ASPECTS OF THE RELATIVE CONTRIBUTION OF PARTICLE SIZE VERSUS PARTICLE

COMPOSITION IN THE OVERALL TOXICITY OF NANOCRYSTALLINE MATERIALS

Speranta Tanasescu, Cornelia Marinescu

Institute of Physical Chemistry of the Romanian Academy

Splaiul Independentei 202, 060021 Bucharest, ROMANIA

Seminar national “nano” - 2 martie 2006

This work is part of the FP6 CA Project,

“Improving the understanding of the impact of nanoparticles on human Improving the understanding of the impact of nanoparticles on human health and the environment - ImPart”health and the environment - ImPart”

The project brings together research institutes, universities, toxicologists, environmental specialists, manufacturers and ethicists in order to elucidate the state of the art, reduce duplication of effort and improve the current level of understanding of the impact of nanoparticles on health and the

environment.

Not simply hazard identificationIdentify key parameters important for evaluating safety/toxicity - Role of composition, size

- Shape, conformation, deformability

- Surface coatings

- Physico-chemical properties Best practices for safety evaluationBy what routes do UFPs get into the body and then where do they travel toGuidance for development of safe nanomaterials

ImPart’s Goal

This work is part of the FP6 CA Project,

“Improving the understanding of the impact of nanoparticles on human Improving the understanding of the impact of nanoparticles on human health and the environment - ImPart”health and the environment - ImPart”

The contribution is based on the former research experience existing in the Laboratory of Chemical Thermodynamics as concerns the large potentialities offered by the Applied Chemical Thermodynamics to characterize and investigate from the energetic point of view the advanced materials involved in the complex modern systems and the new technologies

Contribution to the ImPart’s data base with respect to nano-metal oxides, emphasizing on the following topics:

Critical size assessments and general consideration

on Nanocrystalline Materials

Questions about the relativecontribution of particle

size versus particle composition in the overall toxicity

of ultrafine particles (UFP)

Particle size versus energetics

of nanomaterials

Critical size assessments

Particle Category Size Coarse Particles with an average diameter of 10 m

(m = micron) Fine Particles with an average diameter of 2.5 m

Ultrafine (Nanoparticles)

Particles with an average diameter of 0.1 m ( 100nm)

Ultrafine

(Nanoparticles) UFP – Approx. size

Potential Entry Point

70 nm alveolar surface of the lung 50 nm cells 30 nm central nervous system 20 nm no comprehensive scientific data

as yet

Materials Avg. Particle Size (nm)

Specific Surface Area (m2/g)

Toxicity/ Risk Statements

Al2O3 20 75 Possible risk of introduction of those nanoparticles to soils and aquatic environments

