Effect Of Ultrafine Particles Research Articles

The impact of airborne ultrafine particulate matter on human keratinocyte stem cells.

Air pollution is today fully acknowledged to be a significant public health problem. Rapid urbanization exposed us to a variety of unhealthy ambient air pollutants at high concentrations. The emergence of airborne ultrafine particles has added an additional dimension to this already complex problem of air pollution. The skin has different functions, one of them being the protection against the deleterious effect of external agents. The aim of this study is to evaluate the impact of airborne ultrafine particles (UFP) pollution on skin aging and on keratinocyte differentiation. Ex vivo human skin biopsies and cultured keratinocytes stem cells (KSC) were submitted to diesel exhaust-derived UFP. Reactive oxygen species (ROS) production was assessed with the MitoSOX™ probe. Keratinocyte stemness potential was evaluated by the immunodetection of keratin 15 (K15) and p63 (∆N isoforms). Effect of UFP on the epithelial niche maintenance was evaluated by immunodetection of Sox9. Reconstructed epidermis model was used to assess the impact of UFP on keratinocyte differentiation and aging. UFP exposure induced ROS production and disturbed K15, ∆Np63 and Sox9 expression in KSC or ex vivo skin. Finally, investigations on reconstructed epidermis revealed a phenotype marked by impaired keratinocyte differentiation. These results indicate that UFP pollution is a potent extrinsic factor of skin aging, affecting the keratinocyte stem cell potential and the skin renewal process.

Ultrafine particle exposure and biomarkers of effect on small airways in children

The small size and large surface area of ultrafine particles (UFP) enhance their ability to deposit in the lung periphery and their reactivity. The Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH) cross-sectional study was conducted in 8–11-year-old schoolchildren attending 25 primary (elementary) schools, randomly selected from the Brisbane Metropolitan Area, Queensland, Australia. Main study findings outlined indirect evidence of distal airway deposition (raised C reactive protein) but as yet, there is no direct evidence in the literature of effects of UFP exposure on peripheral airway function. We present further UPTECH study data from two sensitive peripheral airway function tests, Oscillometry and Multiple Breath Nitrogen Washout (MBNW), performed in 577 and 627 children (88% and 96% of UPTECH study cohort) respectively: mean(SD) age 10.1(0.9) years, 46% male, with 50% atopy and 14% current asthma. Bayesian generalised linear mixed effects regression models were used to estimate the effect of UFP particle number count (PNC) exposure on key oscillometry (airway resistance, (Rrs), and reactance, (Xrs)) and MBNW (lung clearance index, (LCI) and functional residual capacity, (FRC)) indices. We adjusted for age, sex, and height, and potential confounders including socio-economic disadvantage, PM2.5 and NO2 exposure. All models contained an interaction term between UFP PNC exposure and atopy, allowing estimation of the effect of exposure on non-atopic and atopic students. Increasing UFP PNC was associated with greater lung stiffness as evidenced by a decrease in Xrs [mean (95% credible interval) −1.63 (−3.36 to −0.05)%] per 1000#.cm−3]. It was also associated with greater lung stiffness (decrease in Xrs) in atopic subjects across all models [mean change ranging from −2.06 to −2.40% per 1000#.cm−3]. A paradoxical positive effect was observed for Rrs across all models [mean change ranging from −1.55 to −1.70% per 1000#.cm−3] (decreases in Rrs indicating an increase in airway calibre), which was present for both atopic and non-atopic subjects. No effects on MBNW indices were observed. In conclusion, a modest detrimental effect of UFP on peripheral airway function among atopic subjects, as assessed by respiratory system reactance, was observed extending the main UPTECH study findings which reported a positive association with a biomarker for systemic inflammation, C-reactive protein (CRP). Further studies are warranted to explore the pathophysiological mechanisms underlying increased respiratory stiffness, and whether it persists through to adolescence and adulthood.

