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Sample records for nanoparticle exposure disrupts

  1. Intravenous and Gastric Cerium Dioxide Nanoparticle Exposure Disrupts Microvascular Smooth Muscle Signaling

    PubMed Central

    Minarchick, Valerie C.; Stapleton, Phoebe A.; Fix, Natalie R.; Leonard, Stephen S.; Sabolsky, Edward M.; Nurkiewicz, Timothy R.

    2015-01-01

    Cerium dioxide nanoparticles (CeO2 NP) hold great therapeutic potential, but the in vivo effects of non-pulmonary exposure routes are unclear. The first aim was to determine whether microvascular function is impaired after intravenous and gastric CeO2 NP exposure. The second aim was to investigate the mechanism(s) of action underlying microvascular dysfunction following CeO2 NP exposure. Rats were exposed to CeO2 NP (primary diameter: 4 ± 1 nm, surface area: 81.36 m2/g) by intratracheal instillation, intravenous injection, or gastric gavage. Mesenteric arterioles were harvested 24 h post-exposure and vascular function was assessed using an isolated arteriole preparation. Endothelium-dependent and independent function and vascular smooth muscle (VSM) signaling (soluble guanylyl cyclase [sGC] and cyclic guanosine monophosphate [cGMP]) were assessed. Reactive oxygen species (ROS) generation and nitric oxide (NO) production were analyzed. Compared with controls, endothelium-dependent and independent dilation were impaired following intravenous injection (by 61% and 45%) and gastric gavage (by 63% and 49%). However, intravenous injection resulted in greater microvascular impairment (16% and 35%) compared with gastric gavage at an identical dose (100 µg). Furthermore, sGC activation and cGMP responsiveness were impaired following pulmonary, intravenous, and gastric CeO2 NP treatment. Finally, nanoparticle exposure resulted in route-dependent, increased ROS generation and decreased NO production. These results indicate that CeO2 NP exposure route differentially impairs microvascular function, which may be mechanistically linked to decreased NO production and subsequent VSM signaling. Fully understanding the mechanisms behind CeO2 NP in vivo effects is a critical step in the continued therapeutic development of this nanoparticle. PMID:25481005

  2. Oral exposure to polystyrene nanoparticles affects iron absorption

    NASA Astrophysics Data System (ADS)

    Mahler, Gretchen J.; Esch, Mandy B.; Tako, Elad; Southard, Teresa L.; Archer, Shivaun D.; Glahn, Raymond P.; Shuler, Michael L.

    2012-04-01

    The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron transport in an in vitro model of the intestinal epithelium and an in vivo chicken intestinal loop model. Intestinal cells that are exposed to high doses of nanoparticles showed increased iron transport due to nanoparticle disruption of the cell membrane. Chickens acutely exposed to carboxylated particles (50 nm in diameter) had a lower iron absorption than unexposed or chronically exposed birds. Chronic exposure caused remodelling of the intestinal villi, which increased the surface area available for iron absorption. The agreement between the in vitro and in vivo results suggests that our in vitro intestinal epithelium model is potentially useful for toxicology studies.

  3. Challenges and Perspectives of Nanoparticle Exposure Assessment

    PubMed Central

    Lee, Ji Hyun; Moon, Min Chaul; Lee, Joon Yeob

    2010-01-01

    Nanoparticle exposure assessment presents a unique challenge in the field of occupational and environmental health. With the commercialization of nanotechnology, exposure usually starts from the workplace and then spreads to environment and consumer exposure. This report discusses the current trends of nanoparticle exposure assessment, including the definition of nanotechnology relevant terms, essential physicochemical properties for nanomaterial characterization, current international activities related nanomaterial safety, and exposure assessment standard development for nanotechnology. Further this report describes challenges of nanoparticle exposure assessment such as background measurement, metrics of nanoparticle exposure assessment and personal sampling. PMID:24278511

  4. Prenatal Smoking Exposure, Low Birth Weight, and Disruptive Behavior Disorders

    ERIC Educational Resources Information Center

    Nigg, Joel T.; Breslau, Naomi

    2007-01-01

    Background: Prenatal problems are among theorized etiologies for child disruptive behavior problems. A key question concerns whether etiological contributors are shared across the broad range of disruptive psychopathology or are partially or largely distinct. Method: We examined prenatal smoking exposure and low birth weight as risk factors for…

  5. Exposure to Engineered Nanomaterial Results in Disruption of Brush Borders in Epithelia Models in vitro

    NASA Astrophysics Data System (ADS)

    Faust, James J.

    Engineered nanoparticles (NP; 10-9 m) have found use in a variety of consumer goods and medical devices because of the unique changes in material properties that occur when synthesized on the nanoscale. Although many definitions for nanoparticle exist, from the perspective of size, nanoparticle is defined as particles with diameters less than 100 nm in any external dimension. Examples of their use include titanium dioxide added as a pigment in products intended to be ingested by humans, silicon dioxide NPs are used in foods as an anticaking agent, and gold or iron oxide NPs can be used as vectors for drug delivery or contrast agents for specialized medical imaging. Although the intended use of these NPs is often to improve human health, it has come to the attention of investigators that NPs can have unintended or even detrimental effects on the organism. This work describes one such unintended effect of NP exposure from the perspective of exposure via the oral route. First, this Dissertation will explain an event referred to as brush border disruption that occurred after nanoparticles interacted with an in vitro model of the human intestinal epithelium. Second, this Dissertation will identify and characterize several consumer goods that were shown to contain titanium dioxide that are intended to be ingested. Third, this Dissertation shows that sedimentation due to gravity does not artifactually result in disruption of brush borders as a consequence of exposure to food grade titanium dioxide in vitro. Finally, this Dissertation will demonstrate that iron oxide nanoparticles elicited similar effects after exposure to an in vitro brush border expressing model of the human placenta. Together, these data suggest that brush border disruption is not an artifact of the material/cell culture model, but instead represents a bona fide biological response as a result of exposure to nanomaterial.

  6. CHILDREN'S EXPOSURES TO ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    EPA is committed to protecting children's health by identifying, assessing, and reducing the risks from chemicals present in the air they breathe, food they eat, water they drink, and surfaces they touch. The Agency is committed to understanding the extent of children's exposure...

  7. Prior Cocaine Exposure Disrupts Extinction of Fear Conditioning

    ERIC Educational Resources Information Center

    Gugsa, Nishan; Schoenbaum, Geoffrey; Burke, Kathryn A.; Franz, Theresa M.

    2006-01-01

    Psychostimulant exposure has been shown to cause molecular and cellular changes in prefrontal cortex. It has been hypothesized that these drug-induced changes might affect the operation of prefrontal-limbic circuits, disrupting their normal role in controlling behavior and thereby leading to compulsive drug-seeking. To test this hypothesis, we…

  8. Biomembrane disruption by silica-core nanoparticles: effect of surface functional group measured using a tethered bilayer lipid membrane

    PubMed Central

    Liu, Ying; Zhang, Zhen; Zhang, Quanxuan; Baker, Gregory L.; Worden, R. Mark

    2013-01-01

    Engineered nanomaterials (ENM) have desirable properties that make them well suited for many commercial applications. However, a limited understanding of how ENM’s properties influence their molecular interactions with biomembranes hampers efforts to design ENM that are both safe and effective. This paper describes the use of a tethered bilayer lipid membrane (tBLM) to characterize biomembrane disruption by functionalized silica-core nanoparticles. Electrochemical impedance spectroscopy was used to measure the time trajectory of tBLM resistance following nanoparticle exposure. Statistical analysis of parameters from an exponential resistance decay model was then used to quantify and analyze differences between the impedance profiles of nanoparticles that were unfunctionalized, amine-functionalized, or carboxyl-functionalized. All of the nanoparticles triggered a decrease in membrane resistance, indicating nanoparticle-induced disruption of the tBLM. Hierarchical clustering allowed the potency of nanoparticles for reducing tBLM resistance to be ranked in the order amine > carboxyl ~ bare silica. Dynamic light scattering analysis revealed that tBLM exposure triggered minor coalescence for bare and amine-functionalized silica nanoparticles but not for carboxyl-functionalized silica nanoparticles. These results indicate that the tBLM method can reproducibly characterize ENM-induced biomembrane disruption and can distinguish the BLM-disruption patterns of nanoparticles that are identical except for their surface functional groups. The method provides insight into mechanisms of molecular interaction involving biomembranes and is suitable for miniaturization and automation for high-throughput applications to help assess the health risk of nanomaterial exposure or identify ENM having a desired mode of interaction with biomembranes. PMID:24060565

  9. Coverage and disruption of phospholipid membranes by oxide nanoparticles.

    PubMed

    Pera, Harke; Nolte, Tom M; Leermakers, Frans A M; Kleijn, J Mieke

    2014-12-01

    We studied the interactions of silica and titanium dioxide nanoparticles with phospholipid membranes and show how electrostatics plays an important role. For this, we systematically varied the charge density of both the membranes by changing their lipid composition and the oxide particles by changing the pH. For the silica nanoparticles, results from our recently presented fluorescence vesicle leakage assay are combined with data on particle adsorption onto supported lipid bilayers obtained by optical reflectometry. Because of the strong tendency of the TiO2 nanoparticles to aggregate, the interaction of these particles with the bilayer was studied only in the leakage assay. Self-consistent field (SCF) modeling was applied to interpret the results on a molecular level. At low charge densities of either the silica nanoparticles or the lipid bilayers, no electrostatic barrier to adsorption exists. However, the adsorption rate and adsorbed amounts drop with increasing (negative) charge densities on particles and membranes because of electric double-layer repulsion, which is confirmed by the effect of the ionic strength. SCF calculations show that charged particles change the structure of lipid bilayers by a reorientation of a fraction of the zwitterionic phosphatidylcholine (PC) headgroups. This explains the affinity of the silica particles for pure PC lipid layers, even at relatively high particle charge densities. Particle adsorption does not always lead to the disruption of the membrane integrity, as is clear from a comparison of the leakage and adsorption data for the silica particles. The attraction should be strong enough, and in line with this, we found that for positively charged TiO2 particles vesicle disruption increases with increasing negative charge density on the membranes. Our results may be extrapolated to a broader range of oxide nanoparticles and ultimately may be used for establishing more accurate nanoparticle toxicity assessments and drug

  10. Silver nanoparticles at sublethal concentrations disrupt cytoskeleton and neurite dynamics in cultured adult neural stem cells.

    PubMed

    Cooper, Robert J; Spitzer, Nadja

    2015-05-01

    Silver nanoparticles (AgNPs) have potent antimicrobial properties at concentrations far below those that cause cytotoxic and genotoxic effects in eukaryotic cells. This property has resulted in the widespread use of AgNPs in consumer products, leading to environmental exposures at sub-lethal levels through ingestion and inhalation. Although the toxicity of AgNPs has been well characterized, effects of environmentally relevant exposures have not been extensively investigated in spite of studies that suggest accumulation of silver in tissues, including brain. To assess the sublethal effects of AgNPs on neural cell function, we used cultured SVZ-NSCs, a model of neurogenesis and neural cells. Throughout life, neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricles proliferate and migrate via the rostral migratory stream to the olfactory bulb. Once there, they complete differentiation into neurons and glia and integrate into existing circuits. This process of neurogenesis is tightly regulated, and is considered a part of healthy brain function. We found that 1.0 μg/mL AgNP exposure in cultured differentiating NSCs induced the formation of f-actin inclusions, indicating a disruption of actin function. These inclusions did not co-localize with AgNPs, and therefore do not represent sequestered nanoparticles. Further, AgNP exposure led to a reduction in neurite extension and branching in live cells, cytoskeleton-mediated processes vital to neurogenesis. We conclude that AgNPs at sublethal concentrations disrupt actin dynamics in SVZ-NSCs, and that an associated disruption in neurogenesis may contribute to documented deficits in brain function following AgNP exposure. PMID:25952507

  11. Effects of ZnO nanoparticles on perfluorooctane sulfonate induced thyroid-disrupting on zebrafish larvae.

    PubMed

    Du, Jia; Wang, Shutao; You, Hong; Liu, Zhongqiang

    2016-09-01

    Perfluorooctane sulfonate (PFOS) and ZnO nanoparticles (nano-ZnO) are widely distributed in the environment. However, the potential toxicity of co-exposure to PFOS and nano-ZnO remains to be fully elucidated. The test investigated the effects of co-exposure to PFOS and nano-ZnO on the hypothalamic-pituitary-thyroid (HPT) axis in zebrafish. Zebrafish embryos were exposed to a combination of PFOS (0.2, 0.4, 0.8mg/L) and nano-ZnO (50mg/L) from their early stages of life (0-14days). The whole-body content of TH and the expression of genes and proteins related to the HPT axis were analyzed. The co-exposure decreased the body length and increased the malformation rates compared with exposure to PFOS alone. Co-exposure also increased the triiodothyronine (T3) levels, whereas the thyroxine (T4) content remained unchanged. Compared with the exposure to PFOS alone, exposure to both PFOS (0.8mg/L) and nano-ZnO (50mg/L) significantly up-regulated the expression of corticotropin-releasing factor, sodium/iodidesymporter, iodothyronine deiodinases and thyroid receptors and significantly down-regulated the expression of thyroid-stimulating hormone, thyroglobulin (TG), transthyretin (TTR) and thyroid receptors. The protein expression levels of TG and TTR were also significantly down-regulated in the co-exposure groups. In addition, the expression of the thyroid peroxidase gene was unchanged in all groups. The results demonstrated that PFOS and nano-ZnO co-exposure could cause more serious thyroid-disrupting effects in zebrafish than exposure to PFOS alone. Our results also provide insight into the mechanism of disruption of the thyroid status by PFOS and nano-ZnO. PMID:27593282

  12. Exposure to Endocrine Disrupting Chemicals and Male Reproductive Health

    PubMed Central

    Jeng, Hueiwang Anna

    2014-01-01

    Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance and may exert adverse consequences on humans. The male reproductive system may be susceptible to the effects of such environmental toxicants. This review discusses the recent progress in scientific data mainly from epidemiology studies on the associations between EDCs and male reproductive health and our understanding of possible mechanisms associated with the effects of EDCs on male reproductive health. Finally, the review provides recommendations on future research to enhance our understanding of EDCs and male reproductive health. The review highlights the need for (1) well-defined longitudinal epidemiology studies, with appropriately designed exposure assessment to determine potential causal relationships; (2) chemical and biochemical approaches aimed at a better understanding of the mechanism of action of xenoestrogens with regard to low-dose effects, and assessment of identify genetic susceptibility factors associated with the risk of adverse effects following exposure to EDCs. PMID:24926476

  13. Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans†

    PubMed Central

    Page, Kathryn E.; White, Keith N.; McCrohan, Catherine R.

    2013-01-01

    Aluminium (Al) is highly abundant in the environment and can elicit a variety of toxic responses in biological systems. Here we characterize the effects of Al on Caenorhabditis elegans by identifying phenotypic abnormalities and disruption in whole-body metal homeostasis (metallostasis) following Al exposure in food. Widespread changes to the elemental content of adult nematodes were observed when chronically exposed to Al from the first larval stage (L1). Specifically, we saw increased barium, chromium, copper and iron content, and a reduction in calcium levels. Lifespan was decreased in worms exposed to low levels of Al, but unexpectedly increased when the Al concentration reached higher levels (4.8 mM). This bi-phasic phenotype was only observed when Al exposure occurred during development, as lifespan was unaffected by Al exposure during adulthood. Lower levels of Al slowed C. elegans developmental progression, and reduced hermaphrodite self-fertility and adult body size. Significant developmental delay was observed even when Al exposure was restricted to embryogenesis. Similar changes in Al have been noted in association with Al toxicity in humans and other mammals, suggesting that C. elegans may be of use as a model for understanding the mechanisms of Al toxicity in mammalian systems. PMID:22534883

  14. Size dependent disruption of tethered lipid bilayers by functionalized polystyrene nanoparticles.

    PubMed

    Liu, Ying; Mark Worden, R

    2015-01-01

    Molecular interactions between engineered nanomaterials (ENM) and biomembranes are not well understood. This study investigated the effects of particle size and surface functional group on polystyrene nanoparticles' (PNPs) potency for biomembrane disruption. Electrochemical impedance spectroscopy was used to measure changes in the electrical resistance (Rm) of a tethered bilayer lipid membrane BLM (tBLM) composed of 1,2-dioleoyl-sn-glycero-phosphocholine (DOPC) following PNP exposure. All PNPs tested triggered a decline in the Rm that could be described using an exponential-decay model. Statistical hierarchical clustering analysis of two model parameters (exponential rate constant and fractional loss of Rm) could distinguish between the PNPs based on both size and surface functional group. For COOH modified nanoparticles, 20nm PNPs were more potent in reducing Rm than 100nm PNP. However, for amidine modified nanoparticles, 120nm PNPs were more potent in reducing Rm than 23nm PNP. The COOH modified PNPs were more potent in reducing Rm than amidine modified PNP, which tended to aggregate following exposure to a tBLM. Ultra performance liquid chromatography-mass spectroscopy analysis suggested that the aggregation may have been triggered by DOPC that was removed from the tBLM by the amidine PNP. PMID:25285435

  15. TCDD exposure disrupts mammary epithelial cell differentiation and function

    PubMed Central

    Collins, Loretta L.; Lew, Betina J.; Lawrence, B. Paige

    2011-01-01

    Mammary gland growth and differentiation during pregnancy is a developmental process that is sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a widespread environmental contaminant and a potent ligand for the aryl hydrocarbon receptor (AhR). We demonstrate reduced β-casein protein induction in mouse mammary glands and in cultured SCp2 mammary epithelial cells following exposure to TCDD. SCp2 cells exposed to TCDD also show reduced cell clustering and less alveolar-like structure formation. SCp2 cells express transcriptionally active AhR, and exposure to TCDD induces expression of the AhR target gene CYP1B1. Exposure to TCDD during pregnancy reduced expression of the cell adhesion molecule E-cadherin in the mammary gland and decreased phosphorylation of STAT5, a known regulator of β-casein gene expression. These data provide morphological and molecular evidence that TCDD-mediated AhR activation disrupts structural and functional differentiation of the mammary gland, and present an in vitro model for studying the effects of TCDD on mammary epithelial cell function. PMID:19490989

  16. Endocrine Disruption of Brain Sexual Differentiation by Developmental PCB Exposure

    PubMed Central

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Patisaul, Heather B.; Woller, Michael J.

    2011-01-01

    In mammals, sexual differentiation of the hypothalamus occurs during prenatal and early postnatal development due in large part to sex differences in hormones. These early organizational processes are critically important for the attainment and maintenance of adult reproductive functions. We tested the hypothesis that perinatal exposure to polychlorinated biphenyls (PCBs) that disrupt hormonal pathways would perturb reproductive maturation and the sexually dimorphic development of neuroendocrine systems in the preoptic area (POA). Pregnant Sprague-Dawley rats were injected on gestational d 16 and 18 with vehicle (dimethylsulfoxide), Aroclor 1221 (A1221, an estrogenic PCB mix), a reconstituted PCB mixture representing those highest in human body burden (PCBs 138, 153, 180), or estradiol benzoate, an estrogenic control. Male and female pups were monitored for somatic and reproductive development. In adulthood, some rats were perfused and used for immunohistochemistry of estrogen receptor α, kisspeptin, and coexpression of Fos in GnRH neurons. Other rats were used to obtain fresh-frozen POA dissections for use in a PCR-based 48-gene expression array. Pubertal onset was advanced and estrous cyclicity irregular in endocrine-disrupted females. Furthermore, sexual differentiation of female neuroendocrine systems was masculinized/defeminized. Specifically, in the adult female anteroventral periventricular nucleus, estrogen receptor α-cell numbers and kisspeptin fiber density were significantly decreased, as was GnRH-Fos coexpression. PCR analysis identified androgen receptor, IGF-I, N-methyl-d-aspartate receptor subunit NR2b, and TGFβ1 mRNAs as significantly down-regulated in endocrine-disrupted female POAs. These data suggest that developmental PCBs profoundly impair the sexual differentiation of the female hypothalamus. PMID:21190954

  17. Occupational Exposure to Nanoparticles and Medical Safety

    NASA Astrophysics Data System (ADS)

    Brochard, Patrick; Bloch, Daniel; Pairon, Jean-Claude

    The problem of occupational exposure to nanoparticles (NP) has raised many questions which remain unanswered today: When airborne NPs, either dissociated or more commonly in the form of aggregates, are inhaled by humans, will they produce a biological and/or tissular response where they are deposited, i.e., in the respiratory tract, or at some distance from the deposition area, i.e., an indirect effect secondary to the inflammatory response of the respiratory tract or a direct effect due to translocation of nanoparticles through the biological membranes?

  18. Oral exposure to polystyrene nanoparticles effects iron absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of engineered nanoparticles in food and pharmaceuticals is expected to increase, but the impact of chronic oral exposure to nanoparticles on human health remains unknown. Here, we show that chronic and acute oral exposure to polystyrene nanoparticles can influence iron uptake and iron trans...

  19. Prenatal exposure to bisphenol A disrupts mouse fetal lung development.

    PubMed

    Hijazi, Ayten; Guan, Haiyan; Cernea, Maria; Yang, Kaiping

    2015-12-01

    Developmental exposure to bisphenol A (BPA) is associated with lung dysfunction and diseases. However, it is unknown if this association has a fetal origin. The present study addressed this important question by examining the effects of BPA on fetal lung development. BPA was administered to pregnant mice via diet from embryonic day (E) 7.5 to E18.5. Fetal lungs were analyzed at E18.5 for changes in structure and expression of key molecular markers of lung maturation. Our main findings were as follows: BPA severely retards fetal lung maturation, as evidenced by diminished alveolar airspace (15% of control) and thickened septa, hallmarks of lung immaturity; this immaturity is characterized by aberrant alveolar epithelial type I cell differentiation because expression of the type I cell marker, aquaporin 5, but not type II cell markers, is dramatically reduced (16% of control); and the effects of BPA are likely mediated through the glucocorticoid signaling pathway because the expression of epithelial sodium channel γ and glutathione peroxidase, 2 well-known glucocorticoid target genes, is down-regulated in BPA-exposed fetal lungs, and, importantly, maternal dexamethasone administration rescues the lung immaturity phenotype. Taken together, these findings demonstrate that BPA disrupts fetal lung maturation, thus suggesting a fetal origin for BPA-induced lung diseases. PMID:26283537

  20. Epigenomic Disruption: The Effects of Early Developmental Exposures

    PubMed Central

    Bernal, Autumn J.; Jirtle, Randy L.

    2010-01-01

    Through DNA methylation, histone modifications, and small regulatory RNAs the epigenome systematically controls gene expression during development-- both in utero and throughout life. The epigenome is also a very reactionary system; its labile nature allows it to sense and respond to environmental perturbations to ensure survival during fetal growth. This pliability can lead to aberrant epigenetic modifications that persist into later life and induce numerous disease states. Endocrine disrupting compounds (EDCs) are ubiquitous chemicals that interfere with growth and development. Several EDCs also interfere with epigenetic programming. The investigation of the epigenotoxic effects of bisphenol A (BPA), an EDC used in the production of plastics and resins, has further raised concern for the impact of EDCs on the epigenome. Using the Agouti viable yellow (Avy) mouse model, dietary BPA exposure was shown to hypomethylate both the Avy and the CabpIAP metastable epialleles. This hypomethylating effect was counteracted with dietary supplementation of methyl donors or genistein. These results are consistent with reports of BPA and other EDCs causing epigenetic effects. Epigenotoxicity could lead to numerous developmental, metabolic, and behavioral disorders in exposed populations. The heritable nature of epigenetic changes also increases the risk for transgenerational inheritance of phenotypes. Thus, epigenotoxicity must be considered when assessing these compounds for safety. PMID:20568270

  1. Whole-Body Nanoparticle Aerosol Inhalation Exposures

    PubMed Central

    Yi, Jinghai; Chen, Bean T.; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L.; Stapleton, Phoebe A.; Minarchick, Valerie C.; Nurkiewicz, Timothy R.

    2013-01-01

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σg < 2.5 5. The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size 6, which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria 5. A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m3 whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm3) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m3). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpreand Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is

  2. Whole-body nanoparticle aerosol inhalation exposures.

    PubMed

    Yi, Jinghai; Chen, Bean T; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L; Stapleton, Phoebe A; Minarchick, Valerie C; Nurkiewicz, Timothy R

    2013-01-01

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σg < 2.5 (5). The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M

  3. Nanoparticle exposure biomonitoring: exposure/effect indicator development approaches

    NASA Astrophysics Data System (ADS)

    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.

  4. Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure

    PubMed Central

    Grewen, Karen; Salzwedel, Andrew P.; Gao, Wei

    2015-01-01

    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 selective serotonin reuptake inhibitors; −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 hypo-connectivity 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 hyper-connectivity of left amygdala seed with orbital frontal cortex and hypo-connectivity of posterior thalamus seed with hippocampus, suggesting vulnerability to multiple drugs in these circuits. PMID:26582983

  5. Silver nanoparticle toxicity is related to coating materials and disruption of sodium concentration regulation.

    PubMed

    Kwok, Kevin W H; Dong, Wu; Marinakos, Stella M; Liu, Jie; Chilkoti, Ashutosh; Wiesner, Mark R; Chernick, Melissa; Hinton, David E

    2016-11-01

    Silver nanoparticles (AgNPs) have been increasingly commercialized and their release into the environment is imminent. Toxicity of AgNP has been studied with a wide spectrum of organisms, yet the mechanism of toxicity remains largely unknown. This study systematically compared toxicity of 10 AgNPs of different particle diameters and coatings to Japanese medaka (Oryzias latipes) larvae to understand how characteristics of AgNP relate to toxicity. Dissolution of AgNPs was largely dependent on particle size, but their aggregation behavior and toxicity were more dependent on coating materials. 96 h lethal concentration 50% (LC50) values correlated with AgNP aggregate size rather than size of individual nanoparticles. Of the AgNPs studied, the dissolved Ag concentration in the test suspensions did not account for all of the observed toxicity, indicating the role of NP-specific characteristics in resultant toxicity. Exposure to AgNP led to decrease of sodium concentration in the tissue and increased expression of Na(+)/K(+ )ATPase. Gene expression patterns also suggested that toxicity was related to disruption of sodium regulation and not to oxidative stress. PMID:27345576

  6. Exposure to endocrine disrupting chemicals and neurodevelopmental alterations.

    PubMed

    Pinson, A; Bourguignon, J P; Parent, A S

    2016-07-01

    The developing brain is remarkably malleable as neural circuits are formed and these circuits are strongly dependent on hormones for their development. For those reasons, the brain is very vulnerable to the effects of endocrine-disrupting chemicals (EDCs) during critical periods of development. This review focuses on three ubiquitous endocrine disruptors that are known to disrupt the thyroid function and are associated with neurobehavioral deficits: polychlorinated biphenyls, polybrominated diphenyl ethers, and bisphenol A. The human and rodent data suggesting effects of those EDCs on memory, cognition, and social behavior are discussed. Their mechanisms of action go beyond relative hypothyroidism with effects on neurotransmitter release and calcium signaling. PMID:27285165

  7. Semihydrophobic nanoparticle-induced disruption of supported lipid bilayers: specific ion effect.

    PubMed

    Jing, Benxin; Abot, Rosary C T; Zhu, Yingxi

    2014-11-20

    The interaction of nanoparticles with cell membranes is critical to understand and control the structural change and molecular transport of cell membranes for medicines and medical diagnostics, in which hydrophobic interaction is often involved. We examine the specific ion effect on the interaction of semihydrophobic nanoparticle with zwitterionic phospholipid bilayer in aqueous media added with different types of salts. Specifically, we compare the effect of different anions or cations on the adsorption of carboxyl-functionalized polystyrene nanoparticle on supported lipid bilayer and its induced bilayer disruption. By adding different anions at the same ionic concentration to the nanoparticle-lipid bilayer interface, we observe that the growth rate of nanoparticle-induced lipid-poor regions follows the exact Hofmeister anion order of CH3COO(-) > Cl(-) > NO3(-) ≫ SCN(-), suggesting the regulated hydrophobic interaction by anions. In contrast, the specific cation effect on nanoparticle-induced disruption rate of lipid bilayer does not follow the Hofmeister cation order and instead exhibits a trend of Cs(+) ∼ Rb(+) > Na(+) ≫ N(CH3)4(+). It is suggested that the effect of specific ions can be exploited as a simple and efficient approach to modify the nanoparticles-biomembrane interactions with the implication from drug delivery to nontoxic nanomaterial design. PMID:25337793

  8. Cationic nanoparticles induce nanoscale disruption in living cell plasma membranes.

    PubMed

    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. PMID:19606833

  9. Cationic Peptide Exposure Enhances Pulsed-Electric-Field-Mediated Membrane Disruption

    PubMed Central

    Kennedy, Stephen M.; Aiken, Erik J.; Beres, Kaytlyn A.; Hahn, Adam R.; Kamin, Samantha J.; Hagness, Susan C.; Booske, John H.; Murphy, William L.

    2014-01-01

    Background The use of pulsed electric fields (PEFs) to irreversibly electroporate cells is a promising approach for destroying undesirable cells. This approach may gain enhanced applicability if the intensity of the PEF required to electrically disrupt cell membranes can be reduced via exposure to a molecular deliverable. This will be particularly impactful if that reduced PEF minimally influences cells that are not exposed to the deliverable. We hypothesized that the introduction of charged molecules to the cell surfaces would create regions of enhanced transmembrane electric potential in the vicinity of each charged molecule, thereby lowering the PEF intensity required to disrupt the plasma membranes. This study will therefore examine if exposure to cationic peptides can enhance a PEF’s ability to disrupt plasma membranes. Methodology/Principal Findings We exposed leukemia cells to 40 μs PEFs in media containing varying concentrations of a cationic peptide, polyarginine. We observed the internalization of a membrane integrity indicator, propidium iodide (PI), in real time. Based on an individual cell’s PI fluorescence versus time signature, we were able to determine the relative degree of membrane disruption. When using 1–2 kV/cm, exposure to >50 μg/ml of polyarginine resulted in immediate and high levels of PI uptake, indicating severe membrane disruption, whereas in the absence of peptide, cells predominantly exhibited signatures indicative of no membrane disruption. Additionally, PI entered cells through the anode-facing membrane when exposed to cationic peptide, which was theoretically expected. Conclusions/Significance Exposure to cationic peptides reduced the PEF intensity required to induce rapid and irreversible membrane disruption. Critically, peptide exposure reduced the PEF intensities required to elicit irreversible membrane disruption at normally sub-electroporation intensities. We believe that these cationic peptides, when coupled with

  10. Miniature nanoparticle sensors for exposure measurement and TEM sampling

    NASA Astrophysics Data System (ADS)

    Fierz, Martin; Meier, Dominik; Steigmeier, Peter; Burtscher, Heinz

    2015-05-01

    Nanoparticles in workplaces may pose a threat to the health of the workers involved. With the general boom in nanotechnology, an increasing number of workers is potentially exposed, and therefore a comprehensive risk management with respect to nanoparticles appears necessary. One (of many) components of such a risk management is the measurement of personal exposure. Traditional nanoparticle detectors are often cumbersome to use, large, heavy and expensive. We have developed small, reliable and easy to use devices that can be used for routine personal exposure measurement in workplaces.

  11. ASSESSING ENDOCRINE-DISRUPTING CHEMICAL EXPOSURE IN INDIGENOUS AQUATIC POPULATIONS IN THE OHIO RIVER

    EPA Science Inventory

    The NERL has launched a collaborative study with the ORSANCO to determine the degree of ecologically relevant endocrine-disrupting chemical (EDC) exposure in the New Cumberland Pool of the Ohio River under the Environmental Monitoring and Assessment Program - Great Rivers Project...

  12. Lack of reliability in the disruption of cognitive performance following exposure to protons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of three replications were run to determine the reliability with which exposure to protons produces a disruption of cognitive performance, using a novel object recognition task and operant responding on an ascending fixed-ratio task. For the first two replications, rats were exposed to hea...

  13. DEVELOPMENTAL EXPOSURE TO A THYROID DISRUPTING CHEMICAL STIMULATES PHAGOCYTOSIS IN JUVENILE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Developmental Exposure to a Thyroid Disrupting Chemical Stimulates Phagocytosis in Juvenile Sprague-Dawley Rats.
    AA Rooney1, R Matulka2, and R Luebke3. 1NCSU/US EPA CVM, Department of Anatomy, Physiological Sciences and Radiology, Raleigh, NC;2UNC Department of Toxicology, Cha...

