Effects of Zinc Oxide Nanoparticle Exposure on Human Glial Cells and Zebrafish Embryos.

Zinc oxide nanoparticles (ZnO NPs) are among the most widely used nanomaterials. They have multiple applications in cosmetics, textiles, paints, electronics and, recently, also in biomedicine. This extensive use of ZnO NPs notably increases the probability that both humans and wildlife are subjected to undesirable effects. Despite being among the most studied NPs from a toxicological point of view, much remains unknown about their ecotoxicological effects or how they may affect specific cell types, such as cells of the central nervous system. The main objective of this work was to investigate the effects of ZnO NPs on human glial cells and zebrafish embryo development and to explore the role of the released Zn2+ ions in these effects. The effects on cell viability on human A172 glial cells were assessed with an MTT assay and morphological analysis. The potential acute and developmental toxicity was assessed employing zebrafish (Danio rerio) embryos. To determine the role of Zn2+ ions in the in vitro and in vivo observed effects, we measured their release from ZnO NPs with flame atomic absorption spectrometry. Then, cells and zebrafish embryos were treated with a water-soluble salt (zinc sulfate) at concentrations that equal the number of Zn2+ ions released by the tested concentrations of ZnO NPs. Exposure to ZnO NPs induced morphological alterations and a significant decrease in cell viability depending on the concentration and duration of treatment, even after removing the overestimation due to NP interference. Although there were no signs of acute toxicity in zebrafish embryos, a decrease in hatching was detected after exposure to the highest ZnO NP concentrations tested. The ability of ZnO NPs to release Zn2+ ions into the medium in a concentration-dependent manner was confirmed. Zn2+ ions did not seem entirely responsible for the effects observed in the glial cells, but they were likely responsible for the decrease in zebrafish hatching rate. The results obtained in this work contribute to the knowledge of the toxicological potential of ZnO NPs.

Editorial of Special Issue: The Toxicity of Nanomaterials and Legacy Contaminants: Risks to the Environment and Human Health.

Nanotechnology and the incorporation of nanomaterials (NM) into everyday products help to solve problems in society and improve the quality of life, allowing for major advances in the technological, industrial, and medical fields [...].

Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models.

Several studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relationship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an overview of the available human respiratory models and exposure systems for in vitro testing, advantages, limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.

In Vitro Hepatotoxic and Neurotoxic Effects of Titanium and Cerium Dioxide Nanoparticles, Arsenic and Mercury Co-Exposure.

Considering the increasing emergence of new contaminants, such as nanomaterials, mixing with legacy contaminants, including metal(loid)s, it becomes imperative to understand the toxic profile resulting from these interactions. This work aimed at assessing and comparing the individual and combined hepatotoxic and neurotoxic potential of titanium dioxide nanoparticles (TiO2NPs 0.75-75 mg/L), cerium oxide nanoparticles (CeO2NPs 0.075-10 µg/L), arsenic (As 0.01-2.5 mg/L), and mercury (Hg 0.5-100 mg/L) on human hepatoma (HepG2) and neuroblastoma (SH-SY5Y) cells. Viability was assessed through WST-1 (24 h) and clonogenic (7 days) assays and it was affected in a dose-, time- and cell-dependent manner. Higher concentrations caused greater toxicity, while prolonged exposure caused inhibition of cell proliferation, even at low concentrations, for both cell lines. Cell cycle progression, explored by flow cytometry 24 h post-exposure, revealed that TiO2NPs, As and Hg but not CeO2NPs, changed the profiles of SH-SY5Y and HepG2 cells in a dose-dependent manner, and that the cell cycle was, overall, more affected by exposure to mixtures. Exposure to binary mixtures revealed either potentiation or antagonistic effects depending on the composition, cell type and time of exposure. These findings prove that joint toxicity of contaminants cannot be disregarded and must be further explored.

Urinary cotinine assessment of maternal smoking and environmental tobacco smoke exposure status and its associations with perinatal outcomes: a cross-sectional birth study.

