy tissue in the less toxic prodrug form.

  17. A novel method for assessing the toxicity of silver nanoparticles in Caenorhabditis elegans.

    PubMed

    Luo, Xun; Xu, Shengmin; Yang, Yaning; Zhang, Yajun; Wang, Shunchang; Chen, Shaopeng; Xu, An; Wu, Lijun

    2017-02-01

    At present, nanotechnology has been producing nanoscale materials with unprecedented speed. Nanomaterials could be inevitably released into the environment owing to their widespread use, and their potential toxicity has caused a great concern. With regard to assessment of nanomaterial toxicity, many studies probably don't truly reflect their toxicity, because the nanoparticles were not stable and uniformly dispersed in the medium. In the present study, the semi-fluid nematode growth gelrite medium (NGG) was used to achieve better distribution of silver nanoparticles (AgNPs). We aimed to evaluate the toxicity of AgNPs in three different culture methods, such as the NGG, nematode growth medium (NGM) and K-medium (KM). Our transmission electron microscopy, hydrodynamic diameter, and inductively coupled plasma-atomic emission spectrometry results demonstrated that AgNPs homogeneously and stably dispersed in NGG compared to that in liquid KM. Furthermore, the conventional toxicity end points, such as body length, fecundity, lifespan, population growth, germline cell apoptosis, reactive oxygen species, and mitochondrial membrane potential were used to assess the toxicity of AgNPs to Caenorhabditis elegans (C. elegans) in NGG, NGM and KM. Our results showed that the toxicity of AgNPs obtained in the NGG test medium was much higher than that in the standard NGM and KM. In addition to the improved dispersion of nanoparticles, NGG also offered advantages for long-term studies and likely provided a convenient nematode toxicity testing method. These results revealed that the NGG test medium was a suitable and sensitive culture method for the evaluation of AgNPs toxicity using C. elegans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Mechanistically Probing Lipid-siRNA Nanoparticle-associated Toxicities Identifies Jak Inhibitors Effective in Mitigating Multifaceted Toxic Responses

    PubMed Central

    Tao, Weikang; Mao, Xianzhi; Davide, Joseph P; Ng, Bruce; Cai, Mingmei; Burke, Paul A; Sachs, Alan B; Sepp-Lorenzino, Laura

    2011-01-01

    A major hurdle for harnessing small interfering RNA (siRNA) for therapeutic application is an effective and safe delivery of siRNA to target tissues and cells via systemic administration. While lipid nanoparticles (LNPs) composed of a cationic lipid, poly-(ethylene glycol) lipid and cholesterol, are effective in delivering siRNA to hepatocytes via systemic administration, they may induce multi-faceted toxicities in a dose-dependent manner, independently of target silencing. To understand the underlying mechanism of toxicities, pharmacological probes including anti-inflammation drugs and specific inhibitors blocking different pathways of innate immunity were evaluated for their abilities to mitigate LNP-siRNA-induced toxicities in rodents. Three categories of rescue effects were observed: (i) pretreatment with a Janus kinase (Jak) inhibitor or dexamethasone abrogated LNP-siRNA-mediated lethality and toxicities including cytokine induction, organ impairments, thrombocytopenia and coagulopathy without affecting siRNA-mediated gene silencing; (ii) inhibitors of PI3K, mammalian target of rapamycin (mTOR), p38 and IκB kinase (IKK)1/2 exhibited a partial alleviative effect; (iii) FK506 and etoricoxib displayed no protection. Furthermore, knockout of Jak3, tumor necrosis factor receptors (Tnfr)p55/p75, interleukin 6 (IL-6) or interferon (IFN)-γ alone was insufficient to alleviate LNP-siRNA-associated toxicities in mice. These indicate that activation of innate immune response is a primary trigger of systemic toxicities and that multiple innate immune pathways and cytokines can mediate toxic responses. Jak inhibitors are effective in mitigating LNP-siRNA-induced toxicities. PMID:21179008

  19. Mechanistically probing lipid-siRNA nanoparticle-associated toxicities identifies Jak inhibitors effective in mitigating multifaceted toxic responses.

    PubMed

    Tao, Weikang; Mao, Xianzhi; Davide, Joseph P; Ng, Bruce; Cai, Mingmei; Burke, Paul A; Sachs, Alan B; Sepp-Lorenzino, Laura

    2011-03-01

    A major hurdle for harnessing small interfering RNA (siRNA) for therapeutic application is an effective and safe delivery of siRNA to target tissues and cells via systemic administration. While lipid nanoparticles (LNPs) composed of a cationic lipid, poly-(ethylene glycol) lipid and cholesterol, are effective in delivering siRNA to hepatocytes via systemic administration, they may induce multi-faceted toxicities in a dose-dependent manner, independently of target silencing. To understand the underlying mechanism of toxicities, pharmacological probes including anti-inflammation drugs and specific inhibitors blocking different pathways of innate immunity were evaluated for their abilities to mitigate LNP-siRNA-induced toxicities in rodents. Three categories of rescue effects were observed: (i) pretreatment with a Janus kinase (Jak) inhibitor or dexamethasone abrogated LNP-siRNA-mediated lethality and toxicities including cytokine induction, organ impairments, thrombocytopenia and coagulopathy without affecting siRNA-mediated gene silencing; (ii) inhibitors of PI3K, mammalian target of rapamycin (mTOR), p38 and IκB kinase (IKK)1/2 exhibited a partial alleviative effect; (iii) FK506 and etoricoxib displayed no protection. Furthermore, knockout of Jak3, tumor necrosis factor receptors (Tnfr)p55/p75, interleukin 6 (IL-6) or interferon (IFN)-γ alone was insufficient to alleviate LNP-siRNA-associated toxicities in mice. These indicate that activation of innate immune response is a primary trigger of systemic toxicities and that multiple innate immune pathways and cytokines can mediate toxic responses. Jak inhibitors are effective in mitigating LNP-siRNA-induced toxicities.

  20. Alterations in welding process voltage affect the generation of ultrafine particles, fume composition, and pulmonary toxicity.

    PubMed

    Antonini, James M; Keane, Michael; Chen, Bean T; Stone, Samuel; Roberts, Jenny R; Schwegler-Berry, Diane; Andrews, Ronnee N; Frazer, David G; Sriram, Krishnan

    2011-12-01

    The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m³ (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile.

