conference on nanotechnology for biological and biomedical...
TRANSCRIPT
2268-12
Conference on Nanotechnology for Biological and Biomedical Applications (Nano-Bio-Med)
Harald F. KRUG
10 - 14 October 2011
SFLMST, EMPA, Lerchenfeldstr. 5 CH-9014 St Gallen
SWITZERLAND
Nanotoxicology - Quo Vadis?
Materials Science & Te<:hnology:
NANOTO~Cot: GY-
!Harald F. Krug Empa, Department Materials Meet Life, St. Gall en, Switzerland
Coating technology for Nanoc:omposites
Fibers
Dlotechnorogy Developing tailor .. made Enzymes for industrial Applications
Functionalised clothing for the Monitoring of Body Functions
Thomas Hartung, ohns Hopkins University - ...
Materials MHt Ute
• • (tnt~ (o, Alttno.ei,..l • Anim•l Ttlting
Promoting for 29 years alternatives to animal testing where they are not fit for purpose
Thomas Hartung~Johns Hopkins University _ ...
Materials Meet Ute
R22 harmful If swallowed (LD50 = 150-200mg/kg In rats) R 36 irritant to eyes R 37 respiratory Irritant R 38 irritant to skin
Not carcinogenic, but co-carcinogen (promotor) Unclear mutagenicity Embryonic malformations in cat, dog, rat, mice, rabbit, monkey
Unlikely to be brought to the market today
.. ___ ,_ .............. _ EMPA. •
-C.L. Haynes (2010): The emerging field of nanotoxicology Anal. Bioanal. Chern 398, 587-588. --
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Materials MHt Ute ..
Same Size - Diff:raent Materials - ... 25
20
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- 0 • + Ti0 2 CB Cc02 Zr02 ZnO AIOOH
Materials Meet Ute
EMPA9 •
nan C a re
121: no, 10·20 nm Carbon Black (CB) 15 nm Ce02 20 nm Zr02 1 0·25 nm Zn040 nm AIOOH 40 nm
0.5, 5 and 251'gicm2
Zinc-Story- esse~ial or toxic on the Nano-Level? - ... nnnom unE .z.
Materials MHt Ute
....... ~~ -~~' ~<arqllnska \!,J.,,,/ 1nst1tutet
EMPA9 '
No difference bet~en nano or bulk ZnO particles - ...
., --8"5! .. -" .c: "' :r:: -· ., ~
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•"" .... :;..~r~; Karqlinska ~ Il-r.~ ln.stitutet .........
Materials Meet Ute
TUNEL 24 ht
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- ZIIO - ZIIOIXIIk
0 1 10 2550100 1 10 25 50100 1 10 25 50100
Concentration (llg/ml)
ZnO Toxicity is delending on the ZnO-material - ... ....... ,. 110.01_ 1 ... (Jo.Ot,t ...
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Materials Meet Ute
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Hypothetical Mode~f ZnO-NP Toxicity in Jurkat Cells _ .. ZnO-NPs dissolve mainly exttaoel llarty and znz... rapidy entei'S the oels. To oopGwith the excess free Zrfl'", Zn2> is stOC'ed in zinoosomes and the exp-ession of MT is upregulated. If theoonoenttalion of free Z~ is stJI too high, apoptolic oell death is Initiated by a yet unknO\\£n med'lan$m (not via dassical apoptctic pathways but involving the production of ROS and the induction of endonudeases which fragment the DNA).
• • • Zn2-• • ZRTt /2 ~~
• 7TA1 zn:t• 1fi1 .,_ __...-;- • .. . 7. · zn-MTr metaiiO· ..,-_. ZRCt t \ · 1...-··· ·· proteins stored COT1 ? ...., ~·· ' . .. .... . "f T~•onein l Zn k" I ox. stress Zn·MTFl Zn-MT zfncosomes •nas "\. ~ w
pllolsphatases / '\ _!1!mRNA Zn•prot@ins I MBE !...._
apoptos.is
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a
CNT-Story- Med~al Tool or highly Toxic - ...