The Effect of Ultrafine Particles (PM0.1) on Neurological Disorders in New York State

BACKGROUND AND AIM: Ultrafine particles (UFPs) are a significant air pollutant, yet related health research is rare. Among these studies, respiratory and cardiovascular outcomes have been analyzed far more than other health outcomes. This study evaluated the effects of UFP exposure on overall and various neurological disorders; and we examined if these associations differed by or interacted with social-demographics and meteorological factors. METHODS: We gathered emergency department (ED) visit data from New York State (NYS) Department of Health with a primary diagnosis of several neurological disorders in NYS from 2013-2018. The concentrations of UFPs and other air pollutants (as confounders) were obtained from high resolution simulations using a validated chemical transport model with size-resolved particle microphysics. We used a case-crossover design and conditional logistic regression to estimate the excess risk of ED admission for all neurological disorders and the sub-types of dementia, Parkinson’s disease, multiple sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and stroke. We also analyzed interactions between UFP and gender, race, ethnicity, age, relative humidity (RH), temperature, and season. RESULTS:An inter-quartile range (IQR) increase in UFP number concentration increased general neurological disorders on individual lags (Lag 0 & 1: 0.7%, 95% CI: 0.1-1.2%) and all cumulative lags (Excessive Risk ranged from 0.7-1.4, all p0.05). UFP exposure also increased ED visits for dementia (1.4%; 95% CI: 0.1-1.2%), Parkinson’s disease (1.7%; 95% CI: 0.2-3.2%), and ALS (5.5%, 95% CI: 0.5-10.7%). Gender and age interacted with these health effects, with females and adults being more susceptible. Finally, mild temperatures (90th percentile) made individuals more vulnerable to UFP’s effects. CONCLUSIONS:Exposure to UFPs significantly increased the risk of ED visits for general neurological disorders across all lag days, especially for dementia Parkinson’s disease, and ALS. The associations varied by demographics and weather factors. More epidemiological research is needed to examine the relationships between UFPs and neurological health outcomes. KEYWORDS: Air pollution, neurological disorders, ultrafine particles

Ammonium Sulfate and Ultrafine Particles Affect Early Onset of Alzheimer’s Disease

Recent environmental studies have shown the impact of air quality on human health and in particular, toxicological effect of particulate matter (PM) and ultrafine particles (UFPs) on progression of neurodegenerative diseases. While in-vivo experiments reveal enhanced concentration of amyloid beta peptides in the brains of animals after the exposure to PM and UFPs, the molecular interactions between peptides and atmospheric pollutants remain obscure. In this study, molecular dynamics simulations were performed to investigate the effect of UFPs on the aggregation of amyloid beta peptides, associated with the development of Alzheimer’s Disease (AD) in human brain. In particular, the changes in the structure of eight As16-21 peptides, the segment of As1-42 peptide with the high propensity to aggregate were investigated. The aggregation kinetics of As16-21 peptides and amount of beta sheets in their secondary structures were studied in the presence of varying concentrations of NH4+ and SO4-2 ions, common secondary inorganic ions found in the environmental realm from the different sources of atmospheric pollution. Moreover, the effect of hydrophobic UFP, modelled by C60 molecule, on the structure of peptides was analysed. The aggregation kinetics was calculated by estimating the time necessary to reach Solvent Accessible Surface Area (SASA) of peptides of 60 nm2. The study demonstrated that, although, the inhibitory effect of hydrophobic UFP on the formation of beta sheets was revealed, there could be a synergistic effect of the concentration of (NH4)2SO4 salt and presence of UFP on the aggregation kinetics of peptides. Among three different salt concentrations of 0.15 M, 0.25 M and 0.35 M, the slowest aggregation of peptides in the absence of C60 molecule and the fastest aggregation in the presence of C60 were observed at 0.25 M of (NH4)2SO4.

UFP exposure and biomarkers of exposure/effect on small airways in school children

