NANOTECHNOLOGY: AN INDUSTRIAL HYGIENE PERSPECTIVE

The Potential Hazards of Nanomaterials

THERESA REPASO-SUBANG, DABTMarch 21, 2013

Agenda Definitions Background

Categories and types of nanoparticles Relative size Structures Key particle characteristics

Occupational exposures Challenges Summary

Uses of Nanomaterials

Widely used in industrial and public sectors

Increasing concern raised over the potential impacts of NPs on human health

Definitions

Nanotechnology Understanding and control of matter at

dimensions between 1 - 100 nm Encompasses nanoscale science,

engineering and technology Involves imaging, measuring and

manipulating matter at this length scale(National Nanotechnology Initiative, 2007; definition adopted by ISO, 2008)

Nanomaterial Any material consisting of, or containing

structures with at least one dimension between 1 – 100 nm(Ellenbecker and Tsai, 2011)

Categories of Nanoparticles

Nanoparticles (NPs)

Anthropogenic

Incidental(eg. welding fumes,

diesel exhaust, combustion smoke)

Engineered(carbon black, carbon nanotubes, quantum

dots)

Natural

volcanic eruptionforest fires

salt particles produced by oceanic waves

Relative Size of Nanoparticles

(Stern and McNeil, 2008; Mohanpuria et al., 2008)

Types of Nanoparticles

Single-walled carbon nanotubes (SWNT)

Multi-Walled carbon Nanotubes (MWNT)

Key Nanoparticle Characteristics

Nanoparticle Interactions with Cells

Production of reactive oxygen species (ROS)

inflammation Membrane stability directly

(physical damage) and indirectly (oxidation)

Cell death Fullerenes and Carbon nanotubes

(NTs): mitochondrial damage TiO2, carbon nanotubes,

polystyrene and Ag: mitochondrial function apoptosis

Nanoparticle Studies Related to Occupational Exposures

(Editorial, Journal of Toxicology, 269 (2010) 89-91)

Occupational Exposure Studies

Kuhlbusch et al, Particle and Fibre Toxicology, 2011, 8:22 reviewed exposure related nanoparticle measurements at workplaces workplaces included industrial production facilities, processing plants, pilot plant

investigations, crafting of nanomaterials as well as research related work settings Release of agglomerated NPs, mainly >300 nm observed during open handling of dry

nanomaterials Release of NPs <100 nm was also observed in some cases

Entry Routes into the Body

Characterizing Potential Exposure and Effects

Using conventional Risk Assessment (RA) approach Dose = C * T

Difficult to estimate for NPs Require consideration

of direct and/or indirect technologies to determine how many particles are reaching target organ/tissue.

Oberdorster, G. et al (2005) Principles of characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2,8

Carbon Nanotubes

single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs)

Used as carriers for drug and gene delivery and as scaffolds for tissue engineering (global market estimated at approx. $1B by 2014)

Toxicity studies indicated: Cell death Membrane damage Release of cytokines (e.g., tumor necrosis factors)

Love et al, Assessing Nanoparticle Toxicity, Annual Review of Analytical Chemistry, 2012, 5:181-205

Silver Nanoparticles

Commonly used NP in consumer products

Used as an antimicrobial agent, clothing, washing machines

Studies indicated that Ag NPs are taken up by cells, then distributed in various cell compartments with a range of pHs

Release of Ag+ from NP is the primary cause of toxicity

Silver Nanoparticles

Zhang et al, Modeling the primary size effects of citrate-coated silver nanoparticles on their ion release kinetics. Environ. Sci. Technol., 2011, 45:4422-28

Titanium Dioxide Nanoparticles Crystalline and occurs in three forms

Rutile, anatase and brookite

Wide use in application from cosmetics, sunscreen to heterogenous catalyst

TiO2 NPs tend to aggregate in solution without surface modification which influences their effective size and may affect toxicity

TiO2 NPs are taken up into cells and tend to localize within lysosomes or vesicles of the cells as aggregates

Titanium Dioxide

Love et al, Assessing Nanoparticle Toxicity, Annual Review of Analytical Chemistry, 2012, 5:181-205

Challenges

Material Characterization

• Consistency in engineered materials (reference materials)• Confirmation/validation of results• Standardization of analytical techniques and protocols

Exposure Characterization

• Exposures to agglomerated NPs• Release from consumer products and subsequent exposures• Exposure from unintended use (e.g., garment containing NP)• Exposure monitoring

Characterization of Toxicity

• Lack of exposure standards• Difficult to characterize toxicity as a result of varied structures and physicochemical properties• Dose as a key parameter is essential in hazard identification and risk assessment. How to

determine safe dose for NPs?

CONCLUSIONS

Uptake, distribution in the body and toxicity of NPs are different due to the varied physicochemical characteristics of nanoparticles

The hazard identification and dose response assessment for nanomaterials are challenged by the lack of characterization data that allows understanding of their toxicity and enable to set appropriate dose metrics.

Difficult to test reproducibility of health effects when challenged by heterogeneity and reproducibility of nanoparticles

THANK YOU!

Theresa Repaso-Subang, DABTGolder Associates Ltd.

6925 Century Avenue, Suite #100Mississauga, Ontario, Canada L5N 7K2

Tel: (905) 567-4444email: TRepasoSubang@golder.com