Characterization of exposure to silver nanoparticles in a manufacturing facility

Science.gov (United States)

Park, Junsu; Kwak, Byoung Kyu; Bae, Eunjoo; Lee, Jeongjin; Kim, Younghun; Choi, Kyunghee; Yi, Jongheop

2009-10-01

An assessment of the extent of exposure to nanomaterials in the workplace will be helpful in improving the occupational safety of workers. It is essential that the exposure data in the workplace are concerned with risk management to evaluate and reduce worker exposure. In a manufacturing facility dealing with nanomaterials, some exposure data for gas-phase reactions are available, but much less information is available regarding liquid-phase reactions. Although the potential for inhaling nanomaterials in a liquid-phase process is less than that for gas-phase, the risks of exposure during wet-chemistry processes are not negligible. In this study, we monitored and analyzed the exposure characteristics of silver nanoparticles during a liquid-phase process in a commercial production facility. Based on the measured exposure data, the source of Ag nanoparticles emitted during the production processes was indentified and a mechanism for the growth of Ag nanoparticle released is proposed. The data reported in this study could be used to establish occupational safety guidelines in the nanotechnology workplace, especially in a liquid-phase production facility.

Safety assessment of chronic oral exposure to iron oxide nanoparticles

International Nuclear Information System (INIS)

Chamorro, Susana; Vaquero, María Pilar; Brenes, Agustín; Gutiérrez, Lucía; Salas, Gorka; Luengo, Yurena; Verdoy, Dolores; José Teran, Francisco

2015-01-01

Iron oxide nanoparticles with engineered physical and biochemical properties are finding a rapidly increasing number of biomedical applications. However, a wide variety of safety concerns, especially those related to oral exposure, still need to be addressed for iron oxide nanoparticles in order to reach clinical practice. Here, we report on the effects of chronic oral exposure to low doses of γ-Fe 2 O 3 nanoparticles in growing chickens. Animal observation, weight, and diet intake reveal no adverse signs, symptoms, or mortality. No nanoparticle accumulation was observed in liver, spleen, and duodenum, with feces as the main excretion route. Liver iron level and duodenal villi morphology reflect the bioavailability of the iron released from the partial transformation of γ-Fe 2 O 3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe 2 O 3 nanoparticles indicate the enhancement of a ferric over ferrous pathway supporting the role of mucins. Our findings reveal that oral administration of iron oxide nanoparticles is a safe route for drug delivery at low nanoparticle doses. (paper)

Exposure of juvenile turbot (Scophthalmus maximus) to silver nanoparticles and 17α-ethinylestradiol mixtures

DEFF Research Database (Denmark)

Farkas, Julia; Salaberria, Iurgi; Styrishave, Bjarne

2017-01-01

Combined exposure to engineered nanoparticles (ENPs) and anthropogenic contaminants can lead to changes in bioavailability, uptake and thus effects of both groups of contaminants. In this study we investigated effects of single and combined exposures of silver (Ag) nanoparticles (AgNPs) and the s......Combined exposure to engineered nanoparticles (ENPs) and anthropogenic contaminants can lead to changes in bioavailability, uptake and thus effects of both groups of contaminants. In this study we investigated effects of single and combined exposures of silver (Ag) nanoparticles (Ag...

Video exposure monitoring as part of a strategy to assess exposure to nanoparticles

NARCIS (Netherlands)

Beurskens-Comuth, P.A.W.V.; Verbist, K.; Brouwer, D.

2011-01-01

Objectives: There is a growing awareness of the potential risks for human health of exposure to ultrafine particles or nanoparticles. In that context, workplace air measurements become important, and various strategies have been developed to monitor exposure. In addition, observations and

Trophic transfer potential of aluminium oxide nanoparticles using representative primary producer (Chlorella ellipsoides) and a primary consumer (Ceriodaphnia dubia)

International Nuclear Information System (INIS)

Pakrashi, Sunandan; Dalai, Swayamprava; Chandrasekaran, Natarajan; Mukherjee, Amitava

2014-01-01

Highlights: • Trophic transfer of alumina nanoparticles using Chlorella ellipsoides and Ceriodaphnia dubia. • Subtle alterations in the feeding behaviour of the daphnids. • Disruption the energy flow through the food chain. • Transmission electron microscopy validated the disrupted feeding behaviour. - Abstract: The transfer of nanoparticles through the food chain can lead to bioaccumulation and biomagnification resulting in a long term negative impact on the ecosystem functions. The primary objective of this study was evaluation of aluminium oxide nanoparticles transfer from primary producers to primary consumers. A simple set up consisting of a primary producer (Chlorella ellipsoides) and a primary consumer (Ceriodaphnia dubia) was used. Here, C. ellipsoides were exposed to the varying concentrations of the nanoparticles ranging from 20 to 120 μg/mL (196 to 1176 μM) for 48 h and the infested algal cells were used as the feed to C. dubia. The bioaccumulation of the nanoparticles into the daphnids was noted and the biomagnification factors were computed. The exposure was noted to cause subtle alterations in the feeding behaviour of the daphnids. This might have long term consequences in the energy flow through the food chain. The reproductive behaviour of the daphnids remained unaffected upon exposure to nanoparticle infested algal feed. Distinct observations at ultra-structural scale using transmission electron microscopy provided visual evidences for the disrupted feeding behaviour upon exposure to nanoparticle treated algae. Internalization of nanoparticle like inclusion bodies in the intracellular space of algae was also detected. The findings were further substantiated by a detailed analysis of hydrodynamic stability, bioavailability and dissolution of ions from the nanoparticles over the exposure period. Altogether, the study brings out the first of its kind of observation of trophic transfer potential/behaviour of aluminium oxide nanoparticles and

Trophic transfer potential of aluminium oxide nanoparticles using representative primary producer (Chlorella ellipsoides) and a primary consumer (Ceriodaphnia dubia)

Energy Technology Data Exchange (ETDEWEB)

Pakrashi, Sunandan; Dalai, Swayamprava; Chandrasekaran, Natarajan; Mukherjee, Amitava, E-mail: amit.mookerjea@gmail.com

2014-07-01

Highlights: • Trophic transfer of alumina nanoparticles using Chlorella ellipsoides and Ceriodaphnia dubia. • Subtle alterations in the feeding behaviour of the daphnids. • Disruption the energy flow through the food chain. • Transmission electron microscopy validated the disrupted feeding behaviour. - Abstract: The transfer of nanoparticles through the food chain can lead to bioaccumulation and biomagnification resulting in a long term negative impact on the ecosystem functions. The primary objective of this study was evaluation of aluminium oxide nanoparticles transfer from primary producers to primary consumers. A simple set up consisting of a primary producer (Chlorella ellipsoides) and a primary consumer (Ceriodaphnia dubia) was used. Here, C. ellipsoides were exposed to the varying concentrations of the nanoparticles ranging from 20 to 120 μg/mL (196 to 1176 μM) for 48 h and the infested algal cells were used as the feed to C. dubia. The bioaccumulation of the nanoparticles into the daphnids was noted and the biomagnification factors were computed. The exposure was noted to cause subtle alterations in the feeding behaviour of the daphnids. This might have long term consequences in the energy flow through the food chain. The reproductive behaviour of the daphnids remained unaffected upon exposure to nanoparticle infested algal feed. Distinct observations at ultra-structural scale using transmission electron microscopy provided visual evidences for the disrupted feeding behaviour upon exposure to nanoparticle treated algae. Internalization of nanoparticle like inclusion bodies in the intracellular space of algae was also detected. The findings were further substantiated by a detailed analysis of hydrodynamic stability, bioavailability and dissolution of ions from the nanoparticles over the exposure period. Altogether, the study brings out the first of its kind of observation of trophic transfer potential/behaviour of aluminium oxide nanoparticles and

Endocrine disrupting compounds exposure and testis development in mammals

Science.gov (United States)

Egbowona, Biola F.; Mustapha, Olajide A.

2011-01-01

In the last few decades, there is substantial evidence that male reproductive function is deteriorating in humans and wildlife and this is associated with unintentional exposure to widely used synthetic chemicals. Subsequently, much has been done to show that certain chemicals in the environment adversely interfere with the developing fetal gonads of the laboratory animals. Some in vitro studies have demonstrated treatment-induced reproductive problems in offspring exposed to endocrine disrupting compounds (EDC) which are similar to those observed in wildlife and human population. Few EDC studies have demonstrated that there are certain periods of gestation when the developing fetus is highly sensitive and at risk of small endocrine changes. Similar observations have been made in the sewage sludge model, however, while animal studies have been insightful in providing valuable information about the range of effects that can be attributed to in utero exposure to EDCs, varying levels of maternal doses administered in different studies exaggerated extrapolation of these results to human. Thus the EDC concentration representative of fetal exposure levels is uncertain because of the complexities of its nature. So far, the level of fetal exposure can only be roughly estimated. There is substantial evidence from animal data to prove that EDCs can adversely affect reproductive development and function in male and more has accumulated on the mechanisms by which they exert their effects. This paper therefore, reviews previous studies to highlight the extent to which testis development can be disrupted during fetal life. PMID:29255381

Early Life Exposure to Endocrine Disrupting Chemicals and Childhood Obesity and Neurodevelopment

Science.gov (United States)

Braun, Joseph M.

2017-01-01

Endocrine disrupting chemicals (EDCs) may increase the risk of childhood diseases by disrupting hormonally mediated processes critical for growth and development during gestation, infancy, or childhood. The fetus, infant, and child may have enhanced sensitivity to environmental stressors like EDCs due to rapid development and greater exposure to some EDCs that results from their developmentally appropriate behavior, anatomy, and physiology. This review summarizes epidemiological studies examining the relations of early-life exposure to bisphenol A (BPA), phthalates, triclosan, and perfluoroalkyl substance (PFAS) with childhood neurobehavioral disorders and obesity. The available epidemiological evidence suggests that prenatal exposure to several of these ubiquitous EDCs is associated with adverse neurobehavior (BPA and phthalates) and excess adiposity or increased risk of obesity/overweight (PFAS). Quantifying the effects of EDC mixtures, improving EDC exposure assessment, reducing bias from confounding, identifying periods of heightened vulnerability, and elucidating the presence and nature of sexually dimorphic EDC effects would result in stronger inferences from epidemiological studies. Ultimately, better estimates of the causal effects of EDC exposures on child health could help identify susceptible sub-populations and lead to public health interventions to reduce these exposures. PMID:27857130

Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats.

Science.gov (United States)

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

2014-11-17

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.

Workplace exposure to nanoparticles from gas metal arc welding process

International Nuclear Information System (INIS)

Zhang, Meibian; Jian, Le; Bin, Pingfan; Xing, Mingluan; Lou, Jianlin; Cong, Liming; Zou, Hua

2013-01-01

Workplace exposure to nanoparticles from gas metal arc welding (GMAW) process in an automobile manufacturing factory was investigated using a combination of multiple metrics and a comparison with background particles. The number concentration (NC), lung-deposited surface area concentration (SAC), estimated SAC and mass concentration (MC) of nanoparticles produced from the GMAW process were significantly higher than those of background particles before welding (P < 0.01). A bimodal size distribution by mass for welding particles with two peak values (i.e., 10,000–18,000 and 560–320 nm) and a unimodal size distribution by number with 190.7-nm mode size or 154.9-nm geometric size were observed. Nanoparticles by number comprised 60.7 % of particles, whereas nanoparticles by mass only accounted for 18.2 % of the total particles. The morphology of welding particles was dominated by the formation of chain-like agglomerates of primary particles. The metal composition of these welding particles consisted primarily of Fe, Mn, and Zn. The size distribution, morphology, and elemental compositions of welding particles were significantly different from background particles. Working activities, sampling distances from the source, air velocity, engineering control measures, and background particles in working places had significant influences on concentrations of airborne nanoparticle. In addition, SAC showed a high correlation with NC and a relatively low correlation with MC. These findings indicate that the GMAW process is able to generate significant levels of nanoparticles. It is recommended that a combination of multiple metrics is measured as part of a well-designed sampling strategy for airborne nanoparticles. Key exposure factors, such as particle agglomeration/aggregation, background particles, working activities, temporal and spatial distributions of the particles, air velocity, engineering control measures, should be investigated when measuring workplace

Workplace exposure to nanoparticles from gas metal arc welding process

Energy Technology Data Exchange (ETDEWEB)

Zhang, Meibian [Zhejiang Provincial Center for Disease Control and Prevention (China); Jian, Le [Curtin University of Technology, School of Public Health, Curtin Health Innovation Research Institute (Australia); Bin, Pingfan [Wujin District Center for Disease Control and Prevention (China); Xing, Mingluan [Zhejiang Provincial Center for Disease Control and Prevention (China); Lou, Jianlin [Zhejiang Academy of Medical Sciences (China); Cong, Liming; Zou, Hua, E-mail: hzou@cdc.zj.cn [Zhejiang Provincial Center for Disease Control and Prevention (China)

2013-11-15

Workplace exposure to nanoparticles from gas metal arc welding (GMAW) process in an automobile manufacturing factory was investigated using a combination of multiple metrics and a comparison with background particles. The number concentration (NC), lung-deposited surface area concentration (SAC), estimated SAC and mass concentration (MC) of nanoparticles produced from the GMAW process were significantly higher than those of background particles before welding (P < 0.01). A bimodal size distribution by mass for welding particles with two peak values (i.e., 10,000–18,000 and 560–320 nm) and a unimodal size distribution by number with 190.7-nm mode size or 154.9-nm geometric size were observed. Nanoparticles by number comprised 60.7 % of particles, whereas nanoparticles by mass only accounted for 18.2 % of the total particles. The morphology of welding particles was dominated by the formation of chain-like agglomerates of primary particles. The metal composition of these welding particles consisted primarily of Fe, Mn, and Zn. The size distribution, morphology, and elemental compositions of welding particles were significantly different from background particles. Working activities, sampling distances from the source, air velocity, engineering control measures, and background particles in working places had significant influences on concentrations of airborne nanoparticle. In addition, SAC showed a high correlation with NC and a relatively low correlation with MC. These findings indicate that the GMAW process is able to generate significant levels of nanoparticles. It is recommended that a combination of multiple metrics is measured as part of a well-designed sampling strategy for airborne nanoparticles. Key exposure factors, such as particle agglomeration/aggregation, background particles, working activities, temporal and spatial distributions of the particles, air velocity, engineering control measures, should be investigated when measuring workplace

Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

Directory of Open Access Journals (Sweden)

Lu Kong

2014-11-01

Full Text Available 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.

The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells.

Science.gov (United States)

Liberda, Eric N; Cuevas, Azita K; Qu, Qingshan; Chen, Lung Chi

2014-08-01

The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures, such as increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone and potentiated atherosclerosis in murine species. Following an acute whole body inhalation exposure to 500 µg/m(3) of nickel nanoparticles for 5 h, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells (CEPCs), circulating endothelial cells (CECs) and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure. Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. These data provide new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration (OSHA) permissible exposure limit may adversely affect EPCs and exacerbate cardiovascular disease states.

Exposure to TiO2 nanoparticles increases Staphylococcusaureusinfection of HeLa cells

Science.gov (United States)

Xu, Yan; Wei, Ming-Tzo; Walker, Stephen. G.; Wang, Hong Zhan; Gondon, Chris; Brink, Peter; Guterman, Shoshana; Zawacki, Emma; Applebaum, Eliana; Rafailovich, Miriam; Ou-Yang, H. Daniel; Mironava, Tatsiana

TiO2 is one of the most common nanoparticles in industry from food additives to energy generation. Even though TiO2 is also used as an anti-bacterial agent in combination with UV, we found that, in the absence of UV, exposure of HeLa cells to TiO2 nanoparticles largely increased their risk of bacterial invasion. HeLa cells cultured with low dosage rutile and anatase TiO2 nanoparticles (0.1 mg/ml) for 24 hrs prior to exposure to bacteria had 350% and 250% respectively more bacteria infected per cell. The increase was attributed to increased LDH leakage, and changes in the mechanical response of the cell membrane. On the other hand, macrophages exposed to TiO2 particles ingested 40% fewer bacteria, further increasing the risk of infection. In combination, these two factors raise serious concerns regarding the impact of exposure to TiO2 nanoparticles on the ability of organisms to resist bacterial infection.

Inhalation exposure during spray application and subsequent sanding of a wood sealant containing zinc oxide nanoparticles.

Science.gov (United States)

Cooper, Michael R; West, Gavin H; Burrelli, Leonard G; Dresser, Daniel; Griffin, Kelsey N; Segrave, Alan M; Perrenoud, Jon; Lippy, Bruce E

2017-07-01

Nano-enabled construction products have entered into commerce. There are concerns about the safety of manufactured nanomaterials, and exposure assessments are needed for a more complete understanding of risk. This study assessed potential inhalation exposure to ZnO nanoparticles during spray application and power sanding of a commercially available wood sealant and evaluated the effectiveness of local exhaust ventilation in reducing exposure. A tradesperson performed the spraying and sanding inside an environmentally-controlled chamber. Dust control methods during sanding were compared. Filter-based sampling, electron microscopy, and real-time particle counters provided measures of exposure. Airborne nanoparticles above background levels were detected by particle counters for all exposure scenarios. Nanoparticle number concentrations and particle size distributions were similar for sanding of treated versus untreated wood. Very few unbound nanoparticles were detected in aerosol samples via electron microscopy, rather nano-sized ZnO was contained within, or on the surface of larger airborne particles. Whether the presence of nanoscale ZnO in these aerosols affects toxicity merits further investigation. Mass-based exposure measurements were below the NIOSH Recommended Exposure Limit for Zn, although there are no established exposure limits for nanoscale ZnO. Local exhaust ventilation was effective, reducing airborne nanoparticle number concentrations by up to 92% and reducing personal exposure to total dust by at least 80% in terms of mass. Given the discrepancies between the particle count data and electron microscopy observations, the chemical identity of the airborne nanoparticles detected by the particle counters remains uncertain. Prior studies attributed the main source of nanoparticle emissions during sanding to copper nanoparticles generated from electric sander motors. Potentially contrary results are presented suggesting the sander motor may not have been

Potential exposure to endocrine disrupting chemicals and selected adverse pregnancy outcomes

DEFF Research Database (Denmark)

Bengtsson, Jessica; Thygesen, Pernille Søgaard; Kaerlev, Linda

2017-01-01

potential occupational exposure to endocrine disrupting chemicals (EDC) of the mother during pregnancy is associated with preterm birth and low birth weight. Methods: Pregnant women referred to an Occupational Health Clinic (OHC) in two Danish regions (Copenhagen or Aarhus) between 1984 and 2010, suspected...

Current understanding of the toxicological risk posed to the fetus following maternal exposure to nanoparticles.

Science.gov (United States)

Zhang, Yanli; Wu, Junrong; Feng, Xiaoli; Wang, Ruolan; Chen, Aijie; Shao, Longquan

2017-12-01

With the broad use of nanotechnology, the number and variety of nanoparticles that humans can be exposed to has further increased. Consequently, there is growing concern about the potential effect of maternal exposure to various nanoparticles during pregnancy on a fetus. However, the nature of this risk is not fully known. Areas covered: In this review, materno-fetal transfer of nanoparticles through the placenta is described. Both prenatal and postnatal adverse effects, such as fetal resorption, malformation and injury to various organs in mice exposed to nanoparticles are reviewed. The potential mechanisms of toxicity are also discussed. Expert opinion: The toxicology and safe application of recently developed nanoparticles has attracted much attention in the past few years. Although many studies have demonstrated the toxicology of nanoparticles in various species, only a small number of studies have examined the effect on a fetus after maternal exposure to nanoparticles. This is particularly important, because the developing fetus is especially vulnerable to the toxic effects of nanoparticles during fetal development due to the unique physical stage of the fetus. Nanoparticles may directly or indirectly impair fetal development and growth after maternal exposure to nanoparticles.

Nanoparticle exposure biomonitoring: exposure/effect indicator development approaches

Science.gov (United States)

Marie-Desvergne, C.; Dubosson, M.; Lacombe, M.; Brun, V.; Mossuz, V.

2015-05-01

The use of engineered nanoparticles (NP) is more and more widespread in various industrial sectors. The inhalation route of exposure is a matter of concern (adverse effects of air pollution by ultrafine particles and asbestos). No NP biomonitoring recommendations or standards are available so far. The LBM laboratory is currently studying several approaches to develop bioindicators for occupational health applications. As regards exposure indicators, new tools are being implemented to assess potentially inhaled NP in non-invasive respiratory sampling (nasal sampling and exhaled breath condensates (EBC)). Diverse NP analytical characterization methods are used (ICP-MS, dynamic light scattering and electron microscopy coupled to energy-dispersive X-ray analysis). As regards effect indicators, a methodology has been developed to assess a range of 29 cytokines in EBCs (potential respiratory inflammation due to NP exposure). Secondly, collaboration between the LBM laboratory and the EDyp team has allowed the EBC proteome to be characterized by means of an LC-MS/MS process. These projects are expected to facilitate the development of individual NP exposure biomonitoring tools and the analysis of early potential impacts on health. Innovative techniques such as field-flow fractionation combined with ICP-MS and single particle-ICPMS are currently being explored. These tools are directly intended to assist occupational physicians in the identification of exposure situations.

Nanoparticle exposure biomonitoring: exposure/effect indicator development approaches

International Nuclear Information System (INIS)

Marie-Desvergne, C; Dubosson, M; Mossuz, V; Lacombe, M; Brun, V

2015-01-01

The use of engineered nanoparticles (NP) is more and more widespread in various industrial sectors. The inhalation route of exposure is a matter of concern (adverse effects of air pollution by ultrafine particles and asbestos). No NP biomonitoring recommendations or standards are available so far. The LBM laboratory is currently studying several approaches to develop bioindicators for occupational health applications. As regards exposure indicators, new tools are being implemented to assess potentially inhaled NP in non-invasive respiratory sampling (nasal sampling and exhaled breath condensates (EBC)). Diverse NP analytical characterization methods are used (ICP-MS, dynamic light scattering and electron microscopy coupled to energy-dispersive X-ray analysis). As regards effect indicators, a methodology has been developed to assess a range of 29 cytokines in EBCs (potential respiratory inflammation due to NP exposure). Secondly, collaboration between the LBM laboratory and the EDyp team has allowed the EBC proteome to be characterized by means of an LC-MS/MS process. These projects are expected to facilitate the development of individual NP exposure biomonitoring tools and the analysis of early potential impacts on health. Innovative techniques such as field-flow fractionation combined with ICP-MS and single particle-ICPMS are currently being explored. These tools are directly intended to assist occupational physicians in the identification of exposure situations. (paper)

Potential inhalation exposure and containment efficiency when using hoods for handling nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Tsai, Candace Su-Jung, E-mail: tsai51@purdue.edu [Purdue University, School of Health Science (United States)

2013-09-15

Inhalation exposure to airborne nanoparticles (NPs) has been reported during manual activities using typical fume hoods. This research studied potential inhalation exposure associated with the manual handling of NPs using two new nanoparticle-handling enclosures and two biological safety cabinets, and discussed the ability to contain NPs in the hoods to reduce environmental release and exposure. Airborne concentrations of 5 nm to 20 {mu}m diameter particles were measured while handling nanoalumina particles in various ventilated enclosures. Tests were conducted using two handling conditions and concentrations were measured using real-time particle counters, and particles were collected on transmission electron microscope grids to determine particle morphology and elemental composition. Airflow patterns were characterized visually using a laser-light sheet and fog. The average number concentration increase at breathing zone outside the enclosure was less than 1,400 particle/cm{sup 3} for each particle size at all tested conditions and the estimated overall mass concentration was about 83 {mu}g/m{sup 3} which was less than the dosage of typical nanoparticle inhalation exposure studies. The typical front-to-back airflow was used in the studied hoods, which could potentially induce reverse turbulence in the wake region. However, containment of NPs using studied hoods was demonstrated with excellent performance. Smoke tests showed that worker's hand motion could potentially cause nanoparticle escape. The challenge of front-to-back airflow can be partially overcome by gentle motion, low face velocity, and front exhaust to reduce nanoparticle escape.

Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

International Nuclear Information System (INIS)

Asimakopoulou, Akrivi; Daskalos, Emmanouil; Papaioannou, Eleni; Konstandopoulos, Athanasios G; Lewinski, Nastassja; Riediker, Michael

2013-01-01

In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

Science.gov (United States)

Asimakopoulou, Akrivi; Daskalos, Emmanouil; Lewinski, Nastassja; Riediker, Michael; Papaioannou, Eleni; Konstandopoulos, Athanasios G.

2013-04-01

In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

Excitation of high energy levels under laser exposure of suspensions of nanoparticles in liquids

Energy Technology Data Exchange (ETDEWEB)

Shafeev, G.A. [Wave Research Center of A.M. Prokhorov General Physics Institute, 38, Vavilov Street, 119991 Moscow (Russian Federation)], E-mail: shafeev@kapella.gpi.ru; Simakin, A.V. [Wave Research Center of A.M. Prokhorov General Physics Institute, 38, Vavilov Street, 119991 Moscow (Russian Federation); Bozon-Verduraz, F. [ITODYS, UMR CNRS 7086, Universite Paris 7-Denis Diderot, 2, place Jussieu, 75251 Paris cedex 05 (France); Robert, M. [Laboratoire d' Electrochimie Moleculaire, UMR CNRS 7591, Universite Paris 7 Denis Diderot, 2, place Jussieu, 75251 Paris cedex 05 (France)

2007-12-15

Laser exposure of suspensions of nanoparticles in liquids leads to excitation of high energy levels in both liquid and nanoparticle material. The emission spectrum of the colloidal solution under exposure of a suspension metallic nanoparticles in water to radiation of a Nd:YAG laser of a picosecond range of pulse duration is discussed. Excitation of nuclear energy levels and neutron release is experimentally studied on the model system of transmutation of Hg into Au that occurs under exposure of Hg nanodrops suspended in D{sub 2}O. The proposed mechanism involves: (i) emission of X-ray photons by Hg nanoparticles upon laser exposure, leading to neutron release from D{sub 2}O, (ii) initiation of Hg {yields} Au transmutation by the capture of neutrons. The effect of transmutation is more pronounced using {sup 196}Hg isotope instead of Hg of natural isotope composition. The influence of laser pulse duration on the degree of transmutation (from fs through ns range) is discussed.

Enhanced eyeblink conditioning in behaviorally inhibited individuals is disrupted by proactive interference following US alone pre-exposures.

Directory of Open Access Journals (Sweden)

Michael Todd Allen

2016-03-01

Full Text Available Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from CS or US alone pre-exposures (Holloway et al., 2012. US alone pre-exposures disrupt subsequent CR acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al., (2012 reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioural Inhibition (AMBI. Sixty six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI individuals exhibited enhanced proactive interference as compared to non-inhibited (NI individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible learned helplessness. Applications of these findings of

Enhanced Eyeblink Conditioning in Behaviorally Inhibited Individuals is Disrupted by Proactive Interference Following US Alone Pre-exposures.

Science.gov (United States)

Allen, Michael Todd; Miller, Daniel P

2016-01-01

Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from conditioned stimulus (CS) or unconditioned stimulus (US) alone pre-exposures (Holloway et al., 2012). US alone pre-exposures disrupt subsequent conditioned response (CR) acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al. (2012) reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioral Inhibition (AMBI). Sixty-six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI) individuals exhibited enhanced proactive interference as compared to non-inhibited (NI) individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible

The Human Stratum Corneum Prevents Small Gold Nanoparticle Penetration and Their Potential Toxic Metabolic Consequences

Directory of Open Access Journals (Sweden)

David C. Liu

2012-01-01

Full Text Available Nanoparticles are being used in multiple applications, ranging from biomedical and skin care products (e.g., sunscreen through to industrial manufacturing processes (e.g., water purification. The increase in exposure has led to multiple reports on nanoparticle penetration and toxicity. However, the correlation between nanoparticle size and its penetration without physical/chemical enhancers through the skin is poorly understood—with studies instead focusing primarily on skin penetration under disrupted conditions. In this paper, we investigate the penetration and metabolic effects of 10 nm, 30 nm, and 60 nm gold nanoparticles within viable excised human skin after 24-hour exposure using multiphoton tomograph-fluorescence lifetime imaging microscopy. After 24 hour treatment with the 10, 30, and 60 nm gold nanoparticles, there was no significant penetration detected below the stratum corneum. Furthermore, there were no changes in metabolic output (total NAD(PH in the viable epidermis posttreatment correlating with lack of penetration of nanoparticles. These results are significant for estimating topical nanoparticle exposure in humans where other model systems may overestimate the exposure of nanoparticles to the viable epidermis. Our data shows that viable human skin resists permeation of small nanoparticles in a size range that has been reported to penetrate deeply in other skin models.

Gills are an initial target of zinc oxide nanoparticles in oysters Crassostrea gigas, leading to mitochondrial disruption and oxidative stress

International Nuclear Information System (INIS)

Trevisan, Rafael; Delapedra, Gabriel; Mello, Danielle F.; Arl, Miriam; Schmidt, Éder C.; Meder, Fabian; Monopoli, Marco; Cargnin-Ferreira, Eduardo; Bouzon, Zenilda L.; Fisher, Andrew S.; Sheehan, David; Dafre, Alcir L.

2014-01-01

Graphical abstract: - Highlights: • ZnONP exposure causes an initial accumulation of zinc in gills and later in digestive gland. • Zinc burden occurs by ZnONP endocytosis or uptake of ionic zinc after dissociation. • ZnONP exposure disrupts mitochondrial ultrastructure in both tissues. • Mitochondrial damage and oxidative stress are major features of ZnONP acute toxicity. - Abstract: The increasing industrial use of nanomaterials during the last decades poses a potential threat to the environment and in particular to organisms living in the aquatic environment. In the present study, the toxicity of zinc oxide nanoparticles (ZnONP) was investigated in Pacific oysters Crassostrea gigas. The nanoscale of ZnONP, in vehicle or ultrapure water, was confirmed, presenting an average size ranging from 28 to 88 nm. In seawater, aggregation was detected by TEM and DLS analysis, with an increased average size ranging from 1 to 2 μm. Soluble or nanoparticulated zinc presented similar toxicity, displaying a LC 50 (96 h) around 30 mg/L. High zinc dissociation from ZnONP, releasing ionic zinc in seawater, is a potential route for zinc assimilation and ZnONP toxicity. To investigate mechanisms of toxicity, oysters were treated with 4 mg/L ZnONP for 6, 24 or 48 h. ZnONP accumulated in gills (24 and 48 h) and digestive glands (48 h). Ultrastructural analysis of gills revealed electron-dense vesicles near the cell membrane and loss of mitochondrial cristae (6 h). Swollen mitochondria and a more conspicuous loss of mitochondrial cristae were observed after 24 h. Mitochondria with disrupted membranes and an increased number of cytosolic vesicles displaying electron-dense material were observed 48 h post exposure. Digestive gland showed similar changes, but these were delayed relative to gills. ZnONP exposure did not greatly affect thiol homeostasis (reduced and oxidized glutathione) or immunological parameters (phagocytosis, hemocyte viability and activation and total hemocyte

Gills are an initial target of zinc oxide nanoparticles in oysters Crassostrea gigas, leading to mitochondrial disruption and oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Trevisan, Rafael; Delapedra, Gabriel; Mello, Danielle F.; Arl, Miriam [Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Schmidt, Éder C. [Department of Cell Biology, Embryology and Genetic, Federal University of Santa Catarina, 88049-900 Florianópolis, SC (Brazil); Meder, Fabian; Monopoli, Marco [Centre for Bionano Interactions, University College Dublin, Dublin (Ireland); Cargnin-Ferreira, Eduardo [Federal Institute of Santa Catarina, Campus Garopaba, Laboratory of Histological Markers, 88495-000 Garopaba, SC (Brazil); Bouzon, Zenilda L. [Department of Cell Biology, Embryology and Genetic, Federal University of Santa Catarina, 88049-900 Florianópolis, SC (Brazil); Fisher, Andrew S. [School of Geography, Earth and Environmental Sciences, University of Plymouth, PL4 8AA Plymouth (United Kingdom); Sheehan, David [Department of Biochemistry, University College Cork, Cork (Ireland); Dafre, Alcir L., E-mail: alcir.dafre@ufsc.br [Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil)

2014-08-15

Graphical abstract: - Highlights: • ZnONP exposure causes an initial accumulation of zinc in gills and later in digestive gland. • Zinc burden occurs by ZnONP endocytosis or uptake of ionic zinc after dissociation. • ZnONP exposure disrupts mitochondrial ultrastructure in both tissues. • Mitochondrial damage and oxidative stress are major features of ZnONP acute toxicity. - Abstract: The increasing industrial use of nanomaterials during the last decades poses a potential threat to the environment and in particular to organisms living in the aquatic environment. In the present study, the toxicity of zinc oxide nanoparticles (ZnONP) was investigated in Pacific oysters Crassostrea gigas. The nanoscale of ZnONP, in vehicle or ultrapure water, was confirmed, presenting an average size ranging from 28 to 88 nm. In seawater, aggregation was detected by TEM and DLS analysis, with an increased average size ranging from 1 to 2 μm. Soluble or nanoparticulated zinc presented similar toxicity, displaying a LC{sub 50} (96 h) around 30 mg/L. High zinc dissociation from ZnONP, releasing ionic zinc in seawater, is a potential route for zinc assimilation and ZnONP toxicity. To investigate mechanisms of toxicity, oysters were treated with 4 mg/L ZnONP for 6, 24 or 48 h. ZnONP accumulated in gills (24 and 48 h) and digestive glands (48 h). Ultrastructural analysis of gills revealed electron-dense vesicles near the cell membrane and loss of mitochondrial cristae (6 h). Swollen mitochondria and a more conspicuous loss of mitochondrial cristae were observed after 24 h. Mitochondria with disrupted membranes and an increased number of cytosolic vesicles displaying electron-dense material were observed 48 h post exposure. Digestive gland showed similar changes, but these were delayed relative to gills. ZnONP exposure did not greatly affect thiol homeostasis (reduced and oxidized glutathione) or immunological parameters (phagocytosis, hemocyte viability and activation and total

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

Science.gov (United States)

Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

2015-01-01

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. Copyright © 2014 Elsevier Inc. All rights reserved.

Cellular internalization, transcellular transport, and cellular effects of silver nanoparticles in polarized Caco-2 cells following apical or basolateral exposure

International Nuclear Information System (INIS)

Imai, Shunji; Morishita, Yuki; Hata, Tomoyuki; Kondoh, Masuo; Yagi, Kiyohito; Gao, Jian-Qing; Nagano, Kazuya; Higashisaka, Kazuma; Yoshioka, Yasuo; Tsutsumi, Yasuo

2017-01-01

When considering the safety of ingested nanomaterials, it is important to quantitate their transfer across intestinal cells; however, little information exists about the effects of nanomaterial size or exposure side (apical versus basolateral epithelial surface) on nanomaterial transfer. Here, we examined cellular internalization and transcellular transport, and the effects of nanomaterials on Caco-2 monolayers after apical or basolateral exposure to Ag or Au nanoparticles with various sizes. After apical treatment, both internalization and transfer to the basolateral side of the monolayers were greater for smaller Ag nanoparticles than for larger Ag nanoparticles. In contrast, after basolateral treatment, larger Ag nanoparticles were more internalized than smaller Ag nanoparticles, but the transfer to the apical side was greater for smaller Ag nanoparticles. Au nanoparticles showed different rules of internalization and transcellular transport compared with Ag nanoparticles. Furthermore, the paracellular permeability of the Caco-2 monolayers was temporarily increased by Ag nanoparticles (5 μg/mL; diameters, ≤10 nm) following basolateral but not apical exposure. We conclude that the internalization, transfer, and effects of nanomaterials in epithelial cell monolayers depend on the size and composition of nanomaterials, and the exposure side. - Highlights: • Ag and Au nanoparticles can transfer across Caco-2 monolayers. • Cellular uptake of nanoparticles change between apical and basolateral exposure. • Basolateral Ag nanoparticle exposure increases the permeability of Caco-2 monolayers.

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

Energy Technology Data Exchange (ETDEWEB)

Zhou, Changqing; Gao, Liying; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2017-03-01

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.

Benzopyrene exposure disrupts DNA methylation and growth dynamics in breast cancer cells

International Nuclear Information System (INIS)

Sadikovic, Bekim; Rodenhiser, David I.

2006-01-01

Exposures to environmental carcinogens and unhealthy lifestyle choices increase the incidence of breast cancer. One such compound, benzo(a)pyrene (BaP), leads to covalent DNA modifications and the deregulation of gene expression. To date, these mechanisms of BaP-induced carcinogenesis are poorly understood, particularly in the case of breast cancer. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in four breast cancer cell lines since disruptions in DNA methylation lead to deregulated gene expression and the loss of genomic integrity. We observed robust time- and concentration-dependent loss of proliferation, S phase and G2M accumulation and apoptosis in p53 positive MCF-7 and T47-D cells. We observed minimal responses in p53 negative HCC-1086 and MDA MB 231 cells. Furthermore, BaP increased p53 levels in both p53 positive cell lines, as well as p21 levels in MCF-7 cells, an effect that was prevented by the p53-specific inhibitor pifithrin-α. No changes in global levels of DNA methylation levels induced by BaP were detected by the methyl acceptor assay (MAA) in any cell line, however, methylation profiling by AIMS (amplification of intermethylated sites) analysis showed dynamic, sequence-specific hypo- and hypermethylation events in all cell lines. We also identified BaP-induced hypomethylation events at a number of genomic repeats. Our data confirm the p53-specific disruption of the cell cycle as well as the disruption of DNA methylation as a consequence of BaP treatment, thus reinforcing the link between environmental exposures, DNA methylation and breast cancer

Occupational Exposure of Nanoparticles In Forensic Science: A Need Of Safe Use

OpenAIRE

Shukla RK

2013-01-01

The rapid advancement in nanotechnology sets new paradigms in science and technology, but simultaneously increased apprehensions about the health risks of nano-objects. Recently, various types of nanoparticles used in several areas of forensic including paint, inks, security document and to develop the latent fingerprint. Objective: Despite bright outlooks of nanoparticles used in various fields of forensic science, an increasing occupational as well as laboratory exposure of nanoparticles...

Oral Gingival Cell Cigarette Smoke Exposure Induces Muscle Cell Metabolic Disruption

Directory of Open Access Journals (Sweden)

Andrea C. Baeder

2016-01-01

Full Text Available Cigarette smoke exposure compromises health through damaging multiple physiological systems, including disrupting metabolic function. The purpose of this study was to determine the role of oral gingiva in mediating the deleterious metabolic effects of cigarette smoke exposure on skeletal muscle metabolic function. Using an in vitro conditioned medium cell model, skeletal muscle cells were incubated with medium from gingival cells treated with normal medium or medium containing suspended cigarette smoke extract (CSE. Following incubation of muscle cells with gingival cell conditioned medium, muscle cell mitochondrial respiration and insulin signaling and action were determined as an indication of overall muscle metabolic health. Skeletal muscle cells incubated with conditioned medium of CSE-treated gingival cells had a profound reduction in mitochondrial respiration and respiratory control. Furthermore, skeletal muscle cells had a greatly reduced response in insulin-stimulated Akt phosphorylation and glycogen synthesis. Altogether, these results provide a novel perspective on the mechanism whereby cigarette smoke affects systemic metabolic function. In conclusion, we found that oral gingival cells treated with CSE create an altered milieu that is sufficient to both disrupted skeletal muscle cell mitochondrial function and insulin sensitivity.

In vitro toxicological nanoparticle studies under flow exposure

International Nuclear Information System (INIS)

Sambale, Franziska; Stahl, Frank; Bahnemann, Detlef; Scheper, Thomas

2015-01-01

The use of nanoparticles is becoming increasingly common in industry and everyday objects. Thus, extensive risk management concerning the potential health risk of nanoparticles is important. Currently, in vitro nanoparticle testing is mainly performed under static culture conditions without any shear stress. However, shear stress is an important biomechanical parameter. Therefore, in this study, a defined physiological flow to different mammalian cell lines such as A549 cells and NIH-3T3 cells has been applied. The effects of zinc oxide and titanium dioxide nanoparticles (TiO 2 -NP), respectively, were investigated under both static and dynamic conditions. Cell viability, cell morphology, and adhesion were proven and compared to the static cell culture. Flow exposure had an impact on the cellular morphology of the cells. NIH-3T3 cells were elongated in the direction of flow and A549 cells exhibited vesicles inside the cells. Zinc oxide nanoparticles reduced the cell viability in the static and in the dynamic culture; however, the dynamic cultures were more sensitive. In the static culture and in the dynamic culture, TiO 2 -NP did not affect cell viability. In conclusion, dynamic culture conditions are important for further in vitro investigations and provide more relevant results than static culture conditions

In vitro toxicological nanoparticle studies under flow exposure

Energy Technology Data Exchange (ETDEWEB)

Sambale, Franziska, E-mail: sambale@iftc.uni-hannover.de; Stahl, Frank; Bahnemann, Detlef; Scheper, Thomas [Gottfried Wilhelm Leibniz University Hanover, Institute for Technical Chemistry (Germany)

2015-07-15

The use of nanoparticles is becoming increasingly common in industry and everyday objects. Thus, extensive risk management concerning the potential health risk of nanoparticles is important. Currently, in vitro nanoparticle testing is mainly performed under static culture conditions without any shear stress. However, shear stress is an important biomechanical parameter. Therefore, in this study, a defined physiological flow to different mammalian cell lines such as A549 cells and NIH-3T3 cells has been applied. The effects of zinc oxide and titanium dioxide nanoparticles (TiO{sub 2}-NP), respectively, were investigated under both static and dynamic conditions. Cell viability, cell morphology, and adhesion were proven and compared to the static cell culture. Flow exposure had an impact on the cellular morphology of the cells. NIH-3T3 cells were elongated in the direction of flow and A549 cells exhibited vesicles inside the cells. Zinc oxide nanoparticles reduced the cell viability in the static and in the dynamic culture; however, the dynamic cultures were more sensitive. In the static culture and in the dynamic culture, TiO{sub 2}-NP did not affect cell viability. In conclusion, dynamic culture conditions are important for further in vitro investigations and provide more relevant results than static culture conditions.

Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation

DEFF Research Database (Denmark)

Birks, Laura; Casas, Maribel; Garcia, Ana M.

2016-01-01

Background: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth.Objectives: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure...... women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW [odds ratio (OR) = 1.25; 95% CI: 1.04, 1.49], as were most specific EDC groups; this association was consistent...... groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates.Results: Eleven percent of pregnant...

Continuous 3-day exposure assessment of workplace manufacturing silver nanoparticles

International Nuclear Information System (INIS)

Lee, Ji Hyun; Ahn, Kangho; Kim, Sun Man; Jeon, Ki Soo; Lee, Jong Seong; Yu, Il Je

2012-01-01

With the increased production and widespread use of nanomaterials, human and environmental exposure to nanomaterials is inevitably increasing. Therefore, this study monitored the possible nanoparticle exposure at a workplace that manufactures silver nanoparticles. To estimate the potential exposure of workers, personal sampling, area monitoring, and real-time monitoring were conducted over 3 days using a scanning mobility particle sizer and dust monitor at a workplace where the workers handle nanomaterials. The area sampling concentrations obtained from the injection room showed the highest concentration, ranging from 0.00501 to 0.28873 mg/m 3 . However, apart from the injection room, none of the area samplings obtained from other locations showed a concentration higher than 0.0013 mg/m 3 . Meanwhile, the personal sampling concentrations ranged from 0.00004 to 0.00243 mg/m 3 over the 3 days of sampling, which was much lower than the silver TLV. The particle number concentrations at the silver nanoparticle manufacturing workplace were 911,170 (1st day), 1,631,230 (2nd day), and 1,265,024 (3rd day) particles/cm 3 with a size range of 15–710.5 nm during the operation of the reactor, while the concentration decreased to 877,364.9 (1st day), 492,732 (2nd day), and 344,343 (3rd day) particles/cm 3 when the reactor was stopped.

Endocrine disruption in a terrestrial isopod under exposure to bisphenol A and vinclozin.

NARCIS (Netherlands)

Lemos, M.F.L.; van Gestel, C.A.M.; Soares, A.M.V.M.

2009-01-01

Background, aim, and scope In the past decade there has been an increasing awareness about the possible consequences of human and wildlife exposure to endocrine disrupting compounds (EDCs). Bisphenol A (BPA) and vinclozolin (Vz) are EDCs which impacts on vertebrates have been largely investigated.

In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

Energy Technology Data Exchange (ETDEWEB)

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.

In-vitro Cell Exposure Studies for the Assessment of Nanoparticle Toxicity in the Lung - A Dialogue between Aerosol Science and Biology

International Nuclear Information System (INIS)

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

2011-01-01

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.

Effects of nickel-oxide nanoparticle pre-exposure dispersion status on bioactivity in the mouse lung.

Science.gov (United States)

Sager, Tina; Wolfarth, Michael; Keane, Michael; Porter, Dale; Castranova, Vincent; Holian, Andrij

2016-01-01

Nanotechnology is emerging as one of the world's most promising new technologies. From a toxicology perspective, nanoparticles possess two features that promote their bioactivity. The first involves physical-chemical characteristics of the nanoparticle, which include the surface area of the nanoparticle. The second feature is the ability of the nanoparticle to traverse cell membranes. These two important nanoparticle characteristics are greatly influenced by placing nanoparticles in liquid medium prior to animal exposure. Nanoparticles tend to agglomerate and clump in suspension, making it difficult to reproducibly deliver them for in vivo or in vitro experiments, possibly affecting experimental variability. Thus, we hypothesize that nanoparticle dispersion status will correlate with the in vivo bioactivity/toxicity of the particle. To test our hypothesis, nano-sized nickel oxide was suspended in four different dispersion media (phosphate-buffered saline (PBS), dispersion medium (DM), a combination of dipalmitoyl-phosphatidyl choline (DPPC) and albumin in concentrations that mimic diluted alveolar lining fluid), Survanta®, or pluronic (Pluronic F-68). Well-dispersed and poorly dispersed suspensions were generated in each media by varying sonication time on ice utilizing a Branson Sonifer 450 (25W continuous output, 20 min or 5 min, respectively). Mice (male, C57BL/6J, 7-weeks-old) were given 0-80 µg/mouse of nano-sized nickel oxide in the different states of dispersion via pharyngeal aspiration. At 1 and 7 d post-exposure, mice underwent whole lung lavage to assess pulmonary inflammation and injury as a function of dispersion status, dose and time. The results show that pre-exposure dispersion status correlates with pulmonary inflammation and injury. These results indicate that a greater degree of pre-exposure dispersion increases pulmonary inflammation and cytotoxicity, as well as decreases in the integrity of the blood-gas barrier in the lung.

Thyroid endocrine disruption in zebrafish larvae after exposure to mono-(2-ethylhexyl phthalate (MEHP.

Directory of Open Access Journals (Sweden)

Wenhui Zhai

Full Text Available Phthalates are extensively used as plasticizers in a variety of daily-life products, resulting in widespread distribution in aquatic environments. However, limited information is available on the endocrine disrupting effects of phthalates in aquatic organisms. The aim of the present study was to examine whether exposure to mono-(2-ethylhexyl phthalate (MEHP, the hydrolytic metabolite of di-(2-ethylhexyl phthalate (DEHP disrupts thyroid endocrine system in fish. In this study, zebrafish (Danio rerio embryos were exposed to different concentrations of MEHP (1.6, 8, 40, and 200 μg/L from 2 h post-fertilization (hpf to 168 hpf. The whole-body content of thyroid hormone and transcription of genes involved in the hypothalamic-pituitary-thyroid (HPT axis were examined. Treatment with MEHP significantly decreased whole-body T4 contents and increased whole-body T3 contents, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (Dio2 and UGT1ab might be responsible for decreased T4 contents. Elevated gene transcription of Dio1 was also observed in this study, which might assist to degrade increased T3 contents. Exposure to MEHP also significantly induced transcription of genes involved in thyroid development (Nkx2.1 and Pax8 and thyroid hormone synthesis (TSHβ, NIS and TG. However, the genes encoding proteins involved in TH transport (transthyretin, TTR was transcriptionally significantly down-regulated after exposure to MEHP. Overall, these results demonstrate that acute exposure to MEHP alters whole-body contents of thyroid hormones in zebrafish embryos/larvae and changes the transcription of genes involved in the HPT axis, thus exerting thyroid endocrine toxicity.

Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts

Directory of Open Access Journals (Sweden)

James C K Lai

2008-12-01

Full Text Available James C K Lai1, Maria B Lai1, Sirisha Jandhyam1, Vikas V Dukhande1, Alok Bhushan1, Christopher K Daniels1, Solomon W Leung21Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, and Biomedical Research Institute; 2Department of Civil and Environmental Engineering, College of Engineering and Biomedical Research Institute, Idaho State University, Pocatello, ID, USAAbstract: The use of titanium dioxide (TiO2 in various industrial applications (eg, production of paper, plastics, cosmetics, and paints has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO2 nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO2 micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO nanoparticles were the most effective, TiO2 nanoparticles the second most effective, and magnesium oxide (MgO nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO2 micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.Keywords: cytotoxicity of titanium dioxide micro- and nanoparticles, cytotoxicity of zinc oxide and magnesium oxide nanoparticles, human neural cells

ENDOCRINE-DISRUPTING CHEMICALS: PREPUBERTAL EXPOSURES AND EFFECTS ON SEXUAL MATURATION AND THYROID FUNCTION IN THE MALE RAT. A FOCUS ON THE EDSTAC RECOMMENDATIONS. ENDOCRINE DISRUPTER SCREENING AND TESTING ADVISORY COMMITTEE

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Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee.Stoker TE, Parks LG, Gray LE, Cooper RL.

Combined exposure to endocrine disrupting pesticides impairs parturition and causes pup mortality in rats

DEFF Research Database (Denmark)

Hansen, Pernille Reimer; Christiansen, Sofie; Boberg, Julie

from gestational day 7 to postnatal day (PND)13 with either vehicle (control) or a mixture of the five pesticides at 25%, 50%, 75% or 100% of their individual NOAELs for causing major effects on pregnancy length and pup survival in our earlier studies. The pregnancy length was dose....... Although laboratory animal studies have shown that some endocrine disrupting pesticides can affect reproduction and sexual differentiation, individual pesticides may appear to be present in human tissues at too low levels to cause concern for adverse reproductive effects. However, recent studies in our...... laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Here, we present results from range finding studies with combined exposure...

Perinatal exposure to mixtures of endocrine disrupting chemicals reduces female rat follicle reserves and accelerates reproductive aging

DEFF Research Database (Denmark)

Johansson, Hanna Katarina Lilith; Jacobsen, Pernille Rosenskjold; Hass, Ulla

2016-01-01

Exposure to endocrine disrupting chemicals (EDCs) during development can have negative consequences later in life. In this study we investigated the effect of perinatal exposure to mixtures of human relevant EDCs on the female reproductive system. Rat dams were exposed to a mixture of phthalates,...

Airborne nanoparticle exposures associated with the manual handling of nanoalumina and nanosilver in fume hoods

International Nuclear Information System (INIS)

Tsai, Su-Jung; Ada, Earl; Isaacs, Jacqueline A.; Ellenbecker, Michael J.

2009-01-01

Manual handling of nanoparticles is a fundamental task of most nanomaterial research; such handling may expose workers to ultrafine or nanoparticles. Recent studies confirm that exposures to ultrafine or nanoparticles produce adverse inflammatory responses in rodent lungs and such particles may translocate to other areas of the body, including the brain. An important method for protecting workers handling nanoparticles from exposure to airborne nanoparticles is the laboratory fume hood. Such hoods rely on the proper face velocity for optimum performance. In addition, several other hood design and operating factors can affect worker exposure. Handling experiments were performed to measure airborne particle concentration while handling nanoparticles in three fume hoods located in different buildings under a range of operating conditions. Nanoalumina and nanosilver were selected to perform handling experiments in the fume hoods. Air samples were also collected on polycarbonate membrane filters and particles were characterized by scanning electron microscopy. Handling tasks included transferring particles from beaker to beaker by spatula and by pouring. Measurement locations were the room background, the researcher's breathing zone and upstream and downstream from the handling location. Variable factors studied included hood design, transfer method, face velocity/sash location and material types. Airborne particle concentrations measured at breathing zone locations were analyzed to characterize exposure level. Statistics were used to test the correlation between data. The test results found that the handling of dry powders consisting of nano-sized particles inside laboratory fume hoods can result in a significant release of airborne nanoparticles from the fume hood into the laboratory environment and the researcher's breathing zone. Many variables were found to affect the extent of particle release including hood design, hood operation (sash height, face velocity

Short-term exposure to gold nanoparticle suspension impairs swimming behavior in a widespread calanoid copepod.

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Michalec, François-Gaël; Holzner, Markus; Barras, Alexandre; Lacoste, Anne-Sophie; Brunet, Loïc; Lee, Jae-Seong; Slomianny, Christian; Boukherroub, Rabah; Souissi, Sami

2017-09-01

Calanoid copepods play an important role in the functioning of marine and brackish ecosystems. Information is scarce on the behavioral toxicity of engineered nanoparticles to these abundant planktonic organisms. We assessed the effects of short-term exposure to nonfunctionalized gold nanoparticles on the swimming behavior of the widespread estuarine copepod Eurytemora affinis. By means of three-dimensional particle tracking velocimetry, we reconstructed the trajectories of males, ovigerous and non-ovigerous females. We quantified changes in their swimming activity and in the kinematics and geometrical properties of their motion, three important descriptors of the motility patterns of zooplankters. In females, exposure to gold nanoparticles in suspension (11.4 μg L -1 ) for 30 min caused depressed activity and lower velocity and acceleration, whereas the same exposure caused minimal effects in males. This response differs clearly from the hyperactive behavior that is commonly observed in zooplankters exposed to pollutants, and from the generally lower sensitivity of female copepods to toxicants. Accumulation of gold nanoparticles on the external appendages was not observed, precluding mechanical effects. Only very few nanoparticles appeared sporadically in the inner part of the gut in some samples, either as aggregates or as isolated nanoparticles, which does not suggest systemic toxicity resulting from pronounced ingestion. Hence, the precise mechanisms underlying the behavioral toxicity observed here remain to be elucidated. These results demonstrate that gold nanoparticles can induce marked behavioral alterations at very low concentration and short exposure duration. They illustrate the applicability of swimming behavior as a suitable and sensitive endpoint for investigating the toxicity of nanomaterials present in estuarine and marine environments. Changes in swimming behavior may impair the ability of planktonic copepods to interact with their environment

Airborne nanoparticle exposures associated with the manual handling of nanoalumina and nanosilver in fume hoods

Energy Technology Data Exchange (ETDEWEB)

Tsai, Su-Jung, E-mail: candace.umass@gmail.com; Ada, Earl [University of Massachusetts Lowell, NSF Center for High-rate Nanomanufacturing (CHN) (United States); Isaacs, Jacqueline A. [Northeastern University, NSF Center for High-rate Nanomanufacturing (CHN) (United States); Ellenbecker, Michael J. [University of Massachusetts Lowell, NSF Center for High-rate Nanomanufacturing (CHN) (United States)

2009-01-15

Manual handling of nanoparticles is a fundamental task of most nanomaterial research; such handling may expose workers to ultrafine or nanoparticles. Recent studies confirm that exposures to ultrafine or nanoparticles produce adverse inflammatory responses in rodent lungs and such particles may translocate to other areas of the body, including the brain. An important method for protecting workers handling nanoparticles from exposure to airborne nanoparticles is the laboratory fume hood. Such hoods rely on the proper face velocity for optimum performance. In addition, several other hood design and operating factors can affect worker exposure. Handling experiments were performed to measure airborne particle concentration while handling nanoparticles in three fume hoods located in different buildings under a range of operating conditions. Nanoalumina and nanosilver were selected to perform handling experiments in the fume hoods. Air samples were also collected on polycarbonate membrane filters and particles were characterized by scanning electron microscopy. Handling tasks included transferring particles from beaker to beaker by spatula and by pouring. Measurement locations were the room background, the researcher's breathing zone and upstream and downstream from the handling location. Variable factors studied included hood design, transfer method, face velocity/sash location and material types. Airborne particle concentrations measured at breathing zone locations were analyzed to characterize exposure level. Statistics were used to test the correlation between data. The test results found that the handling of dry powders consisting of nano-sized particles inside laboratory fume hoods can result in a significant release of airborne nanoparticles from the fume hood into the laboratory environment and the researcher's breathing zone. Many variables were found to affect the extent of particle release including hood design, hood operation (sash height, face

Quantification of dermal exposure to nanoparticles from solid nanocomposites by using single particle ICP-MS

DEFF Research Database (Denmark)

Mackevica, Aiga; Olsson, Mikael Emil; Hansen, Steffen Foss

2016-01-01

, optical or photocatalytical properties. There is a lot of research focusing on effects exerted by nanoparticles, but the knowledge concerning release and subsequential exposure to nanoparticles is very limited, and information regarding potential dermal exposure from nanomaterial containing solid articles...... and characterization. In this study, we have investigated the potential dermal exposure to three different types of nano-enabled consumer products: Ag-containing keyboard covers, TiO2 coated ceramic tiles, and wood painted with CuO containing paint. The potential for dermal transfer from the aforementioned surfaces...

