Multi-walled carbon nanotubes (MWCNTs) are commonly used in polymer formulations to improve strength, conductivity, and other attributes. A developing concern is the potential for carbon nanotube ...polymer nanocomposites to release nanoparticles into the environment as the polymer matrix degrades or is mechanically stressed. Here, we review characteristics related to release potential of five sets of polymer systems: epoxy, polyamide, polyurethane, polyethylene, and polycarbonate. Our review includes consideration of general characteristics and use of the polymer (as related to potential MWCNT release) and its MWCNT composites; general potential for nanomaterial release (particularly MWCNTs) due to degradation and mechanical stresses during use; and potential effects of stabilizers and plasticizers on polymer degradation. We examine UV degradation, temperature extremes, acid–base catalysis, and stresses such as sanding. Based on a high-level summary of the characteristics considered, the potential for release of MWCNT with typical, intended consumer use is expected to be low.
Objective: Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted ...testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information. Data sources: We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources. Data extraction: ACToR contains chemical structure information; physical-chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals. Data synthesis: We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high- and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants. Conclusions: Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated Risk Information System, and the National Toxicology Program.
For nanotechnology to meet its potential as a game-changing and sustainable technology, it is important to ensure that the engineered nanomaterials and nanoenabled products that gain entry to the ...marketplace are safe and effective. Tools and methods are needed for regulatory purposes to allow rapid material categorization according to human health and environmental risk potential, so that materials of high concern can be targeted for additional scrutiny, while material categories that pose the least risk can receive expedited review. Using carbon nanotubes as an example, we discuss how data from alternative testing strategies can be used to facilitate engineered nanomaterial categorization according to risk potential and how such an approach could facilitate regulatory decision-making in the future.
Positron emission tomography (PET) is becoming an important tool for the investigation of emerging infectious diseases in animal models. Usually, PET imaging is performed after intravenous (IV) ...radiotracer administration. However, IV injections are difficult to perform in some small animals, such as golden hamsters. This challenge is particularly evident in longitudinal imaging studies, and even more so in maximum containment settings used to study high-consequence pathogens. We propose the use of intramuscular (IM) administration of 2-deoxy-2
Ffluoro-D-glucose (
FF-FDG) for PET imaging of hamsters in a biosafety level 4 (BSL-4) laboratory setting. After
FF-FDG administration via IM or IV (through surgically implanted vascular access ports), eight hamsters underwent static or dynamic PET scans. Time-activity curves (TACs) and standardized uptake values (SUVs) in major regions of interest (ROIs) were used to compare the two injection routes. Immediately after injection, TACs differed between the two routes. At 60 min post-injection,
FF-FDG activity for both routes reached a plateau in most ROIs except the brain, with higher accumulation in the liver, lungs, brain, and nasal cavities observed in the IM group. IM delivery of
FF-FDG is an easy, safe, and reliable alternative for longitudinal PET imaging of hamsters in a BSL-4 laboratory setting.
Nipah virus (NiV) infection can lead to severe respiratory or neurological disease in humans. Transmission of NiV has been shown to occur through contact with virus contaminated fomites or ...consumption of contaminated food. Previous results using the African green monkey (AGM) model of NiV infection identified aspects of infection that, while similar to humans, don't fully recapitulate disease. Previous studies also demonstrate near uniform lethality that is not consistent with human NiV infection. In these studies, aerosol exposure using an intermediate particle size (7μm) was used to mimic potential human exposure by facilitating virus deposition in the upper respiratory tract. Computed tomography evaluation found some animals developed pulmonary parenchymal disease including consolidations, ground-glass opacities, and reactive adenopathy. Despite the lack of neurological signs, magnetic resonance imaging identified distinct brain lesions in three animals, similar to those previously reported in NiV-infected patients. Immunological characterization of tissues collected at necropsy suggested a local pulmonary inflammatory response with increased levels of macrophages in the lung, but a limited neurologic response. These data provide the first clear evidence of neurological involvement in the AGM that recapitulates human disease. With the development of a disease model that is more representative of human disease, these data suggest that NiV infection in the AGM may be appropriate for evaluating therapeutic countermeasures directed at virus-induced neuropathogenesis.
•Hazard data for many ENMs are inadequate for setting OELs by traditional methods.•Bridging from rodent instillation data can be a useful approach for setting OELs.•Several promising categorical ...approaches for setting OELs for ENMs are discussed.•Better instruments and techniques to measure worker exposure to ENMs are needed.•Development of OELs for ENMs will need to be an on-going collaborative effort.
Occupational exposure limits (OELs) are important tools for managing worker exposures to chemicals; however, hazard data for many engineered nanomaterials (ENMs) are insufficient for deriving OELs by traditional methods. Technical challenges and questions about how best to measure worker exposures to ENMs also pose barriers to implementing OELs. New varieties of ENMs are being developed and introduced into commerce at a rapid pace, further compounding the issue of OEL development for ENMs. A Workshop on Strategies for Setting Occupational Exposure Limits for Engineered Nanomaterials, held in September 2012, provided an opportunity for occupational health experts from various stakeholder groups to discuss possible alternative approaches for setting OELs for ENMs and issues related to their implementation. This report summarizes the workshop proceedings and findings, identifies areas for additional research, and suggests potential avenues for further progress on this important topic.
