Exposure to fine airborne particulate matter (PM(2.5)) is associated with cardiovascular events and mortality in older and cardiac patients. Potential physiologic effects of in-vehicle, roadside, and ambient PM(2.5) were investigated in young, healthy, nonsmoking, male North Carolina Highway Patrol troopers. Nine troopers (age 23 to 30) were monitored on 4 successive days while working a 3 P.M. to midnight shift. Each patrol car was equipped with air-quality monitors. Blood was drawn 14 hours after each shift, and ambulatory monitors recorded the electrocardiogram throughout the shift and until the next morning. Data were analyzed using mixed models. In-vehicle PM(2.5) (average of 24 microg/m(3)) was associated with decreased lymphocytes (-11% per 10 microg/m(3)) and increased red blood cell indices (1% mean corpuscular volume), neutrophils (6%), C-reactive protein (32%), von Willebrand factor (12%), next-morning heart beat cycle length (6%), next-morning heart rate variability parameters, and ectopic beats throughout the recording (20%). Controlling for potential confounders had little impact on the effect estimates. The associations of these health endpoints with ambient and roadside PM(2.5) were smaller and less significant. The observations in these healthy young men suggest that in-vehicle exposure to PM(2.5) may cause pathophysiologic changes that involve inflammation, coagulation, and cardiac rhythm.

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This review paper reports the consensus of a technical workshop hosted by the European network, NanoImpactNet (NIN). The workshop aimed to review the collective experience of working at the bench with manufactured nanomaterials (MNMs), and to recommend modifications to existing experimental methods and OECD protocols. Current procedures for cleaning glassware are appropriate for most MNMs, although interference with electrodes may occur. Maintaining exposure is more difficult with MNMs compared to conventional chemicals. A metal salt control is recommended for experiments with metallic MNMs that may release free metal ions. Dispersing agents should be avoided, but if they must be used, then natural or synthetic dispersing agents are possible, and dispersion controls essential. Time constraints and technology gaps indicate that full characterisation of test media during ecotoxicity tests is currently not practical. Details of electron microscopy, dark-field microscopy, a range of spectroscopic methods (EDX, XRD, XANES, EXAFS), light scattering techniques (DLS, SLS) and chromatography are discussed. The development of user-friendly software to predict particle behaviour in test media according to DLVO theory is in progress, and simple optical methods are available to estimate the settling behaviour of suspensions during experiments. However, for soil matrices such simple approaches may not be applicable. Alternatively, a Critical Body Residue approach may be taken in which body concentrations in organisms are related to effects, and toxicity thresholds derived. For microbial assays, the cell wall is a formidable barrier to MNMs and end points that rely on the test substance penetrating the cell may be insensitive. Instead assays based on the cell envelope should be developed for MNMs. In algal growth tests, the abiotic factors that promote particle aggregation in the media (e.g. ionic strength) are also important in providing nutrients, and manipulation of the media to control the dispersion may also inhibit growth. Controls to quantify shading effects, and precise details of lighting regimes, shaking or mixing should be reported in algal tests. Photosynthesis may be more sensitive than traditional growth end points for algae and plants. Tests with invertebrates should consider non-chemical toxicity from particle adherence to the organisms. The use of semi-static exposure methods with fish can reduce the logistical issues of waste water disposal and facilitate aspects of animal husbandry relevant to MMNs. There are concerns that the existing bioaccumulation tests are conceptually flawed for MNMs and that new test(s) are required. In vitro testing strategies, as exemplified by genotoxicity assays, can be modified for MNMs, but the risk of false negatives in some assays is highlighted. In conclusion, most protocols will require some modifications and recommendations are made to aid the researcher at the bench.

This article reviews nanoparticulate-chemotherapeutic systems that have been developed for human therapy, considering the components of the nanoparticles, the therapeutic agents associated with the nanoparticles and the clinical indications these therapeutic nanoparticles have been developed for. In this evaluation we have put into perspective the types of nanomaterials and their therapeutic indications. We have reviewed the nanoparticulate-chemotherapeutic systems that have been published, approved and marketed and that are currently in clinical use. We have also analyzed the nanoparticulate-chemotherapeutic systems that are in clinical trials and under preclinical development.

One of the key challenges in the field of nanoparticle (NP) analysis is in producing reliable and reproducible characterisation data for nanomaterials. This study looks at the reproducibility using a relatively new, but rapidly adopted, technique, Nanoparticle Tracking Analysis (NTA) on a range of particle sizes and materials in several different media. It describes the protocol development and presents both the data and analysis of results obtained from 12 laboratories, mostly based in Europe, who are primarily QualityNano members. QualityNano is an EU FP7 funded Research Infrastructure that integrates 28 European analytical and experimental facilities in nanotechnology, medicine and natural sciences with the goal of developing and implementing best practice and quality in all aspects of nanosafety assessment. This study looks at both the development of the protocol and how this leads to highly reproducible results amongst participants. In this study, the parameter being measured is the modal particle size.