  1. Toxicogenomic analysis of the pulmonary toxic effects of hexanal in F344 rat.

    PubMed

    Cho, Yoon; Lim, Jung-Hee; Song, Mi-Kyung; Jeong, Seung-Chan; Lee, Kyuhong; Heo, Yongju; Kim, Tae Sung; Ryu, Jae-Chun

    2017-02-01

    Hexanal is a major component of indoor air pollutants and is a kind of aldehydes; it has adverse effects on human health. We performed an in vivo inhalation study and transcriptomic analysis to determine the mode of toxic actions in response to hexanal. Fischer 344 rats of both sexes were exposed by inhalation to hexanal aerosol for 4 h day(-1) , 5 days week(-1) for 4 weeks at 0, 600, 1000, and 1500 ppm. Throughout our microarray-based genome-wide expression analysis, we identified 56 differentially expressed genes in three doses of hexanal; among these genes, 11 genes showed dose-dependent expression patterns (10 downregulated and 1 upregulated, 1.5-fold, p < 0.05). Through a comparative toxicogenomics database (CTD) analysis of 11 genes, we determined that five genes (CCL12, DDIT4, KLF2, CEBPD, and ADH6) are linked to diverse disease categories such as cancer, respiratory tract disease, and immune system disease. These diseases were previously known for being induced by volatile organic compounds (VOCs). Our data demonstrated that the hexanal-induced dose-dependent altered genes could be valuable quantitative biomarkers to predict hexanal exposure and to perform relative risk assessments, including pulmonary toxicity. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 382-396, 2017. © 2016 Wiley Periodicals, Inc.

  2. Improved corneal toxicity and permeability of tranilast by the preparation of ophthalmic formulations containing its nanoparticles.

    PubMed

    Nagai, Noriaki; Ono, Hikaru; Hashino, Miho; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

    2014-01-01

    We prepared ophthalmic formulations containing 0.5% tranilast (TL) nanoparticles using 0.005% benzalkonium chloride (BAC), 0.5% D-mannitol, and 2-hydroxypropyl-β-cyclodextrin (HPβCD), and investigated their usefulness in the ophthalmologic field by evaluating corneal toxicity and permeability. TL nanoparticles were prepared using zirconia beads and Bead Smash 12, which allowed the preparation of high quality dispersions containing 0.5% TL nanoparticles (particle size, 34 ± 20 nm, means ± S.D.). Dispersions containing TL nanoparticles are tolerated better by human corneal epithelium cells than a commercially available 0.5% TL preparation (RIZABEN(®) eye drops). In addition, the addition of TL nanoparticles to the dispersions does not affect the antimicrobial activity of BAC against Escherichia coli (ATCC 8739), and the corneal penetration of TL from dispersions containing TL nanoparticles was significantly higher than in the case of the commercially available 0.5% TL eye drops. It is possible that dispersions containing TL nanoparticles will show increased effectiveness against ocular inflammation, and that ocular drug delivery systems using drug nanoparticles may lead to an expansion of their usefulness for therapy in the ophthalmologic field.

  3. Toxicity assessment of Titanium Dioxide and Cerium Oxide nanoparticles in Arabidopsis thaliana L.

    EPA Science Inventory

    The production and applications of nanoparticles (NP) in diverse fields has steadily increased in recent decades; however, knowledge about risks of NP to human health and ecosystems is still scarce. In this study, we assessed potential toxicity of two commercially used engineere...

  4. Toxicity assessment of Titanium Dioxide and Cerium Oxide nanoparticles in Arabidopsis thaliana L.

    EPA Science Inventory

    The production and applications of nanoparticles (NP) in diverse fields has steadily increased in recent decades; however, knowledge about risks of NP to human health and ecosystems is still scarce. In this study, we assessed potential toxicity of two commercially used engineere...

  5. Effects of Humic and Fulvic Acids on Silver Nanoparticle Stability, Dissolution, and Toxicity.

    PubMed

    Gunsolus, Ian L; Mousavi, Maral P S; Hussein, Kadir; Bühlmann, Philippe; Haynes, Christy L

    2015-07-07

    The colloidal stability of silver nanoparticles (AgNPs) in natural aquatic environments influences their transport and environmental persistence, while their dissolution to Ag(+) influences their toxicity to organisms. Here, we characterize the colloidal stability, dissolution behavior, and toxicity of two industrially relevant classes of AgNPs (i.e., AgNPs stabilized by citrate or polyvinylpyrrolidone) after exposure to natural organic matter (NOM, i.e., Suwannee River Humic and Fulvic Acid Standards and Pony Lake Fulvic Acid Reference). We show that NOM interaction with the nanoparticle surface depends on (i) the NOM's chemical composition, where sulfur- and nitrogen-rich NOM more significantly increases colloidal stability, and (ii) the affinity of the capping agent for the AgNP surface, where nanoparticles with loosely bound capping agents are more effectively stabilized by NOM. Adsorption of NOM is shown to have little effect on AgNP dissolution under most experimental conditions, the exception being when the NOM is rich in sulfur and nitrogen. Similarly, the toxicity of AgNPs to a bacterial model (Shewanella oneidensis MR-1) decreases most significantly in the presence of sulfur- and nitrogen-rich NOM. Our data suggest that the rate of AgNP aggregation and dissolution in aquatic environments containing NOM will depend on the chemical composition of the NOM, and that the toxicity of AgNPs to aquatic microorganisms is controlled primarily by the extent of nanoparticle dissolution.

  6. Toxicity of bare and surfaced functionalized iron oxide nanoparticles towards microalgae.

    PubMed

    Toh, Pey Yi; Tai, Wan Yii; Ahmad, Abdul Latif; Lim, Jit Kang; Chan, Derek Juinn Chieh

    2016-01-01

    This study investigates the toxicity of bare iron oxide nanoparticles (IONPs) and surface functionalization iron oxide nanoparticles (SF-IONPs) to the growth of freshwater microalgae Chlorella sp. This study is important due to the increased interest on the application of the magnetic responsive IONPs in various fields, such as biomedical, wastewater treatment, and microalgae harvesting. This study demonstrated that the toxicity of IONPs was mainly contributed by the indirect light shading effect from the suspending nanoparticles which is nanoparticles concentration-dependent, direct light shading effect caused by the attachment of IONPs on cell and the cell aggregation, and the oxidative stress from the internalization of IONPs into the cells. The results showed that the layer of poly(diallyldimethylammonium chloride) (PDDA) tended to mask the IONPs and hence eliminated oxidative stress toward the protein yield but it in turn tended to enhance the toxicity of IONPs by enabling the IONPs to attach on cell surfaces and cause cell aggregation. Therefore, the choice of the polymer that used for surface functionalize the IONPs is the key factor to determine the toxicity of the IONPs.