Background
The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable ...animal model is currently not available.
18
F-Fluorodeoxyglucose (
18
F-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response.
18
F-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used
18
F-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (
K
i
) in responsive lymphoid tissue
.
Methods
Multiple
18
F-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the
18
F-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate
K
i
for lymphoid tissues by Patlak plot.
Results
Two-way repeated measures analysis of variance revealed alterations in
K
i
that was associated with the time point (
p
< 0.001) after virus exposure and the location of lymphoid tissue (
p
= 0.0004). As revealed by a statistically significant interaction (
p
< 0.0001) between these two factors, the pattern of
K
i
changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in
K
i
was observed in mediastinal lymph nodes (LNs) that correlated to
K
i
changes in axillary LNs. Changes in LNs
K
i
were concurrent with elevations of monocytes in peripheral blood.
Conclusions
18
F-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus.
We propose a method to identify sensitive and reliable whole-lung radiomic features from computed tomography (CT) images in a nonhuman primate model of coronavirus disease 2019 (COVID-19). Criteria ...used for feature selection in this method may improve the performance and robustness of predictive models.
Fourteen crab-eating macaques were assigned to two experimental groups and exposed to either severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or a mock inoculum. High-resolution CT scans were acquired before exposure and on several post-exposure days. Lung volumes were segmented using a deep-learning methodology, and radiomic features were extracted from the original image. The reliability of each feature was assessed by the intraclass correlation coefficient (ICC) using the mock-exposed group data. The sensitivity of each feature was assessed using the virus-exposed group data by defining a factor R that estimates the excess of variation above the maximum normal variation computed in the mock-exposed group. R and ICC were used to rank features and identify non-sensitive and unstable features.
Out of 111 radiomic features, 43% had excellent reliability (
), and 55% had either good (
) or moderate (
) reliability. Nineteen features were not sensitive to the radiological manifestations of SARS-CoV-2 exposure. The sensitivity of features showed patterns that suggested a correlation with the radiological manifestations.
Features were quantified and ranked based on their sensitivity and reliability. Features to be excluded to create more robust models were identified. Applicability to similar viral pneumonia studies is also possible.
We previously demonstrated that small-particle (0.5-3.0 µm) aerosol infection of rhesus monkeys (Macaca mulatta) with cowpox virus (CPXV)-Brighton Red (BR) results in fulminant respiratory tract ...disease characterized by severe lung parenchymal pathology but only limited systemic virus dissemination and limited classic epidermal pox-like lesion development (Johnson et al., 2015). Based on these results, and to further develop CPXV as an improved model of human smallpox, we evaluated a novel large-particle aerosol (7.0-9.0 µm) exposure of rhesus monkeys to CPXV-BR and monitored for respiratory tract disease by serial computed tomography (CT). As expected, the upper respiratory tract and large airways were the major sites of virus-induced pathology following large-particle aerosol exposure. Large-particle aerosol CPXV exposure of rhesus macaques resulted in severe upper airway and large airway pathology with limited systemic dissemination.
Single photon emission computed tomography (SPECT) is frequently used in oncology and cardiology to evaluate disease progression and/or treatment efficacy. Such technology allows for real-time ...evaluation of disease progression and when applied to studying infectious diseases may provide insight into pathogenesis. Insertion of a SPECT-compatible reporter gene into a virus may provide insight into mechanisms of pathogenesis and viral tropism. The human sodium iodide symporter (hNIS), a SPECT and positron emission tomography reporter gene, was inserted into Middle East respiratory syndrome coronavirus (MERS-CoV), a recently emerged virus that can cause severe respiratory disease and death in afflicted humans to obtain a quantifiable and sensitive marker for viral replication to further MERS-CoV animal model development. The recombinant virus was evaluated for fitness, stability, and reporter gene functionality. The recombinant and parental viruses demonstrated equal fitness in terms of peak titer and replication kinetics, were stable for up to six
passages, and were functional. Further
evaluation indicated variable stability, but resolution limits hampered
functional evaluation. These data support the further development of hNIS for monitoring infection in animal models of viral disease.
Advanced medical imaging such as single photon emission computed tomography with computed tomography (SPECT/CT) enhances fields such as oncology and cardiology. Application of SPECT/CT, magnetic resonance imaging, and positron emission tomography to infectious disease may enhance pathogenesis studies and provide alternate biomarkers of disease progression. The experiments described in this article focus on insertion of a SPECT/CT-compatible reporter gene into MERS-CoV to demonstrate that a functional SPECT/CT reporter gene can be inserted into a virus.
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![Intramuscular [ 18 F]F-FDG ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1999-4915/small "Intramuscular [ 18 F]F-FDG Administration for Successful PET Imaging of Golden Hamsters in a Maximum Containment Laboratory Setting")
![Modeling [18F]-FDG lymphoid...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/2191-219X/small "Modeling [18F]-FDG lymphoid tissue kinetics to characterize nonhuman primate immune response to Middle East respiratory syndrome-coronavirus aerosol challenge")
