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Silver nanoparticles (AgNPs) are useful to a wide range of consumer’s and medical products, due to their antimicrobial and anti-inflammatory activities. AgNPs have been used to prevent the microbial colonization, therefore decreasing the risk of infection, on implantable devices, tumor prostheses, bone cement and surgical instruments. However, the putative toxicity of AgNPs to bone cells is still poorly understood. Therefore, this study aimed to contribute to enlighten the role of ionic silver release of small sized NPs on the biological outcomes of bone cells, in particular to what concerns to induction of cytotoxic and genotoxic effects. To achieve that goal osteoblast-like MG-63 cells were exposed to well characterized PVP coated AgNPs of two different primary sizes (10 nm and 20 nm) and evaluated after 24 and 48 h. Our results showed that, the smaller sized AgNPs (10 nm) are more reactive and prone to form large aggregates, being therefore mandatory to provide a careful characterization of the particles, before the toxicity assessment. We also demonstrate that for short period exposures (up to 48 h) ionic silver (from AgNO 3 ) is more toxic than the corresponding dose of AgNP. However, when assessing longer term exposures by the clonogenic assay, we demonstrated the inverse effect, the AgNPs turn out being more toxic, completely inhibiting plate efficiency. Therefore, AgNPs toxicity cannot be attributed to the dissociated Ag + alone. Also, when comparing size-dependent effects, we demonstrate that AgNP20 were found to induce a cell cycle arrest at G0/G1 and apoptosis, while AgNP10 did not induce a cytostatic effect, but rather induced necrosis. Finally, combining the chemical and toxicological profiles of both AgNP sizes, we hypothesize that the size dependent AgNP toxicity may be associated in part with the NPs interference with the cell membranes and consequent uptake/adsorption processes. [ABSTRACT FROM AUTHOR]

Nanomaterials have different chemical, physical and biological characteristics than larger materials of the same chemical composition. These differences give nanotechnology a double identity: their use implies novel and interesting medical and/or industrial applications but also potential danger for human and environmental health. Here, we briefly review the most important types of nanomaterials, the difficulties in assessing safety or toxicity, and describe existing test protocols used in nanomaterial safety evaluation. In general, the big challenge of nanotechnology, particularly for nanomedicine (nano-bioengineering), is to understand which nano-specific characteristics interact with particular biological systems and functions in order to optimize the therapeutic potential and reduce the undesired responses. The evaluation of the safety of medicinal nanomaterials, especially for long-term application, is an important challenge for the near future. At present, it is still too early to predict, on the basis of the characteristics of the nanomaterial, a possible biological response because no reliable database exists. Therefore, a case-by-case approach for hazard identification is still required, so it is difficult to establish a risk assessment framework. [ABSTRACT FROM AUTHOR]

To review epidemiological studies which led to a change in the classification of formaldehyde by the International Agency for Research on Cancer (IARC) in 2004 as well as studies published thereafter, with the objective to examine whether occupational exposure levels for formaldehyde should be adapted. Cohort and case–control studies investigating the association between occupational exposure to formaldehyde and nasopharyngeal cancer (NPC) and reporting estimates of formaldehyde exposure as well as the most recent meta-analyses, published after 1994, were reviewed. Evidence of an association between occupational formaldehyde exposure and NPC appears debatable. Results of the cohort studied by Hauptmann et al. (Am J Epidemiol 159(12):1117–1130, ) were key findings in the IARC evaluation. In this study, mortality from NPC was elevated compared with that of the US general population. However, internal comparison analysis using alternative categorization revealed that none of the relative risk for NPC was statistically significantly increased in any category of exposure (Marsh and Youk in Regul Toxicol Pharmacol 42(3):275–283, ) and re-analyses of the data highlighted the inappropriateness of the exposure assessment used by Hauptmann et al. (Am J Epidemiol 159(12):1117–1130, ) and Marsh et al. (Regul Toxicol Pharmacol 47(1):59–67, ). Two other cohorts (Coggon et al. in J Natl Cancer Inst 95(21):1608–1615, ; Pinkerton et al. in Occup Environ Med 61(3)193–200, ) reported no increase in NPC. Two case–control studies brought some evidence of an increased risk of NPC but the assessment of exposure levels was uncertain. Human studies fail to raise a convincing conclusion concerning the carcinogenicity of formaldehyde and are not helpful to delineate a possible dose–response relationship. Experimental data indicate that in rats, the carcinogenic activity of formaldehyde is associated with cytotoxic/proliferative mechanisms. Therefore protecting from these effects associated with formaldehyde exposure should be sufficient to protect from its potential carcinogenic effects, if any in humans. Current occupational exposure levels to formaldehyde, set to protect against local irritation, should not be adapted. [ABSTRACT FROM AUTHOR]