  7. TLR4 Signaling Is Involved in Brain Vascular Toxicity of PCB153 Bound to Nanoparticles

    PubMed Central

    Zhang, Bei; Choi, Jeong June; Eum, Sung Yong; Daunert, Sylvia; Toborek, Michal

    2013-01-01

    PCBs bind to environmental particles; however, potential toxicity exhibited by such complexes is not well understood. The aim of the present study is to study the hypothesis that assembling onto nanoparticles can influence the PCB153-induced brain endothelial toxicity via interaction with the toll-like receptor 4 (TLR4). To address this hypothesis, TLR4-deficient and wild type control mice (males, 10 week old) were exposed to PCB153 (5 ng/g body weight) bound to chemically inert silica nanoparticles (PCB153-NPs), PCB153 alone, silica nanoparticles (NPs; diameter, 20 nm), or vehicle. Selected animals were also subjected to 40 min ischemia, followed by a 24 h reperfusion. As compared to exposure to PCB153 alone, treatment with PCB153-NP potentiated the brain infarct volume in control mice. Importantly, this effect was attenuated in TLR4-deficient mice. Similarly, PCB153-NP-induced proinflammatory responses and disruption of tight junction integrity were less pronounced in TLR4-deficient mice as compared to control animals. Additional in vitro experiments revealed that TLR4 mediates toxicity of PCB153-NP via recruitment of tumor necrosis factor-associated factor 6 (TRAF6). The results of current study indicate that binding to seemingly inert nanoparticles increase cerebrovascular toxicity of PCBs and suggest that targeting the TLR4/TRAF6 signaling may protect against these effects. PMID:23690990

  8. Surface modification minimizes the toxicity of silver nanoparticles: an in vitro and in vivo study.

    PubMed

    Das, Balaram; Tripathy, Satyajit; Adhikary, Jaydeep; Chattopadhyay, Sourav; Mandal, Debasis; Dash, Sandeep Kumar; Das, Sabyasachi; Dey, Aditi; Dey, Sankar Kumar; Das, Debasis; Roy, Somenath

    2017-08-01

    Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system. Ag-NPs released excess Ag(+) ions leads to activation of NADPH oxidase and helps in generating the reactive oxygen species (ROS). Silver nanoparticles elicit the production of excess amount of ROS results activation of TNF-α. Ag-NPs activates caspase-3 and 9 which are the signature of mitochondrial pathway. Ag-NPs are responsible to decrease the antioxidant enzymes and imbalance the oxidative status into the cells but functionalization with BSA and PEG helps to protect the adverse effect of Ag-NPs on the cells. This study suggested that Ag-NPs are toxic to normal cells which directly lead with human health. Surface functionalization may open the gateway for further use of Ag-NPs in different area such as antimicrobial and anticancer therapy, industrial use or in biomedical sciences.

  9. Effects of Humic and Fulvic Acids on Silver Nanoparticle Stability, Dissolution, and Toxicity

    PubMed Central

    Gunsolus, Ian L.; Mousavi, Maral P. S.; Hussein, Kadir; Bühlmann, Philippe; Haynes, Christy L.

    2015-01-01

    The colloidal stability of silver nanoparticles (AgNPs) in natural aquatic environments influences their transport and environmental persistence, while their dissolution to Ag+ influences their toxicity to organisms. Here, we characterize the colloidal stability, dissolution behavior, and toxicity of two industrially relevant classes of AgNPs (i.e., AgNPs stabilized by citrate or polyvinylpyrrolidone) after exposure to natural organic matter (NOM, i.e., Suwannee River Humic and Fulvic Acid Standards and Pony Lake Fulvic Acid Reference). We show that NOM interaction with the nanoparticle surface depends on (i) the NOM’s chemical composition, where sulfur- and nitrogen-rich NOM more significantly increases colloidal stability, and (ii) the affinity of the capping agent for the AgNP surface, where nanoparticles with loosely bound capping agents are more effectively stabilized by NOM. Adsorption of NOM is shown to have little effect on AgNP dissolution under most experimental conditions, the exception being when the NOM is rich in sulfur and nitrogen. Similarly, the toxicity of AgNPs to a bacterial model (Shewanella oneidensis MR-1) decreases most significantly in the presence of sulfur- and nitrogen-rich NOM. Our data suggest that the rate of AgNP aggregation and dissolution in aquatic environments containing NOM will depend on the chemical composition of the NOM, and that the toxicity of AgNPs to aquatic microorganisms is controlled primarily by the extent of nanoparticle dissolution. PMID:26047330

  10. SDF-1α in Glycan Nanoparticles Exhibits Full Activity and Reduces Pulmonary Hypertension in Rats

    PubMed Central

    Yin, Tao; Bader, Andrew R.; Hou, Tim K.; Maron, Bradley A.; Kao, Derrick D.; Qian, Ray; Kohane, Daniel S.; Handy, Diane E.; Loscalzo, Joseph; Zhang, Ying-Yi

    2013-01-01

    In order to establish a homing signal in the lung to recruit circulating stem cells for tissue repair, we formulated a nanoparticle, SDF-1α NP, by complexing SDF-1α with dextran sulfate and chitosan. The data show that SDF-1α was barely released from the nanoparticles over an extended period of time in vitro (3% in 7 days at 37°C); however, incorporated SDF-1α exhibited full chemotactic activity and receptor activation compared to its free form. The nanoparticles were not endocytosed after incubation with Jurkat cells. When aerosolized into the lungs of rats, SDF-1α NP displayed a greater retention time compared to free SDF-1α (64% vs. 2% remaining at 16 hr). In a rat model of monocrotaline-induced lung injury, SDF-1α NP, but not free form SDF-1α, was found to reduce pulmonary hypertension. These data suggest that the nanoparticle formulation protected SDF-1α from rapid clearance in the lung and sustained its biological function in vivo. PMID:24059347

  11. Silver-doped calcium phosphate nanoparticles: synthesis, characterization, and toxic effects toward mammalian and prokaryotic cells.

    PubMed

    Peetsch, Alexander; Greulich, Christina; Braun, Dieter; Stroetges, Christian; Rehage, Heinz; Siebers, Bettina; Köller, Manfred; Epple, Matthias

    2013-02-01

    Spherical silver-doped calcium phosphate nanoparticles were synthesized in a co-precipitation route from calcium nitrate/silver nitrate and ammonium phosphate in a continuous process and colloidally stabilized by carboxymethyl cellulose. Nanoparticles with 0.39 wt% silver content and a diameter of about 50-60 nm were obtained. The toxic effects toward mammalian and prokaryotic cells were determined by viability tests and determination of the minimal inhibitory and minimal bactericidal concentrations (MIC and MBC). Three mammalian cells lines, i.e. human mesenchymal stem cells (hMSC) and blood peripheral mononuclear cells (PBMC, monocytes and T-lymphocytes), and two prokaryotic strains, i.e. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were used. Silver-doped calcium phosphate nanoparticles and silver acetate showed similar effect toward mammalian and prokaryotic cells with toxic silver concentrations in the range of 1-3 μg mL(-1).

  12. Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new paradigm in nanotoxicology.

    PubMed

    Guarnieri, Daniela; Sabella, Stefania; Muscetti, Ornella; Belli, Valentina; Malvindi, Maria Ada; Fusco, Sabato; De Luca, Elisa; Pompa, Pier Paolo; Netti, Paolo A

    2014-09-07

    The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions.