Tobacco consumption and environmental tobacco smoke (ETS) exposure remains an important public health concern. Pregnant women require particular attention as active and passive smoking during pregnancy are associated with multiple adverse perinatal outcomes. This study aimed to biochemically validate self-reported smoking and ETS exposure status among pregnant women, to more precisely ascertain its association with adverse perinatal outcomes. Data refers to 595 pregnant women who sought prenatal care in a public hospital in Porto, Portugal. A standard questionnaire on smoking and ETS-related variables was completed. Urinary cotinine (UC) concentrations were assessed by solid-phase competitive ELISA, in maternal urine samples collected on the day of delivery. The results showed that the optimal UC cut-off value to distinguish smokers from non-smokers and within non-smokers those who were exposed to ETS from those non-exposed in the third trimester of pregnancy was 74.1 ng/mL (sensitivity and specificity of 96.7% and 98.0%, respectively) and 1.6 ng/mL (sensitivity of 66.2% and specificity of 75.7%, respectively). The agreement between maternal self-reported and UC-based smoking status was very good (κ=0.919, p<0.001), but much lower for ETS exposure (κ=0.386, p<0.001). Maternal active smoking in the third trimester of pregnancy was associated with a significant decrease in birth weight, length and head circumference of 157.66 g (95% CI: -245.81, -69.52; p<0.001), 0.78 cm (95% CI: -1.22, -0.34; p=0.001) and 0.39 cm (95% CI: -0.70, -0.07; p=0.016), respectively. Maternal ETS exposure in the third trimester of pregnancy was associated with a non-significant increase in birth weight of 38.37 g (95% CI: -28.91, 105.64; p=0.263). Furthermore, maternal smoking cessation was associated with the increase of approximately 172 g in birth weight (95% CI: 50.00, 293.19). As such, there is an urgent need for increased public health awareness campaigns to encourage smoking cessation during pregnancy, in order to improve perinatal outcomes.

Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage.

Metal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use.

Anesthesia for Stüve-Wiedemann syndrome: a rare adult patient case report.

Stüve-Wiedemann syndrome (SWS) is a rare genetic disorder characterized by skeletal dysplasia and severe dysautonomia, evidencing a difficult airway approach and likely increased malignant hyperthermia susceptibility. Developmental dysmorphism classically worsens with age, therefore translating in a poor prognosis. In this article, we describe a case of a 27-year-old woman diagnosed with SWS proposed for abscess drainage under dissociative anesthesia. This patient has outlived the life expectancy described for SWS, acknowledging the importance of reporting this rare adult clinical case in what SWS anesthetic management is concerned.

The importance of socioeconomic position in smoking, cessation and environmental tobacco smoke exposure during pregnancy.

Tobacco is still a leading cause of premature death and morbidity. Particular attention has been given to pregnant women due to the scientific evidence on the importance of early life exposures for disease onset later in life. The purpose of this study was to assess smoking prevalence, smoking cessation rate and environmental tobacco smoke (ETS) exposure, and the role of socioeconomic position (SEP) on these behaviors among pregnant women. Cross-sectional data of 619 pregnant women, aged between 18 and 46 years, from Porto Metropolitan Area, Portugal, on current smoking, ETS exposure and SEP indicators was collected, face-to-face, using a questionnaire filled in during a personal interview at the postpartum hospital stay. The smoking prevalence, and ETS exposure among non-smokers before pregnancy was 27.6% and 57.4%, respectively. 4.1% of the participants reported to have stopped smoking before pregnancy, whereas about 41% quitted along pregnancy, resulting in a smoking prevalence at birth of 14.6%. Exposure to ETS also decreased throughout pregnancy to 49.8% at birth. Lower educational level was significantly associated with both higher smoking prevalence and exposure to ETS and lower smoking cessation. This study demonstrates that smoking and ETS exposure during pregnancy remains high, and that there are still significant socioeconomic inequalities in smoking; thus tobacco-focused preventive interventions need to be reinforced.

Unravelling the Potential Cytotoxic Effects of Metal Oxide Nanoparticles and Metal(Loid) Mixtures on A549 Human Cell Line.