  14. Silver nanoparticles disrupt regulation of steroidogenesis in fish ovarian cells.

    PubMed

    Degger, Natalie; Tse, Anna C K; Wu, Rudolf S S

    2015-12-01

    Despite the influx of silver nanoparticles (nAg) into the marine environment, their effects on fish reproduction remain completely unexplored. Using ovarian primary cells from marine medaka (Oryzias melastigma), in vitro studies were carried out to evaluate the effects of two differently coated nAg particles (Oleic Acid, (OA) nAg and Polyvinylpyrrolidone, (PVP) nAg) on fish ovarian tissues, using AgNO3 as a positive control. Cytotoxicity was evaluated by MTT assay and expression of key genes regulating steroidogenesis (StAR, CYP 19a, CYP 11a, 3βHSD and 20βHSD) were determined by Q-RT-PCR. EC50 values for PVP nAg, OA nAg and AgNO3 were 7.25μgL(-1), 924.4μgL(-1), and 42.0μgL(-1) respectively, showing that toxicity of silver was greatly enhanced in the PVP coated nano-form. Down regulation of CYP 19a was observed in both nAg and AgNO3 treatments, while down regulation of 3βHSD was only found in the OA nAg and AgNO3 treatments. For the first time, our results demonstrated that nAg can affect specific genes regulating steroidogenesis, implicating nAg as a potential endocrine disruptor. PMID:26546908

  15. Inside-out disruption of silica/gold core-shell nanoparticles by pulsed laser irradiation.

    PubMed

    Prasad, V; Mikhailovsky, A; Zasadzinski, J A

    2005-08-01

    Near-infrared (NIR) femtosecond laser irradiation of metallodielectric core-shell silica-gold (SiO(2)-Au) nanoparticles can induce extreme local heating prior to the rapid dissipation of energy caused by the large surface area/volume ratio of nanometer-scale objects. At low pulse intensities, the dielectric silica core is removed, leaving an incomplete gold shell behind. The gold shells with water inside and out still efficiently absorb NIR light from subsequent pulses, showing that a complete shell is not necessary for absorption. At higher pulse intensities, the gold shell itself is melted and disrupted, leading to smaller, approximately 20-nm gold nanoparticles. Spectroscopic measurements show that this disruption is accompanied by optical hole burning of the peak at 730 nm and formation of a new peak at 530 nm. The silica removal and gold shell disruption confirms significant temperature rise of the core-shall nanoparticle. However, the entire process leads to minimal heating of the bulk solution due to the low net energy input. PMID:16042490

  16. Safety assessment of chronic oral exposure to iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    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-Fe2O3 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-Fe2O3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe2O3 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.

  17. Transient Intermittent Hypoxia Exposure Disrupts Neonatal Bone Strength.

    PubMed

    Kim, Gyuyoup; Elnabawi, Omar; Shin, Daehwan; Pae, Eung-Kwon

    2016-01-01

    A brief intermittent hypoxia (IH, ambient O2 levels alternating between room air and 12% O2) for 1 h immediately after birth resulted in pancreatic islet dysfunction associated with zinc deficiency as previously reported. We hypothesized that IH exposure modulates zinc homeostasis in bone as well, which leads to increased bone fragility. To test this hypothesis, we used neonatal rats and human osteoblasts (HObs). To examine IH influences on osteoblasts devoid of neural influences, we quantified amounts of alkaline phosphatase and mineralization in IH-treated HObs. Bones harvested from IH-treated animals showed significantly reduced hardness and elasticity. The IH group also showed discretely decreased levels of alkaline phosphatase and mineralization amounts. The IH group showed a decreased expression of ZIP8 or Zrt and Irt-like protein 8 (a zinc uptake transporter), Runx2 (or Runt-related transcription factor 2, a master protein in bone formation), Collagen-1 (a major protein comprising the extracellular matrix of the bone), osteocalcin, and zinc content. When zinc was eliminated from the media containing HObs using a zinc chelate and added later with zinc sulfate, Runx2, ZIP8, and osteocalcin expression decreased first, and recovered with zinc supplementation. Adenovirus-mediated ZIP8 over-expression in osteoblasts increased mineralization significantly as well. We conclude that IH impairs zinc homeostasis in bones and osteoblasts, and that such disturbances decrease bone strength, which can be recovered by zinc supplementation. PMID:27014665

  18. Transient Intermittent Hypoxia Exposure Disrupts Neonatal Bone Strength

    PubMed Central

    Kim, Gyuyoup; Elnabawi, Omar; Shin, Daehwan; Pae, Eung-Kwon

    2016-01-01

    A brief intermittent hypoxia (IH, ambient O2 levels alternating between room air and 12% O2) for 1 h immediately after birth resulted in pancreatic islet dysfunction associated with zinc deficiency as previously reported. We hypothesized that IH exposure modulates zinc homeostasis in bone as well, which leads to increased bone fragility. To test this hypothesis, we used neonatal rats and human osteoblasts (HObs). To examine IH influences on osteoblasts devoid of neural influences, we quantified amounts of alkaline phosphatase and mineralization in IH-treated HObs. Bones harvested from IH-treated animals showed significantly reduced hardness and elasticity. The IH group also showed discretely decreased levels of alkaline phosphatase and mineralization amounts. The IH group showed a decreased expression of ZIP8 or Zrt and Irt-like protein 8 (a zinc uptake transporter), Runx2 (or Runt-related transcription factor 2, a master protein in bone formation), Collagen-1 (a major protein comprising the extracellular matrix of the bone), osteocalcin, and zinc content. When zinc was eliminated from the media containing HObs using a zinc chelate and added later with zinc sulfate, Runx2, ZIP8, and osteocalcin expression decreased first, and recovered with zinc supplementation. Adenovirus-mediated ZIP8 over-expression in osteoblasts increased mineralization significantly as well. We conclude that IH impairs zinc homeostasis in bones and osteoblasts, and that such disturbances decrease bone strength, which can be recovered by zinc supplementation. PMID:27014665

  19. Assessment of carbon nanoparticle exposure on murine macrophage function

    NASA Astrophysics Data System (ADS)

    Suro-Maldonado, Raquel M.

    There is growing concern about the potential cytotoxicity of nanoparticles. Exposure to respirable ultrafine particles (2.5uM) can adversely affect human health and have been implicated with episodes of increased respiratory diseases such as asthma and allergies. Nanoparticles are of particular interest because of their ability to penetrate into the lung and potentially elicit health effects triggering immune responses. Nanoparticles are structures and devises with length scales in the 1 to 100-nanometer range. Black carbon (BC) nanoparticles have been observed to be products of combustion, especially flame combustion and multi-walled carbon nanotubes (MWCNT) have been shown to be found in both indoor and outdoor air. Furthermore, asbestos, which have been known to cause mesothelioma as well as lung cancer, have been shown to be structurally identical to MWCNTs. The aims of these studies were to examine the effects of carbon nanoparticles on murine macrophage function and clearance mechanisms. Macrophages are immune cells that function as the first line of defense against invading pathogens and are likely to be amongst the first cells affected by nanoparticles. Our research focused on two manufactured nanoparticles, MWCNT and BC. The two were tested against murine-derived macrophages in a chronic contact model. We hypothesized that long-term chronic exposure to carbon nanoparticles would decrease macrophages ability to effectively respond to immunological challenge. Production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), cell surface macrophage; activation markers, reactive oxygen species formation (ROS), and antigen processing and presentation were examined in response to lipopolysaccharide (LPS) following a 144hr exposure to the particulates. Data demonstrated an increase in TNF-alpha, and NO production; a decrease in phagocytosis and antigen processing and presentation; and a decrease in the expression levels of cell surface macrophage

  20. pH-activated Nanoparticles for Controlled Topical Delivery of Farnesol to Disrupt Oral Biofilm Virulence

    PubMed Central

    Horev, Benjamin; Klein, Marlise I.; Hwang, Geelsu; Li, Yong; Kim, Dongyeop; Koo, Hyun; Benoit, Danielle S.W.

    2015-01-01

    Development of effective therapies to control oral biofilms is challenging, as topically introduced agents must avoid rapid clearance from biofilm-tooth interfaces while targeting biofilm microenvironments. Additionally, exopolysaccharide matrix and acidification of biofilm microenvironments are associated with cariogenic (caries-producing) biofilm virulence. Thus, nanoparticle carriers capable of binding to hydroxyapatite (HA), saliva-coated HA (sHA), and exopolysaccharides with enhanced drug-release at acidic pH were developed. Nanoparticles are formed from diblock copolymers composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA), butyl methacrylate (BMA), and 2-propylacrylic acid (PAA) (p(DMAEMA)-b-p(DMAEMA-co-BMA-co-PAA)) that self-assemble into ~21 nm cationic nanoparticles. Nanoparticles exhibit outstanding adsorption affinities (~244 L-mmol−1) to negatively-charged HA, sHA, and exopolysaccharide-coated sHA due to strong electrostatic interactions via multivalent tertiary amines of p(DMAEMA). Owing to hydrophobic cores, Nanoparticles load farnesol, a hydrophobic antibacterial drug, at ~22 wt%. Farnesol release is pH-dependent with t1/2=7 and 15 h for release at pH 4.5 and 7.2, as Nanoparticles undergo core destabilization at acidic pH, characteristic of cariogenic biofilm microenvironments. Importantly, topical applications of farnesol-loaded nanoparticles disrupted Streptococcus mutans biofilms 4-fold more effectively than free farnesol. Mechanical stability of biofilms treated with drug-loaded nanoparticles was compromised, resulting in >2-fold enhancement in biofilm removal under shear stress compared to free farnesol and controls. Farnesol-loaded nanoparticles effectively attenuated biofilm virulence in vivo using a clinically-relevant topical treatment regimen (2×/day) in a rodent dental caries disease model. Treatment with farnesol-loaded nanoparticles reduced both the number and severity of carious lesions, while free-farnesol had no effect

  1. pH-activated nanoparticles for controlled topical delivery of farnesol to disrupt oral biofilm virulence.

    PubMed

    Horev, Benjamin; Klein, Marlise I; Hwang, Geelsu; Li, Yong; Kim, Dongyeop; Koo, Hyun; Benoit, Danielle S W

    2015-03-24

    Development of effective therapies to control oral biofilms is challenging, as topically introduced agents must avoid rapid clearance from biofilm-tooth interfaces while targeting biofilm microenvironments. Additionally, exopolysaccharides-matrix and acidification of biofilm microenvironments are associated with cariogenic (caries-producing) biofilm virulence. Thus, nanoparticle carriers capable of binding to hydroxyapatite (HA), saliva-coated HA (sHA), and exopolysaccharides with enhanced drug release at acidic pH were developed. Nanoparticles are formed from diblock copolymers composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA), butyl methacrylate (BMA), and 2-propylacrylic acid (PAA) (p(DMAEMA)-b-p(DMAEMA-co-BMA-co-PAA)) that self-assemble into ∼21 nm cationic nanoparticles. Nanoparticles exhibit outstanding adsorption affinities (∼244 L-mmol(-1)) to negatively charged HA, sHA, and exopolysaccharide-coated sHA due to strong electrostatic interactions via multivalent tertiary amines of p(DMAEMA). Owing to hydrophobic cores, nanoparticles load farnesol, a hydrophobic antibacterial drug, at ∼22 wt %. Farnesol release is pH-dependent with t1/2 = 7 and 15 h for release at pH 4.5 and 7.2, as nanoparticles undergo core destabilization at acidic pH, characteristic of cariogenic biofilm microenvironments. Importantly, topical applications of farnesol-loaded nanoparticles disrupted Streptococcus mutans biofilms 4-fold more effectively than free farnesol. Mechanical stability of biofilms treated with drug-loaded nanoparticles was compromised, resulting in >2-fold enhancement in biofilm removal under shear stress compared to free farnesol and controls. Farnesol-loaded nanoparticles effectively attenuated biofilm virulence in vivo using a clinically relevant topical treatment regimen (2×/day) in a rodent dental caries disease model. Strikingly, treatment with farnesol-loaded nanoparticles reduced both the number and severity of carious lesions, while free

  2. [Exposure to endocrine disrupting chemicals and children's health: problems in epidemiological studies].

    PubMed

    Kishi, Reiko; Sata, Fumihiro; Saijo, Yasuaki; Kurahashi, Norie; Kato, Shizue; Nakajima, Sonomi; Sasaki, Seiko

    2006-01-01

    Most endocrine disrupting chemicals are characterized by their properties to induce marked phenotypic changes in offspring such as congenital anomalies and neurodevelopmental dysfunctions. Although an increase in the prevalence of hypospadias or cryptorchidism has been reported in various countries, improvement in diagnostic techniques and more attention to the features of the diseases have also been emphasized. Although there have been a few reports that hypospadias or cryptorchidism had been associated with diethylstilbestrol (DES), pesticides and so on, the associations between these diseases and endocrine disrupting chemicals remain unclear. Recently, the association between maternal metabolic polymorphism or paternal smoking during pregnancy and these diseases has been reported. There are also variable clinical features in children's neurobehavioral development, and thyroid and immune functions in relation to exposure to endocrine disrupting chemicals such as polychlorinated biphenyls (PCBs) and dioxins. Only a few Dutch studies have suggested that perinatal exposure to background level of PCB/dioxin confers immunity to allergy development. Genetic susceptibility to environmental endocrine disrupting chemicals may be related to adverse pregnancy outcomes. It is suggested that well-designed epidemiological studies such as prospective cohort studies should be performed to elucidate this association. PMID:16506651

  3. Exposure to butachlor causes thyroid endocrine disruption and promotion of metamorphosis in Xenopus laevis.

    PubMed

    Li, Shuying; Li, Meng; Wang, Qiangwei; Gui, Wenjun; Zhu, Guonian

    2016-06-01

    Butachlor is extensively applied in rice paddy ecosystem in china, and has been widespread contaminant in the aquatic environment. Here, Xenopus laevis was used for the evaluation of teratogenesis developmental toxicity, and disruption of thyroid system when exposure to different concentrations of butachlor by window phase exposure. Acute toxicity investigation shown that 96 h-LC50 value of butachlor was 1.424 mg L(-1) and 0.962 mg L(-1) for tadpoles (starting from stages 46/47) and embryos (starting from stages 8/9), respectively. Exposure to butachlor caused malformation, including abnormal eye, pericardial edema, enlarged proctodaeum and bent tail. Window phase exposure test indicated that butachlor significantly promote the contents of whole-body thyroid hormones (THs, T3 and T4) at higher levels, indicating thyroid endocrine disruption. At 7 days, exposure to butachlor up-regulated the mRNA expression of genes involved in THs synthesis and metabolism (tshα, tg, tpo and dio1) and THs receptors (trα and trβ). At 14 days, up-regulation of the mRNA expression of genes related to THs synthesis and metabolism (tshα, tshβ, tg, tpo, dio1, dio2 and ttr) and THs receptors (trβ) were also observed after the exposure to butachlor. At 21 days, butachlor up-regulated the mRNA expression of tshα, tg, tpo genes and down-regulated the mRNA expression of tshβ, tg, dio1, ttr and trα genes. These results showed that butachlor could change the mRNA expression of genes involved in the HPT axis and increase whole-body thyroid hormones levels of X. laevis tadpoles in a dose- and time-dependent manner, causing thyroid endocrine disruption and developmental toxicity. PMID:26971167

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

    PubMed Central

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

    2014-01-01

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

  5. Subchronic exposure of titanium dioxide nanoparticles to hairless rat skin.

    PubMed

    Adachi, Koji; Yamada, Nanako; Yoshida, Yuichi; Yamamoto, Osamu

    2013-04-01

    The evaluation of the biological effects of industrial nanoparticles on the skin is necessary for their risk assessment. To clarify the influence of TiO2 nanoparticles on the skin, we carried out a subchronic exposure study of TiO2 nanoparticles to hairless rat skin. W/O emulsion containing 10 wt% TiO2 nanoparticles and control emulsion was applied to the dorsal skin of Hairless Wistar Yagi rats once a day for a maximum period of 56 consecutive days. After 2, 4 and 8 weeks, skin samples were taken from the exposed skin area. Histopathologically, the particles were only located in the stratum corneum layer of epidermis and follicular epithelium. Focal parakeratosis and spongiosis were observed in the epidermis. Transmission electron microscopy with energy-dispersive X-ray spectrometry (EDX) analysis failed to show TiO2 nanoparticles in the viable skin areas. There was no evidence of TiO2 penetration in the viable skin areas. In addition, titanium contents in several organs were determined using inductively coupled plasma mass spectroscopy. Increased titanium concentration was detected in lung samples of the TiO2 emulsion-treated groups after 8 weeks. It was most likely that the presence of TiO2 in the lungs was not caused by direct absorption of nanoparticles from the skin but was due to rats inhaling the nanoparticle. We did not find any obvious evidences of nano-TiO2 particle skin penetration using several morphological methods after the subchronic exposure. We believe that the influence of subchronic exposure of TiO2 is not significant based on our study. PMID:23528214

  6. [Transthyretin-binding activity of hexabromocyclododecanes (HBCDs) and its thyroid hormone disrupting effects after developmental exposure].

    PubMed

    Ji, Xiu-Ling; Liu, Yang; Liu, Fang; Lu, Yue; Zhong, Gao-Ren

    2010-09-01

    In vivo and in vitro research approaches were carried out to survey the potential health risk of environmental exposure by hexabromocyclododecanes (HBCDs). Transthyretin-binding assay was designed to test for the potency of HBCDs to compete with thyroxine (T4) for binding to the transport protein. The results showed that the binding of 25I-T4 and T4 was only slightly inhabited even at the highest competitive concentration of HBCDs (75.08%, 80 micromol x L(-1)), indicating the marginally interfere potency of HBCDs in the transportation of T4. Sprague-Dawley rats of 3-days old were exposed to 0.2 mg/kg and 1 mg/kg HBCDs for 21 d to examine the thyroid hormones (THs) disrupting effects of HBCDs after developmental exposure. Compared with the controls, levels of total 3,3',5-triiodothyronine (TT3), free 3,3',5-triiodothyronine (FT3), increased significantly (p < 0.05, p < 0.05) in low- and high-dose exposures, thyroid stimulating hormone (TSH) also increased slightly while the total thyroxine (TT4), free thyroxine (FT4) had a decline about two-fold inversely. Combined both the in vivo and in vitro results, the possible mode of action of HBCDs on THs disruption may through the synergy or substitution effect of T3. The findings support further investigation of the potential THs disrupting effects of HBCDs on public health, especially on children during brain development. PMID:21072945

  7. Lack of reliability in the disruption of cognitive performance following exposure to protons.

    PubMed

    Rabin, Bernard M; Heroux, Nicholas A; Shukitt-Hale, Barbara; Carrihill-Knoll, Kirsty L; Beck, Zachary; Baxter, Chelsea

    2015-08-01

    A series of three replications were run to determine the reliability with which exposure to protons produces a disruption of cognitive performance, using a novel object recognition task and operant responding on an ascending fixed-ratio task. For the first two replications, rats were exposed to head-only exposures to 1000 MeV/n protons at the NASA Space Radiation Laboratory. For the third replication, subjects were given head-only or whole-body exposures to both 1000 and 150 MeV/n protons. The results were characterized by a lack of consistency in the effects of exposure to protons on the performance of these cognitive tasks, both within and between replications. The factors that might influence the lack of consistency and the implications for exploratory class missions are discussed. PMID:25935209

  8. Nanoparticle exposure at nanotechnology workplaces: A review

    PubMed Central

    2011-01-01

    Risk, associated with nanomaterial use, is determined by exposure and hazard potential of these materials. Both topics cannot be evaluated absolutely independently. Realistic dose concentrations should be tested based on stringent exposure assessments for the corresponding nanomaterial taking into account also the environmental and product matrix. This review focuses on current available information from peer reviewed publications related to airborne nanomaterial exposure. Two approaches to derive realistic exposure values are differentiated and independently presented; those based on workplace measurements and the others based on simulations in laboratories. An assessment of the current available workplace measurement data using a matrix, which is related to nanomaterials and work processes, shows, that data are available on the likelihood of release and possible exposure. Laboratory studies are seen as an important complementary source of information on particle release processes and hence for possible exposure. In both cases, whether workplace measurements or laboratories studies, the issue of background particles is a major problem. From this review, major areas for future activities and focal points are identified. PMID:21794132

  9. Airline Pilot Cosmic Radiation and Circadian Disruption Exposure Assessment from Logbooks and Company Records

    PubMed Central

    Grajewski, Barbara; Waters, Martha A.; Yong, Lee C.; Tseng, Chih-Yu; Zivkovich, Zachary; Cassinelli II, Rick T.

    2011-01-01

    Objectives: US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots. Methods: Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments’ block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty. Results: Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (Ptrend < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman’s r = 0.61–0.69). Conclusions: The methods

  10. Effective biological dose from occupational exposure during nanoparticle synthesis

    NASA Astrophysics Data System (ADS)

    Demou, Evangelia; Tran, Lang; Housiadas, Christos

    2009-02-01

    Nanomaterial and nanotechnology safety require the characterization of occupational exposure levels for completing a risk assessment. However, equally important is the estimation of the effective internal dose via lung deposition, transport and clearance mechanisms. An integrated source-to-biological dose assessment study is presented using real monitoring data collected during nanoparticle synthesis. Experimental monitoring data of airborne exposure levels during nanoparticle synthesis of CaSO4 and BiPO4 nanoparticles in a research laboratory is coupled with a human lung transport and deposition model, which solves in an Eulerian framework the general dynamic equation for polydisperse aerosols using particle specific physical-chemical properties. Subsequently, the lung deposition model is coupled with a mathematical particle clearance model providing the effective biological dose as well as the time course of the biological dose build-up after exposure. The results for the example of BiPO4 demonstrate that even short exposures throughout the day can lead to particle doses of 1.10·E+08#/(kg-bw·8h-shift), with the majority accumulating in the pulmonary region. Clearance of particles is slow and is not completed within a working shift following a 1 hour exposure. It mostly occurs via macrophage activity in the alveolar region, with small amounts transported to the interstitium and less to the lymph nodes.

  11. Hydrogen emission under laser exposure of colloidal solutions of nanoparticles

    NASA Astrophysics Data System (ADS)

    Barmina, E. V.; Simakin, A. V.; Shafeev, G. A.

    2016-07-01

    We report the generation of molecular hydrogen from water by laser irradiation, without any electrodes and photocatalysts. A near infrared pulsed nanosecond laser is used for exposure of colloidal solution of Au nanoparticles suspended in water. Laser exposure of the colloidal solution results in formation of breakdown plasma in liquid and emission of H2. The rate of H2 emission depends critically on the energy of laser pulses. There is a certain threshold in laser fluence in liquid (around 50 J/cm2) below which plasma disappears and H2 emission stops. H2 emission from colloidal solution of Au nanoparticles in ethanol is higher than that from similar water colloid. It is found that formation of plasma and emission of H2 or D2 can be induced by laser exposure of pure liquids, either H2O or D2O, respectively. The results are interpreted as water molecules splitting by direct electron impact from breakdown plasma.

  12. Nanoparticle Delivered Vascular Disrupting Agents (VDAs): Use of TNF-alpha conjugated Gold Nanoparticles for Multimodal Cancer Therapy

    PubMed Central

    Shenoi, Mithun M.; Iltis, Isabelle; Choi, Jeunghwan; Koonce, Nathan A.; Metzger, Gregory J.; Griffin, Robert J.; Bischof, John C.

    2013-01-01

    Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors. Unfortunately, there is still an unmet need for VDAs with more favorable safety profiles and fewer side effects. Recent work has demonstrated that conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor necrosis factor alpha, TNF-α). In this report, we show the potential of a gold conjugated TNF-α nanoparticle (NP-TNF) to improve multimodal cancer therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of prostate cancer, we found that NP-TNF disrupts endothelial barrier function and induces a significant increase in vascular permeability within the first 1–2 hours followed by a dramatic 80% drop in perfusion 2–6 hours after systemic administration. We also demonstrate that the tumor response to the nanoparticle can be verified using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in clinical use. Additionally, multimodal treatment with thermal therapies at the perfusion nadir in the sub- and supra- physiological temperature regimes increases tumor volumetric destruction by over 60% and leads to significant tumor growth delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance thermal therapy in the absence of neutrophil recruitment, suggesting that immune/inflammatory regulation is not central to its power as part of a multimodal approach. Our data demonstrate the potential of nanoparticle-conjugated VDAs to significantly improve cancer therapy by preconditioning tumor vasculature to a secondary insult

  13. Exposure to endocrine disrupting compounds via the food chain: Is packaging a relevant source?

    PubMed

    Muncke, Jane

    2009-08-01

    Contamination of foodstuffs by environmental pollutants (e.g. dioxins, metals) receives much attention. Until recently, food packaging as a source of xenobiotics, especially those with endocrine disrupting properties, has received little awareness despite its ubiquitous use. This article reviews the regulations and use of endocrine disrupting compounds (EDCs) in food packaging and discusses their presence within the context of new toxicology paradigms. I focused on substances known to be legally used in food packaging that have been shown to exhibit endocrine disruptive effects in biological systems. I compiled a list of 50 known or potential EDCs used in food contact materials and examined data of EDCs leaching from packaging into food, with a focus on nonylphenol. I included recent advances in toxicology: mixture effects, the developmental origins of adult disease hypothesis, low-dose effects, and epigenetics. I especially considered the case of bisphenol A. The core hypothesis of this review is that chemicals leaching from packaging into food contribute to human EDCs exposure and might lead to chronic disease in light of the current knowledge. Food contact materials are a major source of food contaminants. Many migrating compounds, possibly with endocrine disruptive properties, remain unidentified. There is a need for information on identity/quantity of chemicals leaching into food, human exposure, and long-term impact on health. Especially EDCs in food packaging are of concern. Even at low concentrations, chronic exposure to EDCs is toxicologically relevant. Concerns increase when humans are exposed to mixtures of similar acting EDCs and/or during sensitive windows of development. In particular, non-intentionally added substances (NIAS) migrating from food contact materials need toxicological characterization; the overall migrate of the finished packaging could be evaluated for biological effects using bioassays. The widespread legal use of EDCs in food

  14. Thyroid endocrine disruption in zebrafish larvae following exposure to hexaconazole and tebuconazole.

    PubMed

    Yu, Liang; Chen, Mengli; Liu, Yihua; Gui, Wenjun; Zhu, Guonian

    2013-08-15

    The widely used triazole fungicides have the potential to disrupt endocrine system, but little is known of such effects or underlying mechanisms of hexaconazole (HEX) and tebuconazole (TEB) in fish. In the present study, zebrafish (Danio rerio) embryos were exposed to various concentrations of HEX (0.625, 1.25 and 2.5 mg/L) and TEB (1, 2 and 4 mg/L) from fertilization to 120 h post-fertilization (hpf). The whole body content of thyroid hormone and transcription of genes in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. The results showed that thyroxine (T4) levels were significantly decreased, while triiodothyronine (T3) concentrations were significantly increased after exposure to HEX and TEB, indicating thyroid endocrine disruption. Exposure to HEX significantly induced the transcription of all the measured genes (i.e., corticotrophin-releasing hormone (CRH), thyroid-stimulating hormone (TSHβ), sodium/iodide symporter (NIS), transthyretin (TTR), uridine diphosphate glucuronosyltransferase (UGT1ab), thyronine deiodinase (Dio1 and Dio2), thyroid hormone receptors (TRα and TRβ) in the HPT axis, but did not affect the transcription of thyroglobulin (TG). However, TEB exposure resulted in the upregulation of all the measured genes, excepting that TG, Dio1and TRα had not changed significantly. The overall results indicated that exposure to HEX and TEB could alter thyroid hormone levels as well as gene transcription in the HPT axis in zebrafish larvae. PMID:23685399

  15. Assessing Human Health Risk to Endocrine Disrupting Chemicals: a Focus on Prenatal Exposures and Oxidative Stress

    PubMed Central

    Neier, Kari; Marchlewicz, Elizabeth H.; Dolinoy, Dana C.; Padmanabhan, Vasantha

    2016-01-01

    Understanding the health risk posed by endocrine disrupting chemicals (EDCs) is a challenge that is receiving intense attention. The following study criteria should be considered to facilitate risk assessment for exposure to EDCs: 1) characterization of target health outcomes and their mediators, 2) study of exposures in the context of critical periods of development, 3) accurate estimates of human exposures and use of human-relevant exposures in animal studies, and 4) cross-species comparisons. In this commentary, we discuss the importance and relevance of each of these criteria in studying the effects of prenatal exposure to EDCs. Our discussion focuses on oxidative stress as a mediator of EDC-related health effects due to its association with both EDC exposure and health outcomes. Our recent study (Veiga-Lopez et al. 2015)1 addressed each of the four outlined criteria and demonstrated that prenatal bisphenol-A exposure is associated with oxidative stress, a risk factor for developing diabetes and cardiovascular diseases in adulthood. PMID:27231701

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

    PubMed

    Zhai, Wenhui; Huang, Zhigang; Chen, Li; Feng, Cong; Li, Bei; Li, Tanshi

    2014-01-01

    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. PMID:24658602

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Endocrine disruption and ovarian morphometric responses in rats following exposure to tetradifon.

    PubMed

    Badraoui, Riadh; Abdelmoula, Nouha B; Feki, Nozha; Ben Nasr, Hmed; Rebai, Tarek

    2010-04-01

    We have investigated whether exposure to tetradifon causes ovary injuries, disrupts folliculogenesis in rat and whether ovary hormones (estrogen and progesterone) to be affected by this endocrine-active agent. Female rats were exposed orally to a dose of 28.9 mg/kg/day for 6 or 12 weeks. After sacrifice, ovary glands were examined for morphometric changes. The serums were used to determine levels of 17beta-estradiol and progesterone. Results showed no sign of toxicity. However, tetradifon promoted a significant increase in the percentage of atretic follicles in the 12-weeks treated rats. Number and the diameter of mature follicles (tertiary and preovulatory) were markedly diminished together with a reduction of the relative weight of ovaries. Compared with controls, the treated rats exhibited significant reduction in serum 17beta-estradiol and progesterone levels. These results suggest an endocrine disruption by tetradifon which may interfere with ovarian follicles development in rat. PMID:19800343

  19. Establishment of Airborne Nanoparticle Exposure Chamber System to Assess Nano TiO2 Induced Mice Lung Effects

    NASA Astrophysics Data System (ADS)

    Chen, Chia-Hua; Li, Jui-Ping; Huang, Nai-Chun; Yang, Chung-Shi; Chen, Jen-Kun

    2011-12-01

    A great many governments have schemed their top priority to support the research and development of emerging nanotechnology, which lead to increasing products containing nanomaterials. However, platforms and protocols to evaluate the safety of nanomaterials are not yet established. We therefore design and fabricate a nanoparticle exposure chamber system (NECS) and try to standardize protocols to assess potential health risk of inhalable nanoparticles. This platform comprises: (1) nano-aerosol generators to produce homogeneous airborne nanoparticles, (2) double isolated container to prevent from unexpected exposure to humans, (3) gas supply system for housing animals or incubating cultured cells, and (4) system for automatic control and airborne nanoparticle analysis. The NECS providing multiple functions includes: (1) a secure environment to handle nanomaterials, (2) real-time measurement for the size and distribution of airborne nanoparticles, (3) SOP of safety evaluation for nanomaterials, and (4) key technology for the development of inhalable pharmaceuticals. We used NECS to mimic occupational environment for exploring potential adverse effects of TiO2 nanoparticles. The adult male ICR mice were exposed to 25nm, well-characterized TiO2 particles for 1 and 4 weeks. More than 90% of the inhaled TiO2 nanoparticles deposit in lung tissue, which tends to be captured by alveolar macrophages. Pulmonary function test does not show significant physiological changes between one and 4 weeks exposure. For plasma biochemistry analysis, there are no obvious inflammation responses after exposure for one and 4 weeks; however, disruption of alveolar septa and increased thickness of alveolar epithelial cells were observed. According to our results, the NECS together with our protocols show comprehensive integration and ideally fit the standard of OECD guildelines-TG403, TG412, TG413; it can be further customized to fulfill diverse demands of industry, government, and third party

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

    SciTech Connect

    Sadikovic, Bekim; Rodenhiser, David I. . E-mail: drodenhi@uwo.ca

    2006-11-01

    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-{alpha}. 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.

