Murdock eL al (2007) also emphaslses LhaL an adequaLe characLerlzaLlon of physlco

chemlcal
properLles ls sLrongly recommended 1he followlng physlcochemlcal proprleLles
should be
characLerlzed before performlng hazardevaluaLlng sLudles
- parLlcle slze and slze dlsLrlbuLlon (weL sLaLe) and surface area (dry sLaLe) ln Lhe
relevanL medla
belng uLlllzed dependlng upon Lhe rouLe of exposure
- crysLal sLrucLure / crysLalllnlLy
- aggregaLlon sLaLus ln Lhe relevanL medla
- composlLlon / surface coaLlngs
- surface reacLlvlLy
- meLhod of nanomaLerlal synLhesls and/or preparaLlon lncludlng posL synLheLlc
modlflcaLlons
(eg neuLrallzaLlon of ulLraflne 1lC2 parLlcleLypes)
- purlLy of Lhe sample 39
W ven Lhough nanoLechnology ls a relaLlvely new
branch of lndusLry numerous appllcaLlons have
W already been developed lL ls esLlmaLed LhaL
Lhere are more Lhan 400 consumer producLs on
Lhe
W markeL whlch lnclude nanomaLerlals 1he
lnvesLmenL and exposure of workers Lo relaLed
rlsks ln
W Lhls Lechnology ls concenLraLed ln followlng
flelds
W xposure Lo englneered nanomaLerlals can be
found malnly ln Lwo ranges one aL lndusLrlal
scale
W whlch means producLlon of nanomaLerlals and
subsequenL formulaLlon and appllcaLlon ln
producLs and
W Lhe oLher aL research scale whlch lncludes
research and unlverslLy laboraLorles
W - ellmlnaLlon of Lhe emlsslon source (full
conLalnmenL process subsLlLuLlon)
W - exhausL venLllaLlon dlrecL aL Lhe source
W - personal proLecLlve equlpmenL perfecL flLLlng
resplraLors wlLh hlgh efflclency parLlculaLe alr
W (P9) fllLers wlLh flbrous fllLers
W - nonwoven fabrlcs agalnsL nanoparLlcle
peneLraLlon
W - use Lwo layers of gloves 331
W sLudles whlch have been done wlLh lonlc sllver lndlcaLe LhaL
lngesLlon of elemenLal and sllver compounds by raLs resulLs ln Lhe
bloaccumulaLlon of sllver ln Lhe braln Llssue of offsprlng and LhaL
lonlc sllver prohlblLs Lhe growLh and dlfferenLlaLlon of nerve Llssue
24 Chronlc exposure Lo elemenLal and lonlc sllver ls known Lo
cause permanenL damage Lo Lhe subcuLaneous and mucous
membranes whlch can lead Lo dlscolouraLlon of Lhe skln 12 lL has
also been known Lo cause lrrlLaLlon of Lhe eyes skln resplraLory
and lnLesLlnal LracLs as well as blood cell changes and damage Lo
Lhe llver and kldneys 12 Whlle some serlous consequences of
exposure Lo sllver have been documenLed 23 17 Lhe effecLs of
nanosllver mlghL be especlally greaL slnce nanosllver parLlcles
provlde a greaLer relaLlve surface area 26 9 allowlng for maxlmal
exposure of sllver wlLhln Lhe body 1hls means LhaL greaLer
absorpLlon of nanosllver could occur aL lower concenLraLlons Lhan
LhaL of oLher forms of sllver 12 9
W lL has been hypoLheslzed LhaL nanosllver can
dlffuse Lhrough Lhe cell membrane and release
sllver lons dlrecLly lnslde Lhe cell 7 LhaL
nanoparLlcles can be absorbed Lhrough Lhe skln
eyes and nose and LhaL Lhey can cross Lhe
bloodbraln barrler 278 ln Lerms of human
healLh consequences lL has been hypoLheslzed
LhaL nanosllver could cause drug Lo drug
lnLeracLlons wlLhln Lhe llver 11 Concern has
even been suggesLed LhaL overuse of nanosllver
for lLs anLlmlcroblal properLles
W pp'bls(2amlmoeLhyl)dlphenylC60 admlnlsLered lnLravenously ln raLs (13 and
W 23 mg/kg) ln[ecLlon of 23 mg/kg caused Lhe deaLh of Lwo LesLed raLs ln 3 mlnuLes
ln
W flve oLher raLs a 13 mg/kg dose dld noL resulL ln any deaLh and showed LhaL Lhe
W compound ls greaLer Lhan 99 bound Lo plasma proLelns and dlsLrlbuLes lnLo
Llssues lL
W also exposed Lhe absence of a renal clearance mechanlsm
W 1suchlya et ol (1996) sboweJ tbot c60 ls JlsttlboteJ tbtooqboot tbe embtyo ooJ
tbe yolk
W sac of mlce 18 hours afLer ln[ecLlon 1hus lL passes Lhrough Lhe placenLal barrler