Background/Aim Ultrafine particles (UFP) are of health concern due to their small size and ability to diffuse into the circulatory system once inhaled. However, epidemiological studies of adverse respiratory effects from UFP exposure are uncommon and evidence is varied. There is a scarcity of data on its effects on small airways. We aimed to study associations between UFP exposure and markers of small airways exposure/impacts in school children. Methods We used a time-integrated model for particle number count (PNC) (UFP indicator), which combined measurements at schools and modelled PNC at home using land use and time trends, to assign annual average daily exposure. We measured biomarkers of small airways exposure/impact: respiratory system resistance (Rrs); respiratory system reactance (Xrs); and lung clearance index (LCI); in 577 children recruited from 25 schools. We estimated the effect of exposure to PNC on these outcomes using Bayesian generalised linear mixed effects regression models. Analyses adjusted for potential confounders, using three models: 1) age, sex, height; 2) Model 1 plus BMI, home air conditioning, carpet, garage, gas cooking, gas heating; home flooded or with visible mould (<12 months); blood cotinine levels (ETS); 3) Model 2 plus PM2.5 mass (24 h prior to clinical testing) and annual average daily NO2 exposure. Results The PNC model explained 26% of the variability of PNC measured at the schools. No statistically significant associations were observed between PNC and LCI or Xrs. Protective statistically significant associations were observed for respiratory resistance in Models 1 and 2, but not 3. Conclusions These results do not demonstrate a detrimental effect of UFP on biomarkers of small airways exposure/impact, and the results for resistance (reflecting airway calibre) are counter-intuitive to expected. This might be due to the low predictive capacity of the exposure model, therefore improved exposure measures are needed in future studies.

Formation of Structure in Clad Abrasion-Resistant Alloys of the Fe – Cr – C – Mo – Ni – Ti – B System Under the Effect of Ultrafine Particles of Titanium Nitride

The behavior of the structure of abrasion-resistant alloys of the Fe – Cr – C – Mo – Ni – Ti – B system during electric arc cladding with introduction of ultrafine particles of titanium nitride into the welding pool in the composition of both the electrode and the filling powder wires is considered. The effect of titanium nitride on the hardness and wear resistance of the experimental clad alloys at normal and elevated temperatures is studied, and the values of the operating properties of the alloys are compared to the respective properties of the commercial counterparts.

Study of the mechanism of removing ultrafine particles using SBA-15

In 2017, China’s industrial dust emissions accounted for 7.96 million tons, of which the iron and steel industry contributed approximately 25%. Particulate matter discharged from the iron and steel industry is mostly of a small size, high in temperature, and complex in composition. The mass concentration of ultrafine particles(UFPs) with particle sizes that are less than0.1 μm is low;however, the proportion of quantity concentration can be as high as 90%. Currently, the commonly used bag filters and electrostatic precipitators are not sufficiently efficient at collecting fine particles. Additionally, owing to the larger specific surface area of fine dust particles, they easily become carriers of adsorbing harmful gases, which has a greater impact on the environment and human health;thus, it is imperative to determine a simple and efficient filtration method to remove ultrafine particles. In this paper, the removal efficiency and mechanism of UFPs(2.5–25 nm) were investigated by using a scanning electromobility particle size spectrometer(SMPS)test system for SBA-15 for different pore sizes. This was done to provide a theoretical basis for the application of mesoporous materials in the control of ultra-low emission of particulate matter in the iron and steel industry. Based on the experimental results and characterization analysis, it is found that a mesoporous filtration medium with a large pore size is more efficient at affecting UFPs entry.There are many affinity sites for UFPs on the inner and outer surfaces of mesoporous materials with a specific pore size. Increasing the complexity of the ends is beneficial for improve the filtration performance of the materials. The presence or absence of nitrogen has little effect on the removal of UFPs. The diffusion effect of UFPs is stronger owing to the existence of mesoporous particles, and the diffusion coefficient is increased when particles enter the pore. Therefore, there is a difference between the theoretical exponent(m=-2/3) in the traditional model for particle diffusion and the actual diffusion results of UFPs in mesoporous materials.

Pure ultra-fine carbon particles do not exert pro-coagulation and inflammatory effects on microvascular endothelial cells.

Pro-thrombotic and inflammatory changes play an important role in cardiovascular morbidity and mortality, resulting from short-term exposure to fine particulate air-pollution. Part of those effects has been attributed to the ultra-fine particles (UFPs) that pass through the lung and directly contact blood-exposed and circulating cells. Despite UFP-induced platelet activation, it is unclear whether the penetrated particles exert any direct effect on endothelial cells. While exposure levels are boosting as a result of world-wide increases in economic development and desertification, which create more air-polluted regions, as well as increase in demands for synthetic UFPs in medicine and various industries, further studies on the health effects of these particles are required. In this study, human pulmonary and cardiac microvascular endothelial cells (MECs) have been exposed to 0.1, 1, 10, and 100μg/ml suspensions of either a natural (carbon black) or a synthetic (multi-walled carbon nano-tubes) type of UFPs, in vitro. As a result, no changes in the levels of coagulation factor VIII, Von Willebrand factor, Interleukin 8, and P-selectin measured in the cells' supernatant were observed prior to and 6, 12, and 24h after exposure. In parallel, the spatio-temporal effect of UFPs on cardiac MECs was evaluated by Transmission Electron Microscopy. Despite phagocytic uptake of pure UFPs observed on cellular sections of the treated cells, Weibel-Palade bodies remained intact in shape and similar in number when compared with the untreated cells. Our work shows that carbon itself is a non-toxic carrier for endothelial cells.

