Occupational Exposure to Incidental Nanomaterials in Metal Additive Manufacturing: An Innovative Approach for Risk Management.

The benefits of metal 3D printing seem unquestionable. However, this additive manufacturing technology brings concerns to occupational safety and health professionals, since recent studies show the existence of airborne nanomaterials in these workplaces. This article explores different approaches to manage the risk of exposure to these incidental nanomaterials, on a case study conducted in a Portuguese organization using Selective Laser Melting (SLM) technology. A monitoring campaign was performed using a condensation particle counter, a canning mobility particle sizer and air sampling for later scanning electron microscopy and energy dispersive X-ray analysis, proving the emission of nano-scale particles and providing insights on number particle concentration, size, shape and chemical composition of airborne matter. Additionally, Control Banding Nanotool v2.0 and Stoffenmanager Nano v1.0 were applied in this case study as qualitative tools, although designed for engineered nanomaterials. This article highlights the limitations of using these quantitative and qualitative approaches when studying metal 3D Printing workstations. As a result, this article proposes the IN Nanotool, a risk management method for incidental nanomaterials designed to overcome the limitations of other existing approaches and to allow non-experts to manage this risk and act preventively to guarantee the safety and health conditions of exposed workers.

Exposure assessment of nanotitanium oxide powder handling using real-time size-selective particle number concentration measurements and X-ray fluorescence spectrometry -The possibility of exposure to nonagglomerated nanomaterials during the handling of nanomaterial fine powders.

In this study, airborne particles were collected using filters, and the particle number concentrations were measured in two nanotitanium dioxide (nanoTiO2)-manufacturing plants. Real-time particle size measurements were performed using both optical and scanning mobility particle sizer and X-ray fluorescence spectrometry (XRF). The respirable particles collected using filters were used to analyze Ti concentrations in the workplace air of two factories engaged in nanoTiO2 powder bagging processes. The XRF analysis revealed sufficient sensitivity to measure 0.03 mg/m3, which is 1/10 the concentration of the recommended occupational exposure limit of nanoTiO2 in both stationary sampling and personal exposure sampling settings. In a factory where outside air was directly introduced, micron-sized aggregated particles were generated because of factory operations; however, nanosized and submicron-sized particles were not observed owing to high background concentrations of incidental nanoparticles. Alternatively, in another factory where particles from the outside air were removed using a high-efficiency particulate air filter, work-related nanoparticles were released. The findings of this study suggest that in nanoparticle powder handling processes, a nanoparticle exposure risk exists in the form of nonagglomerated state in nanoparticle powder handling processes.

Raman Spectroscopy for Quantitative Analysis in the Pharmaceutical Industry.

Raman spectroscopy is a very promising technique increasingly used in the pharmaceutical industry. Due to its development and improved instrumental versatility achieved over recent decades and through the application of chemometric methods, this technique has become highly precise and sensitive for the quantification of drug substances. Thus, it has become fundamental in identifying critical variables and their clinical relevance in the development of new drugs. In process monitoring, it has been used to highlight in-line real-time analysis, and it has been used more commonly since 2004 when the Food and Drug Administration (FDA) launched Process Analytical Technology (PAT), integrated with the concepts of Pharmaceutical Current Good Manufacturing Practices (CGMPs) for the 21st Century. The present review presents advances in the application of this tool in the development of pharmaceutical products and processes in the last six years.

An Exploratory Assessment of Applying Risk Management Practices to Engineered Nanomaterials.