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

    PubMed

    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. PMID:24287426

  2. Microcystin-RR exposure results in growth impairment by disrupting thyroid endocrine in zebrafish larvae.

    PubMed

    Xie, Liqiang; Yan, Wei; Li, Jing; Yu, Liqin; Wang, Jianghua; Li, Guangyu; Chen, Nan; Steinman, Alan D

    2015-07-01

    Recent studies have shown that cyanobacteria-derived microcystins (MCs) have the potential to disrupt endocrine systems. However, the effects of microcystin-RR (MC-RR) and their underlying mechanisms are poorly resolved in fish. In this study, MC-RR exposure through submersion caused serious developmental toxicity, such as growth delay and depressed heart rates in zebrafish larvae. We also detected decreased levels of thyroid hormones (THs), suggesting that MC-RR-triggered thyroid endocrine disruption might contribute to the growth impairment observed in developing zebrafish. To further our understanding of mechanisms of MC-RR-induced endocrine toxicity, quantitative real-time PCR (QPCR) analysis was performed on hypothalamic-pituitary-thyroid (HPT) axis related genes, i.e., corticotropin-releasing factor (CRF), thyroid-stimulating hormone (TSH), sodium/iodide symporter (NIS), thyroglobulin (TG), thyroid receptors (TRα and TRβ) and iodothyronine deiodinases (Dio1 and Dio2), of developing zebrafish embryos exposed to 0, 0.3, 1.0 or 3.0mgL(-1) MC-RR until 96h post-fertilization. Our results showed that transcription pattern of HPT axis related genes were greatly changed by MC-RR exposure, except TG gene. Furthermore, western blot was used to validate the results of gene expression. The results showed protein synthesis of TG was not affected, while that of NIS was significantly up-regulated, which are in accordance with gene expression. The overall results indicated that exposure to MC-RR can induce developmental toxicity, which might be associated with thyroid endocrine disruption in developing zebrafish larvae. PMID:25897773

  3. Disruption of adult expression of sexually selected traits by developmental exposure to bisphenol A.

    PubMed

    Jašarević, Eldin; Sieli, Paizlee T; Twellman, Erin E; Welsh, Thomas H; Schachtman, Todd R; Roberts, R Michael; Geary, David C; Rosenfeld, Cheryl S

    2011-07-12

    Exposure to endocrine disrupting compounds (EDCs), such as bisphenol A (BPA), may cause adverse health effects in wildlife and humans, but controversy remains as to what traits are most sensitive to EDCs and might serve as barometers of exposure. Expression of sexually selected traits that have evolved through intrasexual competition for mates and intersexual choice of mating partner are more dependent on developmental and physical condition of an animal than naturally selected traits and thus might be particularly vulnerable to disruption by developmental exposure to EDCs. We have used the deer mouse (Peromyscus maniculatus) as a model to test this hypothesis. Adult male-male competition for mates in this species is supported by enhanced spatial navigational and exploratory abilities, which enable males to search for prospective, widely dispersed females. Male deer mice exposed to BPA or ethinyl estradiol (EE) through maternal diet showed no changes in external phenotype, sensory development, or adult circulating concentrations of testosterone and corticosterone, but spatial learning abilities and exploratory behaviors were severely compromised compared with control males. Because these traits are not sexually selected in females, BPA exposure predictably had no effect, although EE-exposed females demonstrated enhanced spatial navigational abilities. Both BPA-exposed and control females preferred control males to BPA-exposed males. Our demonstration that developmental exposure to BPA compromises cognitive abilities and behaviors essential for males to reproduce successfully has broad implications for other species, including our own. Thus, sexually selected traits might provide useful biomarkers to assess risk of environmental contamination in animal and human populations. PMID:21709224

  4. Metformin Exposure at Environmentally Relevant Concentrations Causes Potential Endocrine Disruption in Adult Male Fish

    PubMed Central

    Niemuth, Nicholas J; Jordan, Renee; Crago, Jordan; Blanksma, Chad; Johnson, Rodney; Klaper, Rebecca D

    2015-01-01

    Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste, resulting in discharge into surface waters by wastewater treatment plant (WWTP) effluent. One pharmaceutical found in particularly high abundance in recent WWTP effluent and surface water studies is metformin, one of the world's most widely prescribed antidiabetic drugs. Interactions between insulin signaling and steroidogenesis suggest potential endocrine-disrupting effects of metformin found in the aquatic environment. Adult fathead minnows (Pimephales promelas) were chronically exposed to metformin for 4 wk, at 40 µg/L, a level similar to the average found in WWTP effluent in Milwaukee, Wisconsin, USA. Genetic endpoints related to metabolism and endocrine function as well as reproduction-related endpoints were examined. Metformin treatment induced significant up-regulation of messenger ribonucleic acid (mRNA) encoding the egg-protein vitellogenin in male fish, an indication of endocrine disruption. The present study, the first to study the effects of environmentally relevant metformin exposure in fathead minnows, demonstrates the need for further study of the endocrine-disrupting effects of metformin in aquatic organisms. Environ Toxicol Chem 2014;9999:1–6. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of SETAC. PMID:25358780

  5. Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish.

    PubMed

    Niemuth, Nicholas J; Jordan, Renee; Crago, Jordan; Blanksma, Chad; Johnson, Rodney; Klaper, Rebecca D

    2015-02-01

    Pharmaceuticals and personal care products (PPCPs) are emerging contaminants that have been found ubiquitously in wastewater and surface waters around the world. A major source of these compounds is incomplete metabolism in humans and subsequent excretion in human waste, resulting in discharge into surface waters by wastewater treatment plant (WWTP) effluent. One pharmaceutical found in particularly high abundance in recent WWTP effluent and surface water studies is metformin, one of the world's most widely prescribed antidiabetic drugs. Interactions between insulin signaling and steroidogenesis suggest potential endocrine-disrupting effects of metformin found in the aquatic environment. Adult fathead minnows (Pimephales promelas) were chronically exposed to metformin for 4 wk, at 40 µg/L, a level similar to the average found in WWTP effluent in Milwaukee, Wisconsin, USA. Genetic endpoints related to metabolism and endocrine function as well as reproduction-related endpoints were examined. Metformin treatment induced significant up-regulation of messenger ribonucleic acid (mRNA) encoding the egg-protein vitellogenin in male fish, an indication of endocrine disruption. The present study, the first to study the effects of environmentally relevant metformin exposure in fathead minnows, demonstrates the need for further study of the endocrine-disrupting effects of metformin in aquatic organisms. PMID:25358780

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

    PubMed Central

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-01-01

    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. PMID:26501309

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

    PubMed

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-10-01

    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. PMID:26501309

  8. Developmental exposure to endocrine disrupting chemicals alters the epigenome: Identification of reprogrammed targets

    PubMed Central

    Prusinski, Lauren; Al-Hendy, Ayman; Yang, Qiwei

    2016-01-01

    Endocrine disruptions induced by environmental toxicants have placed an immense burden on society to properly diagnose, treat and attempt to alleviate symptoms and disease. Environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life - a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical and cellular events. Humans may encounter endocrine disrupting chemicals (EDCs) daily and during all stages of life, from conception and fetal development through adulthood and senescence. Though puberty and perimenopausal periods may be affected by endocrine disruption due to hormonal effects, prenatal and early postnatal windows are most critical for proper development due to rapid changes in system growth. Developmental reprogramming is shown to be caused by alterations in the epigenome. Development is the time when epigenetic programs are ‘installed’ on the genome by ‘writers’, such as histone methyltransferases (HMTs) and DNA methyltransferases (DNMTs), which add methyl groups to lysine and arginine residues on histone tails and to CpG sites in DNA, respectively. A number of environmental compounds, referred to as estrogenic endocrine disruptors (EEDs), are able to bind to estrogen receptors (ERs) and interfere with the normal cellular development in target tissues including the prostate and uterus. These EEDs, including diethylstilbestrol (DES), bisphenol A (BPA), and genistein (a phytoestrogen derived from soybeans), have been implicated in the malformation of reproductive organs and later development of disease. Due to the lack of fully understanding the underlying mechanisms of how environmental toxicants and their level of exposure affect the human genome, it can be challenging to create clear

  9. Nickel oxide nanoparticle-based method for simultaneous harvesting and disruption of microalgal cells.

    PubMed

    Huang, Wen-Can; Kim, Jong-Duk

    2016-10-01

    Microalgae biodiesel is considered one of the most promising renewable fuels. However, the high cost of the downstream process is a major barrier to large-scale microalgal lipid production. In this study, a novel approach based on nickel oxide nanoparticles (NiO NPs) was developed and its effectiveness for simultaneous harvesting and cell disruption in microalgal lipid production was determined. NiO NPs exhibited a microalgal harvesting efficiency of 98.75% in 1min at pH 7. Moreover, after treating with NiO NPs for 96h, the lipid extraction efficiency of microalgae (with 80% water content) reached 91.08% and was 208.37% compared to that without NiO treatment. This approach is simple and does not necessitate drying; furthermore, no equipment with high energy consumption was required. PMID:27481468

  10. TRANSGENERATIONAL (IN UTERO/LACTATIONAL) EXPOSURE PROTOCOL TO INVESTIGATE THE EFFECTS OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) IN RATS

    EPA Science Inventory

    This protocol is designed to evaluate the effects of Endocrine Disrupting Compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups...

  11. In utero exposure to the oestrogen mimic diethylstilbestrol disrupts gonadal development in a viviparous reptile.

    PubMed

    Parsley, Laura M; Wapstra, Erik; Jones, Susan M

    2015-09-01

    The ubiquitous presence of endocrine-disrupting chemicals (EDCs) in the environment is of major concern. Studies on oviparous reptiles have significantly advanced knowledge in this field; however, 30% of reptilian species are viviparous (live-bearing), a parity mode in which both yolk and a placenta support embryonic development, thus exposure to EDCs may occur via multiple routes. In this first study of endocrine disruption in a viviparous lizard (Niveoscincus metallicus), we aimed to identify effects of the oestrogen mimic diethylstilbestrol (DES) on gonadal development. At the initiation of sexual differentiation, pregnant N. metallicus were treated with a single dose of DES at 100 or 10µgkg(--1), a vehicle solvent or received no treatment. There was no dose-response effect, but the testes of male neonates born to DES-exposed mothers showed reduced organisation of seminiferous tubules and a lack of germ cells compared with those from control groups. The ovaries of female neonates born to DES-exposed mothers exhibited phenotypic abnormalities of ovarian structure, oocytes and follicles compared with controls. The results indicate that, in viviparous lizards, maternal exposure to oestrogenic EDCs during gestation may have profound consequences for offspring reproductive fitness. PMID:24718097

  12. Oral Gingival Cell Cigarette Smoke Exposure Induces Muscle Cell Metabolic Disruption

    PubMed Central

    Baeder, Andrea C.; Napa, Kiran; Richardson, Sarah T.; Taylor, Oliver J.; Andersen, Samantha G.; Wilcox, Shalene H.; Winden, Duane R.; Reynolds, Paul R.

    2016-01-01

    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. PMID:27034671

  13. Prenatal valproic acid exposure disrupts tonotopic c-Fos expression in the rat brainstem.

    PubMed

    Dubiel, A; Kulesza, R J

    2015-12-17

    Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interactions, restricted, repetitive behaviors and sensory abnormalities. Additionally, the vast majority of subjects with ASD suffer some degree of auditory dysfunction and we have previously identified significant hypoplasia and dysmorphology in auditory brainstem centers in individuals with ASD. Prenatal exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of ASD. In rodents, prenatal exposure to VPA is utilized as an animal model of ASD and is associated with a number of anatomical, physiological and behavioral deficits, including hypoplasia and dysmorphology in the auditory brainstem. Based on these observations, we hypothesized that such dysmorphology in VPA-exposed animals would translate into abnormal activity in brainstem circuits and irregular tonotopic maps. Herein, we have subjected control and VPA-exposed animals to 4 or 16 kHz tones and examined neuronal activation with immunohistochemistry for c-Fos. After these sound exposures, we found significantly more c-Fos-positive neurons in the auditory brainstem of VPA-exposed animals. Further, we found a larger dispersion of c-Fos-positive neurons and shifted tonotopic bands in VPA-exposed rats. We interpret these findings to suggest hyper-responsiveness to sounds and disrupted mapping of sound frequencies after prenatal VPA exposure. Based on these findings, we suggest that such abnormal patterns of activation may play a role in auditory processing deficits in ASD. PMID:26518464

  14. Prenatal valproic acid exposure disrupts tonotopic c-Fos expression in the rat brainstem.

    PubMed

    Dubiel, A; Kulesza, R J

    2016-06-01

    Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions characterized by difficulties in communication and social interactions, restricted, repetitive behaviors and sensory abnormalities. Notably, the vast majority of individuals with ASD experience some degree of auditory dysfunction and we have recently reported consistent hypoplasia and dysmorphology in auditory brainstem centers in individuals with ASD. Prenatal exposure to the antiepileptic drug valproic acid (VPA) is associated with an increased risk of ASD. In rodents, prenatal exposure to VPA is employed as an animal model of ASD and is associated with a number of anatomical, physiological and behavioral deficits, including hypoplasia and dysmorphology of auditory brainstem centers. Based on these observations, we hypothesized that such dysmorphology in VPA-exposed animals would translate into abnormal neuronal activity in brainstem circuits and irregular tonotopic maps. Herein, we have subjected control and VPA-exposed animals to 4- or 16-kHz tones and examined neuronal activation with immunohistochemistry for c-Fos. After these exposures, we identified significantly more c-Fos-positive neurons in the auditory brainstem of VPA-exposed animals. Additionally, we observed a larger dispersion of c-Fos-positive neurons and shifted tonotopic bands in VPA-exposed rats. We interpret these findings to suggest hyper-responsiveness to sounds and disrupted mapping of sound frequencies after prenatal VPA exposure. Based on these findings, we suggest that such abnormal patterns of activation may play a role in auditory processing deficits in ASD. PMID:27094734

  15. Exposure to Bisphenol AF disrupts sex hormone levels and vitellogenin expression in zebrafish.

    PubMed

    Yang, Xiaoxi; Liu, Yuchen; Li, Jia; Chen, Minjie; Peng, Di; Liang, Yong; Song, Maoyong; Zhang, Jie; Jiang, Guibin

    2016-03-01

    Bisphenol AF (BPAF) is widely used in food-contact products, electronic devices, and as a cross-linking reagent in fluoroelastomers. There are growing concerns about its toxicity and endocrine-disrupting effects based on its structural similarity with bisphenol A (BPA). The endocrine-disrupting effects of BPAF were studied by exposing 2-month-old zebrafish to 0, 0.05, 0.25, or 1 mg/L BPAF for 28 days and evaluating the effect on growth, histopathology, hormone levels, enzyme activity, and gene expression. The overall fitness was not significantly affected. There were no apparent alterations in the gills and intestine tissues of both sexes after BPAF exposure. However, exposure to 1 mg/L BPAF caused damage to the liver in the male fish, characterized by hepatocellular swelling and vacuolation. There was no obvious effect in the liver of female fish, suggesting that the hepatic toxicity of BPAF is gender dependent. Gonadal examination indicated that exposure to 1 mg/L BPAF caused induction of acellular areas in the testis and retardation of oocyte development in the ovary. BPAF exposure increased free triiodothyronine levels of females in a dose-dependent manner. In males, the testosterone levels decreased in a concentration-dependent manner. In contrast, estradiol levels increased in a concentration-dependent manner and were significantly higher in males exposed to 1 mg/L BPAF compared with the controls. In females, 0.05 and 0.25 mg/L BPAF caused an increase in testosterone levels. Furthermore, the estradiol levels increased in females exposed to 0.05 and 1 mg/L. We observed an upregulation of hepatic vitellogenin in both sexes and significantly higher levels in males exposed to 1 mg/L BPAF and females exposed to 0.25 mg/L BPAF, suggesting that BPAF has an estrogenic activity. Our results indicate that BPAF is an endocrine-disrupting chemical that exerts reproductive toxicity and estrogenic effects on zebrafish. PMID:25213402

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

    PubMed

    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. PMID:27343465

  17. Retinal photoreceptor focal disruption secondary to accidental Nd:YAG laser exposure.

    PubMed

    Milani, Paolo; Pierro, Luisa; Pece, Alfredo; Marino, Valerio; Scialdone, Antonio

    2011-10-01

    Retinal injuries caused by accidental laser exposure include retinal or vitreous hemorrhages, macular holes and edema. We describe the imaging of a bilateral macular lesion secondary to accidental Nd:YAG laser exposure. Observational case report. We performed color photography, fluorescein angiography and autofluorescence (AF) with a scanning laser ophthalmoscope, as well as time-domain and spectral-domain optical coherence tomography (OCT). After accidental exposure to a 1064 nm Nd:YAG laser, a patient experienced blurred vision in the left eye (LE) with visual acuity of 20/60. Color, fluorescein angiography and OCT imaging showed a retinal hemorrhage in the foveal area of the left eye and in the inferomacular region of the asymptomatic right eye. Steroid therapy was then administered, and 5 days later there was rapid improvement with progressive re-absorption of the hemorrhages and functional recovery. At 6 month follow-up, visual acuity was 20/20 in both eyes with unremarkable biomicroscopy, except for focal foveal retinal pigment epithelium (RPE) atrophy in the LE. In comparison to previous hemorrhages, OCT could visualize focal disruption of the photoreceptor IS/OS junction in both eyes. Due to different macular pigment distribution and lesion localization, 787 nm near-infrared AF depicted a small hypofluorescent spot in both eyes, whilst at 488 nm AF a black spot became evident in the right eye only. Despite the re-absorption of foveal hemorrhage and the functional recovery, AF and OCT imaging highlighted the persistence of small focal disruptions of the photoreceptor outer segments and RPE. PMID:22002418

  18. Morphological responses of Legionella pneumophila biofilm to nanoparticle exposure.

    PubMed

    Stojak, Amber R; Raftery, Tara; Klaine, Stephen J; McNealy, Tamara L

    2011-12-01

    Legionella pneumophila is a pathogenic bacterium that forms biofilms in natural and anthropogenic habitats. This feature not only facilitates colonization but also limits the effectiveness of biocides. L. pneumophila was exposed to three sizes of citrate-capped gold nanospheres in both planktonic and biofilm stages. TEM micrographs indicated that gold nanoparticles (AuNPs) adsorbed to the bacterial cell surface, were absorbed into the cells, aggregated within the cells, and integrated into the extrapolymeric matrix of the biofilm. Both 4 and 18 nm, but not 50 nm AuNPs caused an alteration of biofilm morphology. Treatment with 20 nm polystyrene spheres did not induce these changes suggesting that the response was a result of the gold and not just the presence of the nanosphere. The morphological changes observed in the biofilm suggest that aquatic ecosystems may be affected by nanoparticle exposure. This may compromise ecosystem functions such as nutrient cycling facilitated by natural biofilms. PMID:21294606

  19. Obesity, Diabetes, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

    PubMed Central

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

    2015-01-01

    Context: 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. Objective: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. Design: 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. Results: 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

  20. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota

    PubMed Central

    2014-01-01

    Background The microbiota of the mammalian gastrointestinal (GI) tract consists of diverse populations of commensal bacteria that interact with host physiological function. Dysregulating these populations, through exogenous means such as antibiotics or dietary changes, can have adverse consequences on the health of the host. Studies from laboratories such as ours have demonstrated that exposure to psychological stressors disrupts the population profile of intestinal microbiota. To date, such studies have primarily focused on prolonged stressors (repeated across several days) and have assessed fecal bacterial populations. It is not known whether shorter stressors can also impact the microbiota, and whether colonic mucosa-associated populations can also be affected. The mucosa-associated microbiota exist in close proximity to elements of the host immune system and the two are tightly interrelated. Therefore, alterations in these populations should be emphasized. Additionally, stressors can induce differential responses in anxiety-like behavior and corticosterone outputs in variant strains of mice. Thus, whether stressor exposure can have contrasting effects on the colonic microbiota in inbred C57BL/6 mice and outbred CD-1 mice was also examined. Results In the present study, we used high throughput pyrosequencing to assess the effects of a single 2-hour exposure to a social stressor, called social disruption (SDR), on colonic mucosa-associated microbial profiles of C57BL/6 mice. The data indicate that exposure to the stressor significantly changed the community profile and significantly reduced the relative proportions of two genera and one family of highly abundant intestinal bacteria, including the genus Lactobacillus. This finding was confirmed using a quantitative real-time polymerase chain reaction (qPCR) technique. The use of qPCR also identified mouse strain-specific differences in bacterial abundances. L. reuteri, an immunomodulatory species, was decreased in

  1. Modeling Population Exposures to Silver Nanoparticles Present in Consumer Products

    PubMed Central

    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.

    2014-01-01

    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 employs 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. PMID:25745354

  2. Thalamocortical functional connectivity and behavioral disruptions in neonates with prenatal cocaine exposure.

    PubMed

    Salzwedel, Andrew P; Grewen, Karen M; Goldman, Barbara D; Gao, Wei

    2016-01-01

    Prenatal cocaine exposure (PCE) affects neurobehavioral development, however, disentangling direct drug-related mechanisms from contextual effects (e.g., socioeconomic status) has proven challenging in humans. The effects of environmental confounds are minimal immediately after birth thus we aimed to delineate neurobehavioral correlates of PCE in a large cohort of neonates (2-6weeks of age, N=152) with and without drug exposure using resting state functional magnetic resonance imaging (rsfMRI) and developmental assessments at 3months with the Bayley Scales of Infant & Toddler Development, 3rd edition. The cohort included healthy controls and neonates with similar poly-drug exposure±cocaine. We focused on the thalamus given its critical importance in early brain development and its unique positioning in the dopamine system. Our results revealed PCE-related hyper-connectivity between the thalamus and frontal regions and a drug-common hypo-connective signature between the thalamus and motor-related regions. PCE-specific neonatal thalamo-frontal connectivity was inversely related to cognitive and fine motor scores and thalamo-motor connectivity showed a positive relationship with composite (gross plus fine) motor scores. Finally, cocaine by selective-serotonin-reuptake-inhibitor (SSRI) interactions were detected, suggesting the combined use of these drugs during pregnancy could have additional consequences on fetal development. Overall, our findings provide the first delineation of PCE-related disruptions of thalamocortical functional connectivity, neurobehavioral correlations, and drug-drug interactions during infancy. PMID:27242332

  3. In Vitro Manganese Exposure Disrupts MAPK Signaling Pathways in Striatal and Hippocampal Slices from Immature Rats

    PubMed Central

    Peres, Tanara Vieira; Pedro, Daniela Zótico; de Cordova, Fabiano Mendes; Lopes, Mark William; Gonçalves, Filipe Marques; Mendes-de-Aguiar, Cláudia Beatriz Nedel; Walz, Roger; Farina, Marcelo; Aschner, Michael; Leal, Rodrigo Bainy

    2013-01-01

    The molecular mechanisms mediating manganese (Mn)-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs) and tyrosine hydroxylase (TH) could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old). The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10–1,000 μM) caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK) 1/2, as well as c-Jun N-terminal kinase (JNK) 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3) in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain. PMID:24324973

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

    PubMed

    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 < .05), which was prevented by flutamide showing direct androgenic mediation. Gestational T also augmented maternal insulin levels and decreased medium chained acylcarnitines, suggesting increased mitochondrial fatty acid oxidation. These changes were prevented by rosiglitazone, suggesting alterations in maternal fuel use. Gestational T-induced increases in 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). PMID:25763641

  5. Developmental Programming: Exposure to Testosterone Excess Disrupts Steroidal and Metabolic Environment in Pregnant Sheep

    PubMed Central

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

    2015-01-01

    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 < .05), which was prevented by flutamide showing direct androgenic mediation. Gestational T also augmented maternal insulin levels and decreased medium chained acylcarnitines, suggesting increased mitochondrial fatty acid oxidation. These changes were prevented by rosiglitazone, suggesting alterations in maternal fuel use. Gestational T-induced increases in 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). PMID:25763641

  6. Exposure to airborne engineered nanoparticles in the indoor environment

    NASA Astrophysics Data System (ADS)

    Vance, Marina E.; Marr, Linsey C.

    2015-04-01

    This literature review assesses the current state of knowledge about inhalation exposure to airborne, engineered nanoparticles in the indoor environment. We present principal exposure scenarios in indoor environments, complemented by analysis of the published literature and of an inventory of nanotechnology-enhanced consumer products. Of all products listed in the inventory, 10.8% (194 products) present the potential for aerosolization of nanomaterials and subsequent inhalation exposure during use or misuse. Among those, silver-containing products are the most prevalent (68 products). Roughly 50% of products would release wet aerosols and 50% would potentially release dry aerosols. Approximately 14% are cleaning products that can be broadly used in public indoor environments, where building occupants may be exposed. While a variety of nanomaterial compositions have been investigated in the limited number of published release and exposure studies, we identified a need for studies investigating nanofibers (beyond carbon nanotubes), nanofilms, nanoplatelets, and other emerging nanomaterials such as ceria and their nanocomposites. Finally, we provide recommendations for future research to advance the understanding of exposure to airborne nanomaterials indoors, such as studies into indoor chemistry of nanomaterials, better nanomaterial reporting and labeling in consumer products, and safer design of nanomaterial-containing consumer products.

  7. Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males.

    PubMed

    Williams, Michael J; Wiemerslage, Lyle; Gohel, Priya; Kheder, Sania; Kothegala, Lakshmi V; Schiöth, Helgi B

    2016-06-01

    Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care products, as a result people are constantly exposed to these xenobiotics. Recent epidemiological studies have found a correlation between circulating phthalate levels and type 2 diabetes, whereas animal studies indicate that phthalates are capable of disrupting endocrine signaling. Nonetheless, how phthalates interfere with metabolic function is still unclear. Here, we show that feeding Drosophila males the xenobiotic dibutyl phthalate (DBP) affects conserved insulin- and glucagon-like signaling. We report that raising flies on food containing DBP leads to starvation resistance, increased lipid storage, hyperglycemia, and hyperphagia. We go on to show that the starvation-resistance phenotype can be rescued by overexpression of the glucagon analogue adipokinetic hormone (Akh). Furthermore, although acute DBP exposure in adult flies is able to affect insulin levels, only chronic feeding influences Akh expression. We establish that raising flies on DBP-containing food or feeding adults DBP food affects the expression of homologous genes involved in xenobiotic and lipid metabolism (AHR [Drosophila ss], NR1I2 [Hr96], ABCB1 [MDR50], ABCC3 [MRP], and CYP3A4 [Cyp9f2]). Finally, we determined that the expression of these genes is also influenced by Akh. Our results provide comprehensive evidence that DBP can disrupt metabolism in Drosophila males, by regulating genes involved in glucose, lipid, and xenobiotic metabolism. PMID:27100621

  8. Exposure to Exogenous Enkephalins Disrupts Reproductive Development in the Eastern Lubber Grasshopper, Romalea microptera (Insecta: Orthoptera)

    PubMed Central

    Kumar, Sandeep; Ganji, Purnachandra Nagaraju; Song, Hojun; von Kalm, Laurence; Borst, David W.

    2012-01-01

    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. PMID:23226477

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

    PubMed Central

    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.

    2015-01-01

    Context: 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 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. Results: 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. Conclusions: EDC exposures in the EU are likely to contribute substantially to disease and

  10. Waterborne exposure to triadimefon causes thyroid endocrine disruption and developmental delay in Xenopus laevis tadpoles.

    PubMed

    Li, Meng; Li, Shuying; Yao, Tingting; Zhao, Renjie; Wang, Qiangwei; Zhu, Guonian

    2016-08-01

    Triadimefon (TDF) is a triazole-derivative fungicide that is detectable in the environment and target agricultural products, prompting concern over its risk to wildlife and human health. In our study, Nieuwkoop & Faber stage 51 Xenopus laevis tadpoles were exposed to different nominal concentrations TDF (0, 0.112, and 1.12mg/L) for 21 days while the tadpoles were undergoing pre-morphological development. Developmental condition, bioaccumulation and thyroid hormone levels, and mRNA expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Exposure to TDF caused a reduction in developmental rates on pre-metamorphosis of X. laevis. TDF exposure significantly decreased thyroid hormone (T4 and T3) concentrations, indicating thyroid endocrine disruption. The downregulation of thyroglobulin and upregulation of genes related to thyroid hormone metabolism (ugt1ab) might be responsible for the decreased thyroid hormone concentrations. Treatment with TDF also significantly increased mRNA expression of genes involved in thyroid-stimulating hormone as a compensatory mechanism response to decreased thyroid hormone concentrations. Gene expression and in silico ligand docking studies were combined to study the interaction between TDF and thyroid hormone receptor. Results showed that TDF could consequently affect the HPT axis signaling pathway. In addition, bioconcentration of TDF was observed in tadpoles, indicating the bioactivity of this compound. Taken together, the results suggest that TDF alters the HPT axis-related genes and changes thyroid hormone contents in X. laevis tadpoles, thus causing thyroid endocrine disruption and consequently delaying thyroid hormones-dependent metamorphic development. PMID:27289584

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

    PubMed

    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. PMID:25979079

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25979079

  13. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    SciTech Connect

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

    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

  14. Interactions of Graphene Oxide with Model Cell Membranes: Probing Nanoparticle Attachment and Lipid Bilayer Disruption.

