Engineered Nanomaterials Exposure Research Articles

Tracking translocation of industrially relevant engineered nanomaterials (ENMs) across alveolar epithelial monolayers in vitro

Relatively little is known about the fate of industrially relevant engineered nanomaterials (ENMs) in the lungs that can be used to convert administered doses to delivered doses. Inhalation exposure and subsequent translocation of ENMs across the epithelial lining layer of the lung might contribute to clearance, toxic effects or both. To allow precise quantitation of translocation across lung epithelial cells, we developed a method for tracking industrially relevant metal oxide ENMs in vitro using neutron activation. The versatility and sensitivity of the proposed in vitro epithelial translocation (INVET) system was demonstrated using a variety of industry relevant ENMs including CeO2 of various primary particle diameter, ZnO, and SiO2-coated CeO2 and ZnO particles. ENMs were neutron activated, forming gamma emitting isotopes 141Ce and 65Zn, respectively. Calu-3 lung epithelial cells cultured to confluency on transwell inserts were exposed to neutron-activated ENM dispersions at sub-lethal doses to investigate the link between ENM properties and translocation potential. The effects of ENM exposure on monolayer integrity was monitored by various methods. ENM translocation across the cellular monolayer was assessed by gamma spectrometry following 2, 4 and 24 h of exposure. Our results demonstrate that ENMs translocated in small amounts (e.g. <0.01% of the delivered dose at 24 h), predominantly via transcellular pathways without compromising monolayer integrity or disrupting tight junctions. It was also demonstrated that the delivery of particles in suspension to cells in culture is proportional to translocation, emphasizing the importance of accurate dosimetry when comparing ENM–cellular interactions for large panels of materials. The reported INVET system for tracking industrially relevant ENMs while accounting for dosimetry can be a valuable tool for investigating nano–bio interactions in the future.

Engineered Nanomaterials: Knowledge Gaps in Fate, Exposure, Toxicity, and Future Directions

The aim of this study is to identify current knowledge gaps in fate, exposure, and toxicity of engineered nanomaterials (ENMs), highlight research gaps, and suggest future research directions. Humans and other living organisms are exposed to ENMs during production or use of products containing them. To assess the hazards of ENMs, it is important to assess their physiochemical properties and try to relate them to any observed hazard. However, the full determination of these relationships is currently limited by the lack of empirical data. Moreover, most toxicity studies do not use realistic environmental exposure conditions for determining dose‐response parameters, affecting the accurate estimation of health risks associated with the exposure to ENMs. Regulatory aspects of nanotechnology are still developing and are currently the subject of much debate. Synthesis of available studies suggests a number of open questions. These include (i) developing a combination of different analytical methods for determining ENM concentration, size, shape, surface properties, and morphology in different environmental media, (ii) conducting toxicity studies using environmentally relevant exposure conditions and obtaining data relevant to developing quantitative nanostructure‐toxicity relationships (QNTR), and (iii) developing guidelines for regulating exposure of ENMs in the environment.

Adverse Effects of Engineered Nanomaterials Exposure, Toxicology, and Impact on Human Health

Adverse Effects of Engineered Nanomaterials Exposure, Toxicology, and Impact on Human Health

Developmental Neurotoxicity of Engineered Nanomaterials: Identifying Research Needs to Support Human Health Risk Assessment

Increasing use of engineered nanomaterials (ENM) in consumer products and commercial applications has helped drive a rise in research related to the environmental health and safety (EHS) of these materials. Within the cacophony of information on ENM EHS to date are data indicating that these materials may be neurotoxic in adult animals. Evidence of elevated inflammatory responses, increased oxidative stress levels, alterations in neuronal function, and changes in cell morphology in adult animals suggests that ENM exposure during development could elicit developmental neurotoxicity (DNT), especially considering the greater vulnerability of the developing brain to some toxic insults. In this review, we examine current findings related to developmental neurotoxic effects of ENM in the context of identifying research gaps for future risk assessments. The basic risk assessment paradigm is presented, with an emphasis on problem formulation and assessments of exposure, hazard, and dose response for DNT. Limited evidence suggests that in utero and postpartum exposures are possible, while fewer than 10 animal studies have evaluated DNT, with results indicating changes in synaptic plasticity, gene expression, and neurobehavior. Based on the available information, we use current testing guidelines to highlight research gaps that may inform ENM research efforts to develop data for higher throughput methods and future risk assessments for DNT. Although the available evidence is not strong enough to reach conclusions about DNT risk from ENM exposure, the data indicate that consideration of ENM developmental neurotoxic potential is warranted.

