Nanoparticle (NP) toxicity testing comes with many challenges. Characterization of the test substance is of crucial importance and in the case of NPs, agglomeration/aggregation state in physiological ...media needs to be considered. In this study, we have addressed the effect of agglomerated versus single particle suspensions of nano- and submicron sized gold on the inflammatory response in the lung. Rats were exposed to a single dose of 1.6 mg/kg body weight (bw) of spherical gold particles with geometric diameters of 50 nm or 250 nm diluted either by ultrapure water or by adding phosphate buffered saline (PBS). A single dose of 1.6 mg/kg bw DQ12 quartz was used as a positive control for pulmonary inflammation. Extensive characterization of the particle suspensions has been performed by determining the zetapotential, pH, gold concentration and particle size distribution. Primary particle size and particle purity has been verified using transmission electron microscopy (TEM) techniques. Pulmonary inflammation (total cell number, differential cell count and pro-inflammatory cytokines), cell damage (total protein and albumin) and cytotoxicity (alkaline phosphatase and lactate dehydrogenase) were determined in bronchoalveolar lavage fluid (BALF) and acute systemic effects in blood (total cell number, differential cell counts, fibrinogen and C-reactive protein) 3 and 24 hours post exposure. Uptake of gold particles in alveolar macrophages has been determined by TEM.
Particles diluted in ultrapure water are well dispersed, while agglomerates are formed when diluting in PBS. The particle size of the 50 nm particles was confirmed, while the 250 nm particles appear to be 200 nm using tracking analysis and 210 nm using TEM. No major differences in pulmonary and systemic toxicity markers were observed after instillation of agglomerated versus single gold particles of different sizes. Both agglomerated as well as single nanoparticles were taken up by macrophages.
Primary particle size, gold concentration and particle purity are important features to check, since these characteristics may deviate from the manufacturer's description. Suspensions of well dispersed 50 nm and 250 nm particles as well as their agglomerates produced very mild pulmonary inflammation at the same mass based dose. We conclude that single 50 nm gold particles do not pose a greater acute hazard than their agglomerates or slightly larger gold particles when using pulmonary inflammation as a marker for toxicity.
The Risk Assessment Committee of the European Chemicals Agency issued an opinion on classifying titanium dioxide (TiO
2
) as a suspected human carcinogen upon inhalation. Recent animal studies ...indicate that TiO
2
may be carcinogenic through the oral route. There is considerable uncertainty on the carcinogenicity of TiO
2
, which may be decreased if its mechanism of action becomes clearer. Here we consider adverse outcome pathways and present the available information on each of the key events (KEs). Inhalation exposure to TiO
2
can induce lung tumors in rats via a mechanism that is also applicable to other poorly soluble, low-toxicity particles. To reduce uncertainties regarding human relevance, we recommend gathering information on earlier KEs such as oxidative stress in humans. For oral exposure, insufficient information is available to conclude whether TiO
2
can induce intestinal tumors. An oral carcinogenicity study with well-characterized (food-grade) TiO
2
is needed, including an assessment of toxicokinetics and early KEs.
Ambient particulate matter (PM) exposure is associated with respiratory and cardiovascular morbidity and mortality. To what extent such effects are different for PM obtained from different sources or ...locations is still unclear. This study investigated the in vitro toxicity of ambient PM collected at different sites in the Netherlands in relation to PM composition and oxidative potential.
PM was sampled at eight sites: three traffic sites, an underground train station, as well as a harbor, farm, steelworks, and urban background location. Coarse (2.5-10 μm), fine (< 2.5 μm) and quasi ultrafine PM (qUF; < 0.18 μm) were sampled at each site. Murine macrophages (RAW 264.7 cells) were exposed to increasing concentrations of PM from these sites (6.25-12.5-25-50-100 μg/ml; corresponding to 3.68-58.8 μg/cm2). Following overnight incubation, MTT-reduction activity (a measure of metabolic activity) and the release of pro-inflammatory markers (Tumor Necrosis Factor-alpha, TNF-α; Interleukin-6, IL-6; Macrophage Inflammatory Protein-2, MIP-2) were measured. The oxidative potential and the endotoxin content of each PM sample were determined in a DTT- and LAL-assay respectively. Multiple linear regression was used to assess the relationship between the cellular responses and PM characteristics: concentration, site, size fraction, oxidative potential and endotoxin content.