    PubMed

    Liu, Xitong; Chen, Kai Loon

    2015-11-10

    With the rapid growth in the application of graphene oxide (GO) in diverse fields, the toxicity of GO toward bacterial and mammalian cells has recently attracted extensive research attention. While several mechanisms have been proposed for the cytotoxicity of GO, the attachment of GO to cell membranes is expected to be the key initial process that precedes these mechanisms. In this study, we investigate the propensity for GO to attach to and disrupt model cell membranes using supported lipid bilayers (SLBs) and supported vesicular layers (SVLs) that are composed of zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The deposition kinetics of GO on SLBs were determined using quartz crystal microbalance with dissipation monitoring and were observed to increase with increasing electrolyte (NaCl and CaCl2) concentrations, indicating that GO attachment to SLBs was controlled by electrostatic interactions. The GO deposition kinetics measured at elevated electrolyte concentrations were lower than mass-transfer-limited kinetics, likely due to the presence of hydration forces between GO and SLBs. Upon the attachment of GO to supported vesicles that were encapsulated with a fluorescent dye, dye leakage was detected, thus indicating that the lipid vesicles were disrupted. When the exposure of the SVL to the GO suspension was terminated, the leakage of dye decreased significantly, demonstrating that the pores on the lipid bilayers have a self-healing ability. PMID:26466194

  15. Occupational exposure to nanoparticles at commercial photocopy centers.

    PubMed

    Martin, John; Bello, Dhimiter; Bunker, Kristin; Shafer, Martin; Christiani, David; Woskie, Susan; Demokritou, Philip

    2015-11-15

    Photocopiers emit high levels of nanoparticles (PM0.1). To-date little is known of physicochemical composition of PM0.1 in real workplace settings. Here we perform a comprehensive physicochemical and morphological characterization of PM0.1 and raw materials (toners and paper) at eight commercial photocopy centers that use color and monochrome photocopiers over the course of a full week. We document high PM0.1 exposures with complex composition and several ENM in toners and PM0.1. Daily geometric mean PM0.1 concentrations ranged from 3700 to 34000 particles/cubic-centimeter (particles/cm(3)) (GSD 1.4-3.3), up to 12 times greater than background, with transient peaks >1.4 million particles/cm(3). PM0.1 contained 6-63% organic carbon, <1% elemental carbon, and 2-8% metals, including iron, zinc, titania, chromium, nickel and manganese, typically in the <0.01-1% range, and in agreement with toner composition. These findings document widespread ENM in toner formulations and high nanoparticle exposures are an industry-wide phenomenon. It further calls attention to the need to substantially redesign the interface of this technology with workers and consumers. PMID:26148960

  16. Occupational dermal exposure to nanoparticles and nano-enabled products: Part I-Factors affecting skin absorption.

    PubMed

    Larese Filon, Francesca; Bello, Dhimiter; Cherrie, John W; Sleeuwenhoek, Anne; Spaan, Suzanne; Brouwer, Derk H

    2016-08-01

    The paper reviews and critically assesses the evidence on the relevance of various skin uptake pathways for engineered nanoparticles, nano-objects, their agglomerates and aggregates (NOAA). It focuses especially in occupational settings, in the context of nanotoxicology, risk assessment, occupational medicine, medical/epidemiological surveillance efforts, and the development of relevant exposure assessment strategies. Skin uptake of nanoparticles is presented in the context of local and systemic health effects, especially contact dermatitis, skin barrier integrity, physico-chemical properties of NOAA, and predisposing risk factors, such as stratum corneum disruption due to occupational co-exposure to chemicals, and the presence of occupational skin diseases. Attention should be given to: (1) Metal NOAA, since the potential release of ions may induce local skin effects (e.g. irritation and contact dermatitis) and absorption of toxic or sensitizing metals; (2) NOAA with metal catalytic residue, since potential release of ions may also induce local skin effects and absorption of toxic metals; (3) rigid NOAA smaller than 45nm that can penetrate and permeate the skin; (4) non rigid or flexible NOAA, where due to their flexibility liposomes and micelles can penetrate and permeate the intact skin; (5) impaired skin condition of exposed workers. Furthermore, we outline possible situations where health surveillance could be appropriate where there is NOAA occupational skin exposures, e.g. when working with nanoparticles made of sensitizer metals, NOAA containing sensitizer impurities, and/or in occupations with a high prevalence of disrupted skin barrier integrity. The paper furthermore recommends a stepwise approach to evaluate risk related to NOAA to be applied in occupational exposure and risk assessment, and discusses implications related to health surveillance, labelling, and risk communication. PMID:27289581

  17. Press or pulse exposures determine the environmental fate of cerium nanoparticles in stream mesocosms.

    PubMed

    Baker, Leanne F; King, Ryan S; Unrine, Jason M; Castellon, Benjamin T; Lowry, Gregory V; Matson, Cole W

    2016-05-01

    Risk-assessment models indicate that stream ecosystems receiving municipal wastewater effluent may have the greatest potential for exposure to manufactured nanoparticles. The authors determined the fate of cerium oxide (CeO2 ) nanoparticles in outdoor stream mesocosms using 1) 1-time pulse addition of CeO2 nanoparticles, representative of accidental release, and 2) continuous, low-level press addition of CeO2 nanoparticles, representative of exposure via wastewater effluent. The pulse addition led to rapid nanoparticle floc formation, which appeared to preferentially deposit on periphyton in low-energy areas downstream from the location of the input, likely as a result of gravitational sedimentation. Floc formation limited the concentration of suspended nanoparticles in stream water to <5% of target and subsequent downstream movement. In contrast, press addition of nanoparticles led to higher suspended nanoparticle concentrations (77% of target) in stream water, possibly as a result of stabilization of suspended nanoparticles through interaction with dissolved organic carbon. Smaller nanoparticle aggregates appeared to preferentially adsorb to stream surfaces in turbulent sections, where Ce concentrations were highest in the press, likely a result of stochastic encounter with the surface. Streams receiving wastewater effluent containing nanoparticles may lead to exposure of aquatic organisms over a greater spatial extent than a similar amount of nanoparticles from an accidental release. Exposure models must take into account these mechanisms controlling transport and depositional processes. Environ Toxicol Chem 2016;35:1213-1223. © 2015 SETAC. PMID:26576038

  18. Silver nanoparticles disrupt germline stem cell maintenance in the Drosophila testis

    NASA Astrophysics Data System (ADS)

    Ong, Cynthia; Lee, Qian Ying; Cai, Yu; Liu, Xiaoli; Ding, Jun; Yung, Lin-Yue Lanry; Bay, Boon-Huat; Baeg, Gyeong-Hun

    2016-02-01

    Silver nanoparticles (AgNPs), one of the most popular nanomaterials, are commonly used in consumer products and biomedical devices, despite their potential toxicity. Recently, AgNP exposure was reported to be associated with male reproductive toxicity in mammalian models. However, there is still a limited understanding of the effects of AgNPs on spermatogenesis. The fruit fly Drosophila testis is an excellent in vivo model to elucidate the mechanisms underlying AgNP-induced defects in spermatogenesis, as germ lineages can be easily identified and imaged. In this study, we evaluated AgNP-mediated toxicity on spermatogenesis by feeding Drosophila with AgNPs at various concentrations. We first observed a dose-dependent uptake of AgNPs in vivo. Concomitantly, AgNP exposure caused a significant decrease in the viability and delay in the development of Drosophila in a dose-dependent manner. Furthermore, AgNP-treated male flies showed a reduction in fecundity, and the resulting testes contained a decreased number of germline stem cells (GSCs) compared to controls. Interestingly, testes exposed to AgNPs exhibited a dramatic increase in reactive oxygen species levels and showed precocious GSC differentiation. Taken together, our study suggests that AgNP exposure may increase ROS levels in the Drosophila testis, leading to a reduction of GSC number by promoting premature GSC differentiation.

  19. Silver nanoparticles disrupt germline stem cell maintenance in the Drosophila testis

    PubMed Central

    Ong, Cynthia; Lee, Qian Ying; Cai, Yu; Liu, Xiaoli; Ding, Jun; Yung, Lin-Yue Lanry; Bay, Boon-Huat; Baeg, Gyeong-Hun

    2016-01-01

    Silver nanoparticles (AgNPs), one of the most popular nanomaterials, are commonly used in consumer products and biomedical devices, despite their potential toxicity. Recently, AgNP exposure was reported to be associated with male reproductive toxicity in mammalian models. However, there is still a limited understanding of the effects of AgNPs on spermatogenesis. The fruit fly Drosophila testis is an excellent in vivo model to elucidate the mechanisms underlying AgNP-induced defects in spermatogenesis, as germ lineages can be easily identified and imaged. In this study, we evaluated AgNP-mediated toxicity on spermatogenesis by feeding Drosophila with AgNPs at various concentrations. We first observed a dose-dependent uptake of AgNPs in vivo. Concomitantly, AgNP exposure caused a significant decrease in the viability and delay in the development of Drosophila in a dose-dependent manner. Furthermore, AgNP-treated male flies showed a reduction in fecundity, and the resulting testes contained a decreased number of germline stem cells (GSCs) compared to controls. Interestingly, testes exposed to AgNPs exhibited a dramatic increase in reactive oxygen species levels and showed precocious GSC differentiation. Taken together, our study suggests that AgNP exposure may increase ROS levels in the Drosophila testis, leading to a reduction of GSC number by promoting premature GSC differentiation. PMID:26847594

  20. Probabilistic assessment of the cumulative dietary exposure of the population of Denmark to endocrine disrupting pesticides.

    PubMed

    Jensen, Bodil Hamborg; Petersen, Annette; Christiansen, Sofie; Boberg, Julie; Axelstad, Marta; Herrmann, Susan S; Poulsen, Mette Erecius; Hass, Ulla

    2013-05-01

    The four pesticides epoxiconazole, prochloraz, procymidone and tebuconazole, are commonly used pesticides, all suspected of acting as endocrine disrupters. In the present study, we assessed the acute cumulative dietary exposure to the women of child bearing age and the general population of Denmark to these pesticides from the intake of fruit and vegetables. The assessment was carried out using the probabilistic approach combined with the relative potency factor (RPF) approach. Residue data for prochloraz, procymidone, and tebuconazole were obtained from the Danish monitoring programme 2006-2009, while residue data for epoxiconazole were obtained from the Swedish monitoring programme carried out in the period 2007-2009. Food consumption data were obtained from the Danish nationwide dietary survey conducted in 2000-2002. Relative potency factors for the four pesticides were obtained from rat studies. Prochloraz was used as the index compound. All four pesticides increased nipple retention in male offspring, and epoxiconazole, prochloraz, and tebuconazole also increased the gestation period in pregnant rat dams. For women of childbearing age, the high-end cumulative exposure (99.9th percentile) was calculated to 9% of the Adjusted Reference Value (ARV) for the effect on nipple retention and to 1% of the ARV for the effect on increased gestation period. PMID:23333574

  1. Mugilid fish are sentinels of exposure to endocrine disrupting compounds in coastal and estuarine environments.

    PubMed

    Ortiz-Zarragoitia, Maren; Bizarro, Cristina; Rojo-Bartolomé, Iratxe; de Cerio, Oihane Diaz; Cajaraville, Miren P; Cancio, Ibon

    2014-09-01

    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. PMID:25222666

  2. A Hypothesis About How Early Developmental Methylmercury Exposure Disrupts Behavior in Adulthood

    PubMed Central

    Newland, M. Christopher; Reed, Miranda N.; Rasmussen, Erin

    2015-01-01

    Events that disrupt the early development of the nervous system have lifelong, irreversible behavioral consequences. The environmental contaminant, methylmercury (MeHg), impairs neural development with effects that are manifested well into adulthood and even into aging. Noting the sensitivity of the developing brain to MeHg, the current review advances an argument that one outcome of early MeHg exposure is a distortion in the processing of reinforcing consequences that results in impaired choice, poor inhibition of prepotent responding, and perseveration on discrimination reversals (in the absence of alteration of extradimensional shifts). Neurochemical correlates include increased sensitivity to dopamine agonists and decreased sensitivity to gamma-aminobutyric acid (GABA) agonists. This leads to a hypothesis that the prefrontal cortex or dopamine neurotransmission is especially sensitive to even subtle gestational MeHg exposure and suggests that public health assessments of MeHg based on intellectual performance may underestimate the impact of MeHg in public health. Finally, those interested in modeling neural development may benefit from MeHg as an experimental model. PMID:25795099

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

    PubMed Central

    Ortiz-Zarragoitia, Maren; Bizarro, Cristina; Rojo-Bartolomé, Iratxe; Diaz de Cerio, Oihane; Cajaraville, Miren P.; Cancio, Ibon

    2014-01-01

    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. PMID:25222666

  4. Malathion exposure induces the endocrine disruption and growth retardation in the catfish, Clarias batrachus (Linn.).

    PubMed

    Lal, Bechan; Sarang, Mukesh Kumar; Kumar, Pankaj

    2013-01-15

    Many hormones are known for their role in the regulation of metabolic activities and somatic growth in fishes. The present study deals with the effects of malathion (an organophosphorous pesticide) on the levels of metabolic hormones that are responsible for promotion of somatic and ovarian growth of the freshwater catfish, Clarias batrachus. Malathion treatment for thirty days drastically reduced the food intake and body weight of fish. These fish also exhibited a great avoidance to food. Exposure of catfish to malathion reduced the levels of thyroxine (T(4)), triiodothyronine (T(3)), growth hormone (GH), insulin like growth factor-I (IGF-I), testosterone (T) and estradiol-17β (E(2)) in a dose dependent manner during all the studied reproductive phases, in general, except that malathion increased the level of GH during the quiescence phase. Significant reduction in muscle and hepatic protein content also occurred in the malathion-treated fish. Malathion exposure induced lipolysis too in the liver and muscle. The results thus support that malathion treatment disrupts the endocrine functions and the olfactory sensation responsible for food intake and gustatory feeding behavior, which ultimately leads to retardation of fish growth. PMID:23174696

  5. Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy

    NASA Astrophysics Data System (ADS)

    Sykes, Edward A.; Dai, Qin; Tsoi, Kim M.; Hwang, David M.; Chan, Warren C. W.

    2014-05-01

    The increasing use of nanomaterials raises concerns about the long-term effects of chronic nanoparticle exposure on human health. However, nanoparticle exposure is difficult to evaluate non-invasively using current measurement techniques. Here we show that the skin is an important site of nanoparticle accumulation following systemic administration. Mice injected with high doses of gold nanoparticles have visibly blue skin while quantum dot-treated animals fluoresce under ultraviolet excitation. More importantly, elemental analysis of excised skin correlates with the injected dose and nanoparticle accumulation in the liver and spleen. We propose that skin analysis may be a simple strategy to quantify systemic nanoparticle exposure and predict nanoparticle fate in vivo. Our results suggest that in the future, dermal accumulation may also be exploited to trigger the release of ultraviolet and visible light-sensitive therapeutics that are currently impractical in vivo due to limits in optical penetration of tissues at these wavelengths.

  6. Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy.

    PubMed

    Sykes, Edward A; Dai, Qin; Tsoi, Kim M; Hwang, David M; Chan, Warren C W

    2014-01-01

    The increasing use of nanomaterials raises concerns about the long-term effects of chronic nanoparticle exposure on human health. However, nanoparticle exposure is difficult to evaluate non-invasively using current measurement techniques. Here we show that the skin is an important site of nanoparticle accumulation following systemic administration. Mice injected with high doses of gold nanoparticles have visibly blue skin while quantum dot-treated animals fluoresce under ultraviolet excitation. More importantly, elemental analysis of excised skin correlates with the injected dose and nanoparticle accumulation in the liver and spleen. We propose that skin analysis may be a simple strategy to quantify systemic nanoparticle exposure and predict nanoparticle fate in vivo. Our results suggest that in the future, dermal accumulation may also be exploited to trigger the release of ultraviolet and visible light-sensitive therapeutics that are currently impractical in vivo due to limits in optical penetration of tissues at these wavelengths. PMID:24823347

  7. Challenges and future directions to evaluating the association between prenatal exposure to endocrine disrupting chemicals and childhood obesity

    PubMed Central

    Romano, Megan E.; Savitz, David A.; Braun, Joseph M.

    2014-01-01

    Obesity is an increasing public health threat worldwide. However, there has been insufficient research addressing the obesogenic potential of prenatal exposure to environmental endocrine disrupting chemicals, largely due to complexities in the design, analysis, and interpretation of such studies. This review describes relevant biological mechanisms, addresses current challenges for investigators, presents potential strategies for overcoming them, and identifies areas where further development is required to improve future research. Special considerations for exposure assessment, outcome heterogeneity, and complex confounding structures are described. PMID:25328860

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

    NASA Astrophysics Data System (ADS)

    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).

  9. Acute exposure to 17α-ethinylestradiol disrupts audience effect on male-female interactions in Betta splendens.

    PubMed

    Forette, Lindsay M; Mannion, Krystal L; Dzieweczynski, Teresa L

    2015-04-01

    Endocrine disrupting chemicals can negatively impact the morphology and behavior of organisms inhabiting polluted waters. Male-typical behaviors are often reduced after exposure, suggesting that exposure may have population-level effects. One way in which exposure may exert population-level effects is by interfering with communication within a network of individuals. Acute exposure to the estrogen mimic 17α-ethinylestradiol (EE2) disrupts the ability of male Siamese fighting fish, Betta splendens, to modify their behavior during male-male interactions when an audience is present. However, it is unknown whether audience effects during male-female interactions may be similarly altered. To examine this, male-female pairs that were given an acute exposure to EE2 or remained unexposed interacted in the presence of a female, male, or no audience. Sex differences were found between unexposed males and females. More interactant-directed gill flaring was displayed by control males when a male audience was present while control females performed this behavior more in the presence of an audience, regardless of sex. Both males and females in the control group performed more interactant-directed tail beats in the presence of a female audience. EE2 exposure made all audience effects disappear as treated males and females did not differ in their responses between audience types. These results demonstrate that acute exposure to EE2 may disrupt behavioral adjustments to audience type within a social network. This disruption may, in turn, influence population dynamics in this species as both males and females use information obtained from observing interactions in later encounters with the observed individuals. PMID:25697944

  10. Occupational dermal exposure to nanoparticles and nano-enabled products: Part 2, exploration of exposure processes and methods of assessment.

    PubMed

    Brouwer, Derk H; Spaan, Suzanne; Roff, Martin; Sleeuwenhoek, Anne; Tuinman, Ilse; Goede, Henk; van Duuren-Stuurman, Birgit; Filon, Francesca Larese; Bello, Dhimiter; Cherrie, John W

    2016-08-01

    Over the past decade, the primary focus of nanotoxicology and nanoenvironmental health and safety efforts has been largely on inhalation exposure to engineered nanomaterials, at the production stage, and much less on considering risks along the life cycle of nano-enabled products. Dermal exposure to nanomaterials and its health impact has been studied to a much lesser extent, and mostly in the context of intentional exposure to nano-enabled products such as in nanomedicine, cosmetics and personal care products. How concerning is dermal exposure to such nanoparticles in the context of occupational exposures? When and how should we measure it? In the first of a series of two papers (Larese Filon et al., 2016), we focused our attention on identifying conditions or situations, i.e. a combination of nanoparticle physico-chemical properties, skin barrier integrity, and occupations with high prevalence of skin disease, which deserve further investigation. This second paper focuses on the broad question of dermal exposure assessment to nanoparticles and attempts to give an overview of the mechanisms of occupational dermal exposure to nanoparticles and nano-enabled products and explores feasibility and adequacy of various methods of quantifying dermal exposure to NOAA. We provide here a conceptual framework for screening, prioritization, and assessment of dermal exposure to NOAA in occupational settings, and integrate it into a proposed framework for risk assessment. PMID:27283207

  11. Interference in Autophagosome Fusion by Rare Earth Nanoparticles Disrupts Autophagic Flux and Regulation of an Interleukin-1β Producing Inflammasome

    PubMed Central

    2015-01-01

    Engineered nanomaterials (ENMs) including multiwall carbon nanotubes (MWCNTs) and rare earth oxide (REO) nanoparticles, which are capable of activating the NLRP3 inflammasome and inducing IL-1β production, have the potential to cause chronic lung toxicity. Although it is known that lysosome damage is an upstream trigger in initiating this pro-inflammatory response, the same organelle is also an important homeostatic regulator of activated NLRP3 inflammasome complexes, which are engulfed by autophagosomes and then destroyed in lysosomes after fusion. Although a number of ENMs have been shown to induce autophagy, no definitive research has been done on the homeostatic regulation of the NLRP3 inflammasome during autophagic flux. We used a myeloid cell line (THP-1) and bone marrow derived macrophages (BMDM) to compare the role of autophagy in regulating inflammasome activation and IL-1β production by MWCNTs and REO nanoparticles. THP-1 cells express a constitutively active autophagy pathway and are also known to mimic NLRP3 activation in pulmonary macrophages. We demonstrate that, while activated NLRP3 complexes could be effectively removed by autophagosome fusion in cells exposed to MWCNTs, REO nanoparticles interfered in autophagosome fusion with lysosomes. This leads to the accumulation of the REO-activated inflammasomes, resulting in robust and sustained IL-1β production. The mechanism of REO nanoparticle interference in autophagic flux was clarified by showing that they disrupt lysosomal phosphoprotein function and interfere in the acidification that is necessary for lysosome fusion with autophagosomes. Binding of LaPO4 to the REO nanoparticle surfaces leads to urchin-shaped nanoparticles collecting in the lysosomes. All considered, these data demonstrate that in contradistinction to autophagy induction by some ENMs, specific materials such as REOs interfere in autophagic flux, thereby disrupting homeostatic regulation of activated NLRP3 complexes. PMID

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

    PubMed Central

    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

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

    PubMed Central

    Dufault, Renee; Schnoll, Roseanne; Lukiw, Walter J; LeBlanc, Blaise; Cornett, Charles; Patrick, Lyn; Wallinga, David; Gilbert, Steven G; Crider, Raquel

    2009-01-01

    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. PMID:19860886

  14. Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI.

    PubMed

    Mills, Brian D; Pearce, Hadley L; Khan, Omar; Jarrett, Ben R; Fair, Damien A; Lahvis, Garet P

    2016-07-15

    Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rs-fcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability. PMID:27050322

  15. Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats.

    PubMed

    Roepke, Troy A; Yang, Jennifer A; Yasrebi, Ali; Mamounis, Kyle J; Oruc, Elif; Zama, Aparna Mahakali; Uzumcu, Mehmet

    2016-07-01

    Developmental exposure to endocrine-disrupting compounds (EDCs) alters reproduction and energy homeostasis, both of which are regulated by the arcuate nucleus (ARC). Little is known about the effects of EDC on ARC gene expression. In Experiment #1, pregnant dams were treated with either two doses of bisphenol A (BPA) or oil from embryonic day (E)18-21. Neonates were injected from postnatal day (PND)0-7. Vaginal opening, body weights, and ARC gene expression were measured. Chrm3 (muscarinic receptor 3) and Adipor1 (adiponectin receptor 1) were decreased by BPA. Bdnf (brain-derived neurotropic factor), Igf1 (insulin-like growth factor 1), Htr2c (5-hydroxytryptamine receptor), and Cck2r (cholescystokinin 2 receptor) were impacted. In Experiment #2, females were exposed to BPA, diethylstilbestrol (DES), di(2-ethylhexyl)phthalate, or methoxychlor (MXC) during E11-PND7. MXC and DES advanced the age of vaginal opening and ARC gene expression was impacted. These data indicate that EDCs alter ARC genes involved in reproduction and energy homeostasis in females. PMID:27103539

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

    PubMed

    Zong, Teng; Lai, Lidan; Hu, Jia; Guo, Meijun; Li, Mo; Zhang, Lu; Zhong, Chengxue; Yang, Bei; Wu, Lei; Zhang, Dalei; Tang, Min; Kuang, Haibin

    2015-10-30

    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. PMID:25935407

  17. Dermal exposure potential from textiles that contain silver nanoparticles

    PubMed Central

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

    2014-01-01

    Background: Factors that influence exposure to silver particles from the use of textiles are not well understood. Objectives: The aim of this study was to evaluate the influence of product treatment and physiological factors on silver release from two textiles. Methods: 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). Results: 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%); P<0.01. Conclusions: We found that the process (masterbatch vs finishing) used to treat textile fibers was a more influential exposure factor than physiological properties of artificial sweat or saliva. PMID:25000110

  18. Media ionic strength impacts embryonic responses to engineered nanoparticle exposure

    PubMed Central

    Truong, Lisa; Zaikova, Tatiana; Richman, Erik K.; Hutchison, James E.; Tanguay, Robert L.

    2012-01-01

    Embryonic zebrafish were used to assess the impact of solution ion concentrations on agglomeration and resulting in vivo biological responses of gold nanoparticles (AuNPs). The minimum ion concentration necessary to support embryonic development was determined. Surprisingly, zebrafish exhibit no adverse outcomes when raised in nearly ion-free media. During a rapid throughput screening of AuNPs, 1.2-nm 3-mercaptopropionic acid-functionalized AuNPs (1.2-nm 3-MPA-AuNPs) rapidly agglomerate in exposure solutions. When embryos were exposed to 1.2-nm 3-MPA-AuNPs dispersed in low ionic media, both morbidity and mortality were induced, but when suspended in high ionic media, there was little to no biological response. We demonstrated that the media ionic strength greatly affects agglomeration rates and biological responses. Most importantly, the insensitivity of the zebrafish embryo to external ions indicates that it is possible, and necessary, to adjust the exposure media conditions to optimize NP dispersion prior to assessment. PMID:21809903

  19. 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

    EPA Science Inventory

    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.

  20. Fucoidan Extracted from Hijiki Protects Brain Microvessel Endothelial Cells Against Diesel Exhaust Particle Exposure-Induced Disruption.

    PubMed

    Choi, Young-Sook; Eom, Sang-Yong; Kim, In-Soo; Ali, Syed F; Kleinman, Michael T; Kim, Yong-Dae; Kim, Heon

    2016-05-01

    This study was performed to evaluate the protective effects of fucoidan against the decreased function of primary cultured bovine brain microvessel endothelial cells (BBMECs) after exposure to diesel exhaust particles (DEPs). BBMECs were extracted from bovine brains and cultured until confluent. To evaluate the function of BBMECs, we performed a permeability test using cell-by-cell equipment and by Western blot analysis for zonular occludens-1 (ZO-1), which is a tight junction protein of BMECs, and evaluated oxidative stress in BBMECs using the DCFH-DA assay and the CUPRAC-BCS assay. The increased oxidative stress in BBMECs following DEP exposure was suppressed by fucoidan. In addition, permeability of BBMECs induced by DEP exposure was decreased by fucoidan treatment. Our results showed that fucoidan protects against BBMEC disruption induced by DEP exposure. This study provides evidence that fucoidan might protect the central nervous system (CNS) against DEP exposure. PMID:27152978

  1. Green synthesis of silk fibroin-silver nanoparticle composites with effective antibacterial and biofilm-disrupting properties.

    PubMed

    Fei, Xiang; Jia, Minghui; Du, Xin; Yang, Yuhong; Zhang, Ren; Shao, Zhengzhong; Zhao, Xia; Chen, Xin

    2013-12-01

    Natural polymer Bombyx mori silk fibroin is used as a biotemplate to produce silver nanoparticles in situ under light (both incandescent light and sunlight) at room temperature. Silk fibroin provides multiple functions in the whole reaction system, serving as the reducing agent of silver, and the dispersing and stabilizing agent of the resulted silver nanoparticles. As the reaction needs not any other chemicals and only uses light as power source, the synthetic route of silver nanoparticles reported here is rather environment-friendly and energy-saving. The silk fibroin-silver nanoparticle composite prepared by this method can be stably stored in a usual environment (room temperature, exposure to light, and so forth) for at least one month. Such a silk fibroin-silver nanoparticle composite shows an effective antibacterial activity against the methicillin-resistant Staphylococcus aureus (S. aureus) and subsequently inhibits the biofilm formation caused by the same bacterium. Moreover, a maturely formed biofilm created by methicillin-resistant S. aureus can be destroyed by the silk fibroin-silver nanoparticle composite, which meets the demand of clinical application. Therefore, the silk fibroin-silver nanoparticle composite prepared by this clean and facile method is expected to be an effective and economical antimicrobial material in biomedical fields. PMID:24171643

  2. Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure

    PubMed Central

    Williams, Sarah K; Lauder, Jean M; Johns, Josephine M

    2011-01-01

    Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine’s effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure. PMID:22379462

  3. Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure.

    PubMed

    Williams, Sarah K; Lauder, Jean M; Johns, Josephine M

    2011-09-01

    Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine's effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure. PMID:22379462

  4. Oral subchronic exposure to silver nanoparticles in rats.

    PubMed

    Garcia, Tania; Lafuente, Daisy; Blanco, Jordi; Sánchez, Domènec J; Sirvent, Juan J; Domingo, José L; Gómez, Mercedes

    2016-06-01

    Because of their extremely small size, silver nanoparticles (AgNPs) show unique physical and chemical properties, with specific biological effects, which make them particularly attractive for being used in a number of consumer applications. However, these properties also influence the potential toxicity of AgNPs. In this study, we assessed the potential toxic effects of an in vivo oral sub-chronic exposure to polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) in adult male rats. We also assessed if oral PVP-AgNPs exposure could alter the levels of various metals (Fe, Mg, Zn and Cu) in tissues. Rats were orally given 0, 50, 100 and 200 mg/kg/day of PVP-AgNPs. Silver (Ag) accumulation in tissues, Ag excretion, biochemical and hematological parameters, metal levels, as well as histopathological changes and subcellular distribution following PVP-AgNPs exposure, were also investigated. After 90 days of treatment, AgNPs were found within hepatic and ileum cells. The major tissue concentration of Ag was found in ileum of treated animals. However, all tissues of PVP-AgNPs-exposed animals showed increased levels of Ag in comparison with those of rats in the control group. No harmful effects in liver and kidney, as well as in biochemical markers were noted at any treatment dose. In addition, no hematological or histopathological changes were found in treated animals. However, significant differences in Cu and Zn levels were found in thymus and brain of PVP-AgNPs-treated rats. PMID:27090107

  5. Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis.

    PubMed

    Trasande, L; Zoeller, R T; Hass, U; Kortenkamp, A; Grandjean, P; Myers, J P; DiGangi, J; Hunt, P M; Rudel, R; Sathyanarayana, S; Bellanger, M; Hauser, R; Legler, J; Skakkebaek, N E; Heindel, J J

    2016-07-01

    A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; 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 annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs. PMID:27003928

  6. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

    PubMed Central

    Welshons, Wade V; Thayer, Kristina A; Judy, Barbara M; Taylor, Julia A; Curran, Edward M; vom Saal, Frederick S

    2003-01-01

    Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses. These doses are within the range of current exposures to numerous chemicals in wildlife and humans. These problems are exacerbated by the fact that the type of positive and negative controls appropriate to the study of endocrine responses are not part of traditional toxicological testing and are frequently omitted, or when present, have been misinterpreted. PMID:12826473

  7. Bisphenol A exposure disrupts the development of the locus coeruleus-noradrenergic system in mice.

    PubMed

    Tando, So; Itoh, Kyoko; Yaoi, Takeshi; Ogi, Hiroshi; Goto, Shoko; Mori, Miyuki; Fushiki, Shinji

    2014-12-01

    It has been reported that bisphenol A (BPA), a widespread xenoestrogen employed in the production of polycarbonate plastics, affects brain development in both humans and rodents. In the present study employing mice, we examined the effects of exposure to BPA (500 μg/kg/day) during fetal and lactational periods on the development of the locus coeruleus (LC) at the age of embryonic day 18 (E18), postnatal 3 weeks (P3W), P8W and P16W. The number of tyrosine hydroxylase-immunoreactive cells (TH-IR cells) in females exposed to BPA was decreased, compared with the control females at P3W. At P8W, the number of TH-IR cells in females exposed to BPA was significantly decreased, compared with the control females, whereas the number of TH-IR cells in males exposed to BPA was significantly increased, compared with the control males, which resulted in reversed transient sexual differences in the numbers of TH-IR cells observed in the controls at P8W. However, no significant changes were demonstrated at E18 or P16W. Next, we examined the density of the fibers containing norepinephrine transporter (NET) in the anterior cingulate cortex (ACC) and prefrontal cortex, at P3W, P8W and P16W, because NET would be beneficial in identifying the targets of the LC noradrenergic neurons. There were no significant differences shown in the density of the NET-positive fibers, between the control and the groups exposed to BPA. These results suggested that BPA might disrupt the development of physiological sexual differences in the LC-noradrenergic system in mice, although further studies are necessary to clarify the underlying mechanisms. PMID:24985408

  8. Penetration of spherical and rod-like gold nanoparticles into intact and barrier-disrupted human skin

    NASA Astrophysics Data System (ADS)

    Graf, Christina; Nordmeyer, Daniel; Ahlberg, Sebastian; Raabe, Jörg; Vogt, Annika; Lademann, Jürgen; Rancan, Fiorenza; Rühl, Eckart

    2015-03-01

    The penetration of spherical and rod-like gold nanoparticles into human skin is reported. Several skin preparation techniques are applied, including cryo techniques, such as plunge freezing and freeze drying, and the use of wet cells. Their advantages and drawbacks for observing nanoparticle uptake are discussed. Independent of the particle shape no uptake into intact skin is observed by a combination of imaging approaches, including scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and scanning X-ray microscopy (STXM). These results are discussed along with suitable skin preparation approaches. Experiments on barrier-disrupted skin, i.e. mechanical lesions made by pricking, indicate, however, that gold particles can be identified deep in the dermis, as follows from STXM studies on wet skin samples.

  9. Different cell responses induced by exposure to maghemite nanoparticles

    NASA Astrophysics Data System (ADS)

    Luengo, Yurena; Nardecchia, Stefania; Morales, María Puerto; Serrano, M. Concepción

    2013-11-01

    Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in culture media. Overall, conclusions from these studies are of crucial interest for future biomedical applications of iron oxide NPs.Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible

  10. Persistent Seroconversion after Accidental Eye Exposure to Calcifying Nanoparticles

    NASA Technical Reports Server (NTRS)

    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).

  11. The Acute Exposure Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

    PubMed Central

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

    2014-01-01

    Introduction 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, generate reactive oxygen species, alter vasomotor tone, and potentiated atherosclerosis in murine species. Methods Following an acute whole body inhalation exposure to 500μg/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 (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. Results and Conclusions 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. This data provides new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration permissible exposure limit may adversely affect EPCs. PMID:25144474

  12. Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo

    PubMed Central

    Moberly, Andrew H.; Czarnecki, Lindsey A.; Pottackal, Joseph; Rubinstein, Tom; Turkel, Daniel J.; Kass, Marley D.; McGann, John P.

    2012-01-01

    Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled manganese can bypass the blood-brain barrier and reach the central nervous system by transport down the olfactory nerve to the brain’s olfactory bulb. However, the mechanism by which Mn disrupts neural function remains unclear. Here we used optical imaging techniques to visualize exocytosis in olfactory nerve terminals in vivo in the mouse olfactory bulb. Acute Mn exposure via intranasal instillation of 2–200 μg MnCl2 solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 μg MnCl2 and a 90% reduction compared to vehicle controls with a 200 μg exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn’s action is occurring centrally, not peripherally. This is the first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases in the basal ganglia despite normal levels of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn’s action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects. PMID:22542936

  13. Excess titanium dioxide nanoparticles on the cell surface induce cytotoxicity by hindering ion exchange and disrupting exocytosis processes.