  13. Cardiovascular toxicity evaluation of silica nanoparticles in endothelial cells and zebrafish model.

    PubMed

    Duan, Junchao; Yu, Yongbo; Li, Yang; Yu, Yang; Sun, Zhiwei

    2013-07-01

    Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. However, most investigators focus on the evaluation of overall toxicity instead of a certain organism system. In this regard, the evaluation of cardiovascular effects of silica nanoparticles was preformed in vitro and in vivo. It's worth noting that silica nanoparticles induced cytotoxicity as well as oxidative stress and apoptosis. ROS and apoptosis were considered as major factor to endothelial cells dysfunction, involved in several molecular mechanisms of cardiovascular diseases. In vivo study, mortality, malformation, heart rate and whole-embryo cellular death were measured in zebrafish embryos. Results showed that silica nanoparticles induced pericardia toxicity and caused bradycardia. We also examined the expression of cardiovascular-related proteins in embryos by western blot analysis. Silica nanoparticles inhibited the expression of p-VEGFR2 and p-ERK1/2 as well as the downregulation of MEF2C and NKX2.5, revealed that silica nanoparticles could inhibit the angiogenesis and disturb the heart formation and development. In summary, our results suggest that exposure to silica nanoparticles is a possible risk factor to cardiovascular system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Neutral red retention time assay in determination of toxicity of nanoparticles.

    PubMed

    Hu, Wentao; Culloty, Sarah; Darmody, Grainne; Lynch, Sharon; Davenport, John; Ramirez-Garcia, Sonia; Dawson, Kenneth; Lynch, Iseult; Doyle, Hugh; Sheehan, David

    2015-10-01

    The neutral red retention time (NRRT) assay is useful for detecting decreased lysosomal membrane stability in haemocytes sampled from bivalves, a phenomenon often associated with exposure to environmental pollutants including nanomaterials. Bivalves are popular sentinel species in ecotoxicology and use of NRRT in study of species in the genus Mytilus is widespread in environmental monitoring. The NRRT assay has been used as an in vivo test for toxicity of carbon nanoparticles (Moore MN, Readman JAJ, Readman JW, Lowe DM, Frickers PE, Beesley A. 2009. Lysosomal cytotoxicity of carbon nanoparticles in cells of the molluscan immune system: An in vivo study. Nanotoxicology. 3 (1), 40-45). We here report application of this assay adapted to a microtitre plate format to a panel of metal and metal oxide nanoparticles (2 ppm). This showed that copper, chromium and cobalt nanoparticles are toxic by this criterion while gold and titanium nanoparticles are not. As the former three nanoparticles are often reported to be cytotoxic while the latter two are thought to be non-cytotoxic, these data support use of NRRT as a general in vitro assay in nanotoxicology.

  15. Lung toxicities of core–shell nanoparticles composed of carbon, cobalt, and silica

    PubMed Central

    Al Samri, Mohammed T; Silva, Rafael; Almarzooqi, Saeeda; Albawardi, Alia; Othman, Aws Rashad Diab; Al Hanjeri, Ruqayya SMS; Al Dawaar, Shaikha KM; Tariq, Saeed; Souid, Abdul-Kader; Asefa, Tewodros

    2013-01-01

    We present here comparative assessments of murine lung toxicity (biocompatibility) after in vitro and in vivo exposures to carbon (C–SiO2-etched), carbon–silica (C–SiO2), carbon–cobalt–silica (C–Co–SiO2), and carbon–cobalt oxide–silica (C–Co3O4–SiO2) nanoparticles. These nanoparticles have potential applications in clinical medicine and bioimaging, and thus their possible adverse events require thorough investigation. The primary aim of this work was to explore whether the nanoparticles are biocompatible with pneumatocyte bioenergetics (cellular respiration and adenosine triphosphate content). Other objectives included assessments of caspase activity, lung structure, and cellular organelles. Pneumatocyte bioenergetics of murine lung remained preserved after treatment with C–SiO2-etched or C–SiO2 nanoparticles. C–SiO2-etched nanoparticles, however, increased caspase activity and altered lung structure more than C–SiO2 did. Consistent with the known mitochondrial toxicity of cobalt, both C–Co–SiO2 and C–Co3O4–SiO2 impaired lung tissue bioenergetics. C–Co–SiO2, however, increased caspase activity and altered lung structure more than C–Co3O4–SiO2. The results indicate that silica shell is essential for biocompatibility. Furthermore, cobalt oxide is the preferred phase over the zerovalent Co(0) phase to impart biocompatibility to cobalt-based nanoparticles. PMID:23658487

  16. Interference sources in ATP bioluminescence assay of silica nanoparticle toxicity to activated sludge.

    PubMed

    Sibag, Mark; Kim, Seung Hwan; Kim, Choah; Kim, Hee Jun; Cho, Jinwoo

    2015-06-01

    ATP measurement provides an overview of the general state of microbial activity, and thus it has proven useful for the evaluation of nanoparticle toxicity in activated sludge. ATP bioluminescence assay, however, is susceptible to interference by the components of activated sludge other than biomass. This paper presents the interference identified specific to the use of this assay after activated sludge respiration inhibition test of silica nanoparticles (OECD 209). We observed a high degree of interference (90%) in the presence of 100 mg/L silica nanoparticles and a low level of ATP being measured (0.01 μM); and 30% interference by the synthetic medium regardless of silica nanoparticle concentration and ATP level in the samples. ATP measurement in activated sludge with different MLSS concentrations revealed interference of high biomass content. In conclusion, silica nanoparticles, synthetic medium and activated sludge samples themselves interfere with ATP bioluminescence; this will need to be considered in the evaluation of silica nanoparticle toxicity to activated sludge when this type of assay is used.

  17. Toxicity of citrate-coated silver nanoparticles differs according to method of suspension preparation.

    PubMed

    Park, June-Woo; Oh, Ji-Hyun; Kim, Woo-Keun; Lee, Sung-Kyu

    2014-07-01

    To evaluate substance toxicity, it is critical to maintain specific concentrations of test substances throughout the exposure period. During the last decade, the need to improve methods for nanoparticle (NP) suspension preparations has gained attention because many published results on NPs toxicity have been inconsistent. Here, we compared the toxicity of citrate-coated silver nanoparticles (AgNPs) suspended by two different methods (fractionated vs. colloidal) in freshwater organisms (daphnia and medaka). Analytical methods (ICP-OES, DLS and UV absorbance) were employed to characterize behavior of AgNPs in suspension. Results showed that fractionated (stirred and settled) solution was less toxic to daphnia (13.8 µg/L) than colloidal solution (6.1 µg/L), suggesting that method of preparation was a critical factor that affected toxicity. However, differences in toxicity caused by suspension methods were not observed in medaka. Results indicate that the method used to prepare suspensions of NPs can affect toxicity, and that differences can exist among test organisms.