Humans are typically exposed to environmental contaminants' mixtures that result in different toxicity than exposure to the individual counterparts. Yet, the toxicology of chemical mixtures has been overlooked. This work aims at assessing and comparing viability and cell cycle of A549 cells after exposure to single and binary mixtures of: titanium dioxide nanoparticles (TiO2NP) 0.75-75 mg/L; cerium oxide nanoparticles (CeO2NP) 0.0.75-10 µg/L; arsenic (As) 0.75-2.5 mg/L; and mercury (Hg) 5-100 mg/L. Viability was assessed through water-soluble tetrazolium (WST-1) and thiazolyl blue tetrazolium bromide (MTT) (24 h exposure) and clonogenic (seven-day exposure) assays. Cell cycle alterations were explored by flow cytometry. Viability was affected in a dose- and time-dependent manner. Prolonged exposure caused inhibition of cell proliferation even at low concentrations. Cell-cycle progression was affected by TiO2NP 75 mg/L, and As 0.75 and 2.5 µg/L, increasing the cell proportion at G0/G1 phase. Combined exposure of TiO2NP or CeO2NP mitigated As adverse effects, increasing the cell surviving factor, but cell cycle alterations were still observed. Only CeO2NP co-exposure reduced Hg toxicity, translated in a decrease of cells in Sub-G1. Toxicity was diminished for both NPs co-exposure compared to its toxicity alone, but a marked toxicity for the highest concentrations was observed for longer exposures. These findings prove that joint toxicity of contaminants must not be disregarded.

Quality of Medicines in Portugal: A Retrospective Review of Medicine Recalls (2000-2015).

INFARMED, the Portuguese national health authority, alerts the general public and health care professionals about quality or safety issues detected in health products. The present study analyses recalls of substandard medicines in Portugal between 2005 and 2015. All 338 alerts for medicine recalls were analysed, which represents a total of 378 drugs withdrawn. Despite the fact that the total number of medicine alerts has increased during the past decade, the number of actual medicine recalls remained relatively constant. The number of batches affected in each recall varies from only one to several batches. In addition, 294 of the alerts are related to voluntary recalls, that is, those initiated by the marketing authorisation holder, whereas only 40 were mandatory recalls. There are marketing authorisation holders that have had several medicine recalls over the period studied. The main cause of product recall was the pharmaceutical dosage form, followed by packaging problems. Forty-two percent of the withdrawn medicines are from solid oral forms, a value slightly higher than that obtained for the injectables group. Finally, substandard medicines have been accessible in the Portuguese market for a period that varied between one month and over four years. The data seem to show that the number of substandard medicines in Portugal has not been increasing. However, this may be due to a variety of causes, that is, better performance of the industry, non-detection of these cases, and so on.LAY ABSTRACT: INFARMED, the Portuguese national health authority, alerts the general public and health care professionals about quality or safety issues detected in health products. The present study analyses market recalls of substandard medicines in Portugal between 2005 and 2015. All 338 alerts for medicine recalls were analysed, which represents a total of 378 drugs withdrawn. Despite the fact that the total number of medicine alerts has increased during the past decade, the number of actual medicine recalls has remained relatively constant. In addition, 294 of the alerts are related to voluntary recalls, that is, initiated by the marketing authorisation holder, whereas only 40 were mandatory recalls. There are marketing authorisation holders that have had several medicine recalls over the period studied. It was also found that substandard medicines have been accessible in the Portuguese market for a period that varied between 1 month and over 4 years. The data seem to show that the number of substandard medicines in Portugal has not been increasing. However, this may be due to a variety of causes, that is, better performance of the industry, non-detection of these cases, and so on.

Major, minor, trace and rare earth elements in sediments of the Bijagós archipelago, Guinea-Bissau.