Gold nanoparticles administration induced prominent inflammatory, central vein intima disruption, fatty change and Kupffer cells hyperplasia

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Abdelhalim Mohamed

2011-08-01

Full Text Available Abstract Background Advances in nanotechnology have identified promising candidates for many biological, biomedical and biomedicine applications. They are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the effects of administration of gold nanoparticles (GNPs on inflammatory cells infiltration, central vein intima disruption, fatty change, and Kupffer cells hyperplasia in the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of 10, 20 and 50 nm GNPs for 3 or 7 days. Animals were randomly divided into groups, 12 GNPs-treated rats groups and one control group (NG. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and sinusoids. The alterations in the hepatocytes were mainly vacuolar to hydropic degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis. In addition, inflammatory cell infiltration, Kupffer cells hyperplasia, central veins intima disruption, hepatic strands dilatation and occasional fatty change together with a loss of normal architechiture of hepatic strands were also seen. Conclusions The alterations induced by the administration of GNPs were size-dependent with smaller ones induced more affects and related with time exposure of GNPs. These alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the

Potential exposure to endocrine disrupting chemicals and selected adverse pregnancy outcomes

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Bengtsson, Jessica; Thygesen, Pernille Søgaard; Kaerlev, Linda

2017-01-01

potential occupational exposure to endocrine disrupting chemicals (EDC) of the mother during pregnancy is associated with preterm birth and low birth weight. Methods: Pregnant women referred to an Occupational Health Clinic (OHC) in two Danish regions (Copenhagen or Aarhus) between 1984 and 2010, suspected...... on the suspicion of other exposures than EDC (n = 620), and to a sample of births by all occupationally active women in the same geographical regions (n = 346,544), including 1,077 births of the referred women’s non-referred pregnancies. Results: No indications of reduced birth weight or increased risk of preterm...... birth were found among women potentially exposed to EDC. Women potentially exposed to EDC had children with a higher birth weight compared to the sample of occupationally active women but not compared to other women referred to an OHC. Conclusions: Potential maternal exposure to EDC at Danish workplaces...

Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.

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Sifakis, Stavros; Androutsopoulos, Vasilis P; Tsatsakis, Aristeidis M; Spandidos, Demetrios A

2017-04-01

Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system. Copyright © 2017 Elsevier B.V. All rights reserved.

Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

Directory of Open Access Journals (Sweden)

Tianle Tang

2015-10-01

Full Text Available Bisphenol AF (BPAF is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio embryos, whole-body total 3,3′,5-triiodothyronine (TT3, total 3,5,3′,5′-tetraiodothyronine (TT4, free 3,3′,5-triiodothyronine (FT3 and free 3,5,3′,5′-tetraiodothyronine (FT4 levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L. The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae.

Stereoselective degradation and thyroid endocrine disruption of lambda-cyhalothrin in lizards (Eremias argus) following oral exposure.

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Chang, Jing; Hao, Weiyu; Xu, Yuanyuan; Xu, Peng; Li, Wei; Li, Jianzhong; Wang, Huili

2018-01-01

The disturbance of the thyroid system and elimination of chiral pyrethroid pesticides with respect to enantioselectivity in reptiles have so far received limited attention by research. In this study, bioaccumulation, thyroid gland lesions, thyroid hormone levels, and hypothalamus-pituitary-thyroid axis-related gene expression in male Eremias argus were investigated after three weeks oral administration of lambda-cyhalothrin (LCT) enantiomers. In the lizard liver, the concentration of LCT was negatively correlated with the metabolite-3-phenoxybenzoic acid (PBA) level during 21 days of exposure. (+)-LCT exposure induced a higher thyroid follicular epithelium height than (-)-LCT exposure. The thyroxine levels were increased in both treated groups while only (+)-LCT exposure induced a significant change in the triiodothyronine (T3) level. In addition, the expressions of hypothalamus-pituitary-thyroid axis-related genes including thyroid hormone receptors (trs), deiodinases (dios), uridinediphosphate glucuronosyltransferase (udp), and sulfotransferase (sult) were up-regulated after exposure to the two enantiomers. (+)-LCT treatment resulted in higher expression of trs and (-)-LCT exposure led to greater stimulation of dios in the liver, which indicated PBA-induced antagonism on thyroid hormone receptors and LCT-induced disruption of thyroxine (T4) deiodination. The results suggest the (-)-LCT exposure causes higher residual level in lizard liver while induces less disruption on lizard thyroid activity than (+)-LCT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Female exposure to endocrine disrupting chemicals and fecundity: a review.

Science.gov (United States)

Mínguez-Alarcón, Lidia; Gaskins, Audrey J

2017-08-01

Endocrine disrupting chemicals (EDCs) have been known for their ability to interfere with aspects of hormone action resulting in adverse health consequences among animals and humans; however, the effects of EDCs on human fecundity have shown inconsistent findings. This review summarizes the most recent epidemiologic literature from humans on the potential effects of female exposure to nonpersistent EDCs, specifically bisphenol A (BPA), phthalates, parabens, and triclosan, on fecundity, measured by markers of reproductive hormones, markers of ovulation or ovarian reserve, IVF outcomes, and time-to-pregnancy. Although the epidemiologic literature on this topic is growing, the evidence supporting an association between female urinary concentrations of BPA, phthalates, parabens and triclosan, and fecundity remains unclear. The heterogeneous results could be due to methodological differences in recruitment populations (fertile vs. subfertile), study designs (prospective vs. retrospective), assessment of exposure (including differences in the number and timing of urine samples and differences in the analytical methods used to assess the urinary concentrations), residual confounding due to diet or other lifestyle factors, and coexposures to other chemicals. At present, there is limited evidence to conclude that female exposure to nonpersistent EDCs affect fecundity in humans. Further studies focusing on exposure to mixtures of EDCs are needed.

FAR-TECH's Nanoparticle Plasma Jet System and its Application to Disruptions, Deep Fueling, and Diagnostics

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Thompson, J. R.; Bogatu, I. N.; Galkin, S. A.; Kim, J. S.

2012-10-01

Hyper-velocity plasma jets have potential applications in tokamaks for disruption mitigation, deep fueling and diagnostics. Pulsed power based solid-state sources and plasma accelerators offer advantages of rapid response and mass delivery at high velocities. Fast response is critical for some disruption mitigation scenario needs, while high velocity is especially important for penetration into tokamak plasma and its confining magnetic field, as in the case of deep fueling. FAR-TECH is developing the capability of producing large-mass hyper-velocity plasma jets. The prototype solid-state source has produced: 1) >8.4 mg of H2 gas only, and 2) >25 mg of H2 and >180 mg of C60 in a H2/C60 gas mixture. Using a coaxial plasma gun coupled to the source, we have successfully demonstrated the acceleration of composite H/C60 plasma jets, with momentum as high as 0.6 g.km/s, and containing an estimated C60 mass of ˜75 mg. We present the status of FAR-TECH's nanoparticle plasma jet system and discuss its application to disruptions, deep fueling, and diagnostics. A new TiH2/C60 solid-state source capable of generating significantly higher quantities of H2 and C60 in <0.5 ms will be discussed.

Evaluation of cellular influences caused by calcium carbonate nanoparticles.

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Horie, Masanori; Nishio, Keiko; Kato, Haruhisa; Endoh, Shigehisa; Fujita, Katsuhide; Nakamura, Ayako; Kinugasa, Shinichi; Hagihara, Yoshihisa; Yoshida, Yasukazu; Iwahashi, Hitoshi

2014-03-05

The cellular effects of calcium carbonate (CaCO₃) nanoparticles were evaluated. Three kinds of CaCO₃ nanoparticles were employed in our examinations. One of the types of CaCO₃ nanoparticles was highly soluble. And solubility of another type of CaCO₃ nanoparticle was lower. A stable CaCO₃ nanoparticle medium dispersion was prepared and applied to human lung carcinoma A549 cells and human keratinocyte HaCaT cells. Then, mitochondrial activity, cell membrane damage, colony formation ability, DNA injury, induction of oxidative stress, and apoptosis were evaluated. Although the influences of CaCO₃ nanoparticles on mitochondrial activity and cell membrane damage were small, "soluble" CaCO₃ nanoparticles exerted some cellular influences. Soluble CaCO₃ nanoparticles also induced a cell morphological change. Colony formation was inhibited by CaCO₃ nanoparticle exposure. In particular, soluble CaCO₃ nanoparticles completely inhibited colony formation. The influence on intracellular the reactive oxygen species (ROS) level was small. Soluble CaCO₃ nanoparticles caused an increase in C/EBP-homologous protein (CHOP) expression and the activation of caspase-3. Moreover, CaCO₃ exposure increased intracellular the Ca²⁺ level and activated calpain. These results suggest that cellular the influences of CaCO₃ nanoparticles are mainly caused by intracellular calcium release and subsequently disrupt the effect of calcium signaling. In conclusion, there is possibility that soluble CaCO₃ nanoparticles induce cellular influences such as a cell morphological change. Cellular influence of CaCO₃ nanoparticles is caused by intracellular calcium release. If inhaled CaCO₃ nanoparticles have the potential to influence cellular events. However, the effect might be not severe because calcium is omnipresent element in cell. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of P25 TiO2 Nanoparticles on the Free Radical-Scavenging Ability of Antioxidants upon Their Exposure to Simulated Sunlight.

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Li, Meng; Chong, Yu; Fu, Peter P; Xia, Qingsu; Croley, Timothy R; Lo, Y Martin; Yin, Jun-Jie

2017-11-15

Although nanosized ingredients, including TiO 2 nanoparticles (NPs), can be found in a wide range of consumer products, little is known about the effects these particles have on other active compounds in product matrices. These NPs can interact with reactive oxygen species (ROS), potentially disrupting or canceling the benefits expected from antioxidants. We used electron spin resonance spectrometry to assess changes in the antioxidant capacities of six dietary antioxidants (ascorbic acid, α-tocopherol, glutathione, cysteine, epicatechin, and epicatechin gallate) during exposure to P25 TiO 2 and/or simulated sunlight. Specifically, we determined the ability of these antioxidants to scavenge 1-diphenyl-2-picryl-hydrazyl radical, superoxide radical, and hydroxyl radical. Exposure to simulated sunlight alone did not lead to noticeable changes in radical-scavenging abilities; however, in combination with P25 TiO 2 NPs, the scavenging abilities of most antioxidants were weakened. We found glutathione to be the most resistant to treatment with sunlight and NPs among these six antioxidants.

Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Herbert, Katharine J. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Holloway, Adele [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Cook, Anthony L. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Chin, Suyin P. [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia)

2014-11-15

Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

International Nuclear Information System (INIS)

Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

2014-01-01

Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

Food grade titanium dioxide disrupts intestinal brush border microvilli in vitro independent of sedimentation.

Science.gov (United States)

Faust, James J; Doudrick, Kyle; Yang, Yu; Westerhoff, Paul; Capco, David G

2014-06-01

Bulk- and nano-scale titanium dioxide (TiO2) has found use in human food products for controlling color, texture, and moisture. Once ingested, and because of their small size, nano-scale TiO2 can interact with a number of epithelia that line the human gastrointestinal tract. One such epithelium responsible for nutrient absorption is the small intestine, whose constituent cells contain microvilli to increase the total surface area of the gut. Using a combination of scanning and transmission electron microscopy it was found that food grade TiO2 (E171 food additive coded) included ∼25% of the TiO2 as nanoparticles (NPs; TiO2 sedimentation. It was found that TiO2 isolated from the candy coating of chewing gum and a commercially available TiO2 food grade additive samples were of the anatase crystal structure. Exposure to food grade TiO2 additives, containing nanoparticles, at the lowest concentration tested within this experimental paradigm to date at 350 ng/mL (i.e., 100 ng/cm(2) cell surface area) resulted in disruption of the brush border. Through the use of two independent techniques to remove the effects of gravity, and subsequent TiO2 sedimentation, it was found that disruption of the microvilli was independent of sedimentation. These data indicate that food grade TiO2 exposure resulted in the loss of microvilli from the Caco-2BBe1 cell system due to a biological response, and not simply a physical artifact of in vitro exposure.

Electron-hole pairs generated in ZrO2 nanoparticle resist upon exposure to extreme ultraviolet radiation

Science.gov (United States)

Kozawa, Takahiro; Santillan, Julius Joseph; Itani, Toshiro

2018-02-01

Metal oxide nanoparticle resists have attracted much attention as the next-generation resist used for the high-volume production of semiconductor devices. However, the sensitization mechanism of the metal oxide nanoparticle resists is unknown. Understanding the sensitization mechanism is important for the efficient development of resist materials. In this study, the energy deposition in a zirconium oxide (ZrO2) nanoparticle resist was investigated. The numbers of electron-hole pairs generated in a ZrO2 core and an methacrylic acid (MAA) ligand shell upon exposure to 1 mJ cm-2 (exposure dose) extreme ultraviolet (EUV) radiations were theoretically estimated to be 0.16 at most and 0.04-0.17 cm2 mJ-1, respectively. By comparing the calculated distribution of electron-hole pairs with the line-and-space patterns of the ZrO2 nanoparticle resist fabricated by an EUV exposure tool, the number of electron-hole pairs required for the solubility change of the resist films was estimated to be 1.3-2.2 per NP. NP denotes a nanoparticle consisting of a metal oxide core with a ligand shell. In the material design of metal oxide nanoparticle resists, it is important to efficiently use the electron-hole pairs generated in the metal oxide core for the chemical change of ligand molecules.

A versatile generator of nanoparticle aerosols. A novel tool in environmental and occupational exposure assessment.

Science.gov (United States)

Clemente, Alberto; Lobera, M Pilar; Balas, Francisco; Santamaria, Jesus

2018-06-01

The increasing presence of nanotechnology on the market entails a growing probability of finding ENMs in the environment. Nanoparticles aerosols are a yet unknown risk for human and environmental exposure that may normally occur at any point during the nanomaterial lifecycle. There is a research gap in standardized methods to assess the exposure to airborne nanoparticles in different environments. The controllable generation of nanoparticle aerosols has long been a challenging objective for researchers and industries dealing with airborne nanoparticles. In this work, a versatile system to generate nanoparticulate aerosols has been designed. The system allows the production of both i) instantaneous nanoparticle clouds and ii) continuous nanoparticle streams with quasi-stable values of particle concentration and size distribution. This novel device uses a compressed-air pressure pulse to disperse the target material into either the testing environment (instantaneous cloud formation) or a secondary chamber, from which a continuous aerosol stream can be drawn, with a tunable nanoparticle concentration. The system is robust, highly versatile and easy to operate, enabling reproducible generation of aerosols from a variety of sources. The system has been verified with four dry nanomaterials: TiO 2 , ZnO, CuO and CNT bundles. Copyright © 2017 Elsevier B.V. All rights reserved.

A large-scale association study for nanoparticle C60 uncovers mechanisms of nanotoxicity disrupting the native conformations of DNA/RNA.

Science.gov (United States)

Xu, Xue; Wang, Xia; Li, Yan; Wang, Yonghua; Yang, Ling

2012-09-01

Nano-scale particles have attracted a lot of attention for its potential use in medical studies, in particular for the diagnostic and therapeutic purposes. However, the toxicity and other side effects caused by the undesired interaction between nanoparticles and DNA/RNA are not clear. To address this problem, a model to evaluate the general rules governing how nanoparticles interact with DNA/RNA is demanded. Here by, use of an examination of 2254 native nucleotides with molecular dynamics simulation and thermodynamic analysis, we demonstrate how the DNA/RNA native structures are disrupted by the fullerene (C60) in a physiological condition. The nanoparticle was found to bind with the minor grooves of double-stranded DNA and trigger unwinding and disrupting of the DNA helix, which indicates C60 can potentially inhibit the DNA replication and induce potential side effects. In contrast to that of DNA, C60 only binds to the major grooves of RNA helix, which stabilizes the RNA structure or transforms the configuration from stretch to curl. This finding sheds new light on how C60 inhibits reverse transcription as HIV replicates. In addition, the binding of C60 stabilizes the structures of RNA riboswitch, indicating that C60 might regulate the gene expression. The binding energies of C60 with different genomic fragments varies in the range of -56 to -10 kcal mol(-1), which further verifies the role of nanoparticle in DNA/RNA damage. Our findings reveal a general mode by which C60 causes DNA/RNA damage or other toxic effects at a systematic level, suggesting it should be cautious to handle these nanomaterials in various medical applications.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways.

Science.gov (United States)

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-06-27

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.

Optical imaging to trace near infrared fluorescent zinc oxide nanoparticles following oral exposure

Directory of Open Access Journals (Sweden)

Lee CM

2012-06-01

Full Text Available Chang-Moon Lee,1–4,* Hwan-Jeong Jeong,1–4,* Kuk-No Yun,1–3 Dong Wook Kim,1–4 Myung-Hee Sohn,1–4 Jong Kwon Lee,5 Jayoung Jeong,5 Seok Tae Lim1–4 *These authors contributed equally to this work.1Department of Nuclear Medicine; 2Cyclotron Research Center; 3Research Institute of Clinical Medicine; 4Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Osong-Eup, Chungchungbuk-Do, Republic of KoreaBackground: Understanding how nanomaterials are distributed in the body after exposure is important for assessing whether they are safe. In this study, we investigated the behavior and accumulation of nanoscaled and submicron-scaled zinc oxide (ZnO particles in the body using optical imaging following oral exposure.Methods: To trace these nanoparticles in the body, ZnO nanoparticles were conjugated with a monoreactive hydroxysuccinimide ester of Cy5.5 (Cy5.5-NHS, and the conjugation-stabilizing effect of Cy5.5 on the nanoparticles was evaluated in simulated gastric fluid (pH 1.2 for 7 hours. To compare the distribution of Cy5.5-NHS and Cy5.5-conjugated ZnO nanoparticles, Cy5.5-NHS 0.5 mg/kg and Cy5.5-conjugated ZnO nanoparticles 250 mg/kg were administered orally to healthy rats. We collected blood from the rats at predesignated time points for 7 hours after administration, and optical imaging studies were performed at 1, 2, 3, 5, and 7 hours after dosing. To investigate the extent of nanoparticle accumulation in the organs and tissues, the mice were sacrificed at 23 hours after administration, and the organs were removed and imaged.Results: Cy5.5-conjugated ZnO nanoparticles were stable in simulated gastric fluid for 7 hours. The signal intensity of Cy5.5-NHS in blood was highest 3 hours after oral administration, and Cy5.5-conjugated ZnO nanoparticles showed the highest signal

Isotopically modified silver nanoparticles to assess nanosilver bioavailability and toxicity at environmentally relevant exposures

Science.gov (United States)

Croteau, Marie-Noële; Dybowska, Agnieszka D.; Luoma, Samuel N.; Misra, Superb K.; Valsami-Jones, Eugenia

2014-01-01

A major challenge in understanding the environmental implications of nanotechnology lies in studying nanoparticle uptake in organisms at environmentally realistic exposure concentrations. Typically, high exposure concentrations are needed to trigger measurable effects and to detect accumulation above background. But application of tracer techniques can overcome these limitations. Here we synthesised, for the first time, citrate-coated Ag nanoparticles using Ag that was 99.7 % 109Ag. In addition to conducting reactivity and dissolution studies, we assessed the bioavailability and toxicity of these isotopically modified Ag nanoparticles (109Ag NPs) to a freshwater snail under conditions typical of nature. We showed that accumulation of 109Ag from 109Ag NPs is detectable in the tissues of Lymnaea stagnalis after 24-h exposure to aqueous concentrations as low as 6 ng L–1 as well as after 3 h of dietary exposure to concentrations as low as 0.07 μg g–1. Silver uptake from unlabelled Ag NPs would not have been detected under similar exposure conditions. Uptake rates of 109Ag from 109Ag NPs mixed with food or dispersed in water were largely linear over a wide range of concentrations. Particle dissolution was most important at low waterborne concentrations. We estimated that 70 % of the bioaccumulated 109Ag concentration in L. stagnalis at exposures –1 originated from the newly solubilised Ag. Above this concentration, we predicted that 80 % of the bioaccumulated 109Ag concentration originated from the 109Ag NPs. It was not clear if agglomeration had a major influence on uptake rates.

Effects of C60 nanoparticle exposure on earthworms (Lumbricus rubellus) and implications for population dynamics

International Nuclear Information System (INIS)

Ploeg, M.J.C. van der; Baveco, J.M.; Hout, A. van der; Bakker, R.; Rietjens, I.M.C.M.; Brink, N.W. van den

2011-01-01

Effects of C 60 nanoparticles (nominal concentrations 0, 15.4 and 154 mg/kg soil) on mortality, growth and reproduction of Lumbricus rubellus earthworms were assessed. C 60 exposure had a significant effect on cocoon production, juvenile growth rate and mortality. These endpoints were used to model effects on the population level. This demonstrated reduced population growth rate with increasing C 60 concentrations. Furthermore, a shift in stage structure was shown for C 60 exposed populations, i.e. a larger proportion of juveniles. This result implies that the lower juvenile growth rate due to exposure to C 60 resulted in a larger proportion of juveniles, despite increased mortality among juveniles. Overall, this study indicates that C 60 exposure may seriously affect earthworm populations. Furthermore, it was demonstrated that juveniles were more sensitive to C 60 exposure than adults. - C 60 nanoparticle exposure can affect Lumbricus rubellus populations.

Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review.

Science.gov (United States)

Giulivo, Monica; Lopez de Alda, Miren; Capri, Ettore; Barceló, Damià

2016-11-01

Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel approach reveals that zinc oxide nanoparticles are bioavailable and toxic after dietary exposures

Science.gov (United States)

Croteau, M.-N.; Dybowska, A.D.; Luoma, S.N.; Valsami-Jones, E.

2011-01-01

If engineered nanomaterials are released into the environment, some are likely to end up associated with the food of animals due to aggregation and sorption processes. However, few studies have considered dietary exposure of nanomaterials. Here we show that zinc (Zn) from isotopically modified 67ZnO particles is efficiently assimilated by freshwater snails when ingested with food. The 67Zn from nano-sized 67ZnO appears as bioavailable as 67Zn internalized by diatoms. Apparent agglomeration of the zinc oxide (ZnO) particles did not reduce bioavailability, nor preclude toxicity. In the diet, ZnO nanoparticles damage digestion: snails ate less, defecated less and inefficiently processed the ingested food when exposed to high concentrations of ZnO. It was not clear whether the toxicity was due to the high Zn dose achieved with nanoparticles or to the ZnO nanoparticles themselves. Further study of exposure from nanoparticles in food would greatly benefit assessment of ecological and human health risks. ?? 2011 Informa UK, Ltd.

Different routes, same pathways: Molecular mechanisms under silver ion and nanoparticle exposures in the soil sentinel Eisenia fetida

International Nuclear Information System (INIS)

Novo, Marta; Lahive, Elma; Díez-Ortiz, María; Matzke, Marianne; Morgan, Andrew J.; Spurgeon, David J.; Svendsen, Claus; Kille, Peter

2015-01-01

Use of nanotechnology products is increasing; with silver (Ag) nanoparticles particularly widely used. A key uncertainty surrounding the risk assessment of AgNPs is whether their effects are driven through the same mechanism of action that underlies the toxic effects of Ag ions. We present the first full transcriptome study of the effects of Ag ions and NPs in an ecotoxicological model soil invertebrate, the earthworm Eisenia fetida. Gene expression analyses indicated similar mechanisms for both silver forms with toxicity being exerted through pathways related to ribosome function, sugar and protein metabolism, molecular stress, disruption of energy production and histones. The main difference seen between Ag ions and NPs was associated with potential toxicokinetic effects related to cellular internalisation and communication, with pathways related to endocytosis and cilia being significantly enriched. These results point to a common final toxicodynamic response, but initial internalisation driven by different exposure routes and toxicokinetic mechanisms. - Highlights: • Molecular effects underlying Ag ions and NPs exposure were studied in Eisenia fetida. • Full transcriptomic study of a genetically characterised lineage. • NPs and ions presented a similar toxicodynamic response. • Internalisation of the two Ag forms by different toxicokinetic mechanisms. - Transcriptomic analyses after exposure of earthworms to silver NPs or ions showed a final common toxicodynamic response, but internalisation by different toxicokinetic mechanisms

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters.

Science.gov (United States)

Isling, Louise Krag; Boberg, Julie; Jacobsen, Pernille Rosenskjold; Mandrup, Karen Riiber; Axelstad, Marta; Christiansen, Sofie; Vinggaard, Anne Marie; Taxvig, Camilla; Kortenkamp, Andreas; Hass, Ulla

2014-01-01

This study examined late-life effects of perinatal exposure of rats to a mixture of endocrine-disrupting contaminants. Four groups of 14 time-mated Wistar rats were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti-androgenic and estrogenic chemicals including phthalates, pesticides, u.v.-filters, bisphenol A, parabens, and the drug paracetamol. The groups received vehicle (control), a mixture of all 13 chemicals at 150-times (TotalMix150) or 450-times (TotalMix450) high-end human exposure, or 450-times a mixture of nine predominantly anti-androgenic chemicals (AAMix450). Onset of puberty and estrous cyclicity at 9 and 12 months of age were assessed. Few female offspring showed significantly regular estrus cyclicity at 12 months of age in the TotalMix450 and AAMix450 groups compared with controls. In 19-month-old male offspring, epididymal sperm counts were lower than controls, and in ventral prostate an overrepresentation of findings related to hyperplasia was observed in exposed groups compared with controls, particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the AAMix450 group. Developmental exposure of rats to the highest dose of a human-relevant mixture of endocrine disrupters induced adverse effects late in life, manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia, and higher incidence of pituitary tumors. These delayed effects highlight the need for further studies on the role of endocrine disrupters in hormone-related disorders in aging humans.

Effect of copper nanoparticles exposure in the physiology of the common carp (Cyprinus carpio: Biochemical, histological and proteomic approaches

Directory of Open Access Journals (Sweden)

Yugantak Raj Gupta

2016-12-01

Full Text Available Copper nanoparticles (Cu-NPs are serious water pollutants but their impact in teleosts performance remains poorly understood. In the present study, we have exposed juvenile carps (Cyprinus carpio, a freshwater teleost edible in India to two different doses (20 and 100 μg/L of Cu-NPs for seven days. The doses selected were eco-relevant considering the contamination levels of certain water resources. The results indicated that the activity oxidative stress enzymes catalase, superoxide dismutase, and glutathione-S-transferase were significantly increased in the kidney, liver and gills of the treated groups when compared to control. Histological analysis revealed that after exposure, disruption of the secondary lamellae of gills, liver damage with pyknotic nuclei and structural disarray of the kidney occurred. Proteomic analysis of the liver showed down-regulation of several proteins including the ferritin heavy chain, rho guanine nucleotide exchange factor 17-like, cytoglobin-1 and up-regulation of diphosphomevalonate decarboxylase and selenide & water dikinase-1. Taken together, the results of suggest that short-term exposure of juvenile carp to Cu-NPs causes oxidative stress and impart serious deleterious effects in the tissues which may affect fish growth and development.

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders

DEFF Research Database (Denmark)

Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie

2017-01-01

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several con...

Process-generated nanoparticles from ceramic tile sintering: Emissions, exposure and environmental release.

Science.gov (United States)

Fonseca, A S; Maragkidou, A; Viana, M; Querol, X; Hämeri, K; de Francisco, I; Estepa, C; Borrell, C; Lennikov, V; de la Fuente, G F

2016-09-15

The ceramic industry is an industrial sector in need of significant process changes, which may benefit from innovative technologies such as laser sintering of ceramic tiles. Such innovations result in a considerable research gap within exposure assessment studies for process-generated ultrafine and nanoparticles. This study addresses this issue aiming to characterise particle formation, release mechanisms and their impact on personal exposure during a tile sintering activity in an industrial-scale pilot plant, as a follow-up of a previous study in a laboratory-scale plant. In addition, possible particle transformations in the exhaust system, the potential for particle release to the outdoor environment, and the effectiveness of the filtration system were also assessed. For this purpose, a tiered measurement strategy was conducted. The main findings evidence that nanoparticle emission patterns were strongly linked to temperature and tile chemical composition, and mainly independent of the laser treatment. Also, new particle formation (from gaseous precursors) events were detected, with nanoparticles efficiency of the filtration system was successfully tested and evidenced a >87% efficiency in particle number concentrations removal. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust

Energy Technology Data Exchange (ETDEWEB)

Win-Shwe, Tin-Tin, E-mail: tin.tin.win.shwe@nies.go.jp [Center for Environmental Health Sciences, National Institute for Environmental Studies, 16‐2 Onogawa, Tsukuba, Ibaraki 305‐8506 (Japan); Fujimaki, Hidekazu; Fujitani, Yuji; Hirano, Seishiro [Center for Environmental Risk Research, National Institute for Environmental Studies, 16‐2 Onogawa, Tsukuba, Ibaraki 305‐8506 (Japan)

2012-08-01

Recently, our laboratory reported that exposure to nanoparticle-rich diesel exhaust (NRDE) for 3 months impaired hippocampus-dependent spatial learning ability and up-regulated the expressions of memory function-related genes in the hippocampus of female mice. However, whether NRDE affects the hippocampus-dependent non-spatial learning ability and the mechanism of NRDE-induced neurotoxicity was unknown. Female BALB/c mice were exposed to clean air, middle-dose NRDE (M-NRDE, 47 μg/m{sup 3}), high-dose NRDE (H-NRDE, 129 μg/m{sup 3}), or filtered H-NRDE (F-DE) for 3 months. We then investigated the effect of NRDE exposure on non-spatial learning ability and the expression of genes related to glutamate neurotransmission using a novel object recognition test and a real-time RT-PCR analysis, respectively. We also examined microglia marker Iba1 immunoreactivity in the hippocampus using immunohistochemical analyses. Mice exposed to H-NRDE or F-DE could not discriminate between familiar and novel objects. The control and M-NRDE-exposed groups showed a significantly increased discrimination index, compared to the H-NRDE-exposed group. Although no significant changes in the expression levels of the NMDA receptor subunits were observed, the expression of glutamate transporter EAAT4 was decreased and that of glutamic acid decarboxylase GAD65 was increased in the hippocampus of H-NRDE-exposed mice, compared with the expression levels in control mice. We also found that microglia activation was prominent in the hippocampal area of the H-NRDE-exposed mice, compared with the other groups. These results indicated that exposure to NRDE for 3 months impaired the novel object recognition ability. The present study suggests that genes related to glutamate metabolism may be involved in the NRDE-induced neurotoxicity observed in the present mouse model. -- Highlights: ► The effects of nanoparticle-induced neurotoxicity remain unclear. ► We investigated the effect of exposure to

Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust

International Nuclear Information System (INIS)

Win-Shwe, Tin-Tin; Fujimaki, Hidekazu; Fujitani, Yuji; Hirano, Seishiro

2012-01-01

Recently, our laboratory reported that exposure to nanoparticle-rich diesel exhaust (NRDE) for 3 months impaired hippocampus-dependent spatial learning ability and up-regulated the expressions of memory function-related genes in the hippocampus of female mice. However, whether NRDE affects the hippocampus-dependent non-spatial learning ability and the mechanism of NRDE-induced neurotoxicity was unknown. Female BALB/c mice were exposed to clean air, middle-dose NRDE (M-NRDE, 47 μg/m 3 ), high-dose NRDE (H-NRDE, 129 μg/m 3 ), or filtered H-NRDE (F-DE) for 3 months. We then investigated the effect of NRDE exposure on non-spatial learning ability and the expression of genes related to glutamate neurotransmission using a novel object recognition test and a real-time RT-PCR analysis, respectively. We also examined microglia marker Iba1 immunoreactivity in the hippocampus using immunohistochemical analyses. Mice exposed to H-NRDE or F-DE could not discriminate between familiar and novel objects. The control and M-NRDE-exposed groups showed a significantly increased discrimination index, compared to the H-NRDE-exposed group. Although no significant changes in the expression levels of the NMDA receptor subunits were observed, the expression of glutamate transporter EAAT4 was decreased and that of glutamic acid decarboxylase GAD65 was increased in the hippocampus of H-NRDE-exposed mice, compared with the expression levels in control mice. We also found that microglia activation was prominent in the hippocampal area of the H-NRDE-exposed mice, compared with the other groups. These results indicated that exposure to NRDE for 3 months impaired the novel object recognition ability. The present study suggests that genes related to glutamate metabolism may be involved in the NRDE-induced neurotoxicity observed in the present mouse model. -- Highlights: ► The effects of nanoparticle-induced neurotoxicity remain unclear. ► We investigated the effect of exposure to

Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis

Science.gov (United States)

Birks, Laura; Casas, Maribel; Garcia, Ana M.; Alexander, Jan; Barros, Henrique; Bergström, Anna; Bonde, Jens Peter; Burdorf, Alex; Costet, Nathalie; Danileviciute, Asta; Eggesbø, Merete; Fernández, Mariana F.; González-Galarzo, M. Carmen; Hanke, Wojciech; Jaddoe, Vincent; Kogevinas, Manolis; Kull, Inger; Lertxundi, Aitana; Melaki, Vasiliki; Andersen, Anne-Marie Nybo; Olea, Nicolás; Polanska, Kinga; Rusconi, Franca; Santa-Marina, Loreto; Santos, Ana Cristina; Vrijkotte, Tanja; Zugna, Daniela; Nieuwenhuijsen, Mark; Cordier, Sylvaine; Vrijheid, Martine

2016-01-01

Background: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth. Objectives: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery. Methods: Using individual participant data from 133,957 mother–child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates. Results: Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW [odds ratio (OR) = 1.25; 95% CI: 1.04, 1.49], as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR = 2.11; 95% CI: 1.10, 4.06 for exposure to four or more EDC groups). There were few associations (p Olea N, Polanska K, Rusconi F, Santa-Marina L, Santos AC, Vrijkotte T, Zugna D, Nieuwenhuijsen M, Cordier S, Vrijheid M. 2016. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: a European meta-analysis. Environ Health Perspect 124:1785–1793; http://dx.doi.org/10.1289/EHP208 PMID:27152464

Gold Nanoparticles for the Detection of DNA Adducts as Biomarkers of Exposure to Acrylamide

Science.gov (United States)

Larguinho, Miguel Angelo Rodrigues

The main objective of this thesis was the development of a gold nanoparticle-based methodology for detection of DNA adducts as biomarkers, to try and overcome existing drawbacks in currently employed techniques. For this objective to be achieved, the experimental work was divided in three components: sample preparation, method of detection and development of a model for exposure to acrylamide. Different techniques were employed and combined for de-complexation and purification of DNA samples (including ultrasonic energy, nuclease digestion and chromatography), resulting in a complete protocol for sample treatment, prior to detection. The detection of alkylated nucleotides using gold nanoparticles was performed by two distinct methodologies: mass spectrometry and colorimetric detection. In mass spectrometry, gold nanoparticles were employed for laser desorption/ionisation instead of the organic matrix. Identification of nucleotides was possible by fingerprint, however no specific mass signals were denoted when using gold nanoparticles to analyse biological samples. An alternate method using the colorimetric properties of gold nanoparticles was employed for detection. This method inspired in the non-cross-linking assay allowed the identification of glycidamide-guanine adducts and DNA adducts generated in vitro. For the development of a model of exposure, two different aquatic organisms were studies: a goldfish and a mussel. Organisms were exposed to waterborne acrylamide, after which mortality was recorded and effect concentrations were estimated. In goldfish, both genotoxicity and metabolic alterations were assessed and revealed dose-effect relationships of acrylamide. Histopathological alterations were verified primarily in pancreatic cells, but also in hepatocytes. Mussels showed higher effect concentrations than goldfish. Biomarkers of oxidative stress, biotransformation and neurotoxicity were analysed after prolonged exposure, showing mild oxidative stress in

Thyroid stimulating hormone levels in newborns and early life exposure to endocrine disrupting chemicals - analysis of three European mother-child cohorts

NARCIS (Netherlands)

de Cock, Marijke; de Boer, Michiel R; Govarts, Eva; Iszatt, Nina; Palkovicova, Lubica; Lamoree, Marja H; Schoeters, Greet; Eggesbø, Merete; Trnovec, Tomas; Legler, Juliette; van de Bor, Margot

2017-01-01

BACKGROUND: Various studies report interactions between thyroid hormones and early life chemical exposure. Our objective was to analyse associations between markers of endocrine disrupting chemical exposure and thyroid function in newborns, determined in heel prick blood spots. METHODS: Three

The role of peri-traumatic stress and disruption distress in predicting symptoms of major depression following exposure to a natural disaster.

Science.gov (United States)

Bell, Caroline J; Boden, Joseph M; Horwood, L John; Mulder, Roger T

2017-07-01

Few studies have examined the contribution of specific disaster-related experiences to symptoms of depression. The aims of this study were to do this by examining the roles of peri-traumatic stress and distress due to lingering disaster-related disruption in explaining linkages between disaster exposure and major depressive disorder symptoms among a cohort exposed to the 2010-2011 Canterbury (New Zealand) earthquakes. Structural equation models were fitted to data obtained from the Christchurch Health and Development Study at age 35 ( n = 495), 20-24 months following the onset of the disaster. Measures included earthquake exposure, peri-traumatic stress, disruption distress and symptoms of major depressive disorder. The associations between earthquake exposure and major depression were explained largely by the experience of peri-traumatic stress during the earthquakes (β = 0.180, p < 0.01) and not by disruption distress following the earthquakes (β = 0.048, p = 0.47). The results suggest that peri-traumatic stress has been under-recognised as a predictor of major depressive disorder.

Strategy for the lowering and the assessment of exposure to nanoparticles at workspace - Case of study concerning the potential emission of nanoparticles of Lead in an epitaxy laboratory

International Nuclear Information System (INIS)

Artous, Sébastien; Zimmermann, Eric; Locatelli, Dominique; Motellier, Sylvie; Derrough, Samir; Douissard, Paul-Antoine

2015-01-01

The implementation in many products of manufactured nanoparticles is growing fast and raises new questions. For this purpose, the CEA - NanoSafety Platform is developing various research topics for health and safety, environment and nanoparticles exposure in professional activities. The containment optimisation for the exposition lowering, then the exposure assessment to nanoparticles is a strategy for safety improvement at workplace and workspace. The lowering step consists in an optimisation of dynamic and static containment at workplace and/or workspace. Generally, the exposure risk due to the presence of nanoparticles substances does not allow modifying the parameters of containment at workplace and/or workspace. Therefore, gaseous or nanoparticulate tracers are used to evaluate performances of containment. Using a tracer allows to modify safely the parameters of the dynamic containment (ventilation, flow, speed) and to study several configurations of static containment. Moreover, a tracer allows simulating accidental or incidental situation. As a result, a safety procedure can be written more easily in order to manage this type of situation. The step of measurement and characterization of aerosols can therefore be used to assess the exposition at workplace and workspace. The case of study, aim of this paper, concerns the potential emission of Lead nanoparticles at the exhaust of a furnace in an epitaxy laboratory. The use of Helium tracer to evaluate the performance of containment is firstly studied. Secondly, the exposure assessment is characterised in accordance with the French guide “recommendations for characterizing potential emissions and exposure to aerosols released from nanomaterials in workplace operations”. Thirdly the aerosols are sampled, on several places, using collection membranes to try to detect traces of Lead in air. (paper)

Strategy for the lowering and the assessment of exposure to nanoparticles at workspace - Case of study concerning the potential emission of nanoparticles of Lead in an epitaxy laboratory

Science.gov (United States)

Artous, Sébastien; Zimmermann, Eric; Douissard, Paul-Antoine; Locatelli, Dominique; Motellier, Sylvie; Derrough, Samir

2015-05-01

The implementation in many products of manufactured nanoparticles is growing fast and raises new questions. For this purpose, the CEA - NanoSafety Platform is developing various research topics for health and safety, environment and nanoparticles exposure in professional activities. The containment optimisation for the exposition lowering, then the exposure assessment to nanoparticles is a strategy for safety improvement at workplace and workspace. The lowering step consists in an optimisation of dynamic and static containment at workplace and/or workspace. Generally, the exposure risk due to the presence of nanoparticles substances does not allow modifying the parameters of containment at workplace and/or workspace. Therefore, gaseous or nanoparticulate tracers are used to evaluate performances of containment. Using a tracer allows to modify safely the parameters of the dynamic containment (ventilation, flow, speed) and to study several configurations of static containment. Moreover, a tracer allows simulating accidental or incidental situation. As a result, a safety procedure can be written more easily in order to manage this type of situation. The step of measurement and characterization of aerosols can therefore be used to assess the exposition at workplace and workspace. The case of study, aim of this paper, concerns the potential emission of Lead nanoparticles at the exhaust of a furnace in an epitaxy laboratory. The use of Helium tracer to evaluate the performance of containment is firstly studied. Secondly, the exposure assessment is characterised in accordance with the French guide “recommendations for characterizing potential emissions and exposure to aerosols released from nanomaterials in workplace operations”. Thirdly the aerosols are sampled, on several places, using collection membranes to try to detect traces of Lead in air.

Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits.

Science.gov (United States)

Renteria, Rafael; Baltz, Emily T; Gremel, Christina M

2018-01-15

Addiction involves a predominance of habitual control mediated through action selection processes in dorsal striatum. Research has largely focused on neural mechanisms mediating a proposed progression from ventral to dorsal lateral striatal control in addiction. However, over reliance on habit striatal processes may also arise from reduced cortical input to striatum, thereby disrupting executive control over action selection. Here, we identify novel mechanisms through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts top-down control over goal-directed action selection processes to produce habits. We find CIE results in decreased excitability of orbital frontal cortex (OFC) excitatory circuits supporting goal-directed control, and, strikingly, selectively reduces OFC output to the direct output pathway in dorsal medial striatum. Increasing the activity of OFC circuits restores goal-directed control in CIE-exposed mice. Our findings show habitual control in alcohol dependence can arise through disrupted communication between top-down, goal-directed processes onto basal ganglia pathways controlling action selection.

Effects of C{sub 60} nanoparticle exposure on earthworms (Lumbricus rubellus) and implications for population dynamics

Energy Technology Data Exchange (ETDEWEB)

Ploeg, M.J.C. van der, E-mail: merel.vanderploeg@wur.n [Alterra, Wageningen UR, Droevendaalssesteeg 3, 6700 AA, Wageningen (Netherlands); Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE, Wageningen (Netherlands); Baveco, J.M.; Hout, A. van der [Alterra, Wageningen UR, Droevendaalssesteeg 3, 6700 AA, Wageningen (Netherlands); Bakker, R. [RIKILT, Wageningen UR, Akkermaalsbos 2, 6708 WB, Wageningen (Netherlands); Rietjens, I.M.C.M. [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE, Wageningen (Netherlands); Brink, N.W. van den [Alterra, Wageningen UR, Droevendaalssesteeg 3, 6700 AA, Wageningen (Netherlands)

2011-01-15

Effects of C{sub 60} nanoparticles (nominal concentrations 0, 15.4 and 154 mg/kg soil) on mortality, growth and reproduction of Lumbricus rubellus earthworms were assessed. C{sub 60} exposure had a significant effect on cocoon production, juvenile growth rate and mortality. These endpoints were used to model effects on the population level. This demonstrated reduced population growth rate with increasing C{sub 60} concentrations. Furthermore, a shift in stage structure was shown for C{sub 60} exposed populations, i.e. a larger proportion of juveniles. This result implies that the lower juvenile growth rate due to exposure to C{sub 60} resulted in a larger proportion of juveniles, despite increased mortality among juveniles. Overall, this study indicates that C{sub 60} exposure may seriously affect earthworm populations. Furthermore, it was demonstrated that juveniles were more sensitive to C{sub 60} exposure than adults. - C{sub 60} nanoparticle exposure can affect Lumbricus rubellus populations.

Mercury exposure induces cytoskeleton disruption and loss of renal function through epigenetic modulation of MMP9 expression.

Science.gov (United States)

Khan, Hafizurrahman; Singh, Radha Dutt; Tiwari, Ratnakar; Gangopadhyay, Siddhartha; Roy, Somendu Kumar; Singh, Dhirendra; Srivastava, Vikas

2017-07-01

Mercury is one of the major heavy metal pollutants occurring in elemental, inorganic and organic forms. Due to ban on most inorganic mercury containing products, human exposure to mercury generally occurs as methylmercury (MeHg) by consumption of contaminated fish and other sea food. Animal and epidemiological studies indicate that MeHg affects neural and renal function. Our study is focused on nephrotoxic potential of MeHg. In this study, we have shown for the first time how MeHg could epigenetically modulate matrix metalloproteinase 9(MMP9) to promote nephrotoxicity using an animal model of sub chronic MeHg exposure. MeHg caused renal toxicity as was seen by increased levels of serum creatinine and expression of early nephrotoxicity markers (KIM-1, Clusterin, IP-10, and TIMP). MeHg exposure also correlated strongly with induction of MMP9 mRNA and protein in a dose dependent manner. Further, while induction of MMP9 promoted cytoskeleton disruption and loss of cell-cell adhesion (loss of F-actin, Vimentin and Fibronectin), inhibition of MMP9 was found to reduce these disruptions. Mechanistic studies by ChIP analysis showed that MeHg modulated MMP9 by promoting demethylation of its regulatory region to increase its expression. Bisulfite sequencing identified critical CpGs in the first exon of MMP9 which were demethylated following MeHg exposure. ChIP studies also showed loss of methyl binding protein, MeCP2 and transcription factor PEA3 at the demethylated site confirming decreased CpG methylation. Our studies thus show how MeHg could epigenetically modulate MMP9 to promote cytoskeleton disruption leading to loss of renal function. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro inflammatory effects of hard metal (WC–Co nanoparticle exposure

Directory of Open Access Journals (Sweden)

Armstead AL

2016-11-01

Full Text Available Andrea L Armstead,1,2 Bingyun Li1–3 1Department of Orthopaedics, School of Medicine, 2School of Pharmacy, West Virginia University, 3Mary Babb Randolph Cancer Center, Morgantown, WV, USA Abstract: Identifying the toxicity of nanoparticles (NPs is an important area of research as the number of nanomaterial-based consumer and industrial products continually rises. In addition, the potential inflammatory effects resulting from pulmonary NP exposure are emerging as an important aspect of nanotoxicity. In this study, the toxicity and inflammatory state resulting from tungsten carbide–cobalt (WC–Co NP exposure in macrophages and a coculture (CC of lung epithelial cells (BEAS-2B and macrophages (THP-1 at a 3:1 ratio were examined. It was found that the toxicity of nano-WC–Co was cell dependent; significantly less toxicity was observed in THP-1 cells compared to BEAS-2B cells. It was demonstrated that nano-WC–Co caused reduced toxicity in the CC model compared to lung epithelial cell monoculture, which suggested that macrophages may play a protective role against nano-WC–Co-mediated toxicity in CCs. Nano-WC–Co exposure in macrophages resulted in increased levels of interleukin (IL-1β and IL-12 secretion and decreased levels of tumor necrosis factor alpha (TNFα. In addition, the polarizing effects of nano-WC–Co exposure toward the M1 (pro-inflammatory and M2 (anti-inflammatory macrophage phenotypes were investigated. The results of this study indicated that nano-WC–Co exposure stimulated the M1 phenotype, marked by high expression of CD40 M1 macrophage surface markers. Keywords: nanoparticle, nanotoxicity, inflammation, macrophage, lung disease 

Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs

Directory of Open Access Journals (Sweden)

Kevin M. Rice

2015-05-01

Full Text Available Objectives: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2 nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs. Methods: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis. Results: No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05. Conclusions: Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.

Cytotoxicity and inflammation in human alveolar epithelial cells following exposure to occupational levels of gold and silver nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Bachand, George D., E-mail: gdbacha@sandia.gov [Sandia National Laboratories, Center for Integrated Nanotechnologies (United States); Allen, Amy [Sandia National Laboratories, Department of Analytical Science (United States); Bachand, Marlene [Sandia National Laboratories, Department of Nanobiology (United States); Achyuthan, Komandoor E. [Sandia National Laboratories, Department of Biosensors and Nanomaterials (United States); Seagrave, Jean Clare [Lovelace Respiratory Research Institute, Applied Life Science and Toxicology Division (United States); Brozik, Susan M. [Sandia National Laboratories, Department of Biosensors and Nanomaterials (United States)

2012-10-15

While inhalation represents one of the most likely routes of exposure, the toxicity and response of nanoparticles at concentrations expected from such an exposure are not well understood. Here we characterized the in vitro response of human A549 adenocarcinomic alveolar epithelial cells following exposure to gold (AuNP) and silver (AgNP) nanoparticles at levels approximating an occupational exposure. Changes in neither oxidative stress nor cytotoxicity were significantly affected by exposure to AgNPs and AuNPs, regardless of NP type (Ag vs. Au), concentration, surface ligand (citrate or tannic acid), or size. An inflammatory response was, however, observed in response to 20 nm AgNPs and 20 nm AuNPs, where significant differences in the release of interleukin (IL)-8 but not IL-6 were observed. Additional data demonstrated that increased IL-8 secretion was strongly dependent on both nanoparticle size and concentration. Overall these data suggest that, while not acutely toxic, occupational exposure to AuNPs and AgNPs may trigger a significant inflammatory response in alveolar epithelium. Moreover, the differential responses in IL-8 and IL-6 secretion suggest that NPs may induce a response pathway that is distinct from those commonly elicited by allergens and pathogens.

Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

Science.gov (United States)

Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

2016-04-01

Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. Copyright © 2015 John Wiley & Sons, Ltd.

Chronic exposure of zinc oxide nanoparticles causes deviant phenotype in Drosophila melanogaster

Energy Technology Data Exchange (ETDEWEB)

Anand, Avnika Singh; Prasad, Dipti N.; Singh, Shashi Bala; Kohli, Ekta, E-mail: ektakohli@hotmail.com

2017-04-05

Zinc oxide nanoparticles (ZnO NPs) are commonly used nanomaterials (NMs) with versatile applications from high-end technologies to household products. This pervasive utilisation has brought human in the close interface with nanoparticles (NPs), hence questioning their safety prior to usage is a must. In this study, we have assessed the effects of chronic exposure to ZnO NPs (<50 nm) on the model organism Drosophila melanogaster. Potential toxic effects were studied by evaluating longevity, climbing ability, oxidative stress and DNA fragmentation. Ensuing exposure, the F0 (parent), F1, F2, F3 and F4 generation flies were screened for the aberrant phenotype. Flies exposed to ZnO NPs showed distinctive phenotypic changes, like deformed segmented thorax and single or deformed wing, which were transmitted to the offspring’s in subsequent generations. The unique abnormal phenotype is evident of chronic toxicity induced by ZnO NPs, although appalling, it strongly emphasize the importance to understand NPs toxicity for safer use.

Not all that glitters is gold-Electron microscopy study on uptake of gold nanoparticles in Daphnia magna and related artifacts.

Science.gov (United States)

Jensen, Louise Helene Søgaard; Skjolding, Lars Michael; Thit, Amalie; Sørensen, Sara Nørgaard; Købler, Carsten; Mølhave, Kristian; Baun, Anders

2017-06-01

Increasing use of engineered nanoparticles has led to extensive research into their potential hazards to the environment and human health. Cellular uptake from the gut is sparsely investigated, and microscopy techniques applied for uptake studies can result in misinterpretations. Various microscopy techniques were used to investigate internalization of 10-nm gold nanoparticles in Daphnia magna gut lumen and gut epithelial cells following 24-h exposure and outline potential artifacts (i.e., high-contrast precipitates from sample preparation related to these techniques). Light sheet microscopy confirmed accumulation of gold nanoparticles in the gut lumen. Scanning transmission electron microscopy and elemental analysis revealed gold nanoparticles attached to the microvilli of gut cells. Interestingly, the peritrophic membrane appeared to act as a semipermeable barrier between the lumen and the gut epithelium, permitting only single particles through. Structures resembling nanoparticles were also observed inside gut cells. Elemental analysis could not verify these to be gold, and they were likely artifacts from the preparation, such as osmium and iron. Importantly, gold nanoparticles were found inside holocrine cells with disrupted membranes. Thus, false-positive observations of nanoparticle internalization may result from either preparation artifacts or mistaking disrupted cells for intact cells. These findings emphasize the importance of cell integrity and combining elemental analysis with the localization of internalized nanoparticles using transmission electron microscopy. Environ Toxicol Chem 2017;36:1503-1509. © 2016 SETAC. © 2016 SETAC.

Prenatal exposure to vinclozolin disrupts selective aspects of the gonadotropin-releasing hormone neuronal system of the rabbit

OpenAIRE

Wadas, B.C.; Hartshorn, C.A.; Aurand, E.R.; Palmer, J.S.; Roselli, C.E.; Noel, M.L.; Gore, A.C.; Veeramachaneni, D.N.R.; Tobet, S.A.

2010-01-01

Developmental exposure to the agricultural fungicide vinclozolin can impair reproductive function in male rabbits and was previously found to decrease the number of immunoreactive-gonadotropin-releasing hormone (ir-GnRH) neurons in the region of the organum vasculosum of the lamina terminalis (OVLT) and rostral preoptic area (rPOA) by postnatal week (PNW) 6. To further examine the disruption of GnRH neurons by fetal vinclozolin exposure, in the current study, pregnant rabbits were dosed orall...