  18. Toxicity of ZnO nanoparticles to Escherichia coli: mechanism and the influence of medium components.

    PubMed

    Li, Mei; Zhu, Lizhong; Lin, Daohui

    2011-03-01

    Water chemistry can be a major factor regulating the toxicity mechanism of ZnO nanoparticles (nano-ZnO) in water. The effect of five commonly used aqueous media with various chemical properties on the toxicity of nano-ZnO to Escherichia coli O111 (E. coli) was investigated, including ultrapure water, 0.85% NaCl, phosphate-buffered saline (PBS), minimal Davis (MD), and Luria-Bertani (LB). Combined results of physicochemical characterization and antibacterial tests of nano-ZnO in the five media suggest that the toxicity of nano-ZnO is mainly due to the free zinc ions and labile zinc complexes. The toxicity of nano-ZnO in the five media deceased as follows: ultrapure water > NaCl > MD > LB > PBS. The generation of precipitates (Zn(3)(PO(4))(2) in PBS) and zinc complexes (of zinc with citrate and amino acids in MD and LB, respectively) dramatically decreased the concentration of Zn(2+) ions, resulting in the lower toxicity in these media. Additionally, the isotonic and rich nutrient conditions improved the tolerance of E. coli to toxicants. Considering the dramatic difference of the toxicity of nano-ZnO in various aqueous media, the effect of water chemistry on the physicochemical properties of nanoparticles should be paid more attention in future nanotoxicity evaluations.

  19. Standardized toxicity testing may underestimate ecotoxicity: Environmentally relevant food rations increase the toxicity of silver nanoparticles to Daphnia.

    PubMed

    Stevenson, Louise M; Krattenmaker, Katherine E; Johnson, Erica; Bowers, Alexandra J; Adeleye, Adeyemi S; McCauley, Edward; Nisbet, Roger M

    2017-05-29

    Daphnia in the natural environment experience fluctuations in algal food supply, with periods when algal populations bloom and seasons when Daphnia have very little algal food. Standardized chronic toxicity tests, used for ecological risk assessment, dictate that Daphnia must be fed up to 400 times more food than they would experience in the natural environment (outside of algal blooms) for a toxicity test to be valid. This disconnect can lead to underestimating the toxicity of a contaminant. We followed the growth, reproduction, and survival of Daphnia exposed to 75 and 200 µg/L silver nanoparticles (AgNPs) at 4 food rations for up to 99 d and found that AgNP exposure at low, environmentally relevant food rations increased the toxicity of AgNPs. Exposure to AgNP at low food rations decreased the survival and/or reproduction of individuals, with potential consequences for Daphnia populations (based on calculated specific population growth rates). We also found tentative evidence that a sublethal concentration of AgNPs (75 µg/L) caused Daphnia to alter energy allocation away from reproduction and toward survival and growth. The present findings emphasize the need to consider resource availability, and not just exposure, in the environment when estimating the effect of a toxicant. Environ Toxicol Chem 2017;9999:1-11. © 2017 SETAC. © 2017 SETAC.

  20. Transport across the cell-membrane dictates nanoparticle fate and toxicity: a new paradigm in nanotoxicology

    NASA Astrophysics Data System (ADS)

    Guarnieri, Daniela; Sabella, Stefania; Muscetti, Ornella; Belli, Valentina; Malvindi, Maria Ada; Fusco, Sabato; de Luca, Elisa; Pompa, Pier Paolo; Netti, Paolo A.

    2014-08-01

    The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions.The toxicity of metallic nanoparticles (MNPs) has been fully ascertained, but the mechanisms underlying their cytotoxicity remain still largely unclear. Here we demonstrate that the cytotoxicity of MNPs is strictly reliant on the pathway of cellular internalization. In particular, if otherwise toxic gold, silver, and iron oxide NPs are forced through the cell membrane bypassing any form of active mechanism (e.g., endocytosis), no significant cytotoxic effect is registered. Pneumatically driven NPs across the cell membrane show a different distribution within the cytosol compared to NPs entering the cell by active endocytosis. Specifically, they exhibit free random Brownian motions within the cytosol and do not accumulate in lysosomes. Results suggest that intracellular accumulation of metallic nanoparticles into endo-lysosomal compartments is the leading cause of nanotoxicity, due to consequent nanoparticle degradation and in situ release of metal ions. Electronic supplementary information (ESI) available. See DOI

  1. Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress

    PubMed Central

    Naqvi, Saba; Samim, Mohammad; Abdin, MZ; Ahmed, Farhan Jalees; Maitra, AN; Prashant, CK; Dinda, Amit K

    2010-01-01

    Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774) cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15–30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in lower concentrations (25–200 μg/mL) and up to three hours of exposure, whereas at higher concentrations (300–500 μg/mL) and prolonged (six hours) exposure viability reduced to 55%–65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H2DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS) indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury induced by nanoparticles studied using the lactate dehydrogenase assay, showed both concentration- and time-dependent damage. Thus, this study concluded that use of a low optimum concentration of superparamagnetic iron oxide nanoparticles is important for avoidance of oxidative stress-induced cell injury and death. PMID:21187917

  2. Perturbation of cellular mechanistic system by silver nanoparticle toxicity: Cytotoxic, genotoxic and epigenetic potentials.

    PubMed

    Dubey, Poornima; Matai, Ishita; Kumar, S Uday; Sachdev, Abhay; Bhushan, Bharat; Gopinath, P

    2015-07-01

    Currently the applications of silver nanoparticles (Ag NPs) are gaining overwhelming response due to the advancement of nanotechnology. However, only limited information is available with regard to their toxicity mechanism in different species. It is very essential to understand the complete molecular mechanism to explore the functional and long term applications of Ag NPs. Ag NPs could be toxic at cellular, subcellular, biomolecular, and epigenetic levels. Toxicity effects induced by Ag NPs have been evaluated using numerous in vitro and in vivo models, but still there are contradictions in interpretations due to disparity in methodology, test endpoints and several other model parameters which needs to be considered. Thus, this review article focuses on the progressive elucidation of molecular mechanism of toxicity induced by Ag NPs in various in vitro and in vivo models. Apart from these, this review also highlights the various ignored factors which are to be considered during toxicity studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Assessment of the lung toxicity of copper oxide nanoparticles: current status.

    PubMed

    Ahamed, Maqusood; Akhtar, Mohd Javed; Alhadlaq, Hisham A; Alrokayan, Salman A

    2015-01-01

    Copper oxide nanoparticles (CuO NPs) are being used in several industrial and commercial products. Inhalation is one of the most significant routes of metal oxide NP exposure. Hence, the toxicity of CuO NPs in lung tissues is of great concern. In vitro studies have indicated that CuO NPs induce cytotoxicity, oxidative stress and genetic toxicity in cultivated human lung cells. Leaching of Cu ions, reactive oxygen species generation and autophagy appear to be the underlying mechanisms of Cu NP toxicity in lung cells. In vivo studies on the lung toxicity of CuO NPs are largely lacking. Some studies have shown that intratracheal instillation of CuO NPs induced oxidative stress, inflammation and neoplastic lesions in rats. This review critically assessed the current findings of the toxicity of CuO NPs in the lung.