Nano GO Consortium—A Team Science Approach to Assess Engineered Nanomaterials: Reliable Assays and Methods

Nano GO Consortium—A Team Science Approach to Assess Engineered Nanomaterials: Reliable Assays and Methods

Maternal engineered nanomaterial exposure and fetal microvascular function: does the Barker hypothesis apply?

The continued development and use of engineered nanomaterials (ENM) has given rise to concerns over the potential for human health effects. Although the understanding of cardiovascular ENM toxicity is improving, one of the most complex and acutely demanding "special" circulations is the enhanced maternal system to support fetal development. The Barker hypothesis proposes that fetal development within a hostile gestational environment may predispose/program future sensitivity. Therefore, the objective of this study was 2-fold: (1) to determine whether maternal ENM exposure alters uterine and/or fetal microvascular function and (2) test the Barker hypothesis at the microvascular level. Pregnant (gestation day 10) Sprague-Dawley rats were exposed to nano-titanium dioxide aerosols (11.3 ± 0.039 mg/m(3)/hr, 5 hr/d, 8.2 ± 0.85 days) to evaluate the maternal and fetal microvascular consequences of maternal exposure. Microvascular tissue isolation (gestation day 20) and arteriolar reactivity studies (<150 μm passive diameter) of the uterine premyometrial and fetal tail arteries were conducted. ENM exposures led to significant maternal and fetal microvascular dysfunction, which was seen as robustly compromised endothelium-dependent and -independent reactivity to pharmacologic and mechanical stimuli. Isolated maternal uterine arteriolar reactivity was consistent with a metabolically impaired profile and hostile gestational environment that impacted fetal weight. The fetal microvessels that were isolated from exposed dams demonstrated significant impairments to signals of vasodilation specific to mechanistic signaling and shear stress. To our knowledge, this is the first report to provide evidence that maternal ENM inhalation is capable of influencing fetal health and that the Barker hypothesis is applicable at the microvascular level.

French registry of workers handling engineered nanomaterials as an instrument of integrated system for surveillance and research

Despite the lack of data on the human health potential risks related to the engineered nanomaterials (ENM) exposure, ENM handling spreads in industry. The French government officially charged the InVS to develop an epidemiological surveillance of workers occupationally exposed to ENM. An initial surveillance plan was proposed on the basis of literature review and discussions with national and international ENM and occupational safety and health (OSH) experts. In site investigations and technical visits were then carried out to build an adequate surveillance system and to assess its feasibility. The current plan consists of a multi-step methodology where exposure registry construction is paramount. Workers potentially exposed to carbon nanotubes (CNT) or nanometric titanium dioxide (TiO2) will be identified using a 3-level approach: 1-identification and selection of companies concerned with ENM exposure (based on compulsory declaration and questionnaires), 2-in site exposure assessment and identification of the jobs/tasks with ENM exposure (based on job-expose matrix, further supplemented with measurements), and 3-identification of workers concerned. Data of interest will be collected by questionnaire. Companies and workers inclusion questionnaires are designed and currently under validation. This registration is at the moment planned for three years but could be extended and include other ENM. A prospective cohort study will be established from this registry, to pursue surveillance objectives and serve as an infrastructure for performing epidemiological and panel studies with specific research objectives.

ONE Nano: NIEHS’s Strategic Initiative on the Health and Safety Effects of Engineered Nanomaterials

Background: The past decade has seen tremendous expansion in the production and application of engineered nanomaterials (ENMs). The unique properties that make ENMs useful in the marketplace also make their interactions with biological systems difficult to anticipate and critically important to explore. Currently, little is known about the health effects of human exposure to these materials.Objectives: As part of its role in supporting the National Nanotechnology Initiative, the National Institute of Environmental Health Sciences (NIEHS) has developed an integrated, strategic research program—“ONE Nano”—to increase our fundamental understanding of how ENMs interact with living systems, to develop predictive models for quantifying ENM exposure and assessing ENM health impacts, and to guide the design of second-generation ENMs to minimize adverse health effects.Discussion: The NIEHS’s research investments in ENM health and safety include extramural grants and grantee consortia, intramural research activities, and toxicological studies being conducted by the National Toxicology Program (NTP). These efforts have enhanced collaboration within the nanotechnology research community and produced toxicological profiles for selected ENMs, as well as improved methods and protocols for conducting in vitro and in vivo studies to assess ENM health effects.Conclusion: By drawing upon the strengths of the NIEHS’s intramural, extramural, and NTP programs and establishing productive partnerships with other institutes and agencies across the federal government, the NIEHS’s strategic ONE Nano program is working toward new advances to improve our understanding of the health impacts of engineered nanomaterials and support the goals of the National Nanotechnology Initiative.

