Toxicity of Naturally-Occurring and Man-made Nanoparticles Presented by

Toxicity of Naturally-Occurring and Man-made Nanoparticles Presented by: Tina Suen, Nisha Kailai, Denise Lieu, and Ikran Aden BIOL 475 February 29 th, 2012

Agenda • Background information • Naturally-occurring toxic nanoparticles • Incidental man-made particles • Engineered man-made particles • Contemporary cases and Issues

Definition • Nanoparticle: particles that range in size from 1 to 100 nm • Nanometer: = 10 -9 m • Nanotechnology: deals with dimensions less than 100 nm (especially the manipulation of individual atoms and molecules)

History of Nanotechnology

Fun Facts • Nanotechnology is being used everywhere today – even in some surprising products! • i. Phone app: find. Nano

Regulations • Canadian government preventing detrimental effects of nanoparticles to human health and the environment • Nanoparticle use regulated by: - Health Canada - PMRA - CFIA

Why should we care? • Nanoparticles can be found everywhere • Can be ingested, inhaled, or absorbed • If incorporated into other organisms, may enter our food chain and indirectly affect us • Regulations have not yet been established for labelling all nanoparticles • Health concerns: accumulate in tissues

Nanoparticles are everywhere!

Viruses • Definition: small infectious particles that can only replicate intracellularly • Size: vary from 20 nm to 300 nm • Toxicity: depends on virus – Toxic to all forms of life (ie. bacteriophage) • Mode of Transmission: inhaled, ingested, or contact • Health Risk: HIV, influenza, hepatitis, ebola, HPV, smallpox, etc.

Spores • Definition: Structure made by some organisms to survive for a long time in harsh conditions • Size: ~7 nm – >100 nm • Source: Found in many bacteria, plants, and fungi • Toxicity: varies; mold spores are toxic to humans • Mode of Transmission: inhalation or ingestion • Health Risks: Food poisoning (Clostridium botulinum) respiratory tract infections (Bacillus anthracis)

Endotoxins • Definition: toxins released from the death of bacteria, often containing lipopolysaccharides or lipoproteins • Size: ~10 k. Da • Source: outer membranes of Gram-negative bacteria • Toxicity: varies • Mode of Transmission: ingestion or aerosolized • Health Risks: fever, inflammation and endotoxic shock

Unintentional Anthropogenic Nanoparticles

Bioaerosols • Definition: Air-borne particles that contain living organisms or particles that are released from living organisms with biological action indicated by its viability, infectivity, and allergencity. • Size: 20 nm to > 100 micrometer • Primary biological aerosol: virus, bacteria, fungal spores, plants pollen particles. Size range from 10 nm to 100 micrometers • Source: - Processing of wastewater and solid wastes - aerial application of liquid manures for agriculture - meat/poultry/fish processing plants and biological laboratory procedures; vacuuming, etc.

Bioaerosols Toxicity: - For bioaerosols to be infectious or pathogenic, it must be viable. - viability changes with season, weather and geographic location. Modes of transmission to human: - skin, eyes and respiratory system. The most sensitive route is inhalation. Health risk: - allergies, eye irritant - airway constriction

Combustion Derived Nano. Particles (CDNP) • Origin: combustion processes

CDNPs Sources: – Stationary industrial sources (coal/oil/gas boilers, incinerators, metal smelting and refining) – Vehicle emissions Factors of toxicity: - Particle size, solubility and chemical composition Health Risks: – Lungs (inflammation) – Irregular heart rate - Brain (accumulation of Manganese) - Genes (damage to DNA

Toxicity of CDNP to Lungs

Fly Ash • Definition: Particulate Matter from mineral and metal contaminants of organic fuels • Residue behind combustion of coal • Generally spherical in shape • Size: ranges from 0. 5 µm to 100 µm. • Two groups: Residual Oil Fly Ash- ROFA ( from liquid fuel) and solid fuel Electron microscope (SEM): Fly ash particles at 2, 000 x magnification

Fly Ash • Residual oil fly ash (ROFA) contains sulfate and heavy metals. • Solid fuel fly ash from burning of coal. • Toxic trace heavy metal elements in fly ash (eg Arsenic, cadmium, uranium, mercury) • Mode of entry: Inhalation • Environmental Problem: – Ground water, soil and river contamination (leaching) – Health Risks

Fly Ash • Effects on soil: – Fly ash is highly soluble in water and can be easily penetrated into soil – It changes the soil's chemical equilibrium such as increase in p. H, salinity and level of toxic elements • Health Risk: – Lung Damage: Toxic (Coal) particles damage epithelial cells. • Uses: – Increase viscosity of liquid phase (aggregate suspended cement grains) – Improve resistance

Polytetrafluoroethylene (PTFE) • Fluoro-polymer • Thermal stability • Electrical resistance • Average sizes: ~ 90 nm for Carbon Nanofibers (CNFs) ~ 130 nm for PVP ~ 150 nm for alumina ~ 200 nm for silica SEM image of PTFEs on Carbon Nanofibers (CNFs)

Polytetrafluoroethylene (PTFE) Source: Fumes in indoor - PTFE can be generated at a temperature >425 o. C; 18 nm diameter Mode of Transmission to human: Inhalation - Absorption of reactive gases and the radicals Environmental problem: - Air pollution, Health Risk Health risk: - Lung inflammation, oxidative injury, and accumulation of fluid in lungs - Death in rats when they are exposed at the rate of ~0. 05 mg m-3 for 15 min - Case study: A worker had died due to the release of PTFE product in the workplace. Hence it has been proved that even very low concentration is toxic and lethal to human beings.