  4. Irradiation with visible light enhances the antibacterial toxicity of silver nanoparticles produced by laser ablation

    NASA Astrophysics Data System (ADS)

    Ratti, Matthew; Naddeo, J. J.; Tan, Yuying; Griepenburg, Julianne C.; Tomko, John; Trout, Cory; O'Malley, Sean M.; Bubb, Daniel M.; Klein, Eric A.

    2016-04-01

    The rise of antibiotic-resistant bacteria is a rapidly growing global health concern. According to the Center for Disease Control, approximately 2 million illnesses and 23,000 deaths per year occur in the USA due to antibiotic resistance. In recent years, there has been a surge in the use of metal nanoparticles as coatings for orthopedic implants, wound dressings, and food packaging, due to their antimicrobial properties. In this report, we demonstrate that the antibacterial efficacy of silver nanoparticles (AgNPs) is enhanced with exposure to light from the visible spectrum. We find that the increased toxicity is due to augmented silver ion release and bacterial uptake. Interestingly, silver ion toxicity does not appear to depend on the formation of reactive oxygen species. Our findings provide a novel paradigm for using light to regulate the toxicity of AgNPs which may have a significant impact in the development of new antimicrobial therapeutics.

  5. Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

    PubMed Central

    Alkilany, Alaaldin M.

    2010-01-01

    Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems. PMID:21170131

  6. Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

    NASA Astrophysics Data System (ADS)

    Alkilany, Alaaldin M.; Murphy, Catherine J.

    2010-09-01

    Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems.

  7. Glucoxylan-mediated green synthesis of gold and silver nanoparticles and their phyto-toxicity study.

    PubMed

    Iram, Fozia; Iqbal, Mohammad S; Athar, Muhammad M; Saeed, Muhammad Z; Yasmeen, Abida; Ahmad, Riaz

    2014-04-15

    A green synthesis of gold and silver nanoparticles having exceptional high stability is reported. The synthesis involves the use of glucoxylans isolated from seeds of Mimosa pudica and excludes the use of conventional reducing and capping agents. The average particle sizes were 40 and 6 nm for gold and silver, respectively. The size of gold particles obtained in this work is suitable for drug delivery as they are non-cytotoxic. In phyto-toxicity tests the gold and silver nanoparticles did not show any significant effect on germination of radish seeds, whereas in radish seedling root growth assay the two particles behaved differently. The silver nanoparticles exhibited a concentration-dependent stimulatory effect on root length, whereas the gold nanoparticles had no significant effect in this test. The likely mechanism of these effects is discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. The impact of aminated surface ligands and silica shells on the stability, uptake, and toxicity of engineered silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Bonventre, Josephine A.; Pryor, Joseph B.; Harper, Bryan J.; Harper, Stacey L.

    2014-12-01

    Inherent nanomaterial characteristics, composition, surface chemistry, and primary particle size, are known to impact particle stability, uptake, and toxicity. Nanocomposites challenge our ability to predict nanoparticle reactivity in biological systems if they are composed of materials with contrasting relative toxicities. We hypothesized that toxicity would be dominated by the nanoparticle surface (shell vs core), and that modulating the surface ligands would have a direct impact on uptake. We exposed developing zebrafish ( Danio rerio) to a series of 70 nm amine-terminated silver nanoparticles with silica shells (AgSi NPs) to investigate the relative influence of surface amination, composition, and size on toxicity. Like-sized aminated AgSi and Si NPs were more toxic than paired hydroxyl-terminated nanoparticles; however, both AgSi NPs were more toxic than the Si NPs, indicating a significant contribution of the silver core to the toxicity. Incremental increases in surface amination did not linearly increase uptake and toxicity, but did have a marked impact on dispersion stability. Mass-based exposure metrics initially supported the hypothesis that smaller nanoparticles (20 nm) would be more toxic than larger particles (70 nm). However, surface area-based metrics revealed that toxicity was independent of size. Our studies suggest that nanoparticle surfaces play a critical role in the uptake and toxicity of AgSi NPs, while the impact of size may be a function of the exposure metric used. Overall, uptake and toxicity can be dramatically altered by small changes in surface functionalization or exposure media. Only after understanding the magnitude of these changes, can we begin to understand the biologically available dose following nanoparticle exposure.

  9. Brain targeting and toxicity study of odorranalectin-conjugated nanoparticles following intranasal administration.

    PubMed

    Wen, Ziyi; Yan, Zhiqiang; He, Rui; Pang, Zhiqing; Guo, Liangran; Qian, Yong; Jiang, Xinguo; Fang, Liang

    2011-11-01

    In order to improve brain uptake of nanoparticles following nasal administration, odorranalectin (OL), the smallest lectin with much less immunogenicity than other members of lectin family, was conjugated to the surface of poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NP) in this study. The bioactivity of OL conjugated to the nanoparticles was verified by haemagglutination tests.Tissue distribution of OL-modified and unmodified nanoparticles (OL-NP and NP) was evaluated following intranasal (i.n.) administration by in vivo fluorescence imaging technique using DiR as a tracer, comparing with that of unmodified nanoparticles after intravenous (i.v.) injection. Besides, the nasal toxicity of OL-NP was evaluated on Calu-3 cell lines, toad palate and rat nasal mucosa.The results of TEM examination and dynamic light scattering showed a generally spherical shape of OL-NP with an average volume-based diameter around 90 nm. The haemagglutination test proved that OL retained its haemagglutination activity when conjugated to nanoparticles. The brain targeting indexes of NP and OL-NP following i.n. administration and NP following i.v. injection were 5.8, 11.6 and 0.08, respectively.Thus,i.n. administration demonstrated much better brain targeting efficiency than i.v. injection, and OL modification facilitated the nose-to-brain delivery of nanoparticles.Moreover, the toxicity assessment suggested good safety of OL-NP both in vitro and in vivo. In summary, odorranalectin-conjugated nanoparticle could be potentially used as a nose-to-brain drug delivery carrier for the treatment of CNS diseases.

  10. Poor Baseline Pulmonary Function May Not Increase the Risk of Radiation-Induced Lung Toxicity

    SciTech Connect

    Wang, Jingbo; Cao, Jianzhong; Yuan, Shuanghu; Arenberg, Douglas; Stanton, Paul; Tatro, Daniel; Ten Haken, Randall K.; Kong, Feng-Ming

    2013-03-01

    Purpose: Poor pulmonary function (PF) is often considered a contraindication to definitive radiation therapy for lung cancer. This study investigated whether baseline PF was associated with radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) receiving conformal radiation therapy (CRT). Methods and Materials: NSCLC patients treated with CRT and tested for PF at baseline were eligible. Baseline predicted values of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and diffusion capacity of lung for carbon monoxide (DLCO) were analyzed. Additional factors included age, gender, smoking status, Karnofsky performance status, coexisting chronic obstructive pulmonary disease (COPD), tumor location, histology, concurrent chemotherapy, radiation dose, and mean lung dose (MLD) were evaluated for RILT. The primary endpoint was symptomatic RILT (SRILT), including grade ≥2 radiation pneumonitis and fibrosis. Results: There was a total of 260 patients, and SRILT occurred in 58 (22.3%) of them. Mean FEV1 values for SRILT and non-SRILT patients were 71.7% and 65.9% (P=.077). Under univariate analysis, risk of SRILT increased with MLD (P=.008), the absence of COPD (P=.047), and FEV1 (P=.077). Age (65 split) and MLD were significantly associated with SRILT in multivariate analysis. The addition of FEV1 and age with the MLD-based model slightly improved the predictability of SRILT (area under curve from 0.63-0.70, P=.088). Conclusions: Poor baseline PF does not increase the risk of SRILT, and combining FEV1, age, and MLD may improve the predictive ability.