Translocation, transfer, and in vivo safety evaluation of engineered nanomaterials in the non-mammalian alternative toxicity assay model of nematode Caenorhabditis elegans

Translocation, transfer, and safety evaluation of engineered nanomaterials in non-mammalian alternative assay model of Caenorhabditis elegans are summarized and discussed. Due to the extensive applications of engineered nanomaterials (ENMs) in industry, agriculture, medicine and public health, environmental exposure of ENMs to human and environmental organisms is inevitable, therefore studies on translocation, transfer, and toxicology of ENMs receive wide interest. Modelling the nematode C. elegans, a widely recognized non-mammalian alternative toxicity assay system has been proven to be valuable in environmental safety evaluation, toxicological study, and examination of translocation and transfer of toxicants. In this review, we summarize and discuss the values and contributions of C. elegans in studies on environmental safety evaluation, toxicology, and translocation and transfer of ENMs. We introduced acute and chronic toxicity assay systems and discussed environmental safety assessment of specific ENMs at predicted environmental relevant concentrations, and influences of chemical properties of ENMs, exposure routes, developmental, genetic or physiological state, and environmental factors on nanotoxicity formation in nematodes. We then discussed the toxicological mechanisms of ENMs mainly with respect to roles of oxidative stress in normal and stress conditions and signaling pathways, reproductive toxicology, neurotoxicology, and translocation, distribution, transfer and metabolism of ENMs in C. elegans. Ways to eliminate or reduce the toxicities of specific ENMs by chemical modification with surface designs were further discussed. Finally, four important challenges have been raised and discussed by surrounding the aspects of environmental safety assessment, toxicological mechanisms, and designs of new safe ENMs.

Quantifying and Imaging Engineered Nanomaterials In Vivo: Challenges and Techniques

Quantifying and imaging the engineered nanomaterials (ENMs) in vivo can provide information on the bio-distribution and fate of ENMs in living systems. A necessary amount of in vivo quantitative data is indispensable to verify the extrapolation from in vitro tests, to modify the predictive models of ENM exposure, and to underpin the risk management strategy for ENMs. However, it remains a challenge to quantitatively assess the bio-distribution of ENMs under realistic exposure, their long-term deposition (especially in non-targeted tissues), their passage across the natural barriers, and the impacts of nano-bio interactions on their in vivo behaviors. Some commonly used techniques for in vivo ENM quantification, such as electron microscopy, fluorescence-based detection, atomic spectroscopy, radiotracing, and techniques basing on synchrotron radiation are reviewed, and their technical characteristics, the state of the art, limitations, and future prospects are addressed.

Searching for global descriptors of engineered nanomaterial fate and transport in the environment.

Engineered nanomaterials (ENMs) are a new class of environmental pollutants. Researchers are beginning to debate whether new modeling paradigms and experimental tests to obtain model parameters are required for ENMs or if approaches for existing pollutants are robust enough to predict ENM distribution between environmental compartments. This Account outlines how experimental research can yield quantitative data for use in ENM fate and exposure models. We first review experimental testing approaches that are employed with ENMs. Then we compare and contrast ENMs against other pollutants. Finally, we summarize the findings and identify research needs that may yield global descriptors for ENMs that are suitable for use in fate and transport modeling. Over the past decade, researchers have made significant progress in understanding factors that influence the fate and transport of ENMs. In some cases, researchers have developed approaches toward global descriptor models (experimental, conceptual, and quantitative). We suggest the following global descriptors for ENMs: octanol-water partition coefficients, solid-water partition coefficients, attachment coefficients, and rate constants describing reactions such as dissolution, sedimentation, and degradation. ENMs appear to accumulate at the octanol-water interface and readily interact with other interfaces, such as lipid-water interfaces. Batch experiments to investigate factors that influence retention of ENMs on solid phases are very promising. However, ENMs probably do not behave in the same way as dissolved chemicals, and therefore, researchers need to use measurement techniques and concepts more commonly associated with colloids. Despite several years of research with ENMs in column studies, available summaries tend to discuss the effects of ionic strength, pH, organic matter, ENM type, packing media, or other parameters qualitatively rather than reporting quantitative values, such as attachment efficiencies, that would facilitate comparison across studies. Only a few structure-activity relationships have been developed for ENMs so far, but such evaluations will facilitate the understanding of the reactivities of different forms of a single ENM. The establishment of predictive capabilities for ENMs in the environment would enable accurate exposure assessments that would assist in ENM risk management. Such information is also critical for understanding the ultimate disposition of ENMs and may provide a framework for improved engineering of nanomaterials that are more environmentally benign.