W (lnLraperlLoneal admlnlsLraLlon 30 mg/kg day 18 of gesLaLlon)
W prellmlnary sLudy by Moussa et ol (1997) sboweJ tbot tbe c60 folleteoe coolJ be
W deLecLed ln Lhe blood llver and spleen ln mlce one Lwo and slx days afLer an
W lnLraperlLoneal ln[ecLlon
W Metobo/ism
W 1he C60 fullerene can reduce Lhe hepaLlc
enzyme acLlvlLy of gluLaLhlon (gluLaLhloneS
Lransferase
W gluLaLhlon peroxldase eL gluLaLhlon reducLase)
lo vltto lo bomoos (llvet comloq ftom oo
ootopsy)
W mlce and raLs (lwaLa et ol 1998)
W Carc|nogen|c effects
W 1here was no effecL on un synLhesls ln Lhe
appllcaLlon of C60 fullerenes Lo mouse
W skln buL a sllghL lncrease ln ornlLhlne
decarboxylase acLlvlLy (enzyme wlLh a role ln
W Lhe promoLlon of Lumours) was noLed ln Lhe
epldermls (nelson et ol 199J)
W Moreover no lncrease ln cuLaneous Lumours was
observed ln a subchronlc sLudy of
W lnlLlaLlon and promoLlon of carclnogenesls
W eve|opment effects
W n lo vltto ooJ lo vlvo stoJy of tbe effects oo Jevelopmeot of mlce wos petfotmeJ
by
W 1suchlya et ol (1996) 1be pteseoce of c60 folleteoes soloblllzeJ wltb polyvloyl
W pyrrolldone lnhlblLed cellular dlfferenLlaLlon and prollferaLlon of mesencephallc
cells lo
W vltto lottopetltooeol oJmlolsttotloo oo tbe eleveotb Joy of qestotloo cooseJ 100
W nea|th effects of nanopart|c|es IkSS1
W morLallLy and body flexlon anomalles aL 137 mg/kg malformaLlons (head and Lall
W reglon) aL 30 mg/kg and lncreased head volume aL 23 mg/kg L 30 mg/kg C60
was
W dlsLrlbuLed LhroughouL Lhe embryo and Lhe yolk sac was lmpalred 1hus C60
passes
W Lhrough Lhe placenLal barrler dlsrupLs Lhe yolk sac and causes lnLrauLerlne
morLallLy and
W malformaLlons
W enotox|c effects
W Sera et ol (1996) obsetveJ lo vltto motoqeolc octlvlty lo J solmooello sttolos
exposeJ to
W Lhe C60 fullerene and Lo vlslble llghL ln Lhe presence of a meLabollc acLlvaLlon
sysLem
W Zakharenko et ol (1997) obsetveJ oo effect of tbe c60 folleteoe Jotloq oo lo vltto
W somaLlc muLaLlon and recomblnaLlon LesL (SM1) on scbetlcblo coll ooJ oo lo
vlvo
W LesL on tosopbllo meloooqostet lotvoe
W abynln et ol (2002) testeJ tbe motoqeolc octlvlty of tbtee c60 folleteoe
Jetlvotlves oo
W olmooello tbypblmotlom Jlmetboxypbospbotylcotbetboxymetbooofolleteoe
W dlmeLhoxyphosphorylcarbmeLhoxymeLhanofullerene and 1meLhyl2(33dl
LerLbuLyl
W 4hydroxyphenyl)34fulleropyrrolldlne negaLlve resulLs were obLalned for Lhe
flrsL
W and lasL of Lhese derlvaLlves whlle Lhe second proved Lo be anLlmuLagenlc
W Ce||u|ar and humora| effects
W lo vltto exposote to tbe c60 folleteoe (125 q c60cycloJextlo) loJoceJ oxlJotlve
W damage ln raL hepaLlc mlcrosomes 1hls damage can be modulaLed by anLloxldanLs
and
W free radlcal scavengers (kamaL et ol 1998)
W 9hoLolnduced (halogen lamp) cyLoLoxlclLy of fullerenes has been reporLed ln
several
W sLudles ?ang et ol (2002) sboweJ tbot tbls octlvlty coolJ voty wltb tbe oombet of
W malonlc acld molecules added Lo Lhe C60 fullerene (dlmalonlc Lrlmalonlc or
W quadrlmalonlc acld) 9hoLoLoxlc lnhlblLlon of cell growLh was greaLer for dlmalonlc
Lhan
W for Lrlmalonlc and quadrlmalonlc acld ln descendlng order Sayes et ol (2004)
stoJleJ
W Lhe cyLoLoxlclLy (CL30) of four waLersoluble fullerenes on human cells lo vltto (sklo
W flbroblasLs and hepaLlc carlclnoma cells) 1hey showed LhaL LoxlclLy varles wlLh Lhe
W naLure of Lhe funcLlonal group
W Ingest|on exposure
W PydroxylaLed slnglewalled carbon nanoLubes (SWCn1) admlnlsLered by gavage ln
W mlce (100 L of a 13 g/mL soluLlon) are dlsLrlbuLed Lo mosL of Lhe organs and
Llssues
W excepL Lhe braln (Wang et ol 2004)
W Lxposure by other routes
W 1he sLudy by Wang et ol (2004) sbows lo mlce tbot tbe toJlomotkeJ byJtoxyloteJ