  11. Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats.

    PubMed

    Ji, Jun Ho; Jung, Jae Hee; Kim, Sang Soo; Yoon, Jin-Uk; Park, Jung Duck; Choi, Byung Sun; Chung, Yong Hyun; Kwon, Il Hoon; Jeong, Jayoung; Han, Beom Seok; Shin, Jae Hyeg; Sung, Jae Hyuck; Song, Kyung Seuk; Yu, Il Je

    2007-08-01

    The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, and home products. Thus, the exposed population continues to increase as the applications expand. Although previous studies on silver dust, fumes, and silver compounds have revealed some insights, little is yet known about the toxicity of nano-sized silver particles, where the size and surface area are recognized as important determinants for toxicity. Thus, the inhalation toxicity of silver nanoparticles is of particular concern to ensure the health of workers and consumers. However, the dispersion of inhalable ambient nano-sized particles has been an obstacle in evaluating the effect of the inhalation of nano-sized particles on the respiratory system. Accordingly, the present study used a device that generates silver nanoparticles by evaporation/condensation using a small ceramic heater. As such, the generator was able to distribute the desired concentrations of silver nanoparticles to chambers containing experimental animals. The concentrations and distribution of the nanoparticles with respect to size were also measured directly using a differential mobility analyzer and ultrafine condensation particle counter. Therefore, the inhalation toxicity of silver nanoparticles was tested over a period of 28 days. Eight-week-old rats, weighing about 283 g for the males and 192 g for the females, were divided into 4 groups (10 rats in each group): a fresh-air control, a low-dose group (1.73 x 10(4)/cm3), a middle-dose group (1.27 x 10(5)/cm3), and a high-dose group (1.32 x 10(6) particles/cm3, 61 microg/m3). The animals were exposed to the silver nanoparticles for 6 h/day, 5 days/wk, for a total of 4 wk. The male and female rats did not show any significant changes in body weight relative to the concentration of silver nanoparticles during the 28-day experiment. Plus, there were no significant changes in the hematology and blood biochemical values in either

  12. Enhanced pulmonary delivery of fluticasone propionate in rodents by mucus-penetrating nanoparticles.

    PubMed

    Popov, Alexey; Schopf, Lisa; Bourassa, James; Chen, Hongming

    2016-04-11

    Most attempts to achieve sustained drug delivery to pulmonary tissues using nanoparticles have focused on mucoadhesive particles (MAP). However, MAP become trapped in the luminal mucus layer and, as a result, are largely eliminated from the respiratory tract by mucociliary escalator and expiratory clearance, which undermines their sustained release potential. Recent studies have shown that mucus-penetrating particles (MPP) engineered to diffuse through mucus can avoid rapid mucociliary clearance in vivo and persist in the lung longer. Nonetheless, it has not been confirmed that MPP encapsulating small molecules can sustain drug release in the lung longer than MAP of similar size and core composition. As a proof of concept, we encapsulated fluticasone propionate (FP) into poly(lactide)-based MPP and MAP (both ∼ 200 nm diameter, ∼ 30-35% drug loading) and evaluated their pulmonary residence by measuring FP levels in mouse lungs over 24h following intratracheal instillation. Furthermore, we evaluated the duration of action of FP MPP in a rat lung inflammation model compared to that of a non-encapsulated FP control. In rodents, pulmonary delivery of FP formulated as MPP provided a 60% higher local exposure compared to MAP and extended the single dose efficacy by at least 16 h compared to non-encapsulated FP. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The potentiation effect makes the difference: non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro.

    PubMed

    Li, Lingxiangyu; Fernández-Cruz, María Luisa; Connolly, Mona; Conde, Estefanía; Fernández, Marta; Schuster, Michael; Navas, José María

    2015-02-01

    Here we examined whether the addition of a non-toxic concentration (6.25 μg/mL) of zinc oxide nanoparticles (ZnONPs: 19, 35 and 57 nm, respectively) modulates the cytotoxicity of copper nanoparticles (CuNPs, 63 nm in size) in the human hepatoma cell line HepG2. The cytotoxic effect of CuNPs on HepG2 cells was markedly enhanced by the ZnONPs, the largest ZnONPs causing the highest increase in toxicity. However, CuNPs cytotoxicity was not affected by co-incubation with medium containing only zinc ions, indicating the increase in toxicity might be attributed to the particle form of ZnONPs. Transmission electron microscopy (TEM) revealed the presence of CuNPs and ZnONPs inside the cells co-exposed to both types of NP and outflow of cytoplasm through the damaged cell membrane. Inductively coupled plasma mass spectrometry (ICP-MS) determined an increase in the concentration of zinc and a decrease in that of copper in co-exposed cells. On the basis of these results, we propose that accumulation of large numbers of ZnONPs in the cells alters cellular membranes and the cytotoxicity of CuNPs is increased.

  14. Citrate coated silver nanoparticles change heavy metal toxicities and bioaccumulation of Daphnia magna.

    PubMed

    Kim, Injeong; Lee, Byung-Tae; Kim, Hyun-A; Kim, Kyoung-Woong; Kim, Sang Don; Hwang, Yu-Sik

    2016-01-01

    Citrate-coated AgNPs (c-AgNPs) have negatively charged surfaces and their surface interactions with heavy metals can affect metal toxicity in aquatic environments. This study used Daphnia magna to compare the acute toxicities and bioaccumulation of As(V), Cd, and Cu when they interact with c-AgNPs. The 24-h acute toxicities of As(V) and Cu were not affected by the addition of c-AgNPs, while bioaccumulation significantly decreased in the presence of c-AgNPs. In contrast, both the 24-h acute toxicity and bioaccumulation of Cd increased in the presence of c-AgNPs. These toxicity and bioaccumulation trends can be attributed to the interactions between the AgNP surface and the heavy metals. As(V) and c-AgNPs compete by negative charge, decreasing As(V) toxicity. Copper adheres readily to c-AgNP citrate, decreasing Cu bioavailability, and thus reducing Cu toxicity and bioaccumulation. Citrate complexes with divalent cations such as Ca and Mg reduce the competition between divalent cations and Cd on biotic ligand, increasing toxicity and bioaccumulation of Cd. This study shows that surface properties determine the effect of c-AgNPs on heavy metal toxicities and bioaccumulations; hence, further studies on the effect of nanoparticle by it surface properties are warranted.