The widespread industrial application of nanotechnology has increased the number of workers exposed to engineered nanomaterials (ENMs), but it is not clear to what extent prevention guidance is practiced. Our aim was to explore the extent that companies manufacturing and/or using ENMs apply risk assessment and management measures. Thirty-four companies were surveyed with an international 35-item questionnaire investigating company and workforce features, types of ENM handled, and risk evaluation and preventive measures adopted. Among participating companies, 62% had a maximum of 10 employees. Metal-based nanomaterials were most frequently identified (73%). Environmental monitoring was performed by 41% of the companies, while engineering exposure controls were approximately reported by 50%. Information and training programs were indicated by 85% of the sample, only 9% performed specific health surveillance for ENM workers. Personal protective equipment primarily included gloves (100%) and eye/face protection (94%). This small-scale assessment can contribute to the limited amount of published literature on the topic. Future investigations should include a greater number of companies to better represent ENM workplaces and a direct access to industrial settings to collect information on site. Finally, deeper attention should be paid to define standardized frameworks for ENM risk assessment that may guide nano-specific preventive actions.

Distribution, sedimentary record, and persistence of microplastics in the Pearl River catchment, China.

Microplastics (MPs) in the environment have become an issue worldwide. However, data about MPs in freshwater systems are still limited so far. This study investigated sources, fate, and seasonal and spatial distribution of MPs in the main stream Pearl River and its tributaries, as well as in the Pearl River Estuary (PRE), China. MPs were widely detected in the river water, river bed sediment, and estuarine sediment, with abundances of 0.57 ±â€¯0.71 items L-1, 685 ±â€¯342 items kg-1 dry weight (dw), and 258 ±â€¯133 items kg-1 dw, respectively. Sheet, fragmental, and fibrous polyethylene, polypropylene, and ethylene-propylene copolymers were predominant, suggesting that MPs in the Pearl River catchment be mainly derived from fragmentation of discarded plastic wastes. In addition, municipal wastewater was also an important MPs source, especially for polyethylene terephthalate (PET) fibers. Polymers of higher density, such as PET and polyvinyl alcohol were relatively more abundant in the sediment than in the river water, especially in the estuarine sediment. Upward increase of the MP abundance was observed in the sedimentary core, probably indicating increasing release of plastic wastes due to growing production and uses of plastic products. On the other hand, percentage of finer MPs increased with increasing depth. The results revealed persistence and potential downward dispersion of the fine MPs. The MPs abundance was positively related with population density and gross domestic product, demonstrating impacts of human activities and economic development on the MPs contamination. Higher MPs abundance was detected in dry season than in wet season in the river water, suggesting dilution effect of precipitation. It's estimated that 15963 tons of MPs could be released annually into the PRE from the main stream Pearl River and its tributaries.

Nanotoxicity assessment: A challenging application for cutting edge electroanalytical tools.

In the recent years, the number of commercial products containing engineered nanomaterials (ENMs) has increased exponentially. Consequently, the toxicological profile of ENMs on the ecosystems as well as on human health has to be carefully evaluated. Nanotoxicology, an interdisciplinary research area devoted to assessing the hazards associated with ENMs, is expanding rapidly. Many physicochemical techniques and biochemical methodologies have been proposed and are currently used to characterize nanomaterials from a toxicological point of view. Electroanalytical and bioelectrochemical methods can be useful in expanding the repertoire of accessible nanotoxicity-assessment technologies and to accelerate the testing and screening of the toxicological effects of ENMs. These methods can be used for elucidating the toxicological behavior of ENMs at single cell, cell population and whole-organism levels, for in vitro and in vivo measurements, respectively. The aim of this review is to provide an overview on the bioelectrochemical approaches that have been proposed for ENMs toxicity assessment. Furthermore, an overview on cutting-edge electroanalytical devices with a potential impact to this peculiar application is provided.

Developing OECD test guidelines for regulatory testing of nanomaterials to ensure mutual acceptance of test data.