Limitations and information needs for engineered nanomaterial-specific exposure estimation and scenarios: recommendations for improved reporting practices

The aim of this paper is to describe the process and challenges in building exposure scenarios for engineered nanomaterials (ENM), using an exposure scenario format similar to that used for the European Chemicals regulation (REACH). Over 60 exposure scenarios were developed based on information from publicly available sources (literature, books, and reports), publicly available exposure estimation models, occupational sampling campaign data from partnering institutions, and industrial partners regarding their own facilities. The primary focus was on carbon-based nanomaterials, nano-silver (nano-Ag) and nano-titanium dioxide (nano-TiO2), and included occupational and consumer uses of these materials with consideration of the associated environmental release. The process of building exposure scenarios illustrated the availability and limitations of existing information and exposure assessment tools for characterizing exposure to ENM, particularly as it relates to risk assessment. This article describes the gaps in the information reviewed, recommends future areas of ENM exposure research, and proposes types of information that should, at a minimum, be included when reporting the results of such research, so that the information is useful in a wider context.

Health implications of engineered nanomaterials

With the development of nanotechnology, a growing number of people are expected to be exposed to its products, the engineered nanomaterials (ENMs). Some physico-chemical properties of ENMs, linked to their size in the nanoscale (1-100 nm), make them potentially more reactive, and therefore raise concern about possible adverse effects in humans. In this article, I discuss human diseases which may be predicted after exposure to ENMs, and how their pathogenetic mechanisms may be linked to exposure; in this regard, special emphasis has been given to the triad of oxidative stress/inflammation/genotoxicity and to the interaction of ENMs/proteins in different biological compartments. The analysis of possible adverse effects has been made on an organ-by-organ basis, starting from the skin, respiratory system and gastrointestinal tract. These sites are in fact not only those exposed to the highest amounts of ENMs, but are also the portals of entry to internal organs for possible systemic effects. Although the list and the relevance of possible human disorders linked to ENM exposure are at least as impressive as that of their direct or indirect beneficial effects for human health, we must be clear that ENM-linked diseases belong to the realm of possible risk (i.e. cannot be excluded, but are unlikely), whereas ENMs with proven beneficial effects are on the market. Therefore, the mandatory awareness about possible adverse effects of ENMs should in no way be interpreted as a motivation to disregard the great opportunity represented by nanotechnology.

Ecotoxicity test methods for engineered nanomaterials: Practical experiences and recommendations from the bench

Ecotoxicology research is using many methods for engineered nanomaterials (ENMs), but the collective experience from researchers has not been documented. This paper reports the practical issues for working with ENMs and suggests nano-specific modifications to protocols. The review considers generic practical issues, as well as specific issues for aquatic tests, marine grazers, soil organisms, and bioaccumulation studies. Current procedures for cleaning glassware are adequate, but electrodes are problematic. The maintenance of exposure concentration is challenging, but can be achieved with some ENMs. The need to characterize the media during experiments is identified, but rapid analytical methods are not available to do this. The use of sonication and natural/synthetic dispersants are discussed. Nano-specific biological endpoints may be developed for a tiered monitoring scheme to diagnose ENM exposure or effect. A case study of the algal growth test highlights many small deviations in current regulatory test protocols that are allowed (shaking, lighting, mixing methods), but these should be standardized for ENMs. Invertebrate (Daphnia) tests should account for mechanical toxicity of ENMs. Fish tests should consider semistatic exposure to minimize wastewater and animal husbandry. The inclusion of a benthic test is recommended for the base set of ecotoxicity tests with ENMs. The sensitivity of soil tests needs to be increased for ENMs and shortened for logistics reasons; improvements include using Caenorhabditis elegans, aquatic media, and metabolism endpoints in the plant growth tests. The existing bioaccumulation tests are conceptually flawed and require considerable modification, or a new test, to work for ENMs. Overall, most methodologies need some amendments, and recommendations are made to assist researchers.