Engineered Anthropogenic Nanoparticles

Engineered Nanoparticles Metal-based: • Ti. O 2 in sunblock • Silver for antimicrobial surfaces (clothes, furniture, cooking ware) • Quantum dots (imaging) • Electronics • Medicine – joint replacements Carbon-based: • Food packaging • Paints • Electronics • Medicine – drug delivery (in development) • Oil spill remediation • Diamond films • Lubricants • Special rubber additives Other sources: manufacture, wear and tear, waste

The issues • Discrepancies in jargon, classification • Experimental design • Lack of supporting literature

The issues • Discrepancies in jargon, classification – Metal vs organic • Experimental design – Excessive dosing – Dying is boring • Lack of supporting literature • No regulations for labeling, disposal, handling of commercial products eg clothing, sunblock

Buzea et al, 2008

Exposure & Entry Mainly Inhalation, Ingestion - Tendency to translocate Buzea et al, 2008

Factors of nanoparticle toxicity • • Size vs surface area Coatings Agglomeration Production contaminants Surface charge & chemistry Crystal structure Biopersistence (largely unknown)

Size: - Effect is proportional to surface area - Translocation to 2 o sites - Crosses blood brain barrier Buzea et al, 2008 Nayak et al, 2010

• Coatings (Derfus et al 2004) – Hepatocytes exposed to Cd. Se quantum dots: • 66% viability - coated with Zn. S • 6% viability – uncoated • Agglomeration – “Differential protein adsorption”

Modus Operandi: ROS Oberdorster et al, 2007

Metal nanoparticles • Silver – antimicrobial in both ancient and recent history • Heavy metals • LD 50: nanoparticle macroparticle Gold > 5 g/kg (50 nm) > 5 g/kg rat Silver > 2 g/kg 2. 8 g/kg (Ag. O) rat Ti. O 2 >12 g/kg >24 g/kg rat Cu 0. 41 g/kg (23. 5 nm) >5 g/kg (17 um) mice Se 0. 13 g/kg 0. 02 mg/kg (Na. Se) mice Botulism toxin 1 - 3 ng/kg human

24 h postfertilisation (5 ug/m. L) Control Ag-starch Ag-BSA 72 h postfertilisation (100 ug/m. L) Asharani et al, 2008

Root growth on exposure to Al np Corn carrot soy cabbage cucumber Yang & Watt, 2005

Changes in bacterial content of soil exposed to nanosilver Kumar et al, 2011

Carbon Nanoparticles • Different conformation of nanostructure in arrangement of carbon ring structures. • Discovered in 1991. • Fullerene ring structure • Nanotubes • Nanospheres • Nanofibers

Carbon Nanotubes • Cylindrical nanostructure in arrangement of carbon nanotubes. • High tensile strength, electrical conductivity, high ductility, high heat conductivity, chemically inactive.

Nanospheres • Buckminsterfullerene configuration. • Smallest fullerene and most abundant in nature. • Hollow spheres that have vast application capabilities.

Nanofibers • Cyclic nanoparticles with graphite layers. • Can aggregate into cylinders and form nanotubes.

Health Hazards • Carbon nanoparticles enter cytoplasm and cause cell death. • Similar to asbestos fibers and can cause pleural mesothelioma or peritoneal mesothelioma.

Contemporary Cases of Engineered Nanoparticles

Toxicological Studies • Inhalation toxicity of multi-walled carbon nanotubes in rats exposed for 3 months. Ema et al. 2010

Environmental Effects • Toxic effects on green algae. • Effects on Drosophila Melanogaster.

Nanoparticles in the News • 17 year old discovers nanoparticle that detects and kills cancer. • Nanoparticles that boost immune response and strengthens immune system. • Nanoparticle solar cells make light work.

Conclusions • Naturally occuring nanoparticle regulations in the future. • Anthropogenic nanoparticle use in future cancer treatments. • Tighter regulations in development to reduce environmental effects.

Questions?

References • • • Ball, Phillip. "Nanoparticle solar cells make light work. " Nature News [New York] 3 Nov. 2011: 1 -2. Print. Buzea, Christina , Ivan Pacheco Bladino, and Kevin Robbie. "Nanomaterials and nanoparticles: Sources and toxicity. " Biointerphases 2. 4 (2007): 1 -88. Print. De Jong, Wim, and Paul Borm. "Drug Delivery and Nanoparticles: Applications and Hazards. "International Journal of Nanomedicine 2. 3 (2008): 133 -145. Print. Heimbuch, Jaymi. "Carbon Nanotubes in Environment Affect The Growth of Algae. " Discovery [USA] 4 Nov. 2011: 1. Print. "Nanoparticle trick 'boosts body's vaccine response'. " BBC News Health[Britain] 22 Jan. 2012: 1. Print. Oberdörster, Eva, Gunter Oberdörster, and Jan Oberdörster. "Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles. " Environmental Health Perspectives 113. 7 (2005): 823 -836. Print.