The modality of cell–particle interactions drives the toxicity of nanosized CuO and TiO2 in human alveolar epithelial cells

Moschini, Elisa; Gualtieri, Maurizio; Colombo, Miriam; Fascio, Umberto; Camatini, Marina; Mantecca, Paride

doi:10.1016/j.toxlet.2013.07.019

Cited by 88 publications

(80 citation statements)

References 34 publications

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“…CuONPs induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in bronchoalveolar lavage fluid (Kim et al, 2011; Pettibone et al, 2008). Many in vitro studies have investigated the toxic effects of CuONPs on airway cells in submerged culture (Ahamed et al, 2010; Fahmy and Cormier, 2009; Karlsson et al, 2008; Midander et al, 2009; Moschini et al, 2013) or at the ALI (Kim et al, 2013). Fahmy (2009) and Karlsson (2008) have reported that nano-sized CuO toxicity in human lung cells is higher than micron-sized CuO or other metal-based NPs.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air–liquid interface compared with in vivo assessment

Jing

Park

Peters

et al. 2015

Toxicology in Vitro

101

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The toxicity of spark-generated copper oxide nanoparticles (CuONPs) was evaluated in human bronchial epithelial cells (HBEC) and lung adenocarcinoma cells (A549 cells) using an in vitro air-liquid interface (ALI) exposure system. Dose-response results were compared to in vivo inhalation and instillation studies of CuONP. Cells were exposed to particle-free clean air (controls) or spark-generated CuONPs. The number median diameter, geometric standard deviation and total number concentration of CuONPs were 9.2 nm, 1.48 and 2.27×107 particles/cm3, respectively. Outcome measures included cell viability, cytotoxicity, oxidative stress and proinflammatory chemokine production. Exposure to clean air (2 or 4 hr) did not induce toxicity in HBEC or A549 cells. Compared with controls, CuONP exposures significantly reduced cell viability, increased lactate dehydrogenase (LDH) release and elevated levels of reactive oxygen species (ROS) and IL-8 in a dose-dependent manner. A549 cells were significantly more susceptible to CuONP effects than HBEC. Antioxidant treatment reduced CuONP-induced cytotoxicity. When dose was expressed per area of exposed epithelium there was good agreement of toxicity measures with murine in vivo studies. This demonstrates that in vitro ALI studies can provide meaningful data on nanotoxicity of metal oxides.

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Section: Discussionmentioning

confidence: 99%

Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air–liquid interface compared with in vivo assessment

Jing

Park

Peters

et al. 2015

Toxicology in Vitro

101

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“…The presence of metal/metal oxide nanoparticles in the PEPs and the complex chemistry of PM, even at minute concentrations, is concerning because metals/metal oxides have the potential to trigger a toxic response in the lungs and translocate to other organs (Bondarenko et al, 2013, Kumar and Nagesha, 2013, Moschini et al, 2013, Demokritou et al, 2013, Cohen et al, 2014, Zhou et al, 2014). Specifically, metal oxides, such as silica, ceria, iron oxide and zinc oxide have been shown to produce DNA damage to cells exposed at doses as low as 5 μg/ml for 4 hours (Watson et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Consumer exposures to laser printer-emitted engineered nanoparticles: A case study of life-cycle implications from nano-enabled products