Biosynthesis of silver nanoparticle and its application in cell wall disruption to release carbohydrate and lipid from C. vulgaris for biofuel production

Directory of Open Access Journals (Sweden)

Sirajunnisa Abdul Razack

2016-09-01

Full Text Available Microalgae are the fledging feedstocks yielding raw materials for the production of third generation biofuel. Assorted and conventional cell wall disruption techniques were helpful in extracting lipids and carbohydrates, nevertheless the disadvantages have led the biotechnologists to explore new process to lyse cell wall in a faster and an economical manner. Silver nanoparticles have the ability to break the cell wall of microalgae and release biomolecules effectively. Green synthesis of silver nanoparticles was performed using a novel bacterial isolate of Bacillus subtilis. Characterisation of nanosilver and its effect on cell wall lysis of microalgae were extensively analysed. Cell wall damage was confirmed by lactate dehydrogenase assay and visually by SEM analysis. This first piece of research work on direct use of nanoparticles for cell wall lysis would potentially be advantageous over its conventional approaches and a greener, cost effective and non laborious method for the production of biodiesel.

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

Science.gov (United States)

Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

2015-07-15

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects

Directory of Open Access Journals (Sweden)

Swapnalee Sarmah

2013-08-01

Fetal alcohol spectrum disorder (FASD occurs when pregnant mothers consume alcohol, causing embryonic ethanol exposure and characteristic birth defects that include craniofacial, neural and cardiac defects. Gastrulation is a particularly sensitive developmental stage for teratogen exposure, and zebrafish is an outstanding model to study gastrulation and FASD. Epiboly (spreading blastomere cells over the yolk cell, prechordal plate migration and convergence/extension cell movements are sensitive to early ethanol exposure. Here, experiments are presented that characterize mechanisms of ethanol toxicity on epiboly and gastrulation. Epiboly mechanisms include blastomere radial intercalation cell movements and yolk cell microtubule cytoskeleton pulling the embryo to the vegetal pole. Both of these processes were disrupted by ethanol exposure. Ethanol effects on cell migration also indicated that cell adhesion was affected, which was confirmed by cell aggregation assays. E-cadherin cell adhesion molecule expression was not affected by ethanol exposure, but E-cadherin distribution, which controls epiboly and gastrulation, was changed. E-cadherin was redistributed into cytoplasmic aggregates in blastomeres and dramatically redistributed in the extraembryonic yolk cell. Gene expression microarray analysis was used to identify potential causative factors for early development defects, and expression of the cell adhesion molecule protocadherin-18a (pcdh18a, which controls epiboly, was significantly reduced in ethanol exposed embryos. Injecting pcdh18a synthetic mRNA in ethanol treated embryos partially rescued epiboly cell movements, including enveloping layer cell shape changes. Together, data show that epiboly and gastrulation defects induced by ethanol are multifactorial, and include yolk cell (extraembryonic tissue microtubule cytoskeleton disruption and blastomere adhesion defects, in part caused by reduced pcdh18a expression.

Silver nanoparticles cause complications in pregnant mice

Directory of Open Access Journals (Sweden)

Zhang XF

2015-11-01

Full Text Available Xi-Feng Zhang,1,2 Jung-Hyun Park,1 Yun-Jung Choi,1 Min-Hee Kang,1 Sangiliyandi Gurunathan,1 Jin-Hoi Kim11Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea; 2College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People’s Republic of ChinaBackground: Silver nanoparticles (AgNPs have attracted much interest and have been used for antibacterial, antifungal, anticancer, and antiangiogenic applications because of their unique properties. The increased usage of AgNPs leads to a potential hazard to human health. However, the potential effects of AgNPs on animal models are not clear. This study was designed to investigate the potential impact of AgNPs on pregnant mice.Methods: The synthesis of AgNPs was performed using culture extracts of Bacillus cereus. The synthesized AgNPs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. AgNPs were administrated into pregnant mice via intravenous infusion at 1.0 mg/kg doses at 6.5 days postcoitum (dpc. At 13.5, 15.5, and 17.5 dpc, the pregnant mice were euthanized, and the embryo and placenta were isolated. The meiotic status of oocytes was evaluated. DNA methylation studies were performed, and aberrant imprinting disrupted fetal, placental, and postnatal development. Quantitative real-time polymerase chain reaction analysis and Western blot were used to analyze various gene expressions.Results: The synthesized AgNPs were uniformly distributed and were spherical in shape with an average size of 8 nm. AgNPs exposure increased the meiotic progression of female germ cells in the fetal mouse ovaries, and maternal AgNP exposure significantly disrupted imprinted gene expression in 15.5 dpc embryos and placentas, such as Ascl2, Snrpn, Kcnq1ot1, Peg3, Zac1, H19, Igf2r, and Igf2; DNA methylation studies revealed that AgNPs exposure significantly altered the methylation levels of

Short-term exposure to a synthetic estrogen disrupts mating dynamics in a pipefish.

Science.gov (United States)

Partridge, Charlyn; Boettcher, Anne; Jones, Adam G

2010-11-01

Sexual selection is responsible for the evolution of some of the most elaborate traits occurring in nature, many of which play a vital role in competition over access to mates and individual reproductive fitness. Because expression of these traits is typically regulated by sex-steroids there is a significant potential for their expression to be affected by the presence of certain pollutants, such as endocrine disrupting compounds. Endocrine disruptors have been shown to alter primary sexual traits and impact reproduction, but few studies have investigated how these compounds affect secondary sexual trait expression and how that may, in turn, impact mating dynamics. In this study we examine how short-term exposure to a synthetic estrogen impacts secondary sexual trait expression and mating dynamics in the Gulf pipefish, a species displaying sex-role reversal. Our results show that only 10days of exposure to 17α-ethinylestradiol results in adult male pipefish developing female-like secondary sexual traits. While these males are capable of reproduction, females discriminate against exposed males in mate choice trials. In natural populations, this type of discrimination would reduce male mating opportunities, thus potentially reducing their long-term reproductive success. Importantly, the effects of these compounds on mating dynamics and mating opportunity would not be observed using the current standard methods of assessing environmental contamination. However, disrupting these processes could have profound effects on the viability of exposed populations. Copyright © 2010 Elsevier Inc. All rights reserved.

Hemocyte responses of Dreissena polymorpha following a short-term in vivo exposure to titanium dioxide nanoparticles: Preliminary investigations

Energy Technology Data Exchange (ETDEWEB)

Couleau, Nicolas; Techer, Didier [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Pagnout, Christophe [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); International Consortium for the Environmental Implications of Nanotechnology, iCEINT, http://www.i-ceint.org (France); Jomini, Stephane [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); Foucaud, Laurent; Laval-Gilly, Philippe; Falla, Jairo [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Bennasroune, Amar, E-mail: amar.bennasroune@univ-metz.fr [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France)

2012-11-01

The widespread use of titanium-based nanoparticles and their environmental release may pose a significant risk to aquatic organisms within freshwater ecosystems. Suspension-feeder invertebrates like bivalve molluscs represent a unique target group for nanoparticle toxicology. The aim of this work was to investigate the short-term responses of Dreissena polymorpha hemocytes after in vivo exposure to titanium dioxide nanoparticles (TiO{sub 2} NP). For this purpose, freshwater mussels were exposed to P25 TiO{sub 2} NP at the concentrations of 0.1, 1, 5 and 25 mg/L during 24 h. Viability, phagocytosis activity and mitogen activated protein kinase (MAPK) phosphorylation level of ERK 1/2 and p38 in hemocytes extracted from exposed mussels were compared to those from control specimens. Results demonstrated an inhibition of the phagocytosis activity after exposure to TiO{sub 2} NP at 0.1 and 1 mg/L. Similar trends, albeit less pronounced, were reported for higher concentrations of NP. Transmission electron microscopy showed for the first time the internalization of TiO{sub 2} NP into Dreissena polymorpha hemocytes. Besides, exposure to NP increased the ERK 1/2 phosphorylation levels in all treatments. Concerning the phosphorylation level of p38, only exposures to 5 and 25 mg/L of NP induced significant p38 activation in comparison to that of the control. Finally, these short-term effects observed at environmentally relevant concentrations highlighted the need for further studies concerning ecotoxicological evaluation of nanoparticle release into an aquatic environment. -- Highlights: Black-Right-Pointing-Pointer Phagocytosis inhibition at TiO{sub 2} NP exposure concentrations of 0.1 and 1 mg/L. Black-Right-Pointing-Pointer Internalization of TiO{sub 2} NP in freshwater mussel hemocytes. Black-Right-Pointing-Pointer Increased phosphorylation level of p38 and ERK 1/2 after in vivo exposure to TiO{sub 2} NP.

Thyroid effects of endocrine disrupting chemicals

DEFF Research Database (Denmark)

Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

2012-01-01

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert ...... thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties....

Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment

International Nuclear Information System (INIS)

Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

2016-01-01

Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic–pituitary–gonadal–liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic

Infant and mother related outcomes from exposure to metals with endocrine disrupting properties during pregnancy

Energy Technology Data Exchange (ETDEWEB)

Rahman, A. [Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa (Canada); Kumarathasan, P. [Environmental Health Science and Research Bureau, Health Canada, Ottawa (Canada); Gomes, J., E-mail: jgomes@uottawa.ca [Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa (Canada); McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa (Canada)

2016-11-01

Background: Endocrine-related adverse health effects from exposure to heavy metals such as lead, arsenic, cadmium, and mercury are yet to be adequately described. The purpose of this review was to gain insight into maternal exposure to heavy metals, and to identify potential endocrine-related adverse health effects in the mother and the infant. Methods: Relevant databases were searched for original research reports and a total of 46 articles were retained for scrutiny. Required data was extracted from these studies and their methodology was assessed. Results: Impaired fetal growth was observed from exposure to all endocrine disrupting metals, while exposure to lead and arsenic were associated with spontaneous abortion, stillbirth and neonatal deaths. Maternal exposure to arsenic was associated with impaired glucose tolerance in these mothers. Conclusion: Impaired fetal growth, fetal loss, and neonatal deaths were significantly associated with heavy metals exposure during pregnancy; however, hypertension and gestational diabetes require further investigation. - Highlights: • Low and high dose exposure to lead was associated with low birth weight, preterm birth, stillbirths, spontaneous abortions and hypertension. • Exposure to arsenic was associated with fetal loss, stillbirths and spontaneous abortions. • Exposure to cadmium was associated with low birth weight. • Exposure to mercury was associated with spontaneous abortions and neurotoxic effects. • Exposure to copper was associated with low birth weight and spontaneous abortions and exposure to zinc was associated with low birth weight.

Infant and mother related outcomes from exposure to metals with endocrine disrupting properties during pregnancy

International Nuclear Information System (INIS)

Rahman, A.; Kumarathasan, P.; Gomes, J.

2016-01-01

Background: Endocrine-related adverse health effects from exposure to heavy metals such as lead, arsenic, cadmium, and mercury are yet to be adequately described. The purpose of this review was to gain insight into maternal exposure to heavy metals, and to identify potential endocrine-related adverse health effects in the mother and the infant. Methods: Relevant databases were searched for original research reports and a total of 46 articles were retained for scrutiny. Required data was extracted from these studies and their methodology was assessed. Results: Impaired fetal growth was observed from exposure to all endocrine disrupting metals, while exposure to lead and arsenic were associated with spontaneous abortion, stillbirth and neonatal deaths. Maternal exposure to arsenic was associated with impaired glucose tolerance in these mothers. Conclusion: Impaired fetal growth, fetal loss, and neonatal deaths were significantly associated with heavy metals exposure during pregnancy; however, hypertension and gestational diabetes require further investigation. - Highlights: • Low and high dose exposure to lead was associated with low birth weight, preterm birth, stillbirths, spontaneous abortions and hypertension. • Exposure to arsenic was associated with fetal loss, stillbirths and spontaneous abortions. • Exposure to cadmium was associated with low birth weight. • Exposure to mercury was associated with spontaneous abortions and neurotoxic effects. • Exposure to copper was associated with low birth weight and spontaneous abortions and exposure to zinc was associated with low birth weight.

Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis.

Science.gov (United States)

Attina, Teresa M; Hauser, Russ; Sathyanarayana, Sheela; Hunt, Patricia A; Bourguignon, Jean-Pierre; Myers, John Peterson; DiGangi, Joseph; Zoeller, R Thomas; Trasande, Leonardo

2016-12-01

Endocrine-disrupting chemicals (EDCs) contribute to disease and dysfunction and incur high associated costs (>1% of the gross domestic product [GDP] in the European Union). Exposure to EDCs varies widely between the USA and Europe because of differences in regulations and, therefore, we aimed to quantify disease burdens and related economic costs to allow comparison. We used existing models for assessing epidemiological and toxicological studies to reach consensus on probabilities of causation for 15 exposure-response relations between substances and disorders. We used Monte Carlo methods to produce realistic probability ranges for costs across the exposure-response relation, taking into account uncertainties. Estimates were made based on population and costs in the USA in 2010. Costs for the European Union were converted to US$ (€1=$1·33). The disease costs of EDCs were much higher in the USA than in Europe ($340 billion [2·33% of GDP] vs $217 billion [1·28%]). The difference was driven mainly by intelligence quotient (IQ) points loss and intellectual disability due to polybrominated diphenyl ethers (11 million IQ points lost and 43 000 cases costing $266 billion in the USA vs 873 000 IQ points lost and 3290 cases costing $12·6 billion in the European Union). Accounting for probability of causation, in the European Union, organophosphate pesticides were the largest contributor to costs associated with EDC exposure ($121 billion), whereas in the USA costs due to pesticides were much lower ($42 billion). EDC exposure in the USA contributes to disease and dysfunction, with annual costs taking up more than 2% of the GDP. Differences from the European Union suggest the need for improved screening for chemical disruption to endocrine systems and proactive prevention. Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prenatal Nicotine Exposure Disrupts Infant Neural Markers of Orienting.

Science.gov (United States)

King, Erin; Campbell, Alana; Belger, Aysenil; Grewen, Karen

2017-08-17

Prenatal nicotine exposure (PNE) from maternal cigarette-smoking is linked to developmental deficits, including impaired auditory processing, language, generalized intelligence, attention and sleep. Fetal brain undergoes massive growth, organization and connectivity during gestation, making it particularly vulnerable to neurotoxic insult. Nicotine binds to nicotinic acetylcholine receptors, which are extensively involved in growth, connectivity and function of developing neural circuitry and neurotransmitter systems. Thus, PNE may have long-term impact on neurobehavioral development. The purpose of this study was to compare the auditory K-complex, an event-related potential reflective of auditory gating, sleep preservation and memory consolidation during sleep, in infants with and without PNE and to relate these neural correlates to neurobehavioral development. We compared brain responses to an auditory paired-click paradigm in 3 to 5-month-old infants during Stage 2 sleep, when the K-complex is best observed. We measured component amplitude and delta activity during the K-complex. PNE may impair auditory sensory gating, which may contribute to disrupted sleep and to reduced auditory discrimination and learning, attention re-orienting and/or arousal during wakefulness reported in other studies. Links between PNE and reduced K-complex amplitude and delta power may represent altered cholinergic and GABAergic synaptic programming, and possibly reflect early neural bases for PNE-linked disruptions in sleep quality and auditory processing. These may pose significant disadvantage for language acquisition, attention, and social interaction necessary for academic and social success. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Size influences the effect of hydrophobic nanoparticles on lung surfactant model systems.

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Dwivedi, Mridula V; Harishchandra, Rakesh Kumar; Koshkina, Olga; Maskos, Michael; Galla, Hans-Joachim

2014-01-07

The alveolar lung surfactant (LS) is a complex lipid protein mixture that forms an interfacial monolayer reducing the surface tension to near zero values and thus preventing the lungs from collapse. Due to the expanding field of nanotechnology and the corresponding unavoidable exposure of human beings from the air, it is crucial to study the potential effects of nanoparticles (NPs) on the structural organization of the lung surfactant system. In the present study, we investigated both, the domain structure in pure DPPC monolayers as well as in lung surfactant model systems. In the pure lipid system we found that two different sized hydrophobic polymeric nanoparticles with diameter of ~12 nm and ~136 nm have contrasting effect on the functional and structural behavior. The small nanoparticles inserted into fluid domains at the LE-LC phase transition are not visibly disturbing the phase transition but disrupting the domain morphology of the LE phase. The large nanoparticles led to an expanded isotherm and to a significant decrease in the line tension and thus to a drastic disruption of the domain structures at a much lower number of nanoparticles with respect to the lipid. The surface activity of the model LS films again showed drastic variations due to presence of different sized NPs illustrated by the film balance isotherms and the atomic force microscopy. AFM revealed laterally profuse multilayer protrusion formation on compression but only in the presence of 136 nm sized nanoparticles. Moreover we investigated the vesicle insertion process into a preformed monolayer. A severe inhibition was observed only in the presence of ~136 nm NPs compared to minor effects in the presence of ~12 nm NPs. Our study clearly shows that the size of the nanoparticles made of the same material determines the interaction with biological membranes. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Workplace exposure to nanoparticles and the application of provisional nanoreference values in times of uncertain risks

Science.gov (United States)

van Broekhuizen, Pieter; van Broekhuizen, Fleur; Cornelissen, Ralf; Reijnders, Lucas

2012-03-01

Nano reference values (NRVs) for occupational use of nanomaterials were tested as provisional substitute for Occupational Exposure Limits (OELs). NRVs can be used as provisional limit values until Health-Based OELs or derived no-effect levels (DNEL) become available. NRVs were defined for 8 h periods (time weighted average) and for short-term exposure periods (15 min-time weighted average). To assess the usefulness of these NRVs, airborne number concentrations of nanoparticles (NPs) in the workplace environment were measured during paint manufacturing, electroplating, light equipment manufacturing, non-reflective glass production, production of pigment concentrates and car refinishing. Activities monitored were handling of solid engineered NPs (ENP), abrasion, spraying and heating during occupational use of nanomaterials (containing ENPs) and machining nanosurfaces. The measured concentrations are often presumed to contain ENPs as well as process-generated NPs (PGNP). The PGNP are found to be a significant source for potential exposure and cannot be ignored in risk assessment. Levels of NPs identified in workplace air were up to several millions of nanoparticles/cm3. Conventional components in paint manufacturing like CaCO3 and talc may contain a substantial amount of nanosized particulates giving rise to airborne nanoparticle concentrations. It is argued that risk assessments carried out for e.g. paint manufacturing processes using conventional non-nano components should take into account potential nanoparticle emissions as well. The concentrations measured were compared with particle-based NRVs and with mass-based values that have also been proposed for workers protection. It is concluded that NRVs can be used for risk management for handling or processing of nanomaterials at workplaces provided that the scope of NRVs is not limited to ENPs only, but extended to the exposure to process-generated NPs as well.

Workplace exposure to nanoparticles and the application of provisional nanoreference values in times of uncertain risks

International Nuclear Information System (INIS)

Broekhuizen, Pieter van; Broekhuizen, Fleur van; Cornelissen, Ralf; Reijnders, Lucas

2012-01-01

Nano reference values (NRVs) for occupational use of nanomaterials were tested as provisional substitute for Occupational Exposure Limits (OELs). NRVs can be used as provisional limit values until Health-Based OELs or derived no-effect levels (DNEL) become available. NRVs were defined for 8 h periods (time weighted average) and for short-term exposure periods (15 min-time weighted average). To assess the usefulness of these NRVs, airborne number concentrations of nanoparticles (NPs) in the workplace environment were measured during paint manufacturing, electroplating, light equipment manufacturing, non-reflective glass production, production of pigment concentrates and car refinishing. Activities monitored were handling of solid engineered NPs (ENP), abrasion, spraying and heating during occupational use of nanomaterials (containing ENPs) and machining nanosurfaces. The measured concentrations are often presumed to contain ENPs as well as process-generated NPs (PGNP). The PGNP are found to be a significant source for potential exposure and cannot be ignored in risk assessment. Levels of NPs identified in workplace air were up to several millions of nanoparticles/cm 3 . Conventional components in paint manufacturing like CaCO 3 and talc may contain a substantial amount of nanosized particulates giving rise to airborne nanoparticle concentrations. It is argued that risk assessments carried out for e.g. paint manufacturing processes using conventional non-nano components should take into account potential nanoparticle emissions as well. The concentrations measured were compared with particle-based NRVs and with mass-based values that have also been proposed for workers protection. It is concluded that NRVs can be used for risk management for handling or processing of nanomaterials at workplaces provided that the scope of NRVs is not limited to ENPs only, but extended to the exposure to process-generated NPs as well.

Acute and chronic effects from pulse exposure of D. magna to silver and copper oxide nanoparticles

DEFF Research Database (Denmark)

Sørensen, Sara Nørgaard; Lützhøft, Hans-Christian Holten; Rasmussen, Rose

2016-01-01

Aquatic toxicity testing of nanoparticles (NPs) is challenged by their dynamic behavior in test suspensions. The resulting difficulties in controlling and characterizing exposure concentrations are detrimental to the generation of concentration-response data needed for hazard identification of NPs...... is an environmentally relevant exposure scenario for NPs, which for AgNPs and CuONPs enables more stable exposures and cause acute immobility of D. magna comparable to continuous 24 h exposures. Pulse exposure is likely relevant and applicable for other toxic and dissolving metal NPs, but this requires further research....

Webinar Presentation: Exposures to Polycyclic Aromatic Hydrocarbons and Childhood Growth Trajectories and Body Composition: Linkages to Disrupted Self-Regulatory Processes

Science.gov (United States)

This presentation, Exposures to Polycyclic Aromatic Hydrocarbons and Childhood Growth Trajectories and Body Composition: Linkages to Disrupted Self-Regulatory Processes, was given at the NIEHS/EPA Children's Centers 2016 Webinar Series: Childhood Obesity

Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

DEFF Research Database (Denmark)

Modrzynska, Justyna; Berthing, Trine; Ravn-Haren, Gitte

2018-01-01

Background Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during...

Thyroid effects of endocrine disrupting chemicals.

Science.gov (United States)

Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

2012-05-22

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Contaminant mixtures and repoductive health: Developmental toxicity effects in rats after mixed exposure to environmentally relevant endocrine disrupting chemicals, with focus on effects in females

DEFF Research Database (Denmark)

Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Hass, Ulla

proposed that a similar syndrome, called the ovarian dysgenesis syndrome (ODS), exists for females. This syndrome encompasses alterations in reproductive development caused by chemical exposure in sensitive windows of development that may result in fecundity impairments, gravid diseases, gynecological...... disorders or later onset adult diseases. However, experimental evidence on the effects of developmental exposure to environmentally relevant endocrine disrupting chemicals in females has been missing attention. Since chemical exposure can affect female reproductive development it is important to investigate......, mixtures were modeled based on high end human intakes, and the project involved two developmental mixture studies in rats, called Contamed 1 and 2. In these studies 13 chemicals where data on in vivo endocrine disrupting effects and information on human exposures was available, were selected. The tested...

Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles

Science.gov (United States)

Coccini, Teresa; Roda, Elisa; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Manzo, Luigi

2012-08-01

While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, "omics" methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl2-treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl2. These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.

Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles

International Nuclear Information System (INIS)

Coccini, Teresa; Roda, Elisa; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Manzo, Luigi

2012-01-01

While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, “omics” methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl 2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl 2 -treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl 2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl 2 . These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.

Premature reproductive aging in female rats after developmental exposure to mixtures of endocrine disrupters

DEFF Research Database (Denmark)

Jacobsen, Pernille Rosenskjold; Petersen, Marta Axelstad; Christiansen, Sofie

2013-01-01

of 13 estrogenic and anti-androgenic chemicals, including phthalates, pesticides, UV-filters, bisphenol A, butylparaben and paracetamol, and the mixture ratio was chosen to reflect high-end human intakes. Groups received combined exposures of 0,100, 150, 200 or 450 times high-end human intake levels......Long-lasting and delayed reproductive effects of developmental exposure to mixtures of environmental chemicals were investigated in female rats. Wistar rats were dosed during gestation and lactation to mixtures of endocrine disrupters, and effects in offspring were studied. The mixtures consisted....... Additionally, groups received mixtures including only the anti-androgens or estrogens at 200 or 450 times human intake. Female offspring exposed to the high dose mixture of all 13 chemicals showed earlier reproductive aging measured as early onset of irregular estrous cycle as compared to controls...

The effect of nanoparticle uptake on cellular behavior: disrupting or enabling functions?

Directory of Open Access Journals (Sweden)

Miserocchi G

2012-09-01

Full Text Available Alice Panariti, Giuseppe Miserocchi, Ilaria RivoltaDepartment of Experimental Medicine, University of Milano Bicocca, Monza, ItalyAbstract: Nanoparticles (NPs are materials with overall dimensions in the nanoscale range. They have unique physicochemical properties, and have emerged as important players in current research in modern medicine. In the last few decades, several types of NPs and microparticles have been synthesized and proposed for use as contrast agents for diagnostics and imaging and for drug delivery; for example, in cancer therapy. Yet specific targeting that will improve their delivery still represents an unsolved challenge. The mechanism by which NPs enter the cell has important implications not only for their fate but also for their impact on biological systems. Several papers in the literature discuss the potential risks related to NP exposure, and more recently the concept that even sublethal doses of NPs may elicit a cell response has been proposed. In this review, we intend to present an overall view of cell mechanisms that may be perturbed by cell–NP interaction. Published data, in fact, emphasize that NPs should no longer be viewed only as simple carriers for biomedical applications, but that they can also play an active role in mediating biological effects.Keywords: nanoparticles, uptake, intracellular trafficking, bio compatibility

Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages

Directory of Open Access Journals (Sweden)

Dimitri Vanhecke

2017-11-01

Full Text Available Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line were incubated with gold (AuNPs and iron oxide nanoparticles (FeOxNPs either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeOxNPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase. This increase was higher for both AuNPs and FeOxNPs during co-exposure. Cells treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for the delivery of pharmaceutical agents, this can be beneficial. However, co-exposure should also be taken into account in the case of risk assessment of occupational settings. The demonstration of co-exposure-invoked pathway interactions reveals that synergetic nanoparticle effects, either positive or negative, must be considered for nanotechnology and nanomedicine in particular to develop to its full potential.

Elucidating Adverse Nutritional Implications of Exposure to Endocrine-Disrupting Chemicals and Mycotoxins through Stable Isotope Techniques.

Science.gov (United States)

Owino, Victor O; Cornelius, Carolin; Loechl, Cornelia U

2018-03-23

Multiple drivers of the double burden of malnutrition (DBM) include a rapid shift from predominantly plant-based diets to energy-dense foods based on meats, milk, animal fats and vegetable oils. The shift to overweight and obesity is driven by increased exposure to mass media, urbanization, technological advances in food processing, rising income and increased population density associated with increased access to cheap foods. At the same time, undernutrition persists mainly due to food insecurity and lack of access to safe water, sanitation and adequate health care. All known nutrition interventions result in only one third reduction in stunting. Little consideration has been given to hazardous exposure to endocrine disrupting chemicals (EDCs) and microbial toxins as major components of the malnutrition-causal framework. These hazards include microbial toxins, for example, mycotoxins, and environmental pollutants such as persistent organic pollutants (POPs), some of which are known to disrupt the endocrine system. These hazards sit at the cross road of undernutrition and overweight and obesity since the exposure cuts across the critical window of opportunity (the first 1000 days). In this review, we update on the role of food and environmental contaminants, especially EDCs and aflatoxins, in child growth and on the implications for metabolic dysfunction and disease risk in later life, and discuss potential applications of nuclear and isotopic techniques to elucidate the underlying biological mechanisms, outcome indicators, as well as occurrence levels.

Impact of exposure to endocrine disrupters in utero and in childhood on adult reproduction

DEFF Research Database (Denmark)

Norgil Damgaard, Ida; Main, Katharina Maria; Toppari, Jorma

2002-01-01

Recent reports have demonstrated a decline in human male reproductive health: high and probably increasing prevalence of cryptorchidism and hypospadias, low and probably decreasing semen quality, a rising incidence of testicular cancer and a growing demand for assisted reproduction. These changes...... seem to be interrelated and may be symptoms of a common underlying entity, the testicular dysgenesis syndrome, with foundations in fetal life due to adverse environmental influences. Wildlife experience and animal studies have provided evidence that fetal or perinatal exposure to endocrine disrupters...

Nanoparticle-specific changes in Arabidopsis thaliana gene expression after exposure to ZnO, TiO2, and fullerene soot

International Nuclear Information System (INIS)

Landa, Premysl; Vankova, Radomira; Andrlova, Jana; Hodek, Jan; Marsik, Petr; Storchova, Helena; White, Jason C.; Vanek, Tomas

2012-01-01

Highlights: ► Exposure to different nanoparticles resulted in specific changes in gene transcription. ► Nano ZnO caused most dramatic changes in Arabidopsis gene expression. ► Nano ZnO was the most toxic and up-regulated most stress-related genes. ► Fullerene soot caused significant gene expression response – mainly stress-related. ► Nano TiO 2 had weak impact on Arabidopsis gene expression indicating minimal toxicity. - Abstract: The effect of exposure to 100 mg/L zinc oxide (nZnO), fullerene soot (FS) or titanium dioxide (nTiO 2 ) nanoparticles on gene expression in Arabidopsis thaliana roots was studied using microarrays. After 7 d, nZnO, FS, or nTiO 2 exposure resulted in 660 up- and 826 down-regulated genes, 232 up- and 189 down-regulated genes, and 80 up- and 74 down-regulated genes, respectively (expression difference > 2-fold; p[t test] 2 exposure, which resulted in up- and down-regulation of genes involved mainly in responses to biotic and abiotic stimuli. The data clearly indicate that the mechanisms of phytotoxicity are highly nanoparticle dependent despite of a limited overlap in gene expression response.

Exposure to endocrine disrupting chemicals among residents of a rural vegetarian/vegan community.

Science.gov (United States)

Tordjman, Karen; Grinshpan, Laura; Novack, Lena; Göen, Thomas; Segev, Dar; Beacher, Lisa; Stern, Naftali; Berman, Tamar

2016-12-01

Endocrine-disrupting chemicals (EDCs) are increasingly thought to be involved in the rising prevalence of disorders such as obesity, diabetes, and some hormone-dependent cancers. Several lines of evidence have indicated that vegetarian and vegan diets may offer some protection from such diseases. We hypothesized that exposure to selected EDCs among residents of the unique vegetarian/vegan community of Amirim would be lower than what has recently been reported for the omnivorous population in the first Israel Biomonitoring Study (IBMS). We studied 42 Amirim residents (29 vegetarians/13 vegans; 24 women/18men, aged 50.7±13.7y). Subjects answered detailed lifestyle, and multipass, memory-based 24-hr dietary recall questionnaires. Concentrations of bisphenol A (BPA), 11 phthalate metabolites, and the isoflavone phytoestrogens (genistein and daidzein) were determined by GC or LC tandem mass-spectrometry on a spot urine sample. The results were compared to those obtained following the same methodology in the Jewish subgroup of the IBMS (n=184). While a vegetarian/vegan nutritional pattern had no effect on exposure to BPA, it seemed to confer a modest protection (~21%) from exposure to high molecular weight phthalates. Furthermore, the summed metabolites of the high molecular weight phthalate DiNP were 36% lower in vegans compared to vegetarians (P<0.05). In contrast, Amirim residents exhibited a level of exposure to isoflavone phytoestrogens about an order of magnitude higher than in the IBMS (P<0.001). In Israel, a country whose inhabitants demonstrate exposure to EDCs comparable to that of the US and Canada, a voluntary lifestyle of vegetarianism and preference for organic food has a modest, but possibly valuable, impact on exposure to phthalates, while it is associated with a very steep increase in the exposure to phytoestrogens. Major reduction in exposure to EDCs will require regulatory actions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inter-comparison of personal monitors for nanoparticles exposure at workplaces and in the environment

NARCIS (Netherlands)

Todea, A.M.; Beckmann, S.; Kaminski, H.; Bard, D.; Bau, S.; Clavaguera, S.; Dahmann, D.; Dozol, H.; Dziurowitz, N.; Elihn, K.; Fierz, M.; Lidén, G.; Meyer-Plath, A.; Monz, C.; Neumann, V.; Pelzer, J.; Simonow, B.K.; Thali, P.; Tuinman, I.; Vleuten, A. van der; Vroomen, H.; Asbach, C.

2017-01-01

Personal monitors based on unipolar diffusion charging (miniDiSC/DiSCmini, NanoTracer, Partector) can be used to assess the individual exposure to nanoparticles in different environments. The charge acquired by the aerosol particles is nearly proportional to the particle diameter and, by

WO3/Pt nanoparticles are NADPH oxidase biomimetics that mimic effector cells in vitro and in vivo

International Nuclear Information System (INIS)

Clark, Andrea J; Coury, Emma L; Meilhac, Alexandra M; Petty, Howard R

2016-01-01

To provide a means of delivering an artificial immune effector cell-like attack on tumor cells, we report the tumoricidal ability of inorganic WO 3 /Pt nanoparticles that mimic a leukocyte’s functional abilities. These nanoparticles route electrons from organic structures and electron carriers to form hydroxyl radicals within tumor cells. During visible light exposure, WO 3 /Pt nanoparticles manufacture hydroxyl radicals, degrade organic compounds, use NADPH, trigger lipid peroxidation, promote lysosomal membrane disruption, promote the loss of reduced glutathione, and activate apoptosis. In a model of advanced breast cancer metastasis to the eye’s anterior chamber, we show that WO 3 /Pt nanoparticles prolong the survival of 4T1 tumor-bearing Balb/c mice. This new generation of inorganic photosensitizers do not photobleach, and therefore should provide an important therapeutic advance in photodynamic therapy. As biomimetic nanoparticles destroy targeted cells, they may be useful in treating ocular and other forms of cancer. (paper)

WO3/Pt nanoparticles are NADPH oxidase biomimetics that mimic effector cells in vitro and in vivo

Science.gov (United States)

Clark, Andrea J.; Coury, Emma L.; Meilhac, Alexandra M.; Petty, Howard R.

2016-02-01

To provide a means of delivering an artificial immune effector cell-like attack on tumor cells, we report the tumoricidal ability of inorganic WO3/Pt nanoparticles that mimic a leukocyte’s functional abilities. These nanoparticles route electrons from organic structures and electron carriers to form hydroxyl radicals within tumor cells. During visible light exposure, WO3/Pt nanoparticles manufacture hydroxyl radicals, degrade organic compounds, use NADPH, trigger lipid peroxidation, promote lysosomal membrane disruption, promote the loss of reduced glutathione, and activate apoptosis. In a model of advanced breast cancer metastasis to the eye’s anterior chamber, we show that WO3/Pt nanoparticles prolong the survival of 4T1 tumor-bearing Balb/c mice. This new generation of inorganic photosensitizers do not photobleach, and therefore should provide an important therapeutic advance in photodynamic therapy. As biomimetic nanoparticles destroy targeted cells, they may be useful in treating ocular and other forms of cancer.

In ovo exposure quail assay for risk assessment of endocrine disrupting chemicals.

Science.gov (United States)

Kamata, Ryo; Takahashi, Shinji; Shimizu, Akira; Morita, Masatoshi; Shiraishi, Fujio

2006-12-01

Although there are in vivo assays using various organisms for the risk assessment of chemicals with endocrine disrupting properties, effective experimental methods for avian species are still under debate. We have developed an in ovo exposure assay using Japanese quail eggs, aimed at assessing disrupting effects on avian reproductive development and function. Hybrid eggs from Brazilian Brown male and White Egg female quails, which can be genetically sexed by their plumage color after hatching, were prepared, and test materials dissolved in olive oil were injected into the air-chamber on day 10 of incubation. After sexual maturation of hatched chicks, we observed egg production by females and the egg quality and male-typical reproductive behavior, and then examined reproductive system morphology and serum steroid concentrations in both sexes. Treatment with a synthetic estrogen, diethylstilbestrol (DES, 0.5-50 ng/g egg), dose-dependently reduced the eggshell thickness and strength of eggs. A few females treated with 5 ng/g DES per egg produced soft-shelled/ unmarked eggs, and all laying females treated with 50 ng/g egg produced eggs completely lacking shells. DES also induced shortening of the left oviduct and abnormal development of the right oviduct in a dose-dependent manner, while testis weight was reduced symmetrically. In addition, 2,2',4',6'-tetrachlorobiphenyl-4-ol (10-1,000 ng/g egg), which previously showed relatively high estrogenic activity in vitro, caused dose-dependent shortening of the left oviduct and reduction in testis weight. The methods for evaluating endocrine disrupting effects and preparing experimental birds proposed in the present study are expected to facilitate assays for avian reproductive toxicology.

Acute exposure to synthetic pyrethroids causes bioconcentration and disruption of the hypothalamus–pituitary–thyroid axis in zebrafish embryos

International Nuclear Information System (INIS)

Tu, Wenqing; Xu, Chao; Lu, Bin; Lin, Chunmian; Wu, Yongming; Liu, Weiping

2016-01-01

Synthetic pyrethroids (SPs) have the potential to disrupt the thyroid endocrine system in mammals; however, little is known of the effects of SPs and underlying mechanisms in fish. In the current study, embryonic zebrafish were exposed to various concentrations (1, 3 and 10 μg/L) of bifenthrin (BF) or λ-cyhalothrin (λ-CH) until 72 h post fertilization, and body condition, bioaccumulation, thyroid hormone levels and transcription of related genes along the hypothalamus–pituitary–thyroid (HPT) axis examined. Body weight was significantly decreased in the λ-CH exposure groups, but not the BF exposure groups. BF and λ-CH markedly accumulated in the larvae, with concentrations ranging from 90.7 to 596.8 ng/g. In both exposure groups, alterations were observed in thyroxine (T 4 ) and triiodothyronine (T 3 ) levels. In addition, the majority of the HPT axis-related genes examined, including CRH, TSHβ, TTR, UGT1ab, Pax8, Dio2 and TRα, were significantly upregulated in the presence of BF. Compared to BF, λ-CH induced different transcriptional regulation patterns of the tested genes, in particular, significant stimulation of TTR, Pax8, Dio2 and TRα levels along with concomitant downregulation of Dio1. Molecular docking analyses revealed that at the atomic level, BF binds to thyroid hormone receptor (TRα) protein more potently than λ-CH, consequently affecting HPT axis signal transduction. In vitro and in silico experiments disclosed that during the early stages of zebrafish development, BF and λ-CH have the potential to disrupt thyroid endocrine system. - Highlights: • Following respective exposure of embryos to BF and λ-CH, thyroid endocrine disruption was investigated in zebrafish embryos. • Thyroid hormones (T3 and T4 levels) were significantly altered after being exposed to BF and λ-CH. • Gene transcription modulation in the HPT axis was examined. • BF and λ-CH bioconcentration in zebrafish larvae were evident. • BF binds to thyroid hormone

Acute exposure to synthetic pyrethroids causes bioconcentration and disruption of the hypothalamus–pituitary–thyroid axis in zebrafish embryos

Energy Technology Data Exchange (ETDEWEB)

Tu, Wenqing [Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029 (China); Institute of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Xu, Chao, E-mail: chaoxu@zjut.edu.cn [Institute of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Lu, Bin; Lin, Chunmian [Institute of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Wu, Yongming [Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330029 (China); Liu, Weiping [Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

2016-01-15

Synthetic pyrethroids (SPs) have the potential to disrupt the thyroid endocrine system in mammals; however, little is known of the effects of SPs and underlying mechanisms in fish. In the current study, embryonic zebrafish were exposed to various concentrations (1, 3 and 10 μg/L) of bifenthrin (BF) or λ-cyhalothrin (λ-CH) until 72 h post fertilization, and body condition, bioaccumulation, thyroid hormone levels and transcription of related genes along the hypothalamus–pituitary–thyroid (HPT) axis examined. Body weight was significantly decreased in the λ-CH exposure groups, but not the BF exposure groups. BF and λ-CH markedly accumulated in the larvae, with concentrations ranging from 90.7 to 596.8 ng/g. In both exposure groups, alterations were observed in thyroxine (T{sub 4}) and triiodothyronine (T{sub 3}) levels. In addition, the majority of the HPT axis-related genes examined, including CRH, TSHβ, TTR, UGT1ab, Pax8, Dio2 and TRα, were significantly upregulated in the presence of BF. Compared to BF, λ-CH induced different transcriptional regulation patterns of the tested genes, in particular, significant stimulation of TTR, Pax8, Dio2 and TRα levels along with concomitant downregulation of Dio1. Molecular docking analyses revealed that at the atomic level, BF binds to thyroid hormone receptor (TRα) protein more potently than λ-CH, consequently affecting HPT axis signal transduction. In vitro and in silico experiments disclosed that during the early stages of zebrafish development, BF and λ-CH have the potential to disrupt thyroid endocrine system. - Highlights: • Following respective exposure of embryos to BF and λ-CH, thyroid endocrine disruption was investigated in zebrafish embryos. • Thyroid hormones (T3 and T4 levels) were significantly altered after being exposed to BF and λ-CH. • Gene transcription modulation in the HPT axis was examined. • BF and λ-CH bioconcentration in zebrafish larvae were evident. • BF binds to thyroid

Cytotoxic effects of gold nanoparticles exposure employing in vitro animal cell culture system as part of nanobiosafety

Science.gov (United States)

Ambwani, Sonu; Kakade Datta, P.; Kandpal, Deepika; Arora, Sandeep; Ambwani, Tanuj Kumar

2016-04-01

Metal Nanoparticles are exploited in different fields that include biomedical sector where they are utilized in drug and gene delivery, biosensors, cancer treatment and diagnostic tools. Despite of their benefits, there has been serious concerns about possible side effects of several nanoparticles. Gold nanoparticles (AuNPs) are exploited for bio-imaging, biosensing, drug delivery, transfection and diagnosis. These nanoparticles may get released into the environment in high amounts at all stages of production, recycling and disposal. Since the manufacture and use of nanoparticles are increasing, humans/ animals are more likely to be exposed occupationally or via consumer products and the environment. The emergence of the new field of nanotoxicity has spurred great interest in a wide variety of materials and their possible effects on living systems. Animal cell culture system is considered as a sensitive indicator against exposure of such materials. Keeping in view the above scenario, present study was carried out to evaluate effect of AuNPs exposure in primary and cell line culture system employing chicken embryo fibroblast (CEF) culture and HeLa cell line culture through MTT assay. Minimum cytotoxic dose was found to be 60 µg/ml and 50 µg/ml in CEF and HeLa cells, respectively. Thus, it could be inferred that even a very low concentration of AuNPs could lead to cytotoxic effects in cell culture based studies.

Developmental programming: exposure to testosterone excess disrupts steroidal and metabolic environment in pregnant sheep.

Science.gov (United States)

Abi Salloum, B; Veiga-Lopez, A; Abbott, D H; Burant, C F; Padmanabhan, V

2015-06-01

Gestational exposure to excess T leads to intrauterine growth restriction, low birth weight, and adult metabolic/reproductive disorders in female sheep. We hypothesized that as early mediators of such disruptions, gestational T disrupts steroidal and metabolic homeostasis in both the mother and fetus by both androgenic and metabolic pathways. Maternal blood samples were measured weekly for levels of insulin, glucose, and progesterone from four groups of animals: control; gestational T (twice weekly im injections of 100 mg of T propionate from d 30 to d 90 of gestation); T plus an androgen antagonist, flutamide (15 mg/kg·d oral; T-Flutamide); and T plus the insulin sensitizer, rosiglitazone (0.11 mg/kg·d oral; T-Rosi) (n = 10-12/group). On day 90 of gestation, maternal and umbilical cord samples were collected after a 48-hour fast from a subset (n = 6/group) for the measurement of steroids, free fatty acids, amino acids, and acylcarnitines. Gestational T decreased maternal progesterone levels by 36.5% (P fetal estradiol were not prevented by either cotreatment. Gestational T disrupted associations of steroids with metabolites and progesterone with acylcarnitines, which was prevented either by androgen antagonist or insulin sensitizer cotreatment. These findings suggest a future combination of these treatments might be required to prevent alteration in maternal/fetal steroidal and metabolic milieu(s).

TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast-like cells in a size dependent manner.

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Ibrahim, Mohamed; Schoelermann, Julia; Mustafa, Kamal; Cimpan, Mihaela R

2018-04-30

Human exposure to titanium dioxide nanoparticles (nano-TiO 2 ) is increasing. An internal source of nano-TiO 2 is represented by titanium-based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant-bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano-TiO 2 on SaOS-2 human osteoblast-like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano-TiO 2 . Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p-FAK Y397 ) and the expression of vinculin in response to nano-TiO 2 were also assessed. Treatment with nano-TiO 2 disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS-2 cells. The phosphorylation of p-FAK Y397 and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm-exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS-2 cells were affected by the selected nano-TiO 2 in a size dependent manner. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Exposure assessment and engineering control strategies for airborne nanoparticles: an application to emissions from nanocomposite compounding processes

International Nuclear Information System (INIS)

Tsai, Candace S.-J.; White, David; Rodriguez, Henoc; Munoz, Christian E.; Huang, Cheng-Yu; Tsai, Chuen-Jinn; Barry, Carol; Ellenbecker, Michael J.

2012-01-01

In this study, nanoalumina and nanoclay particles were compounded separately with ethylene vinyl acetate (EVA) polymer to produce nanocomposites using a twin-screw extruder to investigate exposure and effective controls. Nanoparticle exposures from compounding processes were elevated under some circumstances and were affected by many factors including inadequate ventilation, surrounding air flow, feeder type, feeding method, and nanoparticle type. Engineering controls such as improved ventilation and enclosure of releasing sources were applied to the process equipment to evaluate the effectiveness of control. The nanoparticle loading device was modified by installing a ventilated enclosure surrounding the loading chamber. Exposures were studied using designed controls for comparison which include three scenarios: (1) no isolation; (2) enclosed sources; and (3) enclosed sources and improved ventilation. Particle number concentrations for diameters from 5 to 20,000 nm measured by the Fast Mobility Particle Sizer and aerodynamic particle sizer were studied. Aerosol particles were sampled on transmission electron microscope grids to characterize particle composition and morphology. Measurements and samples were taken at the near- and far-field areas relative to releasing sources. Airborne particle concentrations were reduced significantly when using the feeder enclosure, and the concentrations were below the baseline when two sources were enclosed, and the ventilation was improved when using either nanoalumina or nanoclay as fillers.

Assessment of functional changes in nanoparticle-exposed neuroendocrine cells with amperometry: exploring the generalizability of nanoparticle-vesicle matrix interactions.

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Love, Sara A; Haynes, Christy L

2010-09-01

Using two of the most commonly synthesized noble metal nanoparticle preparations, citrate-reduced Au and Ag, the impacts of short-term accidental nanoparticle exposure are examined in primary culture murine adrenal medullary chromaffin cells. Transmission electron microscopy (TEM), inductively coupled plasma atomic emission spectroscopy (ICP-AES) and Alamar Blue viability studies revealed that nanoparticles are taken up by cells but do not decrease cell viability within 48 hours of exposure. Carbon-fiber microelectrode amperometry (CFMA) examination of exocytosis in nanoparticle-exposed cells revealed that nanoparticle exposure does lead to decreased secretion of chemical messenger molecules, of up to 32.5% at 48 hours of Au exposure. The kinetics of intravesicular species liberation also slows after nanoparticle exposure, between 30 and 50% for Au and Ag, respectively. Repeated stimulation of exocytosis demonstrated that these effects persisted during subsequent stimulations, meaning that nanoparticles do not interfere directly with the vesicle recycling machinery but also that cellular function is unable to recover following vesicle content expulsion. By comparing these trends with parallel studies done using mast cells, it is clear that similar exocytosis perturbations occur across cell types following noble metal nanoparticle exposure, supporting a generalizable effect of nanoparticle-vesicle interactions.

Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate

DEFF Research Database (Denmark)

Löschner, Katrin; Hadrup, Niels; Qvortrup, Klaus

2011-01-01

Background: The study investigated the distribution of silver after 28 days repeated oral administration of silver nanoparticles (AgNPs) and silver acetate (AgAc) to rats. Oral administration is a relevant route of exposure because of the use of silver nanoparticles in products related to food...... and food contact materials. Results: AgNPs were synthesized with a size distribution of 14 ± 4 nm in diameter (90% of the nanoparticle volume) and stabilized in aqueous suspension by the polymer polyvinylpyrrolidone (PVP). The AgNPs remained stable throughout the duration of the 28-day oral toxicity study...... in rats. The organ distribution pattern of silver following administration of AgNPs and AgAc was similar. However the absolute silver concentrations in tissues were lower following oral exposure to AgNPs. This was in agreement with an indication of a higher fecal excretion following administration of Ag...

Estimating Burden and Disease Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

DEFF Research Database (Denmark)

Trasande, Leonardo; Zoeller, R. Thomas; Hass, Ulla

2015-01-01

Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability. Objective: The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU......). Design: A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine...

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

International Nuclear Information System (INIS)

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2010-01-01

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g -1 , respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to brachytherapy, with

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

Science.gov (United States)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

2010-11-01

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g-1, respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to brachytherapy, with lower

Modeling population exposures to silver nanoparticles present in consumer products

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Royce, Steven G.; Mukherjee, Dwaipayan; Cai, Ting; Xu, Shu S.; Alexander, Jocelyn A.; Mi, Zhongyuan; Calderon, Leonardo; Mainelis, Gediminas; Lee, KiBum; Lioy, Paul J.; Tetley, Teresa D.; Chung, Kian Fan; Zhang, Junfeng; Georgopoulos, Panos G.

2014-11-01

Exposures of the general population to manufactured nanoparticles (MNPs) are expected to keep rising due to increasing use of MNPs in common consumer products (PEN 2014). The present study focuses on characterizing ambient and indoor population exposures to silver MNPs (nAg). For situations where detailed, case-specific exposure-related data are not available, as in the present study, a novel tiered modeling system, Prioritization/Ranking of Toxic Exposures with GIS (geographic information system) Extension (PRoTEGE), has been developed: it employs a product life cycle analysis (LCA) approach coupled with basic human life stage analysis (LSA) to characterize potential exposures to chemicals of current and emerging concern. The PRoTEGE system has been implemented for ambient and indoor environments, utilizing available MNP production, usage, and properties databases, along with laboratory measurements of potential personal exposures from consumer spray products containing nAg. Modeling of environmental and microenvironmental levels of MNPs employs probabilistic material flow analysis combined with product LCA to account for releases during manufacturing, transport, usage, disposal, etc. Human exposure and dose characterization further employ screening microenvironmental modeling and intake fraction methods combined with LSA for potentially exposed populations, to assess differences associated with gender, age, and demographics. Population distributions of intakes, estimated using the PRoTEGE framework, are consistent with published individual-based intake estimates, demonstrating that PRoTEGE is capable of capturing realistic exposure scenarios for the US population. Distributions of intakes are also used to calculate biologically relevant population distributions of uptakes and target tissue doses through human airway dosimetry modeling that takes into account product MNP size distributions and age-relevant physiological parameters.

Long-term exposure to gold nanoparticles accelerates larval metamorphosis without affecting mass in wood frogs (Lithobates sylvaticus) at environmentally relevant concentrations.

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Fong, Peter P; Thompson, Lucas B; Carfagno, Gerardo L F; Sitton, Andrea J

2016-09-01

Nanoparticles are environmental contaminants of emerging concern. Exposure to engineered nanoparticles has been shown to have detrimental effects on aquatic organisms. The authors synthesized gold nanoparticles (18.1 ± 3.5 nm) and tested their effects on time to and weight at metamorphosis in wood frog (Lithobates sylvaticus) tadpoles, a species known to be sensitive to environmental stressors. Continuous exposure to all concentrations of gold nanoparticles (0.05 pM, 0.5 pM, and 5 pM in particles) for up to 55 d significantly reduced time to metamorphosis by as much as an average of 3 d (p metamorphosis. The approximately 18-nm gold nanoparticles used were metastable in dechlorinated tap water, resulting in a change in surface charge and aggregation over time, leading to negatively charged aggregates that were on the order of 60 nm to 110 nm. Nanoparticle aggregation could exacerbate the effect on time to metamorphosis. To the authors' knowledge, the present study is the first report on the effect of engineered nanoparticles of any kind on life-history variables in an amphibian, a taxonomic group that has been declining globally for at least 25 yr. Environ Toxicol Chem 2016;35:2304-2310. © 2016 SETAC. © 2016 SETAC.

Risks from accidental exposures to engineered nanoparticles and neurological health effects: A critical review

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Mattsson Mats-Olof

2010-12-01

Full Text Available Abstract There are certain concerns regarding the safety for the environment and human health from the use of engineered nanoparticles (ENPs which leads to unintended exposures, as opposed to the use of ENPs for medical purposes. This review focuses on the unintended human exposure of ENPs. In particular, possible effects in the brain are discussed and an attempt to assess risks is performed. Animal experiments have shown that investigated ENPs (metallic nanoparticles, quantum dots, carbon nanotubes can translocate to the brain from different entry points (skin, blood, respiratory pathways. After inhalation or instillation into parts of the respiratory tract a very small fraction of the inhaled or instilled ENPs reaches the blood and subsequently secondary organs, including the CNS, at a low translocation rate. Experimental in vivo and in vitro studies have shown that several types of ENPs can have various biological effects in the nervous system. Some of these effects could also imply that ENPs can cause hazards, both acutely and in the long term. The relevance of these data for risk assessment is far from clear. There are at present very few data on exposure of the general public to either acute high dose exposure or on chronic exposure to low levels of air-borne ENPs. It is furthermore unlikely that acute high dose exposures would occur. The risk from such exposures for damaging CNS effects is thus probably very low, irrespective of any biological hazard associated with ENPs. The situation is more complicated regarding chronic exposures, at low doses. The long term accumulation of ENPs can not be excluded. However, we do not have exposure data for the general public regarding ENPs. Although translocation to the brain via respiratory organs and the circulation appears to be very low, there remains a possibility that chronic exposures, and/or biopersistent ENPs, can influence processes within the brain that are triggering or aggravating

Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12.