The European Food Safety Authority (EFSA) has a goal to efficiently conduct aggregate exposure assessments (AEAs) for chemicals using both exposure models and human biomonitoring (HBM) data by 2030. To achieve EFSA's vision, a roadmap for action for advancing aggregate exposure (AE) in the EU was developed. This roadmap was created by performing a series of engagement and data collection activities to map the currently available methods, data, and tools for assessing AE of chemicals, against the needs and priorities of EFSA. This allowed for the creation of a AEA framework, identification of data and knowledge gaps in our current capabilities, and identification of the challenges and blockers that would hinder efforts to fill the gaps. The roadmap identifies interdependent working areas (WAs) where additional research and development are required to achieve EFSA's goal. It also proposes future collaboration opportunities and recommends several project proposals to meet EFSA's goals. Eight proposal projects supported by SWOT analysis are presented for EFSA's consideration. The project proposals inform high‐level recommendations for multi‐annual and multi‐partner projects. Recommendations to improve stakeholder engagement and communication of EFSA's work on AEA were gathered by surveying stakeholders on specific actions to improve EFSA's communication on AE, including webinars, virtual training, social media channels, and newsletters. [ABSTRACT FROM AUTHOR]

Background The expression of HLA-DR on the cell membrane of antigen-presenting cells is of major importance for the induction of an allergic response in the airways. Environmental particulates are thought to play an important role in inducing or enhancing allergic sensitization, possibly by increasing the expression of HLA-DR on the cell membrane of antigen-presenting cells. In addition, these particulates may synergize with common sensitizing agents in inducing or enhancing HLA-DR and thus antigen presentation. Objective In this study, we investigated the potential of three particle types, namely carbon black, diesel exhaust particles and urban air particulates (0.1–1000 ng/cm2 ), to induce the expression of HLA-DR on differentiated THP-1 cells, taken as a model for alveolar macrophages. We also assessed the ‘adjuvant’ potential of the particles on interferon (IFN)-γ, a known enhancer of HLA-DR. Results By themselves, the particles (0.1–1000 ng/cm2 ) were not able to induce HLA-DR on the THP-1 cells after an incubation of 48 h. However, even at very low concentrations, carbon black (from 1 ng/cm2 on) and diesel exhaust particles (from 0.1 ng/cm2 on), interacted with IFN-γ (100 U/mL) to enhance HLA-DR expression (up to 2.5-fold increase). Conclusion This finding may reflect in vitro one of the mechanisms by which pollutant particles exert an ‘adjuvant’ activity and may partially explain how exposure to particles can be related to the enhancement of allergic sensitization. [ABSTRACT FROM AUTHOR]

Background: A few studies have compared indoor allergens and endotoxin levels between urban and rural settings as important determinants for asthma and atopy in children. However, no study was done in the Middle East or investigated refugee camps. Methods: As part of a nested case-control study in Ramallah in 2001, we measured house dust mite and pet allergens, as well as endotoxin in dust collected from 110 children's mattresses and living room floors. Results: Geometric mean (GM) concentrations of Dermatophagoides pteronyssinus (Der p1) antigen were 4.48 μg/g in mattress dust and 1.23 μg/g floor dust. The highest Der p1 levels were seen in refugee camps. Concentrations of Dermatophagoides farinae antigen (Der f1) were much lower (< 0.08 μg/g dust). Concentrations of cat allergen (Fel d1) were highest in villages, and those of dog allergen (Can f1) were highest in mattresses from cities and in floor dust from refugee camps. GM of endotoxin levels were 25.7 EU/mg in mattress dust and 49 EU/mg dust in floor dust. Conclusions: Concentrations of Der p1 were high compared to Western European countries, but were lower compared to UK and Australia. Levels of pet allergens were lower than in Western Europe. Endotoxin levels were higher compared to developed countries. Indoor environmental factors such as dampness seemed to be important determinants for allergen and endotoxin, but living habits such as lack of mattress cover appeared unimportant. [ABSTRACT FROM AUTHOR]