Exposure to Ambient Ultrafine Particles and Nitrogen Dioxide and Incident Acute Myocardial Infarction and Congestive Heart Failure: A Population-Based Cohort Study

Background. Although long-term exposure to traffic-related air pollutants such as nitrogen dioxide (NO2) has been linked to cardiovascular mortality and morbidity, little is known about the effect of ultrafine particles (≤0.1um in diameter; UFPs) on the incidence of major cardiovascular events. We conducted a population-based cohort study to assess the associations of chronic exposure to UFPs and NO2 with the incidence of acute myocardial infarction (AMI) and congestive heart failure (CHF). Methods. We used the Ontario Population Health and Environment Cohort (ONPHEC) to assemble our study cohorts which comprised all long-term Ontario residents who were aged 30 to 100 years and free of respective study outcomes, and lived in the City of Toronto, Canada on January 1st, 1996. Subjects were followed until December 31st, 2012. Outcomes were ascertained using validated province-wide databases. We estimated annual concentrations of UFPs and NO2 using land-use regression models and assigned these estimates to participants’ annual postal-code addresses during the follow-up period. Using random-effects Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for UFPs and NO2, adjusted for individual- and neighborhood-level covariates. We considered both single- and multi-pollutant models. Results. Between 1996 and 2012, we identified 106,644 and 43,745 incident cases of AMI and CHF, respectively. Each interquartile change in exposure to UFPs (~10,000 count/cm3) was associated with increased risk of incident AMI (HR=1.05; 1.02-1.07) and CHF (HR=1.03; 1.02-1.05) after adjusting for all covariates. These results remained unaltered with further control for fine particulate matter (PM2.5) and NO2. Exposure to NO2 was also independently associated with higher incidence of CHF.Conclusion. Exposure to traffic-related air pollution including UFPs and NO2 may increase the risk of incident cardiovascular events.

Association of ultrafine particles with cardiopulmonary health among adult subjects in the urban areas of northern Taiwan

The association between short-term exposure to particulate air pollution, especially fine particles, and cardiopulmonary health has been well-established in previous studies. However, previous findings regarding the effect of ultrafine particles (UFPs) on cardiopulmonary health are inconsistent. We repeatedly measured the mass concentrations of UFPs using a Micro-Orifice Uniform Deposit Impactor (MOUDI) in the apartments of 100 adult participants and collected the participants' health data from the pulmonary outpatient unit of Shuang-Ho Hospital to investigate the association between short-term exposure to UFPs and cardiopulmonary health using mixed-effects models from January 1, 2014 to August 31, 2017. We also collected ambient air pollution monitoring data from the Taiwan Environmental Protection Administration for data analysis. We observed that an interquartile range increase in the 24-hour mean UFPs (0.97 μg/m3) was associated with a 6.3% [95% confidence interval (CI) = 2.9, 9.7], 5.6% (95% CI = 4.1, 7.1) and 8.5% (95% CI = 3.9, 13.1) increase in systolic blood pressure, diastolic blood pressure and high sensitivity-C-reactive protein, respectively. We also observed the association of particulate matter less than or equal to 2.5 μm in diameter and nitrogen dioxide with increased blood pressure and ozone with decreased lung function. A negative trend between UFPs and forced expiratory volume in the first second was observed. We concluded that short-term exposure to UFPs was associated with cardiovascular health in adult subjects in the urban areas of northern Taiwan.