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Taxkdl.U115."""00 •
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Oops They Did It Again! Carbon Nanotubes Hoax Scientists In Viability Assays
f'(.K<oti'P\X<ll'~.WM K•~tiYNW.I~t>loYrwif fqrltYl(~J/)'(10\'J Qwn._..,, ~llt\'1.'.« uj.W."lf,V!MM ilJ...t l:'llt.:r<OW.""~ol r.-Ak<.(~ 1'.0. BllV Jtl4fl JJ.l MJI K ... w.,rw, a..,.,,,.
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Our findings strongly suggest verifying cytotoxicity data with at least two or more ndependent test systems for this new class of materials (nanomaterials). Moreover, we intensely recommend standardizing nanotoxicological assays with regard to the material used: there is a clear need for reference materials.
Materials MHt Ute
-The Mystery of Viability Assays _ ... ... MTT-Assay
I""""::"!;.,...W( )•....-'l 1'!!!!!!1!(1 ....... 103~ -.:.'1 ........ (:1 1 ) .. .....,
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.. WST-Assay
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Pulskamp, K., Diabat6, S., Krug, H.F. (2007) Toxicol. Lett. 168: 58-74
Materials Meet Ute .. Kiug. t•. tG.218tt. N.:~o-6io-Med Triest
c:::l s ~ ¢ . 1 ~._,., c=J 10 ...... 1 tiUo ~'0'111 .. -!111..-.1(31 )~
- 101)~1 0$2.$~., ...
CNT Suspension I Dispersion -lillt..
Organic Solvents I Surfactants
SodiLWn dodecylbenteM sulfonate Na DDBS lst~m et al .. 2003
SDS, TrhonX, chiOtOfonn, DMF, Meth)'~rroUdono NMP, etc.
Materials MHt Life
Biomolecules
doslgned peptide Naf)()+1 Diedlmarm GRetal .. 2003
ssDNA of 81JYSOQUCII)CCI ZMng Met al .. 2003
Morphological Cha~es of Cells -A..
incubation time 3 days; 15 IJQ I ml CNT Wicket al (2007) Tox.icoL Lett. 168, 121-131
Materials Meet Life .. Kiug. t•.tG.21811. N.:~o-6io-Med Triest
adapted from Strano MS et al., 2003 J Nanos.cl Nanoteehnol
Biocompatible Surfactants
pJIXonicF108
EMPA9 "
Nl 5.5wt% y 0.7wt%
SWCNTSO%
control eeU culture
Nl 2.4 w% y 0.4 w%
SWCNT..a%
Small Tubes - B~undles
Carbon nanotubes introduced into the abdominal cavity of m ice show asbestoslike pathogenicity in a pilot study
CliNG A. PUA~· AOOQB' OOf'Ril'. l~ Klt.\OCW AIIOIIEW MAYNAAIY . .. Il l lAMA. H. WU.l.ACE\AUTHOWf SEATON', \ICKI STOJ.P,SN!ltl 900M4', Y.lllWd .. \ld(ff' A~ kftl IXmAtflSONI• ,,.,-.., .. -....-..w---·--·-~u••"-(-•W-OtH•~• _ .. __ .. _'-~-~--...... --·--·-.... - ... -.... -· --·--... ·----·-· - .. ~-·-·-... - · _ ....... t! ..... ~------
·-' Asbestos waomrno' on nanotubes
too•-·""""' .. _ ....... -,.-.... -.._......._.. ......... --.. -_.,_.,_ .... - ..... ._,_ .......... <:_ ---.. --·--~-...... ., _________ _ ---···-··-·--~~
Materials MHt Ute ..
