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1: INTRODUCTION
In this review we analyze the possible toxic human health effects based on different
literatures that can result from exposure to ultrafine particles (UFPs) generated by
anthropogenic activities and natural sources.
1.1: Ultrafine Particles
Particles that are less than 100 nm in aerodynamic diameter range generated mainly from
combustion, gas to particle conversion, nucleation or photochemical processes, with some of
them being primary (emitted directly by the source) and some secondary (formed in the air
from the precursors emitted by the sources) in nature are commonly defined as ultrafine
particles. UFPs are the incidental products of processes involving industrial, combustion,
welding, automobile, diesel, soil, cigarette smoking, nearby quarry operations, windblowndust, sea spray, and volcanic activities. The ambient particulate matter (PM) produced from
these sources contains particles in three sizes: < 0.1 m, 0.1 m, ±2.5 m, and > 2.5 m. The
most important chemical properties of these particles differ in elemental composition, metals,
inorganic ions, carbonaceous compounds (organic and elemental carbon) and polycyclic
aromatic hydrocarbon (PAH) content. Ultrafine particles have the greater organic carbon and
PAH content, than the coarse and fine particles. Most of the particle mass in the ultrafine size
range is < 2.5 m (PM2.5), with the largest number of particles < 0.1 m, can be transported
over thousands of kilometers, and remain suspended in air for several days (Hinds, 1999).UFPs with greater surface area can carry large amounts of adsorbed pollutants, oxidant gases,
organic compounds, and transition metals (Oberdörster 2001).
1.2: Overview on Health Impacts of UFPs
Inhaled UFPs are very small compared with the cellular structures so this may evade
phagocytosis, cross cell membranes, and redistribute to other sites of the body, causing
systemic health effects. The health effects associated with increases in UFPs are attacks of
asthma in patients with pre-existing asthma, attacks of chronic obstructive pulmonary disease
(COPD), cardiovascular causes, eye irritation, death from heart attack, strokes and respiratory
causes.
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2: LITERATURE REVIEW OF HEALTH EFFECT STUDIES
Cardiovascular and pulmonary systems seem to be the main targets of this exposure. New
evidence shows accumulation of UFP in regions of the cerebellum, olfactory bulb and other
areas of the central nervous system. The UFP matter can be breathed, led to and remained in
pulmonary tissue, leading to enhanced probability of pulmonary disease and ultimately, lung
damage.
Chart1: Health problems in Indian populationDue to domestic Bio-fuels
2.1: Exposure Routes, Absorption and Distribution
The main exposure route to UFPs is through the respiratory system (inhalation). The
surface properties of UFPs generated at different sources and during aging of the particles are
dynamically different in toxicity. Therefore, the toxicity and adverse health effects caused byUFPs are heterogeneous, depending on the source and mixed exposures of primary and
secondary UFPs. How deep in the respiratory tree these particles can reach, how long they
settle in and what they do when they deposit depends on their size, shape, density and its
chemical and toxic properties. These particles can harm through smoking, and even as
food components, such as coloring and anti-caking agents. First of all UFP absorption
seems through the lung due to the tiny size of the UFP, these can penetrate the lung
epithelium and enter the bloodstream, then particles can be transferred to liver, bone
marrow, brain and heart, leading to a systematic infection. Studies on rats have shown
a significant transfer of inhaled UFP to the liver (Brunshidle et al. , 2003). In susceptible
individuals with asthma and COPD patients, exacerbation appears to be the important
molecular mechanism by which UFPs exert their toxicity (Silkoff et al. 2005). Inhaled
TiO2 UFPs cross cellular membranes by non-phagocytic mechanisms in the lungs and were
found in capillaries (Geiser et al., 2005). High concentrations of UFP are found on and near
EYE IRRITATION(41%) HEADACHE(25%)
COUGHING(23%) SKIN PROBLEM(11%)
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propagation of cardiovascular disease. Higher the surface area of the UFPs seems to lead to
oxidative stress and calcium changes in macrophages and epithelial cells that are important in
priming and activating cells for inflammation. Most of the free radical activity or oxidative
capacity caused by the UFPs is responsible for the inflammatory responses. Due to higher
surface area and potential to adsorb reactive chemical species from the air, redox activity inUFPs is greater than the larger particles (Brown et al. 2001; Li et al. 2003), it leads to an
increase in glutathione depletion and mitochondrial damage in cells.