et al. 2014

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It is well established that printers emit nanoparticles during their operation. To-date, however, the physicochemical and toxicological characterization of “real world” printer-emitted nanoparticles (PEPs) remains incomplete, hampering proper risk assessment efforts. Here, we investigate our earlier hypothesis that engineered nanomaterials (ENMs) are used in toners and ENMs are released during printing (consumer use). Furthermore, we conduct a detailed physicochemical and morphological characterization of PEPs in support of ongoing toxicological assessment. A comprehensive suite of state of the art analytical methods and tools was employed for the physicochemical and morphological characterization of 11 toners widely utilized in printers from major printer manufacturers and their PEPs. We confirmed that a number of ENMs incorporated into toner formulations (e.g., silica, alumina, titania, iron oxide, zinc oxide, copper oxide, cerium oxide, carbon black among others) and released into the air during printing. All evaluated toners contained large amounts of organic carbon (OC, 42–89%), metals/metal oxides (1–33%), and some elemental carbon (EC, 0.33–12%). The PEPs possess a composition similar to that of toner and contained 50–90% OC, 0.001–0.5% EC and 1–3% metals. While the chemistry of the PEPs generally reflected that of their toners, considerable differences are documented indicative of potential transformations taking place during consumer use (printing). We conclude that: (i) Routine incorporation of ENMs in toners classifies them as nano-enabled products (NEPs); (ii) These ENMs become airborne during printing; (iii) The chemistry of PEPs is complex and it reflects that of the toner and paper. This work highlights the importance of understanding life-cycle (LC) nano-EHS implications of NEPs and assessing real world exposures and associated toxicological properties rather than focusing on “raw” materials used in the synthesis of an NEP.

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“…These results are consistent with previous data that find reduced E2 levels among men exposed to TCDD during infancy [23] and with data that find delayed breast development in girls exposed to PCDD/Fs in utero [24]. Although the precise biological mechanism for these associations is not known, it is thought that these endocrine disrupting chemicals may interfere with the normal action or regulation of reproductive endocrine hormones [25], with estrogen catabolism [26] or with alterations in the aryl hydrocarbon receptor signaling system [27]. Delayed development, particularly in female 8-year olds support our results of reductions in fecundity among women exposed in utero to specific PCBs.…”

Section: Discussionmentioning

confidence: 99%

A Cohort study evaluation of maternal PCB exposure related to time to pregnancy in daughters

et al. 2013

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BackgroundPolychlorinated biphenyls (PCBs) remain ubiquitous environmental contaminants. Developmental exposures are suspected to impact reproduction. Analysis of mixtures of PCBs may be problematic as components have a complex correlation structure, and along with limited sample sizes, standard regression strategies are problematic. We compared the results of a novel, empirical method to those based on categorization of PCB compounds by (1) hypothesized biological activity previously proposed and widely applied, and (2) degree of ortho- substitution (mono, di, tri), in a study of the relation of maternal serum PCBs and daughter’s time to pregnancy.MethodsWe measured PCBs in maternal serum samples collected in the early postpartum in 289 daughters in the Child Health and Development Studies birth cohort. We queried time to pregnancy in these daughters 28–31 years later. We applied a novel weighted quantile sum approach to find the bad-actor compounds in the PCB mixture found in maternal serum. The approach includes empirical estimation of the weights through a bootstrap step which accounts for the variation in the estimated weights.ResultsBootstrap analyses indicated the dominant functionality groups associated with longer TTP were the dioxin-like, anti-estrogenic group (average weight, 22%) and PCBs not previously classified by biological activity (54%). In contrast, the unclassified PCBs were not important in the association with shorter TTP, where the anti-estrogenic groups and the PB-inducers group played a more important role (60% and 23%, respectively). The highly chlorinated PCBs (average weight, 89%) were mostly associated with longer TTP; in contrast, the degree of chlorination was less discriminating for shorter TTP. Finally, PCB 56 was associated with the strongest relationship with TTP with a weight of 47%.ConclusionsOur empirical approach found some associations previously identified by two classification schemes, but also identified other bad actors. This empirical method can generate hypotheses about mixture effects and mechanisms and overcomes some of the limitations of standard regression techniques.

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The modality of cell–particle interactions drives the toxicity of nanosized CuO and TiO2 in human alveolar epithelial cells

Cited by 88 publications

References 34 publications

Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air–liquid interface compared with in vivo assessment

Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air–liquid interface compared with in vivo assessment

Consumer exposures to laser printer-emitted engineered nanoparticles: A case study of life-cycle implications from nano-enabled products

A Cohort study evaluation of maternal PCB exposure related to time to pregnancy in daughters

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