W slngledwalled carbon nanoLubes admlnlsLered lnLraperlLoneally (100 L of a 13
g/mL
W soluLlon) are dlsLrlbuLed LhroughouL Lhe body excepL Lhe braln pass Lhrough
several
W comparLmenLs and are reLalned ln Lhe bones 1hls dlsLrlbuLlon was noL affecLed by
Lhe
W oLher rouLes used (lnLravenous subcuLaneous and gavage)
W In v|tro
W 9anLaroLLo et ol (2004) stoJleJ tbe lottocellolot ttoospott of fooctlooollzeJ JcN1
W le con[ugaLed wlLh lyslne on human and mouse flbroblasLs lo vltto (1 5 ooJ 10
mM)
W 1hey showed LhaL Lhese carbon nanoLubes could pass Lhrough Lhe cellular
membrane
W accumulaLe ln Lhe cell and end up ln Lhe cell nucleus
W Cherukurl et ol (2004) sboweJ tbot cotboo ooootobes coolJ be loqesteJ by moose
W perlLoneal macrophages lo vltto
W MonLelrolvlere et ol (2005) foooJ moltlwolleJ cotboo ooootobes (MJcN1) lo
tbe
W cyLoplasmlc vacuoles of human epldermal keraLocyLes lo vltto (op to J6 m looq)
o
W decrease ln cell vlablllLy and a slgnlflcanL lncrease ln an lnflammaLlon marker
W (lnLerleukln8) 1hls demonsLraLes Lhe capablllLy of MWCn1 Lo peneLraLe Lhe cell
W membrane
WarhelL et ol (2004 2005) stoJleJ tbe polmoooty toxlclty of ocote exposote
Lo a SWCn1 preparaLlon ln male raLs (slngle lnLraLracheal lnsLlllaLlon 0 1
and 3 mg/kg) 1here was no effecL aL 1 mg/kg L 3 mg/kg Lhey reporLed a
hlgh morLallLy raLe (13 ) caused by mechanlcal blockage of Lhe upper
alrway an lncrease ln pulmonary cell prollferaLlon and an lncrease ln
mulLlfocal pulmonary granulomas slgnlflcanL lncrease ln lung welghL a
slgnlflcanL LranslenL lncrease ln bronchoalveolar lavage anomalles
(neuLrophlllc cells proLelns lacLaLe dehydrogenase) were also observed
1here was no effecL on Lhe pulmonary macrophages 1he number of raLs was
noL menLloned 1he duraLlon of posLlnsLlllaLlon observaLlon was Loo shorL Lo
evaluaLe Lhe evoluLlon of pulmonary leslons and Lhelr evenLual regresslon
1he nanoLubes also Lend Lo agglomeraLe formlng larger parLlcles whlch
could have a dlfferenL pulmonary LoxlclLy Lhan unagglomeraLed nanoLubes
no concluslon ls posslble regardlng Lhe lnherenL LoxlclLy of SWCn1
Lam et ol (2004b) stoJleJ tbe polmoooty toxlclty of ocote exposote to
Lffects on the resp|ratory system
Shevedova et ol (200Jo) lo oo lo vltto stoJy tepotteJ tbot JcN1 cooseJ
a slgnlflcanL doseresponse reducLlon of cell vlablllLy and oxldaLlve sLress
blomarkers (eg anLloxldanL reserve) and a slgnlflcanL lncrease ln llpld
IkSS1 nea|th effects of nanopart|c|es
peroxldes ln human bronchlal eplLhellal cells (0 006 012 and 024 mg/mL
of SWCn1 for 18 hours) L a concenLraLlon of 024 mg/mL Lhey deLecLed
lron ln Lhe cells and an lncrease ln apopLosls 1he auLhors menLlon LhaL Lhelr
resulLs lndlcaLe LhaL exposure Lo unreflned SWCn1 can lead Lo an lncrease ln
pulmonary LoxlclLy ln exposed workers due Lo oxldaLlve sLress
W Lffects on the sk|n and mucous membranes
W Shevedova et ol (200Jo) lo oo lo vltto stoJy tepotteJ tbot JcN1
cooseJ
W a slgnlflcanL doseresponse reducLlon of cell vlablllLy and oxldaLlve
sLress
W blomarkers (eg anLloxldanL reserve) and a slgnlflcanL lncrease ln
llpld
W peroxldes ln human epldermal keraLlnocyLes (0 006 012 and 024
mg/mL
W of SWCn1 for 18 hours) 1he auLhors menLlon LhaL accordlng Lo
Lhelr resulLs
W exposure Lo unreflned SWCn1 can lead Lo an lncrease ln cuLaneous
LoxlclLy ln
W exposed workers
W enotox|c effects
W Zheng et ol (200J) sboweJ tbot sloqle
sttooJeJ NA (oospeclfleJ otlqlo) coo wloJ lo
W vltto otoooJ o cotboo ooootobe of
opptoptlote Jlometet ooJ electtlcol
ptopettles 1be
W consequences of such an lnLeracLlon
parLlcularly ln Lhe repllcaLlon and LranscrlpLlon
W processes sLlll have Lo be sLudled
W Ce||u|ar and humora| effects
W Cul et ol (2005) sboweJ tbot JcN1 coolJ loblblt cell ptollfetotloo loJoce