The oxidative capacity of UFPs can be mediated by the substances attached to fine and
ultrafine carbon particles. Carbon particles mainly obtained from combustion processes are
the most numerous particles in the ultrafine range. These carbon particles aggregate easily
into clusters, containing substances like iron, other transition metals, volatile organic
compounds and polycyclic aromatic hydrocarbons (PAH), all of these associated with the
inflammatory reaction caused by particles. The Inflammatory properties of UFPs are
mediated by their large numbers, small size and high penetration rate into the interstitium,
independently of their chemical composition. A clinical study (Mills et al.2005, 2007) shows
that diesel exhaust, which is rich in UFP and elemental carbon, damage both endothelium-
dependent and independent vasodilatation, also exposure to diluted diesel exhaust increases
the myocardial ischemic burden in men with stable coronary artery disease and previous
myocardial infarction. Taken together with other human and animal studies of UFPs
exposure, there is increasingly compelling evidence that inhalation of UFPs impairs systemicendothelial function .
Figure (a) Emissions of 10nm Particles during the Urban and Extra-urban Phases of the ETC
(elemental carbon translocation) (W edekind, 2000). (b) Total global pollution
18%
12%10%
10%
50%
S
2 ¡ ¢ £ ¤ ¥
x ¢
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2.4: Health Effects of Ultrafine Particles
UFPs have a higher number concentration and surface area (Oberdörster et al. 1995),
enhanced oxidant capacity (Brown et al. 2001; Li et al. 2003), greater inflammatory potential
(Oberdörster et al. 1995), and higher pulmonary deposition efficiency (Chalupa et al. 2004;
Daigle et al. 2003). These penetrate epithelium and enter the pulmonary interstitium andvascular space (Stearns et al. 1994). Inhalation of carbon UFPs causes transient reductions in
the pulmonary capillary blood volume and it shows indirect evidence for effects of UFPs on
pulmonary endothelial function .
Inhalation of UFPs may deplete NO by delivering reactive chemical species to the
vascular endothelium. UFPs cross cell membranes via diffusion mechanisms, entering to cell
nuclei and mitochondria (Geiser et al. 2005). UFPs and reactive chemical species may enter
the pulmonary vascular space and then the systemic circulation (Mills et al. 2006; Nemmar et
al. 2002). Reactive oxygen species formed as a result of particle exposure may react with NO,
forming peroxy-nitrite, which in turn perpetuating the oxidant injury that contributes to
endothelial dysfunction and atherosclerosis. Exposure to UFPs alters endothelial function. In
a large panel study of people with diabetes (O¶Neill et al. 2005), several different measures of
UFPs exposure were related to reductions in vascular reactivity. Künzli et al. (2005) found a
significant relationship between long-term UFPs exposure and a marker of atherosclerosis,
the thickness of the carotid artery endothelium measure by ultra-sound. Exposure to
particulate air pollution containing UFPs may also contribute to the cardiovascular effects, partly because of their relatively efficient alveolar deposition and potential to enter the
pulmonary vascular space.
Exposure to carbon UFPs at regular intervals causes a significant
decrease in the pulmonary diffusion capacity for CO (Pietropaoli et al. 2004b), and reduces
peripheral blood leukocyte expression of some adhesion molecules (Frampton et al. 2006).
Both of these effects may result from pulmonary vasoconstriction. Effects on peripheral
blood leukocytes generally maximum after 3.5hr from exposure, this is similar to the timing
of effects on Reactive Hyperemia (RH). So the inhalation of carbon UFPs at regular interval
alters both pulmonary and systemic vascular function.