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Hu, Qinglian; Guo, Fengliang; Zhao, Fenghui; Fu, Zhengwei

2017-04-01

Nanomaterials hold significant potential for industrial and biomedical application these years. Therefore, the relationship between nanoparticles and neurodegenerative disease is of enormous interest. In this contribution, zebrafish embryos and PC12 cell lines were selected for studying neurotoxicity of titanium dioxide nanoparticles (TiO 2 NPs). After exposure of different concentrations of TiO 2 NPs to embryos from fertilization to 96 hpf, the hatching time of zebrafish was decreased, accompanied by an increase in malformation rate. However, no significant increases in mortality relative to control were observed. These results indicated that TiO 2 NPs exposure hold a risk for premature of zebrafish embryos, but not fatal. The further investigation confirmed that TiO 2 NPs could accumulate in the brain of zebrafish larvae, resulting in reactive oxygen species (ROS) generation and cell death of hypothalamus. Meanwhile, q-PCR analysis showed that TiO 2 NPs exposure increased the pink1, parkin, α-syn and uchl1 gene expression, which are related with the formation of Lewy bodies. We also observed loss of dopaminergic neurons in zebrafish and in vitro. These remarkable hallmarks are all linked to these Parkinson's disease (PD) symptoms. Our results indicate that TiO 2 NPs exposure induces neurotoxicity in vivo and in vitro, which poses a significant risk factor for the development of PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the rumors about the silent spring: review of the scientific evidence linking occupational and environmental pesticide exposure to endocrine disruption health effects

Directory of Open Access Journals (Sweden)

Cocco Pierluigi

2002-01-01

Full Text Available Occupational exposure to some pesticides, and particularly DBCP and chlordecone, may adversely affect male fertility. However, apart from the therapeutic use of diethylstilbestrol, the threat to human reproduction posed by "endocrine disrupting" environmental contaminants has not been supported by epidemiological evidence thus far. As it concerns other endocrine effects described in experimental animals, only thyroid inhibition following occupational exposure to amitrole and mancozeb has been confirmed in humans. Cancer of the breast, endometrium, ovary, prostate, testis, and thyroid are hormone-dependent, which fostered research on the potential risk associated with occupational and environmental exposure to the so-called endocrine-disrupting pesticides. The most recent studies have ruled out the hypothesis of DDT derivatives as responsible for excess risks of cancer of the reproductive organs. Still, we cannot exclude a role for high level exposure to o,p'-DDE, particularly in post-menopausal ER+ breast cancer. On the other hand, other organochlorine pesticides and triazine herbicides require further investigation for a possible etiologic role in some hormone-dependent cancers.

Implications of exposure to dextran-coated and uncoated iron oxide nanoparticles to developmental toxicity in zebrafish

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de Oliveira, Giovanna Medeiros Tavares; de Oliveira, Elisa Magno Nunes; Pereira, Talita Carneiro Brandão; Papaléo, Ricardo Meurer; Bogo, Maurício Reis

2017-12-01

Iron oxide nanoparticles (IONPS) have been widely investigated as a platform for a new class of multifunctional theranostic agents. They are considered biocompatible, and some formulations are already available in the market for clinical use. However, contradictory results regarding toxicity of IONPs raise a concern about the potential harm of these nanoparticles. Changes in the nanoparticle (NP) physicochemical properties or exposure media can significantly alter their behavior and, as a consequence, their toxic effects. Here, behavior and two-step RT-qPCR were employed to access the potential toxicological effects of dextran-coated IONPs (CLIO-NH2) and uncoated IONPs (UCIO) in zebrafish larvae. Animals were exposed for 7 days to NP solutions ranging from 0.1-100 μg/mL directly mixed to the system water. UCIO showed high decantation and instability in solution, altering zebrafish mortality but showing no alterations in behavior and molecular expression analysis. CLIO-NH2 exposure did not cause significant mortality or changes in hatching rate of zebrafish larvae; however, behavior and expression profiles of the group exposed to lower concentration (1 μg/mL) presented a tendency to decrease the locomotor activity and apoptotic pathway activation.

Putative effects of endocrine disrupters on pubertal development in the human

DEFF Research Database (Denmark)

Teilmann, Grete; Juul, Anders; Skakkebaek, Niels E

2002-01-01

-called endocrine disrupters. Precocious puberty has been described in several case reports of accidental exposure to oestrogenic compounds in cosmetic products, food and pharmaceuticals. Local epidemics of premature thelarche have also been suggested to be linked to endocrine disrupters. Children adopted from...... developing countries to industrialized countries often develop precocious puberty. Not only precocious puberty, but also delayed puberty can, theoretically, be associated with exposure to endocrine disrupters. While it is very plausible that endocrine disrupters may disturb pubertal development...

Toxicological consequences of TiO2, SiC nanoparticles and multi-walled carbon nanotubes exposure in several mammalian cell types: an in vitro study

International Nuclear Information System (INIS)

Barillet, Sabrina; Simon-Deckers, Angelique; Herlin-Boime, Nathalie; Mayne-L'Hermite, Martine; Reynaud, Cecile; Cassio, Doris; Gouget, Barbara; Carriere, Marie

2010-01-01

The development of nanotechnologies may lead to dissemination of potentially toxic nanoparticles in the environment. Toxicology of these nano-sized particles is thus attracting attention of public and governments worldwide. Our research is focused on the in vitro response of eukaryotic cells to nanoparticles exposure. For this purpose, we used cellular models of primary target organs (lung: A549 alveolar epithelial cells), or secondary target organs (liver: WIF-B9, Can-10 and kidneys: NRK-52E, LLC-PK1 proximal cells), i.e., organs exposed if nanoparticles are translocated through epithelial barriers. These cells were exposed to TiO 2 , SiC nanoparticles or multi-walled carbon nanotubes (MWCNT). The influence of nanoparticles physico-chemical characteristics on various toxicological endpoints (cytotoxicity, reactive oxygen species generation, genotoxicity) was specified. Our data demonstrate that nanoparticles toxicity depend on their size, morphology, and chemical composition, the finest, spherical shaped, and anatase TiO 2 nanoparticles being the more cytotoxic to NRK-52E cells, while SiC nanoparticles exert almost no cytotoxicity. MWCNT cytotoxicity neither depended on their length, nor on the presence of metal impurities. Nanoparticles cytotoxicity also depended on the exposed cell line. All the tested nanoparticles were uptaken by cells and caused intracellular reactive oxygen species generation. Relative to genotoxic effects, DNA strand breaks were detected in NRK-52E cells via the alkaline comet assay after exposure of cells to TiO 2 nanoparticles and to a lesser extent after exposure to MWCNT, but no double strand breaks were detected. The originality of this study lies on the panel of nanomaterials which were tested on a variety of cell lines. All these data may lead to a better understanding of nanomaterial toxicity and hazards for health.

Cytotoxicity of TiO2 nanoparticles towards freshwater sediment microorganisms at low exposure concentrations

International Nuclear Information System (INIS)

Kumari, Jyoti; Kumar, Deepak; Mathur, Ankita; Naseer, Arif; Kumar, Ravi Ranjan; Thanjavur Chandrasekaran, Prathna; Chaudhuri, Gouri; Pulimi, Mrudula; Raichur, Ashok M.; Babu, S.; Chandrasekaran, Natarajan; Nagarajan, R.; Mukherjee, Amitava

2014-01-01

There is a persistent need to assess the effects of TiO 2 nanoparticles on the aquatic ecosystem owing to their increasing usage in consumer products and risk of environmental release. The current study is focused on TiO 2 nanoparticle-induced acute toxicity at sub-ppm level (≤1 ppm) on the three different freshwater sediment bacterial isolates and their consortium under two different irradiation (visible light and dark) conditions. The consortium of the bacterial isolates was found to be less affected by the exposure to the nanoparticles compared to the individual cells. The oxidative stress contributed considerably towards the cytotoxicity under both light and dark conditions. A statistically significant increase in membrane permeability was noted under the dark conditions as compared to the light conditions. The optical and fluorescence microscopic images showed aggregation and chain formation of the bacterial cells, when exposed to the nanoparticles. The electron microscopic (SEM, TEM) observations suggested considerable damage of cells and bio-uptake of nanoparticles. The exopolysaccrides (EPS) production and biofilm formation were noted to increase in the presence of the nanoparticles, and expression of the key genes involved in biofilm formation was studied by RT-PCR. - Highlights: • Toxicity of NPs towards freshwater sediment bacteria at sub-ppm concentrations. • Decreased toxicity of the nanoparticles in the consortium of microorganisms. • Enhanced bacterial resistance through EPS and biofilm formation in the presence of NPs. • Considerable surface damage of cells and internalization of NPs. • Gene expression analyses related to biofilm formation in the presence of NPs

Exposure to modern, widespread environmental endocrine disrupting chemicals and their effect on the reproductive potential of women: an overview of current epidemiological evidence.

Science.gov (United States)

Karwacka, Anetta; Zamkowska, Dorota; Radwan, Michał; Jurewicz, Joanna

2017-07-31

Growing evidence indicates that exposure to widespread, environmental contaminants called endocrine disruptors (EDCs) negatively affects animal and human reproductive health and has been linked to several diseases including infertility. This review aims to evaluate the impact of environmental exposure to endocrine disrupting chemicals [phthalates, parabens, triclosan, bisphenol A (BPA), organochlorine (PCBs) and perfluorinated (PFCs) compounds] on the reproductive potential among women, by reviewing most recently published literature. Epidemiological studies focusing on EDCs exposure and reproductive potential among women for the last 16 years were identified by a search of the PUBMED, MEDLINE, EBSCO and TOXNET literature databases. The results of the presented studies show that exposure to EDCs impacts the reproductive potential in women, measured by ovarian reserve and by assisted reproductive technology outcomes. Exposure to environmental endocrine disrupting chemicals decrease: (i) oestradiol levels (BPA); (ii) anti-Müllerian hormone concentrations (PCBs); (iii) antral follicle count (BPA, parabens, phthalates); (iv) oocyte quality (BPA, triclosan, phthalates, PCBs); (v) fertilization rate (PFCs, PCBs); (vi) implantation (BPA, phthalates, PCBs); (vii) embryo quality (triclosan, PCBs, BPA); (viii) rate of clinical pregnancy and live births (parabens, phthalates). The studies were mostly well-designed and used prospective cohorts with the exposure assessment based on the biomarker of exposure. Considering the suggested health effects, more epidemiological data is urgently needed to confirm the presented findings.

Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs.

Science.gov (United States)

Wu, Wenting; Ichihara, Gaku; Hashimoto, Naozumi; Hasegawa, Yoshinori; Hayashi, Yasuhiko; Tada-Oikawa, Saeko; Suzuki, Yuka; Chang, Jie; Kato, Masashi; D'Alessandro-Gabazza, Corina N; Gabazza, Esteban C; Ichihara, Sahoko

2014-12-30

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.

Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

Directory of Open Access Journals (Sweden)

Ryu HJ

2014-12-01

Full Text Available Hwa Jung Ryu,1,* Nak-won Seong,2,* Byoung Joon So,1 Heung-sik Seo,2 Jun-ho Kim,2 Jeong-Sup Hong,2 Myeong-kyu Park,2 Min-Seok Kim,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Mu yeb Seo,2 Meyoung-Kon Kim,3 Eun Ho Maeng,2 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, South Korea; 2Korea Testing and Research Institute, Gyunggi-Do, South Korea; 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea; 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, South Korea *These authors contributed equally to this work Abstract: Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. Keywords: silica nanoparticles, toxicity, dermal route

Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

DEFF Research Database (Denmark)

Hass, Ulla; Boberg, Julie; Christiansen, Sofie

2012-01-01

The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase...... and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans....

Short-term exposure to dim light at night disrupts rhythmic behaviors and causes neurodegeneration in fly models of tauopathy and Alzheimer's disease.

Science.gov (United States)

Kim, Mari; Subramanian, Manivannan; Cho, Yun-Ho; Kim, Gye-Hyeong; Lee, Eunil; Park, Joong-Jean

2018-01-08

The accumulation and aggregation of phosphorylated tau proteins in the brain are the hallmarks for the onset of Alzheimer's disease (AD). In addition, disruptions in circadian rhythms (CRs) with altered sleep-wake cycles, dysregulation of locomotion, and increased memory defects have been reported in patients with AD. Drosophila flies that have an overexpression of human tau protein in neurons exhibit most of the symptoms of human patients with AD, including locomotion defects and neurodegeneration. Using the fly model for tauopathy/AD, we investigated the effects of an exposure to dim light at night on AD symptoms. We used a light intensity of 10 lux, which is considered the lower limit of light pollution in many countries. After the tauopathy flies were exposed to the dim light at night for 3 days, the flies showed disrupted CRs, altered sleep-wake cycles due to increased pTau proteins and neurodegeneration, in the brains of the AD flies. The results indicate that the nighttime exposure of tauopathy/AD model Drosophila flies to dim light disrupted CR and sleep-wake behavior and promoted neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Endocrine-disrupting chemicals and obesity development in humans: A review

DEFF Research Database (Denmark)

Tang-Péronard, Jeanett; Andersen, Helle Raun; Jensen, Tina Kold

2011-01-01

This study reviewed the literature on the relations between exposure to chemicals with endocrine-disrupting abilities and obesity in humans. The studies generally indicated that exposure to some of the endocrine-disrupting chemicals was associated with an increase in body size in humans...... dibenzofurans found either associations with weight gain or an increase in waist circumference, or no association. The one study investigating relations with bisphenol A found no association. Studies investigating prenatal exposure indicated that exposure in utero may cause permanent physiological changes...

How important is drinking water exposure for the risks of engineered nanoparticles to consumers?

DEFF Research Database (Denmark)

Tiede, Karen; Hansen, Steffen Foss; Westerhoff, Paul

2016-01-01

product types on the UK market as well as release scenarios, their possible fate and behaviour in raw water and during drinking water treatment was performed. Based on the available data, all the ENPs which are likely to reach water sources were identified and categorized. Worst case concentrations......This study explored the potential for engineered nanoparticles (ENPs) to contaminate the UK drinking water supplies and established the significance of the drinking water exposure route compared to other routes of human exposure. A review of the occurrence and quantities of ENPs in different...... drinking waters. Worst case predicted concentrations in drinking waters were in the low- to sub-µg/l range and more realistic estimates were tens of ng/l or less. For the majority of product types, human exposure via drinking water was predicted to be less important than exposure via other routes...

Effect of silver nanoparticles on Mediterranean sea urchin embryonal development is species specific and depends on moment of first exposure.

Science.gov (United States)

Burić, Petra; Jakšić, Željko; Štajner, Lara; Dutour Sikirić, Maja; Jurašin, Darija; Cascio, Claudia; Calzolai, Luigi; Lyons, Daniel Mark

2015-10-01

With the ever growing use of nanoparticles in a broad range of industrial and consumer applications there is increasing likelihood that such nanoparticles will enter the aquatic environment and be transported through freshwater systems, eventually reaching estuarine or marine waters. Due to silver's known antimicrobial properties and widespread use of silver nanoparticles (AgNP), their environmental fate and impact is therefore of particular concern. In this context we have investigated the species-specific effects of low concentrations of 60 nm AgNP on embryonal development in Mediterranean sea urchins Arbacia lixula, Paracentrotus lividus and Sphaerechinus granularis. The sensitivity of urchin embryos was tested by exposing embryos to nanoparticle concentrations in the 1-100 μg L(-1) range, with times of exposure varying from 30 min to 24 h (1 h-48 h for S. granularis) post-fertilisation which corresponded with fertilized egg, 4 cell, blastula and gastrula development phases. The most sensitive species to AgNP was A. lixula with significant modulation of embryonal development at the lowest AgNP concentrations of 1-10 μg L(-1) with high numbers of malformed embryos or arrested development. The greatest impact on development was noted for those embryos first exposed to nanoparticles at 6 and 24 h post fertilisation. For P. lividus, similar effects were noted at higher concentrations of 50 μg L(-1) and 100 μg L(-1) for all times of first exposure. The S. granularis embryos indicated a moderate AgNP impact, and significant developmental abnormalities were recorded in the concentration range of 10-50 μg L(-1). As later post-fertilisation exposure times to AgNP caused greater developmental changes in spite of a shorter total exposure time led us to postulate on additional mechanisms of AgNP toxicity. The results herein indicate that toxic effects of AgNP are species-specific. The moment at which embryos first encounter AgNP is also shown to be

Applying gold nanoparticles as tumor-vascular disrupting agents during brachytherapy: estimation of endothelial dose enhancement

Energy Technology Data Exchange (ETDEWEB)

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I, E-mail: mmakrigiorgos@lroc.harvard.ed [Department of Radiation Oncology, Division of Medical Physics and Biophysics, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115 (United States)

2010-11-07

Tumor vascular disrupting agents (VDAs) represent a promising approach to the treatment of cancer, in view of the tumor vasculature's pivotal role in tumor survival, growth and metastasis. VDAs targeting the tumor's dysmorphic endothelial cells can cause selective and rapid occlusion of the tumor vasculature, leading to tumor cell death from ischemia and extensive hemorrhagic necrosis. In this study, the potential for applying gold nanoparticles (AuNPs) as VDAs, during brachytherapy, is examined. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the endothelial dose enhancement caused by radiation-induced photo/Auger electrons originating from AuNPs targeting the tumor endothelium. The endothelial dose enhancement factor (EDEF), representing the ratio of the dose to the endothelium with and without gold nanoparticles was calculated for different AuNP local concentrations, and endothelial cell thicknesses. Four brachytherapy sources were investigated, I-125, Pd-103, Yb-169, as well as 50 kVp x-rays. The results reveal that, even at relatively low intra-vascular AuNP concentrations, ablative dose enhancement to tumor endothelial cells due to photo/Auger electrons from the AuNPs can be achieved. Pd-103 registered the highest EDEF values of 7.4-271.5 for local AuNP concentrations ranging from 7 to 350 mg g{sup -1}, respectively. Over the same concentration range, I-125, 50 kVp and Yb-169 yielded values of 6.4-219.9, 6.3-214.5 and 4.0-99.7, respectively. Calculations of the EDEF as a function of endothelial cell thickness showed that lower energy sources like Pd-103 reach the maximum EDEF at smaller thicknesses. The results also reveal that the highest contribution to the EDEF comes from Auger electrons, apparently due to their shorter range. Overall, the data suggest that ablative dose enhancement to tumor endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs as adjuvants to

Exposure to widespread environmental endocrine disrupting chemicals and human sperm sex ratio

International Nuclear Information System (INIS)

Jurewicz, Joanna; Radwan, Michał; Sobala, Wojciech; Radwan, Paweł; Jakubowski, Lucjusz; Wielgomas, Bartosz; Ligocka, Danuta; Brzeźnicki, Sławomir; Hanke, Wojciech

2016-01-01

were negatively related to Y:X sperm chromosome ratio. • Our results showed that urinary level of metabolites of synthetic pyrethroids decrease the sperm sex ratio. - Exposure to endocrine disrupting chemicals and Y:X sperm chromosome ratio.

Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.

Science.gov (United States)

Liu, Rong; Colby, Aaron H; Gilmore, Denis; Schulz, Morgan; Zeng, Jialiu; Padera, Robert F; Shirihai, Orian; Grinstaff, Mark W; Colson, Yolonda L

2016-09-01

The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Titanium dioxide nanoparticles: occupational exposure assessment in the photocatalytic paving production

International Nuclear Information System (INIS)

Spinazzè, Andrea; Cattaneo, Andrea; Limonta, Marina; Bollati, Valentina; Bertazzi, Pier Alberto; Cavallo, Domenico M.

2016-01-01

Limited data are available regarding occupational exposure assessment to nano-sized titanium dioxide (nano-TiO_2). The objective of this study is to assess the occupational exposure of workers engaged in the application of nano-TiO_2 onto concrete building materials, by means of a multi-metric approach (mean diameter, number, mass and surface area concentrations). The measurement design consists of the combined use of (i) direct-reading instruments to evaluate the total particle number concentrations relative to the background concentration and the mean size-dependent characteristics of particles (mean diameter and surface area concentration) and to estimate the 8-h time-weighted average (8-h TWA) exposure to nano-TiO_2 for workers involved in different working tasks; and (ii) filter-based air sampling, used for the determination of size-resolved particle mass concentrations. A further estimation was performed to obtain the mean 8-h TWA exposure values expressed as mass concentrations (µg nano-TiO_2/m"3). The multi-metric characterization of occupational exposure to nano-TiO_2 was significantly different both for different work environments and for each work task. Generally, workers were exposed to engineered nanoparticles (ENPs; <100 nm) mean levels lower than the recommended reference values and proposed occupational exposure limits (40,000 particle/cm"3; 300 µg/m"3) and relevant exposures to peak concentration were not likely to be expected. The estimated 8-h TWA exposure showed differences between the unexposed and exposed subjects. For these last, further differences were defined between operators involved in different work tasks. This study provides information on nano-TiO_2 number and mass concentration, size distribution, particles diameter and surface area concentrations, which were used to obtain work shift-averaged exposures.

Titanium dioxide nanoparticles: occupational exposure assessment in the photocatalytic paving production

Energy Technology Data Exchange (ETDEWEB)

Spinazzè, Andrea, E-mail: andrea.spinazze@uninsubria.it; Cattaneo, Andrea; Limonta, Marina [Università degli studi dell’Insubria, Dipartimento di Scienza e Alta Tecnologia (Italy); Bollati, Valentina; Bertazzi, Pier Alberto [Università degli Studi di Milano, EPIGET-Epidemiology, Epigenetics and Toxicology Lab, Dipartimento di Scienze Cliniche e di Comunità (Italy); Cavallo, Domenico M. [Università degli studi dell’Insubria, Dipartimento di Scienza e Alta Tecnologia (Italy)

2016-06-15

Limited data are available regarding occupational exposure assessment to nano-sized titanium dioxide (nano-TiO{sub 2}). The objective of this study is to assess the occupational exposure of workers engaged in the application of nano-TiO{sub 2} onto concrete building materials, by means of a multi-metric approach (mean diameter, number, mass and surface area concentrations). The measurement design consists of the combined use of (i) direct-reading instruments to evaluate the total particle number concentrations relative to the background concentration and the mean size-dependent characteristics of particles (mean diameter and surface area concentration) and to estimate the 8-h time-weighted average (8-h TWA) exposure to nano-TiO{sub 2} for workers involved in different working tasks; and (ii) filter-based air sampling, used for the determination of size-resolved particle mass concentrations. A further estimation was performed to obtain the mean 8-h TWA exposure values expressed as mass concentrations (µg nano-TiO{sub 2}/m{sup 3}). The multi-metric characterization of occupational exposure to nano-TiO{sub 2} was significantly different both for different work environments and for each work task. Generally, workers were exposed to engineered nanoparticles (ENPs; <100 nm) mean levels lower than the recommended reference values and proposed occupational exposure limits (40,000 particle/cm{sup 3}; 300 µg/m{sup 3}) and relevant exposures to peak concentration were not likely to be expected. The estimated 8-h TWA exposure showed differences between the unexposed and exposed subjects. For these last, further differences were defined between operators involved in different work tasks. This study provides information on nano-TiO{sub 2} number and mass concentration, size distribution, particles diameter and surface area concentrations, which were used to obtain work shift-averaged exposures.

Cytotoxicity of TiO{sub 2} nanoparticles towards freshwater sediment microorganisms at low exposure concentrations

Energy Technology Data Exchange (ETDEWEB)

Kumari, Jyoti; Kumar, Deepak; Mathur, Ankita; Naseer, Arif; Kumar, Ravi Ranjan [Centre for Nanobiotechnology, VIT University, Vellore 632014 (India); Thanjavur Chandrasekaran, Prathna [Department of Materials Engineering, Indian Institute of Science, Bangalore (India); Chaudhuri, Gouri; Pulimi, Mrudula [Centre for Nanobiotechnology, VIT University, Vellore 632014 (India); Raichur, Ashok M. [Department of Materials Engineering, Indian Institute of Science, Bangalore (India); Department of Chemical Technology, University of Johannesburg (South Africa); Babu, S. [School of Bio Sciences and Technology, VIT University, Vellore (India); Chandrasekaran, Natarajan [Centre for Nanobiotechnology, VIT University, Vellore 632014 (India); Nagarajan, R. [Department of Chemical Engineering, IIT Madras, Chennai (India); Mukherjee, Amitava, E-mail: amit.mookerjea@gmail.com [Centre for Nanobiotechnology, VIT University, Vellore 632014 (India)

2014-11-15

There is a persistent need to assess the effects of TiO{sub 2} nanoparticles on the aquatic ecosystem owing to their increasing usage in consumer products and risk of environmental release. The current study is focused on TiO{sub 2} nanoparticle-induced acute toxicity at sub-ppm level (≤1 ppm) on the three different freshwater sediment bacterial isolates and their consortium under two different irradiation (visible light and dark) conditions. The consortium of the bacterial isolates was found to be less affected by the exposure to the nanoparticles compared to the individual cells. The oxidative stress contributed considerably towards the cytotoxicity under both light and dark conditions. A statistically significant increase in membrane permeability was noted under the dark conditions as compared to the light conditions. The optical and fluorescence microscopic images showed aggregation and chain formation of the bacterial cells, when exposed to the nanoparticles. The electron microscopic (SEM, TEM) observations suggested considerable damage of cells and bio-uptake of nanoparticles. The exopolysaccrides (EPS) production and biofilm formation were noted to increase in the presence of the nanoparticles, and expression of the key genes involved in biofilm formation was studied by RT-PCR. - Highlights: • Toxicity of NPs towards freshwater sediment bacteria at sub-ppm concentrations. • Decreased toxicity of the nanoparticles in the consortium of microorganisms. • Enhanced bacterial resistance through EPS and biofilm formation in the presence of NPs. • Considerable surface damage of cells and internalization of NPs. • Gene expression analyses related to biofilm formation in the presence of NPs.

Dermal exposure potential from textiles that contain silver nanoparticles.

Science.gov (United States)

Stefaniak, Aleksandr B; Duling, Mathew G; Lawrence, Robert B; Thomas, Treye A; LeBouf, Ryan F; Wade, Eleanor E; Virji, M Abbas

2014-01-01

Factors that influence exposure to silver particles from the use of textiles are not well understood. The aim of this study was to evaluate the influence of product treatment and physiological factors on silver release from two textiles. Atomic and absorbance spectroscopy, electron microscopy, and dynamic light scattering (DLS) were applied to characterize the chemical and physical properties of the textiles and evaluate silver release in artificial sweat and saliva under varying physiological conditions. One textile had silver incorporated into fiber threads (masterbatch process) and the other had silver nanoparticles coated on fiber surfaces (finishing process). Several complementary and confirmatory analytical techniques (spectroscopy, microscopy, etc.) were required to properly assess silver release. Silver released into artificial sweat or saliva was primarily in ionic form. In a simulated "use" and laundering experiment, the total cumulative amount of silver ion released was greater for the finishing process textile (0·51±0·04%) than the masterbatch process textile (0·21±0·01%); Pmasterbatch vs finishing) used to treat textile fibers was a more influential exposure factor than physiological properties of artificial sweat or saliva.

Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

Science.gov (United States)

Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

2015-01-01

Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

Monitor for detecting and assessing exposure to airborne nanoparticles

International Nuclear Information System (INIS)

Marra, Johan; Voetz, Matthias; Kiesling, Heinz-Juergen

2010-01-01

An important safety aspect of the workplace environment concerns the severity of its air pollution with nanoparticles (NP; <100 nm) and ultrafine particles (UFP; <300 nm). Depending on their size and chemical nature, exposure to these particles through inhalation can be hazardous because of their intrinsic ability to deposit in the deep lung regions and the possibility to subsequently pass into the blood stream. Recommended safety measures in the nanomaterials industry are pragmatic, aiming at exposure minimization in general, and advocating continuous control by monitoring both the workplace air pollution level and the personal exposure to airborne NPs. This article describes the design and operation of the Aerasense NP monitor that enables intelligence gathering in particular with respect to airborne particles in the 10-300 nm size range. The NP monitor provides real time information about their number concentration, average size, and surface areas per unit volume of inhaled air that deposit in the various compartments of the respiratory tract. The monitor's functionality relies on electrical charging of airborne particles and subsequent measurements of the total particle charge concentration under various conditions. Information obtained with the NP monitor in a typical workplace environment has been compared with simultaneously recorded data from a Scanning Mobility Particle Sizer (SMPS) capable of measuring the particle size distribution in the 11-1086 nm size range. When the toxicological properties of the engineered and/or released particles in the workplace are known, personal exposure monitoring allows a risk assessment to be made for a worker during each workday, when the workplace-produced particles can be distinguished from other (ambient) particles.

A review of fundamental drivers governing the emissions, dispersion and exposure to vehicle-emitted nanoparticles at signalised traffic intersections

Science.gov (United States)

Goel, Anju; Kumar, Prashant

2014-11-01

Signalised traffic intersections (TIs) are considered as pollution hot-spots in urban areas, but the knowledge of fundamental drivers governing emission, dispersion and exposure to vehicle-emitted nanoparticles (represented by particle number concentration, PNC) at TIs is yet to be established. A number of following key factors, which are important for developing an emission and exposure framework for nanoparticles at TIs, are critically evaluated as a part of this review article. In particular, (i) how do traffic- and wind-flow features affect emission and dispersion of nanoparticles? (ii) What levels of PNCs can be typically expected under diverse signal- and traffic-conditions? (iii) How does the traffic driving condition affect the particle number (PN) emissions and the particle number emission factors (PNEF)? (iv) What is the relative importance of particle transformation processes in affecting the PNCs? (v) What are important considerations for the dispersion modelling of nanoparticles? (vi) What is extent of exposure at TIs with respect to other locations in urban settings? (vii) What are the gaps in current knowledge on this topic where the future research should focus? We found that the accurate consideration of dynamic traffic flow features at TIs is essential for reliable estimates of PN emissions. Wind flow features at TIs are generally complex to generalise. Only a few field studies have monitored PNCs at TIs until now, reporting over an order of magnitude larger peak PNCs (0.7-5.4 × 105 cm-3) compared with average PNCs at typical roadsides (˜0.3 × 105 cm-3). The PN emission and thus the PNEFs can be up to an order of magnitude higher during acceleration compared with steady speed conditions. The time scale analysis suggests nucleation as the fastest transformation process, followed by dilution, deposition, coagulation and condensation. Consideration of appropriate flow features, PNEFs and transformation processes emerged as important parameters for

Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty

DEFF Research Database (Denmark)

Mouritsen, A; Aksglaede, L; Sørensen, K

2010-01-01

and increasing prevalence of adiposity may contribute, but environmental factors are also likely to be involved. In particular, the widespread presence of endocrine-disrupting chemicals (EDCs) is suspected to contribute to the trend of earlier pubertal onset. The factors regulating the physiological onset...... of normal puberty are poorly understood. This hampers investigation of the possible role of environmental influences. There are many types of EDCs. One chemical may have more than one mode of action and the effects may depend on dose and duration of the exposure, as well as the developmental stage......A recent decline in onset of puberty - especially among girls - has been observed, first in the US in the mid-1990s and now also in Europe. The development of breast tissue in girls occurs at a much younger age and the incidence of precocious puberty (PP) is increasing. Genetic factors...

Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment.

Science.gov (United States)

Hou, Jie; Li, Li; Wu, Ning; Su, Yujing; Lin, Wang; Li, Guangyu; Gu, Zemao

2016-01-01

Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic environment

Evaluation of Endocrine Disrupting Effects of Nitrate after In Utero Exposure in Rats and of Nitrate and Nitrite in the H295R and T-Screen Assay

DEFF Research Database (Denmark)

Hansen, Pernille Reimer; Taxvig, Camilla; Christiansen, Sofie

2009-01-01

/l. At GD21, fetuses were examined for anogenital distance, plasma thyroxine levels, testicular and plasma levels of testosterone and progesterone, and testicular testosterone production and histopathology. In addition, endocrine disrupting activity of nitrate and nitrite were studied in two in vitro assays......Animal studies have shown that nitrate acts as an endocrine disrupter affecting the androgen production in adult males. This raises a concern for more severe endocrine disrupting effects after exposure during the sensitive period of prenatal male sexual development. As there are no existing studies...... of effects of nitrate on male sexual development, the aim of the study was to examine how in utero exposure to nitrate would affect male rat fetuses. Pregnant dams were dosed with nitrate in the drinking water from gestational day (GD) 7 to GD21 at the following dose levels 17.5, 50, 150, 450, and 900 mg...

Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

Science.gov (United States)

Legler, Juliette; Fletcher, Tony; Govarts, Eva; Porta, Miquel; Blumberg, Bruce; Heindel, Jerrold J; Trasande, Leonardo

2015-04-01

Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555-5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6-86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200-56 400) with associated costs of €835 million (sensitivity analysis: €835 million-16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion. EDC exposures in the EU contribute

CUMULATIVE DEVELOPMENTAL EFFECTS OF ENDOCRINE DISRUPTERS: SYNERGY OR ADDITIVITY?

Science.gov (United States)

Exposure to chemicals with hormonal activity during critical developmental periods can disrupt reproductive function and development. Within the last decade, several classes of pesticides and toxic substances have been shown to disrupt differentiation of the male rat reproductive...

Exposure of cerium oxide nanoparticles to kidney bean shows disturbance in the plant defense mechanisms

Energy Technology Data Exchange (ETDEWEB)

Majumdar, Sanghamitra [Department of Chemistry, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN) (United States); Peralta-Videa, Jose R. [Department of Chemistry, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); Environmental Science and Engineering PhD Program, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN) (United States); Bandyopadhyay, Susmita [Environmental Science and Engineering PhD Program, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN) (United States); Castillo-Michel, Hiram [European Synchrotron Radiation Facility, B.P. 220-38043 Grenoble, Cedex (France); Hernandez-Viezcas, Jose-Angel [Department of Chemistry, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN) (United States); Sahi, Shivendra [Department of Biology, Western Kentucky University, Bowling Green, KY 42101 (United States); Gardea-Torresdey, Jorge L., E-mail: jgardea@utep.edu [Department of Chemistry, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); Environmental Science and Engineering PhD Program, The University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968 (United States); University of California Center for Environmental Implications of Nanotechnology (UC CEIN) (United States)

2014-08-15

Graphical abstract: - Highlights: • Kidney bean roots uptake nCeO{sub 2} primarily without biotransformation. • Cerium reached the root vascular tissues through gaps in the Casparian strip. • On longer exposure to high concentration, roots demonstrate stress response. • In leaves, guaiacol peroxidase plays a major role in ROS scavenging. - Abstract: Overwhelming use of engineered nanoparticles demands rapid assessment of their environmental impacts. The transport of cerium oxide nanoparticles (nCeO{sub 2}) in plants and their impact on cellular homeostasis as a function of exposure duration is not well understood. In this study, kidney bean plants were exposed to suspensions of ∼8 ± 1 nm nCeO{sub 2} (62.5 to 500 mg/L) for 15 days in hydroponic conditions. Plant parts were analyzed for cerium accumulation after one, seven, and 15 days of nCeO{sub 2} exposure. The primary indicators of stress like lipid peroxidation, antioxidant enzyme activities, total soluble protein and chlorophyll contents were studied. Cerium in tissues was localized using scanning electron microscopy and synchrotron μ-XRF mapping, and the chemical forms were identified using μ-XANES. In the root epidermis, cerium was primarily shown to exist as nCeO{sub 2}, although a small fraction (12%) was biotransformed to Ce(III) compound. Cerium was found to reach the root vascular tissues and translocate to aerial parts with time. Upon prolonged exposure to 500 mg nCeO{sub 2}/L, the root antioxidant enzyme activities were significantly reduced, simultaneously increasing the root soluble protein by 204%. In addition, leaf's guaiacol peroxidase activity was enhanced with nCeO{sub 2} exposure in order to maintain cellular homeostasis.

Determination of "safe" and "critical" nanoparticles exposure to welders in a workshop.

Science.gov (United States)

Gomes, J F; Miranda, R M

2017-01-01

The present study examined consequences of "safe" versus "critical" exposure to nanoparticles (NP) released during welding operations. With this aim in mind, a set of measurements regarding NP emissions was undertaken in a workshop during welding by metal active gas of carbon steel using different mixtures of argon (Ar) and carbon dioxide (CO 2 ) as well as different process parameters which might influence emission of (NP). If these measurements were conducted in several locations away from the welding sources, the graphical representation of the obtained observations with time enabled definition of "safe" and "critical" regions within a welding workshop in terms of welder's exposure. This information may be combined with the results of risk analysis derived by control banding and helps to categorize the sites where regulatory measures such as operation containment or dedicated exhaust ventilation need to be implemented.

Dietary exposure to endocrine disrupting chemicals in metropolitan population from China: a risk assessment based on probabilistic approach.

Science.gov (United States)

He, Dongliang; Ye, Xiaolei; Xiao, Yonghua; Zhao, Nana; Long, Jia; Zhang, Piwei; Fan, Ying; Ding, Shibin; Jin, Xin; Tian, Chong; Xu, Shunqing; Ying, Chenjiang

2015-11-01

The intake of contaminated foods is an important exposure pathway for endocrine disrupting chemicals (EDCs). However, data on the occurrence of EDCs in foodstuffs are sporadic and the resultant risk of co-exposure is rarely concerned. In this study, 450 food samples representing 7 food categories (mainly raw and fresh food), collected from three geographic cities in China, were analyzed for eight EDCs using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Besides estrone (E1), other EDCs including diethylstilbestrol (DES), nonylphenol (NP), bisphenol A (BPA), octylphenol (OP), 17β-estradiol (E2), 17α-ethinylestradiol (EE2), and estriol (E3) were ubiquitous in food. Dose-dependent relationships were found between NP and EE2 (r=0.196, pRisk Assessment (MCRA) system. The 50th and 95th percentile exposure of any EDCs isomer were far below the tolerable daily intake (TDI) value identically. However, the sum of 17β-estradiol equivalents (∑EEQs) exposure in population was considerably larger than the value of exposure to E2, which implied the underlying resultant risk of multiple EDCs in food should be concern. In conclusion, co-exposure via food consumption should be considered rather than individual EDCs during health risk evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: a review of rodent and human data.

Science.gov (United States)

Rasier, G; Toppari, J; Parent, A-S; Bourguignon, J-P

2006-07-25

Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents.

Effects of Exposure to the Endocrine-Disrupting Chemical Bisphenol A During Critical Windows of Murine Pituitary Development.

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Eckstrum, Kirsten S; Edwards, Whitney; Banerjee, Annesha; Wang, Wei; Flaws, Jodi A; Katzenellenbogen, John A; Kim, Sung Hoon; Raetzman, Lori T

2018-01-01

Critical windows of development are often more sensitive to endocrine disruption. The murine pituitary gland has two critical windows of development: embryonic gland establishment and neonatal hormone cell expansion. During embryonic development, one environmentally ubiquitous endocrine-disrupting chemical, bisphenol A (BPA), has been shown to alter pituitary development by increasing proliferation and gonadotrope number in females but not males. However, the effects of exposure during the neonatal period have not been examined. Therefore, we dosed pups from postnatal day (PND)0 to PND7 with 0.05, 0.5, and 50 μg/kg/d BPA, environmentally relevant doses, or 50 μg/kg/d estradiol (E2). Mice were collected after dosing at PND7 and at 5 weeks. Dosing mice neonatally with BPA caused sex-specific gene expression changes distinct from those observed with embryonic exposure. At PND7, pituitary Pit1 messenger RNA (mRNA) expression was decreased with BPA 0.05 and 0.5 μg/kg/d in males only. Expression of Pomc mRNA was decreased at 0.5 μg/kg/d BPA in males and at 0.5 and 50 μg/kg/d BPA in females. Similarly, E2 decreased Pomc mRNA in both males and females. However, no noticeable corresponding changes were found in protein expression. Both E2 and BPA suppressed Pomc mRNA in pituitary organ cultures; this repression appeared to be mediated by estrogen receptor-α and estrogen receptor-β in females and G protein-coupled estrogen receptor in males, as determined by estrogen receptor subtype-selective agonists. These data demonstrated that BPA exposure during neonatal pituitary development has unique sex-specific effects on gene expression and that Pomc repression in males and females can occur through different mechanisms. Copyright © 2018 Endocrine Society.

Cationic nanoparticles induce nanoscale disruption in living cell plasma membranes.

Science.gov (United States)

Chen, Jiumei; Hessler, Jessica A; Putchakayala, Krishna; Panama, Brian K; Khan, Damian P; Hong, Seungpyo; Mullen, Douglas G; Dimaggio, Stassi C; Som, Abhigyan; Tew, Gregory N; Lopatin, Anatoli N; Baker, James R; Holl, Mark M Banaszak; Orr, Bradford G

2009-08-13

It has long been recognized that cationic nanoparticles induce cell membrane permeability. Recently, it has been found that cationic nanoparticles induce the formation and/or growth of nanoscale holes in supported lipid bilayers. In this paper, we show that noncytotoxic concentrations of cationic nanoparticles induce 30-2000 pA currents in 293A (human embryonic kidney) and KB (human epidermoid carcinoma) cells, consistent with a nanoscale defect such as a single hole or group of holes in the cell membrane ranging from 1 to 350 nm(2) in total area. Other forms of nanoscale defects, including the nanoparticle porating agents adsorbing onto or intercalating into the lipid bilayer, are also consistent; although the size of the defect must increase to account for any reduction in ion conduction, as compared to a water channel. An individual defect forming event takes 1-100 ms, while membrane resealing may occur over tens of seconds. Patch-clamp data provide direct evidence for the formation of nanoscale defects in living cell membranes. The cationic polymer data are compared and contrasted with patch-clamp data obtained for an amphiphilic phenylene ethynylene antimicrobial oligomer (AMO-3), a small molecule that is proposed to make well-defined 3.4 nm holes in lipid bilayers. Here, we observe data that are consistent with AMO-3 making approximately 3 nm holes in living cell membranes.

Mechanistic evaluation of endocrine disrupting chemicals

DEFF Research Database (Denmark)

Taxvig, Camilla

BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent for the ...... metabolising system using liver S9 mixtures or hepatic rat microsomes could be a convenient method for the incorporation of metabolic aspects into in vitro testing for endocrine disrupting effects.......BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent......, to be able to detect effects and predict mixture effects. In addition, a new hypothesis have emerge concerning a potential role of exposure to endocrine disrupting chemicals, and the development of obesity and obesity related diseases. AIM: This PhD project aimed to gain more information regarding...

Bisphenol A exposure in utero disrupts early oogenesis in the mouse.

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Martha Susiarjo

2007-01-01

Full Text Available Estrogen plays an essential role in the growth and maturation of the mammalian oocyte, and recent studies suggest that it also influences follicle formation in the neonatal ovary. In the course of studies designed to assess the effect of the estrogenic chemical bisphenol A (BPA on mammalian oogenesis, we uncovered an estrogenic effect at an even earlier stage of oocyte development--at the onset of meiosis in the fetal ovary. Pregnant mice were treated with low, environmentally relevant doses of BPA during mid-gestation to assess the effect of BPA on the developing ovary. Oocytes from exposed female fetuses displayed gross aberrations in meiotic prophase, including synaptic defects and increased levels of recombination. In the mature female, these aberrations were translated into an increase in aneuploid eggs and embryos. Surprisingly, we observed the same constellation of meiotic defects in fetal ovaries of mice homozygous for a targeted disruption of ERbeta, one of the two known estrogen receptors. This, coupled with the finding that BPA exposure elicited no additional effects in ERbeta null females, suggests that BPA exerts its effect on the early oocyte by interfering with the actions of ERbeta. Together, our results show that BPA can influence early meiotic events and, importantly, indicate that the oocyte itself may be directly responsive to estrogen during early oogenesis. This raises concern that brief exposures during fetal development to substances that mimic or antagonize the effects of estrogen may adversely influence oocyte development in the exposed female fetus.

Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells

Science.gov (United States)

Yu, Kyeong-Nam; Chang, Seung-Hee; Park, Soo Jin; Lim, Joohyun; Lee, Jinkyu; Yoon, Tae-Jong; Kim, Jun-Sung; Cho, Myung-Haing

2015-01-01

Nanomaterials are used in diverse fields including food, cosmetic, and medical industries. Titanium dioxide nanoparticles (TiO2-NP) are widely used, but their effects on biological systems and mechanism of toxicity have not been elucidated fully. Here, we report the toxicological mechanism of TiO2-NP in cell organelles. Human bronchial epithelial cells (16HBE14o-) were exposed to 50 and 100 μg/mL TiO2-NP for 24 and 48 h. Our results showed that TiO2-NP induced endoplasmic reticulum (ER) stress in the cells and disrupted the mitochondria-associated endoplasmic reticulum membranes (MAMs) and calcium ion balance, thereby increasing autophagy. In contrast, an inhibitor of ER stress, tauroursodeoxycholic acid (TUDCA), mitigated the cellular toxic response, suggesting that TiO2-NP promoted toxicity via ER stress. This novel mechanism of TiO2-NP toxicity in human bronchial epithelial cells suggests that further exhaustive research on the harmful effects of these nanoparticles in relevant organisms is needed for their safe application. PMID:26121477

Pulmotoxicological effects caused by long-term titanium dioxide nanoparticles exposure in mice

Energy Technology Data Exchange (ETDEWEB)

Sun, Qingqing; Tan, Danning; Ze, Yuguan; Sang, Xuezi [Medical College of Soochow University, Suzhou 215123 (China); Liu, Xiaorun [Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009 (China); Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009 (China); Gui, Suxin; Cheng, Zhe; Cheng, Jie; Hu, Renping; Gao, Guodong; Liu, Gan; Zhu, Min; Zhao, Xiaoyang; Sheng, Lei; Wang, Ling [Medical College of Soochow University, Suzhou 215123 (China); Tang, Meng, E-mail: tm@seu.edu.cn [Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009 (China); Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009 (China); Hong, Fashui, E-mail: Hongfsh_cn@sina.com [Medical College of Soochow University, Suzhou 215123 (China)

2012-10-15

Highlights: Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NPs could be significantly accumulated in the lung. Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NPs caused pulmonary injury in mice. Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NP promoted the expression of inflammatory cytokines in the lung. Black-Right-Pointing-Pointer Exposure to TiO{sub 2} NP caused ROS overproduction in the lung. - Abstract: Exposure to titanium dioxide nanoparticles (TiO{sub 2} NPs) has been demonstrated to result in pulmonary inflammation in animals; however, very little is known about the molecular mechanisms of pulmonary injury due to TiO{sub 2} NPs exposure. The aim of this study was to evaluate the oxidative stress and molecular mechanism associated with pulmonary inflammation in chronic lung toxicity caused by the intratracheal instillation of TiO{sub 2} NPs for 90 consecutive days in mice. Our findings suggest that TiO{sub 2} NPs are significantly accumulated in the lung, leading to an obvious increase in lung indices, inflammation and bleeding in the lung. Exposure to TiO{sub 2} NPs significantly increased the accumulation of reactive oxygen species and the level of lipid peroxidation, and decreased antioxidant capacity in the lung. Furthermore, TiO{sub 2} NPs exposure activated nuclear factor-{kappa}B, increased the levels of tumor necrosis factor-{alpha}, cyclooxygenase-2, heme oxygenase-1, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1{beta}, and CYP1A1 expression. However, TiO{sub 2} NPs exposure decreased NF-{kappa}B-inhibiting factor and heat shock protein 70 expression. Our results suggest that the generation of pulmonary inflammation caused by TiO{sub 2} NPs in mice is closely related to oxidative stress and the expression of inflammatory cytokines.

Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles.

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Jie Ji

Full Text Available Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents.In this study, we successfully established a combination of an exposure system (XposeALI with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC and fibroblast at air-liquid interface (ALI. Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd nanoparticles which sized 6-10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system.Exposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM and apical lavage medium (AM were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM.This combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting.

Development of Combining of Human Bronchial Mucosa Models with XposeALI® for Exposure of Air Pollution Nanoparticles.

Science.gov (United States)

Ji, Jie; Hedelin, Anna; Malmlöf, Maria; Kessler, Vadim; Seisenbaeva, Gulaim; Gerde, Per; Palmberg, Lena

2017-01-01

Exposure to agents via inhalation is of great concerns both in workplace environment and in the daily contact with particles in the ambient air. Reliable human airway exposure systems will most likely replace animal experiment in future toxicity assessment studies of inhaled agents. In this study, we successfully established a combination of an exposure system (XposeALI) with 3D models mimicking both healthy and chronic bronchitis-like mucosa by co-culturing human primary bronchial epithelial cells (PBEC) and fibroblast at air-liquid interface (ALI). Light-, confocal microscopy, scanning- and transmission electron microscopy, transepithelial electrical resistance (TEER) measurement and RT-PCR were performed to identify how the PBEC differentiated under ALI culture condition. Both models were exposed to palladium (Pd) nanoparticles which sized 6-10 nm, analogous to those released from modern car catalysts, at three different concentrations utilizing the XposeALI module of the PreciseInhale® exposure system. Exposing the 3D models to Pd nanoparticles induced increased secretion of IL-8, yet the chronic bronchitis-like model released significantly more IL-8 than the normal model. The levels of IL-8 in basal medium (BM) and apical lavage medium (AM) were in the same ranges, but the secretion of MMP-9 was significantly higher in the AM compared to the BM. This combination of relevant human bronchial mucosa models and sophisticated exposure system can mimic in vivo conditions and serve as a useful alternative animal testing tool when studying adverse effects in humans exposed to aerosols, air pollutants or particles in an occupational setting.

Actual problems of exposure risk assessment of finely dispersed aerosols and aerosols of nanoparticles

Directory of Open Access Journals (Sweden)

A. I. Sevalnev

2018-04-01

Full Text Available Purpose of the study – analysis of the scientific literature on generalization of the data on domestic and foreign experience in risk assessment due to exposure to finely dispersed aerosols and aerosols of nanoparticles (NPs. The article summarizes data of long-term studies on the effect of nanomaterials and nanoparticles on the quality of human habitat and health. The domestic and foreign experience of harm health assessment, safety of new types of nanomaterials for the environment and work-related conditions have been analyzed. There are numerous studies of foreign and domestic scientists on the biological activity of nanoparticles and their effect on experimental animals, namely, on the specificity of their effect on various organs and systems of the body. Classification of nanomaterials, depending on their chemical composition, is presented. Attention is paid to the problems of nanosafety, namely, to the evaluation of nanotoxicity of substances and to the definition of the concept of a “dose” for nanoparticles. The data on the presence of finely dispersed and ultra-fine particles in the atmospheric air, which increase risk of respiratory system diseases among residents of large megacities, is given. There is special importance on assessing work conditions and occupational risks in production and use of materials which contain nanoparticles as well as in production processes with formation of the fine dust and nanoparticles indicated in the article. Due to the lack of a clear system for assessing health risks related to the action of nanoparticles, lack of common criteria of harmfulness and maximum allowable concentrations for most nanoparticles and uniform methods of their control, it is suggested to strictly adhere to protective measures in contact with nanomaterials and active improvement of nanosecurity measures. Conclusions. High toxicity and health hazards of finely dispersed and ultra-fine particles confirm need to control their

Electrothermal piezoresistive cantilever resonators for personal measurements of nanoparticles in workplace exposure

Science.gov (United States)

Wasisto, Hutomo Suryo; Wu, Wenze; Uhde, Erik; Waag, Andreas; Peiner, Erwin

2015-05-01

Low-cost and low-power piezoresistive cantilever resonators with integrated electrothermal heaters are developed to support the sensing module enhancement of the second generation of handheld cantilever-based airborne nanoparticle (NP) detector (CANTOR-2). These sensors are used for direct-reading of exposure to carbon engineered nanoparticles (ENPs) at indoor workplaces. The cantilever structures having various shapes of free ends are created using silicon bulk micromachining technologies (i.e, rectangular, hammer-head, triangular, and U-shaped cantilevers). For a complete wearable CANTOR-2, all components of the proposed detector can be grouped into two main units depending on their packaging placements (i.e., the NP sampler head and the electronics mounted in a handy-format housing). In the NP sampler head, a miniaturized electrophoretic aerosol sampler and a resonant silicon cantilever mass sensor are employed to collect the ENPs from the air stream to the cantilever surfaces and measuring their mass concentration, respectively. After calibration, the detected ENP mass concentrations of CANTOR-2 show a standard deviation from fast mobility particle sizer (FMPS, TSI 3091) of 8-14%.

Maternal exposure to di-(2-ethylhexyl) phthalate disrupts placental growth and development in pregnant mice

Energy Technology Data Exchange (ETDEWEB)

Zong, Teng; Lai, Lidan [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Hu, Jia [Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi (China); Guo, Meijun; Li, Mo; Zhang, Lu; Zhong, Chengxue; Yang, Bei; Wu, Lei; Zhang, Dalei; Tang, Min [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China); Kuang, Haibin, E-mail: kuanghaibin@ncu.edu.cn [Department of Physiology, School of Medicine, Nanchang University, Nanchang, Jiangxi 330006 (China)

2015-10-30

Highlights: • The influence of DEHP on the development of placenta was investigated. • DEHP disrupts the growth and development of placenta. • DEHP disrupts the formation of labyrinth vascularization. • DEHP inhibits the proliferation of ectoplacental cone and placenta. • DEHP induces the apoptosis of placenta via activated MAPK signaling pathway. - Abstract: Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and widely dispersed in the environment. DEHP exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, no detailed information is available about the effect of DEHP on the placentation during pregnancy. Thus, our aim was to explore the effect of DEHP on the growth and development of placenta in vivo. Mice were administered DEHP by gavages at 125, 250, 500 mg/kg/day from gestational days (GD) 1 until sacrifice. Results showed that DEHP treatment significantly reduced the weight of placenta at GD 13. Histopathologically, in DEHP-treated group, the ectoplacental cones significantly became smaller at GD9, and total area of placenta and area of spongiotrophoblast were significantly reduced at GD 13. Expression levels of Ascl2, Esx1 and Fosl1 mRNA dramatically decreased in DEHP-treated placenta at GD 13. DEHP administration disrupted labyrinth vascularization of placentas, and inhibited proliferation and induced apoptosis of placenta by the activation of caspase-3 and -8, up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein at GD 13. In conclusion, these results suggest that adverse pregnancy outcomes including low birth-weight and pregnancy loss exposed to DEHP are possibly mediated, at least in part, via the suppression of placental growth and development.

The Association of Telomere Length With Family Violence and Disruption

Science.gov (United States)

Mabile, Emily; Brett, Zoë H.; Esteves, Kyle; Jones, Edward; Shirtcliff, Elizabeth A.; Theall, Katherine P.

2014-01-01

BACKGROUND: To enhance the understanding of biological mechanisms connecting early adversity and negative health, we examine the association between family interpersonal violence and disruption and telomere length in youth. These specific exposures were selected because of their established links with negative health consequences across the life-course. METHODS: Children, age 5 to 15, were recruited from the greater New Orleans area, and exposure to family disruption and violence was assessed through caregiver report. Telomere length, from buccal cell DNA (buccal telomere length [bTL]), was determined by using monochrome multiplex quantitative real-time polymerase chain reaction. The association between bTL and adversity exposure was tested (n = 80). RESULTS: Cumulative exposure to interpersonal violence and family disruption was correlated with bTL. Controlling for other sociodemographic factors, bTL was significantly shorter in children with higher exposure to family violence and disruption. Witnessing family violence exerted a particularly potent impact. A significant gender interaction was found (β = −0.0086, SE = 0.0031, z test= −2.79, P = .0053) and analysis revealed the effect only in girls. CONCLUSIONS: bTL is a molecular biomarker of adversity and allostatic load that is detectable in childhood. The present results extend previous studies by demonstrating that telomeres are sensitive to adversity within the overarching family domain. These findings suggest that the family ecology may be an important target for interventions to reduce the biological impact of adversity in the lives of children. PMID:24936002

The association of telomere length with family violence and disruption.