opoptosls
W and reduce adherence of human embryonlc kldney cells lo vltto (25 50
100 ooJ 150
W g/mL for 1 Lo 3 days)
W !la et ol (2005) petfotmeJ o compototlve stoJy of tbe cytotoxlclty of
JcN1 moltlwolleJ
W carbon nanoLubes (MWCn1) and Lhe C60 fullerene on alveolar
macrophages ln
W Culnea plgs no cyLoLoxlclLy was observed for fullerenes Powever SWCn1
showed
W hlgher LoxlclLy Lhan MWCn1 1he dose of parLlcles necessary Lo lnduce a
reducLlon of
W macrophage phagocyLosls was lower for SWCn1 Lhan for MWCn1 and
fullerenes
nLAL1n LIILC1S CI INCkANIC
NANCAk1ICLLS
W lnsoluble lnorganlc nanoparLlcles can be
composed of pure meLals or varlous lnorganlc
producLs
W or alloys
Lffects accord|ng to routes of
exposure (adm|n|strat|on)
W o/otioexposure
W ln Lhelr lnhalaLlon sLudles CberdrsLer et ol (1994) ooJ letlo et ol (1992) obsetveJ o
W slgnlflcanL lncrease ln lnflammaLlon slgns or parameLers durlng admlnlsLraLlon of
W 20 nm 1lC2 parLlcles ln comparlson wlLh Lhe same mass of 230 nm parLlcles unLll
W Lhese sLudles performed by Lhe same Leam LlLanlum oxlde was consldered Lo be nonLoxlc
W dusL and served as an lnerL conLrol ln several Loxlcologlcal sLudles uamage Lo
W Lhe pulmonary eplLhellum obsLrucLlon of kohn's pores developmenL of sources of
W lnLersLlLlal flbrosls and alLeraLlon of macrophage funcLlons (lnflammaLlon medlaLors)
W were slgnlflcanLly greaLer 1hese resulLs show LhaL lnerL parLlcles can become
W blologlcally acLlve when nanoscaled
W Zhang et ol (2005b) tepott tbot ooolJsoo (2001) ooJ bls teom boJ ptoveJ tbot
W nanoparLlculaLe forms ( 30 nm) of LlLanlum oxlde alumlnlum oxlde and carbon
W black lncreased Lhe pulmonary lnflammaLlon parameLers 10 Llmes more Lhan
W admlnlsLraLlon of flne parLlcles of Lhe same producLs ormet ol (2004b) lo o looq
W cancer [ournal polnL ouL LhaL low solublllLy parLlcles such as carbon black and
W LlLanlum oxlde are recognlzed Lo cause flbroses neoplaslc leslons and pulmonary
W Lumours ln raLs 1he quanLlLy of Lhese producLs requlred Lo generaLe Lhe same effecLs
W ls much smaller wlLh nanoparLlcles
utoeous exposure
W Lffects on the organs
W cLlcoaL` ls a producL conslsLlng of a nylon/polyesLer mesh Lrapplng polyeLhylene
and
W lncludlng a sllver nanocrysLal layer 1hls producL has been used for several years Lo
W acceleraLe heallng of wounds and reduce bacLerlal colonlzaLlon ln Lhe presence of
W molsLure Lhe producL releases lons and sllver radlcals LhaL would be responslble
for
W anLlbacLerlal acLlon ln an lo vltto stoJy of coltoteJ bomoo ketotloocytes lom et ol
W (2004a) observed a subsLanLlal decrease ln cell vlablllLy (0 Lo 9 cell vlablllLy afLer
30
W mlnuLes of lncubaLlon) and conclude cyLoLoxlclLy of sllver nanocrysLals (0003
001
W of sllver) released by cLlcoaL` 9oon and urd (2004) ln an lo vltto stoJy of
bomoo flbroblasLs and keraLlnocyLes observed an Lu100 aL low concenLraLlons
comparable Lo
W Lhe LherapeuLlc concenLraLlons (7 33 x 104)
W Immuno|og|ca| and a||erg|c effects
W no daLa
W keproduct|ve effects
W no daLa
W eve|opment effects
W no daLa
W enotox|c effects
W no daLa
W Carc|nogen|c effects
W no daLa
W Ce||u|ar and humora| effects
W no daLa
W estioexposure
W no daLa
W xposurebyoterroutes
W Lffects on the organs
W Lffects on the sk|n and mucous membranes
W no daLa
W Lffects on the resp|ratory system
W no daLa
W L|ver effects
W Zhang et ol (2005o) obsetveJ less bepotlc fooctloo oltetotloos lo mlce tbot
W lngesLed selenlum nanoparLlcles (nanoSe) compared Lo Lhose Lo whlch nonnanoparLlculaLe
W sodlum selenlLe had been admlnlsLered
W k|dney effects
W no daLa
W Lffects on the gastro|ntest|na| system
W ln an analysls of human hlsLologlcal speclmens lncludlng conLrol cases CaLLl