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2.5: Effects of Ultrafine Particles on Phagocytosis
Phagocytosis by alveolar macrophages is important in the clearance of particles from the
lungs. The uptake of these was used to judge phagocytic ability. Both ultrafine carbon black
and ultrafine TiO2 had a deleterious effect on phagocytosis of the latex indicator beads
compared with their fine counterparts
Figure
2.6: Epidemiological Studies and Markers of the Disease
UFPs inhalation affects mainly the two organ systems, the heart and the lungs.
The greater pulmonary deposition efficiency of UFPs with larger surface area and transition
metals bound to them are considered most important factor in cardiopulmonary toxicity. The
lungs are mainly affected by carbonaceous UFPs, which induce an inflammatory
reaction. This inflammatory reaction can be measured by the number of
polynucleated lymphocytes during pulmonary lavage (study with rats Brunshidleet al. ,
2003). According to the Orberdorster model exposure to UFPs leads to alveolar
macrophage activation, which further leads to acute inflammation and decreased removal
(Oberdorster,1996). This results in acceleration of particle accumulation leading to chronic
inflammation and also cause lung fibrosis as well as mutations, epithelial cell
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hyperplasia, metaplasia, tumor formation and carcinogenesis. Energy filtering transmission
electron microscopy showed that the intracellular localization of UFP depends on the
particle material. Both particle size and material affect the cellular responses to particle
exposure as measured by the generation of tumour necrosis factor- .
UFPs deposition in the lung takes place by 4 ways (CCOHS, 1999) as follows,
1. Interception: main method for fibers such as asbestos.
2. Impaction: depends on air velocity and particle mass,
3. Sedimentation: most common in bronchi and bronchioles (>0.5µm),
4. Diffusion: in the small airways (nasopharyngeal cavity, tracheobronchial) and the
alveoli region (< 0.5µm). Following Figure is the fate of UFP deposition in human
respiratory tract.
Fig: Model for fractional deposition of inhaled particles ranging from 0.006µm to 20µm in the
nasopharyngeal region and the larynx (NPL0, in the tracheobronchial (TB) and alveolar (A) region of the
human respiratory tree during nasal breathing(Oberdorster et al. , 2003 taken from IRCP, 1994).
Epidemiological studies correlate exposure to UFPs with health effects. Exposures by
mouthpiece, which passes nasal clearance mechanisms and alter the breathing, pattern
(Morawska et al. , 2004). UFPs in size range of 20 nm to 40 nm are predicted to have
relatively low nasal deposition (Daigle et al. 2003).
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In-vitro and in-vivo animal studies also provide evidence of a relationship between particle
inhalation and endothelial dysfunction. Batalha et al. (2002) performed an experiment and
reported that concentrated ambient particles induce vaso-constriction of small pulmonary
arteries in rats. Instillation of residual oil fly ash increases pulmonary artery pressure in rats,
through a mechanisms involving epidermal growth factor (Huang et al. 2002). Urban
particles causes constriction of rat pulmonary artery rings, through angiotensin-I receptor (Li
et al. 20
Peters et al,1997
(German- y)
Size(FP,UFP)
27 non-smokingadultasthmatics
Respir atorymorbidity
Most of the particles (73%) were in the ultrafine fractionwhereas most of the mass (82%) was attributable to particlesin the size range of 0.1 to 0.5 m. Both fractions wereassociated with a decrease of peak expiratory flow (PEF)and an increase in cough and feeling ill during the day. Healtheffects of the 5-d mean of the number of UFPs were larger
than those of the mass of the FP. In addition, the effects of thenumber of the ultrafine particles on PEF were stronger thanthose of PM10. Conclusions: the present stud y suggests th atthe size distribution of ambient particles helps toelucidate the properties of ambient aerosols responsiblefor health effects.