Sb3O4 · SnO2 15-20 30-50 Harmful; Possible risk of irreversible effects Al2O3·TiO2 <20 100-200 Irritating to the respiratory system Sb2O3 90-210 15-20 Harmful; Possible risk of irreversible effects BaFe12O19 30-50 12 - 36 Harmful by inhalation; Harmful if swallowed BaZrO3 <40 20-40 Harmful if swallowed; Routes of Entry: Inhalation, skin, eyes Bi2O3 90-120 3.2-3.5 Irritating to the eyes, , respiratory system and skin CaTiO3 60-100 10-20 Ceramic waste forms for plutonium immobilization CaZrO3 10-20 55-65 Contribution to a “nuclear explosive activity “ AlCeO3 10-25 50-55 Irritating to the respiratory system (CeO2)3·(ZrO2) <20 50-60 Inhalation of zirconium compounds may cause pulmonary granulomas Cr2O3 <40 20-40 Absorbed poorly by inhalation and throught intact skin CeO2 <20 80-100 Avoid contact with skin and eyes Co3O4 12-30 40-45 Possible risk of irreversible effects; Irritating to the eyes, respiratory system CoAl2O4 <40 20-40 Harmful to aquatic organisms; Irritating to the eyes, respiratory system CuAl2O4 40-60 20-40 Harmful if swallowed CuO 30-40 25-45 Harmful if swallowed Dy2O3 60-100 10-20 May cause eye and skin irritation Er2O3 40-60 10-20 Irritating to the eyes, respiratory system and skin Eu2O3 60-100 10-20 Irritating to eyes, respiratory system and skin Gd2O3 40-60 10-20 Avoid contact with the skin; Avoid contact with the eyes Ho2O3 <80 10-20 Toxic by inhalation, in contact with skin and if swallowed In2O3 <40 20-40 Irritating to the eyes, respiratory system and skin In2O3 · SnO2 25-45 20-30 Irritating to the eyes, respiratory system and skin (In2O3)9 · (SnO2) 20-40 20-40 Irritating to the eyes, respiratory system and skin CuFe2O4 60-100 10-20 Irritating to the eyes, respiratory system and skin CuZnFe2O4 60-100 10-20 Irritating to the eyes, respiratory system and skin Fe3O4 20-30 > 60 Irritating to the eyes, respiratory system and skin Fe2NiO4 20-30 55-60 May cause cancer by inhalation NiZnFe2O3 40-60 40-50 May cause cancer by inhalation La2O3 25-65 10-20 Irritating to the eyes, respiratory system and skin

Mg(OH)2 <40 80-100 Irritating to the eyes, respiratory system and skin.

MgO 10-20 80-160 Harmful by inhalation and if swallowed

MnTiO3 40-60 20-40 Risk of explosion by shock, friction, fire

NiCr2O4 <40 20-40 Irritating to the eyes, respiratory system and skin.

NiO CoO 30-100 <10 Dangerous for the environment; Toxic; Harmful if swallowed

Pr6O11 <125 <10 Irritating to the eyes, respiratory system and skin.

Sm2O3 10-80 <10 Risk of explosion by shock, friction, fire

SiO2 10-20 140-180 Avoid contact with the skin ;Avoid contact with the eyes

SiO2 5-15 590-690 Risk of explosion by shock, friction, fire

SrFe12O19 60-100 10-20 Irritating to the eyes

SrTiO3 <100 18-19 Extreme risk of explosion by shock, friction, fire

Tb4O7 60-100 10-20 Extreme risk of explosion by shock, friction, fire

SnO2 15-20 45-50 No data yet exists on the effects of such fine particles on the body