Materials Meet Ute
-
EMPA9 "
TEM micrographs of Jurkat cells after three days af incubation with 30 mglml MWCNT A (a-a"), Bay-Tubos MWCNT B (b-b"), Nanocyl SA MWCNT C (c-c"), Cheap Tubos Inc. Tubes {arrowheads) are present in tho cytoplasm af exposed cells.
nAnommunE Thurn herr et al. 2009, NanotoxlcoiOgy, 3,31t-338
A
ROS and Mitoch~dria
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Materials MHt Ute
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nanommunE Thurnh&rr et al. 2009, NanotoxlcoiOgy, 3, 31t-338
EMPA9 "
:. Inflammatory Effect of SWCNT
- ...
Shvedova et al 2005 Am. J . PhysioL Lung Cell Mot Physiol. 289, L698-L708
I J1l1J'O
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Doses applied: PBS 10~g
20~g
40~g
-Contaminants in CNTs - ... DONALDSON ET AL IU'IXOI.IXK'AtSCIU'>"CES !U(I). S-22 <21.0etJ
Unpurifted nanotube sample
Nanotubes
Slfl!;le·walled M.Jttl-walled
1-3rmdiaiTl(I!OI 10-100 nmdiameter Often form bundes
\',1dely va rylng lergths, typically tens of microns
Metals
T}'Pcally Co, Fe, Ni. Mo
Nanoparticulato Carbonencapsula1ed Oxidos
Residual material
Organics
Amorphow carbon
Microstru::tured carbon (carbon blacks. onions. fibGr$, Ole.)
S...pport
Typically fine ahsnlna. magnesium oxide, or silica.
FIG. 4. Possible componcnl-. in a sample of unpurif!Cd CN'J:
Materials MHt Ute ..
Contaminants and Acute Toxicity _ .. i.l 100
Pulskamp et al. Carbon 45,2241-224 (2007)
EMPA9 "
- eontfOI - NT2-AT - N T2-0MF
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No acute cytotoxicity in vitro in human lung cells
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Fullerene Para~o~~adical Scavenger
Buckmlnsterfullerenol Free Radical Scavengers Reduce Excltotoxlc and Apoptotic Death of Cultured Cortica l Neurons
t.oora l. Dugan; lienSoog l.in,l
Materials MHt Ute
Carboxyfullerene Prevents Iron-Induced Oxidative Stress in Rat Brain
"!Any.t M, Y. Lin. •&. \' C'llyi. tS. D. WillJ.S. ~H.•H, Yu. ~p P. Kc\lu.lkBUttll<l. §T.-Y. Lull. 'C. !\.. Otou. a1X1 •L T. Ho
• ~ .t M~ RAJ"'"" #M l4'11t~ J'(UO'(JOIJ <Mrtl"""'' lf,1P!I'Io'-7111J.'«, fDf;\~ II/ PII)'~D~ MINikfl' l<J.¢~ tW\"""fl)', l~'<Jf ~,. Ml~' o.,;ws. u..t«« c-.
<Wolf.O,~u f/0\lowJt~?; }l(ot.\Of\tf ,,._,. (.M.,.,fl)', T4VW. 1.--
.. Fullerene Para~ox: Oxidative Stress
Research I Article
Manufactured Nanomaterials (Fullerenes, ~I Induce Oxidative Stress in the Brain of Juvenil e largemouth Bass £..., Oh~dOnt•r Du'A' Utl~'f 1\1~11~ l llol:«i::!Of't, BQo:I~Aon,. l kltlt> C•IOII!Il , USA CNpiatll!'latll c t 8 10109(, Sou.,._,n M•thoell$1 lt'll .... ll'l)>, 0$11\:.~. Tcon:;, USA
23
Materials and Methods ""''"' ft.:'llfl()t.:UENTAL
PMfltNIU'6. u~o.atcd 99.5'~ pure fulkrcnu (SES. HcrJ..~!un , TX) wnt WlU(r :solubilitt'd using. st~h.tvd methods (IA'&u<hi et 31. 200)} by the-Un~<:"r !« Bidogiell :md &evlmnmtnul N;w~Clf.Y· R~ Uni•oersity (HOU$!Cln. TX) .. nd. ""'<'l'f" gm(t(I\U si11 r,, dtiJ Mudy. Bridly.li.allcJ<t'les (lOO m;'O were dissoiYCd in re~nhydwlluan (fHF), spargtd with nitro. ~n. n irr«< 0\Ull~~ in th( duk, a.nd Shmd chloush a 0.22-pm nylon Olmonics lilt«
Shon oommonication
Toxjcity of an engineered no:moparticle (fuHerene, C«,) in two aquatk sped es. Daphnia
and fathead 1njnnow 'C1
• r. .. .._...__,.,. rm ... ;w .t .. .--~o '"vi- "'"''""rtc ..... ,~ .. ,,..,_ ,.,.,...,.._ ~ Dl-....,t.....-1,'1 M......,tM:~J. &.\...,,,., ,.,....,.,, n.: U••••"""d! '( p ,..w'"'-
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Materials Meet Life .. Kiug. t•. tG.218tt. N.:~o-6io-Med Triest EMPA
in THF in water
C60 in THF susp. start
• atter weeks
---....J"-..;.su_,spension ....----'~----. No Effect I Toxic Effect Spohn Petal. (2009) Environ.