Background and objectives: The particularly high rate of urbanization in Kinshasa (Democratic Republic of Congo) is associated with environmental degradation. Outdoor and indoor air pollution, as well as water pollution and waste accumulation, are issues of major concern. However, little documented information exists on the nature and extent of this pollution. A biomonitoring study was conducted to document exposure to trace elements in a representative sample of the population in Kinshasa. Methods: Fifteen trace elements were measured by ICP-MS, CV-AAS, or HG-AFS in spot urine samples from 220 individuals (50.5% women) aged 6-70 years living in the urban area and from 50 additional subjects from the rural area of Kinshasa. Data were compiled as geometric means and selected percentiles, expressed without (μg/L) or with creatinine adjustment (μg/g cr). Results: Overall, living in urban Kinshasa was associated with elevated levels of several parameters in urine as compared to the population living in the rural area (Asi, Ba, Cd, Cr, and V) as well as compared to an urban population of the southeast of Congo (Al, As, Cd, Cr, Cu, Pb, Mn, Ni, Se, V, and Zn). Elevated levels were also found by comparison with the reference values in databases involving American, Canadian, French, or German populations. Conclusions: This study provides the first biomonitoring database in the population of Kinshasa, revealing elevated levels for most urinary TE as compared to other databases. Toxicologically relevant elements such as Al, As, Cd, Pb, and Hg reach levels of public health concern. [ABSTRACT FROM AUTHOR]

Abstract: This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children''s cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. [Copyright &y& Elsevier]

Background Chronic rhinosinusitis ( CRS) is a frequent condition that is treated by functional endoscopic sinus surgery ( FESS) when medical treatment fails. Endogenous as well as exogenous factors may be responsible for persisting symptoms after FESS. The role of occupational exposures on success of FESS has never been investigated. Methods In this case-control study, we tested the hypothesis that the outcome of FESS procedures is related to exposures at work. Questionnaires were sent to 890 patients who had undergone one or more FESS procedures and to 182 controls. Three independent experts assessed blindly the reported work exposures to inhaled agents. The relationship between exposure and the number of FESS procedures was analyzed. Results Relevant occupational exposure was reported by 25% of all responding patients undergoing FESS ( n = 467) and 12% of controls ( n = 69). The prevalence of occupational exposures increased linearly with the number of FESS procedures from 21% in those who had one FESS to 44% in those who had four or more FESS (χ2 = 12.74, P < 0.001). Logistic regression analysis with adjustments for potential confounders, including smoking, atopy, and asthma, confirmed that the odds ratio ( OR) for reporting occupational exposures was significantly higher in those needing more than one FESS ( OR = 1.64) or more than two FESS ( OR = 1.97). These results were mainly driven by exposure to low molecular weight agents. Conclusion Exposure at work appears to be a risk factor for the occurrence of CRS and for its recurrence or persistence, as evidenced by the need for revision surgery. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Resin-based dental materials are not inert in the oral environment, and may release components, initially due to incomplete polymerization, and later due to degradation. Since there are concerns regarding potential toxicity, more precise knowledge of the actual quantity of released eluates is necessary. However, due to a great variety in analytical methodology employed in different studies and in the presentation of the results, it is still unclear to which quantities of components a patient may be exposed. The objective of this meta-analytical study was to review the literature on the short- and long-term release of components from resin-based dental materials, and to determine how much (order of magnitude) of those components may leach out in the oral cavity. Methods: Out of an initial set of 71 studies, 22 were included. In spite of the large statistical incertitude due to the great variety in methodology and lack of complete information (detection limits were seldom mentioned), a meta-analytical mean for the evaluated eluates was calculated. To relate the amount of potentially released material components with the size of restorations, the mean size of standard composite restorations was estimated using a 3D graphical program. Results: While the release of monomers was analyzed in many studies, that of additives, such as initiators, inhibitors and stabilizers, was seldom investigated. Significantly more components were found to be released in organic than in water-based media. Resin-based dental materials might account for the total burden of orally ingested bisphenol A, but they may release even higher amounts of monomers, such as HEMA, TEGDMA, BisGMA and UDMA. Compared to these monomers, similar or even higher amounts of additives may elute, even though composites generally only contain very small amounts of additives. A positive correlation was found between the total quantity of released eluates and the volume of extraction solution. Significance: There is a clear need for more accurate and standardized analytical research to determine the long-term release from resin-based materials. Several guidelines for standardization are proposed. [Copyright &y& Elsevier]