TiO2 5-10 200-220 Irritating to the eyes, respiratory system and skin

TiSiO4 5-20 100-115 Irritating to the eyes, respiratory system and skin

WO3 35-40 25-30 Harmful if swallowed

Yb2O3 40-60 10-20 Irritating to the eyes, respiratory system and skin

Y2O3 25-30 40-45 Irritating to the eyes, respiratory system and skin

ZnO 50-70 15-25 Dangerous for the environment

ZnTiO3 <40 20-40 Harmful if swallowed

ZrSiO4 25-30 35-40 Irritating to the eyes, respiratory system and skin

ZrO2 <40 Irritating to the eyes, respiratory system and skin

Potential Applications/Features and Benefits

Cosmetics, Environmental remediation, Demilitarization of chemical and biological warfare agents, Gas sensors (for ozone and nitrogen dioxide),Thermaly conductive adhesives, Ultra-fine abrasives Transparent conducting oxide materials; Advanced ceramic components Permanent memory DRAM (Dynamic Random Access Memory), FRAM (Ferroelectric Random Access Memory)Infrared detectors, mechanical and electrical micro-actuators, electro-optic, pyroelectric sensor, thin films capacitors and surface acoustic wave devices, Thermistors. Varistors.High-density optical data storage, Micro-capacitors, Nonlinear optical devicesOn-chip programmable devices, Optical computing, Optical image processing; Pattern recognitionPhase conjugated mirrors and lasers, Piezoelectric devices, Pyroelectric sensors, Semiconductive ceramics, Refractory ceramics, SOFC, sensorsNitrogen storage material, Semiconductors, Solar energy absorbers nding wheels, Heterogeneous catalysts, Fluorescent powderTransparent conductive electrodes in electronic devices for liquid crystal, displays,solar cells, solid electrolyte cells, photovoltaic devicesUV lasers and detectors, CRT display of color television and personal computer, Electrochromic mirrors,Flat-panel displays,Heat shieldsCeramic Magnets, Additives in plastics, Agglomerates for thermal sprays, Air/fuel ratio controller in automobileCatalysts and catalyst supports, Electrode materials in lithium batteries, Energy converter in solar cells,Inks, Inorganic membranesPhotochemical degradation of toxic chemicals, Piezoelectric capacitors, Pigment for paints, Planarization, Polishing agent, Porcelain; Solid oxide fuel cell, UV protection, Waste water purification

What is so special about What is so special about nanoscale?nanoscale?What is so special about What is so special about nanoscale?nanoscale?

• Every property has a critical length scale where the Every property has a critical length scale where the fundamental physics of fundamental physics of that property starts to changethat property starts to change

• Nanoscale building blocks are within these critical length Nanoscale building blocks are within these critical length scalesscales

• Building blocks impart to the nanostructures new and Building blocks impart to the nanostructures new and improved properties improved properties and functionalities and functionalities

• Essentially any material property can be engineered Essentially any material property can be engineered through the controlled through the controlled size-selective synthesis and assembly of nanoscale size-selective synthesis and assembly of nanoscale building blocksbuilding blocks

• For multifunctional applications, more than one property For multifunctional applications, more than one property and one length scale and one length scale must be considered.must be considered.

Small Particles ImpactSmall Particles Impact

Small ParticleSmall Particle&&

Nano-materialsNano-materialsChemistryChemistry

Small ParticleSmall Particle&&

Nano-materialsNano-materialsChemistryChemistry

CatalysisCatalysisCatalysisCatalysis

Electronics/Electronics/MagneticsMagnetics

Electronics/Electronics/MagneticsMagnetics

NanoscienceNanoscienceNanotechnologyNanotechnologyOxide NanostructuresOxide NanostructuresHard-soft interfaces Hard-soft interfaces

NanoscienceNanoscienceNanotechnologyNanotechnologyOxide NanostructuresOxide NanostructuresHard-soft interfaces Hard-soft interfaces

EnvironmentEnvironmentGeosciencesGeosciences

Waste storageWaste storageContaminant TransportContaminant TransportAtmospheric ChemistryAtmospheric Chemistry

EnvironmentEnvironmentGeosciencesGeosciences

Waste storageWaste storageContaminant TransportContaminant TransportAtmospheric ChemistryAtmospheric Chemistry

EnergyEnergyPhotovoltaicsPhotovoltaics

PhotonicsPhotonicsHydrogen StorageHydrogen Storage

EnergyEnergyPhotovoltaicsPhotovoltaics

PhotonicsPhotonicsHydrogen StorageHydrogen Storage

National National SecuritySecurity

DetectorsDetectorsBiocideBiocide

National National SecuritySecurity

DetectorsDetectorsBiocideBiocide

Small Particles and Nano-structures have impact in each of these areas and some topic cross several areas

The exploitation of the properties associated with the nanoscale is based on a number of discrete differences between features of the nanoscale and those of more conventional sizes, namely the markedly increased surface area of nanoparticles compared to larger particles of the same volume or mass, and also quantum effects. Questions naturally arise as to whether these features pose any inherent threats tohumans and the environment. Bearing in mind that naturally occurring processes, such as volcanoes and fires, in the environment have been generating nanoparticles and other nanostructures for a very long time, it would appear that there is no intrinsic risk associated with the nanoscale per se. As noted above, there is also no reason to believe that processes of self assembly, which are scientifically very important for the generation of nanoscale structures, could lead to uncontrolled self perpetuation. The real issues facing the assessment of risks associated with the nanoscale are largely concerned with the increased exposure levels, of both humans and environmental species, now that engineered nanostructures are being manufactured and generated in larger and larger amounts, in the new materials that are being so generated, and the potentially new routes by which exposure may occur with the current and anticipated applications.