Science.gov (United States)

Drury, Stacy S; Mabile, Emily; Brett, Zoë H; Esteves, Kyle; Jones, Edward; Shirtcliff, Elizabeth A; Theall, Katherine P

2014-07-01

To enhance the understanding of biological mechanisms connecting early adversity and negative health, we examine the association between family interpersonal violence and disruption and telomere length in youth. These specific exposures were selected because of their established links with negative health consequences across the life-course. Children, age 5 to 15, were recruited from the greater New Orleans area, and exposure to family disruption and violence was assessed through caregiver report. Telomere length, from buccal cell DNA (buccal telomere length [bTL]), was determined by using monochrome multiplex quantitative real-time polymerase chain reaction. The association between bTL and adversity exposure was tested (n = 80). Cumulative exposure to interpersonal violence and family disruption was correlated with bTL. Controlling for other sociodemographic factors, bTL was significantly shorter in children with higher exposure to family violence and disruption. Witnessing family violence exerted a particularly potent impact. A significant gender interaction was found (β = -0.0086, SE = 0.0031, z test= -2.79, P = .0053) and analysis revealed the effect only in girls. bTL is a molecular biomarker of adversity and allostatic load that is detectable in childhood. The present results extend previous studies by demonstrating that telomeres are sensitive to adversity within the overarching family domain. These findings suggest that the family ecology may be an important target for interventions to reduce the biological impact of adversity in the lives of children. Copyright © 2014 by the American Academy of Pediatrics.

Nanoparticle-specific changes in Arabidopsis thaliana gene expression after exposure to ZnO, TiO{sub 2}, and fullerene soot

Energy Technology Data Exchange (ETDEWEB)

Landa, Premysl [Laboratory of Plant Biotechnologies, Institute of Experimental Botany AS CR, v.v.i., 165 02 Prague 6 - Lysolaje (Czech Republic); Vankova, Radomira [Laboratory of Hormonal Regulations in Plants, Institute of Experimental Botany AS CR, v.v.i., 165 02 Prague 6 - Lysolaje (Czech Republic); Andrlova, Jana [Laboratory of Plant Biotechnologies, Institute of Experimental Botany AS CR, v.v.i., 165 02 Prague 6 - Lysolaje (Czech Republic); Department of Crop Sciences and Agroforestry, Institute of Tropics and Subtropics, Czech University of Life Sciences Prague, 165 21 Prague 6 - Suchdol (Czech Republic); Hodek, Jan [Department of Molecular Biology, Crop Research Institute, v.v.i., 161 06 Praha 6 - Ruzyne (Czech Republic); Marsik, Petr [Laboratory of Plant Biotechnologies, Institute of Experimental Botany AS CR, v.v.i., 165 02 Prague 6 - Lysolaje (Czech Republic); Storchova, Helena [Plant Reproduction Laboratory, Institute of Experimental Botany AS CR, v.v.i., 165 02 Prague 6 - Lysolaje (Czech Republic); White, Jason C. [Department of Analytical Chemistry, Connecticut Agricultural Experiment Station, 123 Huntington Street, New Haven, CT 06512 (United States); Vanek, Tomas, E-mail: vanek@ueb.cas.cz [Laboratory of Plant Biotechnologies, Institute of Experimental Botany AS CR, v.v.i., 165 02 Prague 6 - Lysolaje (Czech Republic)

2012-11-30

Highlights: Black-Right-Pointing-Pointer Exposure to different nanoparticles resulted in specific changes in gene transcription. Black-Right-Pointing-Pointer Nano ZnO caused most dramatic changes in Arabidopsis gene expression. Black-Right-Pointing-Pointer Nano ZnO was the most toxic and up-regulated most stress-related genes. Black-Right-Pointing-Pointer Fullerene soot caused significant gene expression response - mainly stress-related. Black-Right-Pointing-Pointer Nano TiO{sub 2} had weak impact on Arabidopsis gene expression indicating minimal toxicity. - Abstract: The effect of exposure to 100 mg/L zinc oxide (nZnO), fullerene soot (FS) or titanium dioxide (nTiO{sub 2}) nanoparticles on gene expression in Arabidopsis thaliana roots was studied using microarrays. After 7 d, nZnO, FS, or nTiO{sub 2} exposure resulted in 660 up- and 826 down-regulated genes, 232 up- and 189 down-regulated genes, and 80 up- and 74 down-regulated genes, respectively (expression difference > 2-fold; p[t test] < 0.05). The genes induced by nZnO and FS include mainly ontology groups annotated as stress responsive, including both abiotic (oxidative, salt, water deprivation) and biotic (wounding and defense to pathogens) stimuli. The down-regulated genes upon nZnO exposure were involved in cell organization and biogenesis, including translation, nucleosome assembly and microtubule based process. FS largely repressed the transcription of genes involved in electron transport and energy pathways. Only mild changes in gene expression were observed upon nTiO{sub 2} exposure, which resulted in up- and down-regulation of genes involved mainly in responses to biotic and abiotic stimuli. The data clearly indicate that the mechanisms of phytotoxicity are highly nanoparticle dependent despite of a limited overlap in gene expression response.

Disruption of the thyroid system by the thyroid-disrupting compound Aroclor 1254 in juvenile Japanese flounder (Paralichthys olivaceus.

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Yifei Dong

Full Text Available Polychlorinated biphenyls (PCBs are a group of persistent organochlorine compounds that have the potential to disrupt the homeostasis of thyroid hormones (THs in fish, particularly juveniles. In this study, thyroid histology, plasma TH levels, and iodothyronine deiodinase (IDs, including ID1, ID2, and ID3 gene expression patterns were examined in juvenile Japanese flounder (Paralichthys olivaceus following 25- and 50-day waterborne exposure to environmentally relevant concentrations of a commercial PCB mixture, Aroclor 1254 (10, 100, and 1000 ng/L with two-thirds of the test solutions renewed daily. The results showed that exposure to Aroclor 1254 for 50 d increased follicular cell height, colloid depletion, and hyperplasia. In particular, hypothyroidism, which was induced by the administration of 1000 ng/L Aroclor 1254, significantly decreased plasma TT4, TT3, and FT3 levels. Profiles of the changes in mRNA expression levels of IDs were observed in the liver and kidney after 25 and 50 d PCB exposure, which might be associated with a reduction in plasma THs levels. The expression level of ID2 mRNA in the liver exhibited a dose-dependent increase, indicating that this ID isotype might serve as sensitive and stable indicator for thyroid-disrupting chemical (TDC exposure. Overall, our study confirmed that environmentally relevant concentrations of Aroclor 1254 cause significant thyroid disruption, with juvenile Japanese flounder being suitable candidates for use in TDC studies.

Endocrine disrupting chemicals and other substances of concern in food contact materials: an updated review of exposure, effect and risk assessment.

Science.gov (United States)

Muncke, Jane

2011-10-01

Food contact materials (FCM) are an underestimated source of chemical food contaminants and a potentially relevant route of human exposure to endocrine disrupting chemicals (EDCs). Quantifying the exposure of the general population to substances from FCM relies on estimates of food consumption and leaching into food. Recent studies using polycarbonate plastics show that food simulants do not always predict worst-case leaching of bisphenol A, a common FCM substance. Also, exposure of children to FCM substances is not always realistically predicted using the common conventions and thus possibly misjudged. Further, the exposure of the whole population to substances leaching into dry foods is underestimated. Consumers are exposed to low levels of substances from FCM across their entire lives. Effects of these compounds currently are assessed with a focus on mutagenicity and genotoxicity. This approach however neglects integrating recent new toxicological findings, like endocrine disruption, mixture toxicity, and developmental toxicity. According to these new toxicology paradigms women of childbearing age and during pregnancy are a new sensitive population group requiring more attention. Furthermore, in overweight and obese persons a change in the metabolism of xenobiotics is observed, possibly implying that this group of consumers is insufficiently protected by current risk assessment practice. Innovations in FCM risk assessment should therefore include routine testing for EDCs and an assessment of the whole migrate toxicity of a food packaging, taking into account all sensitive population groups. In this article I focus on recent issues of interest concerning either exposure to or effects of FCM-related substances. Further, I review the use of benzophenones and organotins, two groups of known or suspected EDCs, in FCM authorized in the US and EU. Copyright © 2010 Elsevier Ltd. All rights reserved.

Carbon black nanoparticle exposure during middle and late fetal development induces immune activation in male offspring mice

International Nuclear Information System (INIS)

El-Sayed, Yasser S.; Shimizu, Ryuhei; Onoda, Atsuto; Takeda, Ken; Umezawa, Masakazu

2015-01-01

Increasing exposure to nanoparticles (NPs) has raised concerns regarding their health and safety profiles in humans and animals, especially in developing organisms, which may display increased sensitivity to NP toxicity. The present study examined the effects of gestational exposure to carbon black NP (CB-NP) on the development of the offspring immune system. Pregnant mice were exposed to CB-NP (95 μg/kg body weight) by intranasal instillation on gestational days 9 and 15. The thymus and spleen were collected from their offspring mice on postnatal day (PND) 1, 3 and 5. Thymocyte and splenocyte phenotypes were examined by determining the expression of cell-surface molecules using flow cytometry. Gene expression in the thymus and spleen was examined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Prenatal exposure to CB-NP increased total thymocytes and their immunophenotypes (CD4 − CD8 − and CD4 + CD8 + cells). It also induced an increase in total lymphocytes, and CD4 − CD8 − , particularly CD3 − B220 − cells, at PND 5 in the spleen of newborn male offspring, reflecting the stimulation of immature splenocytes. Furthermore, mRNA expression of genes related to the induction of peripheral tolerance (i.e. thymic Traf6) was upregulated. These data suggest that respiratory exposure to CB-NP during middle and late gestation may have allergic or inflammatory effects in male offspring, and may provide initial information on the potential developmental immunotoxicity of nanoparticles

Effects of benzophenone-3 exposure on endocrine disruption and reproduction of Japanese medaka (Oryzias latipes)—A two generation exposure study

International Nuclear Information System (INIS)

Kim, Sujin; Jung, Dawoon; Kho, Younglim; Choi, Kyungho

2014-01-01

Highlights: • Exposure to BP-3 led to adverse reproduction effects on Japanese medaka at 26 μg/L. • Changes in sex hormones and steroidogenic gene transcription were observed. • Parental exposure to BP-3 influenced on the growth of second generation fish. - Abstract: Benzophenone-3 (BP-3) has been widely used in sunscreens and cosmetics to protect human skin from the harmful effects of UV irradiation. While BP-3 has been frequently detected in surface waters, sediments and biota, only limited information is available on its in vivo toxicity, particularly in fish. In the present study the endocrine disrupting capacity of BP-3 and its underlying mechanisms were investigated using Japanese medaka (Oryzias latipes). Adult Japanese medaka pairs (F0) were exposed to 0, 4.7, 8.4, 26, or 90 μg/L (or 0, 15, 50, 150, or 500 μg/L of BP-3 based on nominal concentration) for 14 d and its effects on sex steroid hormones, and transcription of various associated genes were determined. Following additional 14 d of exposure, the F1 eggs reproduced were counted and were further exposed to 0, 5.4, 12, or 30 μg/L of BP-3 (or 0, 15, 50, or 150 μg/L based on nominal concentrations) until 30 d after hatching. Chemical analysis of the exposed media confirmed transformation of BP-3 to benzophenone-1 (BP-1), a more potent estrogen agonist. After 14 d of the adult fish exposure, plasma concentrations of testosterone (T) significantly increased in male fish. The 17β-estradiol (E2) to T (E2/T) ratio showed significant decreases in both male and female fish. Overall down-regulation of gonadal steroidogenic genes such as star, cyp11a, cyp17, hsd3b, hsd17b3, and cyp19a was also observed. After 28 d of exposure, the daily average egg reproduction per female was significantly reduced at 26 μg/L of BP-3. However, hatchability of F1 eggs was not affected by continuous exposure. After continued exposure until 30 dph, juvenile fish showed concentration-dependent decrease of condition factor

Effects of benzophenone-3 exposure on endocrine disruption and reproduction of Japanese medaka (Oryzias latipes)—A two generation exposure study

Energy Technology Data Exchange (ETDEWEB)

Kim, Sujin; Jung, Dawoon [School of Public Health, Seoul National University, Seoul 151-742 (Korea, Republic of); Kho, Younglim [Department of Health, Environment and Safety, Eulji University, Seongnam 461-713 (Korea, Republic of); Choi, Kyungho, E-mail: kyungho@snu.ac.kr [School of Public Health, Seoul National University, Seoul 151-742 (Korea, Republic of)

2014-10-15

Highlights: • Exposure to BP-3 led to adverse reproduction effects on Japanese medaka at 26 μg/L. • Changes in sex hormones and steroidogenic gene transcription were observed. • Parental exposure to BP-3 influenced on the growth of second generation fish. - Abstract: Benzophenone-3 (BP-3) has been widely used in sunscreens and cosmetics to protect human skin from the harmful effects of UV irradiation. While BP-3 has been frequently detected in surface waters, sediments and biota, only limited information is available on its in vivo toxicity, particularly in fish. In the present study the endocrine disrupting capacity of BP-3 and its underlying mechanisms were investigated using Japanese medaka (Oryzias latipes). Adult Japanese medaka pairs (F0) were exposed to 0, 4.7, 8.4, 26, or 90 μg/L (or 0, 15, 50, 150, or 500 μg/L of BP-3 based on nominal concentration) for 14 d and its effects on sex steroid hormones, and transcription of various associated genes were determined. Following additional 14 d of exposure, the F1 eggs reproduced were counted and were further exposed to 0, 5.4, 12, or 30 μg/L of BP-3 (or 0, 15, 50, or 150 μg/L based on nominal concentrations) until 30 d after hatching. Chemical analysis of the exposed media confirmed transformation of BP-3 to benzophenone-1 (BP-1), a more potent estrogen agonist. After 14 d of the adult fish exposure, plasma concentrations of testosterone (T) significantly increased in male fish. The 17β-estradiol (E2) to T (E2/T) ratio showed significant decreases in both male and female fish. Overall down-regulation of gonadal steroidogenic genes such as star, cyp11a, cyp17, hsd3b, hsd17b3, and cyp19a was also observed. After 28 d of exposure, the daily average egg reproduction per female was significantly reduced at 26 μg/L of BP-3. However, hatchability of F1 eggs was not affected by continuous exposure. After continued exposure until 30 dph, juvenile fish showed concentration-dependent decrease of condition factor

First Production of C60 Nanoparticle Plasma Jet for Study of Disruption Mitigation for ITER

Science.gov (United States)

Bogatu, I. N.; Thompson, J. R.; Galkin, S. A.; Kim, J. S.; Brockington, S.; Case, A.; Messer, S. J.; Witherspoon, F. D.

2012-10-01

Unique fast response and large mass-velocity delivery of nanoparticle plasma jets (NPPJs) provide a novel application for ITER disruption mitigation, runaway electrons diagnostics and deep fueling. NPPJs carry a much larger mass than usual gases. An electromagnetic plasma gun provides a very high injection velocity (many km/s). NPPJ has much higher ram pressure than any standard gas injection method and penetrates the tokamak confining magnetic field. Assimilation is enhanced due to the NP large surface-to-volume ratio. Radially expanding NPPJs help achieving toroidal uniformity of radiation power. FAR-TECH's NPPJ system was successfully tested: a coaxial plasma gun prototype (˜35 cm length, 96 kJ energy) using a solid state TiH2/C60 pulsed power cartridge injector produced a hyper-velocity (>4 km/s), high-density (>10^23 m-3), C60 plasma jet in ˜0.5 ms, with ˜1-2 ms overall response-delivery time. We present the TiH2/C60 cartridge injector output characterization (˜180 mg of sublimated C60 gas) and first production results of a high momentum C60 plasma jet (˜0.6 g.km/s).

Estrogens can disrupt amphibian mating behavior.

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Frauke Hoffmann

Full Text Available The main component of classical contraceptives, 17α-ethinylestradiol (EE2, has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L, alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline.

Species sensitivity and dependence on exposure conditions impacting the phototoxicity of TiO2 nanoparticles to benthic organisms

Science.gov (United States)

Toxicity of TiO2 nanoparticles (nano-TiO2) to aquatic organisms can be greatly increased upon the exposure to ultraviolet radiation (UV). This phenomenon has received some attention for pelagic species, however, investigations of nano-TiO2 phototoxicity in benthic organisms are s...

Characterization of the disassembly and reassembly of the HBV glycoprotein surface antigen, a pliable nanoparticle vaccine platform

International Nuclear Information System (INIS)

Gallagher, John R.; Torian, Udana; McCraw, Dustin M.; Harris, Audray K.

2017-01-01

While nanoparticle vaccine technology is gaining interest due to the success of vaccines like those for the human papillomavirus that is based on viral capsid nanoparticles, little information is available on the disassembly and reassembly of viral surface glycoprotein-based nanoparticles. One such particle is the hepatitis B virus surface antigen (sAg) that exists as nanoparticles. Here we show, using biochemical analysis coupled with electron microscopy, that sAg nanoparticle disassembly requires both reducing agent to disrupt intermolecular disulfide bonds, and detergent to disrupt hydrophobic interactions that stabilize the nanoparticle. Particles were otherwise resistant to salt and urea, suggesting the driving mechanism of particle formation involves hydrophobic interactions. We reassembled isolated sAg protein into nanoparticles by detergent removal and reassembly resulted in a wider distribution of particle diameters. Knowledge of these driving forces of nanoparticle assembly and stability should facilitate construction of epitope-displaying nanoparticles that can be used as immunogens in vaccines.

Characterization of the disassembly and reassembly of the HBV glycoprotein surface antigen, a pliable nanoparticle vaccine platform

Energy Technology Data Exchange (ETDEWEB)

Gallagher, John R.; Torian, Udana; McCraw, Dustin M.; Harris, Audray K., E-mail: harrisau@mail.nih.gov

2017-02-15

While nanoparticle vaccine technology is gaining interest due to the success of vaccines like those for the human papillomavirus that is based on viral capsid nanoparticles, little information is available on the disassembly and reassembly of viral surface glycoprotein-based nanoparticles. One such particle is the hepatitis B virus surface antigen (sAg) that exists as nanoparticles. Here we show, using biochemical analysis coupled with electron microscopy, that sAg nanoparticle disassembly requires both reducing agent to disrupt intermolecular disulfide bonds, and detergent to disrupt hydrophobic interactions that stabilize the nanoparticle. Particles were otherwise resistant to salt and urea, suggesting the driving mechanism of particle formation involves hydrophobic interactions. We reassembled isolated sAg protein into nanoparticles by detergent removal and reassembly resulted in a wider distribution of particle diameters. Knowledge of these driving forces of nanoparticle assembly and stability should facilitate construction of epitope-displaying nanoparticles that can be used as immunogens in vaccines.

Impact of Silver and Iron Nanoparticle Exposure on Cholesterol Uptake by Macrophages

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Jonathan H. Shannahan

2015-01-01

Full Text Available Macrophages are central to the development of atherosclerosis by absorbing lipids, promoting inflammation, and increasing plaque deposition. Nanoparticles (NPs are becoming increasingly common in biomedical applications thereby increasing exposure to the immune and vascular systems. This project investigated the influence of NPs on macrophage function and specifically cholesterol uptake. Macrophages were exposed to 20 nm silver NPs (AgNPs, 110 nm AgNPs, or 20 nm Fe3O4 NPs for 2 h and NP uptake, cytotoxicity, and subsequent uptake of fluorescently labeled cholesterol were assessed. Macrophage uptake of NPs did not induce cytotoxicity at concentrations utilized (25 μg/mL; however, macrophage exposure to 20 nm AgNPs reduced subsequent uptake of cholesterol. Further, we assessed the impact of a cholesterol-rich environment on macrophage function following NP exposure. In these sets of experiments, macrophages internalized NPs, exhibited no cytotoxicity, and altered cholesterol uptake. Alterations in the expression of scavenger receptor-B1 following NP exposure, which likely influences cholesterol uptake, were observed. Overall, NPs alter cholesterol uptake, which may have implications in the progression of vascular or immune mediated diseases. Therefore, for the safe development of NPs for biomedical applications, it is necessary to understand their impact on cellular function and biological interactions in underlying disease environments.

Genotoxicity of Silver Nanoparticles in Lung Cells of Sprague Dawley Rats after 12 Weeks of Inhalation Exposure

Directory of Open Access Journals (Sweden)

Hyun Sun Cho

2013-11-01

Full Text Available Due to the widespread use of silver nanoparticles in consumer products, the toxicity of silver nanoparticles has also been studied in relation to their application. However, most genotoxicity studies of silver nanoparticles have been performed in vitro. Therefore, this study evaluated the DNA damage to lung cells caused by repeated inhalation of silver nanoparticles. Male Sprague Dawley rats were exposed to silver nanoparticles for 12 weeks in a whole-body inhalation chamber. The animals were divided into one control group and three dose groups that were exposed to silver nanoparticles (14–15 nm diameter at concentrations of 0.66 × 106 particles/cm3 (49 μg/m3, low dose, 1.41 × 106 particles/cm3 (117 μg/m3, middle dose, and 3.24 × 106 particles /cm3 (381 μg/m3, high dose, respectively, for six hours/day over 12 weeks. The rats were sacrificed after the 12-week exposure period and the DNA damage assessed using a Comet assay of cells obtained from the right lungs. The olive tail moment values were 2.93 ± 0.19, 3.81 ± 0.23, 3.40 ± 0.22, and 5.16 ± 0.32 for the control, low-, middle-, and high-dose groups, respectively. Although no dose-dependent results were observed, a significant increase in the level of DNA damage was noted for the high-dose group.

The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes.

Science.gov (United States)

Fu, Changhui; Liu, Tianlong; Li, Linlin; Liu, Huiyu; Chen, Dong; Tang, Fangqiong

2013-03-01

Mesoporous silica nanoparticles (MSNs) are emerging as one of the promising nanomaterials for biomedical applications, but the nanomaterials-body interaction exposed by different administration routes remained poorly understood. In the present study, a systematic investigation of the absorption, distribution, excretion and toxicity of silica nanoparticles (SNs) with the average size of 110 nm after four different exposure routes including intravenous, hypodermic, intramuscular injection and oral administration to mice were achieved. The results showed that a fraction of the SNs administrated by the intramuscular and hypodermic injection could cross different biological barriers into the liver but with a low absorption rate. Exposing by oral administration, SNs were absorbed into the intestinal tract and persisted in the liver. And SNs administrated by intravenous injection were mainly present in the liver and spleen. In addition, SNs could cause inflammatory response around the injection sites after intramuscular and hypodermic injection. It was also found that SNs were mainly excreted through urine and feces after different exposure routes. This study will be helpful for selecting the appropriate exposed routes for the development of nanomaterials-based drug delivery system for biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microscopy based studies on the interaction of bio-based silver nanoparticles with Bombyx mori Nuclear Polyhedrosis virus.

Science.gov (United States)

Tamilselvan, Selvaraj; Ashokkumar, Thirunavukkarasu; Govindaraju, Kasivelu

2017-04-01

In the present investigation, silver nanoparticles (AgNPs) interactions with Bombyx mori Nuclear Polyhedrosis virus (BmNPV) were characterized using High-Resolution Scanning Electron Microscopy (HR-SEM), Energy Dispersive X-ray Analysis (EDAX), Transmission Electron Microscopy (TEM), Atomic Force Microcopy (AFM) and Confocal Microscope (CM). HR-SEM study reveals that the biosynthesized AgNPs have interacted with BmNPV and were found on the surface. TEM micrographs of normal and viral polyhedra treated with AgNPs showed that the nanoparticles were accumulated in the membrane and it was noted that some of the AgNPs successfully penetrated the membrane by reaching the capsid of BmNPV. AFM and confocal microscopy studies reveal that the disruption in the shell membrane tends to lose its stability due to exposure of AgNPs to BmNPV. Copyright © 2017 Elsevier B.V. All rights reserved.

Parental occupational exposure to endocrine disrupting chemicals and male genital malformations

DEFF Research Database (Denmark)

Morales-Suárez-Varela, María M; Toft, Gunnar; Jensen, Morten S

2011-01-01

Sex hormones closely regulate development of the male genital organs during fetal life. The hypothesis that xenobiotics may disrupt endogenous hormonal signalling has received considerable scientific attention, but human evidence is scarce.......Sex hormones closely regulate development of the male genital organs during fetal life. The hypothesis that xenobiotics may disrupt endogenous hormonal signalling has received considerable scientific attention, but human evidence is scarce....

Transcriptome alterations in zebrafish embryos after exposure to environmental estrogens and anti-androgens can reveal endocrine disruption.

Science.gov (United States)

Schiller, Viktoria; Wichmann, Arne; Kriehuber, Ralf; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

2013-12-01

Exposure to environmental chemicals known as endocrine disruptors (EDs) is in many cases associated with an unpredictable hazard for wildlife and human health. The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable ED assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17α-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Copyright © 2013 Elsevier Inc. All rights reserved.

Putative effects of endocrine disrupters on pubertal development in the human

DEFF Research Database (Denmark)

Teilmann, Grete; Juul, Anders; Skakkebaek, Niels E

2002-01-01

developing countries to industrialized countries often develop precocious puberty. Not only precocious puberty, but also delayed puberty can, theoretically, be associated with exposure to endocrine disrupters. While it is very plausible that endocrine disrupters may disturb pubertal development...

Bird populations as sentinels of endocrine disrupting chemicals.

Science.gov (United States)

Carere, Claudio; Costantini, David; Sorace, Alberto; Santucci, Daniela; Alleva, Enrico

2010-01-01

Exposure to endocrine disrupting chemicals (EDCs) is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED) at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

Biomarkers used in Environmental Health with focus on Endocrine Disrupters

DEFF Research Database (Denmark)

Krüger, Tanja; Ghisari, Mandana; Long, Manhai

2012-01-01

Endocrine-disrupting chemicals (EDCs) are compounds that either mimic or block endogenous hormones and can disrupt the normal function of the body. Bio-monitoring is the assessment of internal doses of EDCs and has been used for decades to provide information about exposures to chemicals giving...

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

Science.gov (United States)

Bonde, Jens Peter; Flachs, Esben Meulengracht; Rimborg, Susie; Glazer, Clara Helene; Giwercman, Aleksander; Ramlau-Hansen, Cecilia Høst; Hougaard, Karin Sørig; Høyer, Birgit Bjerre; Hærvig, Katia Keglberg; Petersen, Sesilje Bondo; Rylander, Lars; Specht, Ina Olmer; Toft, Gunnar; Bräuner, Elvira Vaclavik

2016-12-01

More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95

Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European union.

Science.gov (United States)

Trasande, Leonardo; Zoeller, R Thomas; Hass, Ulla; Kortenkamp, Andreas; Grandjean, Philippe; Myers, John Peterson; DiGangi, Joseph; Bellanger, Martine; Hauser, Russ; Legler, Juliette; Skakkebaek, Niels E; Heindel, Jerrold J

2015-04-01

Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability. The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU). A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine disruptor mechanism. To evaluate the epidemiological evidence, the Steering Committee adapted the World Health Organization Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria, whereas the Steering Committee adapted definitions recently promulgated by the Danish Environmental Protection Agency for evaluating laboratory and animal evidence of endocrine disruption. Expert panels used the Delphi method to make decisions on the strength of the data. Expert panels achieved consensus at least for probable (>20%) EDC causation for IQ loss and associated intellectual disability, autism, attention-deficit hyperactivity disorder, childhood obesity, adult obesity, adult diabetes, cryptorchidism, male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median cost of €157 billion (or $209 billion, corresponding to 1.23% of EU gross domestic product) annually across 1000 simulations. Notably, using the lowest end of the probability range for each relationship in the Monte Carlo simulations produced a median range of €109 billion that differed modestly from base case probability inputs. EDC exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in

The Role of Epigenetics in the Latent Effects of Early Life Exposure to Obesogenic Endocrine Disrupting Chemicals.

Science.gov (United States)

Stel, Jente; Legler, Juliette

2015-10-01

Recent research supports a role for exposure to endocrine-disrupting chemicals (EDCs) in the global obesity epidemic. Obesogenic EDCs have the potential to inappropriately stimulate adipogenesis and fat storage, influence metabolism and energy balance and increase susceptibility to obesity. Developmental exposure to obesogenic EDCs is proposed to interfere with epigenetic programming of gene regulation, partly by activation of nuclear receptors, thereby influencing the risk of obesity later in life. The goal of this minireview is to briefly describe the epigenetic mechanisms underlying developmental plasticity and to evaluate the evidence of a mechanistic link between altered epigenetic gene regulation by early life EDC exposure and latent onset of obesity. We summarize the results of recent in vitro, in vivo, and transgenerational studies, which clearly show that the obesogenic effects of EDCs such as tributyltin, brominated diphenyl ether 47, and polycyclic aromatic hydrocarbons are mediated by the activation and associated altered methylation of peroxisome proliferator-activated receptor-γ, the master regulator of adipogenesis, or its target genes. Importantly, studies are emerging that assess the effects of EDCs on the interplay between DNA methylation and histone modifications in altered chromatin structure. These types of studies coupled with genome-wide rather than gene-specific analyses are needed to improve mechanistic understanding of epigenetic changes by EDC exposure. Current advances in the field of epigenomics have led to the first potential epigenetic markers for obesity that can be detected at birth, providing an important basis to determine the effects of developmental exposure to obesogenic EDCs in humans.

Bioaccumulation and toxicity of CuO nanoparticles by a freshwater invertebrate after waterborne and dietborne exposures

Science.gov (United States)

Croteau, Marie-Noele; Misra, Superb K.; Luoma, Samuel N.; Valsami-Jones, Eugenia

2014-01-01

The incidental ingestion of engineered nanoparticles (NPs) can be an important route of uptake for aquatic organisms. Yet, knowledge of dietary bioavailability and toxicity of NPs is scarce. Here we used isotopically modified copper oxide (65CuO) NPs to characterize the processes governing their bioaccumulation in a freshwater snail after waterborne and dietborne exposures. Lymnaea stagnalis efficiently accumulated 65Cu after aqueous and dietary exposures to 65CuO NPs. Cu assimilation efficiency and feeding rates averaged 83% and 0.61 g g–1 d–1 at low exposure concentrations (–1), and declined by nearly 50% above this concentration. We estimated that 80–90% of the bioaccumulated 65Cu concentration in L. stagnalis originated from the 65CuO NPs, suggesting that dissolution had a negligible influence on Cu uptake from the NPs under our experimental conditions. The physiological loss of 65Cu incorporated into tissues after exposures to 65CuO NPs was rapid over the first days of depuration and not detectable thereafter. As a result, large Cu body concentrations are expected in L. stagnalis after exposure to CuO NPs. To the degree that there is a link between bioaccumulation and toxicity, dietborne exposures to CuO NPs are likely to elicit adverse effects more readily than waterborne exposures.

Disruption of thyroid hormone functions by low dose exposure of tributyltin: an in vitro and in vivo approach.

Science.gov (United States)

Sharan, Shruti; Nikhil, Kumar; Roy, Partha

2014-09-15

Triorganotins, such as tributyltin chloride (TBTCl), are environmental contaminants that are commonly found in the antifouling paints used in ships and other vessels. The importance of TBTCl as an endocrine-disrupting chemical (EDC) in different animal models is well known; however, its adverse effects on the thyroid gland are less understood. Hence, in the present study, we aimed to evaluate the thyroid-disrupting effects of this chemical using both in vitro and in vivo approaches. We used HepG2 hepatocarcinoma cells for the in vitro studies, as they are a thyroid hormone receptor (TR)-positive and thyroid responsive cell line. For the in vivo studies, Swiss albino male mice were exposed to three doses of TBTCl (0.5, 5 and 50μg/kg/day) for 45days. TBTCl showed a hypo-thyroidal effect in vivo. Low-dose treatment of TBTCl exposure markedly decreased the serum thyroid hormone levels via the down-regulation of the thyroid peroxidase (TPO) and thyroglobulin (Tg) genes by 40% and 25%, respectively, while augmenting the thyroid stimulating hormone (TSH) levels. Thyroid-stimulating hormone receptor (TSHR) expression was up-regulated in the thyroid glands of treated mice by 6.6-fold relative to vehicle-treated mice (p<0.05). In the transient transactivation assays, TBTCl suppressed T3 mediated transcriptional activity in a dose-dependent manner. In addition, TBTCl was found to decrease the expression of TR. The present study thus indicates that low concentrations of TBTCl suppress TR transcription by disrupting the physiological concentrations of T3/T4, followed by the recruitment of NCoR to TR, providing a novel insight into the thyroid hormone-disrupting effects of this chemical. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

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Grassian Vicki H

2011-09-01

Full Text Available Abstract Background Human exposure to nanoparticles (NPs and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p. in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3 and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse. Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH activity, and inflammatory cytokines in bronchoalveolar lavage (BAL fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse. Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection.

Bird populations as sentinels of endocrine disrupting chemicals

Directory of Open Access Journals (Sweden)

Claudio Carere

2010-03-01

Full Text Available Exposure to endocrine disrupting chemicals (EDCs is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

Effects of Short-Term Exposure to Sublethal Concentrations of Silver Nanoparticles on Histopathology and Electron Microscope Ultrastructure of Zebrafish (Danio Rerio Gills

Directory of Open Access Journals (Sweden)

Borhan Mansouri

2015-11-01

Full Text Available Background: The increasing use of nanomaterials and nanoproducts has increased the possibility of contamination of the environment, which may have adverse effects on different organisms. The aim of this study was to evaluate the effects of silver nanoparticles on histopathology and gill ultrastructure of zebrafish (Danio rerio under laboratory conditions. Methods: Zebrafish were exposed to four concentrations of silver nanoparticles (0.0015, 0.00375, 0.0075, and 0.015 mg/l for a period of 4 days. Gill ultrastructure and histopathological changes were studied using scanning electron microscope and haematoxylin - eosin staining. Results: Exposure to silver nanoparticles significantly (P < 0.001 increased the diameter of gill filaments and secondary lamellae, while silver nanoparticles significantly reduced the length of the secondary gills in zebrafish. Moreover, other changes such as vacuolization, dilated and clubbed tips, hyperplasia, edema, fusion, swelling of mucocytes, hypertrophy, and necrosis were observed. The effects of silver nanoparticles in zebrafish gills were dose dependent. Conclusion: Based on the adverse effects of AgNPs on zebrafish gills, silver nanoparticle solutions can be hazardous pollutants for the environment.

In vitro toxicity of zinc oxide nanoparticles: a review

International Nuclear Information System (INIS)

Pandurangan, Muthuraman; Kim, Doo Hwan

2015-01-01

The toxic effect of ZnO nanoparticles is due to their solubility. ZnO nanoparticles dissolve in the extracellular region, which in turn increases the intracellular [Zn 2+ ] level. The mechanism for increased intracellular [Zn 2+ ] level and ZnO nanoparticles dissolution in the medium is still unclear. Cytotoxicity, increased oxidative stress, increased intracellular [Ca 2+ ] 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

In vitro toxicity of zinc oxide nanoparticles: a review

Energy Technology Data Exchange (ETDEWEB)

Pandurangan, Muthuraman; Kim, Doo Hwan, E-mail: frenzram1980@gmail.com [Konkuk University, Department of Bioresources and Food Sciences (Korea, Republic of)

2015-03-15

The toxic effect of ZnO nanoparticles is due to their solubility. ZnO nanoparticles dissolve in the extracellular region, which in turn increases the intracellular [Zn{sup 2+}] level. The mechanism for increased intracellular [Zn{sup 2+}] level and ZnO nanoparticles dissolution in the medium is still unclear. Cytotoxicity, increased oxidative stress, increased intracellular [Ca{sup 2+}] 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.

Current research and prospects for health effects of nanoparticles on offspring

International Nuclear Information System (INIS)

Umezawa, M; Takeda, K

2011-01-01

Caution in handling ceramic nanoparticles is required by workers and consumers if they are to be used safely and profitably. The small size of nanoparticles can bestow high reactivity and unique translocational properties. Studies have shown that exposure to some types of nanoparticles affects the respiratory, cardiovascular and central nervous systems and various organs. When pregnant mice were exposed to nanoparticles, various organs of offspring are also affected. Our recent studies showed that prenatal exposure to nanoparticles (carbon black and titanium dioxide) causes long-term adverse effects on the reproductive, respiratory and central nervous systems of offspring. The effects of nanoparticles on fetuses and children and the possibility of them leading to the onset of diseases in adulthood are of concern. Thus, it is important to research the risk of unintentional exposure to nanoparticles, including ceramic nanoparticles, from the environment and to attempt to identify methods to protect against their toxicity.

Current research and prospects for health effects of nanoparticles on offspring

Energy Technology Data Exchange (ETDEWEB)

Umezawa, M [Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510 (Japan); Takeda, K, E-mail: masa-ume@rs.noda.tus.ac.jp

2011-10-29

Caution in handling ceramic nanoparticles is required by workers and consumers if they are to be used safely and profitably. The small size of nanoparticles can bestow high reactivity and unique translocational properties. Studies have shown that exposure to some types of nanoparticles affects the respiratory, cardiovascular and central nervous systems and various organs. When pregnant mice were exposed to nanoparticles, various organs of offspring are also affected. Our recent studies showed that prenatal exposure to nanoparticles (carbon black and titanium dioxide) causes long-term adverse effects on the reproductive, respiratory and central nervous systems of offspring. The effects of nanoparticles on fetuses and children and the possibility of them leading to the onset of diseases in adulthood are of concern. Thus, it is important to research the risk of unintentional exposure to nanoparticles, including ceramic nanoparticles, from the environment and to attempt to identify methods to protect against their toxicity.

Hemopexin as biomarkers for analyzing the biological responses associated with exposure to silica nanoparticles

Science.gov (United States)

Higashisaka, Kazuma; Yoshioka, Yasuo; Yamashita, Kohei; Morishita, Yuki; Pan, Huiyan; Ogura, Toshinobu; Nagano, Takashi; Kunieda, Akiyoshi; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

2012-10-01

Practical uses of nanomaterials are rapidly spreading to a wide variety of fields. However, potential harmful effects of nanomaterials are raising concerns about their safety. Therefore, it is important that a risk assessment system is developed so that the safety of nanomaterials can be evaluated or predicted. Here, we attempted to identify novel biomarkers of nanomaterial-induced health effects by a comprehensive screen of plasma proteins using two-dimensional differential in gel electrophoresis (2D-DIGE) analysis. Initially, we used 2D-DIGE to analyze changes in the level of plasma proteins in mice after intravenous injection via tail veins of 0.8 mg/mouse silica nanoparticles with diameters of 70 nm (nSP70) or saline as controls. By quantitative image analysis, protein spots representing >2.0-fold alteration in expression were found and identified by mass spectrometry. Among these proteins, we focused on hemopexin as a potential biomarker. The levels of hemopexin in the plasma increased as the silica particle size decreased. In addition, the production of hemopexin depended on the characteristics of the nanomaterials. These results suggested that hemopexin could be an additional biomarker for analyzing the biological responses associated with exposure to silica nanoparticles. We believe that this study will contribute to the development of biomarkers to ensure the safety of silica nanoparticles.

Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

Science.gov (United States)

Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

2015-10-01

Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. Published by Elsevier Ltd.

Action spectrum for photochemical retinal pigment epithelium (RPE) disruption in an in vivo monkey model

Science.gov (United States)

Zhang, Jie; Sabarinathan, Ranjani; Bubel, Tracy; Williams, David R.; Hunter, Jennifer J.

2016-03-01

Observations of RPE disruption and autofluorescence (AF) photobleaching at light levels below the ANSI photochemical maximum permissible exposure (MPE) (Morgan et al., 2008) indicates a demand to modify future light safety standards to protect the retina from harm. To establish safe light exposures, we measured the visible light action spectrum for RPE disruption in an in vivo monkey model with fluorescence adaptive optics retinal imaging. Using this high resolution imaging modality can provide insight into the consequences of light on a cellular level and allow for longitudinal monitoring of retinal changes. The threshold retinal radiant exposures (RRE) for RPE disruption were determined for 4 wavelengths (460, 488, 544, and 594 nm). The anaesthetized macaque retina was exposed to a uniform 0.5° × 0.5° field of view (FOV). Imaging within a 2° × 2° FOV was performed before, immediately after and at 2 week intervals for 10 weeks. At each wavelength, multiple RREs were tested with 4 repetitions each to determine the threshold for RPE disruption. For qualitative analysis, RPE disruption is defined as any detectable change from the pre exposure condition in the cell mosaic in the exposed region relative to the corresponding mosaic in the immediately surrounding area. We have tested several metrics to evaluate the RPE images obtained before and after exposure. The measured action spectrum for photochemical RPE disruption has a shallower slope than the current ANSI photochemical MPE for the same conditions and suggests that longer wavelength light is more hazardous than other measurements would suggest.

Functional connectivity disruption in neonates with prenatal marijuana exposure

Directory of Open Access Journals (Sweden)

Karen eGrewen

2015-11-01

Full Text Available Prenatal marijuana exposure (PME is linked to neurobehavioral and cognitive impairments, however findings in childhood and adolescence are inconsistent. Type-1 cannabinoid receptors (CB1R modulate fetal neurodevelopment, mediating PME effects on growth of functional circuitry sub-serving behaviors critical for academic and social success. The purpose of this study was to investigate the effects of prenatal marijuana on development of early brain functional circuitry prior to prolonged postnatal environmental influences. We measured resting state functional connectivity during unsedated sleep in infants at 2-6 weeks (+MJ: 20 with PME in combination with nicotine, alcohol, opiates, and/or SSRI; -MJ: 23 exposed to the same other drugs without marijuana, CTR: 20 drug free controls. Connectivity of subcortical seed regions with high fetal CB1R expression was examined. Marijuana-specific differences were observed in insula and three striatal connections: anterior insula – cerebellum, right caudate – cerebellum, right caudate – right fusiform gyrus/inferior occipital, left caudate – cerebellum. +MJ neonates had hypoconnectivity in all clusters compared with -MJ and CTR groups. Altered striatal connectivity to areas involved in visual spatial and motor learning, attention, and in fine-tuning of motor outputs involved in movement and language production may contribute to neurobehavioral deficits reported in this at-risk group. Disrupted anterior insula connectivity may contribute to altered integration of interoceptive signals with salience estimates, motivation, decision-making, and later drug use. Compared with CTRs, both +MJ and -MJ groups demonstrated hyperconnectivity of left amygdala seed with orbital frontal cortex and hypoconnectivity of posterior thalamus seed with hippocampus, suggesting vulnerability to multiple drugs in these circuits.

Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

Science.gov (United States)

Bellanger, Martine; Demeneix, Barbara; Grandjean, Philippe; Zoeller, R Thomas; Trasande, Leonardo

2015-04-01

Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients and Participants, and Intervention: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. The panel identified a 70-100% probability that polybrominated diphenyl ether and organophosphate exposures contribute to IQ loss in the European population. Polybrominated diphenyl ether exposures were associated with 873,000 (sensitivity analysis, 148,000 to 2.02 million) lost IQ points and 3290 (sensitivity analysis, 3290 to 8080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis, €1.58 billion to €22.4 billion). Organophosphate exposures were associated with 13.0 million (sensitivity analysis, 4.24 million to 17.1 million) lost IQ points and 59 300 (sensitivity analysis, 16,500 to 84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis, €46.8 billion to €194 billion). Autism spectrum disorder causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis, 126-631) attributable cases at a cost of €199 million

Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles.

Science.gov (United States)

Bhattacharya, Kunal; Naha, Pratap C; Naydenova, Izabela; Mintova, Svetlana; Byrne, Hugh J

2012-12-17

Increasing utilization of engineered nanoparticles in the field of electronics and biomedical applications demands an assessment of risk associated with deliberate or accidental exposure. Metal based nanoparticles are potentially most important of all the nanoparticles in terms of health risks. Microporous alumino-silicates and pure silicates named as zeolites and zeo-type materials with variety of structures, chemical compositions, particle sizes and morphologies have a significant number of industrial uses such as in catalysis, sorption and ion-exchange processes. In particular, the nanosized particles due to their unique properties are used in hybrid organic-inorganic materials for photography, photonics, electronics, labeling, imaging, and sensing. The aim of the current study is to investigate pure silica MFI-type zeolites nanoparticles with sizes of 50nm and 100nm (samples MFI-50 and MFI-100) under suspended conditions and their toxicological effects on human lung alveolar (A549) cells under in vitro conditions. Live cell imaging showed that the nanoparticles precipitated from the colloidal suspension of cell culture media as large agglomerates, coming in contact with the cell surface through sedimentation. A cellular proliferative capacity test showed the zeolite nanoparticles to exhibit no significant cytotoxicity below a concentration of 100μg/ml. However, both the MFI-50 and MFI-100 nanoparticles induced high intracellular reactive oxygen species (ROS) generation and elevated mitochondrial membrane potential in the A549 cells over the measured time period of 12h and at concentrations up to ≤50μg/ml. DNA fragmentation analysis using the comet assay showed that the MFI-50 and MFI-100 nanoparticles cause genotoxicity in a concentration dependent manner. Furthermore, the rate at which maximum genomic damage was caused by MFI-100 nanoparticles in the A549 cells was found to be high as compared to the MFI-50 nanoparticles. However, the damage caused by the

Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex

International Nuclear Information System (INIS)

Guo, Bao-Qiang; Yan, Chong-Huai; Cai, Shi-Zhong; Yuan, Xiao-Bing; Shen, Xiao-Ming

2013-01-01

Highlights: ► Low level MeHg exposure causes migratory defect of rat cerebrocortical neurons. ► The migration defect is due to the impact of MeHg on the neuronal migration itself. ► Rho GTPases seem to be involved in MeHg-induced disruption of neuronal migration. -- Abstract: We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11–21. Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats. Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself. Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway. In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg

The emerging case of nanopollutants in the aquatic environment: analytical challenges for the exposure assessment of silver and zinc oxide nanoparticles

CSIR Research Space (South Africa)

Thwala, Melusi

2016-09-01

Full Text Available of emerging environmental contaminants partly due to limited capability to detect and quantify them in environmental matrices. The current paper presents findings from the exposure assessments of silver and zinc oxide nanoparticles (Ag and ZnO NPs...

Fate of nanoparticles during life cycle of polymer nanocomposites

International Nuclear Information System (INIS)

Nguyen, T; Pellegrin, B; Bernard, C; Gu, X; Gorham, J M; Stutzman, P; Stanley, D; Shapiro, A; Byrd, E; Hettenhouser, R; Chin, J

2011-01-01

Nanoparticles are increasingly used in consumer and structural polymeric products to enhance a variety of properties. Under the influence of environmental factors (e.g., ultraviolet, moisture, temperature) and mechanical actions (e.g., scratching, vibrations, abrasion), nanoparticles could potentially release from the products and thus have negative effects on the environment, health and safety. The fate of nanoparticles in polymer nanocomposites during their exposure to UV environment has been investigated. Epoxy polymer containing multi-walled carbon nanotubes (MWCNTs) and silica nanoparticles were studied. Specially-designed cells containing nanocomposite specimens were irradiated with UV radiation between 295 nm and 400 nm. Chemical degradation, mass loss and surface morphology of the epoxy nanocomposites, and release of nanoparticles were measured. Epoxy containing MWCNTs exposed to UV radiation degraded at a much slower rate than the unfilled epoxy or the epoxy/nanosilica composite. Photodegradation of the matrix resulted in substantial accumulation of nanoparticles on the composite surfaces. Silica nanoparticles were found to release into the environment, but MWCNTs formed a dense network on the composite surface, with no evidence of release even after prolonged exposure. Conceptual models for silica nanoparticle release and MWCNT retention on the surface during UV exposure of nanocomposites are presented.

Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

Directory of Open Access Journals (Sweden)

Ken-Ichiro Inoue

2011-01-01

Full Text Available Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related. Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

Mugilid Fish Are Sentinels of Exposure to Endocrine Disrupting Compounds in Coastal and Estuarine Environments

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Maren Ortiz-Zarragoitia

2014-09-01

Full Text Available Effects on fish reproduction can result from a variety of toxicity mechanisms first operating at the molecular level. Notably, the presence in the environment of some compounds termed endocrine disrupting chemicals (EDCs can cause adverse effects on reproduction by interfering with the endocrine system. In some cases, exposure to EDCs leads to the animal feminization and male fish may develop oocytes in testis (intersex condition. Mugilid fish are well suited sentinel organisms to study the effects of reproductive EDCs in the monitoring of estuarine/marine environments. Up-regulation of aromatases and vitellogenins in males and juveniles and the presence of intersex individuals have been described in a wide array of mullet species worldwide. There is a need to develop new molecular markers to identify early feminization responses and intersex condition in fish populations, studying mechanisms that regulate gonad differentiation under exposure to xenoestrogens. Interestingly, an electrophoresis of gonad RNA, shows a strong expression of 5S rRNA in oocytes, indicating the potential of 5S rRNA and its regulating proteins to become useful molecular makers of oocyte presence in testis. Therefore, the use of these oocyte markers to sex and identify intersex mullets could constitute powerful molecular biomarkers to assess xenoestrogenicity in field conditions.

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

Science.gov (United States)

Hauser, Russ; Skakkebaek, Niels E; Hass, Ulla; Toppari, Jorma; Juul, Anders; Andersson, Anna Maria; Kortenkamp, Andreas; Heindel, Jerrold J; Trasande, Leonardo

2015-04-01

Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual

Endocrine Disrupting Contaminants—Beyond the Dogma

Science.gov (United States)

Guillette, Louis J.

2006-01-01

Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters

DEFF Research Database (Denmark)

Isling, Louise Krag; Boberg, Julie; Jacobsen, Pernille Rosenskjold

2014-01-01

). Onset of puberty and estrous cyclicity at 9 and 12 months of age were assessed. Few female offspring showed significantly regular estrus cyclicity at 12 months of age in the TotalMix450 and AAMix450 groups compared with controls. In 19-month-old male offspring, epididymal sperm counts were lower than...... controls, and in ventral prostate an overrepresentation of findings related to hyperplasia was observed in exposed groups compared with controls, particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the AAMix450...... group. Developmental exposure of rats to the highest dose of a human-relevant mixture of endocrine disrupters induced adverse effects late in life, manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia, and higher incidence...

Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice.

Science.gov (United States)

Sundarraj, Kiruthika; Manickam, Vijayprakash; Raghunath, Azhwar; Periyasamy, Madhivadhani; Viswanathan, Mangala Priya; Perumal, Ekambaram

2017-02-01

The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe 2 O 3 -NPs) could be toxic to mice testis. Fe 2 O 3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe 2 O 3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe 2 O 3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe 2 O 3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved-caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe 2 O 3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe 2 O 3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe 2 O 3 -NPs exposure may be associated with Fe 2 O 3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe 2 O 3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe 2 O 3 -NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017. © 2016 Wiley Periodicals, Inc.

Characterization of nanoparticles released during construction of photocatalytic pavements using engineered nanoparticles

International Nuclear Information System (INIS)

Dylla, Heather; Hassan, Marwa M.

2012-01-01

With the increasing use of titanium dioxide (TiO 2 ) nanoparticles in self-cleaning materials such as photocatalytic concrete pavements, the release of nanoparticles into the environment is inevitable. Nanoparticle concentration, particle size, surface area, elemental composition, and surface morphology are pertinent to determine the associated risks. In this study, the potential of exposure to synthetic nanoparticles released during construction activities for application of photocatalytic pavements was measured during laboratory-simulated construction activities of photocatalytic mortar overlays and in an actual field application of photocatalytic spray coat. A scanning mobility particle sizer system measured the size distribution of nanoparticles released during laboratory and field activities. Since incidental nanoparticles are released during construction activities, nanoparticle emissions were compared to those from similar activities without nano-TiO 2 . Nanoparticle counts and size distribution suggest that synthetic nanoparticles are released during application of photocatalytic pavements. In order to identify the nanoparticle source, nanoparticles were also collected for offline characterization using transmission electron microscopy. However, positive identification of synthetic nanoparticles was not possible due to difficulties in obtaining high-resolution images. As a result, further research is recommended to identify nanoparticle composition and sources.

Assessment of exposure to composite nanomaterials and development of a personal respiratory deposition sampler for nanoparticles

Science.gov (United States)

Cena, Lorenzo

2011-12-01

The overall goals of this doctoral dissertation are to provide knowledge of workers' exposure to nanomaterials and to assist in the development of standard methods to measure personal exposure to nanomaterials in workplace environments. To achieve the first goal, a field study investigated airborne particles generated from the weighing of bulk carbon nanotubes (CNTs) and the manual sanding of epoxy test samples reinforced with CNTs. This study also evaluated the effectiveness of three local exhaust ventilation (LEV) conditions (no LEV, custom fume hood and biosafety cabinet) for control of exposure to particles generated during sanding of CNT-epoxy nanocomposites. Particle number and respirable mass concentrations were measured with direct-read instruments, and particle morphology was determined by electron microscopy. Sanding of CNT-epoxy nanocomposites released respirable size airborne particles with protruding CNTs very different in morphology from bulk CNTs that tended to remain in clusters (>1mum). Respirable mass concentrations in the operator's breathing zone were significantly greater when sanding took place in the custom hood (p <0.0001) compared to the other LEV conditions. This study found that workers' exposure was to particles containing protruding CNTs rather than to bulk CNT particles. Particular attention should be placed in the design and selection of hoods to minimize exposure. Two laboratory studies were conducted to realize the second goal. Collection efficiency of submicrometer particles was evaluated for nylon mesh screens with three pore sizes (60, 100 and 180 mum) at three flow rates (2.5, 4, and 6 Lpm). Single-fiber efficiency of nylon mesh screens was then calculated and compared to a theoretical estimation expression. The effects of particle morphology on collection efficiency were also experimentally measured. The collection efficiency of the screens was found to vary by less than 4% regardless of particle morphology. Single

Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children

Directory of Open Access Journals (Sweden)

Patrick Lyn

2009-10-01

Full Text Available Abstract Among dietary factors, learning and behavior are influenced not only by nutrients, but also by exposure to toxic food contaminants such as mercury that can disrupt metabolic processes and alter neuronal plasticity. Neurons lacking in plasticity are a factor in neurodevelopmental disorders such as autism and mental retardation. Essential nutrients help maintain normal neuronal plasticity. Nutritional deficiencies, including deficiencies in the long chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder. Nutritional deficiencies and mercury exposure have been shown to alter neuronal function and increase oxidative stress among children with autism. These dietary factors may be directly related to the development of behavior disorders and learning disabilities. Mercury, either individually or in concert with other factors, may be harmful if ingested in above average amounts or by sensitive individuals. High fructose corn syrup has been shown to contain trace amounts of mercury as a result of some manufacturing processes, and its consumption can also lead to zinc loss. Consumption of certain artificial food color additives has also been shown to lead to zinc deficiency. Dietary zinc is essential for maintaining the metabolic processes required for mercury elimination. Since high fructose corn syrup and artificial food color additives are common ingredients in many foodstuffs, their consumption should be considered in those individuals with nutritional deficits such as zinc deficiency or who are allergic or sensitive to the effects of mercury or unable to effectively metabolize and eliminate it from the body.

Comparing exposure zones by different exposure metrics using statistical parameters: contrast and precision.