The OECD Working Party on Manufactured Nanomaterials (WPMN) provides a global forum for discussion of nano-safety issues. Together with the OECD Test Guidelines Programme (TGP) the WPMN has explored the need for adaptation of some of the existing OECD Test Guidelines (TGs) and Guidance Documents (GDs) as well as developing new TGs and GDs to specifically address NM issues. An overview is provided of progress in the TGP and WPMN, and information on supporting initiatives, regarding the development of TGs for nanomaterials addressing Physical Chemical Properties, Effects on Biotic Systems, Environmental Fate and Behaviour, and Health Effects. Three TGs specifically addressing manufactured nanomaterials have been adopted: a new TG318 ″Dispersion Stability of Nanomaterials in Simulated Environmental Media", and adaptation of TG412 and TG413 on Subacute Inhalation Toxicity: 28-Day Study/90-day Study. The associated GD39 on Inhalation Toxicity Testing has also been revised. The TGP current develops four new TGs and four GDs. One new TG and six GDs are developed in the WPMN. Six new proposals were submitted to the TGP in 2018. Furthermore, as TGs are accompanied by OECD harmonised templates (OHTs) for data collection, an outline of recently developed OHTs particularly relevant for NMs is also included.

An assessment of applicability of existing approaches to predicting the bioaccumulation of conventional substances in nanomaterials.

The experimental determination of bioaccumulation is challenging, and a number of approaches have been developed for its prediction. It is important to assess the applicability of these predictive approaches to nanomaterials (NMs), which have been shown to bioaccumulate. The octanol/water partition coefficient (KOW ) may not be applicable to some NMs that are not found in either the octanol or water phases but rather are found at the interface. Thus the KOW values obtained for certain NMs are shown not to correlate well with the experimentally determined bioaccumulation. Implementation of quantitative structure-activity relationships (QSARs) for NMs is also challenging because the bioaccumulation of NMs depends on nano-specific properties such as shape, size, and surface area. Thus there is a need to develop new QSAR models based on these new nanodescriptors; current efforts appear to focus on digital processing of NM images as well as the conversion of surface chemistry parameters into adsorption indices. Water solubility can be used as a screening tool for the exclusion of NMs with short half-lives. Adaptation of fugacity/aquivalence models, which include physicochemical properties, may give some insights into the bioaccumulation potential of NMs, especially with the addition of a biota component. The use of kinetic models, including physiologically based pharmacokinetic models, appears to be the most suitable approach for predicting bioaccumulation of NMs. Furthermore, because bioaccumulation of NMs depends on a number of biotic and abiotic factors, it is important to take these factors into account when one is modeling bioaccumulation and interpreting bioaccumulation results. Environ Toxicol Chem 2018;37:2972-2988. © 2018 SETAC.

A Review of Workplace Risk Management Measures for Nanomaterials to Mitigate Inhalation and Dermal Exposure.

This review describes an evaluation of the effectiveness of Risk Management Measures (RMM) for nanomaterials in the workplace. Our aim was to review the effectiveness of workplace RMM for nanomaterials and to determine whether established effectiveness values of conventional chemical substances applied for modelling purposes should be adopted or revised based on available evidence. A literature review was conducted to collate nano-specific data on workplace RMM. Besides the quantitative efficacy values, the library was populated with important covariables such as the study design, measurement type, size of particles or agglomerates/aggregates, and metrics applied. In total 770 records were retrieved from 41 studies for three general types of RMM (engineering controls, respiratory equipment and skin protective equipment: gloves and clothing). Records were found for various sub-categories of the different types of RMM although the number of records for each was generally limited. Significant variation in efficacy values was observed within RMM categories while also considering the respective covariables. Based on a comparative evaluation with efficacy values applied for conventional substances, adapted efficacy values are proposed for various RMM sub-categories (e.g. containment, fume cupboards, FFP2 respirators). It is concluded that RMM efficacy data for nanomaterials are limited and often inconclusive to propose effectiveness values. This review also shed some light on the current knowledge gaps for nanomaterials related to RMM effectiveness (e.g. ventilated walk-in enclosures and clean rooms) and the challenges foreseen to derive reliable RMM efficacy values from aggregated data in the future.

Assessment of occupational exposure to engineered nanomaterials in research laboratories using personal monitors.