Precaution on nano-scalePrecaution on nano-scalePrecaution on nano-scalePrecaution on nano-scale

Questions about UFPs

What is the relative contribution of particle size versus particle

composition in the overall toxicity of UFPs?

By what routes do UFPs

get into the body and then where do they travel to?

What is the mechanism of toxic action and how does the reactive

surface of UFPs interacts with ‘wet biochemistry’ in the body?

Precaution on nano-scalePrecaution on nano-scale

Particle size versus particle compositionReduction in size to the nanoscale level results in an enormous increase of surface to volume ratio, so relatively more molecules of the chemical are present on the surface, thus enhancing the intrinsic toxicity (Donaldson et al 2004). This may be one of the reasons why nanoparticles are generally more toxic than larger particles of the same insoluble material when compared on a mass dose base. The dose expressed as surface area or number of particles administered shows a better relationship with biological and/or toxic effects than dose expressed as mass (toxicity ofTiO2 and BaSO4 - Tran et al 2000).

Materials* Avg. Particle Size (nm)* Specific Surface Area (m2/g)**

Al2O3 20 nm 30 nm 40 nm

75 50 38

Al2O3 2-4 X 2800 Organically coated for dispersion in polar solvents

350-750

Al2O3 10% dispersion in water

<20 > 100

CeO2 10% suspension in water

<20 80-100

CeO2 5% suspension in water <20 60-80 CoAl2O4 <40 20-40 CuAl2O4 40-60 20-40 Dy2O3 60-100 10-20 Dy2O3 solution <80 10-20 Fe3O4 20-30 > 60 Fe2O3 20-25 50-55 Sm2O3 10-80 <10 Sm2O3 <80 < 10 SiO2 5-15 590-690 SiO2 10% dispersion in water <20 150-175 TiO2 5-10 200-220 TiO2 60-100 10-20 TiO2 10% dispersion in water

<40 20-40

TiO2 5% dispersion in water

<40 20-40

TiSiO4 5-20 100-115 ZnO 50-70 15-25

The chemical composition and the intrinsic toxicological properties of the chemical are of importance for the toxicity of particles (Donaldson et al 2004). For micron sized biomaterial particles, the in vivo distribution was dependent on the composition of the material.

Donaldson et al. (2004) comparatively have discussed the effect of transitional metals oxides / ultrafine carbon black as a source of oxidative stress. For micron sized particles the effect of carbon black has been shown to be more severe than that of titanium dioxide (Renwick et al 2004), while for both compounds the nanoparticles induced lung inflammation and epithelial damage in rats at greater extent than their larger counterparts. UFPs are able to transport transition metals, which have been implicated in the proinflammatory effects and toxicity. For several different nanoscale particles (polyvinyl chloride, TiO2, SiO2, Co, Ni), differences in cytotoxicity are obtained due to size difference at the nanoscale, as the particle size ranged from a mean diameter of 14nm to 120 nm and even clusters of 420 nm (Peters et al 2004).

ConclusionConclusionThe contribution of size vs. the contribution of material composition to a particle’s toxicity has not been clearly established. However, it does seem, in the light of current knowledge, that the size effect is considerably more important to UFP toxicity than the actual composition of the material. The biological behaviour of nanoparticles is determined not only by the chemical composition, including coatings on the surface, but also by the corresponding shifts in chemical and physical properties, associated to the increase in surface to volume ratio.

Particle size versus particle composition

Contribution to answer the following topics are expected:Contribution to answer the following topics are expected:

Which are the general implications for nanophase stability relations?

Are there compositional or crystal chemical systematics in the energetics of polymorphism and surface energies?