~=~ ... --t:=~P~olll.ll. 157:1134-1139
Materials MHt Ute .. t•.tG.21811. N.:~o-6io-Med Triest EMPA9 "
w Conclusion for Toxicity of Nanomaterials (1) - ... • Zinc as an essential element exhibits toxicity in high doses
• ZnO-NP induce toxicity exclusively via the dissolution of zn>+ ions
• Carbon Nanotubes exhibit toxicity in dependence on their contaminant content and length
• If purified (no amorphous carbon, no or less catalytic metals) biological activity is strongly reduced
• Long term studies (several months) within cells in culture reveal no biological alterations or responses but the uptake and accumulation within vesicular structures of the cells
• MWCNTs start to have a biological effect in vitro when highly agglomerated
• In vivo the situation is clearly changed and frustrated macrophages induce severe reactions when exposed to long and rigid CNTs
• Fullerenes seem not to induce any oxidative stress response
Materials Meet Ute
More Pitfalls a~d Flaws _ ...
Materials MHt Ute
T~E. GAlli PET'$. TOO THIC.I( $0 l: c.uT
1<\ @,IT 01'1' THE 1>0011:
EMPA9 "'
High Dosage/ Concentrations
Materials Meet Ute
Same Size - Diff~ent Materials - ... nan C a re
25
20
15 121: 3! no, 10-20 nm
10 .£ Carbon Black (CB) 15 nm • 8 )( Ce02 20 nm -c Zr02 1 0·25 nm 0 ;:: ., 6 Zn040 nm ~ AIOOH 40 nm u .,
(/) 4 ~ ....
2
- 0.5, 5 and 25pg/cm2 0
+ Ti0 2 CB Ce02 Zr02 ZnO AIOOH
Materials MHt Ute ..
.... Excessive Delivery of Nanostructured Matter to Submersed Cells ...... . _ ..
A B
• • • • • • • • • • • • • • • • • .. • • • • • • ••• • • ., , • • • • • •
Schematic illustrations of the conceivable interaction of insoluble particles with submersed cells grown at the bottom of a well, filled with an appropriate medium of height h. (A) Previously employed picture, (B) more appropriate concept discussed in this study. The number of particles in (A) and (B) is the same.
WiHmaack, K. (2011)ACS Nano, 5: 3766-3778
Materials Meet Ute
I h
I
.... Excessive Delivery of Nanostructured Matter to Submersed Cells ...... . _ ..
Ti02(80) particles (27 IJg/ml)
At the quoted heights (h) of the media, the mass concentration converts to maximum achievable areal densities of (A-C) 8.4 1Jg/cm2 and (D-J) 25.2 IJg/cm2 (corresponding thicknesses 21.5 and 64.5 ,. , nm) ·, .:
WiHmaack. K. (2011)ACS Nano, 5: 3766-3778
Materials MHt Ute
,: . . . .
