ultrafine particle

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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.



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%)



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%

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2 ¡ ¢ £ ¤ ¥

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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.



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



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).



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.



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.



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.



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.



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.



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.



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



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



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



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.

ultrafine particle

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