Tiittanen etal,1999(Finland)
Size(UFP,FP, CP),Mass(PM2.5,PM10)
49childrenwithchronicrespiratorysymptoms
Respir atorymorbidity
No consistent effect of particles was found as theassociations varied by lag. Of lags examined, only 1-daylagged PM2.5 was statistically significantly associated withdecreased morning peak expiratory flow ( PEF).Evening P E F was significantly associated with the 1-daylagged number of particles in the size range of 0.1-1.0 m.One-day lagged PM10, PM2.5, and PM2.5-10, and the 4-day average of PM2.5 were significantly associatedwith increased risk of cough.Given the short duration of the study, separating the effects of different types of particleswas difficult.
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Table 3: Inflammatory Processes (Animal In-Vivo Studies)
Ref Effectsstudied
Study Description Findings/ Conclusions studied
Baggset al.,(1997).
Rats Pulmonaryinflammatory
Male Fisher 344 rats were exposedfor 6 hours a day, 5 days aweek, for 3 months to 1) filteredair (control); 2) TiO2-D, 20nm particle size, 23.5 mg/m; 3)TiO2-F, 250 nm, 22.3 mg/m3; or 4) crystalline SiO2, a positive Control particle (similar to 800 nm particle size, 1.3 mg/m3). Groupsof 3-4 animals were Sacrificed at 6and 12 months following thecompletion of exposure. Pulmonaryeffects of exposure were
evaluated usingstandardhematoxylinandeosinstainsections,histochemicalstainsforcollagen, andimmunohistochemical assays for cell turnover.
Six months after animals were exposed to SiO2,they had moderate focal i n t e r s t i t i a l fibrosisand moderately s e v e r e f o c a l alveolitis.Animals exposed to TiO2-D had slightly lessfibrosis. The least fibrosis was seen in the TiO2-Fgroup. At 1 year after exposure, fibrosis was still present but decreased in the SiO2 group. Theamount of interstitial fibrosis in the TiO2-D- andTiO2-F-treated animals had largely returned tountreated. Although initially irritant, TiO2-inducedlesions regressed during a 1 -year pe r i o dfollowing cessation of exposure. Inhaled ultrafine particles of TiO
2(TiO
2-D, 20 nm particle
size) lead to a greater pulmonary inflammatoryresponse than larger pigment-grade particles(TiO2-F, 250 nm).
Brown etal.,(2001).
Rats
Respirator y
Investigated proinflammatoryresponses to various sizes of polystyrene particles as aSimple m o d e l o f p a r t i c l e so f varying s i z e Includingultrafine.
There w as a significantly greater neutrophilinflux into the rat lung after instillation of 64 nm polystyrene particles compared with 202- and535 nm particles and this was mirrored in other parameters of lung inflammation, such asincreased protein and lactate dehydrogenase in bronchoalveolar lavage. Conclusions: the resultssuggest that ultrafine particles composed of low-toxicity material such as polystyrene have proinflammatory activity as a consequence of their large surface area.
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Cassee etal.,(2002a)
Rats:healthy &with
pulmonary
hypertensi on
Pulmonarytoxicity
Tested the hypothesis thatsecondary model aerosols exertacute pulmonary adverseeffects in rats, and that rats with pulmonary
hypertension (PH), induced by
monocrotaline(MCT), are more sensitiveto these components than normalhealthy animals. In addition,tested the hypothesis that fine particles exert more effects thanultrafines. Healthy and PH ratswere exposed to ultrafine (0.07-0.10 m; 4 x 105 particles/cm3)and fine(0.57-0.64 m;9 x 103
particles/cm3) Ammonium aerosols during 4h/day f o r 3 consecutive days.The mean massconcentrations ranged from 70 to420 g/m3), respectively, for ultrafineammonium bisulfate,nitrate, and ferrosulfate andfrom 275 to 410 g/m3 for fine-mode aerosols.Bronchoalveolar lavage fluid(BALF) analysis andhistopathological examinationwerePerformed on animals sacrificed1 day after the last exposure.