Science.gov (United States)

Park, Ji Young; Ramachandran, Gurumurthy; Raynor, Peter C; Eberly, Lynn E; Olson, Greg

2010-10-01

Recently, the appropriateness of using the 'mass concentration' metric for ultrafine particles has been questioned and surface area (SA) or number concentration metrics has been proposed as alternatives. To assess the abilities of various exposure metrics to distinguish between different exposure zones in workplaces with nanoparticle aerosols, exposure concentrations were measured in preassigned 'high-' and 'low-'exposure zones in a restaurant, an aluminum die-casting factory, and a diesel engine laboratory using SA, number, and mass concentration metrics. Predetermined exposure classifications were compared by each metric using statistical parameters and concentration ratios that were calculated from the different exposure concentrations. In the restaurant, SA and fine particle number concentrations showed significant differences between the high- and low-exposure zones and they had higher contrast (the ratio of between-zone variance to the sum of the between-zone and within-zone variances) than mass concentrations. Mass concentrations did not show significant differences. In the die cast facility, concentrations of all metrics were significantly greater in the high zone than in the low zone. SA and fine particle number concentrations showed larger concentration ratios between the high and low zones and higher contrast than mass concentrations. None of the metrics were significantly different between the high- and low-exposure zones in the diesel engine laboratory. The SA and fine particle number concentrations appeared to be better at differentiating exposure zones and finding the particle generation sources in workplaces generating nanoparticles. Because the choice of an exposure metric has significant implications for epidemiologic studies and industrial hygiene practice, a multimetric sampling approach is recommended for nanoparticle exposure assessment.

Elucidating the mechanisms of nanodiamond-promoted structural disruption of crystallised lipid.

Science.gov (United States)

Hughes, Zak E; Walsh, Tiffany R

2016-10-12

The removal or structural disruption of crystallised lipid is a pivotal but energy-intensive step in a wide range of industrial and biological processes. Strategies to disrupt the structure of crystallised lipid in aqueous solution at lower temperatures are much needed, where nanoparticle-based strategies show enormous promise. Using the aqueous tristearin bilayer as a model for crystallised lipid, we demonstrate that the synergistic use of surfactant and detonation nanodiamonds can depress the onset temperature at which disruption of the crystallised lipid structure occurs. Our simulations reveal the molecular-scale mechanisms by which this disruption takes place, indicating that the nanodiamonds serve a dual purpose. First, the nanodiamonds are predicted to facilitate delivery of surfactant to the lipid/water interface, and second, nanodiamond adsorption acts to roughen the lipid/water interface, enhancing ingress of surfactant into the bilayer. We find the balance of the hydrophobic surface area of the nanodiamond and the nanodiamond surface charge density to be a key determinant of the effectiveness of using nanodiamonds to facilitate lipid disruption. For the nanodiamond size considered here, we identify a moderate surface charge density, that ensures the nanodiamonds are neither too hydrophobic nor too hydrophilic, to be optimal.

Neonatal Persistent Exposure to 6-Propyl-2-thiouracil, a Thyroid-Disrupting Chemical, Differentially Modulates Expression of Hepatic Catalase and C/EBP-β in Adult Rats.

Science.gov (United States)

Bunker, Suresh Kumar; Dandapat, Jagneshwar; Sahoo, Sunil Kumar; Roy, Anita; Chainy, Gagan B N

2016-02-01

Persistent exposure of rats to 6-propyl-2-thiouracil (PTU) from birth resulted in decreases in plasma thyroid hormone (TH) levels and hepatic expression of catalase and CCAAT enhancer binding protein β (C/EBP-β). Catalase promoter region (-185 to +52) that contains binding sites for C/EBP-β showed an augmentation in the methylation level along with a change in methylation pattern of CpG islands in response to PTU treatment. PTU withdrawal on 30 days of birth restored TH levels and C/EBP-β to control rats in adulthood. Although catalase expression was restored to some extent in adult rats in response to PTU withdrawal, a permanent change in its promoter CpG methylation pattern was recorded. The results suggest that downregulation of adult hepatic catalase gene in response to persistent neonatal PTU exposure may not solely be attributed to thyroid-disrupting properties of PTU. It is possible that besides thyroid-disrupting behavior, PTU may impair expression of hepatic catalase by altering methylation pattern of its promoter. © 2015 Wiley Periodicals, Inc.

Comparative study between chemostat and batch reactors to quantify membrane permeability changes on bacteria exposed to silver nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Anaya, Nelson M.; Faghihzadeh, Fatemeh [Department of Civil and Environmental Engineering, University of Rhode Island, 1 Lippitt Rd., Bliss Hall 203, Kingston, RI 02881 (United States); Ganji, Nasim; Bothun, Geoff [Department of Chemical Engineering, University of Rhode Island, 16 Greenhouse Rd., Crawford Hall, Kingston, RI 02881 (United States); Oyanedel-Craver, Vinka, E-mail: craver@uri.edu [Department of Civil and Environmental Engineering, University of Rhode Island, 1 Lippitt Rd., Bliss Hall 203, Kingston, RI 02881 (United States)

2016-09-15

Continuous and batch reactors were used to assess the effect of the exposure of casein-coated silver nanoparticles (AgNPs) on Escherichia coli (E. coli). Additionally, E. coli membrane extracts, membrane permeability and Langmuir film balance assays were used to determine integrity and changes in lipid composition in response to AgNPs exposure. Results showed that batch conditions were not appropriate for the tests due to the production of exopolymeric substances (EPS) during the growth phase. After 5 h of contact between AgNPs and the used growth media containing EPS, the nanoparticles increased in size from 86 nm to 282 nm reducing the stability and thus limiting cell-nanoparticle interactions. AgNPs reduced E. coli growth by 20% at 1 mg/L, in terms of Optical Density 670 (OD670), while no effect was detected at 15 mg/L. At 50 mg/L of AgNPs was not possible to perform the test due to aggregation and sedimentation of the nanoparticles. Membrane extract assays showed that at 1 mg/L AgNPs had a greater change in area (− 4.4cm{sup 2}) on bacteria compared to 15 mg/L (− 4.0cm{sup 2}). This area increment suggested that membrane disruption caused by AgNPs had a stabilizing/rigidifying effect where the cells responded by shifting their lipid composition to more unsaturated lipids to counteract membrane rigidification. In chemostats, the constant inflow of fresh media and aeration resulted in less AgNPs aggregation, thus increased the AgNPs-bacteria interactions, in comparison to batch conditions. AgNPs at 1 mg/L, 15 mg/L, and 50 mg/L inhibited the growth (OD670 reduction) by 0%, 11% and 16.3%, respectively. Membrane extracts exposed to 1 mg/L, 15 mg/L, and 50 mg/L of AgNPs required greater changes in area by − 0.5 cm{sup 2}, 2.7 cm{sup 2} and 3.6 cm{sup 2}, respectively, indicating that the bacterial membranes were disrupted and bacteria responded by synthesizing lipids that stabilize or strengthen membranes. This study showed that the chemostat is more

Endocrine Disrupting Chemicals and Disease Susceptibility

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Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

2011-01-01

Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

The effect of perinatal exposure to ethinyl oestradiol or a mixture of endocrine disrupting pesticides on kisspeptin neurons in the rat hypothalamus

DEFF Research Database (Denmark)

Overgaard, Agnete; Holst, Klaus; Mandrup, Karen

2013-01-01

Early life exposure to endocrine disruptors is considered to disturb normal development of hormone sensitive parameters and contribute to advanced puberty and reduced fecundity in humans. Kisspeptin is a positive regulator of the hypothalamic–pituitary–gonadal axis, and plays a key role in the in......Early life exposure to endocrine disruptors is considered to disturb normal development of hormone sensitive parameters and contribute to advanced puberty and reduced fecundity in humans. Kisspeptin is a positive regulator of the hypothalamic–pituitary–gonadal axis, and plays a key role.......We find that perinatal EE2 exposure did not affect Kiss1 mRNA expression in this study designed to model human exposure to estrogenic compounds, and we find only minor effects on puberty onset. Further, the Kiss1 system does not exhibit persistent changes and puberty onset is not affected after perinatal...... exposure to a pesticide mixture in this experimental setting. However, we find that the pesticide mancozeb tends to increase Kiss1 expression in the ARC, presumably through neurotoxic mechanisms rather than via classical endocrine disruption, calling for increased awareness that Kiss1 expression can...

Metal-based nanoparticle interactions with the nervous system: the challenge of brain entry and the risk of retention in the organism.

Science.gov (United States)

Yokel, Robert; Grulke, Eric; MacPhail, Robert

2013-01-01

This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical-chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in vivo methods, and very few human studies. The routes of uptake into the nervous system and mechanisms of nanoparticle uptake by cells are presented with examples. Brain nanoparticle uptake inversely correlates with size. The influence of shape has not been reported. Surface charge has not been clearly shown to affect flux across the blood-brain barrier. There is very little evidence for metal-based nanoparticle distribution into brain parenchyma. Metal-based nanoparticle disruption of the blood-brain barrier and adverse brain changes have been shown, and are more pronounced for spheres than rods. Study concentrations need to be put in exposure contexts. Work with dorsal root ganglion cells and brain cells in vitro show the potential for metal-based nanoparticles to produce toxicity. Interpretation of these results must consider the ability of nanoparticles to distribute across the barriers protecting the nervous system. Effects of the persistence of poorly soluble metal-based nanoparticles are of particular concern. Copyright © 2013 Wiley Periodicals, Inc.

Synthesis, Characterization, and Cytotoxicity of Iron Oxide Nanoparticles

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S. Kanagesan

2013-01-01

Full Text Available In order to study the response of human breast cancer cells' exposure to nanoparticle, iron oxide (α-Fe2O3 nanoparticles were synthesized by a simple low temperature combustion method using Fe(NO33·9H2O as raw material. X-ray diffraction studies confirmed that the resultant powders are pure α-Fe2O3. Transmission electron microscopy study revealed the spherical shape of the primary particles, and the size of the iron oxide nanoparticles is in the range of 19 nm. The magnetic hysteresis loops demonstrated that the sample exposed ferromagnetic behaviors with a relatively low coercivity. The cytotoxicity of α-Fe2O3 nanoparticle was also evaluated on human breast cancer cells to address the current deficient knowledge of cellular response to nanoparticle exposure.

Oral Exposure to Atrazine Induces Oxidative Stress and Calcium Homeostasis Disruption in Spleen of Mice

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Shuying Gao

2016-01-01

Full Text Available The widely used herbicide atrazine (ATR can cause many adverse effects including immunotoxicity, but the underlying mechanisms are not fully understood. The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice. ATR at doses of 0, 100, 200, or 400 mg/kg body weight was administered to Balb/c mice daily for 21 days by oral gavage. The studies performed 24 hr after the final exposure showed that ATR could induce the generation of reactive oxygen species in the spleen of the mice, increase the level of advanced oxidation protein product (AOPP in the host serum, and cause the depletion of reduced glutathione in the serum, each in a dose-related manner. In addition, DNA damage was observed in isolated splenocytes as evidenced by increase in DNA comet tail formation. ATR exposure also caused increases in intracellular Ca2+ within splenocytes. Moreover, ATR treatment led to increased expression of genes for some antioxidant enzymes, such as HO-1 and Gpx1, as well as increased expression of NF-κB and Ref-1 proteins in the spleen. In conclusion, it appears that oxidative stress and disruptions in calcium homeostasis might play an important role in the induction of immunotoxicity in mice by ATR.

Effect of disruptions on plasma-facing components

International Nuclear Information System (INIS)

Gilligan, J.G.; Bourham, M.A.; Tucker, E.C.

1995-01-01

Erosion of plasma-facing components during disruptions is a limiting factor in the design of large tokamaks like ITER. During a disruption, much of the stored thermal energy of the plasma will be dumped onto divertor plates, resulting in local heat fluxes, which may exceed 100 GW/m 2 over a period of about 0.1--1.0 msec. Melted and/or vaporized material is produced which is redistributed in the divertor region. Simulation of disruption damage is summarized from code results and from experimental exposure of materials to high heat-flux plasmas in plasma guns. In the US several codes have been used to predict both melt/vaporization and heat transfer on surfaces as well as energy and momentum transport in the vapor/plasma shield produced at the surface

Persistent Seroconversion after Accidental Eye Exposure to Calcifying Nanoparticles

Science.gov (United States)

Ciftcioglu, Neva; Aho, Katja M.; McKay, David S.; Kajander, E. Olavi

2007-01-01

Biosafety of nanomaterials has attracted much attention recently. We report here a case where accidental human eye exposure to biogenic nanosized calcium phosphate in the form of calcifying nanoparticles (CNP) raised a strong IgG immune response against proteins carried by CNP. The antibody titer has persisted over ten years at the high level. The IgG was detected by ELISA using CNPs propagated in media containing bovine and human serum as antigen. The exposure incident occurred to a woman scientist (WS) at a research laboratory in Finland at 1993. CNP, also termed "nanobacteria", is a unique self-replicating agent that has not been fully characterized and no data on biohazards were available at that time. Before the accident, her serum samples were negative for both CNP antigen and anti-CNP antibody using specific ELISA tests (Nanobac Oy, Kuopio, Finland). The accident occurred while WS was harvesting CNP cultures. Due to a high pressure in pipetting, CNP pellet splashed into her right eye. Both eyes were immediately washed with water and saline. The following days there was irritation and redness in the right eye. These symptoms disappeared within two weeks without any treatment. Three months after the accident, blood and urine samples of WS were tested for CNP cultures (2), CNP-specific ELISA tests, and blood cell counts. Blood cell counts were normal, CNP antigen and culture tests were negative. A high IgG anti-CNP antibody titer was detected (see Figure). The antibodies of this person have been used thereafter as positive control and standard in ELISA manufacturing (Nano-Sero IgG ELISA, Nanobac Oy, Kuopio, Finland).

Metabolic disruption in context: Clinical avenues for synergistic perturbations in energy homeostasis by endocrine disrupting chemicals.

Science.gov (United States)

Sargis, Robert M

2015-01-01

The global epidemic of metabolic disease is a clear and present danger to both individual and societal health. Understanding the myriad factors contributing to obesity and diabetes is essential for curbing their decades-long expansion. Emerging data implicate environmental endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases such as obesity and diabetes. The phenylsulfamide fungicide and anti-fouling agent tolylfluanid (TF) was recently added to the list of EDCs promoting metabolic dysfunction. Dietary exposure to this novel metabolic disruptor promoted weight gain, increased adiposity, and glucose intolerance as well as systemic and cellular insulin resistance. Interestingly, the increase in body weight and adipose mass was not a consequence of increased food consumption; rather, it may have resulted from disruptions in diurnal patterns of energy intake, raising the possibility that EDCs may promote metabolic dysfunction through alterations in circadian rhythms. While these studies provide further evidence that EDCs may promote the development of obesity and diabetes, many questions remain regarding the clinical factors that modulate patient-specific consequences of EDC exposure, including the impact of genetics, diet, lifestyle, underlying disease, pharmacological treatments, and clinical states of fat redistribution. Currently, little is known regarding the impact of these factors on an individual's susceptibility to environmentally-mediated metabolic disruption. Advances in these areas will be critical for translating EDC science into the clinic to enable physicians to stratify an individual's risk of developing EDC-induced metabolic disease and to provide direction for treating exposed patients.

Dip coating of air purifier ceramic honeycombs with photocatalytic TiO₂ nanoparticles: A case study for occupational exposure

DEFF Research Database (Denmark)

Koivisto, Antti Joonas; Kling, Kirsten Inga; Fonseca, Ana Sofia

2018-01-01

Nanoscale TiO2 (nTiO2) is manufactured in high volumes and is of potential concern in occupational health. Here, we measured workers exposure levels while ceramic honeycombs were dip coated with liquid photoactive nanoparticle suspension and dried with an air blade. The measured nTiO2 concentrati...

Toxicological Effects of Caco-2 Cells Following Short-Term and Long-Term Exposure to Ag Nanoparticles

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Ni Chen

2016-06-01

Full Text Available Extensive utilization increases the exposure of humans to Ag nanoparticles (NPs via the oral pathway. To comprehensively address the action of Ag NPs to the gastrointestinal systems in real situations, i.e., the long-term low-dose exposure, we evaluated and compared the toxicity of three Ag NPs (20–30 nm with different surface coatings to the human intestine cell Caco-2 after 1-day and 21-day exposures, using various biological assays. In both the short- and long-term exposures, the variety of surface coating predominated the toxicity of Ag NPs in a descending order of citrate-coated Ag NP (Ag-CIT, bare Ag NP (Ag-B, and poly (N-vinyl-2-pyrrolidone-coated Ag NP (Ag-PVP. The short-term exposure induced cell growth inhibition and death. The cell viability loss appeared after cells were exposed to 0.7 μg/mL Ag-CIT, 0.9 μg/mL Ag-B or >1.0 μg/mL Ag-PVP for 24 h. The short-term and higher-dose exposure also induced reactive oxygen species (ROS generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation (IL-8 level. The long-term exposure only inhibited the cell proliferation. After 21-day exposure to 0.4 μg/mL Ag-CIT, the cell viability dropped to less than 50%, while cells exposed to 0.5 μg/mL Ag-PVP remained normal as the control. Generally, 0.3 μg/mL is the non-toxic dose for the long-term exposure of Caco-2 cells to Ag NPs in this study. However, cells presented inflammation after exposure to Ag NPs with the non-toxic dose in the long-term exposure.

Viability and proliferation of endothelial cells upon exposure to GaN nanoparticles.

Science.gov (United States)

Braniste, Tudor; Tiginyanu, Ion; Horvath, Tibor; Raevschi, Simion; Cebotari, Serghei; Lux, Marco; Haverich, Axel; Hilfiker, Andres

2016-01-01

Nanotechnology is a rapidly growing and promising field of interest in medicine; however, nanoparticle-cell interactions are not yet fully understood. The goal of this work was to examine the interaction between endothelial cells and gallium nitride (GaN) semiconductor nanoparticles. Cellular viability, adhesion, proliferation, and uptake of nanoparticles by endothelial cells were investigated. The effect of free GaN nanoparticles versus the effect of growing endothelial cells on GaN functionalized surfaces was examined. To functionalize surfaces with GaN, GaN nanoparticles were synthesized on a sacrificial layer of zinc oxide (ZnO) nanoparticles using hydride vapor phase epitaxy. The uptake of GaN nanoparticles by porcine endothelial cells was strongly dependent upon whether they were fixed to the substrate surface or free floating in the medium. The endothelial cells grown on surfaces functionalized with GaN nanoparticles demonstrated excellent adhesion and proliferation, suggesting good biocompatibility of the nanostructured GaN.

Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

DEFF Research Database (Denmark)

Petersen, Marta Axelstad; Christiansen, Sofie; Boberg, Julie

2014-01-01

Reproductive toxicity was investigated in rats after developmental exposure to a mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic and cosmetic ingredients, and paracetamol. The mixture was composed on the basis of information about high-end human exposures...

Endocrine disrupting chemicals: harmful substances and how to test them

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Olea-Serrano Nicolás

2002-01-01

Full Text Available This paper presents an analysis of the opinions of different groups from: scientists, international regulatory bodies, non-governmental organizations and industry; with an interest in the problem of identifying chemical substances with endocrine disrupting activity. There is also discussion of the consequences that exposure to endocrine disruptors may have for human health, considering concrete issues related to: the estimation of risk; the tests that must be used to detect endocrine disruption; the difficulties to establish an association between dose, time of exposure, individual susceptibility, and effect; and the attempts to create a census of endocrine disruptors. Finally, it is proposed that not all hormonal mimics should be included under the single generic denomination of endocrine disruptors.

Incorporation of metal nanoparticles into wood substrate and methods

Science.gov (United States)

Rector, Kirk D; Lucas, Marcel

2015-11-04

Metal nanoparticles were incorporated into wood. Ionic liquids were used to expand the wood cell wall structure for nanoparticle incorporation into the cell wall structure. Nanoparticles of elemental gold or silver were found to be effective surface enhanced Raman spectroscopy (SERS) imaging contrast or sensing agents. Nanoparticles of elemental iron were found to be efficient microwave absorbers and caused localized heating for disrupting the integrity of the lignocellulosic matrix. Controls suggest that the localized heating around the iron nanoparticles reduces losses of cellulose in the form of water, volatiles and CO.sub.2. The ionic liquid is needed during the incorporation process at room temperature. The use of small amounts of ionic liquid combined with the absence of an ionic liquid purification step and a lower energy and water use are expected to reduce costs in an up-scaled pretreatment process.

Long-term exposure of bacterial and protozoan communities to TiO2 nanoparticles in an aerobic-sequencing batch reactor

International Nuclear Information System (INIS)

Supha, Chitpisud; Boonto, Yuphada; Jindakaraked, Manee; Ananpattarachai, Jirapat; Kajitvichyanukul, Puangrat

2015-01-01

Titanium dioxide (TiO 2 ) nanopowders at different concentrations (0–50 mg L −1 ) were injected into an aerobic-sequencing batch reactor (SBR) to investigate the effects of long-term exposure to nanoparticles on bacterial and protozoan communities. The detection of nanoparticles in the bioflocs was analyzed by scanning electron microscopy, transmission electron microscopy, and energy-dispersive x-ray spectroscopy. The SBR wastewater experiments were conducted under the influence of ultraviolet light with photocatalytic TiO 2 . The intrusion of TiO 2 nanoparticles was found both on the surface and inside of the bioflocs. The change of microbial population in terms of mixed liquor-suspended solids and the sludge volume index was monitored. The TiO 2 nanoparticles tentatively exerted an adverse effect on the microbial population, causing the reduction of microorganisms (both bacteria and protozoa) in the SBR. The respiration inhibition rate of the bacteria was increased, and the viability of the microbial population was reduced at the high concentration (50 mg L −1 ) of TiO 2 . The decreasing number of protozoa in the presence of TiO 2 nanoparticles during 20 days of treatment with 0.5 and 1.0 mg L −1 TiO 2 is clearly demonstrated. The measured chemical oxygen demand (COD) in the effluent tends to increase with a long-term operation. The increase of COD in the system suggests a decrease in the efficiency of the wastewater treatment plant. However, the SBR can effectively remove the TiO 2 nanoparticles (up to 50 mg L −1 ) from the effluent. (focus issue paper)

Imaging carbon nanoparticles and related cytotoxicity

International Nuclear Information System (INIS)

Cheng, C; Porter, A E; Welland, M; Muller, K; Skepper, J N; Koziol, K; Midgley, P

2009-01-01

Carbon-based nanoparticles have attracted significant attention due to their unique physical, chemical, and electrical properties. Numerous studies have been published on carbon nanoparticle toxicity; however, the results remain contradictory. An ideal approach is to combine a cell viability assay with nanometer scale imaging to elucidate the detailed physiological and structural effects of cellular exposure to nanoparticles. We have developed and applied a combination of advanced microscopy techniques to image carbon nanoparticles within cells. Specifically, we have used EFTEM, HAADF-STEM, and tomography and confocal microscopy to generate 3-D images enabling determination of nanoparticle spatial distribution in a cell. With these techniques, we can differentiate between the carbon nanoparticles and the cell in both stained and unstained sections. We found carbon nanoparticles (C 60 , single-walled carbon nanotubes (SWNT), and multi-walled carbon nanotubes (MWNT)) within the cytoplasm, lysosomes, and nucleus of human monocyte-derived macrophage cells (HMM). C 60 aggregated along the plasma and nuclear membrane while MWNTs and SWNTs were seen penetrating the plasma and nuclear membranes. Both the Neutral Red (NR) assay and ultra-structural analysis showed an increase in cell death after exposure to MWNTs and SWNTs. SWNTs were more toxic than MWNTs. For both MWNTs and SWNTs, we correlated uptake of the nanoparticles with a significant increase in necrosis. In conclusion, high resolution imaging studies provide us with significant insight into the localised interactions between carbon nanoparticles and cells. Viability assays alone only provide a broad toxicological picture of nanoparticle effects on cells whereas the high resolution images associate the spatial distributions of the nanoparticles within the cell with increased incidence of necrosis. This combined approach will enable us to probe the mechanisms of particle uptake and subsequent chemical changes within

Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride

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Inkielewicz-Stepniak I

2014-04-01

Full Text Available Iwona Inkielewicz-Stepniak,1,* Maria Jose Santos-Martinez,2–4,* Carlos Medina,2,4 Marek W Radomski2,41Department of Medicinal Chemistry, Medical University Gdansk, Debinki, Poland; 2The School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 3School of Medicine, Trinity College Dublin, Dublin, Ireland; 4Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland*These authors contributed equally to this workBackground: Silver nanoparticles (AgNPs and fluoride (F are pharmacological agents widely used in oral medicine and dental practice due to their anti-microbial/anti-cavity properties. However, risks associated with the co-exposure of local cells and tissues to these xenobiotics are not clear. Therefore, we have evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast cells.Methods: Human gingival fibroblast cells (CRL-2014 were exposed to AgNPs and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs was examined by transmission electron microscopy. Downstream inflammatory effects and oxidative stress were measured by real-time quantitative polymerase chain reaction (PCR and reactive oxygen species (ROS generation. Cytotoxicity and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and real-time quantitative PCR and flow cytometry, respectively. Finally, the involvement of mitogen-activated protein kinases (MAPK was studied using Western blot.Results: We found that AgNPs penetrated the cell membrane and localized inside the mitochondria. Co-incubation experiments resulted in increased oxidative stress, inflammation, and apoptosis. In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK, particularly p42/44 MAPK.Conclusion: A combined exposure of human fibroblasts to AgNPs and F results in increased cellular damage. Further studies are needed in order to evaluate

Progress in Development of C60 Nanoparticle Plasma Jet for Diagnostic of Runaway Electron Beam-Plasma Interaction and Disruption Mitigation Study for ITER

Science.gov (United States)

Bogatu, I. N.; Thompson, J. R.; Galkin, S. A.; Kim, J. S.

2013-10-01

We produced a C60 nanoparticle plasma jet (NPPJ) with uniquely fast response-to-delivery time (~ 1 - 2 ms) and unprecedentedly high momentum (~ 0 . 6 g .km/s). The C60 NPPJ was obtained by using a solid state TiH2/C60 pulsed power cartridge producing ~180 mg of C60 molecular gas by sublimation and by electromagnetic acceleration of the C60 plasma in a coaxial gun (~35 cm length, 96 kJ energy) with the output of a high-density (>1023 m-3) hyper-velocity (>4 km/s) plasma jet. The ~ 75 mg C60/C plasma jet has the potential to rapidly and deeply deliver enough mass to significantly increase electron density (to ne ~ 2 . 4 ×1021 m-3, i.e. ~ 60 times larger than typical DIII-D pre-disruption value, ne 0 ~ 4 ×1019 m-3), and to modify the 'critical electric field' and the runaway electrons (REs) collisional drag during different phases of REs dynamics. The C60 NPPJ, as a novel injection technique, allows RE beam-plasma interaction diagnostic by quantitative spectroscopy of C ions visible/UV line intensity. The system is scalable to ~ 1 - 2 g C60/C plasma jet output and technology is adaptable to ITER acceptable materials (BN and Be) for disruption mitigation. Work supported by US DOE DE-FG02-08ER85196 grant.

Surface transport mechanisms in molecular glasses probed by the exposure of nano-particles

Science.gov (United States)

Ruan, Shigang; Musumeci, Daniele; Zhang, Wei; Gujral, Ankit; Ediger, M. D.; Yu, Lian

2017-05-01

For a glass-forming liquid, the mechanism by which its surface contour evolves can change from bulk viscous flow at high temperatures to surface diffusion at low temperatures. We show that this mechanistic change can be conveniently detected by the exposure of nano-particles native in the material. Despite its high chemical purity, the often-studied molecular glass indomethacin contains low-concentration particles approximately 100 nm in size and 0.3% in volume fraction. Similar particles are present in polystyrene, another often-used model. In the surface-diffusion regime, particles are gradually exposed in regions vacated by host molecules, for example, the peak of a surface grating and the depletion zone near a surface crystal. In the viscous-flow regime, particle exposure is not observed. The surface contour around an exposed particle widens over time in a self-similar manner as 3 (Bt)1/4, where B is a surface mobility constant and the same constant obtained by surface grating decay. This work suggests that in a binary system composed of slow- and fast-diffusing molecules, slow-diffusing molecules can be stranded in surface regions vacated by fast-diffusing molecules, effectively leading to phase separation.

Exposure to exogenous enkephalins disrupts reproductive development in the Eastern lubber grasshopper, Romalea microptera (Insecta: Orthoptera.

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Sandeep Kumar

Full Text Available Enkephalins play a major role in reproductive physiology in crustaceans; however their role in reproductive development in insects is largely unknown. We investigated the effect of exposure to exogenous leucine-enkephalin (Leu-Enk, methionine-enkephalin (Met-Enk, and the opioid antagonist naloxone on gonad development in the Eastern lubber grasshopper, Romalea microptera. Injection of either Leu-Enk or naloxone alone significantly increased the testicular index and testicular follicular diameter in males, and the ovarian index, oocyte length, and oocyte diameter in females. In contrast, injection of Met-Enk inhibited all measures of reproductive development in both sexes. Surprisingly, co-injection of naloxone with either enkephalin enhanced the effect associated with administration of the enkephalin alone. This study clearly demonstrates the ability of enkephalins to disrupt insect sexual development and also suggests the existence of conserved enkephaline-dependent regulatory mechanisms in insects and crustaceans.

Modeling of interactions between nanoparticles and cell membranes

Science.gov (United States)

Ban, Young-Min

Rapid development of nanotechnology and ability to manufacture materials and devices with nanometer feature size leads to exciting innovations in many areas including the medical and electronic fields. However, the possible health and environmental impacts of manufactured nanomaterials are not fully known. Recent experimental reports suggest that some of the manufactured nanomaterials, such as fullerenes and carbon nanotubes, are highly toxic even in small concentrations. The goal of the current work is to understand the mechanisms responsible for the toxicity of nanomaterials. In the current study coarse-grained molecular dynamics simulations are employed to investigate the interactions between NPs and cellular membranes at a molecular level. One of the possible toxicity mechanisms of the nanomaterials is membrane disruption. Possibility of membrane disruption exposed to the manufactured nanomaterials are examined by considering chemical reactions and non-reactive physical interactions as chemical as well as physical mechanisms. Mechanisms of transport of carbon-based nanoparticles (fullerene and its derivative) across a phospholipid bilayer are investigated. The free energy profile is obtained using constrained simulations. It is shown that the considered nanoparticles are hydrophobic and therefore they tend to reside in the interior of the lipid bilayer. In addition, the dynamics of the membrane fluctuations is significantly affected by the nanoparticles at the bilayer-water interface. The hydrophobic interaction between the particles and membrane core induces the strong coupling between the nanoparticle motion and membrane deformation. It is observed that the considered nanoparticles affect several physical properties of the membrane. The nanoparticles embedded into the membrane interior lead to the membrane softening, which becomes more significant with increase in CNT length and concentration. The lateral pressure profile and membrane energy in the membrane

Nanoparticle exposures from nano-enabled toner-based printing equipment and human health: state of science and future research needs.

Science.gov (United States)

Pirela, Sandra Vanessa; Martin, John; Bello, Dhimiter; Demokritou, Philip

2017-09-01

Toner formulations used by laser printers (LP) and photocopiers (PC), collectively called "toner-based printing equipment" (TPE), are nano-enabled products (NEP) because they contain several engineered nanomaterials (ENM) that improve toner performance. It has been shown that during consumer use (printing), these ENM are released in the air, together with other semi-volatile organic nanoparticles, and newly formed gaseous co-pollutants such as volatile organic compounds (VOC). The aim of this review is to detail and analyze physico-chemical and morphological (PCM), as well as the toxicological properties of particulate matter (PM) emissions from TPE. The review covers evolution of science since the early 2000, when this printing technology first became a subject of public interest, as well as the lagging regulatory framework around it. Important studies that have significantly changed our understanding of these exposures are also highlighted. The review continues with a critical appraisal of the most up-to-date cellular, animal and human toxicological evidence on the potential adverse human health effects of PM emitted from TPE. We highlight several limitations of existing studies, including (i) use of high and often unrealistic doses in vitro or in vivo; (ii) unrealistically high-dose rates in intratracheal instillation studies; (iii) improper use of toners as surrogate for emitted nanoparticles; (iv) lack of or inadequate PCM characterization of exposures; and (v) lack of dosimetry considerations in in vitro studies. Presently, there is compelling evidence that the PM 0.1 from TPE are biologically active and capable of inducing oxidative stress in vitro and in vivo, respiratory tract inflammation in vivo (in rats) and in humans, several endpoints of cellular injury in monocultures and co-cultures, including moderate epigenetic modifications in vitro. In humans, limited epidemiological studies report typically 2-3 times higher prevalence of chronic cough, wheezing

Characterizing exposures to airborne metals and nanoparticle emissions in a refinery.

Science.gov (United States)

Miller, Arthur; Drake, Pamela L; Hintz, Patrick; Habjan, Matt

2010-07-01

An air quality survey was conducted at a precious metals refinery in order to evaluate worker exposures to airborne metals and to provide detailed characterization of the aerosols. Two areas within the refinery were characterized: a furnace room and an electro-refining area. In line with standard survey practices, both personal and area air filter samples were collected on 37-mm filters and analyzed for metals by inductively coupled plasma-atomic emission spectroscopy. In addition to the standard sampling, measurements were conducted using other tools, designed to provide enhanced characterization of the workplace aerosols. The number concentration and number-weighted particle size distribution of airborne particles were measured with a fast mobility particle sizer (FMPS). Custom-designed software was used to correlate particle concentration data with spatial location data to generate contour maps of particle number concentrations in the work areas. Short-term samples were collected in areas of localized high concentrations and analyzed using transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS) to determine particle morphology and elemental chemistry. Analysis of filter samples indicated that all of the workers were exposed to levels of silver above the Occupational Safety and Health Administration permissible exposure limit of 0.01 mg m(-3) even though the localized ventilation was functioning. Measurements with the FMPS indicated that particle number concentrations near the furnace increased up to 1000-fold above the baseline during the pouring of molten metal. Spatial mapping revealed localized elevated particle concentrations near the furnaces and plumes of particles rising into the stairwells and traveling to the upper work areas. Results of TEM/EDS analyses confirmed the high number of nanoparticles measured by the FMPS and indicated the aerosols were rich in metals including silver, lead, antimony, selenium, and zinc. Results of

Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals in the European Union.

Science.gov (United States)

Hunt, Patricia A; Sathyanarayana, Sheela; Fowler, Paul A; Trasande, Leonardo

2016-04-01

A growing body of evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to female reproductive disorders. To calculate the associated combined health care and economic costs attributable to specific EDC exposures within the European Union (EU). An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. Cost-of-illness estimation used multiple peer-reviewed sources. Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. The most robust EDC-related data for female reproductive disorders exist for 1) diphenyldichloroethene-attributable fibroids and 2) phthalate-attributable endometriosis in Europe. In both cases, the strength of epidemiological evidence was rated as low and the toxicological evidence as moderate, with an assigned probability of causation of 20%–39%. Across the EU, attributable cases were estimated to be 56 700 and 145 000 women, respectively, with total combined economic and health care costs potentially reaching €163 million and €1.25 billion. EDCs (diphenyldichloroethene and phthalates) may contribute substantially to the most common reproductive disorders in women, endometriosis and fibroids, costing nearly €1.5 billion annually. These estimates represent only EDCs for which there were sufficient epidemiologic studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.

Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

Science.gov (United States)

Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

2013-09-01

Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

Multifunctional Polymer Nanoparticles for Dual Drug Release and Cancer Cell Targeting

Directory of Open Access Journals (Sweden)

Yu-Han Wen

2017-06-01

Full Text Available Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid-co-histidine/doxorubicin/biotin (HBD in which doxorubicin (DOX was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ, to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine.

Solid lipid nanoparticles loaded with edaravone for inner ear protection after noise exposure.

Science.gov (United States)

Gao, Gang; Liu, Ya; Zhou, Chang-Hua; Jiang, Ping; Sun, Jian-Jun

2015-01-20

Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs), in steady noise-exposed guinea pigs. SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL) noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR) threshold measurements, reactive oxygen species (ROS) were detected in their cochleas with electron spin resonance (ESR), and outer hair cells (OHCs) were counted with silvernitrate (AgNO 3 ) staining at 1, 4, and 6 days. The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL).

Solid Lipid Nanoparticles Loaded with Edaravone for Inner Ear Protection After Noise Exposure

Directory of Open Access Journals (Sweden)

Gang Gao

2015-01-01

Full Text Available Background: Antioxidants and the duration of treatment after noise exposure on hearing recovery are important. We investigated the protective effects of an antioxidant substance, edaravone, and its slow-release dosage form, edaravone solid lipid nanoparticles (SLNs, in steady noise-exposed guinea pigs. Methods: SLNs loaded with edaravone were produced by an ultrasound technique. Edaravone solution or edaravone SLNs were administered by intratympanic or intravenous injection after the 1 st day of noise exposure. Guinea pigs were exposed to 110 dB sound pressure level (SPL noise, centered at 0.25-4.0 kHz, for 4 days at 2 h/d. After noise exposure, the guinea pigs underwent auditory brainstem response (ABR threshold measurements, reactive oxygen species (ROS were detected in their cochleas with electron spin resonance (ESR, and outer hair cells (OHCs were counted with silvernitrate (AgNO 3 staining at 1, 4, and 6 days. Results: The ultrasound technique was able to prepare adequate edaravone SLNs with a mean particle size of 93.6 nm and entrapment efficiency of 76.7%. Acoustic stress-induced ROS formation and edaravone exerted a protective effect on the cochlea. Comparisons of hearing thresholds and ROS changes in different animal groups showed that the threshold shift and ROS generation were significantly lower in treated animals than in those without treatment, especially in the edaravone SLN intratympanic injection group. Conclusions: Edaravone SLNs show noticeable slow-release effects and have certain protective effects against noise-induced hearing loss (NIHL.

Disrupting circadian rhythms in rats induces retrograde amnesia

NARCIS (Netherlands)

Fekete, Mátyás; Ree, J.M. van; Niesink, Raymond J.M.; Wied, D. de

1985-01-01

Disrupting circadian organization in rats by phase-shifting the illumination cycle or by exposure to a reversed day/night cycle or to continuous light, resulted in retrograde amnesia for passive avoidance behavior. This retrograde amnesia induced by phase-shifting lasted at least 2 days, and

Titanium dioxide nanoparticles cause genotoxicity in human lung epithelial cells

Science.gov (United States)

The use of engineered nanoparticles in consumer products is steadily increasing. However, the health effects of exposure to these nanoparticles are not thoroughly understood. This study investigated the genotoxicity of six titanium dioxide and two cerium oxide nanoparticles of va...

Recent Advances on Endocrine Disrupting Effects of UV Filters

Directory of Open Access Journals (Sweden)

Jiaying Wang

2016-08-01

Full Text Available Ultraviolet (UV filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives.

Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats

DEFF Research Database (Denmark)

Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Boberg, Julie

2010-01-01

Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development...... were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup...... survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual...

Cellular and molecular responses of adult zebrafish after exposure to CuO nanoparticles or ionic copper.

Science.gov (United States)

Vicario-Parés, Unai; Lacave, Jose M; Reip, Paul; Cajaraville, Miren P; Orbea, Amaia

2018-01-01

Due to their antimicrobial, electrical and magnetic properties, copper nanoparticles (NPs) are suitable for a vast array of applications. Copper can be toxic to biota, making it necessary to assess the potential hazard of copper nanomaterials. Zebrafish (Danio rerio) were exposed to 10 µg Cu/L of CuO NPs of ≈100 nm (CuO-poly) or ionic copper to compare the effects provoked after 3 and 21 days of exposure and at 6 months post-exposure (mpe). At 21 days, significant copper accumulation was only detected in fish exposed to ionic copper. Exposure to both copper forms caused histopathological alterations that could reduce gill functionality, more markedly in the case of ionic copper. Nevertheless, at 6 mpe higher prevalences of gill lesions were detected in fish previously exposed to CuO-poly NPs. No relevant histological alterations were detected in liver, but the lysosomal membrane stability test showed significantly impaired general health status after exposure to both metal forms that lasted up to 6 mpe. 69 transcripts appeared regulated after 3 days of exposure to CuO-poly NPs, suggesting that NPs could produce oxidative stress and reduce metabolism and transport processes. Thirty transcripts were regulated after 21 days of exposure to ionic copper, indicating possible DNA damage. Genes of the circadian clock were identified as the key genes involved in time-dependent differences between the two copper forms. In conclusion, each copper form showed a distinct pattern of liver transcriptome regulation, but both caused gill histopathological alterations and long lasting impaired health status in adult zebrafish.

Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer

Science.gov (United States)

Dauchy, Robert T.; Xiang, Shulin; Mao, Lulu; Brimer, Samantha; Wren, Melissa A.; Yuan, Lin; Anbalagan, Muralidharan; Hauch, Adam; Frasch, Tripp; Rowan, Brian G.; Blask, David E.; Hill, Steven M.

2014-01-01

Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to anti-estrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of ERα+ MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speeds the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characters were not produced in animals where circadian rhythms were not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to re-establish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen. PMID:25062775

Electronic cigarette aerosols and copper nanoparticles induce mitochondrial stress and promote DNA fragmentation in lung fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Lerner, Chad A.; Rutagarama, Pierrot; Ahmad, Tanveer; Sundar, Isaac K.; Elder, Alison; Rahman, Irfan, E-mail: irfan_rahman@urmc.rochester.edu

2016-09-02

Oxidants or nanoparticles have recently been identified as constituents of aerosols released from various styles of electronic cigarettes (E-cigs). Cells in the lung may be directly exposed to these constituents and harbor reactive properties capable of incurring acute cell injury. Our results show mitochondria are sensitive to both E-cig aerosols and aerosol containing copper nanoparticles when exposed to human lung fibroblasts (HFL-1) using an Air-Liquid Interface culture system, evident by elevated levels of mitochondrial ROS (mtROS). Increased mtROS after aerosol exposure is associated with reduced stability of OxPhos electron transport chain (ETC) complex IV subunit and nuclear DNA fragmentation. Increased levels of IL-8 and IL-6 in HFL-1 conditioned media were also observed. These findings reveal both mitochondrial, genotoxic, and inflammatory stresses are features of direct cell exposure to E-cig aerosols which are ensued by inflammatory duress, raising a concern on deleterious effect of vaping. - Graphical abstract: Oxidants and possibly reactive properties of metal particles in E-cig aerosols impart mitochondrial oxidative stress and DNA damage. These biological effects accompany inflammatory response which may raise concern regarding long term E-cig use. Mitochondria may be particularly sensitive to reactive properties of E-cig aerosols in addition to the potential for them to induce genotoxic stress by generating increased ROS. - Highlights: • Mitochondria are sensitive to both E-cig aerosols and metal nanoparticles. • Increased mtROS by E-cig aerosol is associated with disrupted mitochondrial energy. • E-cig causes nuclear DNA fragmentation. • E-cig aerosols induce pro-inflammatory response in human fibroblasts.

Electronic cigarette aerosols and copper nanoparticles induce mitochondrial stress and promote DNA fragmentation in lung fibroblasts

International Nuclear Information System (INIS)

Lerner, Chad A.; Rutagarama, Pierrot; Ahmad, Tanveer; Sundar, Isaac K.; Elder, Alison; Rahman, Irfan

2016-01-01

Oxidants or nanoparticles have recently been identified as constituents of aerosols released from various styles of electronic cigarettes (E-cigs). Cells in the lung may be directly exposed to these constituents and harbor reactive properties capable of incurring acute cell injury. Our results show mitochondria are sensitive to both E-cig aerosols and aerosol containing copper nanoparticles when exposed to human lung fibroblasts (HFL-1) using an Air-Liquid Interface culture system, evident by elevated levels of mitochondrial ROS (mtROS). Increased mtROS after aerosol exposure is associated with reduced stability of OxPhos electron transport chain (ETC) complex IV subunit and nuclear DNA fragmentation. Increased levels of IL-8 and IL-6 in HFL-1 conditioned media were also observed. These findings reveal both mitochondrial, genotoxic, and inflammatory stresses are features of direct cell exposure to E-cig aerosols which are ensued by inflammatory duress, raising a concern on deleterious effect of vaping. - Graphical abstract: Oxidants and possibly reactive properties of metal particles in E-cig aerosols impart mitochondrial oxidative stress and DNA damage. These biological effects accompany inflammatory response which may raise concern regarding long term E-cig use. Mitochondria may be particularly sensitive to reactive properties of E-cig aerosols in addition to the potential for them to induce genotoxic stress by generating increased ROS. - Highlights: • Mitochondria are sensitive to both E-cig aerosols and metal nanoparticles. • Increased mtROS by E-cig aerosol is associated with disrupted mitochondrial energy. • E-cig causes nuclear DNA fragmentation. • E-cig aerosols induce pro-inflammatory response in human fibroblasts.

Assay to detect lipid peroxidation upon exposure to nanoparticles.

Science.gov (United States)

Potter, Timothy M; Neun, Barry W; Stern, Stephan T

2011-01-01

This chapter describes a method for the analysis of human hepatocarcinoma cells (HEP G2) for lipid peroxidation products, such as malondialdehyde (MDA), following treatment with nanoparticle formulations. Oxidative stress has been identified as a likely mechanism of nanoparticle toxicity, and cell-based in vitro systems for evaluation of nanoparticle-induced oxidative stress are widely considered to be an important component of biocompatibility screens. The products of lipid peroxidation, lipid hydroperoxides, and aldehydes, such as MDA, can be measured via a thiobarbituric acid reactive substances (TBARS) assay. In this assay, which can be performed in cell culture or in cell lysate, MDA combines with thiobarbituric acid (TBA) to form a fluorescent adduct that can be detected at an excitation wavelength of 530 nm and an emission wavelength of 550 nm. The results are then expressed as MDA equivalents, normalized to total cellular protein (determined by Bradford assay).

The Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

Science.gov (United States)

Liberda, Eric N.

Introduction. Particulate air pollution, specifically nickel found on or in particulate matter, has been associated with an increased risk of mortality in human population studies and can cause increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiate atherosclerosis in murine exposures. With the discovery of endothelial progenitor cells (EPCs), a door has been opened which may explain these observed cardiovascular effects associated with inhaled air particles and nickel exposure. In order to further quantify the effects of inhaled nickel nanoparticles and attempt to elucidate how the observed findings from other studies may occur, several whole body inhalation exposure experiments to nickel nanoparticles were performed. Methods. Following whole body exposure to approximately 500mug/m3 of nickel nanoparticles for 5 hrs, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation, and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells, circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the inhalation exposure. Plasma proteins were assessed using the 2D DIGE proteomic approach and commercially available ELISAs. Results and Conclusions. Exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation. CECs were significantly upregulated suggesting that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. This decrease in EPC function

Endocrine disrupting chemicals and growth of children.

Science.gov (United States)

Botton, Jérémie; Kadawathagedara, Manik; de Lauzon-Guillain, Blandine

2017-06-01

According to the "environmental obesogen hypothesis", early-life (including in utero) exposure to endocrine disrupting chemicals (EDCs) may disturb the mechanisms involved in adipogenesis or energy storage, and thus may increase the susceptibility to overweight and obesity. Animal models have shown that exposure to several of these chemicals could induce adipogenesis and mechanisms have been described. Epidemiological studies are crucial to know whether this effect could also be observed in humans. We aimed at summarizing the literature in epidemiology on the relationship between EDCs exposure and child's growth. Overall, epidemiological studies suggest that pre- and/or early postnatal exposure to some EDCs may increase the risk of overweight or obesity during childhood. In that review, we present some limitations of these studies, mainly in exposure assessment, that currently prevent to conclude about causality. Recent advances in epidemiology should bring further knowledge. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

Energy Technology Data Exchange (ETDEWEB)

Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak [University of Ljubljana, Department of Biology, Biotechnical Faculty (Slovenia); Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd, E-mail: gorazd.drevensek@mf.uni-lj.si [University of Ljubljana, Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine (Slovenia)

2016-10-15

The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes (n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

Non-hazardous anticancerous and antibacterial colloidal 'green' silver nanoparticles.

Science.gov (United States)

Barua, Shaswat; Konwarh, Rocktotpal; Bhattacharya, Satya Sundar; Das, Pallabi; Devi, K Sanjana P; Maiti, Tapas K; Mandal, Manabendra; Karak, Niranjan

2013-05-01

Poly(ethylene glycol) stabilized colloidal silver nanoparticles were prepared using the reductive potency of the aqueous extract of Thuja occidentalis leaves under ambient conditions. The nanoparticles were well dispersed within a narrow size spectrum (7-14 nm) and displayed characteristic surface plasmon resonance peak at around 420 nm and Bragg's reflection planes of fcc structure. MTT assay revealed the dose-dependent cytocompatibility and toxicity of the nanoparticles with the L929 normal cell line. On the other hand, the antiproliferative action of the nanoparticles was evaluated on HeLa cell (cancerous cells) line. Fluorescence and phase contrast microscopic imaging indicated the appearance of multinucleate stages with aggregation and nuclear membrane disruption of the HeLa cells post treatment with the nanoparticles. The interaction at the prokaryotic level was also assessed via differential antibacterial efficacy against Staphylococcus aureus (MTCC 3160) and Escherichia coli (MTCC 40). Under these perspectives, it is also necessary to observe the environmental impact of the prepared silver nanoparticles. Hence, the dose dependent toxicity of silver nanoparticles was evaluated upon the earthworm species Eisenia fetida. Neither the survival nor the reproduction was affected by the addition of silver nanoparticles up to 1000 ppm. Thus these 'green' silver nanoparticles have promising potential as future materials. Copyright © 2012 Elsevier B.V. All rights reserved.

Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles

Science.gov (United States)

Wilson, Christina L.; Natarajan, Vaishaali; Hayward, Stephen L.; Khalimonchuk, Oleh; Kidambi, Srivatsan

2015-11-01

Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker® Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 +/- 10.56 ppm, 136.0 +/- 31.73 ppm and 62.37 +/- 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte-mediated neurological dysfunction.Titanium dioxide (Ti

Pre-exposure to wheel running disrupts taste aversion conditioning.

Science.gov (United States)

Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C

2002-05-01

When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.

Facilitating Effects of Nanoparticles/Materials on Sensitive Immune-Related Lung Disorders

International Nuclear Information System (INIS)

Inoue, K.I.; Takano, H.

2011-01-01

Although the adverse health effects of nanoparticles/materials have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions have not been fully examined. In this paper, we provide insights into the immunotoxicity of nanoparticles/materials as an aggravating factor in hyper susceptible subjects, especially those with immune-related respiratory disorders using our in vivo experimental model. We first exhibit the effects of nanoparticles/materials on lung inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS) in vivo as a disease model in innate immunity, and demonstrated that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Secondly, we introduce the effects of nanoparticles/materials on allergic asthma in vivo as a disease model in adaptive immunity, and showed that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic airway inflammation, including adjuvant effects on Th2-milieu. Taken together, nanoparticle exposure may synergistically facilitate pathological inflammatory conditions in the lung via both innate and adaptive immunological abnormalities.

Cytoprotective effect of glutaraldehyde erythropoietin on HEK293 kidney cells after silver nanoparticle exposure

Directory of Open Access Journals (Sweden)

Sooklert K

2016-02-01

Full Text Available Kanidta Sooklert,1,2 Supreecha Chattong,3 Krissanapong Manotham,3 Chawikan Boonwong,1 I-yanut Klaharn,1 Depicha Jindatip,4 Amornpun Sereemaspun1,4 1Nanobiomedicine Laboratory, Department of Anatomy, Faculty of Medicine, 2Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, 3Renal Unit, Department of Medicine, Lerdsin General Hospital, 4Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandAbstract: The toxic effects from exposure to silver nanoparticles (AgNPs, which are broadly present in many consumer products, have long raised concerns. Many studies have focused on the mechanisms of nanosilver, which cause toxicity in human cells, but little is known about prevention of this type of injury. This study investigated the in vitro effects of glutaraldehyde erythropoietin (GEPO, a cytoprotective compound derived from erythropoietin, in terms of cell protection against AgNP-induced injury. HEK293 cells were pretreated with or without GEPO before administration of AgNPs. The protective effects of GEPO in this cell line were assessed by the percentage of viable cells, alterations of cell morphology, and the proliferative capability of the cells. In addition, we assessed the role of GEPO in lowering cellular oxidative stress and regulating expression of the anti-apoptotic protein Bcl2. The results showed rescue effects on the percentage of viable and proliferative cells among GEPO pretreated cells. Pretreatment with GEPO maintained the normal cell shape and ultrastructural morphology. Moreover, GEPO reduced the generation of reactive oxygen species in cells and activated expression of Bcl2, which are the major mechanisms in protection against cellular toxicity induced by AgNPs. In conclusion, our study showed that the cytotoxic effects from exposure to AgNPs can be prevented by GEPO. Keywords: glutaraldehyde erythropoietin, silver nanoparticles, cytoprotection

Controlled ultrasound-induced blood-brain barrier disruption using passive acoustic emissions monitoring.

Directory of Open Access Journals (Sweden)

Costas D Arvanitis

Full Text Available The ability of ultrasonically-induced oscillations of circulating microbubbles to permeabilize vascular barriers such as the blood-brain barrier (BBB holds great promise for noninvasive targeted drug delivery. A major issue has been a lack of control over the procedure to ensure both safe and effective treatment. Here, we evaluated the use of passively-recorded acoustic emissions as a means to achieve this control. An acoustic emissions monitoring system was constructed and integrated into a clinical transcranial MRI-guided focused ultrasound system. Recordings were analyzed using a spectroscopic method that isolates the acoustic emissions caused by the microbubbles during sonication. This analysis characterized and quantified harmonic oscillations that occur when the BBB is disrupted, and broadband emissions that occur when tissue damage occurs. After validating the system's performance in pilot studies that explored a wide range of exposure levels, the measurements were used to control the ultrasound exposure level during transcranial sonications at 104 volumes over 22 weekly sessions in four macaques. We found that increasing the exposure level until a large harmonic emissions signal was observed was an effective means to ensure BBB disruption without broadband emissions. We had a success rate of 96% in inducing BBB disruption as measured by in contrast-enhanced MRI, and we detected broadband emissions in less than 0.2% of the applied bursts. The magnitude of the harmonic emissions signals was significantly (P<0.001 larger for sonications where BBB disruption was detected, and it correlated with BBB permeabilization as indicated by the magnitude of the MRI signal enhancement after MRI contrast administration (R(2 = 0.78. Overall, the results indicate that harmonic emissions can be a used to control focused ultrasound-induced BBB disruption. These results are promising for clinical translation of this technology.

Photochemical transformation of silver nanoparticles by combining blue and green irradiation

Energy Technology Data Exchange (ETDEWEB)

Cardoso-Avila, P. E.; Pichardo-Molina, J. L., E-mail: jpichardo@cio.mx [Centro de Investigaciones en Optica A.C (Mexico); Krishna, C. Murali [Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Center (TMC) (India); Castro-Beltran, R. [Centro de Investigaciones en Optica A.C (Mexico)

2015-03-15

Spherical silver nanoparticles (diameter 3 nm) were transformed by means of photochemical synthesis using superluminescent LEDs. Flat rounded (21 nm) and decahedral nanoparticles (78 nm) were, respectively, obtained when the colloid was exposed to green and blue radiation. Furthermore, by changing from blue to green radiation at different exposure times, various morphologies and sizes were obtained. Exposure times shorter than 30 min of blue radiation followed by green radiation resulted on different morphologies such as twine rounded (42 nm), flat elongated (peanuts, 17 nm), and flat rounded nanoparticles (11 and 24 nm). Times longer than 45 min produced decahedral nanoparticles with corners ranging from rounded to sharp (size 71–78 nm). Additionally, these results showed that by controlling morphologies and sizes through the combination of blue and green light at different exposure times, it was possible to tune the plasmon band from 511 to 594 nm. Moreover, controlling the morphology of nanoparticles is of prime importance in order to exploit their properties as part of novel emerging technologies.