Lung Carcinogenic Bioassay of CuO and Ti02 Nanoparticles wltb I ntratracheal InsrlUatlon Uslng F344 Male Rats
Materials Meet Ute
~·1as3Jlao Yokolbm1. Nozom.i Hasltllll0to1. Keiko Yaul3kawa1. SiUoilii SuZ\tki1. K<l\lSUke Sooo1• T <l6itiy.~ Ku!lo1• :utd Kat~unti ltllaida1
0.5 mg/rat lung: no evidence for carcinogenicity
frlltafaliOtJ T(U100111lgy. 2009; 2 1(51): l 'l:l-157
RESEARCH ARTICU:
Carcinogenicity of inhaled nanopartides
Markus RoUer
A minimum of 5 X 3 mg/rat lung, maximum 20 x 6 mg/rat lung by instillation • carcinogenicity!
' Calculated Overload - ... Rat lung weight: 0.9 g
Macrophage count : 1.200.000
0,5mgllung • 416 pg I cell : no effects (Yokohira et al., 2009)
15mgllung • 12.500 pg I cell }
n tumour induction (Roller, 2009) 120mg ung • 100.000 pg I cell
Irreversible Pulmonary Changes Induced in Rat Lung by Dust Overload
tiM~ 8~ i'mptoiVI'.J tN. tn.pp. mfJ..m. M1 by Bernd Bellmann, 1 Hartwig Muhle, 1
Otto Creutzenberg, 1 and Robert Mermelstein•
3mg/lung"' 2.500 pg I cell reflects overload conditions
Materials MHt Ute ..
Experiments and""lheir Consequences - ... Nanoparticles activate the NLR pyrin domain containing 3 (Nirp3) inflammasome and cause pulmonary inflammation through release of ll-1a and ll-113 Amir S. Yazdi", Greta Guarda". NKolas Ri teaub, Stefan K. DrexM<r'". Aubty Tardivet•, lsa~le Couillint>. and JUrg Ts(hopp·>.t
"'tl)o)rll'!lerll ol &Odlemls:b"f, Urrlw:l'~ly ol Liv!OaMt, Ol·i~6 [l)lll!iQtS. Swhull<l!id.. ~d 11i.alx>r<ll<HYOt 1.4<11«"'- inwou110~if1 IF'Id fl'l'i.llyoiCQ'I. Vt<i.o~l\itrtlf <>~~ • "d (oe"t~ N.!ti-lde ._ ~d!oe Sci~ntifiQ~. ~5011 Of~l'l'l. ,,~
it~a1 11:.11m-TiO:: l>hOuld 1~~: usc~ v.ith gr~;u .. ·r SiJltibr 'A'Ords ol C3~tion ..-.'l:rc expre~cd in the bst tti11Ui) '
::~~~~;~~~Til.: 1n:m.u~accurc M TiO~ nan(~ f<lllowing th.: fi~l .:\•itl..:ncr tor <li..otia tittn bc~wocn lung infl<ml-2 rmlll\'lfl tous · )~~:~r ati: nl rt linn :tnd :t."\I'CIII~ inh:tl:tlitltl. Vel il 1110&: fllnlO!i"l Ill'! y, :md
. e.'untk:'' fa tJIItk-. ttll lti ltil~~:'h" Y..a.' 1\IIII K:~I ft \NIIU "oC. Oit't:n tiM lt!<l.IC..,.t•~ :md TiO: .:uti , jmilltr l)ttlillllallmtacoty ~i,ilic~ ~iu ll·l R ~tafing tht\~.1gh the ac.1 i~\lll it•n t~r citlk:t 11..-lo and I L..· ll}.