Nrf2 Deficiency in Dendritic Cells Enhances the Adjuvant Effect of Ambient Ultrafine Particles on Allergic Sensitization

Particulate matter (PM) is an important risk factor for asthma. Generation of oxidative stress by PM is a major mechanism of its health effects. Transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) mediates antioxidant and phase II enzymes and is essential in protecting against oxidative stress and lung inflammation. We have previously shown that ambient ultrafine particles (UFP) could exert a potent adjuvant effect on allergic sensitization to ovalbumin (OVA) in mice. We hypothesized that Nrf2 deficiency in dendritic cells (DC) could enhance the adjuvant potential of UFP on allergic sensitization. We show that the adjuvant effect of intranasally instilled UFP is significantly enhanced in Nrf2 knockout (Nrf2^-/-) mice compared with their wild-type (Nrf2^+/+) counterparts. Under resting conditions, Nrf2^-/- DC displayed an intrinsic predilection to a T helper 2-favoring cytokine profile characterized by a low level of IL-12p70 and a high level of IL-6 as compared to Nrf2^+/+ DC. Adoptive transfer of OVA/UFP-treated Nrf2^-/- DC provoked a more severe allergic inflammation in the lung than Nrf2^+/+ DC in the same treatment group. We conclude that Nrf2 deficiency in DC may promote a constitutive immune-polarizing cytokine milieu, which we propose may have contributed to the augmented adjuvant effect of UFP on allergic sensitization.

The effect of ultrafine particles of activating fluxes on the laser welding process

The results of investigations of the effect of ultrafine activating fluxes on the variation of the parameters of the process of penetration of S235JR steel and the quality of welded joints, produced at low laser welding speeds, are presented.

Ambient ultrafine particles promote vascular calcification

Exposure to ambient particulate matter (PM < 2.5 μm in diameter) is a modifiable risk factor to cardiovascular morbidity and mortality. Vascular calcification is intimately involved in differentiation and calcium formation of vascular smooth muscle cells in atherosclerotic lesions. In this study, we investigated the mechanisms whereby ultrafine particles (UFP) derived from ambient pollutants induced vascular calcification.We examined the direct effect of UFP on calcifying vascular cells (CVC) ‐ mesenchymal stem cells that spontaneously calcify in vitro. Treatment of CVC with UFP resulted in a significant increase in calcification (3.45 ± 1.66 fold, n=3) and alkaline phosphatase activity (4.48 ± 1.52 fold, n=3) – an important marker for calcification. UFP treatment activated NF‐κB signaling as demonstrated by reporter gene assay (2.08 ± 0.79 fold, n=2). NF‐κB inhibitor, CAY10512, blocked UFP‐stimulated ALP activity, suggesting that UFP stimulated calcification via the NF‐κB pathway. Conditioned media from THP‐1 differentiated macrophage further increased ALP activity and NF‐κB reporter activity. Thus, UFP is implicated in inducing vascular calcification via NF‐κB ‐ ALP signaling.Funding Sources: NIH R01 HL083015‐06, NIH R01 HD069305‐01

Coarse and fine particles but not ultrafine particles in urban air trigger hospital admission for asthma in children

BackgroundShort-term exposure to air pollution can trigger hospital admissions for asthma in children, but it is not known which components of air pollution are most important. There are no available...

BETA BLOCKERS MODIFY THE EFFECT OF ULTRAFINE PARTICLES ON VAGAL TONE IN SUBJECTS WITH ISCHEMIC HEART DISEASE – RESULTS FROM THE PMCARE STUDY

Background and Aims: Particulate matter exposure has been associated with increased cardiovascular morbidity and mortality, and several studies showed that exposure to fine particles may influence vagal regulation of heart rhythm. We studied the effect of exposure to ultrafine particles (UFP) on heart rate variability (HRV) in subjects with ischemic heart disease. Methods: Personal exposure to UFP (number concentration) was continuously monitored during 24-hr, in the warm and in the cold season, in 37 non-smokers individuals with ischemic heart disease. Simultaneously, a 24-hr ambulatory ECG was recorded to measure the standard deviation of normal-to-normal intervals (SDNN), a marker of overall HRV, and two HRV markers of vagal modulation, i.e. the percentage of intervals that vary more than 50 ms from the previous interval (pNN50) and the power in high frequency (HF). The associations between UFP exposure (lag0 and 1-hr to 4-hr moving averages, MA) and HRV indices were assessed with mixed effects models. Results: A negative association was observed between UFP exposure and all investigated HRV indices only in subjects not taking beta-blockers. This effect was greater on pNN50, with a -6.2% decrease (95% confidence interval (CI) -8.6 to -3.7) and on SDNN with a -3.1% decrease (95%CI -4.9 to -1.2) for an interquartile increase in 1-hr average UFP (13.59*103#/cm3). The interaction with beta-blockers was significant for pNN50 (p<0.001) and SDNN (p<0.002), and marginally significant (p=0.052) for HF. Conclusions: Our results suggest an acute effect of UFP on vagal tone modified by beta-blockers use, and confirm previous findings for fine particles (de Hartog et al 2009).