    PubMed

    Wang, Yanli; Yao, Chenjie; Li, Chenchen; Ding, Lin; Liu, Jian; Dong, Peng; Fang, Haiping; Lei, Zhendong; Shi, Guosheng; Wu, Minghong

    2015-08-14

    To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K(+), Ca(2+), Na(+), Mg(2+) and SO4(2-) decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L(-1)) and a long nano-TiO2 deposition time (48 h), the concentration of Na(+) decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L(-1), respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO4(2-) decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L(-1), respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials. PMID:26176908

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

    PubMed

    Johansson, Hanna Katarina Lilith; Jacobsen, Pernille Rosenskjold; Hass, Ulla; Svingen, Terje; Vinggaard, Anne Marie; Isling, Louise Krag; Axelstad, Marta; Christiansen, Sofie; Boberg, Julie

    2016-06-01

    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, pesticides, UV-filters, bisphenol A, butylparaben, as well as paracetamol. The compounds were tested together (Totalmix) or in subgroups with anti-androgenic (AAmix) or estrogenic (Emix) potentials. Paracetamol was tested separately. In pre-pubertal rats, a significant reduction in primordial follicle numbers was seen in AAmix and PM groups, and reduced plasma levels of prolactin was seen in AAmix. In one-year-old animals, the incidence of irregular estrous cycles was higher after Totalmix-exposure and reduced ovary weights were seen in Totalmix, AAmix, and PM groups. These findings resemble premature ovarian insufficiency in humans, and raises concern regarding potential effects of mixtures of EDCs on female reproductive function. PMID:27049580

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

    PubMed

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

    2015-10-01

    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. PMID:26204059

  16. Prenatal Ethanol Exposure Disrupts Intraneocortical Circuitry, Cortical Gene Expression, and Behavior in a Mouse Model of FASD

    PubMed Central

    El Shawa, Hani; Abbott, Charles W.

    2013-01-01

    In utero ethanol exposure from a mother's consumption of alcoholic beverages impacts brain and cognitive development, creating a range of deficits in the child (Levitt, 1998; Lebel et al., 2012). Children diagnosed with fetal alcohol spectrum disorders (FASD) are often born with facial dysmorphology and may exhibit cognitive, behavioral, and motor deficits from ethanol-related neurobiological damage in early development. Prenatal ethanol exposure (PrEE) is the number one cause of preventable mental and intellectual dysfunction globally, therefore the neurobiological underpinnings warrant systematic research. We document novel anatomical and gene expression abnormalities in the neocortex of newborn mice exposed to ethanol in utero. This is the first study to demonstrate large-scale changes in intraneocortical connections and disruption of normal patterns of neocortical gene expression in any prenatal ethanol exposure animal model. Neuroanatomical defects and abnormal neocortical RZRβ, Id2, and Cadherin8 expression patterns are observed in PrEE newborns, and abnormal behavior is present in 20-d-old PrEE mice. The vast network of neocortical connections is responsible for high-level sensory and motor processing as well as complex cognitive thought and behavior in humans. Disruptions to this network from PrEE-related changes in gene expression may underlie some of the cognitive-behavioral phenotypes observed in children with FASD. PMID:24285895

  17. Prenatal ethanol exposure disrupts intraneocortical circuitry, cortical gene expression, and behavior in a mouse model of FASD.

    PubMed

    El Shawa, Hani; Abbott, Charles W; Huffman, Kelly J

    2013-11-27

    In utero ethanol exposure from a mother's consumption of alcoholic beverages impacts brain and cognitive development, creating a range of deficits in the child (Levitt, 1998; Lebel et al., 2012). Children diagnosed with fetal alcohol spectrum disorders (FASD) are often born with facial dysmorphology and may exhibit cognitive, behavioral, and motor deficits from ethanol-related neurobiological damage in early development. Prenatal ethanol exposure (PrEE) is the number one cause of preventable mental and intellectual dysfunction globally, therefore the neurobiological underpinnings warrant systematic research. We document novel anatomical and gene expression abnormalities in the neocortex of newborn mice exposed to ethanol in utero. This is the first study to demonstrate large-scale changes in intraneocortical connections and disruption of normal patterns of neocortical gene expression in any prenatal ethanol exposure animal model. Neuroanatomical defects and abnormal neocortical RZRβ, Id2, and Cadherin8 expression patterns are observed in PrEE newborns, and abnormal behavior is present in 20-d-old PrEE mice. The vast network of neocortical connections is responsible for high-level sensory and motor processing as well as complex cognitive thought and behavior in humans. Disruptions to this network from PrEE-related changes in gene expression may underlie some of the cognitive-behavioral phenotypes observed in children with FASD. PMID:24285895

  18. Novel active personal nanoparticle sampler for the exposure assessment of nanoparticles in workplaces.

    PubMed

    Tsai, Chuen-Jinn; Liu, Chun-Nan; Hung, Shao-Ming; Chen, Sheng-Chieh; Uang, Shi-Nian; Cheng, Yung-Sung; Zhou, Yue

    2012-04-17

    A novel active personal nanoparticle sampler (PENS), which enables the collection of both respirable particulate mass (RPM) and nanoparticles (NPs) simultaneously, was developed to meet the critical demand for personal sampling of engineered nanomaterials (ENMs) in workplaces. The PENS consists of a respirable cyclone and a micro-orifice impactor with the cutoff aerodynamic diameter (d(pa50)) of 4 μm and 100 nm, respectively. The micro-orifice impactor has a fixed micro-orifice plate (137 nozzles of 55 μm in the inner diameter) and a rotating, silicone oil-coated Teflon filter substrate at 1 rpm to achieve a uniform particle deposition and avoid solid particle bounce. A final filter is used after the impactor to collect the NPs. Calibration results show that the d(pa50) of the respirable cyclone and the micro-orifice impactor are 3.92 ± 0.22 μm and 101.4 ± 0.1 nm, respectively. The d(pa50) at the loaded micro-Al(2)O(3) mass of 0.36-3.18 mg is shifted to 102.9-101.2 nm, respectively, while it is shifted to 98.9-97.8 nm at the loaded nano-TiO(2) mass of 0.92-1.78 mg, respectively. That is, the shift of d(pa50) due to solid particle loading is small if the PENS is not overloaded. Both NPs and RPM concentrations were found to agree well with those of the IOSH respirable cyclone and MOUDI. By using the present PENS, the collected samples can be further analyzed for chemical species concentrations besides gravimetric analysis to determine the actual exposure concentrations of ENMs in both RPM and NPs fractions in workplaces, which are often influenced by the background or incident pollution sources. PMID:22435654

  19. NEONATAL EXPOSURE TO TRIMETHYLTIN DISRUPTS SPATIAL DELAYED ALTERNATION LEARNING IN PREWEANLING RATS

    EPA Science Inventory

    Trimethyltin is an organotin compound that produces potent neurotoxicity in both adult and developing animals. he limbic system is a primary CNS target site for this toxicity and a prominent behavioral effect of TMT is disruption of learning and memory. mpairment of cognitive dev...

  20. Using biological endpoints for assessing exposures to endocrine disrupting contaminants of emerging concern

    EPA Science Inventory

    Most of what is known about the implications of endocrine disrupting chemicals (EDCs) in the environment is site- or compound-specific. There are numerous reports of gonadal histological abnormalities, alterations in sex ratios, and high vitellogenin protein levels in fish below ...

  1. Postweaning Exposure to Dietary Zearalenone, a Mycotoxin, Promotes Premature Onset of Puberty and Disrupts Early Pregnancy Events in Female Mice

    PubMed Central

    Ye, Xiaoqin

    2013-01-01

    Zearalenone (ZEA) is a mycotoxin commonly found in contaminated livestock feed and human food with levels in the range of ppb and low ppm. It was hypothesized that ZEA, an endocrine disruptor, could affect puberty and early pregnancy. To test this hypothesis, newly weaned (3 weeks old) C57BL/6J female mice were exposed to 0, 0.002, 4, 10, and 40 ppm ZEA and 0.05 ppm diethylstilbestrol (positive control) in phytoestrogen-free AIN-93G diet. Females exposed to 10 and 40 ppm ZEA diets showed earlier onset of vaginal opening. Those treated with 40 ppm ZEA diet also had earlier first copulation plug and irregular estrous cyclicity. At 8 weeks old, all females were mated with untreated stud males on AIN-93G diet during mating. Treatment resumed upon identification of a vaginal plug on gestation day 0.5 (D0.5). Embryo implantation was assessed on D4.5. Exposure to 40 ppm ZEA diet resulted in reduced percentage of plugged mice with implantation sites, distended uterine appearance, and retained expression of progesterone receptor in D4.5 uterine epithelium. To determine the exposure timing and mechanisms of disrupted embryo implantation, four groups of females were fed with 0 or 40 ppm ZEA diets during premating (weaning to mating) and postmating (D0.5–D4.5), respectively. Premating exposure to 40 ppm ZEA diet reduced fertilization rate, whereas postmating exposure to 40 ppm ZEA diet delayed embryo transport and preimplantation embryo development, which subsequently affected embryo implantation. These data demonstrate that postweaning exposure to dietary ZEA can promote premature onset of puberty and disrupt early pregnancy events. PMID:23291560

  2. Timing of androgen receptor disruption and estrogen exposure underlies a spectrum of congenital penile anomalies

    PubMed Central

    Armfield, Brooke A.; Cohn, Martin J.

    2015-01-01

    Congenital penile anomalies (CPAs) are among the most common human birth defects. Reports of CPAs, which include hypospadias, chordee, micropenis, and ambiguous genitalia, have risen sharply in recent decades, but the causes of these malformations are rarely identified. Both genetic anomalies and environmental factors, such as antiandrogenic and estrogenic endocrine disrupting chemicals (EDCs), are suspected to cause CPAs; however, little is known about the temporal window(s) of sensitivity to EDCs, or the tissue-specific roles and downstream targets of the androgen receptor (AR) in external genitalia. Here, we show that the full spectrum of CPAs can be produced by disrupting AR at different developmental stages and in specific cell types in the mouse genital tubercle. Inactivation of AR during a narrow window of prenatal development results in hypospadias and chordee, whereas earlier disruptions cause ambiguous genitalia and later disruptions cause micropenis. The neonatal phase of penile development is controlled by the balance of AR to estrogen receptor α (ERα) activity; either inhibition of androgen or augmentation of estrogen signaling can induce micropenis. AR and ERα have opposite effects on cell division, apoptosis, and regulation of Hedgehog, fibroblast growth factor, bone morphogenetic protein, and Wnt signaling in the genital tubercle. We identify Indian hedgehog (Ihh) as a novel downstream target of AR in external genitalia and show that conditional deletion of Ihh inhibits penile masculinization. These studies reveal previously unidentified cellular and molecular mechanisms by which antiandrogenic and estrogenic signals induce penile malformations and demonstrate that the timing of endocrine disruption can determine the type of CPA. PMID:26598695

  3. Effects of age on the disruption of cognitive performance by exposure to space radiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to low doses of heavy particles and protons can cause deficits in cognitive performance when measured within a short time (1-4 months) following irradiation. The long-term effects of such exposures and their relationship to the short-term effects remain to be established. The present exp...

  4. Embryonic exposure to carbendazim induces the transcription of genes related to apoptosis, immunotoxicity and endocrine disruption in zebrafish (Danio rerio).

    PubMed

    Jiang, Jinhua; Wu, Shenggan; Wu, Changxing; An, Xuehua; Cai, Leiming; Zhao, Xueping

    2014-12-01

    Carbendazim is one of the most widespread environmental contaminant that can cause major concern to human and animal reproductive system. To date, very few studies have been conducted on the toxic effect of carbendazim in the non-target organism zebrafish (Danio rerio). The study presented here aimed to assess how carbendazim triggers apoptosis, immunotoxicity and endocrine disruption pathways in zebrafish during its embryo development. Our results demonstrated that the expression patterns of many key genes involved in cell apoptosis pathway (e.g. P53, Mdm2, Bbc3 and Cas8) were significantly up-regulated upon the exposure to carbendazim at the concentration of 500 μg/L, while the Bcl2 and Cas3 were down-regulated at the same concentration, interestingly, the expression level of Ogg1 decreased at all the exposure concentrations. It was also observed that the mRNA levels of CXCL-C1C, CCL1, IL-1b and TNFα which were closely related to the innate immune system, were affected in newly hatched zebrafish after exposed to different concentrations of carbendazim. Moreover, the expression of genes that are involved in the hypothalamic-pituitary-gonadal/thyroid (HPG/HPT) axis including VTG, ERα, ERβ2, Dio1, Dio2, Thraa and Thrb were all down-regulated significantly after the exposure to carbendazim. The expression levels of two cytochrome P450 aromatases CYP19a and CYP19b were increased significantly after 20 and 100 μg/L carbendazim exposure, respectively. Taken together, our results indicated that carbendazim had the potential to induce cell apoptosis and cause immune toxicity as well as endocrine disruption in zebrafish during the embryo developmental stage. The information presented here also help to elucidate the environmental risks caused by the carbendazim-induced toxicity in aquatic organisms. PMID:25304545

  5. Zinc oxide nanoparticles in modern sunscreens: an analysis of potential exposure and hazard.

    PubMed

    Osmond, Megan J; McCall, Maxine J

    2010-03-01

    Sunscreens containing metal oxide nanoparticles appear transparent on the skin and provide excellent protection against sunburn caused by UV radiation. While it is likely that nanoparticles remain on the surface of the skin of healthy adult humans, and thus are considered safe for use in sunscreens, there has been no comprehensive assessment of the impact on human health from exposure to the metal oxide nanoparticles destined for use in sunscreens, either in the workplace during the manufacturing process, in long-term use across a range of skin conditions, or upon release into the broader environment, either accidentally or consequent of normal sunscreen use. In this review, we focus on zinc oxide nanoparticles destined for use in modern sunscreens, and discuss the potential for human exposure and the health hazard at each stage of their manufacture and use. We highlight where there is a need for further research. PMID:20795900

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

    PubMed

    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, p<0.05), BPA (r=0.391, p<0.05). Moreover, there existed a correspondencebetween EDCs congener and food category. Based on the obtained database of EDCs concentration combined with local food consumption, dietary EDCs exposure was estimated using the Monte Carlo Risk 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. PMID:26025473

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

    PubMed

    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. PMID:25101840

  8. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    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

    2015-12-01

    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. PMID:26465197

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

    USGS Publications Warehouse

    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.

  10. Cutaneous exposure scenarios for engineered nanoparticles used in semiconductor fabrication: a preliminary investigation of workplace surface contamination

    PubMed Central

    Shepard, Michele; Brenner, Sara

    2014-01-01

    Background: Numerous studies are ongoing in the fields of nanotoxicology and exposure science; however, gaps remain in identifying and evaluating potential exposures from skin contact with engineered nanoparticles in occupational settings. Objectives: The aim of this study was to identify potential cutaneous exposure scenarios at a workplace using engineered nanoparticles (alumina, ceria, amorphous silica) and evaluate the presence of these materials on workplace surfaces. Methods: Process review, workplace observations, and preliminary surface sampling were conducted using microvacuum and wipe sample collection methods and transmission electron microscopy with elemental analysis. Results: Exposure scenarios were identified with potential for incidental contact. Nanoparticles of silica or silica and/or alumina agglomerates (or aggregates) were identified in surface samples from work areas where engineered nanoparticles were used or handled. Conclusions: Additional data are needed to evaluate occupational exposures from skin contact with engineered nanoparticles; precautionary measures should be used to minimize potential cutaneous exposures in the workplace. PMID:25000112

  11. Microglial activation, recruitment and phagocytosis as linked phenomena in ferric oxide nanoparticle exposure.

    PubMed

    Wang, Yun; Wang, Bing; Zhu, Mo-Tao; Li, Ming; Wang, Hua-Jian; Wang, Meng; Ouyang, Hong; Chai, Zhi-Fang; Feng, Wei-Yue; Zhao, Yu-Liang

    2011-08-10

    Microglia as the resident macrophage-like cells in the central nervous system (CNS) play a pivotal role in the innate immune responses of CNS. Understanding the reactions of microglia cells to nanoparticle exposure is important in the exploration of neurobiology of nanoparticles. Here we provide a systemic mapping of microglia and the corresponding pathological changes in olfactory-transport related brain areas of mice with Fe(2)O(3)-nanoparticle intranasal treatment. We showed that intranasal exposure of Fe(2)O(3) nanoparticle could lead to pathological alteration in olfactory bulb, hippocampus and striatum, and caused microglial proliferation, activation and recruitment in these areas, especially in olfactory bulb. Further experiments with BV2 microglial cells showed the exposure to Fe(2)O(3) nanoparticles could induce cells proliferation, phagocytosis and generation of ROS and NO, but did not cause significant release of inflammatory factors, including IL-1β, IL-6 and TNF-α. Our results indicate that microglial activation may act as an alarm and defense system in the processes of the exogenous nanoparticles invading and storage in brain. PMID:21596115

  12. Exposure modeling of engineered nanoparticles in the environment.

    PubMed

    Mueller, Nicole C; Nowack, Bernd

    2008-06-15

    The aim of this study was to use a life-cycle perspective to model the quantities of engineered nanoparticles released into the environment. Three types of nanoparticles were studied: nano silver (nano-Ag), nano TiO2 (nano-TiO2), and carbon nanotubes (CNT). The quantification was based on a substance flow analysis from products to air, soil, and water in Switzerland. The following parameters were used as model inputs: estimated worldwide production volume, allocation of the production volume to product categories, particle release from products, and flow coefficients within the environmental compartments. The predicted environmental concentrations (PEC) were then compared to the predicted no effect concentrations (PNEC) derived from the literature to estimate a possible risk. The expected concentrations of the three nanoparticles in the different environmental compartments vary widely, caused by the different life cycles of the nanoparticle-containing products. The PEC values for nano-TiO2 in water are 0.7--16 microg/L and close to or higher than the PNEC value for nano-TiO2 (< 1 microg/L). The risk quotients (PEC/PNEC) for CNT and nano-Ag were much smaller than one, therefore comprising no reason to expect adverse effects from those particles. The results of this study make it possible for the first time to carry out a quantitative risk assessment of nanoparticles in the environment and suggest further detailed studies of nano-TiO2. PMID:18605569

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Disrupted Nitric Oxide Metabolism from Type II Diabetes and Acute Exposure to Particulate Air Pollution

    PubMed Central

    Pettit, Ashley P.; Kipen, Howard; Laumbach, Robert; Ohman-Strickland, Pamela; Kelly-McNeill, Kathleen; Cepeda, Clarimel; Fan, Zhi-Hua; Amorosa, Louis; Lubitz, Sara; Schneider, Stephen; Gow, Andrew

    2015-01-01

    Type II diabetes is an established cause of vascular impairment. Particulate air pollution is known to exacerbate cardiovascular and respiratory conditions, particularly in susceptible populations. This study set out to determine the impact of exposure to traffic pollution, with and without particle filtration, on vascular endothelial function in Type II diabetes. Endothelial production of nitric oxide (NO) has previously been linked to vascular health. Reactive hyperemia induces a significant increase in plasma nitrite, the proximal metabolite of NO, in healthy subjects, while diabetics have a lower and more variable level of response. Twenty type II diabetics and 20 controls (ages 46–70 years) were taken on a 1.5hr roadway traffic air pollution exposure as passengers. We analyzed plasma nitrite, as a measure of vascular function, using forearm ischemia to elicit a reactive hyperemic response before and after exposure to one ride with and one without filtration of the particle components of pollution. Control subjects displayed a significant increase in plasma nitrite levels during reactive hyperemia. This response was no longer present following exposure to traffic air pollution, but did not vary with whether or not the particle phase was filtered out. Diabetics did not display an increase in nitrite levels following reactive hyperemia. This response was not altered following pollution exposure. These data suggest that components of acute traffic pollution exposure diminish vascular reactivity in non-diabetic individuals. It also confirms that type II diabetics have a preexisting diminished ability to appropriately respond to a vascular challenge, and that traffic pollution exposure does not cause a further measureable acute change in plasma nitrite levels in Type II diabetics. PMID:26656561

  15. Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure

    PubMed Central

    Flores-Montoya, Mayra Gisel; Alvarez, Juan Manuel; Sobin, Christina

    2015-01-01

    Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N = 33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 µg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL × sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice. PMID:25936521

  16. In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep

    PubMed Central

    Fowler, Paul A.; Dorà, Natalie J.; McFerran, Helen; Amezaga, Maria R.; Miller, David W.; Lea, Richard G.; Cash, Phillip; McNeilly, Alan S.; Evans, Neil P.; Cotinot, Corinne; Sharpe, Richard M.; Rhind, Stewart M.

    2008-01-01

    Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (n = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (n = 15 control and n = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome. PMID:18436539

  17. Lead Exposure Disrupts Global DNA Methylation in Human Embryonic Stem Cells and Alters Their Neuronal Differentiation

    PubMed Central

    Senut, Marie-Claude; Sen, Arko; Cingolani, Pablo; Shaik, Asra; Land, Susan J.; Ruden, Douglas M.

    2014-01-01

    Exposure to lead (Pb) during childhood can result in learning disabilities and behavioral problems. Although described in animal models, whether Pb exposure also alters neuronal differentiation in the developing brains of exposed children is unknown. Here, we investigated the effects of physiologically relevant concentrations of Pb (from 0.4 to 1.9μM) on the capacity of human embryonic stem cells (hESCs) to progress to a neuronal fate. We found that neither acute nor chronic exposure to Pb prevented hESCs from generating neural progenitor cells (NPCs). NPCs derived from hESCs chronically exposed to 1.9μM Pb throughout the neural differentiation process generated 2.5 times more TUJ1-positive neurons than those derived from control hESCs. Pb exposure of hESCs during the stage of neural rosette formation resulted in a significant decrease in the expression levels of the neural marker genes PAX6 and MSI1. Furthermore, the resulting NPCs differentiated into neurons with shorter neurites and less branching than control neurons, as assessed by Sholl analysis. DNA methylation studies of control, acutely treated hESCs and NPCs derived from chronically exposed hESCs using the Illumina HumanMethylation450 BeadChip demonstrated that Pb exposure induced changes in the methylation status of genes involved in neurogenetic signaling pathways. In summary, our study shows that exposure to Pb subtly alters the neuronal differentiation of exposed hESCs and that these changes could be partly mediated by modifications in the DNA methylation status of genes crucial to brain development. PMID:24519525

  18. Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation.

    PubMed

    Senut, Marie-Claude; Sen, Arko; Cingolani, Pablo; Shaik, Asra; Land, Susan J; Ruden, Douglas M

    2014-05-01

    Exposure to lead (Pb) during childhood can result in learning disabilities and behavioral problems. Although described in animal models, whether Pb exposure also alters neuronal differentiation in the developing brains of exposed children is unknown. Here, we investigated the effects of physiologically relevant concentrations of Pb (from 0.4 to 1.9μM) on the capacity of human embryonic stem cells (hESCs) to progress to a neuronal fate. We found that neither acute nor chronic exposure to Pb prevented hESCs from generating neural progenitor cells (NPCs). NPCs derived from hESCs chronically exposed to 1.9μM Pb throughout the neural differentiation process generated 2.5 times more TUJ1-positive neurons than those derived from control hESCs. Pb exposure of hESCs during the stage of neural rosette formation resulted in a significant decrease in the expression levels of the neural marker genes PAX6 and MSI1. Furthermore, the resulting NPCs differentiated into neurons with shorter neurites and less branching than control neurons, as assessed by Sholl analysis. DNA methylation studies of control, acutely treated hESCs and NPCs derived from chronically exposed hESCs using the Illumina HumanMethylation450 BeadChip demonstrated that Pb exposure induced changes in the methylation status of genes involved in neurogenetic signaling pathways. In summary, our study shows that exposure to Pb subtly alters the neuronal differentiation of exposed hESCs and that these changes could be partly mediated by modifications in the DNA methylation status of genes crucial to brain development. PMID:24519525

  19. Exposure to Endocrine-Disrupting Chemicals during Pregnancy and Weight at 7 Years of Age: A Multi-pollutant Approach

    PubMed Central

    Agay-Shay, Keren; Martinez, David; Valvi, Damaskini; Garcia-Esteban, Raquel; Basagaña, Xavier; Robinson, Oliver; Casas, Maribel; Sunyer, Jordi

    2015-01-01

    Background Prenatal exposure to endocrine-disrupting chemicals (EDCs) may induce weight gain and obesity in children, but the obesogenic effects of mixtures have not been studied. Objective We evaluated the associations between pre- and perinatal biomarker concentrations of 27 EDCs and child weight status at 7 years of age. Methods In pregnant women enrolled in a Spanish birth cohort study between 2004 and 2006, we measured the concentrations of 10 phthalate metabolites, bisphenol A, cadmium, arsenic, and lead in two maternal pregnancy urine samples; 6 organochlorine compounds in maternal pregnancy serum; mercury in cord blood; and 6 polybrominated diphenyl ether congeners in colostrum. Among 470 children at 7 years, body mass index (BMI) z-scores were calculated, and overweight was defined as BMI > 85th percentile. We estimated associations with EDCs in single-pollutant models and applied principal-component analysis (PCA) on the 27 pollutant concentrations. Results In single-pollutant models, HCB (hexachlorobenzene), βHCH (β-hexachlorocyclohexane), and polychlorinated biphenyl (PCB) congeners 138 and 180 were associated with increased child BMI z-scores; and HCB, βHCH, PCB-138, and DDE (dichlorodiphenyldichloroethylene) with overweight risk. PCA generated four factors that accounted for 43.4% of the total variance. The organochlorine factor was positively associated with BMI z-scores and with overweight (adjusted RR, tertile 3 vs. 1: 2.59; 95% CI: 1.19, 5.63), and these associations were robust to adjustment for other EDCs. Exposure in the second tertile of the phthalate factor was inversely associated with overweight. Conclusions Prenatal exposure to organochlorines was positively associated with overweight at age 7 years in our study population. Other EDCs exposures did not confound this association. Citation Agay-Shay K, Martinez D, Valvi D, Garcia-Esteban R, Basagaña X, Robinson O, Casas M, Sunyer J, Vrijheid M. 2015. Exposure to endocrine-disrupting

  20. Exposure to DEHP and MEHP from hatching to adulthood causes reproductive dysfunction and endocrine disruption in marine medaka (Oryzias melastigma).

    PubMed

    Ye, Ting; Kang, Mei; Huang, Qiansheng; Fang, Chao; Chen, Yajie; Shen, Heqing; Dong, Sijun

    2014-01-01

    Concern has increased regarding the adverse effects of di-(2-ethylhexyl)-phthalate (DEHP) on reproduction. However, limited information is available on the effects of DEHP in marine organisms. The aim of the present study was to examine whether long-term exposure to DEHP and its active metabolite mono-(2-ethylhexyl)-phthalate (MEHP) disrupts endocrine function in marine medaka (Oryzias melastigma). Marine medaka larvae were exposed to either DEHP (0.1 and 0.5mg/L) or MEHP (0.1 and 0.5mg/L) for 6 months, and the effects on reproduction, sex steroid hormones, liver vitellogenin (VTG), gonad histology and the expression of genes involved in the hypothalamic-pituitary-gonad (HPG) axis were investigated. Exposure to DEHP, but not MEHP, from hatching to adulthood accelerated the start of spawning and decreased the egg production of exposed females. Moreover, exposure to both DEHP and MEHP resulted in a reduction in the fertilization rate of oocytes spawned by untreated females paired with treated males. A significant increase in plasma 17β-estradiol (E2) along with a significant decrease in testosterone (T)/E2 ratios was observed in males, which was accompanied by the upregulation of ldlr, star, cyp17a1, 17βhsd, and cyp19a transcription in the testis. Increased concentrations of T and E2 were observed in females, which was consistent with the upregulation of ldlr. The expression of brain gnrhr2, fshβ, cyp19b and steroid hormone receptor genes also corresponded well with hormonal and reproductive changes. The liver VTG level was significantly increased after DEHP and MEHP exposure in males. DEHP induced histological changes in the testes and ovaries: the testes displayed a reduced number of spermatozoa, and the ovaries displayed an increased number of atretic follicles. In addition, the tissue concentrations of MEHP, MEHHP and MEOHP in DEHP-exposed groups were much higher than those in MEHP-exposed groups, and there were no dose- or sex-specific effects. Thus, DEHP

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

    PubMed Central

    Stel, Jente

    2015-01-01

    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. PMID:26241072

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

    PubMed

    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. PMID:26241072

  3. Assessment of Nanoparticle Exposure in Nanosilica Handling Process: Including Characteristics of Nanoparticles Leaking from a Vacuum Cleaner

    PubMed Central

    KIM, Boowook; KIM, Hyunwook; YU, Il Je

    2013-01-01

    Nanosilica is one of the most widely used nanomaterials across the world. However, their assessment data on the occupational exposure to nanoparticles is insufficient. The present study performed an exposure monitoring in workplace environments where synthetic powders are prepared using fumed nanosilica. Furthermore, after it was observed during exposure monitoring that nanoparticles were emitted through leakage in a vacuum cleaner (even with a HEPA-filter installed in it), the properties of the leaked nanoparticles were also investigated. Workers were exposed to high-concentration nanosilica emitted into the air while pouring it into a container or transferring the container. The use of a vacuum cleaner with a leak (caused by an inadequate sealing) was found to be the origin of nanosilica dispersion in the indoor air. While the particle size of the nanosilica that emitted into the air (during the handling of nanosilica by a worker) was mostly over 100 nm or several microns (µm) due to the coagulation of particles, the size of nanosilica that leaked out of vacuum cleaner was almost similar to the primary size (mode diameter 11.5 nm). Analysis of area samples resulted in 20% (60% in terms of peak concentration) less than the analysis of the personals sample. PMID:24366536

  4. Excess titanium dioxide nanoparticles on the cell surface induce cytotoxicity by hindering ion exchange and disrupting exocytosis processes

    NASA Astrophysics Data System (ADS)

    Wang, Yanli; Yao, Chenjie; Li, Chenchen; Ding, Lin; Liu, Jian; Dong, Peng; Fang, Haiping; Lei, Zhendong; Shi, Guosheng; Wu, Minghong

    2015-07-01

    To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging. Herein, typically low toxicity nanomaterials were used as a model to investigate the mechanism of cytotoxicity induced by low toxicity nanomaterials. We studied the effect of nano-TiO2, nano-Al2O3 and nano-SiO2 deposition films on the ion concentration on a cell-free system simulating the cell membrane. The results showed that the ion concentration of K+, Ca2+, Na+, Mg2+ and SO42- decreased significantly following filtration of the prepared deposition films. More specifically, at a high nano-TiO2 concentration (200 mg L-1) and a long nano-TiO2 deposition time (48 h), the concentration of Na+ decreased from 2958.01 to 2775.72, 2749.86, 2757.36, and 2719.82 mg L-1, respectively, for the four types of nano-TiO2 studied. Likewise, the concentration of SO42- decreased from 38.83 to 35.00, 35.80, 35.40, and 35.27 mg L-1, respectively. The other two kinds of typical low toxicity nanomaterials (nano-Al2O3 and nano-SiO2) have a similar impact on the ion concentration change trend. Adsorption of ions on nanoparticles and the hydrated shell around the ions strongly hindered the ions through the nanoparticle films. The endocytosed nanoparticles could be released from the cells without inducing cytotoxicity. Hindering the ion exchange and disrupting the exocytosis process are the main factors that induce cytotoxicity in the presence of excess nano-TiO2 on the cell surface. The current findings may offer a universal principle for understanding the mechanism of cytotoxicity induced by low toxicity nanomaterials.To date, considerable effort has been devoted to determine the potential toxicity of nanoparticles to cells and organisms. However, determining the mechanism of cytotoxicity induced by different types of nanoparticles remains challenging

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

    PubMed

    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. PMID:26057477

  6. Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice.

    PubMed

    Sen, Nivedita; Liu, Xiaosong; Craig, Zelieann R

    2015-06-01

    Di-n-butyl phthalate (DBP) is present in many beauty and medical products. Human exposure estimates range from 0.007-0.01 mg/kg/day in the general population and up to 0.233 mg/kg/day in patients taking DBP-coated medications. Levels of phthalates tend to be higher in women, thus, evaluating ovarian effects of DBP exposure is of great importance. Mice were given corn oil (vehicle) or DBP at 0.01, 0.1, and 1000 mg/kg/day (high dose) for 10 days to test whether DBP causes ovarian toxicity. Estrous cyclicity, steroidogenesis, ovarian morphology, and apoptosis and steroidogenesis gene expression were evaluated. DBP exposure decreased serum E2 at all doses, while 0.1DBP increased FSH, decreased antral follicle numbers, and increased mRNA encoding pro-apoptotic genes (Bax, Bad, Bid). Interestingly, mRNAs encoding the steroidogenic enzymes Hsd17b1, Cyp17a1 and Cyp19a1 were increased in all DBP-treated groups. These novel findings show that DBP can disrupt ovarian function in mice at doses relevant to humans. PMID:25765776

  7. A relevant exposure to a food matrix contaminated environmentally by polychlorinated biphenyls induces liver and brain disruption in rats.