, · <•hQ\~, ri~ c>f , "ll.'t hOp! lh:.~l fuhln: d«i::;iOft~ v.-ill be made to ptCVCnt p$Sibk dril.'cn <'.IJnccr is tJ JXU"tirultJr concern. CJ'.PcC"ially for pcopk <"K'<'l· Ull)rJjtJily <tml p:rttalb nt~ll"l<tlily. paticultllly ~d 10 high rollCI:'ntrntion~ of T.O: nanCit)artidcs. lk:tt<.:r Jl'f<.:C<tUtiom; nlll:SI l'l: l<tla;n tO limil llll: itl!-'l:Sti~11l of thcs.,: partkk~. OOth in nlll.Jlttfn«m·itt.g and in <"~'l:'l)'dtJy contact .... i lh Pro c. Nati.Acad. Sci U. S.A 107, 1944-t-19454 (2010) nallO(IIlttidc·et)lll{lini•lE ~~~~I;.II"K\$.
Materials Meet Life
Concentrations ~d Doses - ... In Vitro: In Vivo: Titaniumdioxide and siliciumdioxide Intranasal application and broncho-nanoparticle induce the Nlrp3 alveolar lavage (BAL). Ti02 (7.5-JO inflammasom in mouse- and human mg/kg) in sodiumchloride solution or macrophages and human only medium were administered via keratinocytes. nasal instillation (40 Ill with anesthesia). THP1 cells treated with MSU (300 Peritonitis was induced in 6- to 10-IJQ/ml), Ti02 20 nm (200 IJQ/ml), weeks old mice after injection of 1-1.5 Ti02 80 nm (200 IJQ/ml), Si02 15 nm mg oft rticles. (200 IJQ/ml), and ZnO 15 nm (200 ~ ll g/ml) for 6 h. ~ , : en Donaldson and W'\0 vo ave injected 50pg CNT
\ \)S l • estos per mouse,for the
ft a {3 ce s ~~;:r:~::::;e:~::::;:;::~~?.';::~~~ons ,{""" (Poland et al., 2008)
Materials MHt Ute EMPA9 .,
Wrong Conclusions
Materials Meet Ute
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Nanopartlcles in sun creams can stress brain cells
Tiny grains send cell"' into potentially dangerous overdrive.
" dle tageszeltung creams may dis integrate you brain
Tilallium Diexide (P25) P111duces Reactive Oxygen Species in Immortalized Brain Microglia (BV2): Implications fer Naneparticle Neuretoxicity1
__ ,__ Sun cream coukl c:a!IS4t
~~~~~:~-;,~;;:::!:=::~::';::!.".:':!;;:::.;•• h• HIQci>I•~·S.n.,.,..<.,"""l""'n .......... <lot •"ct. """"" h• Alzh elmecr 's clo N>t>Ofl...,aol anonlho~ ....,, olt • "' ol-Woo ~~"Clio c' ,.. ..• _,
Tinv p/Wtlcl!s lit e tllofe b.lnG r. ~~ $ii"!S(I'floei'IS .lfto ' rtE<I to 1tf(!fllfl f!l()ij~ ~~~~
Materials MHt Ute .. ·----
---·----.. .. -.--... -...... ------·-~----·--·
_____ ,
Nanomaterials - ilie great Uncertainty? - ... TW~ '$CJ£NrlffC COMtiJNtf'(
IS DIV'ItlE.D• \OME SAY NANO S'fOFf r S MNG£R0V~,~ONE Sf\Y
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cuwonhnk.com.. A!l Ri:;hu ~~~
Materials Meet Ute .. Kiug. t•.1G.21811. N.:~o-6io-Med Triest
Risk Assessmenfns Important - ... Exposure
Assessment
Hazard Identification
Hazard Characterisation
Risk Characterisation
Risk Ma nt
Krug & Wick (2011)Angew. Chern .. Int. Ed ., 50 (6): 1260-1278
Risk Prevention
Materials MHt Ute
Risk Miti ion
Risk Communi
• • • •
• •
•
• •
EMPA9 "
Three Nanoto:!"P-rinciples
• The Transport-Principle Umbach LK, Wick P, et al.{2007). Environ. Sci. Techno I. 41:4158-4163
• The Surface-Principle Nel et al. (2006) Science 311: 622-627 Oberdilrstaret al., (2000) HEI-Report 96
• The Material-Principle
Krug & Wick (2011 )Angew. Chem.lnt. Ed., 50 (6): 1260-1 278
Materials MHt Ute
Caveoli (0=1 OOnm)
----------.._~
Materials Meet Ute
EMPA9 "
Small Size but ~rY large specific Surface - -.::: ..__ .. ,.._ ... , .. .,..,.oiM-oo..~ ..... --.--• ........ 1)-• .... "-P-
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Materials MHt Ute EMPA9 "
-One Material- different Modifications and more ... - ...