Phytotoxicity of silver nanoparticles to Lemna minor L

Energy Technology Data Exchange (ETDEWEB)

Gubbins, Eva J. [Department of Geography and Environmental Science, University of Birmingham, Edgbaston, Birmingham, B15 2TT (United Kingdom); Batty, Lesley C., E-mail: l.c.batty@bham.ac.uk [Department of Geography and Environmental Science, University of Birmingham, Edgbaston, Birmingham, B15 2TT (United Kingdom); Lead, Jamie R. [Department of Geography and Environmental Science, University of Birmingham, Edgbaston, Birmingham, B15 2TT (United Kingdom)

2011-06-15

The use of silver nanoparticles (AgNPs) in commercial products has increased significantly in recent years. Although there has been some attempt to determine the toxic effects of AgNPs, there is little information on aquatic plants which have a vital role in ecosystems. This study reports the use of Lemna minor L. clone St to investigate the phytotoxicity of AgNPs under modified OECD test conditions. AgNPs were synthesised, characterised and subsequently presented to the L. minor. Results showed that inhibition of plant growth was evident after exposure to small ({approx}20 nm) and larger ({approx}100 nm) AgNPs at low concentrations (5 {mu}g L{sup -1}) and this effect became more acute with a longer exposure time. There was a linear dose-response relationship after 14 d exposure. Using predicted environmental concentrations for wastewaters it was found that AgNPs may pose a significant potential risk to the environment. - Highlights: > Silver nanoparticles are toxic to Lemna minor at concentrations of 5 {mu}g L{sup -1}. > The effect of silver nanoparticles varies with size and concentration. > Standard toxicity tests are not appropriate for application to NPs. > Silver nanoparticles pose a potential environmental risk based on modelled environmental concentrations. - Silver nanoparticles are toxic to Lemna minor at low concentrations and constitute a significant environmental risk.

Phytotoxicity of silver nanoparticles to Lemna minor L

International Nuclear Information System (INIS)

Gubbins, Eva J.; Batty, Lesley C.; Lead, Jamie R.

2011-01-01

The use of silver nanoparticles (AgNPs) in commercial products has increased significantly in recent years. Although there has been some attempt to determine the toxic effects of AgNPs, there is little information on aquatic plants which have a vital role in ecosystems. This study reports the use of Lemna minor L. clone St to investigate the phytotoxicity of AgNPs under modified OECD test conditions. AgNPs were synthesised, characterised and subsequently presented to the L. minor. Results showed that inhibition of plant growth was evident after exposure to small (∼20 nm) and larger (∼100 nm) AgNPs at low concentrations (5 μg L -1 ) and this effect became more acute with a longer exposure time. There was a linear dose-response relationship after 14 d exposure. Using predicted environmental concentrations for wastewaters it was found that AgNPs may pose a significant potential risk to the environment. - Highlights: → Silver nanoparticles are toxic to Lemna minor at concentrations of 5 μg L -1 . → The effect of silver nanoparticles varies with size and concentration. → Standard toxicity tests are not appropriate for application to NPs. → Silver nanoparticles pose a potential environmental risk based on modelled environmental concentrations. - Silver nanoparticles are toxic to Lemna minor at low concentrations and constitute a significant environmental risk.

Membrane interactions and antimicrobial effects of layered double hydroxide nanoparticles

DEFF Research Database (Denmark)

Malekkhaiat Häffner, S; Nyström, L; Nordström, R

2017-01-01

Membrane interactions are critical for the successful use of inorganic nanoparticles as antimicrobial agents and as carriers of, or co-actives with, antimicrobial peptides (AMPs). In order to contribute to an increased understanding of these, we here investigate effects of particle size (42-208 nm...... into size-dependent synergistic effects with the antimicrobial peptide LL-37. Due to strong interactions with anionic lipopolysaccharide and peptidoglycan layers, direct membrane disruption of both Gram-negative and Gram-positive bacteria is suppressed. However, LDH nanoparticles cause size-dependent charge...

Workplace performance of a loose-fitting powered air purifying respirator during nanoparticle synthesis

NARCIS (Netherlands)

Koivisto, A.J.; Aromaa, M.; Koponen, I.K.; Fransman, W.; Jensen, K.A.; Mäkelä, J.M.; Hämeri, K.J.

2015-01-01

Nanoparticle (particles with diameter ≤100 nm) exposure is recognized as a potentially harmful size fraction for pulmonary particle exposure. During nanoparticle synthesis, the number concentrations in the process room may exceed 10 × 106 cm−3. During such conditions, it is essential that the

Preparation, characterization of Fe3O4 at TiO2 magnetic nanoparticles and their application for immunoassay of biomarker of exposure to organophosphorus pesticides

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xiao; Wang, Hongbo; Yang, Chunming; Du, Dan; Lin, Yuehe

2013-03-15

Novel Fe3O4 at TiO2 magnetic nanoparticles were prepared and developed for a new nanoparticle-based immunosensor for electrochemical quantification of organophosphorylated butyrylcholinesterase (BChE) in plasma, a specific biomarker of exposure to organophosphorus (OP) agents. The Fe3O4 at TiO2 nanoparticles were synthesized by hydrolysis of tetrabutyltitanate on the surface of Fe3O4 magnetic nanospheres, and characterized by attenuated total reflection Fourier-transform infrared spectra, transmission electron microscope and X-ray diffraction. The functional Fe3O4 at TiO2 nanoparticles were performed as capture antibody to selectively enrich phosphorylated moiety instead of phosphoserine antibody in the traditional sandwich immunoassays. The secondary recognition was served by quantum dots (QDs)-tagged anti-BChE antibody (QDs-anti-BChE). With the help of a magnet, the resulting sandwich-like complex, Fe3O4 at TiO2/OP-BChE/QDs-anti-BChE, was easily isolated from sample solutions and the released cadmium ions were detected on a disposable screen-printed electrode (SPE). The binding affinities were investigated by both surface plasmon resonance (SPR) and square wave voltammetry (SWV). This method not only avoids the drawback of unavailability of commercial OP-specific antibody but also amplifies detection signal by QDs-tags together with easy separation of samples by magnetic forces. The proposed immunosensor yields a linear response over a broad OP-BChE concentrations range from 0.02 to 10 nM, with detection limit of 0.01 nM. Moreover, the disposable nanoparticle-based immunosensor has been validated with human plasma samples. It offers a new method for rapid, sensitive, selective and inexpensive screening/evaluating exposure to OP pesticides.

Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve AgentsOrganophosphate Pesticides and Nerve Agents

Energy Technology Data Exchange (ETDEWEB)

Liu, Guodong; Wang, Jun; Barry, Richard C.; Petersen, Catherine E.; Timchalk, Charles; Gassman, Paul L.; Lin, Yuehe

2008-11-01

A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE) adducts, which is a potential exposure biomarker for organophosphate pesticides (OP) and chemical warfare nerve agent exposures. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to track the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemical stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as a model OP insecticide to prepare the phosphorylated AChE adduct to demonstrate the proof of principle for this sensor technology. The paraoxon-AChE adduct was characterized by Fourier Transform Infrared Spectrum, and the binding affinity of anti-AChE to the paraoxon-AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10 pM to 4 nM paraoxon-AChE, and the limit of detection is estimated to be 8 pM. This new nanoparticle-based electrochemical immunosensor thus provides a sensitive and quantitative tool for biomonitoring exposure to OP pesticides and nerve agents.

Zinc oxide nanoparticle exposure triggers different gene expression patterns in maize shoots and roots

International Nuclear Information System (INIS)

Xun, Hongwei; Ma, Xintong; Chen, Jing; Yang, Zhongzhou; Liu, Bao; Gao, Xiang; Li, Guo; Yu, Jiamiao; Wang, Li; Pang, Jinsong

2017-01-01

The potential impacts of environmentally accumulated zinc oxide nanoparticles (nZnOs) on plant growth have not been well studied. A transcriptome profile analysis of maize exposed to nZnOs showed that the genes in the shoots and roots responded differently. Although the number of differentially expressed genes (DEGs) in the roots was greater than that in the shoots, the number of up- or down-regulated genes in both the shoots and roots was similar. The enrichment of gene ontology (GO) terms was also significantly different in the shoots and roots. The “nitrogen compound metabolism” and “cellular component” terms were specifically and highly up-regulated in the nZnO-exposed roots, whereas the categories “cellular metabolic process”, “primary metabolic process” and “secondary metabolic process” were down-regulated in the exposed roots only. Our results revealed the DEG response patterns in maize shoots and roots after nZnO exposure. - Highlights: • The gene expression patterns of maize exposed to ZnO nanoparticles (nZnO) varied in the shoots and roots. • A majority of the differentially expressed genes induced by nZnO exposure were exclusive to either the shoots or roots. • A similar number of up- and down-regulated genes was observed in the exposed shoots. • More up-regulated than down-regulated genes were found in the exposed roots. • A greater number of GO processes were observed in the nZnO exposed maize roots than in the exposed shoots. • GO terms in the “nitrogen compound metabolic process” category were exclusively and highly expressed in the exposed roots. • GO terms in the “nutrient reservoir” category were exclusively and highly expressed in the exposed roots. • Term “small molecule metabolic process” was also exclusively up-regulated in the exposed roots. • Processes in “cellular metabolic”, “primary metabolic” and “secondary metabolic” were down-regulated in the exposed roots.

Toxicity assessment of TiO2 nanoparticles in zebrafish embryos under different exposure conditions

International Nuclear Information System (INIS)

Clemente, Z.; Castro, V.L.S.S.; Moura, M.A.M.; Jonsson, C.M.; Fraceto, L.F.

2014-01-01

Highlights: •Nano-TiO 2 accelerated hatching of the larvae. •Exposure to anatase/rutile mixture under UV light altered the equilibrium and survival of the larvae. •Nano-TiO 2 caused alterations in the activities of CAT and GST. -- Abstract: The popularity of TiO 2 nanoparticles (nano-TiO 2 ) lies in their wide range of nanotechnological applications, together with low toxicity. Meanwhile, recent studies have shown that the photocatalytic properties of this material can result in alterations in their behavior in the environment, causing effects that have not yet been fully elucidated. The objective of this study was to evaluate the toxicity of two formulations of nano-TiO 2 under different illumination conditions, using an experimental model coherent with the principle of the three Rs of alternative animal experimentation (reduction, refinement, and replacement). Embryos of the fish Danio rerio were exposed for 96 h to different concentrations of nano-TiO 2 in the form of anatase (TA) or an anatase/rutile mixture (TM), under either visible light or a combination of visible and ultraviolet light (UV). The acute toxicity and sublethal parameters evaluated included survival rates, malformation, hatching, equilibrium, and overall length of the larvae, together with biochemical biomarkers (specific activities of catalase (CAT), glutathione S-transferase (GST), and acid phosphatase (AP)). Both TA and TM caused accelerated hatching of the larvae. Under UV irradiation, there was greater mortality of the larvae of the groups exposed to TM, compared to those exposed to TA. Exposure to TM under UV irradiation altered the equilibrium of the larvae. Alterations in the activities of CAT and GST were indicative of oxidative stress, although no clear dose-response relationship was observed. The effects of nano-TiO 2 appeared to depend on both the type of formulation and the illumination condition. The findings contribute to elucidation of the factors involved in the toxicity

Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

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Ana Cristina Nunes

2015-12-01

Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

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M Axelstad

2018-01-01

Full Text Available Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16–20 throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10  months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

Photochemical Study of Silver Nanoparticles Formed from the Reduction of Silver Ions by Humic Acid

Science.gov (United States)

Leslie, Renee M.

This study focuses on the ability of silver ions and humic acid to form silver nanoparticles in the presence of UV and visible light. Silver nanoparticles have a number of industrial applications due primarily to their antimicrobial properties, but these properties pose an environmental threat. Silver nanoparticles can directly disrupt sensitive ecosystems by harming bacteria. Consumption of silver nanoparticles results in silver ions and silver nanoparticles entering waterways; the presence of silver ions raises the question of whether nanoparticles can reform in environmental waters. As our data show, silver nanoparticles can form from the reduction of silver ions by humic acid after irradiation with UV and visible light. In order to better understand the mechanism of these naturally synthesized silver nanoparticles, we investigated the effects of reactant concentration, experimental conditions and presence of ions/reactive species. We monitored silver nanoparticle growth with UV-visible spectroscopy. The evolution in time of nanoparticle size was monitored by dynamic light scattering (DLS).

Effects of silver nitrate and silver nanoparticles on a planktonic community: general trends after short-term exposure.

Directory of Open Access Journals (Sweden)

Jens Boenigk

Full Text Available Among metal pollutants silver ions are one of the most toxic forms, and have thus been assigned to the highest toxicity class. Its toxicity to a wide range of microorganisms combined with its low toxicity to humans lead to the development of a wealth of silver-based products in many bactericidal applications accounting to more than 1000 nano-technology-based consumer products. Accordingly, silver is a widely distributed metal in the environment originating from its different forms of application as metal, salt and nanoparticle. A realistic assessment of silver nanoparticle toxicity in natural waters is, however, problematic and needs to be linked to experimental approaches. Here we apply metatranscriptome sequencing allowing for elucidating reactions of whole communities present in a water sample to stressors. We compared the toxicity of ionic silver and ligand-free silver nanoparticles by short term exposure on a natural community of aquatic microorganisms. We analyzed the effects of the treatments on metabolic pathways and species composition on the eukaryote metatranscriptome level in order to describe immediate molecular responses of organisms using a community approach. We found significant differences between the samples treated with 5 µg/L AgNO3 compared to the controls, but no significant differences in the samples treated with AgNP compared to the control samples. Statistical analysis yielded 126 genes (KO-IDs with significant differential expression with a false discovery rate (FDR <0.05 between the control (KO and AgNO3 (NO3 groups. A KEGG pathway enrichment analysis showed significant results with a FDR below 0.05 for pathways related to photosynthesis. Our study therefore supports the view that ionic silver rather than silver nanoparticles are responsible for silver toxicity. Nevertheless, our results highlight the strength of metatranscriptome approaches for assessing metal toxicity on aquatic communities.

Effect of Nanoparticles Exposure on Fractional Exhaled Nitric Oxide (FENO in Workers Exposed to Nanomaterials

Directory of Open Access Journals (Sweden)

Wei-Te Wu

2014-01-01

Full Text Available Fractional exhaled nitric oxide (FENO measurement is a useful diagnostic test of airway inflammation. However, there have been few studies of FENO in workers exposed to nanomaterials. The purpose of this study was to examine the effect of nanoparticle (NP exposure on FENO and to assess whether the FENO is increased in workers exposed to nanomaterials (NM. In this study, both exposed workers and non-exposed controls were recruited from NM handling plants in Taiwan. A total of 437 subjects (exposed group = 241, non-exposed group = 196 completed the FENO and spirometric measurements from 2009–2011. The authors used a control-banding (CB matrix to categorize the risk level of each participant. In a multivariate linear regression analysis, this study found a significant association between risk level 2 of NP exposure and FENO. Furthermore, asthma, allergic rhinitis, peak expiratory flow rate (PEFR, and NF-κB were also significantly associated with FENO. When the multivariate logistic regression model was adjusted for confounders, nano-TiO2 in all of the NM exposed categories had a significantly increased risk in FENO > 35 ppb. This study found associations between the risk level of NP exposure and FENO (particularly noteworthy for Nano-TiO2. Monitoring FENO in the lung could open up a window into the role nitric oxide (NO may play in pathogenesis.

Synthesis, characterization and frictional wear behavior of ceria hybrid architectures with {111} exposure planes

Energy Technology Data Exchange (ETDEWEB)

Hu, Pengfei [School of Mechanical Engineering, University of South China, Hengyang 421001 (China); Chen, Yong, E-mail: chenyongjsnt@163.com [School of Mechanical Engineering, University of South China, Hengyang 421001 (China); Sun, Rong [Advanced Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai (Japan); Chen, Yue; Yin, Yaru [School of Mechanical Engineering, University of South China, Hengyang 421001 (China); Wang, Zhongchang, E-mail: zcwang@wpi-aimr.tohoku.ac.jp [Advanced Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai (Japan)

2017-04-15

Highlights: • A hybrid architecture comprising three types of cerium nanoparticles (nano-octahedron and its’ ramifications) is synthesized. • The exposure planes of the prepared ceria nanoparticles are {111} crystal planes. • The nanoparticles show markedly material remove capacity and inferior polishing quality. - Abstract: A hybrid architecture comprising three types of cerium nanoparticles, nano-octahedron and its ramifications, is synthesized via a facile yet efficient hydrothermal process. Comprehensive transmission electron microscopy analysis identifies the exposure planes of the cube-shaped ceria nanoparticles as {111} crystal planes. As a result of this unique morphology, the nanoparticles are found to show markedly enhanced material removal capacity and inferior polishing quality compared to the sphere-shaped ceria nanoparticles.

Endocrine disruption of sexual selection by an estrogenic herbicide in the mealworm beetle (Tenebrio molitor).

Science.gov (United States)

McCallum, Malcolm L; Matlock, Makensey; Treas, Justin; Safi, Barroq; Sanson, Wendy; McCallum, Jamie L

2013-12-01

The role that endocrine disruption could play in sexual selection remains relatively untested, and although estrogens occur in insects, little information exists about their biological role in insect reproduction. Atrazine is a commonly applied herbicide that mimics estrogen in vertebrates. Tenebrio molitor were raised from egg to adult under a gradation of environmentally relevant atrazine exposures and a non-treated control. Atrazine was delivered in the drinking water ad libitum. Female T. molitor were provided with a choice between unrelated males raised under three levels of atrazine exposures. Female preference for males demonstrated a non-monotonic inverted U-shaped response to atrazine exposure. There was no significant difference between the control and the high exposure to atrazine. Excluding the control, female preference increased as exposure concentration increased. These results have important repercussions for nonlethal effects of endocrine disruption on populations, their capacity to interfere with sexual selection, and the role of estrogen in pheromone communication among insects.

Differential neurotoxic effects of silver nanoparticles: A review with special emphasis on potential biomarkers

Directory of Open Access Journals (Sweden)

M. Safari

2016-04-01

Full Text Available Silver Nanoparticles (AgNPs have gained considerable interests during the last decade due to their excellent antimicrobial activities. Despite their extensive use, the potential toxicity of these nanoparticles and possible mechanisms by which they may induce adverse reactions have not received sufficient attention and no specific biomarker exist to describe and quantify their toxic effects. Nanoparticles, depending on their physicochemical characteristics and compositions, can interact with vital organs such as the brain and induce toxic effects. A specific concern is that any contact with AgNPs independent of the route of administration is thought to result in significant systemic uptake, internal exposure of sensitive organs, especially in the central nervous system (CNS and different toxic responses. There are considerable evidences that AgNPs can disrupt the Blood-Brain Barrier (BBB and induce subsequent brain edema formation. Therefore, it is essential to understand the differential effects of AgNPs on brain cell with especial emphasis on the possible mechanisms of action. Recently, biomarkers are increasingly used as surrogate indicators of toxic responses in biological monitoring due to the inaccessibility of target organs. Moreover, as the most nanoscale contaminants occur at low concentrations, physiological biomarkers may be better indicators of potential impact of nanomaterials than traditional toxicity testing. This review aims to investigate the effects of AgNPs on CNS targets of toxicity and clarify the role of existing biomarkers especially the role of dopamine levels as a potential biomarker of Ag-NPs neurotoxicity.

Accumulation and Toxicity of CuO and ZnO Nanoparticles through Waterborne and Dietary Exposure of Goldfish (Carassius auratus)

Science.gov (United States)

Ates, Mehmet; Arslan, Zikri; Demir, Veysel; Daniels, James; Farah, Ibrahim O.

2014-01-01

Dietary and waterborne exposure to CuO and ZnO nanoparticles (NPs) was conducted using a simplified model of an aquatic food chain consisting of zooplankton (Artemia salina) and goldfish (Carassius auratus) to determine bioaccumulation, toxic effects and particle transport through trophic levels. Artemia contaminated with NPs were used as food in dietary exposure. Fish were exposed to suspensions of the NPs in waterborne exposure. ICP-MS analysis showed that accumulation primarily occurred in the intestine, followed by the gills and liver. Dietary uptake was lower, but was found to be a potential pathway for transport of NPs to higher organisms. Waterborne exposure resulted in about a tenfold higher accumulation in the intestine. The heart, brain and muscle tissue had no significant Cu or Zn. However, concentrations in muscle increased with NP concentration, which was ascribed to bioaccumulation of Cu and Zn released from NPs. Free Cu concentration in the medium was always higher than that of Zn, indicating CuO NPs dissolved more readily. ZnO NPs were relatively benign, even in waterborne exposure (p≥0.05). In contrast, CuO NPs were toxic. Malondialdehyde levels in the liver and gills increased substantially (p<0.05). Despite lower Cu accumulation, the liver exhibited significant oxidative stress, which could be from chronic exposure to Cu ions. PMID:24860999

Development of magneto-plasmonic nanoparticles for multimodal image-guided therapy to the brain.

Science.gov (United States)

Tomitaka, Asahi; Arami, Hamed; Raymond, Andrea; Yndart, Adriana; Kaushik, Ajeet; Jayant, Rahul Dev; Takemura, Yasushi; Cai, Yong; Toborek, Michal; Nair, Madhavan

2017-01-05

Magneto-plasmonic nanoparticles are one of the emerging multi-functional materials in the field of nanomedicine. Their potential for targeting and multi-modal imaging is highly attractive. In this study, magnetic core/gold shell (MNP@Au) magneto-plasmonic nanoparticles were synthesized by citrate reduction of Au ions on magnetic nanoparticle seeds. Hydrodynamic size and optical properties of magneto-plasmonic nanoparticles synthesized with the variation of Au ions and reducing agent concentrations were evaluated. The synthesized magneto-plasmonic nanoparticles exhibited superparamagnetic properties, and their magnetic properties contributed to the concentration-dependent contrast in magnetic resonance imaging (MRI). The imaging contrast from the gold shell part of the magneto-plasmonic nanoparticles was also confirmed by X-ray computed tomography (CT). The transmigration study of the magneto-plasmonic nanoparticles using an in vitro blood-brain barrier (BBB) model proved enhanced transmigration efficiency without disrupting the integrity of the BBB, and showed potential to be used for brain diseases and neurological disorders.

Isotopically modified nanoparticles for enhanced detection in bioaccumulation studies

Science.gov (United States)

Misra, S.K.; Dybowska, A.; Berhanu, D.; Croteau, M.-N.; Luoma, S.N.; Boccaccini, A.R.; Valsami-Jones, E.

2012-01-01

This work presents results on synthesis of isotopically enriched (99% 65Cu) copper oxide nanoparticles and its application in ecotoxicological studies. 65CuO nanoparticles were synthesized as spheres (7 nm) and rods (7 ?? 40 nm). Significant differences were observed between the reactivity and dissolution of spherical and rod shaped nanoparticles. The extreme sensitivity of the stable isotope tracing technique developed in this study allowed determining Cu uptake at exposure concentrations equivalent to background Cu concentrations in freshwater systems (0.2-30 ??g/L). Without a tracer, detection of newly accumulated Cu was impossible, even at exposure concentrations surpassing some of the most contaminated water systems (>1 mg/L). ?? 2011 American Chemical Society.

Disruption of apoptosis pathways involved in zebrafish gonad differentiation by 17α-ethinylestradiol and fadrozole exposures

International Nuclear Information System (INIS)

Luzio, Ana; Matos, Manuela; Santos, Dércia; Fontaínhas-Fernandes, António A.; Monteiro, Sandra M.

2016-01-01

Highlights: • Apoptosis in females is avoided by anti-apoptotic pathways and in males is essential to the “juvenile ovary” failure. • BIRC5 is central to the regulation of zebrafish spermatogenesis. • EE2 did not change sex ratios, but Fadrozole induced masculinization with a significant increase in male proportion. • The few females identified after exposure to Fadrozole may have avoided sex reversal by increasing anti-apoptotic proteins. • EE2 increased the pro-apoptotic genes/proteins in males, promoting gonad differentiation. - Abstract: Zebrafish (Danio rerio) sex determination seems to involve genetic factors (GSD) but also environmental factors (ESD), such as endocrine disrupting chemicals (EDCs) that are known to mimic endogenous hormones and disrupt gonad differentiation. Apoptosis has also been proposed to play a crucial role in zebrafish gonad differentiation. Nevertheless, the interactions between EDCs and apoptosis have received little attention. Thus, this study aimed to assess if and which apoptotic pathways are involved in zebrafish gonad differentiation and how EDCs may interfere with this process. With these purposes, zebrafish were exposed to 17α-ethinylestradiol (EE_2, 4 ng/L) and fadrozole (Fad, 50 μg/L) from 2 h to 35 days post-fertilization (dpf). Afterwards, a gene expression analysis by qRT-PCR and a stereological analysis, based on systematic sampling and protein immunohistochemistry, were performed. The death receptors (FAS; TRADD), anti-apoptotic (BCL-2; MDM2), pro-apoptotic (CASP-2 and −6) and cell proliferation (BIRC5/survivin; JUN) genes and proteins were evaluated. In general, apoptosis was inhibited in females through the involvement of anti-apoptotic pathways, while in males apoptosis seemed to be crucial to the failure of the “juvenile ovary” development and the induction of testes transformation. The JUN protein was shown to be necessary in juvenile ovaries, while the BIRC5 protein seemed to be involved in

Disruption of apoptosis pathways involved in zebrafish gonad differentiation by 17α-ethinylestradiol and fadrozole exposures

Energy Technology Data Exchange (ETDEWEB)

Luzio, Ana, E-mail: aluzio@utad.pt [Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Departamento de Biologia e Ambiente (DeBA), University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Life Sciences and Environment School, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Matos, Manuela [University of Lisbon, Faculty of Sciences, BioISI– Biosystems & Integrative Sciences Institute, Campo Grande, 1749-016 Lisbon (Portugal); Department of Genetics and Biotechnology, Life Sciences and Environment School (ECVA), University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Santos, Dércia [Life Sciences and Environment School, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Fontaínhas-Fernandes, António A.; Monteiro, Sandra M. [Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Departamento de Biologia e Ambiente (DeBA), University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); Life Sciences and Environment School, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, Vila Real, 5000-801 (Portugal); and others

2016-08-15

Highlights: • Apoptosis in females is avoided by anti-apoptotic pathways and in males is essential to the “juvenile ovary” failure. • BIRC5 is central to the regulation of zebrafish spermatogenesis. • EE2 did not change sex ratios, but Fadrozole induced masculinization with a significant increase in male proportion. • The few females identified after exposure to Fadrozole may have avoided sex reversal by increasing anti-apoptotic proteins. • EE2 increased the pro-apoptotic genes/proteins in males, promoting gonad differentiation. - Abstract: Zebrafish (Danio rerio) sex determination seems to involve genetic factors (GSD) but also environmental factors (ESD), such as endocrine disrupting chemicals (EDCs) that are known to mimic endogenous hormones and disrupt gonad differentiation. Apoptosis has also been proposed to play a crucial role in zebrafish gonad differentiation. Nevertheless, the interactions between EDCs and apoptosis have received little attention. Thus, this study aimed to assess if and which apoptotic pathways are involved in zebrafish gonad differentiation and how EDCs may interfere with this process. With these purposes, zebrafish were exposed to 17α-ethinylestradiol (EE{sub 2}, 4 ng/L) and fadrozole (Fad, 50 μg/L) from 2 h to 35 days post-fertilization (dpf). Afterwards, a gene expression analysis by qRT-PCR and a stereological analysis, based on systematic sampling and protein immunohistochemistry, were performed. The death receptors (FAS; TRADD), anti-apoptotic (BCL-2; MDM2), pro-apoptotic (CASP-2 and −6) and cell proliferation (BIRC5/survivin; JUN) genes and proteins were evaluated. In general, apoptosis was inhibited in females through the involvement of anti-apoptotic pathways, while in males apoptosis seemed to be crucial to the failure of the “juvenile ovary” development and the induction of testes transformation. The JUN protein was shown to be necessary in juvenile ovaries, while the BIRC5 protein seemed to be involved

Facilitating Effects of Nanoparticles/Materials on Sensitive Immune-Related Lung Disorders

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Ken-ichiro Inoue

2011-01-01

Full Text Available Although the adverse health effects of nanoparticles/materials have been proposed and are being clarified, their facilitating effects on preexisting pathological conditions have not been fully examined. In this paper, we provide insights into the immunotoxicity of nanoparticles/materials as an aggravating factor in hypersusceptible subjects, especially those with immune-related respiratory disorders using our in vivo experimental model. We first exhibit the effects of nanoparticles/materials on lung inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS in vivo as a disease model in innate immunity, and demonstrated that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Secondly, we introduce the effects of nanoparticles/materials on allergic asthma in vivo as a disease model in adaptive immunity, and showed that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic airway inflammation, including adjuvant effects on Th2-milieu. Taken together, nanoparticle exposure may synergistically facilitate pathological inflammatory conditions in the lung via both innate and adaptive immunological abnormalities.

Metal Oxide Nanoparticle Photoresists for EUV Patterning

KAUST Repository

Jiang, Jing

2014-01-01

© 2014SPST. Previous studies of methacrylate based nanoparticle have demonstrated the excellent pattern forming capability of these hybrid materials when used as photoresists under 13.5 nm EUV exposure. HfO2 and ZrO2 methacrylate resists have achieved high resolution (∼22 nm) at a very high EUV sensitivity (4.2 mJ/cm2). Further investigations into the patterning process suggests a ligand displacement mechanism, wherein, any combination of a metal oxide with the correct ligand could generate patterns in the presence of the suitable photoactive compound. The current investigation extends this study by developing new nanoparticle compositions with transdimethylacrylic acid and o-toluic acid ligands. This study describes their synthesis and patterning performance under 248 nm KrF laser (DUV) and also under 13.5 nm EUV exposures (dimethylacrylate nanoparticles) for the new resist compositions.

Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract.

Science.gov (United States)

Powell, Jonathan J; Faria, Nuno; Thomas-McKay, Emma; Pele, Laetitia C

2010-05-01

Humans have evolved with oral exposure to dietary microparticles and nanoparticles as a normal occurrence but the ever-growing exploitation of nanotechnology is likely to increase exposure further, both qualitatively and quantitatively. Moreover, unlike the situation with respirable particles, relatively little is known about gastrointestinal intake and handling of nanoparticles. With a long term interest in gut exposure and responses to dietary microparticles, our group is now applying its expertise to nanoparticles in the gastrointestinal tract. Here we aim to address (i) the current challenges associated with the characterisation of particle-host or particle-cell interactions, (ii) the origin and mechanisms of uptake of particles in the gastrointestinal tract, especially via the Peyer's patch and (iii) potential cellular effects of nanoparticles in the generation of reactive oxygen species and inflammasome activation, or microparticles in their adjuvant activity in pro-inflammatory signalling and immune responsiveness. Copyright 2010 Elsevier Ltd. All rights reserved.

Combined Study of Titanium Dioxide Nanoparticle Transport and Toxicity on Microbial Nitrifying Communities under Single and Repeated Exposures in Soil Columns.

Science.gov (United States)

Simonin, Marie; Martins, Jean M F; Uzu, Gaëlle; Vince, Erwann; Richaume, Agnès

2016-10-04

Soils are exposed to nanoparticles (NPs) as a result of their increasing use in many commercial products. Adverse effects of NPs on soil microorganisms have been reported in several ecotoxicological studies using microcosms. Although repeated exposures are more likely to occur in soils, most of these previous studies were performed as a single exposure to NPs. Contrary to single contamination, the study of multiple NP contaminations in soils requires the use of specialized setups. Using a soil column experiment, we compared the influence of single and repeated exposures (one, two, or three exposures that resulted in the same final concentration applied) on the transport of titanium dioxide (TiO 2 ) NPs through soil and the effect of these different exposure scenarios on the abundance and activity of soil nitrifying microbial communities after a 2 month incubation. The transport of TiO 2 NPs was very limited under both single and repeated exposures and was highest for the lowest concentration injected during the first application. Significant decreases in nitrification activity and ammonia-oxidizing archaea and bacteria populations were observed only for the repeated exposure scenario (three TiO 2 NP contaminations). These results suggest that, under repeated exposures, the transport of TiO 2 NPs to deep soil layers and groundwater is limited and that a chronic contamination is more harmful for the soil microbiological functioning than a single exposure.

Effects of Prolonged Silver Nanoparticle Exposure on the Contextual Cognition and Behavior of Mammals

Directory of Open Access Journals (Sweden)

Anna Antsiferova

2018-04-01

Full Text Available Silver nanoparticles have been widely used in the lighting and food industries, in medicine, and in pharmaceutics as an antiseptic agent. Recent research demonstrates that, after prolonged oral administration, silver nanoparticles may cross the blood-brain barrier and accumulate in the brain in rather high amounts. In ex vivo experiments, it has also been shown that silver nanoparticles demonstrate neurotoxicity. The objective of this work was to answer the questions whether silver nanoparticles change cognitive and behavioral functions of mammals after prolonged administration if silver nanoparticles have accumulated in the brain. C57Bl/6 male mice were orally exposed to PVP-coated silver nanoparticles daily for 30, 60, 120 and 180 days. Control mice were exposed to distilled water. After that they were tested in the Open Field, Elevated Plus Maze, Light-Dark Box and contextual fear conditioning task. The data have shown that the experimental mice went through three periods of switching in the behavior caused by adaptation to the toxic silver nanoparticles: anxiety, appearance of research instinct and impairment of long-term memory. This provides evidence of the hazardous effect of silver nanoparticles, which appears after long periods of silver nanoparticle oral administration.

Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

Science.gov (United States)

Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

Introduction: circadian rhythm and its disruption: impact on reproductive function.

Science.gov (United States)

Casper, Robert F; Gladanac, Bojana

2014-08-01

Almost all forms of life have predictable daily or circadian rhythms in molecular, endocrine, and behavioral functions. In mammals, a central pacemaker located in the suprachiasmatic nuclei coordinates the timing of these rhythms. Daily light exposure that affects the retina of the eye directly influences this area, which is required to align endogenous processes to the appropriate time of day. The present "Views and Reviews" articles discuss the influence of circadian rhythms, especially nightly secretion of melatonin, on reproductive function and parturition. In addition, an examination is made of problems that arise from recurrent circadian rhythm disruption associated with changes in light exposure patterns common to modern day society. Finally, a possible solution to prevent disruptions in circadian phase markers by filtering out short wavelengths from nocturnal light is reviewed. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Thyroid-disrupting chemicals and brain development: an update

Directory of Open Access Journals (Sweden)

Bilal B Mughal

2018-04-01

Full Text Available This review covers recent findings on the main categories of thyroid hormone–disrupting chemicals and their effects on brain development. We draw mostly on epidemiological and experimental data published in the last decade. For each chemical class considered, we deal with not only the thyroid hormone–disrupting effects but also briefly mention the main mechanisms by which the same chemicals could modify estrogen and/or androgen signalling, thereby exacerbating adverse effects on endocrine-dependent developmental programmes. Further, we emphasize recent data showing how maternal thyroid hormone signalling during early pregnancy affects not only offspring IQ, but also neurodevelopmental disease risk. These recent findings add to established knowledge on the crucial importance of iodine and thyroid hormone for optimal brain development. We propose that prenatal exposure to mixtures of thyroid hormone–disrupting chemicals provides a plausible biological mechanism contributing to current increases in the incidence of neurodevelopmental disease and IQ loss.

Protein Corona Analysis of Silver Nanoparticles Links to Their Cellular Effects.

Science.gov (United States)

Juling, Sabine; Niedzwiecka, Alicia; Böhmert, Linda; Lichtenstein, Dajana; Selve, Sören; Braeuning, Albert; Thünemann, Andreas F; Krause, Eberhard; Lampen, Alfonso

2017-11-03

The breadth of applications of nanoparticles and the access to food-associated consumer products containing nanosized materials lead to oral human exposure to such particles. In biological fluids nanoparticles dynamically interact with biomolecules and form a protein corona. Knowledge about the protein corona is of great interest for understanding the molecular effects of particles as well as their fate inside the human body. We used a mass spectrometry-based toxicoproteomics approach to elucidate mechanisms of toxicity of silver nanoparticles and to comprehensively characterize the protein corona formed around silver nanoparticles in Caco-2 human intestinal epithelial cells. Results were compared with respect to the cellular function of proteins either affected by exposure to nanoparticles or present in the protein corona. A transcriptomic data set was included in the analyses in order to obtain a combined multiomics view of nanoparticle-affected cellular processes. A relationship between corona proteins and the proteomic or transcriptomic responses was revealed, showing that differentially regulated proteins or transcripts were engaged in the same cellular signaling pathways. Protein corona analyses of nanoparticles in cells might therefore help in obtaining information about the molecular consequences of nanoparticle treatment.

Exposure to a complex cocktail of environmental endocrine-disrupting compounds disturbs the kisspeptin/GPR54 system in ovine hypothalamus and pituitary gland.

Science.gov (United States)

Bellingham, Michelle; Fowler, Paul A; Amezaga, Maria R; Rhind, Stewart M; Cotinot, Corinne; Mandon-Pepin, Beatrice; Sharpe, Richard M; Evans, Neil P

2009-10-01

Ubiquitous environmental chemicals, including endocrine-disrupting chemicals (EDCs), are associated with declining human reproductive health, as well as an increasing incidence of cancers of the reproductive system. Verifying such links requires animal models exposed to "real-life," environmentally relevant concentrations/mixtures of EDC, particularly in utero, when sensitivity to EDC exposure is maximal. We evaluated the effects of maternal exposure to a pollutant cocktail (sewage sludge) on the ovine fetal reproductive neuroendocrine axes, particularly the kisspeptin (KiSS-1)/GPR54 (G-protein-coupled receptor 54) system. KiSS-1, GPR54, and ERalpha (estrogen receptor alpha) mRNA expression was quantified in control (C) and treated (T) maternal and fetal (110-day) hypothalami and pituitary glands using semiquantitative reverse transcription polymerase chain reaction, and colocalization of kisspeptin with LHbeta (luteinizing hormone beta) and ERalpha in C and T fetal pituitary glands quantified using dual-labeling immunohistochemistry. Fetuses exposed in utero to the EDC mixture showed reduced KiSS-1 mRNA expression across three hypothalamic regions examined (rostral, mid, and caudal) and had fewer kisspetin immunopositive cells colocalized with both LHbeta and ERalpha in the pituitary gland. In contrast, treatment had no effect on parameters measured in the adult ewe hypothalamus or pituitary. This study demonstrates that the developing fetus is sensitive to real-world mixtures of environmental chemicals, which cause significant neuroendocrine alterations. The important role of kisspeptin/GPR54 in regulating puberty and adult reproduction means that in utero disruption of this system is likely to have long-term consequences in adulthood and represents a novel, additional pathway through which environmental chemicals perturb human reproduction.

Evaluation of the effects of titanium dioxide nanoparticles on cultured Rana catesbeiana tailfin tissue

Directory of Open Access Journals (Sweden)

S. Austin eHammond

2013-11-01

Full Text Available Nanoparticles (NPs, materials that have one dimension less than 100 nm, are used in manufacturing, health and food products, and consumer products including cosmetics, clothing and household appliances. Their utility to industry is derived from their high surface-area-to-volume ratios and physico-chemical properties distinct from their bulk counterparts, but the near-certainty that NPs will be released into the environment raises the possibility that they could present health risks to humans and wildlife. The thyroid hormones (THs, thyroxine and 3,3’,5-triiodothyronine (T3, are involved in development and metabolism in vertebrates including humans and frogs. Many of the processes of anuran metamorphosis are analogous to human post-embryonic development and disruption of TH action can have drastic effects. These shared features make the metamorphosis of anurans an excellent model for screening for endocrine disrupting chemicals (EDCs. We used the cultured tailfin (C-fin assay to examine the exposure effects of 0.1-10 nM (~8-800 ng/L of three types of ~20 nm TiO2 NPs (P25, M212, M262 and micron-sized TiO2 (μTiO2 ±10 nM T3. The actual Ti levels were 40.9 – 64.7% of the nominal value. Real-time quantitative polymerase chain reaction (QPCR was used to measure the relative amounts of mRNA transcripts encoding TH-responsive thyroid hormone receptors (thra and thrb and Rana larval keratin type I (rlk1, as well as the cellular stress-responsive heat shock protein 30 kDa (hsp30, superoxide dismutase (sod, and catalase (cat. The levels of the TH-responsive transcripts were largely unaffected by any form of TiO2. Some significant effects on stress-related transcripts were observed upon exposure to micron-sized TiO2, P25 and M212 while no effect was observed with M262 exposure. Therefore the risk of adversely affecting amphibian tissue by disrupting TH-signalling or inducing cellular stress is low for these compounds relative to other previously

Toxicity of iron oxide nanoparticles against osteoblasts

International Nuclear Information System (INIS)

Shi Sifeng; Jia Jingfu; Guo Xiaokui; Zhao Yaping; Liu Boyu; Chen Desheng; Guo Yongyuan; Zhang Xianlong

2012-01-01

Magnetic nanoparticles have been widely used for tissue repair, magnetic resonance imaging, immunoassays and drug delivery. They are very promising in orthopaedic applications and several magnetic nanoparticles have been exploited for the treatment of orthopaedic disease. Here, we conducted an in vitro study to examine the interaction of magnetic iron oxide nanoparticles with human osteoblasts to evaluate the dose-related toxicity of the nanoparticles on osteoblasts. A transmission electron microscope was used to visualise the internalised magnetic nanoparticles in osteoblasts. The CCK-8 results revealed increased cell viability (107.5 % vitality compared with the control group) when co-cultured at a low concentration (20 μg/mL) and decreased cell viability (59.5 % vitality in a concentration of 300 μg/mL and 25.9 % in 500 μg/mL) when co-cultured in high concentrations. The flow cytometric detection revealed similar results with 5.48 % of apoptosis in a concentration of 20 μg/mL, 23.40 % of apoptosis in a concentration of 300 μg/mL and 28.49 % in a concentration of 500 μg/mL. The disrupted cytoskeleton of osteoblasts was also revealed using a laser scanning confocal microscope. We concluded that use of a low concentration of magnetic iron oxide nanoparticles is important to avoid damage to osteoblasts.

Toxicity of iron oxide nanoparticles against osteoblasts

Energy Technology Data Exchange (ETDEWEB)

Shi Sifeng [Shanghai Jiao Tong University, Department of Orthopaedic Surgery, Shanghai Sixth People' s Hospital (China); Jia Jingfu [Shanghai Jiao Tong University, School of Chemistry and Chemical Technology (China); Guo Xiaokui [Shanghai Jiao Tong University School of Medicine, Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences (China); Zhao Yaping [Shanghai Jiao Tong University, School of Chemistry and Chemical Technology (China); Liu Boyu [Shanghai Jiao Tong University School of Medicine, Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences (China); Chen Desheng; Guo Yongyuan; Zhang Xianlong, E-mail: zhangxianlong20101@163.com [Shanghai Jiao Tong University, Department of Orthopaedic Surgery, Shanghai Sixth People' s Hospital (China)

2012-09-15

Magnetic nanoparticles have been widely used for tissue repair, magnetic resonance imaging, immunoassays and drug delivery. They are very promising in orthopaedic applications and several magnetic nanoparticles have been exploited for the treatment of orthopaedic disease. Here, we conducted an in vitro study to examine the interaction of magnetic iron oxide nanoparticles with human osteoblasts to evaluate the dose-related toxicity of the nanoparticles on osteoblasts. A transmission electron microscope was used to visualise the internalised magnetic nanoparticles in osteoblasts. The CCK-8 results revealed increased cell viability (107.5 % vitality compared with the control group) when co-cultured at a low concentration (20 {mu}g/mL) and decreased cell viability (59.5 % vitality in a concentration of 300 {mu}g/mL and 25.9 % in 500 {mu}g/mL) when co-cultured in high concentrations. The flow cytometric detection revealed similar results with 5.48 % of apoptosis in a concentration of 20 {mu}g/mL, 23.40 % of apoptosis in a concentration of 300 {mu}g/mL and 28.49 % in a concentration of 500 {mu}g/mL. The disrupted cytoskeleton of osteoblasts was also revealed using a laser scanning confocal microscope. We concluded that use of a low concentration of magnetic iron oxide nanoparticles is important to avoid damage to osteoblasts.

Cytotoxicity and ion release of alloy nanoparticles

International Nuclear Information System (INIS)

Hahn, Anne; Fuhlrott, Jutta; Loos, Anneke; Barcikowski, Stephan

2012-01-01

It is well-known that nanoparticles could cause toxic effects in cells. Alloy nanoparticles with yet unknown health risk may be released from cardiovascular implants made of Nickel–Titanium or Cobalt–Chromium due to abrasion or production failure. We show the bio-response of human primary endothelial and smooth muscle cells exposed to different concentrations of metal and alloy nanoparticles. Nanoparticles having primary particle sizes in the range of 5–250 nm were generated using laser ablation in three different solutions avoiding artificial chemical additives, and giving access to formulations containing nanoparticles only stabilized by biological ligands. Endothelial cells are found to be more sensitive to nanoparticle exposure than smooth muscle cells. Cobalt and Nickel nanoparticles caused the highest cytotoxicity. In contrast, Titanium, Nickel–Iron, and Nickel–Titanium nanoparticles had almost no influence on cells below a nanoparticle concentration of 10 μM. Nanoparticles in cysteine dissolved almost completely, whereas less ions are released when nanoparticles were stabilized in water or citrate solution. Nanoparticles stabilized by cysteine caused less inhibitory effects on cells suggesting cysteine to form metal complexes with bioactive ions in media.

OPTIMIZATION OF CELL DISRUPTION IN RAPHIDOCELIS SUBCAPITATA AND CHLORELLA VULGARIS FOR BIOMARKER EVALUATION

Directory of Open Access Journals (Sweden)

Adeolu Aderemi

2015-06-01

Full Text Available Raphidocelis subcapitata and Chlorella vulgaris are bioassay microalgae with rigid cellulosic cell wall which can hinder the release of intracellular proteins often studied as toxicity biomarkers. Since cell disruption is necessary for recovering intracellular biomolecules in these organisms, this study investigated the efficiency of ultrasonication bath; ultrasonication probe; vortexer; and bead mill in disintegrating the microalgae for anti-oxidative enzyme extraction. The extent of cell disruption was evaluated and quantified using bright field microscopy. Disrupted algae appeared as ghosts. The greatest disintegration of the microalgae (83-99.6 % was achieved using bead mill with 0.42-0.6 mm glass beads while the other methods induced little or no disruption. The degree of cell disruption using bead mill increased with exposure time, beads-solution ratio and agitation speed while larger beads caused less disruption. Findings revealed that bead milling, with specific parameters optimized, is one of the most effective methods of disintegrating the robust algal cells.

Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Yuka; Tada-Oikawa, Saeko [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Ichihara, Gaku [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya (Japan); Yabata, Masayuki; Izuoka, Kiyora [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Suzuki, Masako; Sakai, Kiyoshi [Nagoya City Public Health Research Institute, Nagoya (Japan); Ichihara, Sahoko, E-mail: saho@gene.mie-u.ac.jp [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan)

2014-07-01

Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO{sub 2} and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO{sub 2} particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO{sub 2} nanoparticles.

High-Mobility Group Box 1 Disrupts Metabolic Function with Cigarette Smoke Exposure in a Ceramide-Dependent Manner

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Oliver J. Taylor

2017-05-01

Full Text Available We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1, which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis. Outcomes included assessments of insulin resistance and muscle mitochondrial function. HMGB1 was significantly increased in both human lungs and rodent alveolar macrophages. Further testing revealed that HMGB1 treatment elicited a widespread increase in ceramide species and reduction in myotube mitochondrial respiration, an increase in reactive oxygen species, and reduced insulin-stimulated Akt phosphorylation. Inhibition of ceramide biosynthesis with myriocin was protective. In mice, by comparing treatments of HMGB1 injections with or without myriocin, we found that HMGB1 injections resulted in increased muscle ceramides, especially C16 and C24, which were necessary for reduced muscle mitochondrial respiration and compromised insulin and glucose tolerance. In conclusion, HMGB1 may be a necessary intermediate in the ceramide-dependent metabolic consequences of cigarette smoke exposure.

Immunogenicity and ecotoxicity of engineered nanoparticles

Science.gov (United States)

Maurer-Jones, Melissa Ann

The growing use of nanoscale materials in commercially available products and therapeutics has created an urgent need to determine the toxicity of these materials so that they may be designed and employed safely. As nanoparticles have unique physical and chemical properties, the challenges in determining their physiological and environmental impact have been numerous. It is, therefore, the goal of my thesis work to employ sensitive analytical tools to fundamentally understand the how nanoparticles interact with immunologically and ecologically relevant models. My project approaches nanotoxicity studies starting with a relevant model system exposed to well-characterized nanoparticles to (1) determine if cells/organisms survive exposure using traditional toxicological assays and, if the majority survives exposure, (2) use sensitive analytical tools to determine if there are changes to critical cell/organism function. If perturbation of function is detected, (3) the mechanism or cause of changes in cell function should be determined, including assessment of nanoparticle uptake and localization. Once a mechanism of interaction is determined, this process could begin again with a modified particle that may address the toxic response. Chapter Two describes the impact of metal oxide (TiO2 and SiO2) nanoparticles on mast cells, critical immune system cells, and utilizes the sensitive technique of carbon-fiber microelectrode amperometry (CFMA) to monitor changes in the important mast cell function of exocytosis. Chapter Three expands upon Chapter Two and examines in more detail the mechanism by which TiO2 nanoparticles impact exocytotic cell function, completing the process nanotoxicity described above. From these studies, it was determined that, while nanoparticles do not decrease the viability of mast cells, there are significant changes to exocytosis upon nanoparticle exposure, and in the case of TiO2, these changes in exocytosis are correlated to nanoparticle

Dynamics of Catalyst Nanoparticles

DEFF Research Database (Denmark)

Hansen, Thomas Willum; Cavalca, Filippo; Wagner, Jakob Birkedal

and pharmaceuticals, and the cleanup of exhaust from automobiles and stationary power plants. Sintering, or thermal deactivation, is an important mechanism for the loss of catalyst activity. In order to initiate a systematic study of the dynamics and sintering of nanoparticles, various catalytic systems have been...... under gas exposure, dynamic phenomena such as sintering and growth can be observed with sub-Ångstrøm resolution. Metal nanoparticles contain the active sites in heterogeneous catalysts, which are important for many industrial applications including the production of clean fuels, chemicals...

Photoluminescent carbogenic nanoparticles directly derived from crude biomass

KAUST Repository

Krysmann, Marta J.

2012-01-01

We present an environmentally benign, energy efficient and readily scalable approach to synthesize photoluminescent carbogenic nanoparticles directly from soft tissue biomass. Our approach relies on the pyrolytic decomposition of grass that gives rise to the formation of well-defined nanoparticles. The carbogenic nanoparticles can be readily surface modified, generating a series of highly selective photoluminescent materials that exhibit remarkable stability upon prolonged exposure to aggressive, high-temperature, high-salinity environment. © 2012 The Royal Society of Chemistry.

Methodological issues in human studies of endocrine disrupting chemicals.

