Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.
The CDC recommends that healthcare settings provide influenza patients with facemasks as a means of reducing transmission to staff and other patients, and a recent report suggested that surgical masks can capture influenza virus in large droplet spray. However, there is minimal data on influenza virus aerosol shedding, the infectiousness of exhaled aerosols, and none on the impact of facemasks on viral aerosol shedding from patients with seasonal influenza. We collected samples of exhaled particles (one with and one without a facemask) in two size fractions (“coarse”>5 µm, “fine"≤5 µm) from 37 volunteers within 5 days of seasonal influenza onset, measured viral copy number using quantitative RT-PCR, and tested the fine-particle fraction for culturable virus. Fine particles contained 8.8 (95% CI 4.1 to 19) fold more viral copies than did coarse particles. Surgical masks reduced viral copy numbers in the fine fraction by 2.8 fold (95% CI 1.5 to 5.2) and in the coarse fraction by 25 fold (95% CI 3.5 to 180). Overall, masks produced a 3.4 fold (95% CI 1.8 to 6.3) reduction in viral aerosol shedding. Correlations between nasopharyngeal swab and the aerosol fraction copy numbers were weak (r = 0.17, coarse; r = 0.29, fine fraction). Copy numbers in exhaled breath declined rapidly with day after onset of illness. Two subjects with the highest copy numbers gave culture positive fine particle samples. Surgical masks worn by patients reduce aerosols shedding of virus. The abundance of viral copies in fine particle aerosols and evidence for their infectiousness suggests an important role in seasonal influenza transmission. Monitoring exhaled virus aerosols will be important for validation of experimental transmission studies in humans.
Air-borne particulates from different sources could have different physicochemical properties and inflammatory potentials. This study aims to characterize the chemical compositions and the toxicity of ambient particulate matter (PM) associated with traffic emissions.
Focused beam reflectance measurement (FBRM) was used as a process analytical technology tool to perform inline real-time particle size analysis of a proprietary granulation manufactured using a continuous twin-screw granulation-drying-milling process. A significant relationship between D20, D50, and D80 length-weighted chord length and sieve particle size was observed with a p value of <0.0001 and R (2) of 0.886. A central composite response surface statistical design was used to evaluate the effect of granulator screw speed and Comil® impeller speed on the length-weighted chord length distribution (CLD) and particle size distribution (PSD) determined by FBRM and nested sieve analysis, respectively. The effect of granulator speed and mill speed on bulk density, tapped density, Compressibility Index, and Flowability Index were also investigated. An inline FBRM probe placed below the Comil-generated chord lengths and CLD data at designated times. The collection of the milled samples for sieve analysis and PSD evaluation were coordinated with the timing of the FBRM determinations. Both FBRM and sieve analysis resulted in similar bimodal distributions for all ten manufactured batches studied. Within the experimental space studied, the granulator screw speed (650-850 rpm) and Comil® impeller speed (1,000-2,000 rpm) did not have a significant effect on CLD, PSD, bulk density, tapped density, Compressibility Index, and Flowability Index (p value > 0.05).
- Reviews of environmental contamination and toxicology
- Published over 2 years ago
Fine particulate matter (PM) in the ambient air is implicated in a variety of human health issues throughout the globe. Regulation of fine PM in the atmosphere requires information on the dimension of the problem with respect to variations in concentrations and sources. To understand the current status of fine particles in the atmosphere and their potential harmful health effects in different regions of the world this review article was prepared based on peer-reviewed scientific papers, scientific reports, and database from government organizations published after the year 2000 to evaluate the global scenario of the PM2.5 (particles <2.5 μm in aerodynamic diameter), its exceedance of national and international standards, sources, mechanism of toxicity, and harmful health effects of PM2.5 and its components. PM2.5 levels and exceedances of national and international standards were several times higher in Asian countries, while levels in Europe and USA were mostly well below the respective standards. Vehicular traffic has a significant influence on PM2.5 levels in urban areas; followed by combustion activities (biomass, industrial, and waste burning) and road dust. In urban atmosphere, fine particles are mostly associated with different health effects with old aged people, pregnant women, and more so children being the most susceptible ones. Fine PM chemical constituents severely effect health due to their carcinogenic or mutagenic nature. Most of the research indicated an exceedance of fine PM level of the standards with a diverse array of health effects based on PM2.5 chemical constituents. Emission reduction policies with epidemiological studies are needed to understand the benefits of sustainable control measures for fine PM mitigation.
The potential of the force control agent (FCA) magnesium stearate (MgSt) to enhance the aerosol performance of lactose-based dry powder inhaled (DPI) formulations was investigated in this study. The excipient blends were investigated with analytical techniques including time-of-flight secondary ion mass spectrometry (ToF-SIMS) and Single Particle Aerosol Mass Spectrometry (SPAMS) and particle size, morphology and surface properties were evaluated. Excipient-blends were manufactured either by high-shear or low-shear blending lactose carrier with different amounts of MgSt in the range from 0-10% (w/w). Fluticasone propionate (FP) and salmeterol xinafoate (SX) used as model APIs were added by low-shear mixing. The in vitro aerosol performance in terms of aerodynamic particle size distribution (APSD) and fine particle fraction (FPF) of the FP and SX DPI formulations was evaluated with the Next Generation Impactor (NGI) and also with SPAMS using a Breezhaler® inhalation device. The distribution of MgSt on the lactose carrier in the blends was visualized and found to depend strongly on the blending method. This affected drug particle detachment from the carrier and thus impacted aerosol performance for FP and SX. Compared to blends without FCA, low-shear blending of MgSt increases the FPF of the model drug SX, while high shear blending significantly increased FPF of both SX and FP. The interactions between drug and carrier particles were substantially affected by the choice of blending technique of MgSt with lactose. This allows detailed control of aerosol performance of a DPI by an adequate choice of the blending technique. SPAMS successfully demonstrated that it is capable to distinguish changes in DPI formulations blended with different amounts of MgSt and additional information in terms of dispersibility of fine particles could be generated.
