Speranta Tanasescu, Cornelia Marinescu Institute of Physical Chemistry of the Romanian Academy

1. 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

2. This work is part of the FP6 CA Project, “Improving the understanding of the impact of nanoparticles on human 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. ImPart’s Goal • Not simply hazard identification • Identify key parameters important for evaluating safety/toxicity • - Role of composition, size • - Shape, conformation, deformability • - Surface coatings • - Physico-chemical properties • Best practices for safety evaluation • By what routes do UFPs get into the body and then where do they travel to • Guidance for development of safe nanomaterials

3. This work is part of the FP6 CA Project, “Improving the understanding of the impact of nanoparticles on human 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 Critical size assessments and general consideration on Nanocrystalline Materials • Contribution to the ImPart’s data base with respect to nano-metal oxides, emphasizing on the following topics: Questions about the relative contribution of particle size versus particle composition in the overall toxicity of ultrafine particles (UFP) Particle size versus energetics of nanomaterials

4. Critical size assessments Particle Category Size Coarse < m Particle s with an average diameter of 10 m m ( m = micron) Fine < m Particles with an average diameter of 2.5 m Ultrafine < m < Particles with an average diameter of 0.1 m ( 100nm) (Nanoparticles) Ultrafine UFP – Approx. Potential Entry Po int (Nanoparticles) size 70 nm alveolar surface of the lung 50 nm cells 30 nm central nervous system no comprehensive scientific data < 20 nm as yet

5. 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 devices • On-chip programmable devices, Optical computing, Optical image processing; Pattern recognition • Phase conjugated mirrors and lasers, Piezoelectric devices, Pyroelectric sensors, Semiconductive ceramics, Refractory ceramics, SOFC, sensors • Nitrogen storage material, Semiconductors, Solar energy absorbers nding wheels, Heterogeneous catalysts, Fluorescent powder • Transparent conductive electrodes in electronic devices for liquid crystal, displays,solar cells, solid electrolyte cells, photovoltaic devices • UV lasers and detectors, CRT display of color television and personal computer, Electrochromic mirrors,Flat-panel displays,Heat shields • Ceramic Magnets, Additives in plastics, Agglomerates for thermal sprays, Air/fuel ratio controller in automobile • Catalysts and catalyst supports, Electrode materials in lithium batteries, Energy converter in solar cells,Inks, Inorganic membranes • Photochemical degradation of toxic chemicals, Piezoelectric capacitors, Pigment for paints, Planarization, Polishing agent, Porcelain; Solid oxide fuel cell, UV protection, Waste water purification

6. What is so special about nanoscale? • Every property has a critical length scale where the fundamental physics of • that property starts to change • Nanoscale building blocks are within these critical length scales • Building blocks impart to the nanostructures new and improved properties • and functionalities • Essentially any material property can be engineered through the controlled • size-selective synthesis and assembly of nanoscale building blocks • For multifunctional applications, more than one property and one length scale • must be considered.

7. Energy Photovoltaics Photonics Hydrogen Storage Electronics/ Magnetics Catalysis National Security Detectors Biocide Small Particle & Nano-materials Chemistry Environment Geosciences Waste storage Contaminant Transport Atmospheric Chemistry Nanoscience Nanotechnology Oxide Nanostructures Hard-soft interfaces Small Particles Impact Small Particles and Nano-structures have impact in each of these areas and some topic cross several areas

8. Precaution on nano-scale 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 to humans 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.

9. Questions about UFPs Precaution on nano-scale What is the relative contribution of particle size versus particle composition in the overall toxicity of UFPs? What is the mechanism of toxic action and how does the reactive surface of UFPs interacts with ‘wet biochemistry’ in the body? By what routes do UFPs get into the body and then where do they travel to?

10. Particle size versus particle composition • Reduction 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).

12. Particle size versus particle composition • 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). Conclusion The 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.

13. 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

14. Nanoparticles are often polymorphs of bulk material with different physical and chemical properties 11 nm 11-35 nm >35 nm Interrelationships among “bulk” structure and defects, surface structures, the environment and reactivity mean the nanoparticle properties depend onsize, environmentandhistory. Enthalpy of nanocrystalline samples with respect to bulk rutile (kJ/mol) versus surface area (m2/mol) Ranade, M. R. et al. (2002) Proc. Natl. Acad. Sci. USA 99, 6476-6481

15. Laboratory of Chemical Thermodynamics The size effect on the energetics of the complex perovskites The variation of the and log pO2with the temperature for the doped lanthanum manganites prepared by ■ Solid state reactions (d  5 m)and ▲ Sol-gel method(d  40 nm) The changes of the thermodyamic data can be explained as a consequence of truly grain-size dependent properties

16. Laboratory of Chemical Thermodynamics The variation of the and log pO2with the temperature and the oxygen stoichiometry change for nano- and microstructured lanthanum manganites. Nano-, micro- and oxygen stoichiometry Nanostructure: -significant changes in the overall defect concentration -a reduced energy of oxygen vacancies formation

17. Laboratory of Chemical Thermodynamics 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, 2005 • S. Tanasescu, C. Marinescu, F. Maxim, Solid State Phenomena, 99-100, 2004, p. 117-122 • S. Tanasescu, D. Berger, D. Neiner, N.D. Totir, Solid State Ionics, 157, 2003, p. 365 – 370

18. Laboratory of Chemical Thermodynamics Comparative results of the relative partial molar thermodynamic data of oxygen in the nonstoichiometric compounds prepared by two different methods (1173-1273 K) Nanostructure: the increase in the binding energy of oxygen and an increase of order in the oxygen sublattice of the perovskite-type structure

19. Decreasing with size Bulk Lattice Constants Surface Energy Pb Independent of size Increasing with size Super Paramagnetic Transition at Room Temperature Hematite Goethite Characteristic Sizes for Physical and Chemical NANO Effects Lattice For metals Pt, Pd, Fe and Ta Constants Break down of Hall Petch Grain-Size Hardening Metal Layer Structures Oxide Phase Stability Rutile Anatase Brookite Goethite Hematite Lattice Parameter and Neel Temperature CuO OxideLayers on Fe Air exposed bulk metal Oxygen exposed nanoparticles 1 10 100 Critical or Characteristic Particle Sizes [nm]

20. Summary and Concluding Thoughts • 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