Science.gov (United States)

Lee, Duk-Hee; Jacobs, David R

2015-12-01

Possible harm from endocrine disrupting chemicals (EDCs) in humans is speculated based on two types of evidence; 1) increasing trends of suspected diseases in ecological studies of populations and 2) findings from traditional epidemiological studies of individuals. However, ecological findings are not regarded as direct human evidence of the relation between EDCs and disease, while the evidence among epidemiological studies of individuals is often inconsistent. Thus, a criticism is that linking EDCs and health in human is naively presumed without solid evidence. However, human studies of EDCs are methodologically complex and understanding methodological issues will help to interpret findings from existing human studies and to properly design optimal human studies. The key issues are low reliability of exposure assessment of EDCs with short half-lives, EDC mixtures, possibility of non-monotonic dose-response relationships, non-existence of an unexposed group, difficulties in measuring exposure during critical periods, and interactions with established risk factors. Furthermore, EDC mixtures may affect human health through other mechanisms than traditional endocrine disruption, for example glutathione depletion or mitochondrial dysfunction. Given this complexity, the most plausible scenario in humans is that exposure to EDC mixtures leads to increasing risk of related diseases at the ecological level, but inconsistent associations would be expected in traditional epidemiological studies. Although epidemiologists have long relied on Bradford Hill's criteria to objectively evaluate whether associations observed in epidemiology can be interpreted as causal, there are challenges to use these criteria for EDCs, particularly concerning consistency across studies and the findings of linear dose-response relationships. At the individual level, compared to EDCs with short half-lives, epidemiological studies of EDCs with long half-lives among populations with a relatively low

Toxicity assessment of TiO{sub 2} nanoparticles in zebrafish embryos under different exposure conditions

Energy Technology Data Exchange (ETDEWEB)

Clemente, Z., E-mail: zairaclemente@yahoo.com.br [Laboratório de Ecotoxicologia e Biossegurança, Embrapa CNPMA, Jaguariúna, SP (Brazil); Programa de Pós-graduação em Biologia Funcional e Molecular, UNICAMP, Campinas, SP (Brazil); Castro, V.L.S.S. [Laboratório de Ecotoxicologia e Biossegurança, Embrapa CNPMA, Jaguariúna, SP (Brazil); Moura, M.A.M. [Laboratório da Ciência das Plantas Daninhas, Instituto Biológico, APTA/SAA, Campinas, SP (Brazil); Jonsson, C.M. [Laboratório de Ecotoxicologia e Biossegurança, Embrapa CNPMA, Jaguariúna, SP (Brazil); Fraceto, L.F. [Programa de Pós-graduação em Biologia Funcional e Molecular, UNICAMP, Campinas, SP (Brazil); Departamento de Engenharia Ambiental, UNESP, Sorocaba, SP (Brazil)

2014-02-15

Highlights: •Nano-TiO{sub 2} accelerated hatching of the larvae. •Exposure to anatase/rutile mixture under UV light altered the equilibrium and survival of the larvae. •Nano-TiO{sub 2} caused alterations in the activities of CAT and GST. -- Abstract: The popularity of TiO{sub 2} nanoparticles (nano-TiO{sub 2}) lies in their wide range of nanotechnological applications, together with low toxicity. Meanwhile, recent studies have shown that the photocatalytic properties of this material can result in alterations in their behavior in the environment, causing effects that have not yet been fully elucidated. The objective of this study was to evaluate the toxicity of two formulations of nano-TiO{sub 2} under different illumination conditions, using an experimental model coherent with the principle of the three Rs of alternative animal experimentation (reduction, refinement, and replacement). Embryos of the fish Danio rerio were exposed for 96 h to different concentrations of nano-TiO{sub 2} in the form of anatase (TA) or an anatase/rutile mixture (TM), under either visible light or a combination of visible and ultraviolet light (UV). The acute toxicity and sublethal parameters evaluated included survival rates, malformation, hatching, equilibrium, and overall length of the larvae, together with biochemical biomarkers (specific activities of catalase (CAT), glutathione S-transferase (GST), and acid phosphatase (AP)). Both TA and TM caused accelerated hatching of the larvae. Under UV irradiation, there was greater mortality of the larvae of the groups exposed to TM, compared to those exposed to TA. Exposure to TM under UV irradiation altered the equilibrium of the larvae. Alterations in the activities of CAT and GST were indicative of oxidative stress, although no clear dose-response relationship was observed. The effects of nano-TiO{sub 2} appeared to depend on both the type of formulation and the illumination condition. The findings contribute to elucidation of the

Life-cycle assessment framework for indoor emissions of synthetic nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Walser, Tobias, E-mail: tobias.walser@bag.admin.ch [ETH Zurich, Institute for Environmental Engineering (Switzerland); Meyer, David [U.S. Environmental Protection Agency, National Risk Management Research Laboratory (United States); Fransman, Wouter; Buist, Harrie; Kuijpers, Eelco; Brouwer, Derk [TNO (Netherlands)

2015-06-15

Life-Cycle Assessment (LCA) is a well-established method to evaluate impacts of chemicals on the environment and human health along the lifespan of products. However, the increasingly produced and applied nanomaterials (defined as one dimension <100 nm) show particular characteristics which are different from conventional chemicals or larger particles. As a consequence, LCA does not provide sufficient guidance on how to deal with synthetic nanomaterials, neither in the exposure, nor in the effect assessment. This is particularly true for the workplace, where significant exposure can be expected via the lung, the route of major concern. Therefore, we developed a concise method which allows the inclusion of indoor nanoparticle exposure into LCA. New nanospecific properties are included along the LCA stages with a particular focus on the workplace environment. We built upon existing LCA methods and nanoparticle fate and exposure studies. The impact assessment requires new approaches for nanoparticles, such as guidance on relevant endpoints, nanospecific properties that are relevant for the toxicity, and guidance on the chemical identity of nanomaterials, i.e., categorization and distinction of different forms of nanomaterials. We present a framework which goes beyond traditional approaches of LCA and includes nanospecific fate parameters in the indoor exposure assessment as well as guidance on the development of effect and characterization factors for inhaled nanoparticles. Specifically, the indoor one-box model is amended with new particle-specific parameters developed in the exposure literature. A concentration conversion and parameter estimation tool are presented. Finally, the modification of the traditional intake fraction to capture size-specific deposition and retention rate are discussed along with a strategy for a more robust effect assessment. The paper is a further step toward a fair comparison between conventional and nano-enabled products by integrating

Life-cycle assessment framework for indoor emissions of synthetic nanoparticles

Science.gov (United States)

Walser, Tobias; Meyer, David; Fransman, Wouter; Buist, Harrie; Kuijpers, Eelco; Brouwer, Derk

2015-06-01

Life-Cycle Assessment (LCA) is a well-established method to evaluate impacts of chemicals on the environment and human health along the lifespan of products. However, the increasingly produced and applied nanomaterials (defined as one dimension chemicals or larger particles. As a consequence, LCA does not provide sufficient guidance on how to deal with synthetic nanomaterials, neither in the exposure, nor in the effect assessment. This is particularly true for the workplace, where significant exposure can be expected via the lung, the route of major concern. Therefore, we developed a concise method which allows the inclusion of indoor nanoparticle exposure into LCA. New nanospecific properties are included along the LCA stages with a particular focus on the workplace environment. We built upon existing LCA methods and nanoparticle fate and exposure studies. The impact assessment requires new approaches for nanoparticles, such as guidance on relevant endpoints, nanospecific properties that are relevant for the toxicity, and guidance on the chemical identity of nanomaterials, i.e., categorization and distinction of different forms of nanomaterials. We present a framework which goes beyond traditional approaches of LCA and includes nanospecific fate parameters in the indoor exposure assessment as well as guidance on the development of effect and characterization factors for inhaled nanoparticles. Specifically, the indoor one-box model is amended with new particle-specific parameters developed in the exposure literature. A concentration conversion and parameter estimation tool are presented. Finally, the modification of the traditional intake fraction to capture size-specific deposition and retention rate are discussed along with a strategy for a more robust effect assessment. The paper is a further step toward a fair comparison between conventional and nano-enabled products by integrating occupational exposure to synthetic nanomaterials into LCA.

Life-cycle assessment framework for indoor emissions of synthetic nanoparticles

International Nuclear Information System (INIS)

Walser, Tobias; Meyer, David; Fransman, Wouter; Buist, Harrie; Kuijpers, Eelco; Brouwer, Derk

2015-01-01

Life-Cycle Assessment (LCA) is a well-established method to evaluate impacts of chemicals on the environment and human health along the lifespan of products. However, the increasingly produced and applied nanomaterials (defined as one dimension <100 nm) show particular characteristics which are different from conventional chemicals or larger particles. As a consequence, LCA does not provide sufficient guidance on how to deal with synthetic nanomaterials, neither in the exposure, nor in the effect assessment. This is particularly true for the workplace, where significant exposure can be expected via the lung, the route of major concern. Therefore, we developed a concise method which allows the inclusion of indoor nanoparticle exposure into LCA. New nanospecific properties are included along the LCA stages with a particular focus on the workplace environment. We built upon existing LCA methods and nanoparticle fate and exposure studies. The impact assessment requires new approaches for nanoparticles, such as guidance on relevant endpoints, nanospecific properties that are relevant for the toxicity, and guidance on the chemical identity of nanomaterials, i.e., categorization and distinction of different forms of nanomaterials. We present a framework which goes beyond traditional approaches of LCA and includes nanospecific fate parameters in the indoor exposure assessment as well as guidance on the development of effect and characterization factors for inhaled nanoparticles. Specifically, the indoor one-box model is amended with new particle-specific parameters developed in the exposure literature. A concentration conversion and parameter estimation tool are presented. Finally, the modification of the traditional intake fraction to capture size-specific deposition and retention rate are discussed along with a strategy for a more robust effect assessment. The paper is a further step toward a fair comparison between conventional and nano-enabled products by integrating

Safety issues associated with the use of nanoparticles in human body.

Science.gov (United States)

Sufian, Mian Muhammad; Khattak, Jabar Zaman Khan; Yousaf, Shahzad; Rana, Muhammad Suleman

2017-09-01

Nanotechnology has transformed the world by the introduction of a distinctive class of materials and products in a wide array of fields. It has contributed to the production of innovative materials and devices. Having unique advantages and domestic along with industrial applications, however, has raised the issue of safety for consumers, producers and environment. Having a comparative smaller dimension and other exclusive properties, nanoparticles have the ability to harm human body by interacting through various mechanisms. Here, we endeavoured to review and discuss the characteristics of nanoparticles relevant to their toxicity, conceivable exposure routes of nanoparticles to human body like skin contact, inhalation, and ingestion, and the basic approaches which can aid to control human exposures to toxic nanoparticles have been discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Exposure to acute severe hypoxia leads to increased urea loss and disruptions in acid-base and ionoregulatory balance in dogfish sharks (Squalus acanthias).

Science.gov (United States)

Zimmer, Alex M; Wood, Chris M

2014-01-01

The effects of acute moderate (20% air O2 saturation; 6-h exposure) and severe (5% air O2 saturation; 4-h exposure) hypoxia on N-waste, acid-base, and ion balance in dogfish sharks (Squalus acanthias suckleyi) were evaluated. We predicted that the synthesis and/or retention of urea, which are active processes, would be inhibited by hypoxia. Exposure to moderate hypoxia had negligible effects on N-waste fluxes or systemic physiology, except for a modest rise in plasma lactate. Exposure to severe hypoxia led to a significant increase in urea excretion (Jurea), while plasma, liver, and muscle urea concentrations were unchanged, suggesting a loss of urea retention. Ammonia excretion (Jamm) was elevated during normoxic recovery. Moreover, severe hypoxia led to disruptions in acid-base balance, indicated by a large increase in plasma [lactate] and substantial decreases in arterial pHa and plasma [Formula: see text], as well as loss of ionic homeostasis, indicated by increases in plasma [Mg(2+)], [Ca(2+)], and [Na(+)]. We suggest that severe hypoxia in dogfish sharks leads to a reduction in active gill homeostatic processes, such as urea retention, acid-base regulation and ionoregulation, and/or an osmoregulatory compromise due to increased functional gill surface area. Overall, the results provide a comprehensive picture of the physiological responses to a severe degree of hypoxia in an ancient fish species.

The complexity of nanoparticle dissolution and its importance in nanotoxicological studies

International Nuclear Information System (INIS)

Misra, Superb K.; Dybowska, Agnieszka; Berhanu, Deborah; Luoma, Samuel N.; Valsami-Jones, Eugenia

2012-01-01

Dissolution of nanoparticles (NPs) is an important property that alters their abundance and is often a critical step in determining safety of nanoparticles. The dissolution status of the NPs in exposure media (i.e. whether they remain in particulate form or dissolve — and to what extent), strongly affects the uptake pathway, toxicity mechanisms and the environmental compartment in which NPs will have the highest potential impact. A review of available dissolution data on NPs demonstrates there is a range of potential outcomes depending on the NPs and the exposure media. For example two nominally identical nanoparticles, in terms of size and composition, could have totally different dissolution behaviours, subject to different surface modifications. Therefore, it is imperative that toxicological studies are conducted in conjunction with dissolution of NPs to establish the true biological effect of NPs and hence, assist in their regulation. -- Graphical abstract: Various physicochemical factors affecting dissolution of nanoparticles. Highlights: ► In this study we discuss dissolution of nanoparticles. ► Physicochemical properties of nanoparticles influence dissolution. ► Measuring dissolution of nanoparticles can help to understand their biological response.

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

Energy Technology Data Exchange (ETDEWEB)

Tian, Shuangmei; Pan, Luqing, E-mail: panlq@ouc.edu.cn; Sun, Xiaohua

2013-11-15

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

International Nuclear Information System (INIS)

Tian, Shuangmei; Pan, Luqing; Sun, Xiaohua

2013-01-01

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

Poly(ethyl glyoxylate)-Poly(ethylene oxide) Nanoparticles: Stimuli-Responsive Drug Release via End-to-End Polyglyoxylate Depolymerization.

Science.gov (United States)

Fan, Bo; Gillies, Elizabeth R

2017-08-07

The ability to disrupt polymer assemblies in response to specific stimuli provides the potential to release drugs selectively at certain sites or conditions in vivo. However, most stimuli-responsive delivery systems require many stimuli-initiated events to release drugs. "Self-immolative polymers" offer the potential to provide amplified responses to stimuli as they undergo complete end-to-end depolymerization following the cleavage of a single end-cap. Herein, linker end-caps were developed to conjugate self-immolative poly(ethyl glyoxylate) (PEtG) with poly(ethylene oxide) (PEO) to form amphiphilic block copolymers. These copolymers were self-assembled to form nanoparticles in aqueous solution. Cleavage of the linker end-caps were triggered by a thiol reducing agent, UV light, H 2 O 2 , and combinations of these stimuli, resulting in nanoparticle disintegration. Low stimuli concentrations were effective in rapidly disrupting the nanoparticles. Nile red, doxorubin, and curcumin were encapsulated into the nanoparticles and were selectively released upon application of the appropriate stimulus. The ability to tune the stimuli-responsiveness simply by changing the linker end-cap makes this new platform highly attractive for applications in drug delivery.

Titanium dioxide nanoparticles relieve silk gland damage and increase cocooning of Bombyx mori under phoxim-induced toxicity.

Science.gov (United States)

Li, Bing; Yu, Xiaohong; Gui, Suxin; Xie, Yi; Hong, Jie; Zhao, Xiaoyang; Sheng, Lei; Sang, Xuezi; Sun, Qingqing; Wang, Ling; Shen, Weide; Hong, Fashui

2013-12-18

Organophosphate pesticides are applied widely in the world for agricultural purposes, and their exposures often resulted in non-cocooning of Bombyx mori in China. TiO2 nanoparticles have been demonstrated to increase pesticide resistance of Bombyx mori. While the toxicity of phoxim is well-documented, very limited information exists on the mechanisms of TiO2 nanoparticles improving the cocooning function of Bombyx mori following exposure to phoxim. The present study was, therefore, undertaken to determine whether TiO2 nanoparticles attenuate silk gland injury and elevate cocooning of B. mori following exposure to phoxim. The findings suggested that phoxim exposure resulted in severe damages of the silk gland structure and significantly decreased the cocooning in the silk gland of Bombyx mori. Furthermore, phoxim exposure significantly resulted in reductions of total protein concentrations and suppressed expressions of silk protein synthesis-related genes, including Fib-L, Fib-H, P25, Ser-2, and Ser-3, in the silk gland. TiO2 nanoparticle pretreatment, however, could significantly relieve silk gland injury of Bombyx mori. Importantly, TiO2 nanoparticles could remarkably elevate cocooning and total protein contents and promote expressions of Fib-L, Fib-H, P25, Ser-2, and Ser-3 in the silk gland following exposure to phoxim.

Interaction of nanoparticles with lipid layers

Science.gov (United States)

Park, Jonghyun; Lu, Wei

2009-08-01

Poly (amidoamine) dendrimer nanoparticles are used extensively in diverse biological and medical applications. Examples include gene and drug delivery, where nanoparticles disrupt cell membranes to allow the transport of material into cells. The size and surface chemistry of these particles have a strong effect on their interaction with membranes. This paper proposes a three-dimensional phase-field model to investigate how the interaction drives deformation and morphological evolution of the membrane. Attention is focused on the hole-formation process in the membrane. The simulations have demonstrated that a larger amine-terminated generation 7 dendrimer, which has positive charges, causes the formation of a hole in the membrane. The displaced membrane molecules enclose the particle and form a dendrimer-filled membrane vesicle. The effect is significantly reduced for a smaller dendrimer. An acetamide-terminated dendrimer, which has a neutral charge at the surface, does not cause hole formation. These results agree with experimental observations from atomic force microscopy. The study will provide insight into the design of appropriate nanoparticle surface properties for medical applications.

Intergenerational effects of endocrine-disrupting compounds: a review of the Michigan polybrominated biphenyl registry.

Science.gov (United States)

Curtis, Sarah W; Conneely, Karen N; Marder, Mary E; Terrell, Metrecia L; Marcus, Michele; Smith, Alicia K

2018-06-11

Endocrine-disrupting compounds (EDCs) are a broad class of chemicals present in many residential products that can disrupt hormone signaling and cause health problems in humans. Multigenerational cohorts, like the Michigan polybrominated biphenyl registry, are ideal for studying the effects of intergenerational exposure. Registry participants report hormone-related health problems, particularly in those exposed before puberty or those in the second generation exposed through placental transfer or breastfeeding. However, more research is needed to determine how EDCs cause health problems and the mechanisms underlying intergenerational exposure. Utilizing existing data in this registry, along with genetic and epigenetic approaches, could provide insight to how EDCs cause human disease and help to determine the risk to exposed populations and future generations.

Toxicity of laser irradiated photoactive fluoride PrF3 nanoparticles toward bacteria

International Nuclear Information System (INIS)

Pudovkin, M S; Korableva, S L; Krasheninnicova, A O; Nizamutdinov, A S; Semashko, V V; Zelenihin, P V; Alakshin, E M; Nevzorova, T A

2014-01-01

The article is devoted to exploration of biological effects of crystalline PrF 3 nanoparticles toward Salmonella typhimurium TA 98 bacteria under the laser irradiation. Obtained results show bactericidal activity of PrF 3 nanoparticles and optimal parameters of laser irradiation (power of laser irradiation, wavelength, diameter of the laser spoil, and exposure time) have been found under which the effects of bactericidal activity become the most significant. Survival of bacterial cells under laser irradiation with wavelength 532 nm in colloidal solution of PrF 3 nanoparticles was 39%, 34%, 20% for exposure times 5 minutes, 15 minutes and 30 minutes, correspondingly

Iontophoresis on minoxidil sulphate-loaded chitosan nanoparticles accelerates drug release, decreasing their targeting effect to hair follicles

Directory of Open Access Journals (Sweden)

Breno N. Matos

Full Text Available The experiments described in this paper tested the hypothesis whether iontophoresis applied on a chitosan nanoparticle formulation could combine the enhanced drug accumulation into the follicular casts obtained using iontophoresis and the sustained drug release, reducing dermal exposure, provided by nanoparticles. Results showed that even though iontophoresis presented comparable minoxidil targeting potential to hair follicles than passive delivery of chitosan-nanoparticles (4.1 ± 0.9 and 5.3 ± 1.0 µg cm-2, respectively, it was less effective on preventing dermal exposure, since chitosan-nanoparticles presented a drug permeation in the receptor solution of 15.3 ± 4.3 µg cm-2 after 6 h of iontophoresis, while drug amounts from passive nanoparticle delivery were not detected. Drug release experiments showed particles were not able to sustain the drug release under the influence of a potential gradient. In conclusion, the application of MXS-loaded chitosan nanoparticles remains the best way to target MXS to the hair follicles while preventing dermal exposure.

Investigating Disruption

DEFF Research Database (Denmark)

Lundgaard, Stine Schmieg; Rosenstand, Claus Andreas Foss

This book shares knowledge collected from 2015 and onward within the Consortium for Digital Disruption anchored at Aalborg University (www.dd.aau.dk). Evidenced by this publication, the field of disruptive innovation research has gone through several stages of operationalizing the theory. In recent...... years, researchers are increasingly looking back towards the origins of the theory in attempts to cure it from its most obvious flaws. This is especially true for the use of the theory in making predictions about future disruptions. In order to continue to develop a valuable theory of disruption, we...... find it useful to first review what the theory of disruptive innovation initially was, how it has developed, and where we are now. A cross section of disruptive innovation literature has been reviewed in order to form a general foundation from which we might better understand the changing world...

Laser induced synthesis of nanoparticles in liquids

Energy Technology Data Exchange (ETDEWEB)

Kazakevich, P.V. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38 Vavilov street, 117942 Moscow (Russian Federation); Simakin, A.V. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38 Vavilov street, 117942 Moscow (Russian Federation); Voronov, V.V. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38 Vavilov street, 117942 Moscow (Russian Federation); Shafeev, G.A. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38 Vavilov street, 117942 Moscow (Russian Federation)]. E-mail: shafeev@kapella.gpi.ru

2006-04-30

The review of results on nanoparticles formation is presented under laser ablation of Ag, Au, and Cu-containing solid targets in liquid environments (H{sub 2}O, C{sub 2}H{sub 5}OH, C{sub 2}H{sub 4}Cl{sub 2}, etc.). X-ray diffractometry (XRD), UV-vis optical transmission spectrometry, and high resolution transmission electron microscopy (HRTEM) characterize the nanoparticles. The morphology of nanoparticles is studied as the function of both laser fluence and nature of the liquid. The possibility to control the shape of nanoparticles by ablation of an Au target by an interference pattern of two laser beams is demonstrated. Formation of alloyed Au-Ag and Ag-Cu nanoparticles is reported under laser exposure of a mixture of individual nanoparticles. The effect of internal segregation of brass nanoparticles is discussed due to their small lateral dimensions. The factors are discussed that determine the distribution function of particles size under laser ablation. The influence of laser parameters as well as the nature on the liquid on the properties of nanoparticles is elucidated.

Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring.

Science.gov (United States)

Dobson, C C; Mongillo, D L; Brien, D C; Stepita, R; Poklewska-Koziell, M; Winterborn, A; Holloway, A C; Brien, J F; Reynolds, J N

2012-12-17

Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg(-1) maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation. Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1-7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100-140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150-200), CPEE offspring also had increased pancreatic adipocyte area and decreased β-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets. CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.

Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Directory of Open Access Journals (Sweden)

Hussain S

2012-03-01

were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO2 nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO2 nanoparticles followed by lipopolysaccharide exposure.Conclusion: CeO2 nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.Keywords: cerium dioxide, nanoparticle, nanomedicine, inflammation, human monocyte, lipopolysaccharides

Effects of exposure to four endocrine disrupting-chemicals on fertilization and embryonic development of Barbel chub ( Squaliobarbus curriculus)

Science.gov (United States)

Niu, Cuijuan; Wang, Wei; Gao, Ying; Li, Li

2013-09-01

The toxicities of 4 common endocrine-disrupting chemicals (EDCs), 17β-estradiol (E2), p,p'-dichlorodiphenyldichloro-ethylene (DDE), 4-nonylphenol (NP) and tributyltin (TBT), to sperm motility, fertilization rate, hatching rate and embryonic development of Barbel chub ( Squaliobarbus curriculus) were investigated in this study. The duration of sperm motility was significantly shortened by exposure to the EDCs at the threshold concentrations of 10 ng L-1 for E2 and TBT, 1 μg L-1 for NP and 100 μg L-1 for DDE, respectively. The fertilization rate was substantially reduced by the EDCs at the lowest observable effect concentrations (LOECs) of 10 ng L-1 for E2 and TBT and 10 μg L-1 for DDE and NP, respectively. Of the tested properties of S. curriculus, larval deformity rate was most sensitive to EDC exposure and was significantly increased by DDE at the lowest experimental level of 0.1 μg L-1. Other EDCs increased the larval deformity rate at the LOECs of 1 ng L-1 for E2, 10 ng L-1 for TBT and 1 μg L-1 for NP, respectively. Despite their decreases with the increasing EDC concentrations, the hatching rate and larval survival rate of S. curriculus were not significantly affected by the exposure to EDCs. The results indicated that all the 4 EDCs affected significantly and negatively the early life stages of the freshwater fish S. curriculus. Overall, E2 and TBT were more toxic than NP and DDE, while DDE might be more toxic to larval deformity rate than to other measured parameters. Thus, the 4 EDCs showed potential negative influences on natural population dynamics of S. curriculus. Our findings provided valuable basic data for the ecological risk assessment of E2, DDE, NP and TBT.

The genotoxicity of titanium dioxide and cerium oxide nanoparticles in vitro

Science.gov (United States)

The use ofengineered nanoparticles in both current and future consumer products is steadily increasing. However, the health effects of exposure to these nanoparticles are not thoroughly understood. Recently, particular emphasis has been placed on particle characterization and the...

Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

Directory of Open Access Journals (Sweden)

Shi Xianglin

2009-01-01

Full Text Available Abstract Background Engineered iron nanoparticles are being explored for the development of biomedical applications and many other industry purposes. However, to date little is known concerning the precise mechanisms of translocation of iron nanoparticles into targeted tissues and organs from blood circulation, as well as the underlying implications of potential harmful health effects in human. Results The confocal microscopy imaging analysis demonstrates that exposure to engineered iron nanoparticles induces an increase in cell permeability in human microvascular endothelial cells. Our studies further reveal iron nanoparticles enhance the permeability through the production of reactive oxygen species (ROS and the stabilization of microtubules. We also showed Akt/GSK-3β signaling pathways are involved in iron nanoparticle-induced cell permeability. The inhibition of ROS demonstrate ROS play a major role in regulating Akt/GSK-3β – mediated cell permeability upon iron nanoparticle exposure. These results provide new insights into the bioreactivity of engineered iron nanoparticles which can inform potential applications in medical imaging or drug delivery. Conclusion Our results indicate that exposure to iron nanoparticles induces an increase in endothelial cell permeability through ROS oxidative stress-modulated microtubule remodeling. The findings from this study provide new understandings on the effects of nanoparticles on vascular transport of macromolecules and drugs.

Natural colloids are the dominant factor in the sedimentation of nanoparticles

NARCIS (Netherlands)

Quik, J.T.K.; Cohen Stuart, M.A.; Wouterse, M.; Peijnenburg, W.; Hendriks, A.J.; Meent, van de D.

2012-01-01

Estimating the environmental exposure to manufactured nanomaterials is part of risk assessment. Because nanoparticles aggregate with each other (homoaggregation) and with other particles (heteroaggregation), the main route of the removal of most nanoparticles from water is aggregation, followed by

Thyroid endocrine system disruption by pentachlorophenol: an in vitro and in vivo assay.

Science.gov (United States)

Guo, Yongyong; Zhou, Bingsheng

2013-10-15

The present study aimed to evaluate the disruption caused to the thyroid endocrine system by pentachlorophenol (PCP) using in vitro and in vivo assays. In the in vitro assay, rat pituitary GH3 cells were exposed to 0, 0.1, 0.3, and 1.0 μM PCP. PCP exposure significantly downregulated basal and triiodothyronine (T3)-induced Dio 1 transcription, indicating the antagonistic activity of PCP in vitro. In the in vivo assay, zebrafish embryos were exposed to 0, 1, 3, and 10 μg/L of PCP until 14 days post-fertilization. PCP exposure resulted in decreased thyroxine (T4) levels, but elevated contents of whole-body T3. PCP exposure significantly upregulated the mRNA expression of genes along hypothalamic-pituitary-thyroid (HPT) axis, including those encoding thyroid-stimulating hormone, sodium/iodide symporter, thyroglobulin, Dio 1 and Dio 2, alpha and beta thyroid hormone receptor, and uridinediphosphate-glucuronosyl-transferase. PCP exposure did not influence the transcription of the transthyretin (TTR) gene. The results indicate that PCP potentially disrupts the thyroid endocrine system both in vitro and in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

Brief exposure to obesogenic diet disrupts brain dopamine networks.

Directory of Open Access Journals (Sweden)

Robert L Barry

Full Text Available We have previously demonstrated that insulin signaling, through the downstream signaling kinase Akt, is a potent modulator of dopamine transporter (DAT activity, which fine-tunes dopamine (DA signaling at the synapse. This suggests a mechanism by which impaired neuronal insulin receptor signaling, a hallmark of diet-induced obesity, may contribute to impaired DA transmission. We tested whether a short-term (two-week obesogenic high-fat (HF diet could reduce striatal Akt activity, a marker of central insulin, receptor signaling and blunt striatal and dopaminergic network responsiveness to amphetamine (AMPH.We examined the effects of a two-week HF diet on striatal DAT activity in rats, using AMPH as a probe in a functional magnetic resonance imaging (fMRI assay, and mapped the disruption in AMPH-evoked functional connectivity between key dopaminergic targets and their projection areas using correlation and permutation analyses. We used phosphorylation of the Akt substrate GSK3α in striatal extracts as a measure of insulin receptor signaling. Finally, we confirmed the impact of HF diet on striatal DA D2 receptor (D2R availability using [18F]fallypride positron emission tomography (PET.We found that rats fed a HF diet for only two weeks have reductions in striatal Akt activity, a marker of decreased striatal insulin receptor signaling and blunted striatal responsiveness to AMPH. HF feeding also reduced interactions between elements of the mesolimbic (nucleus accumbens-anterior cingulate and sensorimotor circuits (caudate/putamen-thalamus-sensorimotor cortex implicated in hedonic feeding. D2R availability was reduced in HF-fed animals.These studies support the hypothesis that central insulin signaling and dopaminergic neurotransmission are already altered after short-term HF feeding. Because AMPH induces DA efflux and brain activation, in large part via DAT, these findings suggest that blunted central nervous system insulin receptor signaling

Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

International Nuclear Information System (INIS)

Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

2011-01-01

Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

Transport of silver nanoparticles by runoff and erosion – A flume experiment

NARCIS (Netherlands)

Mahdi, Karrar N.M.; Commelin, Meindert; Peters, Ruud J.B.; Baartman, Jantiene E.M.; Ritsema, Coen; Geissen, Violette

2017-01-01

Silver nanoparticles (AgNPs) are being used in many products as they have unique antimicrobial-biocidal properties. After disposal of these products AgNPs can reach the soil environment possibly affecting soil organisms and disrupting plants. This work aimed to study the transport of AgNPs by

Digital Disruption

DEFF Research Database (Denmark)

Rosenstand, Claus Andreas Foss

det digitale domæne ud over det niveau, der kendetegner den nuværende debat, så præsenteres der ny viden om digital disruption. Som noget nyt udlægges Clayton Christens teori om disruptiv innovation med et særligt fokus på små organisationers mulighed for eksponentiel vækst. Specielt udfoldes...... forholdet mellem disruption og den stadig accelererende digitale udvikling i konturerne til ny teoridannelse om digital disruption. Bogens undertitel ”faretruende og fascinerende forandringer” peger på, at der er behov for en nuanceret debat om digital disruption i modsætning til den tone, der er slået an i...... videre kalder et ”disruption-råd”. Faktisk er rådet skrevet ind i 2016 regeringsgrundlaget for VLK-regeringen. Disruption af organisationer er ikke et nyt fænomen; men hastigheden, hvormed det sker, er stadig accelererende. Årsagen er den globale mega-trend: Digitalisering. Og derfor er specielt digital...

Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

Science.gov (United States)

Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

2014-02-01

Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

Single-cell nanotoxicity assays of superparamagnetic iron oxide nanoparticles.

Science.gov (United States)

Eustaquio, Trisha; Leary, James F

2012-01-01

Properly evaluating the nanotoxicity of nanoparticles involves much more than bulk-cell assays of cell death by necrosis. Cells exposed to nanoparticles may undergo repairable oxidative stress and DNA damage or be induced into apoptosis. Exposure to nanoparticles may cause the cells to alter their proliferation or differentiation or their cell-cell signaling with neighboring cells in a tissue. Nanoparticles are usually more toxic to some cell subpopulations than others, and toxicity often varies with cell cycle. All of these facts dictate that any nanotoxicity assay must be at the single-cell level and must try whenever feasible and reasonable to include many of these other factors. Focusing on one type of quantitative measure of nanotoxicity, we describe flow and scanning image cytometry approaches to measuring nanotoxicity at the single-cell level by using a commonly used assay for distinguishing between necrotic and apoptotic causes of cell death by one type of nanoparticle. Flow cytometry is fast and quantitative, provided that the cells can be prepared into a single-cell suspension for analysis. But when cells cannot be put into suspension without altering nanotoxicity results, or if morphology, attachment, and stain location are important, a scanning image cytometry approach must be used. Both methods are described with application to a particular type of nanoparticle, a superparamagnetic iron oxide nanoparticle (SPION), as an example of how these assays may be applied to the more general problem of determining the effects of nanomaterial exposure to living cells.

Combustion-derived nanoparticles: A review of their toxicology following inhalation exposure

Directory of Open Access Journals (Sweden)

Mills Nicholas

2005-10-01

Full Text Available Abstract This review considers the molecular toxicology of combustion-derived nanoparticles (CDNP following inhalation exposure. CDNP originate from a number of sources and in this review we consider diesel soot, welding fume, carbon black and coal fly ash. A substantial literature demonstrates that these pose a hazard to the lungs through their potential to cause oxidative stress, inflammation and cancer; they also have the potential to redistribute to other organs following pulmonary deposition. These different CDNP show considerable heterogeneity in composition and solubility, meaning that oxidative stress may originate from different components depending on the particle under consideration. Key CDNP-associated properties of large surface area and the presence of metals and organics all have the potential to produce oxidative stress. CDNP may also exert genotoxic effects, depending on their composition. CDNP and their components also have the potential to translocate to the brain and also the blood, and thereby reach other targets such as the cardiovascular system, spleen and liver. CDNP therefore can be seen as a group of particulate toxins unified by a common mechanism of injury and properties of translocation which have the potential to mediate a range of adverse effects in the lungs and other organs and warrant further research.

Gold nanoparticles produced in a microalga

International Nuclear Information System (INIS)

Luangpipat, Tiyaporn; Beattie, Isabel R.; Chisti, Yusuf; Haverkamp, Richard G.

2011-01-01

An efficient biological route to production of gold nanoparticles which allows the nanoparticles to be easily recovered remains elusive. Live cells of the green microalga Chlorella vulgaris were incubated with a solution of gold chloride and harvested by centrifugation. Nanoparticles inside intact cells were identified by transmission electron microscopy and confirmed to be metallic gold by synchrotron based X-ray powder diffraction and X-ray absorption spectroscopy. These intracellular gold nanoparticles were 40–60 nm in diameter. At a concentration of 1.4% Au in the alga, a better than 97% recovery of the gold from solution was achieved. A maximum of 4.2% Au in the alga was obtained. Exposure of C. vulgaris to solutions containing dissolved salts of palladium, ruthenium, and rhodium also resulted in the production of the corresponding nanoparticles within the cells. These were surmised to be also metallic, but were produced at a much lower intracellular concentration than achieved with gold. Iridium was apparently toxic to the alga. No nanoparticles were observed using platinum solutions. C. vulgaris provides a possible route to large scale production of gold nanoparticles.

Drug delivery and nanoparticles: Applications and hazards

Directory of Open Access Journals (Sweden)

Wim H De Jong

2008-06-01

Full Text Available Wim H De Jong1, Paul JA Borm2,31Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands; 2Zuyd University, Centre of Expertise in Life Sciences, Heerlen, The Netherlands; 3Magnamedics GmbH, Aachen, GermanyAbstract: The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation

Metabolic targets of endocrine disrupting chemicals assessed by cord blood transcriptome profiling

DEFF Research Database (Denmark)

Remy, Sylvie; Govarts, Eva; Wens, Britt

2016-01-01

Early life exposure to endocrine disrupting chemicals (EDCs) has been frequently associated with impaired perinatal growth, an important risk factor for later onset of metabolic disorders. We analyzed whether the cord blood transcriptome showed early indications of alterations in metabolic...

Synthesis of gold nanoparticles by blue-green algae Spirulina platensis

International Nuclear Information System (INIS)

Kalabegishvili, T.; Kirkesali, E.; Rcheulishvili, A.

2012-01-01

The synthesis of gold nanoparticles by one of the many popular microorganisms - blue-green algae Spirulina platensis was studied. The complex of optical and analytical methods was applied for investigation of experimental samples after exposure to chloroaurate (HAuCl 4 ) solution at different doses and for different time intervals. To characterize formed gold nanoparticles UV-vis, TEM, SEM, EDAX, and XRD were used. It was shown that after 1.5-2 days of exposure the extracellular formation of nanoparticles of spherical form and the distribution peak within the interval of 20-30 nm took place. To determine gold concentrations in the Spirulina platensis biomass, neutron activation analysis (NAA) and atomic absorption spectrometry (AAS) were applied. The results obtained evidence that the concentration of gold accumulated by Spirulina biomass is rapidly growing in the beginning, followed by some increase for the next few days. The obtained substance of Spirulina biomass with gold nanoparticles may be used for medical, pharmaceutical, and technological purposes

Exposure of maternal mice to cis-bifenthrin enantioselectively disrupts the transcription of genes related to testosterone synthesis in male offspring.

Science.gov (United States)

Jin, Yuanxiang; Wang, Jiangcong; Sun, Xueqing; Ye, Yang; Xu, Minjie; Wang, Jianai; Chen, Shaoping; Fu, Zhengwei

2013-12-01

The commercial bifenthrin (BF) contains two cis isomers. In the present study, a dose of 15mg/kg of 1R-cis-BF or 1S-cis-BF was orally administered for 3 weeks to female mice before or during pregnancy. Then, the expression of steroidogenesis related genes which were considered as effective biomarkers of endocrine disruption were analyzed in the male offspring. Maternal exposure to 1S-cis-BF during pregnancy significantly reduced the mRNA levels of peripheral benzodiazepine receptor (PBR) and steroidogenic acute regulatory protein (StAR) in the testes of 3- or 6-week old male offspring. In addition, a significant decrease of cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α) was also observed in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during pregnancy but not before pregnancy. Moreover, the scavenger receptor class B type 1 (SRB1) and cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) decreased significantly in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during and before pregnancy. Thus, oral administration of the maternal mice to cis-BF for 3 weeks, particularly during pregnancy, resulted in endocrine disruption in the male offspring, with the 1S-cis-BF causing more significant alterations than the 1R-cis-BF form. Copyright © 2013 Elsevier Inc. All rights reserved.

Disruption of Circadian Rhythms by Light During Day and Night.

Science.gov (United States)

Figueiro, Mariana G

2017-06-01

This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease. Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night. To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.

Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles

International Nuclear Information System (INIS)

Stępnik, Maciej; Arkusz, Joanna; Smok-Pieniążek, Anna; Bratek-Skicki, Anna; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A.; Gromadzińska, Jolanta; De Jong, Wim H.; Rydzyński, Konrad

2012-01-01

The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells. -- Highlights: ► Ludox CL silica NPs are cytotoxic to WI-38 fibroblasts but not to 3T3-L1 fibroblasts. ► Ludox CL-X silica NPs are cytotoxic to both cell lines. ► In clonogenic assay both silica NPs induce cytotoxicity, higher for CL-X silica. ► Cell cycle analysis shows

NON-INVASIVE RADIOFREQUENCY ABLATION OF CANCER TARGETED BY GOLD NANOPARTICLES

Science.gov (United States)

Cardinal, Jon; Klune, John Robert; Chory, Eamon; Jeyabalan, Geetha; Kanzius, John S.; Nalesnik, Michael; Geller, David A.

2008-01-01

Introduction Current radiofrequency ablation (RFA) techniques require invasive needle placement and are limited by accuracy of targeting. The purpose of this study was to test a novel non-invasive radiowave machine that uses RF energy to thermally destroy tissue. Gold nanoparticles were designed and produced to facilitate tissue heating by the radiowaves. Methods A solid state radiowave machine consisting of a power generator and transmitting/receiving couplers which transmit radiowaves at 13.56 MHz was used. Gold nanoparticles were produced by citrate reduction and exposed to the RF field either in solutions testing or after incubation with HepG2 cells. A rat hepatoma model using JM-1 cells and Fisher rats was employed using direct injection of nanoparticles into the tumor to focus the radiowaves for select heating. Temperatures were measured using a fiber-optic thermometer for real-time data. Results Solutions containing gold nanoparticles heated in a time- and power-dependent manner. HepG2 liver cancer cells cultured in the presence of gold nanoparticles achieved adequate heating to cause cell death upon exposure to the RF field with no cytotoxicity attributable to the gold nanoparticles themselves. In vivo rat exposures at 35W using gold nanoparticles for tissue injection resulted in significant temperature increases and thermal injury at subcutaneous injection sites as compared to vehicle (water) injected controls. Discussion These data show that non-invasive radiowave thermal ablation of cancer cells is feasible when facilitated by gold nanoparticles. Future studies will focus on tumor selective targeting of nanoparticles for in vivo tumor destruction. PMID:18656617

Studying the Mechanism of Hybrid Nanoparticle Photoresists: Effect of Particle Size on Photopatterning

KAUST Repository

Li, Li

2015-07-28

© 2015 American Chemical Society. Hf-based hybrid photoresist materials with three different organic ligands were prepared by a sol-gel-based method, and their patterning mechanism was investigated in detail. All hybrid nanoparticle resists are patternable using UV exposure. Their particle sizes show a dramatic increase from the initial 3-4 nm to submicron size after exposure, with no apparent inorganic content or thermal property change detected. XPS results showed that the mass percentage of the carboxylic group in the structure of nanoparticles decreased with increasing exposure duration. The particle coarsening sensitivities of those hybrid nanoparticles are consistent with their EUV performance. The current work provides an understanding for the development mechanism and future guidance for the design and processing of high performance resist materials for large-scale microelectronics device fabrication.

Multiple endocrine disrupting effects in rats perinatally exposed to butylparaben

DEFF Research Database (Denmark)

Boberg, Julie; Petersen, Marta Axelstad; Svingen, Terje

2016-01-01

) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group......Parabens comprise a group of preservatives commonly added to cosmetics, lotions and other consumer products. Butylparaben has estrogenic and anti-androgenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine...

Bacterial exposure to metal-oxide nanoparticles: Methods, physical interactions, and biological effects

Science.gov (United States)

Horst, Allison Marie

Nanotechnology is a major endeavor of this century, with proposed applications in fields ranging from agriculture to energy to medicine. Nanoscale titanium dioxide (nano-TiO2) is among the most widely produced nanoparticles worldwide, and already exists in consumer products including impermanent personal care products and surface coatings. Inevitably, nano-TiO2 will be transported into the environment via consumer or industrial waste, where its effects on organisms are largely unknown. Out of concern for the possible ill-effects of nanoparticles in the environment, there is now a field of study in nanotoxicology. Bacteria are ideal organisms for nanotoxicology research because they are environmentally important, respond rapidly to intoxication, and provide evidence for effects in higher organisms. My doctoral research focuses on the effects and interactions of nano-TiO2 in aqueous systems with planktonic bacteria. This dissertation describes four projects and the outcomes of the research: (1) A discovery, using a combination of environmental- and cryogenic-scanning electron microscopy and dynamic light scattering (DLS), that initially agglomerated nano-TiO2 is dispersed upon bacterial contact, as nanoparticles preferentially sorbed to cell surfaces. (2) Establishment of a method to disperse nanoparticles in an aqueous culture medium for nanotoxicology studies. A combination of electrostatic repulsion, steric hindrance and sonication yielded a high initial level of nano-TiO2 dispersion (i.e. E. coli growth and membrane processes. Together, this research is towards: better understanding outcomes of interactions between nanoparticles and bacteria, advancing methods in the relatively new field of nanotoxicology that are transferable to other nanoparticle and media chemistries, and improving our understanding of structure-activity relationships (e.g. size and doping effects) leading to intoxication in environmental organisms.

Disruption?

DEFF Research Database (Denmark)

2016-01-01

This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray......This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray...

Association between prenatal polychlorinated biphenyl exposure and obesity development at ages 5 and 7 y

DEFF Research Database (Denmark)

Tang-Péronard, Jeanett L; Heitmann, Berit L; Andersen, Helle R

2014-01-01

Chemicals with endocrine-disrupting abilities may act as obesogens and interfere with the body's natural weight-control mechanisms, especially if exposure occurs during prenatal life.......Chemicals with endocrine-disrupting abilities may act as obesogens and interfere with the body's natural weight-control mechanisms, especially if exposure occurs during prenatal life....

Exposure of agricultural crops to nanoparticle CeO2 in biochar-amended soil.

Science.gov (United States)

Servin, Alia D; De la Torre-Roche, Roberto; Castillo-Michel, Hiram; Pagano, Luca; Hawthorne, Joseph; Musante, Craig; Pignatello, Joseph; Uchimiya, Minori; White, Jason C

2017-01-01

Biochar is seeing increased usage as an amendment in agricultural soils but the significance of nanoscale interactions between this additive and engineered nanoparticles (ENP) remains unknown. Corn, lettuce, soybean and zucchini were grown for 28 d in two different soils (agricultural, residential) amended with 0-2000 mg engineered nanoparticle (ENP) CeO 2  kg -1 and biochar (350 °C or 600 °C) at application rates of 0-5% (w/w). At harvest, plants were analyzed for biomass, Ce content, chlorophyll and lipid peroxidation. Biomass from the four species grown in residential soil varied with species and biochar type. However, biomass in the agricultural soil amended with biochar 600 °C was largely unaffected. Biochar co-exposure had minimal impact on Ce accumulation, with reduced or increased Ce content occurring at the highest (5%) biochar level. Soil-specific and biochar-specific effects on Ce accumulation were observed in the four species. For example, zucchini grown in agricultural soil with 2000 mg CeO 2  kg -1 and 350 °C biochar (0.5-5%) accumulated greater Ce than the control. However, for the 600 °C biochar, the opposite effect was evident, with decreased Ce content as biochar increased. A principal component analysis showed that biochar type accounted for 56-99% of the variance in chlorophyll and lipid peroxidation across the plants. SEM and μ-XRF showed Ce association with specific biochar and soil components, while μ-XANES analysis confirmed that after 28 d in soil, the Ce remained largely as CeO 2 . The current study demonstrates that biochar synthesis conditions significantly impact interactions with ENP, with subsequent effects on particle fate and effects. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Zinc oxide nanoparticle exposure triggers different gene expression patterns in maize shoots and roots.

Science.gov (United States)

Xun, Hongwei; Ma, Xintong; Chen, Jing; Yang, Zhongzhou; Liu, Bao; Gao, Xiang; Li, Guo; Yu, Jiamiao; Wang, Li; Pang, Jinsong

2017-10-01

The potential impacts of environmentally accumulated zinc oxide nanoparticles (nZnOs) on plant growth have not been well studied. A transcriptome profile analysis of maize exposed to nZnOs showed that the genes in the shoots and roots responded differently. Although the number of differentially expressed genes (DEGs) in the roots was greater than that in the shoots, the number of up- or down-regulated genes in both the shoots and roots was similar. The enrichment of gene ontology (GO) terms was also significantly different in the shoots and roots. The "nitrogen compound metabolism" and "cellular component" terms were specifically and highly up-regulated in the nZnO-exposed roots, whereas the categories "cellular metabolic process", "primary metabolic process" and "secondary metabolic process" were down-regulated in the exposed roots only. Our results revealed the DEG response patterns in maize shoots and roots after nZnO exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Direct observation of a single nanoparticle-ubiquitin corona formation

Science.gov (United States)

Ding, Feng; Radic, Slaven; Chen, Ran; Chen, Pengyu; Geitner, Nicholas K.; Brown, Jared M.; Ke, Pu Chun

2013-09-01

The advancement of nanomedicine and the increasing applications of nanoparticles in consumer products have led to administered biological exposure and unintentional environmental accumulation of nanoparticles, causing concerns over the biocompatibility and sustainability of nanotechnology. Upon entering physiological environments, nanoparticles readily assume the form of a nanoparticle-protein corona that dictates their biological identity. Consequently, understanding the structure and dynamics of a nanoparticle-protein corona is essential for predicting the fate, transport, and toxicity of nanomaterials in living systems and for enabling the vast applications of nanomedicine. Here we combined multiscale molecular dynamics simulations and complementary experiments to characterize the silver nanoparticle-ubiquitin corona formation. Notably, ubiquitins competed with citrates for the nanoparticle surface, governed by specific electrostatic interactions. Under a high protein/nanoparticle stoichiometry, ubiquitins formed a multi-layer corona on the particle surface. The binding exhibited an unusual stretched-exponential behavior, suggesting a rich binding kinetics. Furthermore, the binding destabilized the α-helices while increasing the β-sheet content of the proteins. This study revealed the atomic and molecular details of the structural and dynamic characteristics of nanoparticle-protein corona formation.The advancement of nanomedicine and the increasing applications of nanoparticles in consumer products have led to administered biological exposure and unintentional environmental accumulation of nanoparticles, causing concerns over the biocompatibility and sustainability of nanotechnology. Upon entering physiological environments, nanoparticles readily assume the form of a nanoparticle-protein corona that dictates their biological identity. Consequently, understanding the structure and dynamics of a nanoparticle-protein corona is essential for predicting the fate

Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

International Nuclear Information System (INIS)

Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju; Shivashangari, Kanchi Subramanian; Ravikumar, Vilwanathan

2014-01-01

The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India); Shivashangari, Kanchi Subramanian, E-mail: shivashangari@gmail.com [Regional Forensic Science Laboratory, Tiruchirapalli, Tamilnadu (India); Ravikumar, Vilwanathan, E-mail: ravikumarbdu@gmail.com [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India)

2014-11-01

The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

Polymer Nanoparticle-Based Chemotherapy for Spinal Malignancies

Directory of Open Access Journals (Sweden)

Hongyun Ma

2016-01-01

Full Text Available Malignant spinal tumors, categorized into primary and metastatic ones, are one of the most serious diseases due to their high morbidity and mortality rates. Common primary spinal tumors include chordoma, chondrosarcoma, osteosarcoma, Ewing’s sarcoma, and multiple myeloma. Spinal malignancies are not only locally invasive and destructive to adjacent structures, such as bone, neural, and vascular structures, but also disruptive to distant organs (e.g., lung. Current treatments for spinal malignancies, including wide resection, radiotherapy, and chemotherapy, have made significant progress like improving patients’ quality of life. Among them, chemotherapy plays an important role, but its potential for clinical application is limited by severe side effects and drug resistance. To ameliorate the current situation, various polymer nanoparticles have been developed as promising excipients to facilitate the effective treatment of spinal malignancies by utilizing their potent advantages, for example, targeting, stimuli response, and synergetic effect. This review overviews the development of polymer nanoparticles for antineoplastic delivery in the treatment of spinal malignancies and discusses future prospects of polymer nanoparticle-based treatment methods.

Understanding and managing sleep disruption in children with fetal alcohol spectrum disorder.

Science.gov (United States)

Hanlon-Dearman, Ana; Chen, Maida Lynn; Olson, Heather Carmichael

2018-04-01

Accumulating evidence has revealed high rates of sleep disruption among children with fetal alcohol spectrum disorder (FASD). Multiple animal and clinical studies have found a clear association between sleep problems and prenatal alcohol exposure, and recent research is beginning to characterize the types and extent of sleep disruption in FASD. Nevertheless, sleep disruption in children with FASD often goes unrecognized or is treated without referring to an evidence base. Children's disrupted sleep interferes with parental sleep and increases caregiver burden, which is of particular importance for families raising children with FASD, a group with very high levels of caregiving stress. The literature supporting an association between sleep problems and deficits in emotional, behavioral, and cognitive function in children is compelling, but needs further investigation in children with FASD. This paper will review the current state of knowledge on sleep in FASD and recommend a rational approach to sleep interventions for affected children and their families.

Deleterious Effects From Occupational Exposure to Ethylene Thiourea in Pregnant Women.

Science.gov (United States)

Mutic, Abby D; Baker, Brenda J; McCauley, Linda A

2017-12-01

Human exposure to endocrine disrupting chemicals (EDCs) has become common as a result of widespread application of these chemicals to the food supply, environmental contamination, and occupational exposures (Caserta et al., 2011). However, relatively little is known about the effects of EDCs such as ethylene thiourea (ETU) in developing fetuses and the lasting implications of this disruption on human development from birth through adulthood. Of highest concern are chronic, low-dose exposures among industrial and agricultural workers. Current knowledge regarding the significance of endocrine thyroid signaling on normal human development raises serious concerns about the possible deleterious effects of EDCs in the developing fetus, children, and mature adults. Occupational health nurses are critical in identifying women and families at increased risk of ETU exposure and mitigating early exposures in pregnancy.

Exposure Assessment and Inflammatory Response Among Workers Producing Calcium Carbonate Nanomaterials

Science.gov (United States)

Cui, Ling

Problem: Nanotechnology is one of the most rapidly growing fields of science and engineering, and its applications have expanded to numerous research and industrial sectors, from consumer products to medicine to energy. Nano-materials and nanotechnology promise substantial benefits. However, there are many uncertainties and concerns regarding human health and the environment. Numerous toxicological studies on animals and cells in vitro have demonstrated that nanomaterials could cause various adverse health effects, including inflammation, oxidative stress, fibrosis and mutagenesis in the lungs, and cardiovascular and nervous system impairment. Objectives: The overall objective of this study was to characterize particulate exposures in a calcium carbonate nanoparticle manufacturing facility, investigate possible respiratory and cardiovascular effects, and explore the plausibility of an inflammatory mechanism. The associations between exposure level and various health outcomes were investigated. Methodology: Each job was characterized by mass, number and surface area concentration. Job classification was performed based on ranking of the exposure level and statistical models. Lung function tests, exhaled NO and blood pressure (BP) were measured before and after the workshift in the year of 2011. Inflammatory cytokines from induced sputum were measured cross-sectionally in the year of 2011. Data of lung function tests and blood pressure were collected cross-sectionally in the year of 2012. The associations between each exposure metric and health measures in 2012 were investigated. Only mass concentration was linked to both 2011 and 2012 health outcomes. Results: The sampling and analytic methodology used in the study presents the potential to characterize nanoparticle exposure for a variety of operational processes. We found the highest mass exposure occurred at bagging job whereas the highest number and surface area concentration was found at modification

Prenatal and adolescent exposure to tobacco smoke modulates the development of white matter microstructure.

Science.gov (United States)

Jacobsen, Leslie K; Picciotto, Marina R; Heath, Christopher J; Frost, Stephen J; Tsou, Kristen A; Dwan, Rita A; Jackowski, Marcel P; Constable, Robert T; Mencl, W Einar

2007-12-05

Prenatal exposure to maternal smoking has been linked to cognitive and auditory processing deficits in offspring. Preclinical studies have demonstrated that exposure to nicotine disrupts neurodevelopment during gestation and adolescence, possibly by disrupting the trophic effects of acetylcholine. Given recent clinical and preclinical work suggesting that neurocircuits that support auditory processing may be particularly vulnerable to developmental disruption by nicotine, we examined white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. The groups did not differ in age, educational attainment, IQ, years of parent education, or symptoms of inattention. Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired, and auditory attention was assessed, in all subjects. Both prenatal exposure and adolescent exposure to tobacco smoke was associated with increased fractional anisotropy (FA) in anterior cortical white matter. Adolescent smoking was also associated with increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers. FA of the posterior limb of the left internal capsule was positively correlated with reaction time during performance of an auditory attention task in smokers but not in nonsmokers. Development of anterior cortical and internal capsule fibers may be particularly vulnerable to disruption in cholinergic signaling induced by nicotine in tobacco smoke. Nicotine-induced disruption of the development of auditory corticofugal fibers may interfere with the ability of these fibers to modulate ascending auditory signals, leading to greater noise and reduced efficiency of neurocircuitry that supports auditory processing.

Developmental programming: Impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus

International Nuclear Information System (INIS)

Mahoney, Megan M.; Padmanabhan, Vasantha

2010-01-01

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5 mg/kg/day) from day 30 to 90 of gestation (term 147 d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F 2α , just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female.

Developmental programming: impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus.

Science.gov (United States)

Mahoney, Megan M; Padmanabhan, Vasantha

2010-09-01

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5mg/kg/day) from day 30 to 90 of gestation (term 147d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F(2alpha), just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female. 2010 Elsevier Inc. All rights reserved.

Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?

Science.gov (United States)

Moosa, Amer; Shu, Henry; Sarachana, Tewarit; Hu, Valerie W

2017-10-23

Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice.

Science.gov (United States)

Zhao, Bingxia; Chen, Yihan; Liu, Jinfeng; Zhang, Li; Wang, Jing; Yang, Yali; Lv, Qing; Xie, Mingxing

2018-01-12

To investigate the effects of the microbubble (MB) dose, mechanism index (MI) and sonication duration on blood-brain barrier (BBB) disruption induced by diagnostic ultrasound combined with MBs as well as to investigate the potential molecular mechanism. The extent of BBB disruption increased with MB dose, MI and sonication duration. A relatively larger extent of BBB disruption associated with minimal tissue damage was achieved by an appropriate MB dose and ultrasound exposure parameters with diagnostic ultrasound. Decreased expression of ZO-1, occludin and claudin-5 were correlated with disruption of the BBB, as confirmed by paracellular passage of the tracer lanthanum nitrate into the brain parenchyma after BBB disruption. These findings indicated that this technique is a promising tool for promoting brain delivery of diagnostic and therapeutic agents in the diagnosis and treatment of brain diseases. The extent of BBB disruption was qualitatively assessed by Evans blue (EB) staining and quantitatively analyzed by an EB extravasation measurement. A histological examination was performed to evaluate tissue damage. Expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5 was determined by western blotting analysis and immunohistofluorescence. Transmission electron microscopy was performed to observe ultrastructure changes of TJs after BBB disruption.

Mimicking exposures to acute and lifetime concentrations of inhaled silver nanoparticles by two different in vitro approaches