Most PM samples induced a concentration-dependent decrease in MTT-reduction activity and an increase in pro-inflammatory markers with the exception of the urban background and stop & go traffic samples. Fine and qUF samples of traffic locations, characterized by a high concentration of elemental and organic carbon, induced the highest pro-inflammatory activity. The pro-inflammatory response to coarse samples was associated with the endotoxin level, which was found to increase dramatically during a three-day sample concentration procedure in the laboratory. The underground samples, characterized by a high content of transition metals, showed the largest decrease in MTT-reduction activity. PM size fraction was not related to MTT-reduction activity, whereas there was a statistically significant difference in pro-inflammatory activity between Fine and qUF PM. Furthermore, there was a statistically significant negative association between PM oxidative potential and MTT-reduction activity.
The response of RAW264.7 cells to ambient PM was markedly different using samples collected at various sites in the Netherlands that differed in their local PM emission sources. Our results are in support of other investigations showing that the chemical composition as well as oxidative potential are determinants of PM induced toxicity in vitro.
Epidemiological studies link inhalation of particles to increased risk of cardiovascular disease. Inhaled particles may induce cardiovascular disease by several different mechanisms including ...translocation of particles to systemic circulation, activation of airway sensory nerves resulting in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential expression of ca. 50 different acute phase proteins including C-reactive protein and Serum amyloid A, which are the most differentially up-regulated acute phase response proteins. Blood levels of these two acute phase proteins are closely associated with risk of cardiovascular disease in epidemiological studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monsé et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well below the current mass-based occupational exposure limits in a number of countries including Germany, The Netherlands, UK, Sweden, Denmark and the US.Given the evidence suggesting a causal relationship between increased levels of serum amyloid A and atherosclerosis, the current results call for a re-evaluation of occupational exposure limits for a number of particle exposures including ZnO taking induction of acute phase response into account. Furthermore, it underscores cardiovascular disease as an occupational disease.
Current air quality standards for particulate matter (PM) use the PM mass concentration PM with aerodynamic diameters ≤ 10 μm (PM(10)) or ≤ 2.5 μm (PM(2.5)) as a metric. It has been suggested that ...particles from combustion sources are more relevant to human health than are particles from other sources, but the impact of policies directed at reducing PM from combustion processes is usually relatively small when effects are estimated for a reduction in the total mass concentration.
We evaluated the value of black carbon particles (BCP) as an additional indicator in air quality management.
We performed a systematic review and meta-analysis of health effects of BCP compared with PM mass based on data from time-series studies and cohort studies that measured both exposures. We compared the potential health benefits of a hypothetical traffic abatement measure, using near-roadway concentration increments of BCP and PM(2.5) based on data from prior studies.
Estimated health effects of a 1-μg/m3 increase in exposure were greater for BCP than for PM(10) or PM(2.5), but estimated effects of an interquartile range increase were similar. Two-pollutant models in time-series studies suggested that the effect of BCP was more robust than the effect of PM mass. The estimated increase in life expectancy associated with a hypothetical traffic abatement measure was four to nine times higher when expressed in BCP compared with an equivalent change in PM(2.5) mass.
BCP is a valuable additional air quality indicator to evaluate the health risks of air quality dominated by primary combustion particles.
BACKGROUND: Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations ...among, and differential measurement errors of, individual components contribute to this uncertainty. OBJECTIVES: We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers. METHODS: We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittendy, three to seven times at different locations during March— October 2009. We measured PM₁₀ , PM₂.₅, particle number concentrations (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function FEV₁ (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEF₂₅_₇₅ (forced expiratory flow at 25-75% of vital capacity), and PEF (peak expiratory flow) and fractional exhaled nitric oxide (FENQ) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression. RESULTS: An interquartile increase in PNC (33,000 particles/cm³) was associated with an 11% 95% confidence interval (CI): 5, 17% and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV₁ with PNC, NO₂ (nitrogen dioxide), and NOX (nitrogen oxides). CONCLUSIONS: Changes in PNC, NO₂, and NOX were associated with evidence of acute airway inflammation (i. e., FENO) and impaired lung function. PM mass concentration and PM₁₀ oxidative potential were not predictive of the observed acute responses.