Exposure assessment is a key stage in the risk assessment/management of engineered nanomaterials. Although different sampling strategies and instruments have been used to define the occupational exposure to nano-scale materials, currently there is no international consensus regarding measurement strategy, metrics and limit values. In fact, the assessment of individual exposure to engineered nanomaterials remains a critical issue despite recent innovative developments in personal monitors and samplers. Hence, we used several of these instruments to evaluate the workers' personal exposure in a large research laboratory where engineered nanomaterials are produced, handled, and characterized in order to provide input data for nanomaterial exposure assessment strategies and future epidemiological studies. The results obtained using personal monitors showed that the workplace concentrations of engineered nanomaterials (lung deposited surface area and particle number concentrations) were quite low in all the different workplaces monitored, with short spikes during the execution of some specific job tasks. The sampling strategy was been adopted on the basis of an Organisation for Economic Cooperation and Development (OECD) suggestion for a tiered approach and was found to be suitable for determining the individual exposure and for identifying possible sources of emission, even those with very low emission rates. The use of these instruments may lead to a significant improvement not only in the exposure assessment stage but, more generally, in the entire risk assessment and management process.

Nanomaterials: certain aspects of application, risk assessment and risk communication.

Development and market introduction of new nanomaterials trigger the need for an adequate risk assessment of such products alongside suitable risk communication measures. Current application of classical and new nanomaterials is analyzed in context of regulatory requirements and standardization for chemicals, food and consumer products. The challenges of nanomaterial characterization as the main bottleneck of risk assessment and regulation are presented. In some areas, e.g., quantification of nanomaterials within complex matrices, the establishment and adaptation of analytical techniques such as laser ablation inductively coupled plasma mass spectrometry and others are potentially suited to meet the requirements. As an example, we here provide an approach for the reliable characterization of human exposure to nanomaterials resulting from food packaging. Furthermore, results of nanomaterial toxicity and ecotoxicity testing are discussed, with concluding key criteria such as solubility and fiber rigidity as important parameters to be considered in material development and regulation. Although an analysis of the public opinion has revealed a distinguished rating depending on the particular field of application, a rather positive perception of nanotechnology could be ascertained for the German public in general. An improvement of material characterization in both toxicological testing as well as end-product control was concluded as being the main obstacle to ensure not only safe use of materials, but also wide acceptance of this and any novel technology in the general public.

Nanomaterials in food contact materials; considerations for risk assessment

Nanotechnology applications in the food industry, including food contact materials, offer many potential benefits for consumers and manufacturers alike. The article discusses the migration of nanoparticles from food contact materials and the possible health risks associated with in the context of insufficient knowledge of the potential exposure to nanomaterial. The importance of gaps in the general knowledge on the behaviour and biological interactions of nanomaterials in biological systems becomes crucial for risk assessment. The article also discussed numerous doubts concerning the measurements of biological reactions in animal tests and the need for new approaches in the interpretation of data from nanoparticles studies in vivo. The article underlines the need to develop predictive and validated toxicological tests that can be used to screen for potential hazards, and also to develop new methodology for measuring nanoparticles in biological matrices to assess human exposure. Further studies should focus on understanding the mechanisms of action. Nanoparticles exhibit chemical and physical properties that significantly differ from those substances at a large size. Different properties of nanoparticles may lead to different toxicological properties. From that reason nanoparticles, in each case, are individually assessed by the European Food Standard Agency (EFSA) in terms of health risk before the European Commission authorizes them to be used in food contact materials.

[Nanomaterials in foodstuffs - toxicological properties and risk assessment]. / Nanomaterialien in Lebensmitteln ­ toxikologische Eigenschaften und Risikobewertung.