In-pram babies are more susceptible to air pollution effects, yet studies assessing their exposure are limited. We measured size-resolved particle mass (PMC; 0.25-32 μm) and number (PNC; 0.2-1 μm) concentrations on a 2.7 km route. The instruments were placed inside a baby pram. The route passed through 4 traffic intersections (TIs) and a bus stand. A total of ∼87 km road length was covered through 64 trips, made during school drop-in (morning) and pick-up (afternoon) hours. The objectives were to assess PMC and PNC exposure to in-pram babies at different route segments, understand their physicochemical characteristics and exposure differences between in-pram babies and adults carrying them. Over 5-fold variability (14.1-78.2 μg m(-3)) was observed in PMCs. Small-sized particles, including ultrafine particles, were always higher by 66% (PM1), 29% (PM2.5) and 31% (PNC) during the morning than afternoon. Coarse particles (PM2.5-10) showed an opposite trend with 70% higher concentration during afternoon than morning. TIs emerged as pollution hotspots for all the particle types. For example, PM2.5, PM2.5-10 and PNCs during the morning (afternoon) at TIs were 7 (10)%, 19 (10)% and 68 (62)% higher, respectively, compared with the rest of the route. Bus stand was also a section of enhanced exposure to PNC and PM2.5, although not so much for PM2.5-10. EDX analyses revealed Cl, Na and Fe as dominant elements. Road salt might be a source of NaCl due to de-icing during the measurements while Fe contributed by non-exhaust emissions from brake abrasion. The respiratory deposition rates imitated the trend of PMC, with higher doses of coarse and fine particles during the afternoon and morning runs, respectively. Special protection measures during conveyance of in-pram babies, especially at pollution hotspots such as traffic intersections and bus stands, could help to limit their exposure.
[This retracts the article on p. 139 in vol. 4, PMID: 27433467.].
Human-induced resuspension of floor dust is a dynamic process that can serve as a major indoor source of biological particulate matter (bioPM). Inhalation exposure to the microbial content of indoor dust is associated with adverse and protective health effects. This study evaluates infant and adult inhalation exposures and respiratory tract deposited dose rates of resuspended bioPM from carpets. Chamber experiments were conducted with a robotic crawling infant and an adult performing a walking sequence. Breathing zone (BZ) size distributions of resuspended fluorescent biological aerosol particles (FBAPs), a bioPM proxy, were monitored in real-time. FBAP exposures were highly transient during periods of locomotion. Both crawling and walking delivered a significant number of resuspended FBAPs to the BZ, with concentrations ranging from 0.5-2 cm(-3). Infants and adults are primarily exposed to a unimodal FBAP size distribution between 2 and 6 μm, with infants receiving greater exposures to super-10 μm FBAPs. In just one minute of crawling or walking, 10(2)-10(3) resuspended FBAPs can deposit in the respiratory tract, with an infant receiving much of their respiratory tract deposited dose in their lower airways. Per kg body mass, an infant will receive nearly four times greater respiratory tract deposited dose of resuspended FBAPs compared to an adult.
Background: Growing evidence indicates that toxicity of fine particulate matter ≤ 2.5 μm in diameter (PM2.5) differs by chemical component. Exposure to components may differ by population.Objectives: We investigated whether exposures to PM2.5 components differ by race/ethnicity, age, and socioeconomic status (SES).Methods: Long-term exposures (2000 through 2006) were estimated for 215 U.S. census tracts for PM2.5 and for 14 PM2.5 components. Population-weighted exposures were combined to generate overall estimated exposures by race/ethnicity, education, poverty status, employment, age, and earnings. We compared population characteristics for tracts with and without PM2.5 component monitors.Results: Larger disparities in estimated exposures were observed for components than for PM2.5 total mass. For race/ethnicity, whites generally had the lowest exposures. Non-Hispanic blacks had higher exposures than did whites for 13 of the 14 components. Hispanics generally had the highest exposures (e.g., 152% higher than whites for chlorine, 94% higher for aluminum). Young persons (0-19 years of age) had levels as high as or higher than other ages for all exposures except sulfate. Persons with lower SES had higher estimated exposures, with some exceptions. For example, a 10% increase in the proportion unemployed was associated with a 20.0% increase in vanadium and an 18.3% increase in elemental carbon. Census tracts with monitors had more non-Hispanic blacks, lower education and earnings, and higher unemployment and poverty than did tracts without monitors.Conclusions: Exposures to PM2.5 components differed by race/ethnicity, age, and SES. If some components are more toxic than others, certain populations are likely to suffer higher health burdens. Demographics differed between populations covered and not covered by monitors.