Histopathology of the lungs did not reveal testatmosphere-related abnormalities in either healthy or PH rats exposed to the ammoniumsalts, or to a combination of CB + nitrate.Alveolar macrophages in rats exposed to CBonly revealed the presence of black material
intheir cytoplasm. There were no signs of cytotoxicity due to the aerosol exposures (asmeasured with lactate dehydrogenase [LDH], protein, and albumin contents in BALF).Macrophages were not activated after MCTtreatment or the test atmospheres, since nochanges were observed in N-acetylglucosaminidase (NAG). Cell differentiation profiles w e r e i n c o n s i s t e n t , partlycaused b y an a l r e a d y pr e s e n t infectionwith Haemophilus sp. The results show thatat exposure levels of ammonium salts at leastone order of magnitude higher than ambientlevels, marked adverse health effects were
absent in both healthy and PH rats.
Dick et al.,(2003).
Rats,in- vitro
Toxicity,Inflammation
By using four types of ultrafine particles, carbon black (UFCB),cobalt (UFCo), nickel (UFNi),and titanium dioxide(UFTi), determined the attributesof the ultrafine particles (surfacearea, chemical composition, particle number, or surfacereactivity) that contribute mostto its toxicity and proinflammatory effects both in-vivo and in- vitro .
The results suggest that ultrafine particles maycause adverse effects via oxidative stress, and thiscould have implications for susceptibleindividuals. Susceptible individuals, such asthose with COPD or asthma, already exhibit pre-existing oxidative stress and hence are in a primedstate for further oxidative stress induced by PM.
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Osier Rats Inflammati
onCompared the response of ratsexposed by intratrachealinhalation to fine" (similar to250 nm) and "ultrafine" (similar to 21 nm)Titanium dioxide particles with
rats exposed to similar doses byintratracheal instillation.
Animals receiving particles through inhalationshowed a decreased pulmonary responsemeasured by bronchoalveolar lavage parameters, in both severity and persistence, when compared withthose receivingParticles through instillation. These results
demonstrate a difference inPulmonary response to inhaled vs an instilled dose,which may be due t o di f f e r e n c e s i n doser a t e , p a r t i c l e d i s t r i b u t i o n , or a l t e r e d clearance between the two methods.
Takenakaet al.,(2000).
Rats, in-vitro(macropha
gecells)
Inflammation
Investigated the fate of agglomerated ultrafine particles inmacrophages in-vitro and in-vivo .Metallic s i l v e r ( Ag) wasused as a t e s t particle. For the in-vitro study, J774macrophage cell suspensions(200,000 cells in 400 lmedium) were plated insmall chambers. Six hours later,100 mu l of the silver-PBSsuspension was added to eachchamber. For the in-vivo studyusing F344 rats, 50 g Ag particles were instilledintratracheally. On days 1, 4, and 7following instillation, rats weresacrificed and the lungs wereexamined morphologically.
Both in-vitro and in-vivo studies suggested thatagglomerated Ag particles remained in targetsfor a given period of time-at least up to 7 days.
Takenakaet al.,(2001 b)
Rats Cardiovascular
Pulmonary and systemicdistribution of inhaled ultrafineelemental silver (EAg) particlesw a s investigated on t h e ba s i s o f morphology andinducti vely coupled plasma massspectrometry (ICP-MS) analysis.Rats were exposed for 6 hr at aconcentration of 133 g EAg per m3 (3 x 106 per cm 3), 15 nmmodal diameter) and weresacrificed on days
0, 1, 4, and7
Found that although instilled agglomerates of ultrafine EAg particles were retained in the lung,Ag was rapidly cleared from the lung after inhalation of ultrafine EAg particles, as well asafter instillation of AgNO3, and entered systemic pathways.
Several toxicological studies have shown that particles cause inflammatory reactionin
vitro and in vivo . Particles from the environment cause inflammatory reactions in rat lungs,
rat cell lines and human cell lines.