Nanomaterials measure below 100 nm in size in at least one dimension. In general, organic and inorganic nanoparticles can be distinguished. In addition, nanosized structures may differ substantially with regard to their shape, chemical composition and physical properties. They may originate either from natural processes or can be manufactured intentionally. The possible specific toxicological properties of nanoparticles that might be based on their enhanced reactivity due to an increased surface-to-volume ratio, as compared to larger particles, or which might result from preferential uptake in cells and tissues, are the subject of current toxicological research. Consumers are exposed to nanomaterials via the oral route by foodstuffs containing naturally formed, unknowingly incorporated or intentionally added nanoparticles. In the course of this work, an overview of the occurrence of nanomaterials in foodstuffs, including the legal definition and labeling requirements, will be given. Furthermore, specific characteristics of the oral uptake of nanomaterials will be presented alongside challenges for experimental investigation of gastrointestinal uptake and the effects of nanoscaled particles. These will be discussed in relation to potentially relevant toxicological properties and modes of action. Despite a plethora of available experimental studies, there are still knowledge gaps with regard to the exposure against orally ingested nanoparticles and with regard to possible toxicological consequences of such particles in order to allow for accurate risk assessment of the materials in foodstuffs and food packaging.

Environmental and human health assessment of life cycle of nanoTiO2 functionalized porcelain stoneware tile.

Recently, there has been a rise in the interest in nanotechnology due to its enormous potential for the development of new products and applications with higher performance and new functionalities. However, while nanotechnology might revolutionize a number of industrial and consumer sectors, there are uncertainties and knowledge gaps regarding toxicological effects of this emerging science. The goal of this research concerns the implementation into Life Cycle Assessment (LCA) of preliminary frameworks developed to evaluate human toxicity and exposure factors related to the potential nanoparticle releases that could occur during the life cycle steps of a functionalized building material. The present LCA case study examines the ecodesign of nanoTiO2 functionalized porcelain stoneware tile production. The aim of this investigation is to manufacture new eco-friendly products in order to protect human health and ecosystem quality and to offer the market, materials with higher technological properties obtained by the addition of specific nanomaterials.

Gold Nanomaterials in Consumer Cosmetics Nanoproducts: Analyses, Characterization, and Dermal Safety Assessment.

Establishment of analytical methods of engineered nanomaterials in consumer products for their human and environmental risk assessment becomes urgent for both academic and industrial needs. Owing to the difficulties and challenges around nanomaterials in complex media, proper chemical separation and biological assays of nanomaterials from nanoproducts needs to be firstly developed. Herein, a facile and rapid method to separate and analyze gold nanomaterials in cosmetics is reported. Gold nanomaterials are successfully separated from different facial or eye creams and their physiochemical properties are analyzed by quantitative and qualitative state-of-the art techniques with high sensitivity or high spatial resolution. In turn, a protocol including quantification of gold by inductively coupled plasma mass spectrometry and thorough characterization of morphology, size distribution, and surface property by electron microscopes, atomic force microscope, and X-ray photoelectron spectroscope is developed. Subsequently, the preliminary toxicity assessment indicates that gold nanomaterials in cosmetic creams have no observable toxicity to human keratinocytes even after 24 h exposure up to a concentration of 200 µg mL-1 . The environmental scanning electron microscope reveals that gold nanomaterials are mostly attached on the cell membrane. Thus, the present study provides a full analysis protocol for toxicity assessment of gold nanomaterials in consumer products (cosmetic creams).

Evaluation of Decision Rules in a Tiered Assessment of Inhalation Exposure to Nanomaterials.

Tiered or stepwise approaches to assess occupational exposure to nano-objects, and their agglomerates and aggregates have been proposed, which require decision rules (DRs) to move to a next tier, or terminate the assessment. In a desk study the performance of a number of DRs based on the evaluation of results from direct reading instruments was investigated by both statistical simulations and the application of the DRs to real workplace data sets. A statistical model that accounts for autocorrelation patterns in time-series, i.e. autoregressive integrated moving average (ARIMA), was used as 'gold' standard. The simulations showed that none of the proposed DRs covered the entire range of simulated scenarios with respect to the ARIMA model parameters, however, a combined DR showed a slightly better agreement. Application of the DRs to real workplace datasets (n = 117) revealed sensitivity up to 0.72, whereas the lowest observed specificity was 0.95. The selection of the most appropriate DR is very much dependent on the consequences of the decision, i.e. ruling in or ruling out of scenarios for further evaluation. Since a basic assessment may also comprise of other type of measurements and information, an evaluation logic was proposed which embeds the DRs, but furthermore supports decision making in view of a tiered-approach exposure assessment.