The effect of ultrafine particles produced by office equipment to peripheral mononuclear blood cells

The effect of ultrafine particles produced by office equipment to peripheral mononuclear blood cells

Effect of ultrafine particles of activating fluxes on the laser welding process

It is established that use of activating flux superdispersed powders in laser welding of steels allows for improvement of the quality of welded joints, for reducing joint gap width and increasing penetration depth: in so doing, process productivity goes up by 7–45%.

The Adjuvant Effect of Ambient Particulate Matter Is Closely Reflected by the Particulate Oxidant Potential

The Adjuvant Effect of Ambient Particulate Matter Is Closely Reflected by the Particulate Oxidant Potential

Properties of concrete made with recycled epoxy/glass particles

This paper is aimed at evaluating the properties and effectiveness of concretes containing recycled epoxy/glass (EG) particles, which were chopped and grounded waste copper‐clad laminates or printed circuit board scrap. Recycled EG particles are divided into two portions according to their size: a substitutive material for natural fine aggregate and ultra fine filler, according to the particle size of 150 μm. The percentages of EG particles substituted for natural fine aggregate for the control mix were 10, 20, and 30 wt.% by considering suitable workability. Concrete strength can be significantly improved with EG particles due to the filling effect of ultra fine particles. However, as the substitute percentage of EG particles increases, the slump of fresh concrete drops and low workability is observed in the mixes with 30% EG particle even though superplasticizer is applied. Resistivity increases and absorption decreases as the percentage of fine EG particles substituted increases. The weight loss from sulfate immersion test reduces with the use of EG particles. Test results indicate that the proper application of EG particles would effectively modify the pore system, reduce permeability, and inhibit ions penetration in concrete. By considering the saving of land‐fill disposal cost of waste epoxy and glass fiber scraps, enhancement of concrete properties, non‐toxic waste leaching, and raw materials cost reduction, the effective utilization of recycled EG particles in concrete would be successfully achieved.

Ultrafine particles exert prothrombotic but not inflammatory effects on the hepatic microcirculation in healthy mice in vivo.

Air pollution episodes are strongly associated with increased cardiovascular morbidity and mortality. The effect of ultrafine particles (UFPs), when translocated after inhalation, on the microcirculation of extrapulmonary organs remains unclear. In C57BL/6 mice, either carbon black UFPs (1x10(7) and 5x10(7)) or vehicle was infused intra-arterially. Two hours after infusion, platelet- and leukocyte-endothelial cell interactions, sinusoidal perfusion, endothelial fibrin(ogen) deposition, and phagocytic activity of Kupffer cells were analyzed by intravital video fluorescence microscopy in the liver microvasculature. Expression of fibrin(ogen), von Willebrand factor (vWF), and P-selectin on hepatic endothelium was determined by immunostaining. Apoptotic cells were quantified in TUNEL-stained tissue sections. Application of UFPs caused significantly enhanced platelet accumulation on endothelium of postsinusoidal venules and sinusoids in healthy mice. UFP-induced platelet adhesion was not preceded by platelet rolling but was strongly associated with fibrin deposition and an increase in vWF expression on the endothelial surface. In contrast, inflammatory parameters such as the number of rolling/adherent leukocytes, P-selectin expression/translocation, and the number of apoptotic cells were not elevated 2 hours after UFP exposure. In addition, UFPs did not affect sinusoidal perfusion and Kupffer cell function. UFPs induce platelet accumulation in the hepatic microvasculature of healthy mice that is associated with prothrombotic changes on the endothelial surface of hepatic microvessels. Accumulation of particles in the liver exerts a strong procoagulatory impact but does not trigger an inflammatory reaction and does not induce microvascular/hepatocellular tissue injury.