  15. Toxicity of iron oxide nanoparticles to grass litter decomposition in a sandy soil

    PubMed Central

    Rashid, Muhammad Imtiaz; Shahzad, Tanvir; Shahid, Muhammad; Imran, Muhammad; Dhavamani, Jeyakumar; Ismail, Iqbal M. I.; Basahi, Jalal M.; Almeelbi, Talal

    2017-01-01

    We examined time-dependent effect of iron oxide nanoparticles (IONPs) at a rate of 2000 mg kg−1 soil on Cynodon dactylon litter (3 g kg−1) decomposition in an arid sandy soil. Overall, heterotrophic cultivable bacterial and fungal colonies, and microbial biomass carbon were significantly decreased in litter-amended soil by the application of nanoparticles after 90 and 180 days of incubation. Time dependent effect of nanoparticles was significant for microbial biomass in litter-amended soil where nanoparticles decreased this variable from 27% after 90 days to 49% after 180 days. IONPs decreased CO2 emission by 28 and 30% from litter-amended soil after 90 and 180 days, respectively. These observations indicated that time-dependent effect was not significant on grass-litter carbon mineralization efficiency. Alternatively, nanoparticles application significantly reduced mineral nitrogen content in litter-amended soil in both time intervals. Therefore, nitrogen mineralization efficiency was decreased to 60% after 180 days compared to that after 90 days in nanoparticles grass-litter amended soil. These effects can be explained by the presence of labile Fe in microbial biomass after 180 days in nanoparticles amendment. Hence, our results suggest that toxicity of IONPs to soil functioning should consider before recommending their use in agro-ecosystems. PMID:28155886

  16. Toxicity of iron oxide nanoparticles to grass litter decomposition in a sandy soil

    NASA Astrophysics Data System (ADS)

    Rashid, Muhammad Imtiaz; Shahzad, Tanvir; Shahid, Muhammad; Imran, Muhammad; Dhavamani, Jeyakumar; Ismail, Iqbal M. I.; Basahi, Jalal M.; Almeelbi, Talal

    2017-02-01

    We examined time-dependent effect of iron oxide nanoparticles (IONPs) at a rate of 2000 mg kg‑1 soil on Cynodon dactylon litter (3 g kg‑1) decomposition in an arid sandy soil. Overall, heterotrophic cultivable bacterial and fungal colonies, and microbial biomass carbon were significantly decreased in litter-amended soil by the application of nanoparticles after 90 and 180 days of incubation. Time dependent effect of nanoparticles was significant for microbial biomass in litter-amended soil where nanoparticles decreased this variable from 27% after 90 days to 49% after 180 days. IONPs decreased CO2 emission by 28 and 30% from litter-amended soil after 90 and 180 days, respectively. These observations indicated that time-dependent effect was not significant on grass-litter carbon mineralization efficiency. Alternatively, nanoparticles application significantly reduced mineral nitrogen content in litter-amended soil in both time intervals. Therefore, nitrogen mineralization efficiency was decreased to 60% after 180 days compared to that after 90 days in nanoparticles grass-litter amended soil. These effects can be explained by the presence of labile Fe in microbial biomass after 180 days in nanoparticles amendment. Hence, our results suggest that toxicity of IONPs to soil functioning should consider before recommending their use in agro-ecosystems.

  17. Toxicity of iron oxide nanoparticles to grass litter decomposition in a sandy soil.

    PubMed

    Rashid, Muhammad Imtiaz; Shahzad, Tanvir; Shahid, Muhammad; Imran, Muhammad; Dhavamani, Jeyakumar; Ismail, Iqbal M I; Basahi, Jalal M; Almeelbi, Talal

    2017-02-03

    We examined time-dependent effect of iron oxide nanoparticles (IONPs) at a rate of 2000 mg kg(-1) soil on Cynodon dactylon litter (3 g kg(-1)) decomposition in an arid sandy soil. Overall, heterotrophic cultivable bacterial and fungal colonies, and microbial biomass carbon were significantly decreased in litter-amended soil by the application of nanoparticles after 90 and 180 days of incubation. Time dependent effect of nanoparticles was significant for microbial biomass in litter-amended soil where nanoparticles decreased this variable from 27% after 90 days to 49% after 180 days. IONPs decreased CO2 emission by 28 and 30% from litter-amended soil after 90 and 180 days, respectively. These observations indicated that time-dependent effect was not significant on grass-litter carbon mineralization efficiency. Alternatively, nanoparticles application significantly reduced mineral nitrogen content in litter-amended soil in both time intervals. Therefore, nitrogen mineralization efficiency was decreased to 60% after 180 days compared to that after 90 days in nanoparticles grass-litter amended soil. These effects can be explained by the presence of labile Fe in microbial biomass after 180 days in nanoparticles amendment. Hence, our results suggest that toxicity of IONPs to soil functioning should consider before recommending their use in agro-ecosystems.

  18. Natural inorganic nanoparticles--formation, fate, and toxicity in the environment.

    PubMed

    Sharma, Virender K; Filip, Jan; Zboril, Radek; Varma, Rajender S

    2015-12-07

    The synthesis, stability, and toxicity of engineered metal nanoparticles (ENPs) have been extensively studied during the past two decades. In contrast, research on the formation, fate, and ecological effects of naturally-occurring nanoparticles (NNPs) has become a focus of attention only recently. The natural existence of metal nanoparticles and their oxides/sulfides in waters, wastewaters, ore deposits, mining regions, and hydrothermal vents, as exemplified by the formation of nanoparticles containing silver and gold (AgNPs and AuNPs), Fe, Mn, pyrite (FeS2), Ag2S, CuS, CdS, and ZnS, is dictated largely by environmental conditions (temperature, pH, oxic/anoxic, light, and concentration and characteristics of natural organic matter (NOM)). Examples include the formation of nanoparticles containing pyrite, Cu and Zn-containing pyrite, and iron in hydrothermal vent black smoker emissions. Metal sulfide nanoparticles can be formed directly from their precursor ions or indirectly by sulfide ion-assisted transformation of the corresponding metal oxides under anaerobic conditions. This tutorial focuses on the formation mechanisms, fate, and toxicity of natural metal nanoparticles. Natural waters containing Ag(I) and Au(III) ions in the presence of NOM generate AgNPs and AuNPs under thermal, non-thermal, and photochemical conditions. These processes are significantly accelerated by existing redox species of iron (Fe(II)/Fe(III)). NOM, metal-NOM complexes, and reactive oxygen species (ROS) such as O2˙(-), ˙OH, and H2O2 are largely responsible for the natural occurrence of nanoparticles. AgNPs and AuNPs emanating from Ag(I)/Au(III)-NOM reactions are stable for several months, thus indicating their potential to be transported over long distances from their point of origin. However, endogenous cations present in nat