    PubMed

    Ounnas, Fayçal; Privé, Florence; Lamarche, Fréderic; Salen, Patricia; Favier-Hininger, Isabelle; Marchand, Philippe; Le Bizec, Bruno; Venisseau, Anais; Batandier, Cécile; Fontaine, Eric; de Lorgeril, Michel; Demeilliers, Christine

    2016-10-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants present in dietary fats. Most studies evaluating PCB effects have been conducted with a single compound or a mixture of PCBs given as a single acute dose. The purpose of this study was to evaluate in vivo PCB toxicity in a realistic model of exposure: a low daily dose of PCBs (twice the tolerable daily intake (TDI)), chronically administered (8 weeks) to rats in contaminated goat milk. Liver and brain PCB toxicities were investigated by evaluating oxidative stress status and mitochondrial function. PCB toxicity in the liver was also estimated by transaminase enzymatic activity. This study shows that even at low doses, chronic PCB exposure resulted in a statistically significant reduction of mitochondrial function in liver and brain. In the liver, oxygen consumption in the condition of adenosine triphosphate (ATP) production (state 3) decreased by 22-29% (p < 0.01), according to the respiratory substrates. In the brain, respiratory chain complexes II and III were reduced by 24% and 39%, respectively (p < 0.005). The exposed rats presented higher lipid peroxidation status (+20%, p < 0.05) and transaminase activity (+30%, p < 0.05) in the blood. Thus, our study showed that exposure of rats to a daily realistic dose of PCBs (twice the TDI in a food complex mixture of environmental origin) resulted in multiple disruptions in the liver and brain. PMID:27421104

  8. MODERATE LEVEL PRENATAL ALCOHOL EXPOSURE ENHANCES ACOUSTIC STARTLE MAGNITUDE AND DISRUPTS PREPULSE INHIBITION IN ADULT RHESUS MONKEYS

    PubMed Central

    Schneider, Mary L.; Larson, Julie A.; Rypstat, Craig W.; Resch, Leslie M.; Roberts, Andrew; Moore, Colleen F.

    2013-01-01

    Background Prenatal alcohol exposure can contribute to a wide range of neurodevelopmental impairments in children and adults including behavioral and neuropsychiatric disorders. In rhesus monkeys we examined whether moderate level prenatal alcohol exposure would alter acoustic startle responses and prepulse inhibition of the acoustic startle (PPI). PPI is a highly quantifiable measure of inhibitory neural processes or sensorimotor gating associated with neuropsychiatric disorders. Methods Acoustic startle and PPI of the acoustic startle was tested in 37 adult rhesus monkeys (Macaca mulatta) from four experimental conditions: (a) moderate level prenatal alcohol-exposed, (b) prenatally-stressed, (c) moderate level prenatal alcohol-exposed + prenatally-stressed, and (d) sucrose controls. Results Prenatal alcohol-exposed monkeys showed a higher magnitude of acoustic startle response and disrupted PPI compared with monkeys not exposed to alcohol prenatally. Monkeys in all conditions showed higher HPA-axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI. Conclusion Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is one effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the co-morbidity between FASD and mental health conditions. PMID:23763712

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

    PubMed

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

    2016-06-01

    In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio. The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20-300 mln/ml or with slight oligozoospermia (semen concentration of 15-20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method. After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively). As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations. PMID:27031570

  10. PERINATAL EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS: POTENTIAL ROLE OF HORMONAL ALTERATIONS IN INITIATING ADULT REPRODUCTIVE ANOMALIES

    EPA Science Inventory

    The primary hypothesis to be tested in this series of studies is whether or not exposure to environmental agents, during certain key periods of development, will increase the risk of specific anomalies of the reproductive system. Embedded in this hypothesis is the assumption that...

  11. In utero dimethadione exposure causes postnatal disruption in cardiac structure and function in the rat.

    PubMed

    Aasa, Kristiina L; Purssell, Elizabeth; Adams, Michael A; Ozolinš, Terence R S

    2014-12-01

    In utero exposure of rat embryos to dimethadione (DMO), the N-demethylated teratogenic metabolite of the anticonvulsant trimethadione, induces a high incidence of cardiac heart defects including ventricular septal defects (VSDs). The same exposure regimen also leads to in utero cardiac functional deficits, including bradycardia, dysrhythmia, and a reduction in cardiac output (CO) and ejection fraction that persist until parturition (10 days after the final dose). Despite a high rate of spontaneous postnatal VSD closure, we hypothesize that functional sequelae will persist into adulthood. Pregnant Sprague Dawley rats were administered six 300 mg/kg doses of DMO, one every 12 h in mid-pregnancy beginning on the evening of gestation day 8. Postnatal cardiac function was assessed in control (CTL) and DMO-exposed offspring using radiotelemetry and ultrasound at 3 and 11 months of age, respectively. Adult rats exposed to DMO in utero had an increased incidence of arrhythmia, elevated blood pressure and CO, greater left ventricular volume and elevated locomotor activity versus CTL. The mean arterial pressure of DMO-exposed rats was more sensitive to changes in dietary salt load compared with CTL. Importantly, most treated rats had functional deficits in the absence of a persistent structural defect. It was concluded that in utero DMO exposure causes cardiovascular deficits that persist into postnatal life in the rat, despite absence of visible structural anomalies. We speculate this is not unique to DMO, suggesting possible health implications for infants with unrecognized gestational chemical exposures. PMID:25239635

  12. Neurobehavioral Deficits, Diseases, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

    PubMed Central

    Bellanger, Martine; Demeneix, Barbara; Grandjean, Philippe; Zoeller, R. Thomas

    2015-01-01

    Context: Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. Objective: The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. Design: 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. Results: 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

  13. The Role of Nanoparticle Surface Functionality in the Disruption of Model Cell Membranes

    PubMed Central

    Moghadam, Babak Y.; Hou, Wen-Che; Corredor, Charlie; Westerhoff, Paul; Posner, Jonathan D.

    2012-01-01

    Lipid bilayers are biomembranes common to cellular life and constitute a continuous barrier between cells and their environment. Understanding the interaction of engineered nanomaterials (ENMs) with lipid bilayers is an important step toward predicting subsequent biological effects. In this study, we assess the effect of varying the surface functionality and concentration of 10 nm-diameter gold (Au) and titanium dioxide (TiO2) ENMs on the disruption of negatively charged lipid bilayer vesicles (liposomes) using a dye leakage assay. Our findings show that Au ENMs having both positive and negative surface charge induce leakage that reaches a steady state after several hours. Positively charged particles with identical surface functionality and different core composition show similar leakage effects and result in faster and greater leakage than negatively charged particles, which suggests that surface functionality, not particle core composition, is a critical factor in determining the interaction between ENMs and lipid bilayers. The results suggest that particles permanently adsorb to bilayers and that only one positively charged particle is required to disrupt a liposome and trigger leakage of its entire contents in contrast to mellitin molecules, the most widely studied membrane lytic peptide, which requires hundred of molecules to generate leakage. PMID:22921268

  14. Exposure to bisphenol A disrupts meiotic progression during spermatogenesis in adult rats through estrogen-like activity

    PubMed Central

    Liu, C; Duan, W; Li, R; Xu, S; Zhang, L; Chen, C; He, M; Lu, Y; Wu, H; Pi, H; Luo, X; Zhang, Y; Zhong, M; Yu, Z; Zhou, Z

    2013-01-01

    The effect of bisphenol A (BPA) on the reproductive system is highly debated but has been associated with meiotic abnormalities. However, evidence is lacking with regard to the mechanisms involved. In order to explore the underlying mechanisms of BPA-induced meiotic abnormalities in adult male rats, we exposed 9-week-old male Wistar rats to BPA by gavage at 0, 2, 20 or 200 μg/kg body weight (bw)/day for 60 consecutive days. 17β-Estradiol (E2) was administered at 10 μg/kg bw/day as the estrogenic positive control. Treatments with 200 μg/kg bw/day of BPA and E2 significantly decreased sperm counts and inhibited spermiation, characterized by an increase in stage VII and decrease in stage VIII in the seminiferous epithelium. This was concomitant with a disruption in the progression of meiosis I and the persistence of meiotic DNA strand breaks in pachytene spermatocytes,and the ataxia–telangiectasia-mutated and checkpoint kinase 2 signal pathway was also activated; Eventually, germ cell apoptosis was triggered as evaluated by terminal dUTP nick-end labeling assay and western blot for caspase 3. Using the estrogen receptor (ER) antagonist ICI 182780, we determined that ER signaling mediated BPA-induced meiotic disruption and reproductive impairment. Our results suggest that ER signaling-mediated meiotic disruption may be a major contributor to the molecular events leading to BPA-related male reproductive disorders. These rodent data support the growing association between BPA exposure and the rapid increase in the incidence of male reproductive disorders. PMID:23788033

  15. Prenatal Exposure to Silver Nanoparticles Causes Depression Like Responses in Mice

    PubMed Central

    Tabatabaei, S. R. F.; Moshrefi, M.; Askaripour, M.

    2015-01-01

    Despite increasing studies on silver nanoparticles, their mechanism of action is not so clear, especially their probable toxicity on reproduction procedure, developmental process and offspring behavior. Therefore in the present study the effect of silver nanoparticles exposure during gestational period on offspring's depression behavior was assessed. Thirty virgin female mice were divided into three groups (n=10 for each group) including: one control and two experimental groups, which received an equal volume (0.2 ml) of suspension containing 0, 0.2 and 2 mg/kg of silver nanoparticles, respectively. After mating, the suspension was injected and repeated every 3 days till accouchement. Depression behaviors were assessed by tail suspension test and forced swimming test, in 45-day-old male and female progenies (6 groups, n=10). In males, both dose of silver nanoparticles (0.2 and 2 mg/kg) decreased mobility and increased immobility time in forced swimming test (P<0.05), but in female no effects were observed in mobility and immobility time. In tail suspension test, 2 mg/kg of silver nanoparticles lead to decrease of mobility time (P<0.05) and increase of immobility time (P<0.05) in female offspring but in males no significant effect was observed on mobility and immobility time. We may concluded that the prenatal exposure to silver nanoparticles probably cause gender-specific depression like behaviors in offspring, possibly through neurotoxic effect during neuronal development. PMID:26997695

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

    PubMed Central

    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

  17. Endosulfan exposure disrupts pheromonal systems in the red-spotted newt: a mechanism for subtle effects of environmental chemicals.

    PubMed Central

    Park, D; Hempleman, S C; Propper, C R

    2001-01-01

    Because chemicals introduced into the environment by humans can affect both long-term survivorship and reproduction of amphibians, discovering the specific mechanisms through which these chemicals act may facilitate the development of plans for amphibian conservation. We investigated the amphibian pheromonal system as a potential target of common environmental chemicals. By treating female red-spotted newts, Notophthalmus viridescens, to a commonly used insecticide, endosulfan, we found that the pheromonal system is highly susceptible to low-concentration exposure. The impairment of the pheromonal system directly led to disrupted mate choice and lowered mating success. There were no other notable physiologic or behavioral changes demonstrated by the animals at the insecticide concentrations administered. Our findings suggest that the amphibian pheromonal system is one of the systems subject to subtle negative effects of environmental chemicals. PMID:11485864

  18. Dioxin Exposure, from Infancy through Puberty, Produces Endocrine Disruption and Affects Human Semen Quality

    PubMed Central

    Mocarelli, Paolo; Gerthoux, Pier Mario; Patterson, Donald G.; Milani, Silvano; Limonta, Giuseppe; Bertona, Maria; Signorini, Stefano; Tramacere, Pierluigi; Colombo, Laura; Crespi, Carla; Brambilla, Paolo; Sarto, Cecilia; Carreri, Vittorio; Sampson, Eric J.; Turner, Wayman E.; Needham, Larry L.

    2008-01-01

    Background Environmental toxicants are allegedly involved in decreasing semen quality in recent decades; however, definitive proof is not yet available. In 1976 an accident exposed residents in Seveso, Italy, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Objective The purpose of this study was to investigate reproductive hormones and sperm quality in exposed males. Methods We studied 135 males exposed to TCDD at three age groups, infancy/prepuberty (1–9 years), puberty (10–17 years), and adulthood (18–26 years), and 184 healthy male comparisons using 1976 serum TCDD levels and semen quality and reproductive hormones from samples collected 22 years later. Results Relative to comparisons, 71 men (mean age at exposure, 6.2 years; median serum TCDD, 210 ppt) at 22–31 years of age showed reductions in sperm concentration (53.6 vs. 72.5 million/mL; p = 0.025); percent progressive motility (33.2% vs. 40.8%; p < 0.001); total motile sperm count (44.2 vs. 77.5 × 106; p = 0.018); estradiol (76.2 vs. 95.9 pmol/L; p = 0.001); and an increase in follicle-stimulating hormone (FSH; 3.58 vs. 2.98 IU/L; p = 0.055). Forty-four men (mean age at exposure, 13.2 years; median serum TCDD, 164 ppt) at 32–39 years of age showed increased total sperm count (272 vs. 191.9 × 106; p = 0.042), total motile sperm count (105 vs. 64.9 ×106; p = 0.036), FSH (4.1 vs. 3.2 UI/L; p = 0.038), and reduced estradiol (74.4 vs. 92.9 pmol/L; p < 0.001). No effects were observed in 20 men, 40–47 years of age, who were exposed to TCDD (median, 123 ppt) as adults (mean age at exposure, 21.5 years). Conclusions Exposure to TCDD in infancy reduces sperm concentration and motility, and an opposite effect is seen with exposure during puberty. Exposure in either period leads to permanent reduction of estradiol and increased FSH. These effects are permanent and occur at TCDD concentrations < 68 ppt, which is within one order of magnitude of those in the industrialized world in the 1970s and 1980s and

  19. Effects of Exposure to Semiconductor Nanoparticles on Aquatic Organisms

    PubMed Central

    Leigh, Kenton; Bouldin, Jennifer; Buchanan, Roger

    2012-01-01

    Because of their unique physical, optical, and mechanical properties, nanomaterials hold great promise in improving on a wide variety of current technologies. Consequently, their use in research and consumer products is increasing rapidly, and contamination of the environment with various nanomaterials seems inevitable. Because surface waters receive pollutants and contaminants from many sources including nanoparticles and act as reservoirs and conduits for many environmental contaminants, understanding the potential impacts of nanoparticles on the organisms within these environments is critical to evaluating their potential toxicity. While there is much to be learned about interactions between nanomaterials and aquatic systems, there have been a number of recent reports of interactions of quantum dots (QDs) with aquatic environments and aquatic organisms. This review is focused on providing a summary of recent work investigating the impacts of quantum dots on aquatic organisms. PMID:22131989

  20. Behavioral response of Daphnia magna to silver salt and nanoparticle exposure

    EPA Science Inventory

    Endpoints in the investigation of the toxicity of metallic nanoparticles have varied from genetic and molecular through whole organism responses such as death and reproduction. The work presented here is an effort to quantify behavioral responses of Daphnia magna to exposure to s...

  1. Chronic exposure to mono-(2-ethylhexyl)-phthalate causes endocrine disruption and reproductive dysfunction in zebrafish.

    PubMed

    Zhu, Yongtong; Hua, Rui; Zhou, Yao; Li, Hong; Quan, Song; Yu, Yanhong

    2016-08-01

    Phthalic acid esters are frequently detected in aquatic environments. In the present study, zebrafish were exposed to low concentrations (0 µg/L, 0.46 µg/L, 4.0 µg/L, and 37.5 µg/L) of mono-(2-ethylhexyl) phthalate (MEHP) for 81 d, and the effects on reproduction, gamete quality, plasma vitellogenin (VTG), sex steroids, and transcriptional profiles of key genes involved in steroidogenesis were investigated. The results demonstrated that egg production and sperm quality were decreased after exposure to MEHP, which also resulted in reduced egg diameter and eggshell as well as decreased egg protein content. Significant inductions in plasma testosterone and 17β-estradiol (E2) were observed in females, which might have resulted from up-regulation of CYP19a and 17β-HSD gene transcription in the ovary. A significant increase in plasma E2 along with a decrease in plasma 11-keto testosterone was also observed in males, which was accompanied by up-regulation of CYP19a and inhibition of CYP11b transcription in the testis. In addition, plasma vitellogenin levels were significantly increased after MEHP exposure in both sexes. Moreover, continuous MEHP exposure in the F1 embryos resulted in worse hatching rates and increased malformation rates compared with embryos without MEHP exposure. Taken together, these results demonstrate that MEHP has the potential to cause reproductive dysfunction and impair the development of offspring. However, it should be noted that most of the significant effects were observed at higher concentrations, and MEHP at typically measured concentrations may not have major effects on fish reproduction and development. Environ Toxicol Chem 2016;35:2117-2124. © 2016 SETAC. PMID:26762230

  2. Dioxin Exposure Disrupts the Differentiation of Mouse Embryonic Stem Cells into Cardiomyocytes

    PubMed Central

    Wang, Ying; Fan, Yunxia; Puga, Alvaro

    2010-01-01

    Experimental exposure of fish, birds, and rodents to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) causes multiple Ah receptor–mediated developmental abnormalities, an observation consistent with compelling evidence in human populations that TCDD exposure is responsible for a significant incidence of birth defects. To characterize molecular mechanisms that might explain the developmental effects of dioxin, we have studied the consequences of TCDD exposure on the differentiation of mouse embryonic stem (ES) cells in culture and on the expression of genes, including those coding for homeodomain containing transcription factors, with a role in progression of tissue differentiation and embryonic identity during development. We find that TCDD treatment causes expression changes in a number of homeobox genes concomitant with Ah receptor recruitment to the promoters of many of these genes, whether under naïve or dioxin-activated conditions. TCDD exposure also derails temporal expression trajectories of developmentally regulated genes in a wide diversity of differentiation pathways, including genes with functions in neural and cardiovascular development, self-renewal, hematopoiesis and mesenchymal lineage specification, and Notch and Wnt pathways. Among these, we find that TCDD represses the expression of the cardiac development–specific Nkx2.5 homeobox transcription factor, of cardiac troponin-T and of α- and β-myosin heavy chains, inhibiting the formation of beating cardiomyocytes, a characteristic phenotype of differentiating mouse ES cells in culture. These data identify potential pathways for dioxin to act as a developmental teratogen, possibly critical to cardiovascular development and disease, and provide molecular targets that may help us understand the molecular basis of Ah receptor–mediated developmental toxicity. PMID:20130022

  3. The uptake and elimination of ZnO and CuO nanoparticles in Daphnia magna under chronic exposure scenarios.

    PubMed

    Adam, Nathalie; Leroux, Frédéric; Knapen, Dries; Bals, Sara; Blust, Ronny

    2015-01-01

    In this study, the uptake and elimination of ZnO and CuO nanoparticles in Daphnia magna was tested. Daphnids were exposed during 10 days to sublethal concentrations of ZnO and CuO nanoparticles and corresponding metal salts (ZnCl₂ and CuCl₂.2H₂O), after which they were transferred to unexposed medium for another 10 days. At different times during the exposure and none-exposure, the total and internal zinc or copper concentration of the daphnids was determined and the nanoparticles were localized in the organism using electron microscopy. The exposure concentrations were characterized by measuring the dissolved, nanoparticle and aggregated fraction in the medium. The results showed that the ZnO nanoparticles quickly dissolved after addition to the medium. Contrarily, only a small fraction (corresponding to the dissolved metal salt) of the CuO nanoparticles dissolved, while most of these nanoparticles formed large aggregates. Despite an initial increase in zinc and copper concentration during the first 48 h to 5 day exposure, the body concentration reached a plateau level that was comparable for the ZnO nanoparticles and ZnCl₂, but much higher for the CuO nanoparticles (with visible aggregates accumulating in the gut) than CuCl₂.2H₂O. During the remaining exposure and subsequent none-exposure phase, the zinc and copper concentration decreased fast to concentrations comparable with the unexposed daphnids. The results indicate that D. magna can regulate its internal zinc and copper concentration after exposure to ZnO and CuO nanoparticles, similar as after exposure to metal salts. The combined dissolution, accumulation and toxicity results confirm that the toxicity of ZnO and CuO nanoparticles is caused by the dissolved fraction. PMID:25462733

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

    PubMed

    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. PMID:26493272

  5. Oral exposure of pubertal male mice to endocrine-disrupting chemicals alters fat metabolism in adult livers.

    PubMed

    Jin, Yuanxiang; Lin, Xiaojian; Miao, Wenyu; Wang, Linggang; Wu, Yan; Fu, Zhengwei

    2015-12-01

    The potential for the exposure of humans and wildlife to environmental endocrine-disrupting chemicals (EDCs) has been increasing. Risk assessment for such EDCs is primarily based on detecting the main endpoints related to the endocrine and reproductive systems, while the effects on glucose and fat metabolism have only received limited attention. In this study, pubertal male C57BL/6J mice were orally administered 10 mg/kg body weight cypermethrin (CYP), 100 mg/kg body weight atrazine (ATZ), and 0.1 mg/kg body weight 17α-ethynyestradiol (EE2) for 4 weeks and then switched to a high-energy diet (HD) for 8 weeks. The body weight gain in the EDC-treated groups was lower than that in the control group during exposure and then tended to show values similar to the HD group. The epididymal fat weight, cell size and serum triacylglycerol (TG) and total cholesterol (TCH) levels in the EDC-HD groups were lower than those in the HD group. The transcription of genes related to glycolytic and gluconeogenic processes in the liver was affected by EDC exposure. Furthermore, the expression levels of transcriptional factors including PPARα, PPARγ, and SREBP1C and their target genes related to fatty acid synthesis and oxidation in the liver were also influenced by early life EDC administration. The results showed that early-life-stage exposure to high doses of various environmental EDCs affected the homeostasis of glucose and fatty acid metabolism in the livers of adult male mice. PMID:24916741

  6. Occupation and occupational exposure to endocrine disrupting chemicals in male breast cancer: a case-control study in Europe

    PubMed Central

    Villeneuve, Sara; Cyr, Diane; Lynge, Elsebeth; Orsi, Laurent; Sabroe, Svend; Merletti, Franco; Gorini, Giuseppe; Morales-Suarez-Varela, Maria; Ahrens, Wolfgang; Baumgardt-Elms, Cornelia; Kaerlev, Linda; Eriksson, Mikael; Hardell, Lennart; Févotte, Joëlle; Guénel, Pascal

    2010-01-01

    Objectives Male breast cancer is a rare disease of largely unknown etiology. Besides genetic or hormone-related risk factors, a large number of environmental chemicals are suspected to play a role in breast cancer. The identification of occupations or occupational exposures associated with an increased incidence of breast cancer in men may help to identify mammary carcinogens in the environment. Methods Occupational risk factors of male breast cancer were investigated in a multi-centre case-control study conducted in 8 European countries, including 104 cases and 1901 controls. Lifetime work history was obtained during in-person interviews. Occupational exposures to endocrine disrupting chemicals (alkylphenolic compounds, phthalates, PCBs and dioxins) were assessed on a case-by-case basis from expert judgment. Results Male breast cancer incidence was more particularly increased in motor vehicle mechanics (OR=2.1, CI 1.0–4.4) with a dose-effect relationship with duration employment. It was also increased in paper makers and painters, and in workers in forestry and logging, health and social work, and manufacture of furniture. The odds ratio for exposure to alkylphenolic compounds above median was 3.8 (CI 1.5–9.5). This association persisted after adjustment for occupational exposures to other environmental estrogens. Conclusion These findings suggest that some environmental chemicals are possible mammary carcinogens. Gasoline, organic petroleum solvents or PAH can be suspected from the consistent elevated risk of male breast cancer observed in motor vehicle mechanics. Endocrine disruptors such as alkylphenolic compounds may play a role in breast cancer. PMID:20798010

  7. Early Life Exposure to Ractopamine Causes Endocrine-Disrupting Effects in Japanese Medaka (Oryzias latipes).

    PubMed

    Sun, Liwei; Wang, Sisi; Lin, Xia; Tan, Hana; Fu, Zhengwei

    2016-02-01

    β-Agonists, which are used as human pharmaceuticals or feed additives, have been detected in aquatic environments. β-Agonists have also been proposed for use in aquaculture. However, there are limited data available regarding the adverse effects of β-agonists in aquatic organisms. In this study, ractopamine was selected as the representative β-agonist, and medaka embryos were exposed at concentrations ranging from 5 to 625 μg/L for 44 days. In contrast to what has been found in mammals, ractopamine caused no growth response in medaka. However, the transcriptional changes of genes related to the hypothalamic-pituitary-gonadal (HPG) axis, especially in females, suggested that β-agonists may have the potential to disrupt the endocrine system. Moreover, genes involved in anti-oxidative activity or detoxification were affected in a gender-specific manner. These findings, particularly the effects on the endocrine system of fish, will advance our understanding of the ecotoxicity of β-agonists. PMID:26395355

  8. Hydrophilic nanoparticles stabilising mesophase curvature at low concentration but disrupting mesophase order at higher concentrations.

    PubMed

    Beddoes, Charlotte M; Berge, Johanna; Bartenstein, Julia E; Lange, Kathrin; Smith, Andrew J; Heenan, Richard K; Briscoe, Wuge H

    2016-07-13

    Using high pressure small angle X-ray scattering (HP-SAXS), we have studied monoolein (MO) mesophases at 18 wt% hydration in the presence of 10 nm silica nanoparticles (NPs) at NP-lipid number ratios (ν) of 1 × 10(-6), 1 × 10(-5) and 1 × 10(-4) over the pressure range 1-2700 bar and temperature range 20-60 °C. In the absence of the silica NPs, the pressure-temperature (p-T) phase diagram of monoolein exhibited inverse bicontinuous cubic gyroid (Q), lamellar alpha (Lα), and lamellar crystalline (Lc) phases. The addition of the NPs significantly altered the p-T phase diagram, changing the pressure (p) and the temperature (T) at which the transitions between these mesophases occurred. In particular, a strong NP concentration effect on the mesophase behaviour was observed. At low NP concentration, the p-T region pervaded by the Q phase and the Lα-Q mixture increased, and we attribute this behaviour to the NPs forming clusters at the mesophase domain boundaries, encouraging transition to the mesophase with a higher curvature. At high NP concentrations, the Q phase was no longer observed in the p-T phase diagram. Instead, it was dominated by the lamellar (L) phases until the transition to a fluid isotropic (FI) phase at 60 °C at low pressure. We speculate that NPs formed aggregates with a "chain of pearls" structure at the mesophase domain boundaries, hindering transitions to the mesophases with higher curvatures. These observations were supported by small angle neutron scattering (SANS) and scanning electron microscopy (SEM). Our results have implications to nanocomposite materials and nanoparticle cellular entry where the interactions between NPs and organised lipid structures are an important consideration. PMID:27340807

  9. Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos.

    PubMed

    Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J

    2015-12-01

    We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants. PMID:26419632

  10. Occupational exposure limit for silver nanoparticles: considerations on the derivation of a general health-based value.

    PubMed

    Weldon, Brittany A; M Faustman, Elaine; Oberdörster, Günter; Workman, Tomomi; Griffith, William C; Kneuer, Carsten; Yu, Il Je

    2016-09-01

    With the increased production and widespread commercial use of silver nanoparticles (AgNPs), human and environmental exposures to silver nanoparticles are inevitably increasing. In particular, persons manufacturing and handling silver nanoparticles and silver nanoparticle containing products are at risk of exposure, potentially resulting in health hazards. While silver dusts, consisting of micro-sized particles and soluble compounds have established occupational exposure limits (OELs), silver nanoparticles exhibit different physicochemical properties from bulk materials. Therefore, we assessed silver nanoparticle exposure and related health hazards in order to determine whether an additional OEL may be needed. Dosimetric evaluations in our study identified the liver as the most sensitive target organ following inhalation exposure, and as such serves as the critical target organ for setting an occupational exposure standard for airborne silver nanoparticles. This study proposes an OEL of 0.19 μg/m(3) for silver nanoparticles derived from benchmark concentrations (BMCs) from subchronic rat inhalation toxicity assessments and the human equivalent concentration (HEC) with kinetic considerations and additional uncertainty factors. It is anticipated that this level will protect workers from potential health hazards, including lung, liver, and skin damage. PMID:26982810

  11. Simultaneous exposure to estrogen and androgen resulted in feminization and endocrine disruption.

    PubMed

    Chen, Lili; Jiang, Xiaolong; Feng, Haiwei; Shi, Hongjuan; Sun, Lina; Tao, Wenjing; Xi, Qingping; Wang, Deshou

    2016-03-01

    Estrogen, which is synthesized earlier in females than androgen in males, is critical for sex determination in non-mammalian vertebrates. However, it remains unknown that what would happen to the gonadal phenotype if estrogen and androgen were administrated simultaneously. In this study, XY and XX tilapia fry were treated with the same dose of 17α-methyltestosterone (MT) and 17β-estradiol (E2) alone and in combination from 0 to 30 days after hatching. Treatment of XY fish with E2 resulted in male to female sex reversal, while treatment of XX fish with MT resulted in female to male sex reversal. In contrast, simultaneous treatment of XX and XY fish with MT and E2 resulted in female, but with cyp11b2 and cyp19a1a co-expressed in the ovary. Serum 11-ketotestosteron level of the MT and E2 simultaneously treated XX and XY female was similar to that of the XY control, while serum E2 level of these two groups was similar to that of the XX control. Transcriptomic cluster analysis revealed that the MT and E2 treated XX and XY gonads clustered into the same branch with the XX control. However a small fraction of genes, which showed disordered expression, may be associated with stress response. These results demonstrated that estrogen could maintain the female phenotype of XX fish and feminize XY fish even in the presence of androgen. Simultaneous treatment with estrogen and androgen up-regulated the endogenous estrogen and androgen synthesis, and resulted in disordered gene expression and endocrine disruption in tilapia. PMID:26759274

  12. Disruption of columnar and laminar cognitive processing in primate prefrontal cortex following cocaine exposure

    PubMed Central

    Opris, Ioan; Gerhardt, Greg A.; Hampson, Robert E.; Deadwyler, Sam A.

    2015-01-01

    Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell layers 2/3 and 5. Animals were reinforced with juice for correct responses. The first half of the recording session (control) was conducted following saline injection and in the second half of the same session cocaine was administered. Prefrontal neuron activity with respect to inter- and intra-laminar firing in layers 2/3 and 5 was assessed in the DMS task before and after the injection of cocaine. Results showed that firing rates of both pyramidal cells and interneurons increased on Match phase presentation and the Match Response (MR) in both control and cocaine halves of the session. Differential firing under cocaine vs. control in the Match phase was increased for interneurons but decreased for pyramidal cells. In addition, functional’ interactions between prefrontal pyramidal cells in layer 2/3 and 5 decreased while intra-laminar cross-correlations in both layers increased. These neural recordings demonstrate that prefrontal neurons differentially encode and process information within and between cortical cell layers via cortical columns which is disrupted in a differential manner by cocaine: administration. PMID:26074787

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

    PubMed Central

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

    2015-01-01

    Introduction: Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. Purpose: 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). Methods: 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. Results: 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. Conclusions: EDCs may contribute substantially to male

  14. Improving Nanoparticle Penetration in Tumors by Vascular Disruption with Acoustic Droplet Vaporization.

    PubMed

    Ho, Yi-Ju; Chang, Yuan-Chih; Yeh, Chih-Kuang

    2016-01-01

    Drug penetration influences the efficacy of tumor therapy. Although the leaky vessels of tumors can improve the penetration of nanodrugs via the enhanced permeability and retention (EPR) effect, various aspects of the tumor microenvironment still restrict this process. This study investigated whether vascular disruption using the acoustic vaporization of micro- or nanoscale droplets (MDs or NDs) induced by ultrasound sonication can overcome the limitations of the EPR effect to allow drug diffusion into extensive regions. The intravital penetration of DiI-labeled liposomes (as a drug model with red fluorescence) was observed using an acousto-optical integrated system comprising a 2-MHz focused ultrasound transducer (transmitting a three-cycle single pulse and a peak negative pressure of 10 MPa) in a window-chamber mouse model. Histology images of the solid tumor were also used to quantify and demonstrate the locations where DiI-labeled liposomes accumulated. In the intravital image analyses, the cumulative diffusion area and fluorescence intensity at 180 min were 0.08±0.01 mm(2) (mean±standard deviation) and 8.5±0.4%, respectively, in the EPR group, 0.33±0.01 mm(2) and 13.1±0.4% in the MD group (p<0.01), and 0.63±0.01 mm(2) and 18.9±1.1% in the ND group (p<0.01). The intratumoral accumulations of DiI-labeled liposomes were 1.7- and 2.3-fold higher in the MD and ND groups, respectively, than in the EPR group. These results demonstrate that vascular disruption induced by acoustic droplet vaporization can improve drug penetration more than utilizing the EPR effect. The NDs showed longer lifetime in vivo than MDs and provided potential abilities of long periods of treatment, intertissue ND vaporization, and intertissue NDs-converted bubble cavitation to improve the drug penetration and transport distance. PMID:26909113

  15. Improving Nanoparticle Penetration in Tumors by Vascular Disruption with Acoustic Droplet Vaporization

    PubMed Central

    Ho, Yi-Ju; Chang, Yuan-Chih; Yeh, Chih-Kuang

    2016-01-01

    Drug penetration influences the efficacy of tumor therapy. Although the leaky vessels of tumors can improve the penetration of nanodrugs via the enhanced permeability and retention (EPR) effect, various aspects of the tumor microenvironment still restrict this process. This study investigated whether vascular disruption using the acoustic vaporization of micro- or nanoscale droplets (MDs or NDs) induced by ultrasound sonication can overcome the limitations of the EPR effect to allow drug diffusion into extensive regions. The intravital penetration of DiI-labeled liposomes (as a drug model with red fluorescence) was observed using an acousto-optical integrated system comprising a 2-MHz focused ultrasound transducer (transmitting a three-cycle single pulse and a peak negative pressure of 10 MPa) in a window-chamber mouse model. Histology images of the solid tumor were also used to quantify and demonstrate the locations where DiI-labeled liposomes accumulated. In the intravital image analyses, the cumulative diffusion area and fluorescence intensity at 180 min were 0.08±0.01 mm2 (mean±standard deviation) and 8.5±0.4%, respectively, in the EPR group, 0.33±0.01 mm2 and 13.1±0.4% in the MD group (p<0.01), and 0.63±0.01 mm2 and 18.9±1.1% in the ND group (p<0.01). The intratumoral accumulations of DiI-labeled liposomes were 1.7- and 2.3-fold higher in the MD and ND groups, respectively, than in the EPR group. These results demonstrate that vascular disruption induced by acoustic droplet vaporization can improve drug penetration more than utilizing the EPR effect. The NDs showed longer lifetime in vivo than MDs and provided potential abilities of long periods of treatment, intertissue ND vaporization, and intertissue NDs-converted bubble cavitation to improve the drug penetration and transport distance. PMID:26909113

  16. Prenatal Exposure of Guinea Pigs to the Organophosphorus Pesticide Chlorpyrifos Disrupts the Structural and Functional Integrity of the Brain

    PubMed Central

    Mullins, Roger J.; Xu, Su; Pereira, Edna F.R.; Pescrille, Joseph D.; Todd, Spencer W.; Mamczarz, Jacek; Albuquerque, Edson X.; Gullapalli, Rao P.