A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials

A novel method is presented which is suitable for assessing in vivo the link between the physicochemical properties of engineered nanomaterials (ENM) and their biological outcomes. The ability of the technique to generate a variety of industry-relevant, property-controlled ENM exposure atmospheres for inhalation studies was systematically investigated. The primary particle size for Fe2O3, SiO2, Ag and Ag/SiO2 was controlled from 4 to 25 nm, while the corresponding agglomerate mobility diameter of the aerosol was also controlled and varied from 40 to 120 nm. The suitability of the technique to characterize the pulmonary and cardiovascular effects of inhaled ENMs in intact animal models is also demonstrated using in vivo chemiluminescence (IVCL). The IVCL technique is a highly sensitive method for identifying cardiopulmonary responses to inhaled ENMs under relatively small doses and acute exposures. It is shown that moderate and acute exposures to inhaled nanostructured Fe2O3 can cause both pulmonary and cardiovascular effects.

Nanotechnologies, engineered nanomaterials and occupational health and safety – A review

The significance of engineered nanomaterials (ENM) and nanotechnologies grows rapidly. Nanotechnology applications may have a positive marked impact on many aspects of on human every day life, for example by providing means for the production of clean energy and pure drinking water. Hundreds of consumer nano-based products are already on the market. However, very little is known of the risks of ENM to occupational safety and health (OSH), even though workers are likely to be at extra risk, as compared with other potentially exposed groups of people, because the levels of exposure are usually higher at workplaces than in other environments. However, knowledge of the exposure to, or effects of, ENM on human health and safety in occupational environments is limited and does not allow reliable assessment of risks of ENM on workers’ health. Several issues related to ENM in the workplaces require marked attention. The most topical issues include: (1) improved understanding of ENM metrics associated with ENM toxicity; (2) development of monitoring devices for ENM exposure assessment; (3) understanding the changes of ENM structure and state of agglomeration at different concentrations in aerosols; (4) understanding translocation of ENM in the human body; (5) identifying the key health effects of ENM including pulmonary toxicity, genotoxicity, carcinogenic effects, and effects on circulation; (6) development of tiered approaches for testing of safety of ENM; and (7) utilizing these data for health risk assessment, with a special emphasis on occupational environment. Available data on several ENM – ability to enter the body and reach almost any organ, to cause pulmonary inflammation and fibrosis, and even to cause increased risk of mesotheliomas in animal models, call for immediate action. It is crucial to identify those ENM that may cause occupational health and safety risks from those ENM which are innocent, hence allowing prioritization of regulatory and preventive actions at workplaces at national, regional and global levels.

P019 Perception and reproduction of whole body rotation in standing subjects

Metal-based engineered nanomaterials (ENMs) are known to affect bacterial processes and metabolic activities. While testing their negative effects on biological components, studies traditionally rely on initial exposure concentrations and thereby do not take into consideration the dynamic behavior of ENMs that ultimately determines exposure and toxicity (e.g. ion release). Moreover, functional responses of soil microbial communities to ENMs exposure can be caused by both the particulate forms and the ionic forms, yet their relative contributions remain poorly understood. Therefore, we investigated the dynamic changes of exposure concentrations of three different types of ENMs (nano-ZnO, -Cu and -Pb) and submicron particles (SMPs) in relation to their impact on the capacity of soil bacterial communities to utilize carbon substrates. The different ENMs were chosen to differ in dissolution potential. The dynamic exposures of ENMs were considered using a time weighted average (TWA) approach. The joint toxicity of the particulate forms and the ionic forms of ENMs was evaluated using a response addition model. Our results showed that the effect concentrations of spherical nano-ZnO, -Cu and SMPs, and Pb-based perovskites expressed as TWA were lower than expressed as initial concentrations. Both particulate forms and ionic forms of spherical 18 nm, 43 nm nano-ZnO and 50 nm, 100 nm nano-Cu contribute to the overall response at the EC50 levels. The particulate forms for 150 nm, 200 nm and 900 nm ZnO SMPs and rod-shaped 78 nm nano-Cu mainly affected the soil microbial metabolic potential, while the Cu ions released from spherical 25 nm nano-Cu, 500 nm Cu SMPs and Pb ions released from perovskites mainly described the effects to bacterial communities. Our results indicate that the dynamic exposure of ENMs and relative contributions of particles and ions require consideration in order to pursue a naturally realistic assessment of environmental risks of metal-based ENMs.