W (2004) showed a correlaLlon of Lhe presence of mlcroparLlcles or
W nanoparLlcles wlLh colon cancer and Crhn's dlsease an lnflammaLory
W lnLesLlne dlsease 1he composlLlon of Lhe lncluslons ln Lhe lnLesLlnal Llssues
W was varled and Lhe auLhor posLulaLes a posslble assoclaLlon wlLh ceramlcs or
W oLher denLal producLs prosLheLlc alloys food polluLanLs or prevlous exposure
W Lo barlumbased colourlngs
W Lffects on the heart and b|ood c|rcu|at|on
W no daLa
Lffects on the heart and the
hematopo|et|c system
W ln an experlmenL lnLended Lo assess Lhe blood
compaLlblllLy of varlous forms
W of LlLanlum oxlde (1lC2) MalLz et ol (200J)
JlJ oot obsetve ooy effects of
W Lhe nanocrysLalllne form on several
parameLers of plaLeleLrlch human plasma
W (plaLeleL aggregaLlon and coagulaLlon Llme)
W Lffects on the nervous system
W no daLa
W Immuno|og|ca| and a||erg|c effects
W no daLa
W keproduct|ve effects
W no daLa
W eve|opment effects
W Zhang et ol (2005o) obsetveJ o lowet loclJeoce of tetotJeJ qtowtb lo mlce oftet
W lngesLlon of Lhe nanoparLlculaLe form of selenlum (nanoSe) ln comparlson wlLh
W anlmals LhaL recelved nonnanoparLlculaLe sodlum selenlLe
W enotox|c effects
W no daLa
W Carc|nogen|c effects
W 1he oneyear survlval raLe of mlce wlLh lnduced breasL Lumours ln Lhe Palnfeld et ol
W (2004) experlmenL was hlgh (86 ) even aL Lhe maxlmum dose of gold nanoparLlcles
W (concenLraLlon of 270 mg/cc) admlnlsLered lnLravenously for LherapeuLlc purposes
W before radloLherapy 1hese resulLs glve reason Lo belleve ln Lhe low LoxlclLy of Lhls Lype
W of formulaLlon
W Ce||u|ar and humora| effects
W n lo vltto stoJy by locotelll et ol (2004) sboweJ tbot lO2 ooJ cobolt (co)
W nanoparLlcles exhlblLed slgnlflcanL prolnflammaLory acLlvlLy for Lhe acLlvlLy of human
W marrow monocyLes whlle 1lC2 and ZrC2 nanoparLlcles were less acLlve
W 1kachenkoet ol (2004) bove obtoloeJ votloos Jeqtees of lo vltto coptote of moJlfleJ
W gold parLlcles by Lhe nuclel of human cervlcal by llver Lumor cells and by mouse
W flbroblasLoma cells nanoparLlcles could pass Lhrough Lhe Lhree barrlers (cellular
W endosomal and nuclear membrane) Lo reach Lhe nucleus xLrapolaLlon of Lhese resulLs
W Lo healLhy human cells remalns llmlLed because only Lumour cells have been sLudled
W 9eLers et ol (2004) stoJyloq tbe bebovloot ooJ vloblllty of bomoo eoJotbellol cells lo
W vlvo obsetveJ tbot lvc 1lO2 lO2 ooJ co oooopottlcles wete locotpototeJ loto tbe
W cell vacuoles 1he Co nanoparLlcles showed hlgh prolnflammaLory and cyLoLoxlc
W poLenLlal whlle Lhe SlC2 nanoparLlcles had low prolnflammaLory poLenLlal and Lhe 1lC2
W nanoparLlcles had even lower poLenLlal alLhough sLlll observable desplLe Lhe facL LhaL
W Lhls subsLance ls ofLen consldered blologlcally amorphous 1he 9IC and nl
W nanoparLlcles dld noL generaLe Lhese effecLs
Cermaln et ol (200J) compoteJ tbe lo vltto cytotoxlclty of oooopottlcles of o coboltcbtomlom
(Co/Cr) alloy3 and alumlna ceramlc whlch were produced by slmulaLed wear
of prosLheLlc [olnLs 1wo concenLraLlons were LesLed on hlsLlocyLes pulmonary flbroblasLs ln mlce Cell vlablllLy was LesLed 3 days afLer exposure 1he Co/Cr
nanoparLlcles (3 20 nm) Lrlggered hlgh cyLoLoxlclLy ln human hlsLlocyLes whlch
depended on Lhe concenLraLlon (respecLlve reducLlons of cell vlablllLy3 from 97 and
42 Lo 30 and 3 m) and mouse flbroblasLs (respecLlve reducLlons of 93 and 73)
Co/Cr parLlcles of 10 m had no slgnlflcanL effecL on cell vlablllLy lumlna ceramlc
nanoparLlcles (3 20 nm) only produced low cyLoLoxlclLy ln human hlsLlocyLes (18
reducLlon) and only aL hlgh concenLraLlons
1he lo vltto cytotoxlclty of MMlc 1 qolJ oooopottlcles (cotloolc oooopottlcle wltb o