    2015-01-01

    This study was designed to test the hypothesis that prenatal exposure of guinea pigs to the organophosphorus (OP) pesticide chlorpyrifos (CPF) disrupts the structural and functional integrity of the brain. Pregnant guinea pigs were injected with chlorpyrifos (20 mg/kg, s.c.) or vehicle (peanut oil) once per day for ten consecutive days, starting approximately on the 50th day of gestation. Cognitive behavior of female offspring was examined starting at 40–45 post-natal days (PND) using the Morris Water Maze (MWM), and brain structural integrity was analyzed at PND 70 using magnetic resonance imaging (MRI) methods, including T2-weighted anatomical scans and Diffusion Kurtosis Imaging (DKI). The offspring of exposed mothers had significantly decreased body weight and brain volume, particularly in the frontal regions of the brain including the striatum. Furthermore, the offspring demonstrated significant spatial learning deficits in MWM recall compared to the vehicle group. Diffusion measures revealed reduced white matter integrity within the striatum and amygdala that correlated with spatial learning performance. These findings reveal the lasting effect of pre-natal exposure to CPF as well as the danger of mother to child transmission of CPF in the environment. PMID:25704171

  17. Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows

    PubMed Central

    Noyes, Pamela D.; Lema, Sean C.; Macaulay, Laura J.; Douglas, Nora K.; Stapleton, Heather M.

    2013-01-01

    Polybrominated diphenyl ether (PBDE) flame retardants have been shown to disrupt thyroid hormone regulation, neurodevelopment, and reproduction in some animals. However, effects of the most heavily used PBDE, decabromodiphenyl ether (BDE-209), on thyroid functioning remain unclear. This study examined low-dose effects of BDE-209 on thyroid hormone levels and signaling in fathead minnows. Adult males received dietary exposures of BDE-209 at a low dose (~3 ng/g bw-day) and high dose (~300 ng/g bw-day) for 28 days followed by a 14-day depuration to evaluate recovery. Compared to controls, fish exposed to the low dose for 28 days experienced a 53% and 46% decline in circulating total thyroxine (TT4) and 3,5,3'-triiodothyronine (TT3), respectively, while TT4 and TT3 deficits at the high dose were 59% and 62%. Brain deiodinase activity (T4-ORD) was reduced by ~65% at both doses. BDE-209 elevated the relative mRNA expression of genes encoding deiodinases, nuclear thyroid receptors, and membrane transporters in the brain and liver in patterns that varied with time and dose, likely in compensation to hypothyroidism. Declines in the gonadal-somatic index (GSI) and increased mortality were also measured. Effects at the low dose were consistent with the high dose, suggesting non-linear relationships between BDE-209 exposures and thyroid dysfunction. PMID:23899252

  18. Exposure to monocrotophos pesticide causes disruption of the hypothalamic-pituitary-thyroid axis in adult male goldfish (Carassius auratus).

    PubMed

    Zhang, Xiaona; Tian, Hua; Wang, Wei; Ru, Shaoguo

    2013-11-01

    The thyroid hormones (THs) 3,3',5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic-pituitary-thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone β subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis. PMID:23948368

  19. Potential for Inhalation Exposure to Engineered Nanoparticles from Nanotechnology-Based Cosmetic Powders

    PubMed Central

    Nazarenko, Yevgen; Zhen, Huajun; Han, Taewon; Lioy, Paul J.

    2012-01-01

    Background: The market of nanotechnology-based consumer products is rapidly expanding, and the lack of scientific evidence describing the accompanying exposure and health risks stalls the discussion regarding its guidance and regulation. Objectives: We investigated the potential for human contact and inhalation exposure to nanomaterials when using nanotechnology-based cosmetic powders and compare them with analogous products not marketed as nanotechnology based. Methods: We characterized the products using transmission electron microscopy (TEM) and laser diffraction spectroscopy and found nanoparticles in five of six tested products. TEM photomicrographs showed highly agglomerated states of nanoparticles in the products. We realistically simulated the use of cosmetic powders by applying them to the face of a human mannequin head while simultaneously sampling the released airborne particles through the ports installed in the mannequin’s nostrils. Results: We found that a user would be exposed to nanomaterial predominantly through nanoparticle-containing agglomerates larger than the 1–100-nm aerosol fraction. Conclusions: Predominant deposition of nanomaterial(s) will occur in the tracheobronchial and head airways—not in the alveolar region as would be expected based on the size of primary nanoparticles. This could potentially lead to different health effects than expected based on the current understanding of nanoparticle behavior and toxicology studies for the alveolar region. PMID:22394622

  20. Subchronic atrazine exposure changes defensive behaviour profile and disrupts brain acetylcholinesterase activity of zebrafish.

    PubMed

    Schmidel, Ademir J; Assmann, Karla L; Werlang, Chariane C; Bertoncello, Kanandra T; Francescon, Francini; Rambo, Cassiano L; Beltrame, Gabriela M; Calegari, Daiane; Batista, Cibele B; Blaser, Rachel E; Roman Júnior, Walter A; Conterato, Greicy M M; Piato, Angelo L; Zanatta, Leila; Magro, Jacir Dal; Rosemberg, Denis B

    2014-01-01

    Animal behaviour is the interaction between environment and an individual organism, which also can be influenced by its neighbours. Variations in environmental conditions, as those caused by contaminants, may lead to neurochemical impairments altering the pattern of the behavioural repertoire of the species. Atrazine (ATZ) is an herbicide widely used in agriculture that is frequently detected in surface water, affecting non-target species. The zebrafish is a valuable model organism to assess behavioural and neurochemical effects of different contaminants since it presents a robust behavioural repertoire and also all major neurotransmitter systems described for mammalian species. The goal of this study was to evaluate the effects of subchronic ATZ exposure in defensive behaviours of zebrafish (shoaling, thigmotaxis, and depth preference) using the split depth tank. Furthermore, to investigate a putative role of cholinergic signalling on ATZ-mediated effects, we tested whether this herbicide alters acetylcholinesterase (AChE) activity in brain and muscle preparations. Fish were exposed to ATZ for 14days and the following groups were tested: control (0.2% acetone) and ATZ (10 and 1000μg/L). The behaviour of four animals in the same tank was recorded for 6min and biological samples were prepared. Our results showed that 1000μg/L ATZ significantly increased the inter-fish distance, as well as the nearest and farthest neighbour distances. This group also presented an increase in the shoal area with decreased social interaction. No significant differences were detected for the number of animals in the shallow area, latency to enter the shallow and time spent in shallow and deep areas of the apparatus, but the ATZ 1000 group spent significantly more time near the walls. Although ATZ did not affect muscular AChE, it significantly reduced AChE activity in brain. Exposure to 10μg/L ATZ did not affect behaviour or AChE activity. These data suggest that ATZ impairs defensive

  1. Exposure assessment and risk management of engineered nanoparticles: Investigation in semiconductor wafer processing

    NASA Astrophysics Data System (ADS)

    Shepard, Michele N.

    Engineered nanomaterials (ENMs) are currently used in hundreds of commercial products and industrial processes, with more applications being investigated. Nanomaterials have unique properties that differ from bulk materials. While these properties may enable technological advancements, the potential risks of ENMs to people and the environment are not yet fully understood. Certain low solubility nanoparticles are more toxic than their bulk material, such that existing occupational exposure limits may not be sufficiently protective for workers. Risk assessments are currently challenging due to gaps in data on the numerous emerging materials and applications as well as method uncertainties and limitations. Chemical mechanical planarization (CMP) processes with engineered nanoparticle abrasives are used for research and commercial manufacturing applications in the semiconductor and related industries. Despite growing use, no published studies addressed occupational exposures to nanoparticles associated with CMP or risk assessment and management practices for these scenarios. Additional studies are needed to evaluate potential sources of workplace exposure or emission, as well as to help test and refine assessment methods. This research was conducted to: identify the lifecycle stages and potential exposure sources for ENMs in CMP processes; characterize worker exposure; determine recommended engineering controls and compare risk assessment models. The study included workplace air and surface sampling and an evaluation of qualitative risk banding approaches. Exposure assessment results indicated the potential for worker contact with ENMs on workplace surfaces but did not identify nanoparticles readily dispersed in air during work tasks. Some increases in respirable particle concentrations were identified, but not consistently. Measured aerosol concentrations by number and mass were well below current reference values for poorly soluble low toxicity nanoparticles. From

  2. Microsporidia parasites disrupt the responses to cadmium exposure in a gammarid.

    PubMed

    Gismondi, Eric; Rigaud, Thierry; Beisel, Jean-Nicolas; Cossu-Leguille, Carole

    2012-01-01

    Microsporidia parasites are commonly found in amphipods, where they are often asymptomatic, vertically-transmitted and have several effects on host sexuality and behaviour. As amphipods are often used as models in ecotoxicological studies, we investigated the effect of microsporidian infections on energy reserves and defence capacities of Gammarus roeseli under cadmium stress. Only females were infected by two microsporidia parasites: Dictyocoela roeselum or Dictyocoela muelleri. In physiological conditions, microsporidia had no major effect on energy reserves and defence capacities of G. roeseli, while under cadmium exposure, energy reserves and antioxidant defence were weaker in infected females. Moreover, higher malondialdehyde levels detected in infected females revealed that they suffered more cellular damages. Our results suggest that microsporidia may affect gammarid fitness in stressful conditions, when parasitic stress cannot be compensated by the host. Consequently, microsporidia parasites should be a factor necessary to take into account in ecotoxicology studies involving amphipods. PMID:22035920

  3. Exposure to TiO2 nanoparticles increases Staphylococcusaureusinfection of HeLa cells

    NASA Astrophysics Data System (ADS)

    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.

  4. Effects of exposure to four endocrine disrupting-chemicals on fertilization and embryonic development of Barbel chub ( Squaliobarbus curriculus)

    NASA Astrophysics Data System (ADS)

    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.

  5. In utero exposure to environmentally relevant concentrations of PCB 153 and PCB 118 disrupts fetal testis development in sheep.

    PubMed

    Krogenæs, Anette K; Ropstad, Erik; Gutleb, Arno C; Hårdnes, Nina; Berg, Vidar; Dahl, Ellen; Fowler, Paul A

    2014-01-01

    Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production. PMID:24754397

  6. Trophic transfer of silver nanoparticles from earthworms disrupts the locomotion of springtails (Collembola).

    PubMed

    Kwak, Jin Il; An, Youn-Joo

    2016-09-01

    Understanding how nanomaterials are transferred through food chains and evaluating their resulting toxicity is important. However, limited research has been conducted on the toxic consequences of trophically transferred nanomaterials in terrestrial ecosystems. In this study, we documented the adverse effects of trophically transferred silver nanoparticles (AgNPs) in a soil-earthworm (Eisenia andrei)-Collembola (Lobella sokamensis) food chain. We exposed E. andrei to soil with AgNPs at concentrations of 50, 200, and 500μg AgNPs/g soil dry weight and assessed their survival after 7days. Trophic-transfer containers were then prepared and E. andrei that survived the 7days test period were washed, killed in boiling water, and added to the containers with L. sokamensis. We noted negligible effects and low bioaccumulation at the lowest AgNP concentration (50μg AgNPs/g soil dry weight) in earthworms and the L. sokamensis that fed on them. The highest concentration of AgNPs (500μg AgNPs/g soil dry weight) resulted in juvenile earthworm mortality and increased transfer of AgNPs to Collembola, which subsequently inhibited their locomotion. To our knowledge, this is the first study to document the trophic transfer and adverse effects of AgNPs in a soil-earthworm-Collembola food chain, a common prey-decomposer interaction in soil ecosystems. PMID:27187058

  7. Gold-nanoparticles ingestion disrupts reproduction and development in the German cockroach.

    PubMed

    Small, Taika; Ochoa-Zapater, M Amparo; Gallello, Gianni; Ribera, Antonio; Romero, Francisco M; Torreblanca, Amparo; Garcerá, M Dolores

    2016-09-15

    The present work shows the effects of gold nanoparticles (AuNPs) orally administered on reproduction and development of the insect Blattella germanica. Newly emerged females were provided with food containing AuNPs (87.44μg/g) of a size between 15 and 30nm (mean 21.8nm), and were allowed to mate with males. Food ingestion, mortality, reproductive parameters (time to ootheca formation and eclosion, ootheca viability and fertility) as well as postembryonic developmental parameters of the first ootheca (nymphal survival and life span) were recorded throughout the experiment. Gold from AuNPs was accumulated by adults of B. germanica with a bioaccumulation factor of 0.1. Ingestion of AuNPs did not disturb the time for ootheca formation nor ootheca eclosion. However, ootheca viability was decreased almost by 25% in AuNPs treated females in comparison to controls. At the same time the number of hatched nymphs was decreased by 32.8% (p<0.001) in AuNP group respect to control one. The postembryonic developmental parameters were also affected by AuNPs treatment, with a 35.8% of decrease (p<0.01) in number of nymphs that moulted to second and third instars and a reduction of their life span. Ingestion of AuNPs causes sublethal effects in B. germanica that compromises life-traits involved in population dynamics. B. germanica is proposed as a model species in nanotoxicological studies for urban environments. PMID:26905368

  8. Potential exposure of German consumers to engineered nanoparticles in cosmetics and personal care products.

    PubMed

    Lorenz, Christiane; Von Goetz, Natalie; Scheringer, Martin; Wormuth, Matthias; Hungerbühler, Konrad

    2011-03-01

    The rapid increase in the number of consumer products containing engineered nanoparticles (ENP) raises concerns about an appropriate risk assessment of these products. Along with toxicological data, exposure estimates are essential for assessing risk. Currently, cosmetics and personal care products (C&PCP) represent the largest ENP-containing consumer product class on the market. We analyzed factors influencing the likelihood that ENP-containing products are available to consumers. We modelled potential external exposure of German consumers, assuming a maximum possible case where only ENP-containing products are used. The distribution of exposure levels within the population due to different behavior patterns was included by using data from an extensive database on consumer behavior. Exposure levels were found to vary significantly between products and between consumers showing different behavior patterns. The assessment scheme developed here represents a basis for refined exposure modelling as soon as more specific information about ENPs in C&PCP becomes available. PMID:21417685

  9. ENDOCRINE-DISRUPTING CHEMICALS: PREPUBERTAL EXPOSURES AND EFFECTS ON SEXUAL MATURATION AND THYROID ACTIVITY IN THE FEMALE RAT. A FOCUS ON THE EDSTAC RECOMMENDATIONS

    EPA Science Inventory

    Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid activity in the female rat. A focus on the EDSTAC recommendations.

    Goldman JM, Laws SC, Balchak SK, Cooper RL, Kavlock RJ.

    Reproductive Toxicology Division, National H...

  10. Early Postnatal Exposure to Ultrafine Particulate Matter Air Pollution: Persistent Ventriculomegaly, Neurochemical Disruption, and Glial Activation Preferentially in Male Mice

    PubMed Central

    Allen, Joshua L.; Liu, Xiufang; Pelkowski, Sean; Palmer, Brian; Conrad, Katherine; Oberdörster, Günter; Weston, Douglas; Mayer-Pröschel, Margot

    2014-01-01

    mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans. Citation: Allen JL, Liu X, Pelkowski S, Palmer B, Conrad K, Oberdörster G, Weston D, Mayer-Pröschel M, Cory-Slechta DA. 2014. Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice. Environ Health Perspect 122:939–945; http://dx.doi.org/10.1289/ehp.1307984 PMID:24901756

  11. CHANGES IN GENE AND PROTEIN EXPRESSION IN ZEBRAFISH (DANIO RERIO) FOLLOWING EXPOSURE TO ENVIRONMENTALLY-RELEVANT ENDOCRINE DISRUPTING COMPOUNDS (EDCS)

    EPA Science Inventory

    Endocrine-disrupting chemicals (EDCs) are increasingly being reported in waterways worldwide and have been shown to affect fish species by disrupting numerous aspects of development, behavior, reproduction, and survival. Furthermore, new data have suggested that the reduced repr...

  12. Effects of Silver Nanoparticle Exposure on Germination and Early Growth of Eleven Wetland Plants

    PubMed Central

    Yin, Liyan; Colman, Benjamin P.; McGill, Bonnie M.; Wright, Justin P.; Bernhardt, Emily S.

    2012-01-01

    The increasing commercial production of engineered nanoparticles (ENPs) has led to concerns over the potential adverse impacts of these ENPs on biota in natural environments. Silver nanoparticles (AgNPs) are one of the most widely used ENPs and are expected to enter natural ecosystems. Here we examined the effects of AgNPs on germination and growth of eleven species of common wetland plants. We examined plant responses to AgNP exposure in simple pure culture experiments (direct exposure) and for seeds planted in homogenized field soils in a greenhouse experiment (soil exposure). We compared the effects of two AgNPs–20-nm polyvinylpyrrolidine-coated silver nanoparticles (PVP-AgNPs) and 6-nm gum arabic coated silver nanoparticles (GA-AgNPs)–to the effects of AgNO3 exposure added at equivalent Ag concentrations (1, 10 or 40 mg Ag L−1). In the direct exposure experiments, PVP-AgNP had no effect on germination while 40 mg Ag L−1 GA-AgNP exposure significantly reduced the germination rate of three species and enhanced the germination rate of one species. In contrast, 40 mg Ag L−1 AgNO3 enhanced the germination rate of five species. In general root growth was much more affected by Ag exposure than was leaf growth. The magnitude of inhibition was always greater for GA-AgNPs than for AgNO3 and PVP-AgNPs. In the soil exposure experiment, germination effects were less pronounced. The plant growth response differed by taxa with Lolium multiflorum growing more rapidly under both AgNO3 and GA-AgNP exposures and all other taxa having significantly reduced growth under GA-AgNP exposure. AgNO3 did not reduce the growth of any species while PVP-AgNPs significantly inhibited the growth of only one species. Our findings suggest important new avenues of research for understanding the fate and transport of NPs in natural media, the interactions between NPs and plants, and indirect and direct effects of NPs in mixed plant communities. PMID:23091638

  13. Irreversible thyroid disruption induced after subchronic exposure to hexachlorobenzene in male rats.

    PubMed

    Chalouati, Hela; Gamet-Payrastre, Laurence; Saad, Moncef Ben

    2016-05-01

    Thyroid hormones play a complex role in the toxicity of hexachlorobenzene (HCB) and related compounds. Time-course and dose-response experiments for free- and total thyroxine (T4) and triiodothyronine (T3) plasma levels for thyroid-stimulating hormone (TSH) and thyroid gland histomorphology were determined in male Wistar rats. Also, we examined the possible reversibility of changes noted after removal of HCB. Rats treated with this organochlorine compound resulted in a hypertrophy of the thyroid gland and altered thyroid function by decreasing significantly the levels of total- and free T4 in a dose-dependent manner (total T4: 28 and 51%; free T4: 21 and 37%), and this decrease was seen as early as 21 days and thereafter. Free T3 was also decreased by 21% with the highest dose starting from day 21. No significant changes were observed in the circulating levels of total T3 In response to the decrease of thyroid hormones, a dose-dependent increase of TSH levels (27 and 31%, respectively, for 4 mg and 16 mg/kg of HCB body weight) was observed after 21 days of HCB treatment. We have observed a hypertrophy and hyperplasia of follicular cells and a decrease in colloid volume in histological picture. When HCB was removed and changed by vehicle, the thyroid relative weight and plasma TSH continued to rise and serum thyroid hormones remained suppressed. These findings suggest that subchronic exposure of rats to HCB induced an irreversible hypothyroidism state. PMID:24311623

  14. In utero exposures to environmental organic pollutants disrupt epigenetic marks linked to fetoplacental development

    PubMed Central

    Kappil, Maya A.; Li, Qian; Li, An; Dassanayake, Priyanthi S.; Xia, Yulin; Nanes, Jessica A.; Landrigan, Philip J.; Stodgell, Christopher J.; Aagaard, Kjersti M.; Schadt, Eric E.; Dole, Nancy; Varner, Michael; Moye, John; Kasten, Carol; Miller, Richard K.; Ma, Yula; Chen, Jia; Lambertini, Luca

    2016-01-01

    While the developing fetus is largely shielded from the external environment through the protective barrier provided by the placenta, it is increasingly appreciated that environmental agents are able to cross and even accumulate in this vital organ for fetal development. To examine the potential influence of environmental pollutants on the placenta, we assessed the relationship between polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and several epigenetic marks linked to fetoplacental development. We measured IGF2/H19 imprint control region methylation, IGF2 and H19 expression, IGF2 loss of imprinting (LOI) and global DNA methylation levels in placenta (n = 116) collected in a formative research project of the National Children’s Study to explore the relationship between these epigenetic marks and the selected organic environmental pollutants. A positive association was observed between global DNA methylation and total PBDE levels (P <0.01) and between H19 expression and total PCB levels (P = 0.04). These findings suggest that differences in specific epigenetic marks linked to fetoplacental development occur in association with some, but not all, measured environmental exposures. PMID:27308065

  15. Silver nanoparticles disrupt wheat (Triticum aestivum L.) growth in a sand matrix.

    PubMed

    Dimkpa, Christian O; McLean, Joan E; Martineau, Nicole; Britt, David W; Haverkamp, Richard; Anderson, Anne J

    2013-01-15

    Hydroponic plant growth studies indicate that silver nanoparticles (Ag NPs) are phytotoxic. In this work, the phytotoxicity of commercial Ag NPs (10 nm) was evaluated in a sand growth matrix. Both NPs and soluble Ag were recovered from water extracts of the sand after growth of plants challenged with the commercial product; the surface charge of the Ag NPs in this extract was slightly reduced compared to the stock NPs. The Ag NPs reduced the length of shoots and roots of wheat in a dose-dependent manner. Furthermore, 2.5 mg/kg of the NPs increased branching in the roots of wheat (Triticum aestivum L.), thereby affecting plant biomass. Micron-sized (bulk) Ag particles (2.5 mg/kg) as well as Ag ions (63 μg Ag/kg) equivalent to the amount of soluble Ag in planted sand with Ag NPs (2.5 mg/kg) did not affect plant growth compared to control. In contrast, higher levels of Ag ions (2.5 mg/kg) reduced plant growth to a similar extent as the Ag NPs. Accumulation of Ag was detected in the shoots, indicating an uptake and transport of the metal from the Ag NPs in the sand. Transmision electron microscopy indicated that Ag NPs were present in shoots of plants with roots exposed to the Ag NPs or high levels of Ag ions. Both of these treatments caused oxidative stress in roots, as indicated by accumulation of oxidized glutathione, and induced expression of a gene encoding a metallothionein involved in detoxification by metal ion sequestration. Our findings demonstrate the potential effects of environmental contamination by Ag NPs on the metabolism and growth of food crops in a solid matrix. PMID:23259709

  16. Transcriptomic gene-network analysis of exposure to silver nanoparticle reveals potentially neurodegenerative progression in mouse brain neural cells.

    PubMed

    Lin, Ho-Chen; Huang, Chin-Lin; Huang, Yuh-Jeen; Hsiao, I-Lun; Yang, Chung-Wei; Chuang, Chun-Yu

    2016-08-01

    Silver nanoparticles (AgNPs) are commonly used in daily living products. AgNPs can induce inflammatory response in neuronal cells, and potentially develop neurological disorders. The gene networks in response to AgNPs-induced neurodegenerative progression have not been clarified in various brain neural cells. This study found that 3-5nm AgNPs were detectable to enter the nuclei of mouse neuronal cells after 24-h of exposure. The differentially expressed genes in mouse brain neural cells exposure to AgNPs were further identified using Phalanx Mouse OneArray® chip, and permitted to explore the gene network pathway regulating in neurodegenerative progression according to Cytoscape analysis. In focal adhesion pathway of ALT astrocytes, AgNPs induced the gene expression of RasGRF1 and reduced its downstream BCL2 gene for apoptosis. In cytosolic DNA sensing pathway of microglial BV2 cells, AgNPs reduced the gene expression of TREX1 and decreased IRF7 to release pro-inflammatory cytokines for inflammation and cellular activation. In MAPK pathway of neuronal N2a cells, AgNPs elevated GADD45α gene expression, and attenuated its downstream PTPRR gene to interfere with neuron growth and differentiation. Moreover, AgNPs induced beta amyloid deposition in N2a cells, and decreased PSEN1 and PSEN2, which may disrupt calcium homeostasis and presynaptic dysfunction for Alzheimer's disease development. These findings suggested that AgNPs exposure reveals the potency to induce the progression of neurodegenerative disorder. PMID:27131904

  17. Risk Evaluation of Endocrine-Disrupting Chemicals: Effects of Developmental Exposure to Low Doses of Bisphenol A on Behavior and Physiology in Mice (Mus musculus).

    PubMed

    Gioiosa, Laura; Palanza, Paola; Parmigiani, Stefano; Vom Saal, Frederick S

    2015-01-01

    We review here our studies on early exposure to low doses of the estrogenic endocrine-disrupting chemical bisphenol A (BPA) on behavior and metabolism in CD-1 mice. Mice were exposed in utero from gestation day (GD) 11 to delivery (prenatal exposure) or via maternal milk from birth to postnatal day 7 (postnatal exposure) to 10 µg/kg body weight/d of BPA or no BPA (controls). Bisphenol A exposure resulted in long-term disruption of sexually dimorphic behaviors. Females exposed to BPA pre- and postnatally showed increased anxiety and behavioral profiles similar to control males. We also evaluated metabolic effects in prenatally exposed adult male offspring of dams fed (from GD 9 to 18) with BPA at doses ranging from 5 to 50 000 µg/kg/d. The males showed an age-related significant change in a number of metabolic indexes ranging from food intake to glucose regulation at BPA doses below the no observed adverse effect level (5000 µg/kg/d). Consistent with prior findings, low but not high BPA doses produced significant effects for many outcomes. These findings provide further evidence of the potential risks that developmental exposure to low doses of the endocrine disrupter BPA may pose to human health, with fetuses and infants being highly vulnerable. PMID:26740806

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

    PubMed

    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 <30nm in diameter being formed during the thermal treatment. In addition, ultrafine and nano-sized airborne particles were generated and emitted into workplace air during sintering process on a statistically significant level. These results evidence the risk of occupational exposure to ultrafine and nanoparticles during tile sintering activity since workers would be exposed to concentrations above the nano reference value (NRV; 4×10(4)cm(-3)), with 8-hour time weighted average concentrations in the range of 1.4×10(5)cm(-3) and 5.3×10(5)cm(-3). A potential risk for nanoparticle and ultrafine particle release to the environment was also identified, despite the fact that the efficiency of the filtration system was successfully tested and evidenced a >87% efficiency in particle number concentrations removal. PMID:26848012

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

    USGS Publications Warehouse

    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.

  20. Blood-Brain Barrier Disruption and Oxidative Stress in Guinea Pig after Systemic Exposure to Modified Cell-Free Hemoglobin

    PubMed Central

    Butt, Omer I.; Buehler, Paul W.; D'Agnillo, Felice

    2011-01-01

    Systemic exposure to cell-free hemoglobin (Hb) or its breakdown products after hemolysis or with the use of Hb-based oxygen therapeutics may alter the function and integrity of the blood-brain barrier. Using a guinea pig exchange transfusion model, we investigated the effect of a polymerized cell-free Hb (HbG) on the expression of endothelial tight junction proteins (zonula occludens 1, claudin-5, and occludin), astrocyte activation, IgG extravasation, heme oxygenase (HO), iron deposition, oxidative end products (4-hydroxynonenal adducts and 8-hydroxydeoxyguanosine), and apoptosis (cleaved caspase 3). Reduced zonula occludens 1 expression was observed after HbG transfusion as evidenced by Western blot and confocal microscopy. Claudin-5 distribution was altered in small- to medium-sized vessels. However, total expression of claudin-5 and occludin remained unchanged except for a notable increase in occludin 72 hours after HbG transfusion. HbG-transfused animals also showed increased astrocytic glial fibrillary acidic protein expression and IgG extravasation after 72 hours. Increased HO activity and HO-1 expression with prominent enhancement of HO-1 immunoreactivity in CD163-expressing perivascular cells and infiltrating monocytes/macrophages were also observed. Consistent with oxidative stress, HbG increased iron deposition, 4-hydroxynonenal and 8-hydroxydeoxyguanosine immunoreactivity, and cleaved caspase-3 expression. Systemic exposure to an extracellular Hb triggers blood-brain barrier disruption and oxidative stress, which may have important implications for the use of Hb-based therapeutics and may provide indirect insight on the central nervous system vasculopathies associated with excessive hemolysis. PMID:21356382

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

    USGS Publications Warehouse

    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.

  2. Endocrine disrupting chemicals-Linking internal exposure to vitellogenin levels and ovotestis in Abramis brama from Dutch surface waters.

    PubMed

    Reinen, Jelle; Suter, Marc J-F; Vögeli, A Christiane; Fernandez, Mariana F; Kiviranta, Hannu; Eggen, Rik I L; Vermeulen, Nico P E

    2010-11-01

    The exposure of male bream from three Dutch freshwater locations to endocrine disrupting compounds (EDCs) and corresponding effects are described in this study. Fish specimen displaying reproductive disorders associated with high levels of plasma vitellogenin (VTG) concentrations and occurrence of ovotestis (OT) were investigated. To provide information on the full spectrum of EDCs in fish tissue, adipose tissue samples of individual fish were analyzed for nearly 130 chemicals targeting different compound classes (bisphenols, alkylphenols, pesticides, polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), hydroxylated polychlorinated biphenyls (OH-PCBs), polybrominated diphenyl ethers (PBDEs) and biphenyls (PBBs)) and steroid hormones. To establish whether tissue from specimen with reproductive disorders shows a spectrum of EDCs that is qualitatively and quantitatively different from that of controls free of symptoms, bioassay-directed fractionation was performed using the recombinant yeast estrogen screen (YES), the E-Screen bioassay, the human sulfotransferase 1E1 (SULT1E1) inhibition assay, and the coumestrol-based estrogen receptor α (ERα) high resolution screening (HRS) assay. No differences in estrogenicity could be observed between the cases and controls and steroidal estrogens accounted for the majority of estrogenicity found in the complex mixtures. In this study, the combination of the different assays employed to measure total estrogenicity and the SULT1E1 inhibition does not predict the outcome of unwanted physiological effects, however, it can be used to determine the presence of EDCs in fish samples and their estrogenic effects. PMID:21787654

  3. Analytical methods for the assessment of endocrine disrupting chemical exposure during human fetal and lactation stages: a review.