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Table 4: Inflammatory Processes (Animal In-Vitro Studies)
Ref Study Description Findings/ Conclusions studied studied
Beck-Speier etal., (2001).
In-vitro (immu-necells)
Physiolo-gicresponsesof immunecells
Evaluated physiologic responses of immune cells on exposure to theagglomerates of 77 nm.Elemental carbon [(EC); specificsurface area 750 m2/g] and 21 nmtitanium dioxide (TiO2) particles(specific surface area 50 m2/g) bythe release of lipid mediators byalveolar macrophages (AMs). .
The results indicate that surface area rather than mass concentration determines theeffect of ultrafine particles, andthat activation of phospholipase A(2)and COX pathway occurs at a lower particle surface area than that of 5- LO-Pathway.
Bolandet al.(2000)
In-vitro (human bronchi-alepitheli-alcells)
Lunginflammation
Studied the mechanisms underlyingthe increase in GM-CSF releaseelicited by DEPs using the human bronchial epithelial cell line.
DEP treatments increased GM-CSFmRNA levels. Comparison of theeffects of DEPs, extracted DEPs, or extracts of DEPs revealed that theincrease in GM-CSF release is mainly dueto the adsorbed organic compounds and notto the metals present on the DEP surface.Conclusions-the increase in GM-CSF releaseis mainly due to the adsorbed organicc o m p o u n d s a n d t h a t the e f f e c to f n a t i v e D E P s requires endocytosisof the particles. Reactive oxygen species andtyrosine kinase(s) may be involved in theDEP-triggered signalling of the GM-CSF
response.
Churg etal.,(1998a)
In-vitro(rattrachealexplants)
Inflammation
Examined the relationship between particle uptake by pu lm on ar yepithelial cell s and particlesize. Exposed rat tracheal explantsto fine particles (FPs; 0.12 m) or ultrafine particles (ultrafine particles; 0.021 m) of titaniumdioxide for 3 or 7 days.
The results suggest that the behaviour of particles of different size is complex:ultrafine particles persist in the tissues asrelatively large aggregates, whereas the sizeof FP aggregates becomes smaller over time. Ultrafine particles appear to enter theepithelium faster, and once in theepithelium, a greater proportion of them aretranslocated to the subepithelial spacecompared with FPs. However, if it isassumed that the volume proportion is
representative of particle number, thenumber of particles reaching the interstitialspace is directly proportional to the number applied; i.e., overall, there is no preferential transport from lumen tointerstitium by size.
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Churg etal.,(1999).
In-vitro(rattracheal
Inflammati--on
Examined whether part icle sizeaffects media to r generation.Exposed rat tracheal explants,an
The results suggest that ultrafine particles are intrinsically able to induce procollagen expression even in the absenceof
Table 5 : Translocation of UFPs to Brain and CNS
References ExperimentalGroups
Research Evidence Findings and Conclusions
Dorman et al. ,2004
Rats Particles:Mn sulfateMn phosphate
No indication of alteration in brain (GlialFibrilliary Acidic Protein) GFAP levelsfollowing exposure.
Mn transfer to the olfactory bulb,cerebellum and striatum was measured. Asmall increase in Mn content was foundonly in the olfactory bulb.
Henriksson andTjalve, 2000
Rats Particles:Mn chloride
Nasal instillation
Changes in GFAP and S-100b were reported,markers of astrocyte activation in different brain regions.
Oberdorster et al. ,2004
Rats Particles:13C, 0.035µm
Inhalation and full body exposure
Particle accumulation in the olfactory bulb wasobserved.
Tjalve et al. ,1995 Esox Lucius Particles: Non-ionic
Nasal instillation
Ionic Mn was shown to have the ability to passthrough synaptic junctions and migrate from theolfactory region to more distant regions,including the hypothalamus.