Chronic exposure to inhalable PM plausibly relates to neurotoxicity and neurodegeneration.Both direct and indirect particle effects may be implicated.Care should be taken when extrapolating animal ...data to humans.Research is needed to identify specific particle properties and underlying mechanisms.
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The world⿿s population is steadily ageing and as a result, health conditions related to ageing, such as dementia, have become a major public health concern. In 2001, it was estimated that there were almost 5 million Europeans suffering from Alzheimer⿿s disease (AD) and this figure has been projected to almost double by 2040. About 40% of people over 85 suffer from AD, and another 10% from Parkinson⿿s disease (PD). The majority of AD and PD cases are of sporadic origin and environmental factors play an important role in the aetiology. Epidemiological research identified airborne particulate matter (PM) as one of the environmental factors potentially involved in AD and PD pathogenesis. Also, cumulating evidence demonstrates that the smallest sizes of the inhalable fraction of ambient particulate matter, also referred to as ultrafine particulate matter or nano-sized particles, are capable of inducing effects beyond the respiratory system. Translocation of very small particles via the olfactory epithelium in the nose or via uptake into the circulation has been demonstrated through experimental rodent studies with engineered nanoparticles. Outdoor air pollution has been linked to several health effects including oxidative stress and neuroinflammation that may ultimately result in neurodegeneration and cognitive impairment. This review aims to evaluate the relationship between exposure to inhaled ambient particles and neurodegeneration.
Micro- and nanoplastic particles (MNP) are omnipresent as either pollution or intentionally used in consumer products, released from packaging or even food. There is an exponential increase in the ...production of plastics. With the realization of bioaccumulation in humans, toxicity research is quickly expanding. There is a rapid increase in the number of papers published on the potential implications of exposure to MNP which necessitates a call for quality criteria to be applied when doing the research. At present, most papers on MNP describe the effects of commercially available polymer (mostly polystyrene) beads that are typically not the MNP of greatest concern. This is not a fault of the research community, necessarily, as the MNPs to which humans are exposed are usually not available in the quantities needed for toxicological research and innovations are needed to supply environmentally-relevant MNP models. In addition, like we have learned from decades of research with particulate matter and engineered nanomaterials, sample physicochemical characteristics and preparation can have major impacts on the biological responses and interpretation of the research findings. Lastly, MNP dosimetry may pose challenges as (1) we are seeing early evidence that plastics are already in the human body at quite high levels that may be difficult to achieve in acute in vitro studies and (2) plastics are already in the diets fed to preclinical models. This commentary highlights the pitfalls and recommendations for particle and fibre toxicologists that should be considered when performing and disseminating the research.
The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. ...Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum.
Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-kappaB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-alpha and TNF Receptor-subtype I (TNF-RI).
Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to what extent the observed changes may impact the normal function and cellular integrity of unique brain regions.
Advances of nanoscale science have produced nanomaterials with unique physical and chemical properties at commercial levels which are now incorporated into over 1000 products. Nanoscale cerium (di) ...oxide (CeO2) has recently gained a wide range of applications which includes coatings, electronics, biomedical, energy and fuel additives. Many applications of engineered CeO2 nanoparticles are dispersive in nature increasing the risk of exposure and interactions with a variety of environmental media with unknown health, safety and environmental implications. As evident from a risk assessment perspective, the health effects of CeO2 nanoparticles are not only dependent on their intrinsic toxicity but also on the level of exposure to these novel materials. Although this may seem logical, numerous studies have assessed the health effects of nanoparticles without this simple but critical risk assessment perspective. This review extends previous exposure and toxicological assessments for CeO2 particles by summarizing the current state of micro and nano-scale cerium exposure and health risks derived from epidemiology, air quality monitoring, fuel combustion and toxicological studies to serve as a contemporary comprehensive and integrated toxicological assessment. Based on the new information presented in this review there is an ongoing exposure to a large population to new diesel emissions generated using fuel additives containing CeO2 nanoparticles for which the environmental (air quality and climate change) and public health impacts of this new technology are not known. Therefore, there is an absolute critical need for integrated exposure and toxicological studies in order to accurately assess the environmental, ecological and health implications of nanotechnology enabled diesel fuel additives with existing as well as new engine designs and fuel formulations.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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