quaLernary ammonlum complex) and MM9C 2 (carboxyllc nanoparLlcle ln lLs anlonlc
form recognlzed as noL bondlng Lo un) was sLudled by Coodman et ol (2004) lo
prlmaLe cells human red corpuscles and coll boctetlo 1be teseotcbets obsetveJ
cyLoLoxlclLy ln Lhe MM9C 1 caLlonlc nanoparLlcles afLer one hour of lncubaLlon (Lu30
10 03 11 01 31 06) 1he MM9C2 nanoparLlcles dld noL cause slgnlflcanL
LoxlclLy even afLer 24 hours of lncubaLlon 1he auLhors posLulaLe an lnLeracLlon of
nanoparLlcles wlLh Lhe cellular membrane and Lhe presence of elecLrosLaLlc aLLracLlon
mechanlsms
ln an experlmenL conducLed by lnLraLracheal lnsLlllaLlon ln raLs Pohr et ol (2002)
exposed an lncrease ln pulmonary neuLrophlles early parameLers of lnflammaLlon for
2030 nm 1lC2 nanoparLlcles 1hls effecL was noL as slgnlflcanL wlLh admlnlsLraLlon of
180 nm parLlcles CoaLlng by meLhylaLlon Lo render Lhe parLlcles hydrophoblc and Lhus
less soluble sllghLly reduced neuLrophlle producLlon for Lhe 2 parLlculaLe dlmenslons of
1lC2 when Lhe doses were 1 mg buL had llLLle lmpacL on 6 mg doses 1he auLhors
conclude LhaL parLlcle surface ls Lhe deLermlnlng facLor ln pulmonary lnflammaLlon
whlle coaLlng by meLhylaLlon played a marglnal role ln Lhe lnflammaLlon parameLers
Zhang et ol (2000) stoJleJ tbe effect lo tots of lottottocbeol lostlllotloo of tbe
nanoparLlculaLe form of cobalL (20 nm) ln comparlson wlLh Lhe admlnlsLraLlon of 3 m
cobalL parLlcles 1 3 7 13 and 30 days afLer exposure 1he auLhors observed much
greaLer slgns of pulmonary lnflammaLlon wlLh Lhe nanomeLrlc fracLlon nalysls of
bronchoalveolar lavage fluld revealed an lncrease ln pulmonary permeablllLy and
lnflammaLlon (lncrease ln neuLrophlles and proLelns lncrease ln LuP acLlvlLy) CyLoklns
lndlcaLlng an lnflammaLory reacLlon modulaLed by macrophages or monocyLes were also
presenL wlLh Lhe Lwo forms of cobalL buL ln greaLer quanLlLy and on a more susLalned
basls afLer admlnlsLraLlon of Lhe nanomeLrlc fracLlon
arlow et ol (2005) exposeJ bovloe fetol setom to cotboo block floe pottlcles (260 om
ln dlameLer 10 mg/mL) and carbon black nanoparLlcles (14 nm ln dlameLer 3 and 10
mg/mL) 1hey showed LhaL subsLances presenL ln serum exposed Lo 10 mg/mL of carbon
black nanoparLlcles were responslble for 18 Llmes more mlgraLlon of macrophages
(from mouse alveoll) Lhan carbon black flne parLlcles 1he effecL seemed Lo be llnked Lo
an oxldaLlve phenomenon because lL was reduced by addlng anLloxldanLs
nLAL1n LIILC1S CI CkANIC
NANCAk1ICLLS
W s ln Lhe case of lnorganlc nanoparLlcles (ChapLer 6) lnsoluble
organlc nanoparLlcles can be
W composed of varlous organlc subsLances ofLen lnsoluble polymers
Lo whlch dlfferenL organlc
W radlcals can be grafLed Some subsLances can also be made soluble
under speclflc condlLlons
W CfLen only Lhelr nanomeLrlc dlmenslons dlsLlngulsh organlc
nanoparLlcles from Lhe same
W producLs normally found on a larger scale Powever lL ls preclsely
because of Lhelr unlque nanoscaled
W properLles LhaL Lhese parLlcles are produced Cn Lhe nanoscale
Lhey dlsplay caLalyLlc
W chemlcal or oLher properLles LhaL do noL exlsL when ln larger
dlmenslon
Lffects accord|ng to routes of
exposure (adm|n|strat|on)
W o/otioexposure
W no daLa
W utoeous exposure
W no daLa
W estioexposure
W no daLa
W xposurebyoterroutes
W Lffects on the organs
W Lffects on the sk|n and mucous membranes
W kanLe et ol (1982) JlJ oot obsetve ooy lttltoot effects ot tbe lojectloo slte of
W poly(lsobuLyl cyanoacrylaLe) and poly(polybuLyl cyanoacrylaLe) nanoparLlcles
W (02 m ln dlameLer slngle lnLravenous ln[ecLlon 0 123 Lo 40 mL/kg)
W durlng an acuLe LoxlclLy (uL30) leLhal dose deLermlnaLlon LesL ln mlce
W Lffects on the resp|ratory system
W no daLa
W L|ver effects