4Kantonsschule Frauenfeld, Frauenfeld, SwitzerlandCombustion-derived and manufactured nanoparticles (NPs) are known to provoke oxidative stress and inflammatory responses in human lung cells; therefore, they play an important role during the development of adverse health effects. As the lungs are composed of more than 40 different cell types, it is of particular interest to perform toxicological studies with co-cultures systems, rather than with monocultures of only one cell type, to gain a better understanding of complex cellular reactions upon exposure to toxic substances. Monocultures of A549 human epithelial lung cells, human monocyte-derived macrophages and monocyte-derived dendritic cells (MDDCs) as well as triple cell co-cultures consisting of all three cell types were exposed to combustion-derived NPs (diesel exhaust particles) and to manufactured NPs (titanium dioxide and single-walled carbon nanotubes). The penetration of particles into cells was analysed by transmission electron microscopy. The amount of intracellular reactive oxygen species (ROS), the total antioxidant capacity (TAC) and the production of tumour necrosis factor (TNF)-a and interleukin (IL)-8 were quantified. The results of the monocultures were summed with an adjustment for the number of each single cell type in the triple cell co-culture. All three particle types were found in all cell and culture types. The production of ROS was induced by all particle types in all cell cultures except in monocultures of MDDCs. The TAC and the ( pro-) inflammatory reactions were not statistically significantly increased by particle exposure in any of the cell cultures. Interestingly, in the triple cell co-cultures, the TAC and IL-8 concentrations were lower and the TNF-a concentrations were higher than the expected values calculated from the monocultures. The interplay of different lung cell types seems to substantially modulate the oxidative stress and the inflammatory responses after NP exposure.

IMPORTANCE Individuals with asymptomatic or mild coronavirus disease 2019 (COVID-19) have been reported to frequently transmit the disease even without direct contact. The severe acute respiratory syndrome coronavirus 2 has been found at very high concentrations in swab and sputum samples from such individuals. OBJECTIVE To estimate the virus levels released from individuals with asymptomatic to moderate COVID-19 into different aerosol sizes by normal breathing and coughing, and to determine what exposure could result from this in a room shared with such individuals. DESIGN, SETTING, AND PARTICIPANTS This mathematical modeling study combined the sizedistribution of exhaled breath microdroplets for coughing and normal breathing with viral swab and sputum concentrations as approximation for lung lining liquid to obtain an estimate of emitted virus levels. Viral data were obtained from studies published as of May 20, 2020. The resulting emission data fed a single-compartment model of airborne concentrations in a room of 50 m 3 , the size of a small office or medical examination room. MAIN OUTCOMES AND MEASURES Modeling was used to estimate the viral load emitted by individuals breathing normally or coughing, and the concentrations expected in the simulated room at different ventilation rates. RESULTS The mean estimated viral load in microdroplets emitted by simulated individuals while breathing regularly was 0.0000049 copies/cm 3 , with a range of 0.0000000049 to 0.637 copies/ cm 3. The corresponding estimates for simulated coughing individuals were a mean of 0.277 copies/cm 3 per cough, with a range of 0.000277 to 36 030 copies/cm 3 per cough. The estimated concentrations in a room with an individual who was coughing frequently were very high, with a maximum of 7.44 million copies/m 3 from an individual who was a high emitter. However, regular breathing from an individual who was a high emitter was modeled to result in lower room concentrations of up to 1248 copies/m 3. CONCLUSIONS AND RELEVANCE In this modeling study, breathing and coughing were estimated to release large numbers of viruses, ranging from thousands to millions of virus copies per cubic meter in a room with an individual with COVID-19 with a high viral load, depending on ventilation and microdroplet formation process. The estimated infectious risk posed by a person with typical viral load who breathes normally was low. The results suggest that only few people with very high viral load pose an infection risk in poorly ventilated closed environments. These findings suggest that strict respiratory protection may be needed when there is a chance to be in the same small room with an individual, whether symptomatic or not, especially for a prolonged period.

This paper presents the outcomes from a workshop of the European Network on the Health and Environmental Impact of Nanomaterials (NanoImpactNet). During the workshop, 45 experts in the field of safety assessment of engineered nanomaterials addressed the need to systematically study sets of engineered nanomaterials with specific metrics to generate a data set which would allow the establishment of dose-response relations. The group concluded that international cooperation and worldwide standardization of terminology, reference materials and protocols are needed to make progress in establishing lists of essential metrics. High quality data necessitates the development of harmonized study approaches and adequate reporting of data. Priority metrics can only be based on well-characterized dose-response relations derived from the systematic study of the bio-kinetics and bio-interactions of nanomaterials at both organism and (sub)-cellular levels. In addition, increased effort is needed to develop and validate analytical methods to determine these metrics in a complex matrix.