Sixty sediment samples from four sites in the Bijagós archipelago were characterized for fine fraction, loss on ignition, major, minor and trace elemental composition (Al, Fe, Ca, Mg, Ti, P, Zr, Mn, Cr, Sr, Ba, B, V, Li, Zn, Ni, Pb, As, Co, U, Cu, Cs and Cd), and the elements of the La-Lu series. Element concentrations were largely explained by the Al content and the proportion of fine fraction content, with the exception of Ca and Sr. Sediments showed enhanced Ti, U, Cr, As and Cd concentrations with respect to estimated upper crust values, most likely mirroring a regional signature. Rare earth elements were in deficit relatively to the North American Shale Composite (NASC), mainly in coarser material. No pronounced Ce-anomaly was observed, while Eu-anomalies were positive in most analyzed sediments.

Extractability and mobility of mercury from agricultural soils surrounding industrial and mining contaminated areas.

This study focussed on a comparison of the extractability of mercury in soils with two different contamination sources (a chlor-alkali plant and mining activities) and on the evaluation of the influence of specific soil properties on the behaviour of the contaminant. The method applied here did not target the identification of individual species, but instead provided information concerning the mobility of mercury species in soil. Mercury fractions were classified as mobile, semi-mobile and non-mobile. The fractionation study revealed that in all samples mercury was mainly present in the semi-mobile phase (between 63% and 97%). The highest mercury mobility (2.7 mg kg(-1)) was found in soils from the industrial area. Mining soils exhibited higher percentage of non-mobile mercury, up to 35%, due to their elevated sulfur content. Results of factor analysis indicate that the presence of mercury in the mobile phase could be related to manganese and aluminium soil contents. A positive relation between mercury in the semi-mobile fraction and the aluminium content was also observed. By contrary, organic matter and sulfur contents contributed to mercury retention in the soil matrix reducing the mobility of the metal. Despite known limitations of sequential extraction procedures, the methodology applied in this study for the fractionation of mercury in contaminated soil samples provided relevant information on mercury's relative mobility.

Mercury contamination in the vicinity of a chlor-alkali plant and potential risks to local population.

A mercury-cell chlor-alkali plant operated in Estarreja (North-western Portugal) for 50 years causing widespread environmental contamination. Although production by this process ceased in 2002, mercury contamination from the plant remains significant. The main objective of this study was to investigate mercury impact on the nearby environment and potential risks to local population. To assess the level of contamination soil samples were collected from agricultural fields in the vicinity of the plant, extending the study by taking samples of the predominant vegetation suitable for animal and human consumption, water samples, and fish species from a nearby coastal lagoon, to gain a preliminary insight into the potential for contamination of the terrestrial and aquatic food web. To determine population exposure to mercury, hair samples were collected from local residents. Total mercury concentration in the 0-15 cm layer of soil was found to be highly variable, ranging between 0.010 and 91 mg kg(-1), although mercury contamination of soils was found to be restricted to a confined area. Lolium perenne roots contained between 0.0070 and 2.0 mg kg(-1), and there is evidence that root systems uptake mercury from the soil. Levels of mercury in the aerial parts of plants ranged between 0.018 and 0.98 mg kg(-1). It appears that plants with higher mercury concentration in soils and roots also display higher mercury concentration in leaves. Total mercury concentration in water samples ranged between 12 and 846 ng L(-1), all samples presenting concentrations below the maximum level allowable for drinking water defined in the Portuguese law (1.0 microg L(-1)). Mercury levels in fish samples were below the maximum limit defined in the Portuguese law (0.5 mg kg(-1)), ranging from 0.0040 to 0.24 mg kg(-1). Vegetables collected presented maximum mercury concentration of 0.17 mg kg(-1). In general, food is not contaminated and should not be responsible for major human exposure to the metal. Mercury determined in human hair samples (0.090-4.2 mg kg(-1); mean 1.5 mg kg(-1)) can be considered within normal limits, according to WHO guidelines suggesting that it is not affecting the local population. Despite being subject to decades of mercury emissions, nowadays this pollutant is only found in limited small areas and must not constitute a risk for human health, should these areas be restricted and monitored. Considering the present data, it appears that the population from Estarreja is currently not being affected by mercury levels that still remain in the environment.