W ernandezurrusuno et ol (1997) sboweJ tbot sloqle ot tepeoteJ lottoveooos
W ln[ecLlon of 214 nm poly(lsobuLyl cyanoacrylaLe) nanoparLlcles or 128 nm
W polysLyrene can Lemporarlly reduce Lhe anLloxldanL defence of lsolaLed raL
W hepaLocyLes
W k|dney effects
W no daLa
W Lffects on the gastro|ntest|na| system
W no daLa
W Lffects on the heart and b|ood c|rcu|at|on
W no daLa
W Lffects on the heart and the hematopo|et|c system
W no daLa
W Lffects on the nervous system
W no daLa
W Immuno|og|ca| and a||erg|c effects
W Meng et ol (2004) lo o blocompotlblllty ossessmeot JlJ oot obsetve ooy botmfol
W effecLs ln anlmals (lnflammaLlon eLc) durlng muscle lmplanLaLlon of a maLerlal
W composed of hydroxapaLlLe and polyamlde nanocrysLals
W keproduct|ve effects
W no daLa
W eve|opment effects
W no daLa
W enotox|c effects
W kanLe et ol (1982) JlJ oot obsetve ooy motoqeolc effect of poly(botyl cyooooctylote)
W and poly(meLhyl cyanoacrylaLe) nanoparLlcles and Lhelr degradaLlon producLs wlLh 3
W dlfferenL olmooello typblmotlom sttolos)
W LeongMorgenLhaler et ol (1997) sboweJ tbot beozo(o)pyteoe JlssolveJ lo sooflowet
W oll and encapsulaLed ln llpld nanoparLlcles exerclsed a muLagenlc acLlon on human cells
W lo vltto slmllot to beozo(o)pyteoe JlssolveJ lo Jlmetbyl solpboxlJe A sloqle Jose wos
W LesLed
W Carc|nogen|c effects
W no daLa
W Ce||u|ar and humora| effects
W no daLa
nLAL1n LIILC1S CI NANCCASULLS
NANCSnLkLS AN
NANCSnLLLS
W nanocapsules nanospheres and nanoshells can be
composed of a wlde varleLy of lnsoluble
W organlc polymers Some of Lhese sLrucLures are
developed Lo be capable of lnLegraLlon wlLh oLher
W subsLances ofLen medlcaLlons 1he surface of Lhese
nanoparLlcles can also be modlfled Lo lnLeracL
W speclflcally wlLh cerLaln slLes of Lhe body ecause of
Lhelr nanomeLrlc dlmenslons Lhese
W parLlcles can clrculaLe ln a llvlng organlsm serve as a
drug vecLor or flx Lo speclflc cells 1hey
W represenL a very acLlve research secLor wlLh poLenLlally
ma[or medlcal splnoffs
Lffects accord|ng to routes of
exposure (adm|n|strat|on)
W o/otioexposure
W no daLa
W utoeous exposure
W no daLa
W estioexposure
W no daLa
W xposurebyoterroutes
W Lffects on the organs
W no daLa
W Immuno|og|ca| and a||erg|c effects
W no daLa
W keproduct|ve effects
W no daLa
W eve|opment effects
W no daLa
W enotox|c effects
W no daLa
W Carc|nogen|c effects
W no daLa
W Ce||u|ar and humora| effects
W 1orresLugo et ol (2002) stoJleJ tbe lo vltto cytotoxlclty of byJtoqel oooospbetes
W subsLances LhaL can bypass Lhe upper dlgesLlve LracL and acL as pharmacologlcal vecLors
W dlrecLly ln Lhe lnLesLlne uslng culLures of human lnLesLlnal cells Lo whlch meLhacryllc
W acld eLhylene glycol nanospheres have been added Lhe auLhors conclude LhaL Lhls
W nanomaLerlal has low LoxlclLy Powever a reverslble alLeraLlon of Lhe elecLrlcal
W reslsLance of Lhe eplLhellal cells as well as openlng of Lhe [uncLlonal membrane
W complexes were observed 1hls ralsed Lhe posslblllLy of cellular LransporL of Lhe
W nanocomplex
W ln an lo vltto stoJy 2boo et ol (2005) sboweJ tbot oppllcotloo of o oooospbete
W formulaLlon Lo admlnlsLer arsenlc Lrloxlde reduces Lhe blood LoxlclLy of Lhls producL
W used agalnsL bladder cancer and renders lLs acLlon more speclflc Lo cancer cells
nLAL1n LIILC1S CI UAN1UM C1S
W ma[or fleld of research for abouL Lhe pasL flve years quanLum doLs (also
called nanocrysLals or
W arLlflclal aLoms) represenL a speclal form of spherlcal nanocrysLals from 1
Lo 10 nm ln dlameLer
W 1hey have been developed ln Lhe form of semlconducLors lnsulaLors
meLals magneLlc maLerlals
W or meLalllc oxldes 1he number of aLoms ln quanLum doLs whlch can
range from 1000 Lo
W 100000 makes Lhem nelLher an exLended solld sLrucLure nor a molecular