    PubMed

    Jiménez-Díaz, I; Vela-Soria, F; Rodríguez-Gómez, R; Zafra-Gómez, A; Ballesteros, O; Navalón, A

    2015-09-10

    In the present work, a review of the analytical methods developed in the last 15 years for the determination of endocrine disrupting chemicals (EDCs) in human samples related with children, including placenta, cord blood, amniotic fluid, maternal blood, maternal urine and breast milk, is proposed. Children are highly vulnerable to toxic chemicals in the environment. Among these environmental contaminants to which children are at risk of exposure are EDCs -substances able to alter the normal hormone function of wildlife and humans-. The work focuses mainly on sample preparation and instrumental techniques used for the detection and quantification of the analytes. The sample preparation techniques include, not only liquid-liquid extraction (LLE) and solid-phase extraction (SPE), but also modern microextraction techniques such as extraction with molecular imprinted polymers (MIPs), stir-bar sorptive extraction (SBSE), hollow-fiber liquid-phase microextraction (HF-LPME), dispersive liquid-liquid microextraction (DLLME), matrix solid phase dispersion (MSPD) or ultrasound-assisted extraction (UAE), which are becoming alternatives in the analysis of human samples. Most studies focus on minimizing the number of steps and using the lowest solvent amounts in the sample treatment. The usual instrumental techniques employed include liquid chromatography (LC), gas chromatography (GC) mainly coupled to tandem mass spectrometry. Multiresidue methods are being developed for the determination of several families of EDCs with one extraction step and limited sample preparation. PMID:26388473

  4. Exposure to endocrine disrupters and nuclear receptor gene expression in infertile and fertile women from different Italian areas.

    PubMed

    La Rocca, Cinzia; Tait, Sabrina; Guerranti, Cristiana; Busani, Luca; Ciardo, Francesca; Bergamasco, Bruno; Stecca, Laura; Perra, Guido; Mancini, Francesca Romana; Marci, Roberto; Bordi, Giulia; Caserta, Donatella; Focardi, Silvano; Moscarini, Massimo; Mantovani, Alberto

    2014-01-01

    Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERa, ERb, AR, AhR, PPARg, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARg. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health. PMID:25268510

  5. Exposure to Endocrine Disrupters and Nuclear Receptor Gene Expression in Infertile and Fertile Women from Different Italian Areas

    PubMed Central

    La Rocca, Cinzia; Tait, Sabrina; Guerranti, Cristiana; Busani, Luca; Ciardo, Francesca; Bergamasco, Bruno; Stecca, Laura; Perra, Guido; Mancini, Francesca Romana; Marci, Roberto; Bordi, Giulia; Caserta, Donatella; Focardi, Silvano; Moscarini, Massimo; Mantovani, Alberto

    2014-01-01

    Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERα, ERβ, AR, AhR, PPARγ, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARγ. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health. PMID:25268510

  6. Immunological and ultrastructural disruptions of T lymphocytes following exposure to the glycopeptidolipid isolated from the Mycobacterium avium complex.

    PubMed

    Pourshafie, M R; Sonnenfeld, G; Barrow, W W

    1999-04-01

    In this study, we examined the effects of the serovar-specific glycopeptidolipid (GPL) on the ultrastructure of purified T lymphocytes and the interleukin secretion by spleen and purified T lymphocytes. Electron microscopy indicated extensive disruption of the cytoplasmic compartment of T lymphocytes, which could result in altered function of immune cells. Despite the cellular damage as viewed by the electron microscopy, the expression of T-cell surface markers, Thy 1.2 and Lyt-2, were not affected. The data indicate that GPL is capable of inducing in-vitro interleukin (IL)-6 and IL-2 production by whole spleen or purified spleen T lymphocytes. The level of production of IL-6 and IL-2 following the exposure of the mycobacteria-infected cells to GPL was approximately the same as the uninfected control. A similar finding was also obtained with the total lipid extraction from the mycobacterium. The results suggest that the ability of the total lipid extraction, in inducing cytokine production, may be attributed to its GPL content. PMID:10219767

  7. Exposure to silica nanoparticles causes reversible damage of the spermatogenic process in mice.

    PubMed

    Xu, Ying; Wang, Na; Yu, Yang; Li, Yang; Li, Yan-Bo; Yu, Yong-Bo; Zhou, Xian-Qing; Sun, Zhi-Wei

    2014-01-01

    Environmental exposure to nanomaterials is inevitable, as nanomaterials have become part of our daily life now. In this study, we firstly investigated the effects of silica nanoparticles on the spermatogenic process according to their time course in male mice. 48 male mice were randomly divided into control group and silica nanoparticle group with 24 mice per group, with three evaluation time points (15, 35 and 60 days after the first dose) per group. Mice were exposed to the vehicle control and silica nanoparticles at a dosage of 20 mg/kg every 3 days, five times over a 13-day period, and were sacrificed at 15, 35 and 60 days after the first dose. The results showed that silica nanoparticles caused damage to the mitochondrial cristae and decreased the levels of ATP, resulting in oxidative stress in the testis by days 15 and 35; however, the damage was repaired by day 60. DNA damage and the decreases in the quantity and quality of epididymal sperm were found by days 15 and 35; but these changes were recovered by day 60. In contrast, the acrosome integrity and fertility in epididymal sperm, the numbers of spermatogonia and sperm in the testes, and the levels of three major sex hormones were not significantly affected throughout the 60-day period. The results suggest that nanoparticles can cause reversible damage to the sperms in the epididymis without affecting fertility, they are more sensitive than both spermatogonia and spermatocytes to silica nanoparticle toxicity. Considering the spermatogenesis time course, silica nanoparticles primarily influence the maturation process of sperm in the epididymis by causing oxidative stress and damage to the mitochondrial structure, resulting in energy metabolism dysfunction. PMID:25003337

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

    SciTech Connect

    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

    2014-11-15

    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.

  9. Effects of carbon-based nanoparticles (CNPs) on the fate of endocrine disrupting chemicals (EDCs) in different agricultural soils.

    NASA Astrophysics Data System (ADS)

    Stumpe, Britta; Wolski, Sabrina; Marschner, Bernd

    2013-04-01

    Nanotechnology is a major innovative scientific and economic growth area. To date there is a lack about possible adverse effects that may be associated with manufactured nanomaterial in terrestrial environments. Since it is known that on the one hand carbon-based nanoparticles (CNPs) and endocrine disrupting chemicals (EDCs) strongly interact in wastewater and that on the other hand CNPs and EDCs are released together via wastewater irrigation to agricultural soils, knowledge of CNP effects on the EDC fate in the soil environment is needed for further risk assessments. The overall goal of this project is to gain a better understanding of interaction of CNPs with EDCs within the soil system. Three different soil samples were applied with different CNPs, EDCs and CNP-EDC complexes and incubated over a period of 6 weeks. The EDC mineralization as well as their uptake by soil microorganisms was monitored to describe impacts of the nanomaterial on the EDC fate. As quality control for the biological soil activity soil respiration, enzyme activities and the soil microbial biomass were monitored in all incubated soil samples. Clearly, EDCs bound in CNP complexes showed a decrease in mineralization. While the free EDCs showed a total mineralization of 34 to 45 %, the nano complexed EDCs were only mineralized to 12 to 15 %. Since no effects of the nanomaterial on the biological soil activity were observed, we conclude that the reduced EDC mineralization is directly linked to their interaction with the CNPs. Since additionally the EDC adsorption to CNPs reduced the EDC uptake by soil microorganism, we assume that CNPs generally form more or less recalcitrant aggregates which likely protect the associated EDCs from degradation.

  10. A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles

    PubMed Central

    2009-01-01

    Background Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), in vitro cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid interface. Results A novel air-liquid interface cell exposure system (ALICE) for nanoparticles in liquids is presented and validated. The ALICE generates a dense cloud of droplets with a vibrating membrane nebulizer and utilizes combined cloud settling and single particle sedimentation for fast (~10 min; entire exposure), repeatable (<12%), low-stress and efficient delivery of nanoparticles, or dissolved substances, to cells cultured at the air-liquid interface. Validation with various types of nanoparticles (Au, ZnO and carbon black nanoparticles) and solutes (such as NaCl) showed that the ALICE provided spatially uniform deposition (<1.6% variability) and had no adverse effect on the viability of a widely used alveolar human epithelial-like cell line (A549). The cell deposited dose can be controlled with a quartz crystal microbalance (QCM) over a dynamic range of at least 0.02-200 μg/cm2. The cell-specific deposition efficiency is currently limited to 0.072 (7.2% for two commercially available 6-er transwell plates), but a deposition efficiency of up to 0.57 (57%) is possible for better cell coverage of the exposure chamber. Dose-response measurements with ZnO nanoparticles (0.3-8.5 μg/cm2) showed significant differences in mRNA expression of pro-inflammatory (IL-8) and oxidative stress (HO-1) markers when comparing submerged and air-liquid interface exposures. Both exposure methods showed no cellular response below 1 μg/cm2 ZnO, which indicates that ZnO nanoparticles are not toxic at occupationally allowed exposure levels. Conclusion The ALICE

  11. Potential for exposure to engineered nanoparticles from nanotechnology-based consumer spray products

    PubMed Central

    NAZARENKO, YEVGEN; HAN, TAE WON; LIOY, PAUL J.; MAINELIS, GEDIMINAS

    2014-01-01

    The potential for human exposure to engineered nanoparticles due to the use of nanotechnology-based consumer sprays (categorized as such by the Nanotechnology Consumer Products Inventory) is examined along with analogous products, which are not specified as nanotechnology-based (regular products). Photon correlation spectroscopy was used to obtain particle size distributions in the initial liquid products. Transmission electron microscopy was used to determine particle size, shape, and agglomeration of the particles. Realistic application of the spray products near the human breathing zone characterized airborne particles that are released during use of the sprays. Aerosolization of sprays with standard nebulizers was used to determine their potential for inhalation exposure. Electron microscopy detected the presence of nanoparticles in some nanotechnology-based sprays as well as in several regular products, whereas the photon correlation spectroscopy indicated the presence of particles <100 nm in all investigated products. During the use of most nanotechnology-based and regular sprays, particles ranging from 13 nm to 20 μm were released, indicating that they could he inhaled and consequently deposited in all regions of the respiratory system. The results indicate that exposures to nanoparticles as well as micrometer-sized particles can be encountered owing to the use of nanotechnology-based sprays as well as regular spray products. PMID:21364702

  12. Pulmonary Cerium Dioxide Nanoparticles Exposure Differentially Impairs Coronary and Mesenteric Arteriolar Reactivity

    PubMed Central

    Minarchick, Valerie C; Stapleton, Phoebe A; Porter, Dale W; Wolfarth, Michael G; Çiftyürek, Engin; Barger, Mark; Sabolsky, Edward M.; Nurkiewicz, Timothy R

    2013-01-01

    Cerium dioxide nanoparticles (CeO2 NPs) are an engineered nanomaterial that possesses unique catalytic, oxidative and reductive properties. Currently, CeO2 NPs are being used as a fuel catalyst but these properties are also utilized in the development of potential drug treatments for radiation and stroke protection. These uses of CeO2 NPs present a risk for human exposure; however, to date no studies have investigated the effects of CeO2 NPs on the microcirculation following pulmonary exposure. Previous studies in our laboratory with other nanomaterials have shown impairments in normal microvascular function after pulmonary exposures. Therefore, we predicted that CeO2 NP exposure would cause microvascular dysfunction that is dependent on the tissue bed and dose. Twenty-four hour post exposure to CeO2 NPs (0–400 μg), mesenteric and coronary arterioles were isolated and microvascular function was assessed. Our results provided evidence that pulmonary CeO2 NP exposure impairs endothelium-dependent and -independent arteriolar dilation in a dose-dependent manner. The CeO2 NP exposure dose which causes a 50% impairment in arteriolar function (EC50) was calculated and ranged from 15 – 100 μg depending on the chemical agonist and microvascular bed. Microvascular assessments with acetylcholine revealed a 33–75% reduction in function following exposure. Additionally, there was a greater sensitivity to CeO2 NP exposure in the mesenteric microvasculature due to the 40% decrease in the calculated EC50 compared to the coronary microvasculature EC50. CeO2 NP exposure increased mean arterial pressure in some groups. Taken together these observed microvascular changes may likely have detrimental effects on local blood flow regulation and contribute to cardiovascular dysfunction associated with particle exposure. PMID:23645470

  13. Engineered nanoparticle respiratory exposure and potential risks for cardiovascular toxicity: predictive tests and biomarkers.

    PubMed

    Simeonova, Petia P; Erdely, Aaron

    2009-07-01

    The most attractive properties of engineered nanomaterials for technological applications, including their small size, large surface area, and high reactivity, are also the main factors for their potential toxicity. Based on ambient ultrafine particle research, it is predicted that nanosized particles may have deeper pulmonary deposition, higher biological activity, and a tendency for extrapulmonary translocation compared to larger particles. In this regard, nanoparticle exposure, by direct or indirect mechanisms, may lead to unexpected distant responses, involving the immune system, cardiovascular system, liver, kidney, and brain. The systemic effects may induce or modify the progression of existing diseases such as cardiovascular disease. Current experimental toxicity evaluation of engineered nanomaterials, specifically carbon nanotubes, demonstrated that deposition of these materials in the lung leads to inflammation and fibrosis. The local toxicity is associated with cardiovascular effects related to atherosclerosis. Although translocation of carbon nanotubes into the systemic circulation is hypothetically possible, there is no current evidence to support this hypothesis. However, studies pointed out that carbon nanotube-induced lung inflammation results in a release of inflammatory mediators and activation of blood cells which can contribute to cardiovascular adverse effects. Furthermore, complex protein and gene expression blood analysis can help in development of biomarkers for application in human screening of nanoparticle exposure. Future studies to evaluate the systemic effects of carbon nanotube exposure under workplace or environmental exposure paradigms should be conducted. PMID:19558236

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

    PubMed Central

    2011-01-01

    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. PMID:21943386

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

    PubMed Central

    2010-01-01

    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 pathological processes. In

  16. Exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of ERK signal pathway.

    PubMed

    Li, Juan; Mao, Rui; Zhou, Qin; Ding, Ling; Tao, Jin; Ran, Mao-Mei; Gao, Er-Sheng; Yuan, Wei; Wang, Jin-Tao; Hou, Li-Fang

    2016-03-01

    Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to human health. Exposure to BPA can negatively impact sperm quality. However, the mechanism remains largely unknown. The objectives of this study were to assess the role of BPA on sperm quality and explore the possible mechanisms. The Wistar male rats (aged 28 days) were administered BPA by oral gavage for 28 days at dose of 50, 100 and 200 mg/kg/day; meanwhile, the negative control with corn oil (0 mg/kg/day BPA) and positive control with E2 at the dose of 100 μg/kg/day. The sperm density, sperm activity and sperm survival rate were analyzed byCASA system, and the sperm abnormality rate was analyzed by improved Papanicolaou stained. The protein expression levels of Src/p-Src, ERK1/2, p-ERK1/2 and CREB/p-CREB were detected by Western bolt. The results showed that the body weight gain, testes weight, testis coefficient, sperm density, sperm activity, sperm survival rate and protein expression levels of p-ERK1, p-ERK2 and p-CREB decreased, but the sperm abnormality rate increased with increasing BPA concentrations. There were positive correlations between sperm density, sperm activity and sperm survival rate with protein expression levels of p-ERK1, p-ERK2 and p-CREB, and negative correlations between sperm abnormality rate with the protein expression levels of p-ERK1, p-ERK2 and p-CREB. Results from the structural equation model demonstrated that BPA retained a significant negative effect to p-ERK, whereas p-ERK retained a significant positive effect to sperm quality and acted as the mediate variable. This study provides a novel insight regarding the potential role of p-ERK1 and p-ERK2 protein kinase on reproductive toxicity of BPA. The adverse effects of BPA on adult male sperm quality may be through the induction of the disruption of ERK signal pathway. However, additional

  17. Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model

    PubMed Central

    Xu, Liming; Dan, Mo; Shao, Anliang; Cheng, Xiang; Zhang, Cuiping; Yokel, Robert A; Takemura, Taro; Hanagata, Nobutaka; Niwa, Masami; Watanabe, Daisuke

    2015-01-01

    Background Silver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood–brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood. Method To investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression of astrocytes was measured using a DNA microarray. Results A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm2. After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the tight junction (TJ) protein ZO-1 was decreased. Discontinuous TJs were also observed between microvascular endothelial cells. After Ag-NPS exposure, severe mitochondrial shrinkage, vacuolations, endoplasmic reticulum expansion, and Ag-NPs were observed in astrocytes by TEM. Global gene expression analysis showed that three genes were upregulated and 20 genes were downregulated in astrocytes treated with Ag-NPS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the 23 genes were associated with metabolic processes, biosynthetic processes, response to stimuli, cell death, the MAPK pathway, and so on. No GO term and KEGG pathways were changed in the released-ion or polystyrene-NP groups. Ag-NPS inhibited the antioxidant defense of the astrocytes by increasing thioredoxin interacting protein, which inhibits the Trx system, and

  18. EFFECTS OF TITANIUM DIOXIDE NANOPARTICLE EXPOSURE ON NEUROIMMUNE RESPONSES IN RAT AIRWAYS

    PubMed Central

    Scuri, Mario; Chen, Bean T.; Castranova, Vincent; Reynolds, Jeffrey S.; Johnson, Victor J.; Samsell, Lennie; Walton, Cheryl; Piedimonte, Giovanni

    2013-01-01

    Exposure to ambient nanoparticles (defined as particulate matter [PM] having one dimension < 100 nm) is associated with increased risk of childhood and adult asthma. Nanomaterials feature a smaller aerodynamic diameter and a higher surface area per unit mass ratio compared to fine or coarse-sized particles, resulting in greater lung deposition efficiency and an increased potential for biological interaction. The neurotrophins nerve growth factor and brain-derived neurotrophic factor are key regulatory elements of neuronal development and responsiveness of airway sensory neurons. Changes in their expression are associated with bronchoconstriction, airway hyperresponsiveness, and airway inflammation. The neurogenic-mediated control of airway responses is a key pathophysiological mechanism of childhood asthma. However, the effects of nanoparticle exposure on neurotrophin-driven airway responses and their potential role as a predisposing factor for developing asthma have not been clearly elucidated. In this study, in vivo inhalation exposure to titanium dioxide nanoparticles (12 mg/m13; 5.6 h/d for 3 d) produced upregulation of lung neurotrophins in weanling (2-wk-old) and newborn (2-d-old) rats but not in adult (12-wk-old) animals compared to controls. This effect was associated with increased airway responsiveness and upregulation of growth-related oncogene/keratine-derived chemokine (GRO/KC; CXCL1, rat equivalent of human interleukin [IL]-8) in bronchoalveolar lavage fluid. These data show for the first time that exposure to nanoparticulate upregulates the expression of lung neurotrophins in an age-dependent fashion and that this effect is associated with airway hyperresponsiveness and inflammation. These results suggest the presence of a critical window of vulnerability in earlier stages of lung development, which may lead to a higher risk of developing asthma. PMID:20818535

  19. Magnetic field enhanced convective diffusion of iron oxide nanoparticles in an osmotically disrupted cell culture model of the blood–brain barrier

    PubMed Central

    Sun, Zhizhi; Worden, Matthew; Wroczynskyj, Yaroslav; Yathindranath, Vinith; van Lierop, Johan; Hegmann, Torsten; Miller, Donald W

    2014-01-01

    Purpose The present study examines the use of an external magnetic field in combination with the disruption of tight junctions to enhance the permeability of iron oxide nanoparticles (IONPs) across an in vitro model of the blood–brain barrier (BBB). The feasibility of such an approach, termed magnetic field enhanced convective diffusion (MFECD), along with the effect of IONP surface charge on permeability, was examined. Methods The effect of magnetic field on the permeability of positively (aminosilane-coated [AmS]-IONPs) and negatively (N-(trimethoxysilylpropyl)ethylenediaminetriacetate [EDT]-IONPs) charged IONPs was evaluated in confluent monolayers of mouse brain endothelial cells under normal and osmotically disrupted conditions. Results Neither IONP formulation was permeable across an intact cell monolayer. However, when tight junctions were disrupted using D-mannitol, flux of EDT-IONPs across the bEnd.3 monolayers was 28%, increasing to 44% when a magnetic field was present. In contrast, the permeability of AmS-IONPs after osmotic disruption was less than 5%. The cellular uptake profile of both IONPs was not altered by the presence of mannitol. Conclusions MFECD improved the permeability of EDT-IONPs through the paracellular route. The MFECD approach favors negatively charged IONPs that have low affinity for the brain endothelial cells and high colloidal stability. This suggests that MFECD may improve IONP-based drug delivery to the brain. PMID:25018630

  20. Silver nanoparticles: their potential toxic effects after oral exposure and underlying mechanisms--a review.

    PubMed

    Gaillet, Sylvie; Rouanet, Jean-Max

    2015-03-01

    Because of their antimicrobial properties, the use of silver nanoparticles (AgNPs) is increasing fast in industry, food, and medicine. In the food industry, nanoparticles are used in packaging to enable better conservation products such as sensors to track their lifetime, and as food additives, such as anti-caking agents and clarifying agents for fruit juices. Nanoemulsions, used to encapsulate, protect and deliver additives are also actively developed. Nanomaterials in foods will be ingested and passed through the digestive tract. Those incorporated in food packaging may also be released unintentionally into food, ending up in the gastrointestinal tract. It is therefore important to make a risk assessment of nanomaterials to the consumer. Thus, exposure to AgNPs is increasing in quantity and it is imperative to know their adverse effects in man. However, controversies still remain with respect to their toxic effects and their mechanisms. Understanding the toxic effects and the interactions of AgNPs with biological systems is necessary to handle these nanoparticles and their use. They usually generate reactive oxygen species resulting in increased pro-inflammatory reactions and oxidative stress via intracellular signalling pathways. Here, we mainly focus on the routes of exposure of AgNPs, toxic effects and the mechanisms underlying the induced toxicity. PMID:25556118

  1. Comparison of the effectiveness of exposure to low LET helium particles (4He) and gamma rays (137Cs) on the disruption of cognitive performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rats were exposed to either Helium (4He) particles (1000 MeV/n; 0.1 – 10 cGy; head-only) or Cesium 137Cs gamma rays (50 – 400 cGy; whole body) and the effects of irradiation on cognitive performance evaluated. The results indicated that exposure to doses of 4He particles as low as 0.1 cGy disrupted...

  2. Toxicological risk assessment of elemental gold following oral exposure to sheets and nanoparticles - A review.

    PubMed

    Hadrup, Niels; Sharma, Anoop K; Poulsen, Morten; Nielsen, Elsa

    2015-07-01

    Elemental gold is used as a food coloring agent and in dental fillings. In addition, gold nanoparticles are gaining increasing attention due to their potential use as inert carriers for medical purposes. Although elemental gold is considered to be inert, there is evidence to suggest the release of gold ions from its surface. Elemental gold, or the released ions, is, to some extent, absorbed in the gastrointestinal tract. Gold is distributed to organs such as the liver, heart, kidneys and lungs. The main excretion route of absorbed gold is through urine. Data on the oral toxicity of elemental gold is limited. The acute toxicity of elemental gold seems to be low, as rats were unaffected by a single dose of 2000mg nanoparticles/kg of body weight. Information on repeated dose toxicity is very limited. Skin rashes have been reported in humans following the ingestion of liquors containing gold. In addition, gold released from dental restorations has been reported to increase the risk of developing gold hypersensitivity. Regarding genotoxicity, in vitro studies indicate that gold nanoparticles induce DNA damage in mammalian cells. In vivo, gold nanoparticles induce genotoxic effects in Drosophila melanogaster; however, genotoxicity studies in mammals are lacking. Overall, based on the literature and taking low human exposure into account, elemental gold via the oral route is not considered to pose a health concern to humans in general. PMID:25929617

  3. Comparative modeling of exposure to airborne nanoparticles released by consumer spray products.

    PubMed

    Riebeling, Christian; Luch, Andreas; Götz, Mario Enrico

    2016-04-01

    Consumer exposure to sprays containing nano-objects is a continuing concern as a potential health hazard. One potential hazard has been formulated in the overload hypothesis. It describes a volume fraction of the macrophages that is occupied by deposited nanoparticles that leads to reduced macrophage mobility. Subsequent chronic inflammation may then lead to severe health consequences including cancer. To calculate lung deposition of spherical particles, the Multiple-Path Particle Dosimetry (MPPD) model (ARA, Albuquerque, NM) provides different kinds of lung models and age settings. Using the MPPD v 2.11 software, we modeled several consumer-related exposure scenarios. Different body orientations and age groups were investigated. Moreover, a number of materials representing different densities were used, and the exposure calculated using MPPD is compared to the hazard derived from the overload hypothesis. Conditions leading to macrophage overload were found for exposures to high particle doses for prolonged times and repeated exposure. Such conditions are unlikely in the context of regular consumer exposure. The overload hypothesis assumes the particles to be inert and biopersistent, a condition that currently lacks a clear regulatory definition and is valid only for a few selected materials. Furthermore, because of material-specific effects and the possibility of surface adsorption of hazardous chemicals, nano-objects in propellant sprays remain of concern for consumer health. PMID:26418667

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

    PubMed

    Tiede, Karen; Hanssen, Steffen Foss; Westerhoff, Paul; Fern, Gordon J; Hankin, Steven M; Aitken, Robert J; Chaudhry, Qasim; Boxall, Alistair B A

    2016-01-01

    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 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 of ENPs in raw water and treated drinking water, using a simple exposure model, were estimated and then qualitatively compared to available estimates for human exposure through other routes. A range of metal, metal oxide and organic-based ENPs were identified that have the potential to contaminate 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. The exceptions were some clothing materials, paints and coatings and cleaning products containing Ag, Al, TiO2, Fe2O3 ENPs and carbon-based materials. PMID:25962682

  5. Graphene-based composite with γ-Fe2O3 nanoparticle for the high-performance removal of endocrine-disrupting compounds from water.

    PubMed

    Sinha, Arjyabaran; Jana, Nikhil R

    2013-04-01

    Graphene is a 2D sp(2)-hybridized carbon sheet and an ideal material for the adsorption-based separation of organic pollutants. However, such potential applications of graphene are largely limited, owing to their poor solubility and extensive aggregation properties through graphene-graphene interactions. Herein, we report the synthesis of graphene-based composites with γ-Fe2O3 nanoparticle for the high-performance removal of endocrine-disrupting compounds (EDC) from water. The γ-Fe2O3 nanoparticles partially inhibit these graphene-graphene interactions and offer water dispersibility of the composite without compromising much of the high surface area of graphene. In their dispersed form, the graphene component offers the efficient adsorption of EDC, whilst the magnetic iron-oxide component offers easier magnetic separation of adsorbed EDC. PMID:23401314

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

    SciTech Connect

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

    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

  7. Silver nanoparticle exposure causes apoptotic response in the earthworm Lumbricus terrestris (Oligochaeta).

    PubMed

    Lapied, Emmanuel; Moudilou, Elara; Exbrayat, Jean-Marie; Oughton, Deborah Helen; Joner, Erik Jautris

    2010-08-01

    In terrestrial ecotoxicology there is a serious lack of data for potential hazards posed by engineered nanoparticles (ENPs). This is partly due to complex interactions between ENPs and the soil matrix, but also to the lack of suitable toxicological end points in organisms that are exposed to ENPs in a relevant manner. Earthworms are key organisms in terrestrial ecosystems, but so far only physiological end points of low sensitivity have been used in ecotoxicity studies with ENPs. We exposed the earthworm Lumbricus terrestris to silver nanoparticles and measured their impact on apoptosis in different tissues. Increased apoptotic activity was detected in a range of tissues both at acute and sublethal concentrations (down to 4 mg/kg soil). Comparing exposure in water and soil showed reduced bioavailability in soil reflected in the apoptotic response. Apoptosis appears to be a sensitive end point and potentially a powerful tool for quantifying environmental hazards of ENPs. PMID:20735231

  8. Zeta potential change of Neuro-2a tumor cells after exposure to alumina nanoparticles

    NASA Astrophysics Data System (ADS)

    Kazantsev, Sergey O.; Fomenko, Alla N.; Korovin, Matvey S.

    2016-08-01

    In recent years, researches have paid much attention to the physical, chemical, biophysical and biochemical properties of a cell surface. It is known that most of the cells' surfaces are charged. This charge depends on the biochemical structure of the cell membranes. Therefore, measurement of a cell surface charge is a significant criterion that gives information about the cell surface. Evaluation of the cells zeta-potential is important to understand the interaction mechanisms of various drugs, antibiotics, as well as the interaction of nanoparticles with the cell surface. In this study, we use the dynamic light scattering method to detect the zeta-potential change of Neuro-2a tumor cells. It has been observed that zeta-potential shifted to negative values after exposure to metal oxide nanoparticles and inducing apoptosis.

  9. Persistent Adult Zebrafish Behavioral Deficits Results from Acute Embryonic Exposure to Gold Nanoparticles

    PubMed Central

    Truong, Lisa; Saili, Katerine S.; Miller, John M.; Hutchison, James E.; Tanguay, Robert L.

    2011-01-01

    As the number of products containing nanomaterials increase, human exposure to nanoparticles (NPs) is unavoidable. Presently, few studies focus on the potential long-term consequences of developmental NP exposure. In this study, zebrafish embryos were acutely exposed to three gold NPs that possess functional groups with differing surface charge. Embryos were exposed to 50 μg/mL of 1.5 nm gold nanoparticles (AuNPs) possessing negatively charged 2-mercaptoethanesulfonic acid (MES) or neutral 2-(2-(2-mercaptoethoxy)ethoxy)ethanol (MEEE) ligands or 10 μg/mL of the AuNPs possessing positively charged trimethylammoniumethanethiol (TMAT). Both MES- and TMAT-AuNP exposed embryos exhibited hypo-locomotor activity, while those exposed to MEEE-AuNPs did not. A subset of embryos that were exposed to 1.5 nm MES- and TMAT-AuNPs during development from 6–120 hours post fertilization were raised to adulthood. Behavioral abnormalities and the number of survivors into adulthood were evaluated at 122 days post fertilization. We found that both treatments induced abnormal startle behavior following a tap stimulus. However, the MES-AuNPs exposed group also exhibited abnormal adult behavior in the light and had a lower survivorship into adulthood. This study demonstrates that acute, developmental exposure to 1.5 nm MES- and TMAT- AuNPs, two NPs differing only in the functional group, affects larval behavior, with behavioral effects persisting into adulthood. PMID:21946249

  10. Recovery from silver-nanoparticle-exposure-induced lung inflammation and lung function changes in Sprague Dawley rats.

    PubMed

    Song, Kyung Seuk; Sung, Jae Hyuck; Ji, Jun Ho; Lee, Ji Hyun; Lee, Jong Seong; Ryu, Hyeon Ryol; Lee, Jin Kyu; Chung, Yong Hyun; Park, Hyun Min; Shin, Beom Soo; Chang, Hee Kyung; Kelman, Bruce; Yu, Il Je

    2013-03-01

    In a previous study, the lung function, as indicated by the tidal volume, minute volume, and peak inspiration flow, decreased during 90 days of exposure to silver nanoparticles and was accompanied by inflammatory lesions in the lung morphology. Therefore, this study investigated the recovery from such lung function changes in rats following the cessation of 12 weeks of nanoparticle exposure. Male and female rats were exposed to silver nanoparticles (14-15 nm diameter) at concentrations of 0.66 × 10(6) particles/cm(3) (49 μg/m(3), low dose), 1.41 × 10(6) particles/cm(3) (117 μg/m(3), middle dose), and 3.24 × 10(6) particles/cm(3) (381 μg/m(3), high dose) for 6 h/day in an inhalation chamber for 12 weeks. The rats were then allowed to recover. The lung function was measured every week during the exposure period and after the cessation of exposure, plus animals were sacrificed after the 12-week exposure period, and 4 weeks and 12 weeks after the exposure cessation. An exposure-related lung function decrease was measured in the male rats after the 12-week exposure period and 12 weeks after the exposure cessation. In contrast, the female rats did not show a consistent lung function decrease either during the exposure period or following the exposure cessation. The histopathology showed a gradual recovery from the lung inflammation in the female rats, whereas the male rats in the high-dose group exhibited persistent inflammation throughout the 12-week recovery period. Therefore, the present results suggest a potential persistence of lung function changes and inflammation induced by silver nanoparticle exposure above the no observed adverse effect level. PMID:22264098