Carbon
Materials Meet Ute
(Materiai)Surfa:_e"i?roperties!
uv
011·
o,
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Materials Meet Ute .. Kiug. t• .tG.21811. N.:~o-6io-Med Triest EMPA9 "
Future Challenge~in Nanotoxicology Outcome of the 2"d Minisymp. Nanotoxicol. Stockholm 2010 - -• Exposure & Environment
• Foreign Entities vs. Endogenous Entities
• Don't Believe a Single Method
• Method Reliability • In Vitro ~ in Vivo Correlation
• Nano-Specific Signatures
• REACH
• Challenges for Regulatory Activities
• Fibre Paradigm Revisited
• Crowns/Coronas out of Proteins, Lipids and ... ?
• How to define " Biopersistence" ?
Materials MHt Ute .. t4.tG.ll811. N~io-Med Triest
Future Needs of N'anotoxicology - ...
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• The huge amount of new chemicals and expected new nanomaterials on the market raises the question for alternative methods for a first screening
• In vitro methods should be reliable, robust, sensitive and predictive
• Without a responsible process of marketing " nanotechnologies" will fail within the next decade
• Support of (nano)toxicological activities/projects is continuously needed; risk characterisation and assessment is crucial
• Comparability of Tox-studies is mandatory and should be achieved by use of standardised methods, reference materials and the appropriate controls in each experimental set-up
Materials Meet Ute .. Kfug. t4.1G.ll811. N~io-Med Triest EMPA.~ 5I
Conclusions _ ~
There is still research need on " nano-risk" but
•
•
We should use improved and comparable methods
We should use the correct controls and, if available, a reference material
• Concentrations should be kept in the right range
• No genotox studies with cytotoxic concentrations or overload conditions
Materials MHt Ute .. 14.11.21811. N~io-Med Triest EMPA9 "
Important questi~ns for Nanotoxicologists _ .... • Do living organisms "see" the nanomaterial?
• How does coverage of nanoparticles by biological material alter toxicity of NP?
• Is agglomeration/aggregation reducing all nanoeffects?
• How can we overcome interference of nanomaterials with the assay systems?
• Why don't we have an agreement on controls and reference/benchmark materials?
• Is the application of huge concentrations in vitro justified by the limitations in treatment-time?
• What about long-term effects?
• Do we need additional millions of animals to test this? Materials Meet Ute .. Kfug.14.1G.ll811. N~io-Med Triest EMPA.9 •
Changing Pa radigms - ... COMMENTARY
Safe handling of nanotechnology
Materials MHt Ute ..
Particle and Fibre Toxicology Partide and Fibre Toxicologr 2005. 2:8
R_e,~w GJ.i l, f i%9 I I I Pr inciples for characterizing the potential human health ef'rects from exposure to nanomaterials.~ elements or a scr~ning strategy COmer Ob~rd~rllte•·•. A•l dteo.>~ ,\t :~y•u.tdZ, Ke1\ Don .• lldson'. Vin<t'nt Camanov.l•, Julie Fit:q):Utick•S, J<e·vin Ausnu n6, Jant'l C:met1, B;ub:ua K;Hn&'. Wolfg;ang Ktt)•lillSto, David l.ai• •. Stephen Oli,,s, .".t.ln<y Mo-slttiro·Ri\'il'fi'u, D.tvid WJ.,heilu, 110111:: Y .1n~H .ln..-1 t\ repoft ffom
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