Tjalve et al. ,1996
Henriksson andTjalve, 1999
Rats Particles:Mn compounds
Inhalation and full body exposure
Mn compound transfer was observed from thenose through the olfactory nerve axons to theolfactory bulb.
Bodian andHowe1941a; 1941b
DeLorenzo1970
Non-human
mammalsParticles:Polio virus, 0.030µm& Collagen-like0.050µm
Transfer ability of solid ultrafine particles wasshown alongside axons of olfactory nerves tothe olfactory bulb.
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Table 6: Possible effects of PM in Human Systems
System Possible Effects
RespiratorySystem
Some epidemiological studies showed adverse effects only in compromised people. Changes in lung function and increase in respiratory pathologic symptoms. Changes in lung histology and structure Changes in respiratory immune mechanisms Asthma exacerbation Chronic bronchitis Pulmonary system infection Macrophage, neutrophil and monocyte concentrations were significantly
greater in the bronchoalveolar lavage of exposed people Significantly higher IL-6 and IL-8 levels in the bronchoalveolar lavage of exposed
people Significantly higher leukocyte counts in the control group in the bronchoalveolar lavage
of exposed people Mild focal interstitial fibrosis
Inflammatory reaction in the lung Lung disease exacerbation (as corroborated by increased numbers of hospitaladmissions, visit to emergency room, school absences, missed work-hours, days of reduced activity due to health problems)
Maybe alterations in FEV1, FVC and PEF and spirometry Increased respiratory morbidity and mortality in sensitive populations
Cardiovascular System
The whole process predisposes the person to cardiovascular damage:1. Damage in epithelial cells from reactive oxygen species and activation of regulationfactors.2. Activation of vascular endothelium and circulatory polymorphonuclear leukocytes.3. Inflammatory cell migration from the blood to tissues.4. Up-regulation of adhesive molecules in vascular endothelium.5. Increased secretion of interleukin ± 6 (IL-6) and tissue factors through
activation of blood factors.6. Mononucleated cells activate C-reactive protein (CRP), amyloid A and fibrinogen. Cardiac ischemic disease Heart attack ST segment depression risk Increasing the sensitivity to myocardial ischemia. Heart disease exacerbation (as corroborated by increased numbers of hospital
admissions, visit to emergency room, school absences, missed work-hours, days of reduced activity due to health problems)
Increased cardiovascular morbidity and mortality in sensitive populations
GastrointestinalSystem
UFPs are related to Crohn¶s disease (chronic recurrent inflammatory intestinal disease). UFPs, deposited and accumulated in the Liver UFPs, deposited and accumulated in the bladder
CirculatorySystem
Changes in blood indicators UPFs penetrate very deep and fast in the interstitial space and could enter blood
circulation
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NervousSystem
CNS Mn ultrafine particles translocated to the olfactory bulb, cerebellum and striatum Particle accumulation in the olfactory bulb was observed Ionic Mn was shown to have the ability to pass through synaptic junctions and
migrate from the olfactory region to more distant regions, including thehypothalamus
Transfer ability of solid ultrafine particles was shown alongside axons of olfactory
nerves to the olfactory bulb ANS
Alterations in Autonomic Nervous System (ANS) function, and changes incardiovascular risk factors such as arterial blood pressure, C-reactive protein andendothelial dysfunction
Urine Thin layer chromatography (TLC) showed the presence of a soluble99mTc type and the
absence of any 99mTc type bound to carbon particles
GeneralSymptoms
Cough Fatigue Muscle Discomfort in the neck Premature mortality
Table 7: Controlled Exposure Studies to Ultrafine Particles (UFPs)
References Researchobjective
Experimentalgroups
Exposuredetails
Results
Frampton etal.,1992
To determinewhether exposure tosulphuric acid particles inducesalveolar reaction
2
10
Healthy,non-smokers20-39 yearsold
Gaschamber exposure
H2SO4 particleswith averagediameter 0.9µm
Exposureduringexercise
Double- blindstudy
Symp toms Four detected an odor Three had cough and four
felt discomfort in the neck during exposure
P leth ysmogra ph y No change in FVC and FEV1
immediately or 18 hoursfollowing exposure
B ronchoalveolar lavage No significant difference in
various cell counts A lveolar macro phage function
No statistical difference was foundin macrophage function
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Holgate et al., 2002
To assess theeffect of short-term exposure todiesel exhaustson induction of airwayinflammation.