enLlLy (lLken et ol
W 2004) 1he prlnclpal research sLudles have focused on semlconducLor
quanLum doLs whlch
W dlsplay dlsLlncLlve quanLal effecLs dependlng on Lhe dlmenslons 1he llghL
emlLLed can be
W ad[usLed Lo Lhe deslred wavelengLh by changlng Lhe overall dlmenslon
(lLken et ol 2004)
Lffects accord|ng to routes of
exposure (adm|n|strat|on)
W o/otioexposure
W no daLa
W utoeous exposure
W no daLa
W estioexposure
W no daLa
W xposurebyoterroutes
W Lffects on the organs
W no daLa
W Immuno|og|ca| and a||erg|c effects
W no daLa
W keproduct|ve effects
W no daLa
W eve|opment effects
W uuberLreL et ol (2002) lojecteJ (cJe)2o oootom Jots cooteJ wltb opoly(etbyleoe
W glycol) phosphaLldyl eLhanolamlne (9C9) and phosphaLldylchollne (9C) lnLo
W xenopus frog embryo cells 1hey conclude an absence of slgnlflcanL LoxlclLy for
W embryo developmenL
W enotox|c effects
W no daLa
W Carc|nogen|c effects
W no daLa
W Ce||u|ar and humora| effects
W ln an lo vltto stoJy etfos et ol (2004) ossesseJ tbe cytotoxlclty of cJe oootom
W doLs 1he vlablllLy of hepaLocyLes lncubaLed ln a soluLlon conLalnlng Lhe quanLum doLs
W decreased accordlng Lo Lhe concenLraLlon (00623 023 1 mg/mL) and dlmlnlshed
W furLher lf Lhe quanLum doLs had been sub[ecLed Lo ulLravloleL (uI) radlaLlon for perlods
W of 1 2 and 4 hours 1he quanLum doLs LhaL had been exposed Lo uI for 8 hours reduced
W Lhe cellular vlablllLy slgnlflcanLly and comparably for Lhe Lhree concenLraLlons (6 cell
W vlablllLy) 1he auLhors conclude LhaL Lhere ls slgnlflcanL cyLoLoxlclLy of CdSe quanLum
W doLs secondary Lo oxldaLlon of Lhelr surface and Lhe release of Cd2+ lons recognlzed as
W carclnogenlc ln humans ncapsulaLlon of quanLum doLs wlLh ZnS Lended Lo reduce Lhls
W effecL (66 cell vlablllLy) buL fell Lo almosL zero lf Lhe quanLum doLs were encapsulaLed
W wlLh 98 bovlne serum albumln
W klrchner et ol (2005) exposeJ tbe cytotoxlclty of cJe ooooctystol solotloos ooJ of
W CdSe / ZnS for Lumour cells and human flbroblasLs 1hls effecL was greaLer lf Lhe
W nanocrysLal coaLlng was made of mercapLoproplonlc acld an unsLable coaLlng whlle
W more sLable coaLlngs (9Cslllca) reduced LoxlclLy ln Lhe concenLraLlons used
W 9hosphoslllcaLe coaLlngs lncreased Lhe effecL produclng Cd+2 lons wlLhln Lhe cell
W 9olymercoaLed lnerL gold nanoparLlcles also had a cyLoLoxlc effecL comparable Lo LhaL
W of CdSe / ZnS nanoparLlcles 1he auLhors conclude LhaL Lhe Loxlc effecL may be llnked Lo
W Lhe dlrecL effecL of preclplLaLed parLlcles on Lhe cells and noL only Lo producLlon of Cd+2
W lons
W Shlohara et ol (2004) stoJleJ tbe lo vltto cytotoxlclty of cJe / 2o oootom Jots
W coaLed wlLh mercapLoundecanolc acld and sheep serum albumln 1hey produced Lhree
W forms of quanLum doLs whlch dlffered accordlng Lo Lhelr phoLolumlnescence 9rlmaLe
W kldney cells human hepaLocyLes and cervlcal cancer cells were exposed Lo 0 003 01
W and 02 mg/mL for 24 hours 1he auLhors observed a decrease ln Lhe vlablllLy of Lhe 3
W cell llnes aL concenLraLlons of 01 and 02 mg/mL whlch lncreased wlLh Lhe
W concenLraLlon
W Creen and Powman (2003) conducLed an lo vltto expetlmeot lo wblcb tbey locoboteJ
W colled doublesLranded un ln a cadmlum selenlde soluLlon encapsulaLed ln zlnc
W sulphlLe funcLlonallzed wlLh surface bloLln ulLravloleL (uI) radlaLlon was also used
W 1he resulLs of Lhls sLudy show LhaL Lhe quanLum doLs alLered Lhe un by produclng SC2
W free radlcals resulLlng from ZnS oxldaLlon 1he proporLlon of un alLeraLlons varled
W accordlng Lo Lhe presence (36) or absence (29) of uI
W
nLAL1n LIILC1S CI C1nLk
NANCMA1LkIALS
W no sLudy could be found on Lhe LoxlclLy of
nanoroboLs nanodevlces nanofllamenLs or
oLher
W nanomaLerlals