A Multilaboratory Toxicological Assessment of a Panel of 10 Engineered Nanomaterials to Human Health--ENPRA Project--The Highlights, Limitations, and Current and Future Challenges.

ENPRA was one of the earlier multidisciplinary European Commission FP7-funded projects aiming to evaluate the risks associated with nanomaterial (NM) exposure on human health across pulmonary, cardiovascular, hepatic, renal, and developmental systems. The outputs from this project have formed the basis of this review. A retrospective interpretation of the findings across a wide range of in vitro and in vivo studies was performed to identify the main highlights from the project. In particular, focus was placed on informing what advances were made in the hazard assessment of NM, as well as offering some suggestions on the future of "nanotoxicology research" based on these observations, shortcomings, and lessons learned from the project. A number of issues related to the hazard assessment of NM are discussed in detail and include use of appropriate NM for nanotoxicology investigations; characterization and dispersion of NM; use of appropriate doses for all related investigations; need for the correct choice of experimental models for risk assessment purposes; and full understanding of the test systems and correct interpretation of data generated from in vitro and in vivo systems. It is hoped that this review may assist in providing information in the implementation of guidelines, model systems, validation of assessment methodology, and integrated testing approaches for risk assessment of NM. It is vital to learn from ongoing and/or completed studies to avoid unnecessary duplication and offer suggestions that might improve different aspects of experimental design.

Refinement of the Nanoparticle Emission Assessment Technique into the Nanomaterial Exposure Assessment Technique (NEAT 2.0).

Engineered nanomaterial emission and exposure characterization studies have been completed at more than 60 different facilities by the National Institute for Occupational Safety and Health (NIOSH). These experiences have provided NIOSH the opportunity to refine an earlier published technique, the Nanoparticle Emission Assessment Technique (NEAT 1.0), into a more comprehensive technique for assessing worker and workplace exposures to engineered nanomaterials. This change is reflected in the new name Nanomaterial Exposure Assessment Technique (NEAT 2.0) which distinguishes it from NEAT 1.0. NEAT 2.0 places a stronger emphasis on time-integrated, filter-based sampling (i.e., elemental mass analysis and particle morphology) in the worker's breathing zone (full shift and task specific) and area samples to develop job exposure matrices. NEAT 2.0 includes a comprehensive assessment of emissions at processes and job tasks, using direct-reading instruments (i.e., particle counters) in data-logging mode to better understand peak emission periods. Evaluation of worker practices, ventilation efficacy, and other engineering exposure control systems and risk management strategies serve to allow for a comprehensive exposure assessment.

Preliminary investigation on the thermal conversion of automotive shredder residue into value-added products: Graphitic carbon and nano-ceramics.

Large increasing production volumes of automotive shredder residue (ASR) and its hazardous content have raised concerns worldwide. ASR has a desirable calorific value, making its pyrolysis a possible, environmentally friendly and economically viable solution. The present work focuses on the pyrolysis of ASR at temperatures between 950 and 1550°C. Despite the high temperatures, the energy consumption can be minimized as the decomposition of ASR can be completed within a short time. In this study, the composition of ASR was investigated. ASR was found to contain about 3% Ti and plastics of high calorific value such as polypropylene, polyethylene, polycarbonate and polyurethane. Based on thermogravimetric analysis (TGA) of ASR, the non-isothermal degradation kinetic parameters were determined using Coats-Redfern's and Freeman and Carroll methods. The evolved gas analysis indicated that the CH4 was consumed by the reduction of some oxides in ASR. The reduction reactions and the presence of Ti, silicates, C and N in ASR at 1550°C favor the formation of specific ceramics such as TiN and SiC. The presence of nano-ceramics along with a highly-crystalline graphitic carbon in the pyrolysis residues obtained at 1550°C was confirmed by scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and Raman imaging microscope (RIM) analyses.