To what extent can the energetic properties of nanocomposites be predicted from properties of the nanoscale end-members?

Which is the influence of different compositional variables on the nanophase energetics?

What environments are likely to harbor nanoscale phenomena, and how would thermodynamic modelling be affected?

How do environmental effects alter nanoparticle structures and change reactivity?

Are the existent thermochemical databases enough comprehensible to prevent or for diminution of ecological hazards?

Are the previously proposed defect structure models suitable to explain the generation of the defects in nanomaterials?

Particle size versus energetics of nanomaterials

SampleTiO2

Hs (J/m2)

(surfaceenthalpy)

Htransf (kJ/mol)(enthalpy of phase

transformation)

S0 (J/ mol K)(298 K)

Surfacearea

(m2/mol)

Averagediameters of

particles (nm)

Rutile 2.2 0.2 50.6 0.61 592 201Anatase 0.4 0.1 2.61 0.41

(bulk rutile - anatase)49.9 0.3 3,174 39

Brookite 1.0 0.2 0.71 0.38 (bulk brookite –

rutile)

592-3,174 206-36

Enthalpy of nanocrystalline samples with respect to bulk rutile (kJ/mol) versus surface

area (m2/mol)

>35 nm

11 nm

11-35 nm

Interrelationships among “bulk” structure and defects, surface

structures, the environment and reactivity mean the nanoparticle

properties depend on sizesize, , environmentenvironment and historyhistory..

Ranade, M. R. et al. (2002) Proc. Natl. Acad. Sci. USA 99, 6476-6481

Nanoparticles are often polymorphs of bulk material with different physical and chemical properties

8 9 10 11 12-22

-20

-18

-16

-14

-12

-10

-8

-6

-4

104 (T/K)-1

log

(p

O2/a

tm)

La0.67

Ca0.33

Mn0.95

Al0.05

O3 nanostructure

La0.67

Ca0.33

Mn0.95

Al0.05

O3 microstructure

Laboratory of Chemical ThermodynamicsLaboratory of Chemical Thermodynamics

The variation of the and log The variation of the and log ppO2O2 with the temperature with the temperature

for the doped lanthanum manganites prepared by for the doped lanthanum manganites prepared by ■■ Solid Solid state reactions (d state reactions (d 5 5 m)m) and ▲ Sol-gel methodand ▲ Sol-gel method ((d d 40 40

nm)nm)

2OG

800 900 1000 1100 1200 1300

-350

-300

-250

-200

-150

T/K

GO

2

/kJ

mo

l-1

La0.67

Ca0.33

Mn0.95

Al0.05

O3 microstructure

La0.67

Ca0.33

Mn0.95

Al0.05

O3 nanostructure

The changes of the thermodyamic data can be explained as a consequence of truly grain-size dependent properties

The size effect on the energetics of the complex perovskites

Laboratory of Chemical ThermodynamicsLaboratory of Chemical Thermodynamics

The variation of the and log The variation of the and log ppO2O2 wwith the temperature ith the temperature and the oxygen and the oxygen

stoichiometry change for nano- and microstructured lanthanum manganites.stoichiometry change for nano- and microstructured lanthanum manganites.2OG

1170 1200 1230 1260 1290

-260

-240

-220

-200

-180

-160

T/K

GO

2/kJ

mo

l-1

La0.67

Ca0.33

Mn0.95

Al0.05

O3 nanostructure

La0.67

Ca0.33

Mn0.95

Al0.05

O3 microstructure

La0.67

Ca0.33

Mn0.95

Al0.05

O3- nanostructure

La0.67

Ca0.33

Mn0.95

Al0.05

O3- microstructure

0.00

0.02

-11.0

-10.5

-10.0

-9.5

-9.0

-8.5

-8.0

-7.5

1150

1200

1250

1173 K

1223 K

1273 K

1173 K

1223 K

1273 K

log

(p

O2/

atm

)

T (K

)