Abstract: Context: Hypothyroidism has been observed in the fifties and sixties as an undesirable side-effect of cobalt therapy used for its erythropoietic properties in the treatment of anemia. Objective: This study aims at evaluating the possible impact of both cumulative (long-term) and recent occupational exposure to cobalt on thyroid function and red blood cells. Methods and setting: A cross-sectional survey was conducted from February 2008 to August 2009 in a population of 249 male workers from a cobalt production department in the North of Belgium. The possible effect of cobalt exposure on thyroid and red blood cells was investigated through multiple regression analyses. Results: Blood cobalt ranged from undetectable to 3.20μg/100ml (median 0.10); urinary cobalt from 0.30 to 204.30μg/gcreat (median 3.90) and long-term exposure to cobalt ranged from 0.15 to 6990.46μg/gcreat·years (median 106.09). No effect of cobalt exposure on thyroid or red blood cell parameters was observed at these levels of exposure. Conclusion: The results support the absence of effects on the thyroid and red blood cells when occupational exposure to cobalt is kept below the recommended biological limit of occupational exposure (15μg Co/gcreat in urine). [Copyright &y& Elsevier]

In a mouse model of chemical-induced asthma, we investigated the effects of multiple challenges, using toluene diisocyanate (TDI), a known cause of occupational asthma. On days 1 and 7, BALB/ c mice received TDI or vehicle (acetone/olive oil). On days 10, 13 and 16 the mice received an intranasal instillation of TDI. Ventilatory function (Penh) was monitored by whole body plethysmography for 40 min after each challenge. Reactivity to methacholine was measured 22 h later. Pulmonary inflammation, TNF-α and MIP-2 levels were assessed 24 h after the last challenge by broncho-alveolar lavage (BAL). Other immunological parameters included total IgE, lymphocyte sub-populations in auricular and cervical lymph nodes, and IL-4, IFN-γ and IL-13 levels in supernatants of lymph node cells, cultured with or without concanavalin A. Early ventilatory function and airway reactivity increased in all groups that received a dermal application and one or multiple intranasal challenges of TDI. After multiple challenges, lung inflammation was characterized by neutrophils (∼15%), and eosinophils (∼4%), along with an increase in BAL MIP-2 and TNF-α levels. The auricular and cervical lymph node cells of all sensitized mice showed an increase in B cells, Th cells and an increased concentration of in vitro release of IL-4, IFN-γ and IL-13 after stimulation with concanavalin A. Total serum IgE was elevated in dermally TDI-sensitized mice. This protocol including multiple challenges results in a model that resembles human asthma, indicating that responses found in the model using a single challenge could be a good first indication for the development of asthma. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have shown a strong association between daily mortality and small particulate with a diameter of <10 µm (PM10) air pollution, but the effects of season have not always been well characterised. Aim: To study the shape of the association between short-term mortality and PM10 across seasons and quintiles of outdoor temperature. Design, setting and participants: Daily data on mortality (n = 354 357), outdoor temperature and PM10 in Flanders, Belgium, from January 1997 to December 2003, were analysed across warm versus cold periods of the year (April-September v October-March), with seasons and quintiles of outdoor temperature as possible effect modifiers. Results: There was a significant (p<0.001) interaction between PM10 and period of the year in relation to mortality. To allow for non-linearity, daily mean PM10 concentrations were categorised into quartiles. Season-specific PM10 quartiles showed a strong and steep linear association between mortality and PM10 in summer and a less linear association in spring and autumn, whereas in winter the association was less strong and mortality was only increased in the highest PM10 quartile. The effect sizes expressed as the percentage increase in mortality on days in the highest season-specific PM10 quartile versus the lowest season-specific PM10 quartile were 7.8% (95% CI 6.1 to 9.6) in summer, 6.3% (4.7 to 7.8) in spring, 2.2% (0.58 to 3.8) in autumn and 1.4% (0.06 to 2.9) in winter. An analysis by quintiles of temperature confirmed these effect sizes. Conclusion: The short-term effect of particulate air pollution on mortality strongly depends on outdoor temperature, even in a temperate climate. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on exercise intolerance among asthmatic persons, published on the previous issue of the journal.

Presents a correction to an error made in the article 'Loss of HIF-2alpha and inhibition of VEGF fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice,' by V. Compernolle et al published in 'Nature Medicine' journal in 2002.