The objective of the study was toassess whether the observedincreasedsensitivity toatmospheric pollutants inasthmatics could be explained byneutrophil-mediatedinflammationor/and enhanced
effect of airwayinflammation,due to dieselexhaustexposure
A sthmatic group
5
10
23-52
years oldMild non-localasthmaSensitivityto at leastonesuspendedallergen
Non-smokers
C ontrol group 9
16
19-42years old Normallungfunction Noallergensensitivity
Gaschamber exposure
Dieselexhaustexposure
Double-
blindstudy
L ung function A mild but statistically significant
increase in airway resistance atthe end of exposure in theasthmatic group
A mild but statistically significantincrease in airway resistance at theend of and one hour after exposurein the control group
No significant change in FVC or FEV
1 P eri pheral blood:
No significant changeCleared blood before and after exposure B ronchoalveolar lavage:
Significantly more neutrophilsin the control but not theasthmatic group
Significantly higher IL-6 andIL-8 levels in the control butnot the asthmatic group
Significantly higher leukocyte counts in thecontrol group
Significantly lower macrophage counts in thecontrol group
Salvi et al., 1999
To test thehypothesis thatdiesel exhaustexposure caninduceinflammatoryreactions inairways and peripheral blood
4
11
21-28 yearsoldHealthynon-smokers
Gas chamber exposure
DEP andPM10
particlesand clean air (control)
Blind study
Spiro metr y: No statistical difference in
the parameters P eri pheral blood:
In the DEP exposed group,the neutrophils and plateletswere increased
In the DEP-exposed group thecellular HLA-DR + was foundless
B ronchoalveolar lavage: In the DEP exposed group
there was a significantly
greater neutrophil number
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CONCLUSIONS:
Environment, health, safety and future aspects
This review provides much clear answers on the associations between ultrafine particles and
health outcomes. UFPs are potentially harmful so understanding of the characteristics anddynamics nature of toxic UFPs is very important to unleash a spectrum of human health
hazards at the present time. The published W orld Health Organization ³Guidelines for
Concentration and Exposure-Response Measurement of Fine and Ultrafine Particulate
Matter for Use in Epidemiological Studies´ (W HO 2002), is an example of the progress in
understanding of how ultrafine particle specifics should be dealt with in study designs to
provide the desirable study outcomes. Such studies and research are much more required in
developing country like India to show the effects of ultrafine particles on health because here
very less data is available related to this context. Particulate matter characteristics (e.g size,
concentration, composition) that could be responsible for the mortality and morbidity
effects; social and medical factors that could aggravate the health risks when particle
pollution increases, precaution is advisable.
Specific recommendations for future health outcome studies include: All the characteristics of ultrafine particles vary in geographical locations (resulting
from the differences in the local sources, their strength and characteristics,
meteorology, topography, etc) as well as the differences in demographic, socio-economic and urban use factors, etc, so knowledge of local condition is also a very
important parameter. Local sources such as traffic dominants the number
concentration of ultrafine particles. The outcomes of such studies would provide an
adequate guidance to the decision makers on the most desirable steps in controlling
exposure to ultrafine particles in India. Longer periods of observation is required that would allow an evaluation of the lag
phase between exposure and effect.
Study designs and statistical approaches used should be such that the effects related to particle size of interest (<0.1 micrometers) could be decoupled from other
characteristics of the particles or complex pollutant mixtures. Studies should be conducted with larger sample sizes and potentially susceptible
subgroups, which give better modeling of the role of age, sex, and other demographic
and clinical variables.
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