Nanostructure:-significant changes in the overall defect concentration-a reduced energy of oxygen vacancies formation

Nano-, micro- and oxygen stoichiometry

Laboratory of Chemical ThermodynamicsLaboratory of Chemical Thermodynamics

0.00

0.02

-275

-250

-225

-200

-175

1200

1250

1273 K

1273 K

1223 K

1223 K

1173 K

1173 K

La0.67

Ca0.33

MnO3

La0.67

Ca0.33

Mn0.95

Al0.05

O3

La0.67

Ca0.33

MnO3-

La0.67

Ca0.33

Mn0.95

Al0.05

O3-

GO

2/kJ

mo

l-1

T (K)

Estimation of the contribution made by oxygen vacancies in balancing the local charge by correlation of the results obtained from EMF + coulometric titration + redox titration measurements

S. Tanasescu, D. Berger, A. Orasanu, J. Schoonmann, International Journal of Thermophysics, 26, 2, 2005S. Tanasescu, C. Marinescu, F. Maxim, Solid State Phenomena, 99-100, 2004, p. 117-122S. Tanasescu, D. Berger, D. Neiner, N.D. Totir, Solid State Ionics, 157, 2003, p. 365 – 370

0.005 0.010 0.015 0.020 0.025 0.030

-640

-620

-600

-580

-560

-540

-520

-500

-480

-460

-440

-0.32

-0.30

-0.28

-0.26

-0.24

-0.22

-0.20

HO

2/kJ

mo

l-1

La0.67

Ca0.33

MnO3-

La0.67

Ca0.33

Mn0.95

Al0.05

O3-

%Mn4+=27

%Mn4+=29

%Mn4+=35

%Mn4+=32

S

O2 /k

J m

ol

-1K-1

La0.67

Ca0.33

MnO3-

La0.67

Ca0.33

Mn0.95

Al0.05

O3-

Laboratory of Chemical ThermodynamicsLaboratory of Chemical Thermodynamics

Comparative results of the relative partial molar thermodynamic data of oxygen in the Comparative results of the relative partial molar thermodynamic data of oxygen in the nonstoichiometric compounds prepared by two different methodsnonstoichiometric compounds prepared by two different methods

(1173-1273 K)(1173-1273 K)

222O OSTOHG

Sample2OH (kJ mol-1)

2OS (kJ mol-1K-1)

La0.67Ca0.33Mn0.95Al0.05O3-

(nanostructurate) -595.6 8.1 -0.304 0.006

La0.67Ca0.33Mn0.95Al0.05O3 –

(microstructurate) -487.2 21.8 -0.200 0.017

Nanostructure:the increase in the binding energy of oxygen and an increase of order in the oxygen sublattice of the perovskite-type structure

Critical or Characteristic Particle Sizes [nm]

1 10 100

Bulk Lattice ConstantsDecreasing with size

Lattice Constants For metals Pt, Pd, Fe and Ta

Oxide Layers on FeAir exposed bulk metal

Oxygen exposed nanoparticles

Characteristic Sizes for Physical and Chemical NANO EffectsCharacteristic Sizes for Physical and Chemical NANO Effects

Surface Energy Pb

Increasing with size Independent of size

Anatase Brookite RutileOxide Phase Stability

HematiteGoethite

Super Paramagnetic Transition at Room Temperature

HematiteGoethite

Break down of Hall Petch Grain-Size Hardening Metal Layer Structures

CuOLattice Parameter and Neel Temperature

• Small particle and nanostructured materials chemistry is relevant to many subjects, including health and environmental topics

• There are many different types of small particle and nano-materials effects as well as many delightful opportunities and scientific challenges

•In contrast to macrothermodynamics, the thermodynamics of a small system will usually be different in different environments

• More and better tools and their use are essential to characterize the properties and environmental effects of/on nanoparticles (multidisciplinary analysis is required). Theory and modeling are useful to successful work in this area

Summary and Concluding Thoughts