1. Exposure Assessment of Engineered Nanoparticles: Challenges, Progress, Opportunities Christopher Long, Sc.D. November 19, 2008 SRA-NE Seminar

2. Overview Key Questions: –How, What or Who, When, Where, How Much? –What data are currently available to evaluate NP exposure potential? –Are existing Best Management Practices for dusts, fumes, and mists effective for engineered NPs? –What are some key challenges and data gaps for understanding potential exposures to nanoparticles?

3. Motivation Risk = function (Hazard, Exposure) Meaning that: With little or no exposure, there can be no significant health risks.

4. Nanotechnology is “Now” Over 800 consumer products worldwide … Photo by David Hawxhurst, Woodrow Wilson Center

5. Not Everything “Nano” is Actually Nano

6. Nano-sized Particles Are Not Novel Natural NPs Ambient air chemistry (e.g., gas-to-particle conversions) Forest fires Volcanoes Viruses Biogenic magnetite Proteins Anthropogenic Incidental NPs Internal combustion engines Fossil fuel power plants Incinerators Jet engines Metal fumes (smelting, welding) Polymer and other fumes Cooking (frying, broiling, grilling, baking, toasting) Heated surfaces Electric motors (vacuum cleaners) Office equipment Candles

7. Nano-sized Particles Are Ubiquitous!

8. What’s Published About NP Exposure Potential?

9. How NP Exposure May Occur

10. Potential Human Exposure Routes and Pathways Potential for inhalation, dermal contact, and ingestion exposures Workplace settings recognized to have greatest exposure potential But general population exposures cannot be overlooked –Direct exposures from use of consumer products –Indirect exposures to NPs in the environment from releases resulting from production, use, and end-of- life (e.g., landfilling, incineration, recycling)

11. NP Sources and Potential Routes to the Environment Sector/Application Nanomaterial Probable Exposure Routes Air Surface Water Ground Water WastewaterSoil Cosmetics and personal- care products TiO 2, ZnO, fullerene (C 60 ), Fe 2 O 3, Ag Catalysts, lubricants and fuel additives CeO 2, Pt, MoS 3 Paints and coatings TiO 2, SiO 2, Ag, quantum dots Water treatment and site remediation Fe, Fe-Pd, polyurethane Agrochemicals SiO 2 (porous) as a carrier Food packagingAg, nanoclay, TiO 2 Pharmaceuticals and medicines Nanomedicines and carriers (Adapted from Boxall et al., 2007)

12. Release Possibilities in the Product Lifecycle

13. Quantifying NP Exposure: What’s the Relevant Exposure Metric? “Each One May Be Right” Schwartz et al. (2002) Monteiller et al. (2006) Stolzel et al. (2007)

14. Many Different Shapes, Chemistries, etc. N. Walker, National Toxicology Program

15. Expanded List of Possible Measures of NP Exposure Mass concentration Surface area Number concentration Surface reactivity State of Agglomeration Weighted size distribution Morphology (Shape) Surface charge Chemical composition

16. Measuring Exposure Mass, Number, Surface Area? MSP Corp. NanoMOUDI-II TSI 3007 Portable CPC TSI 3550 Nanoparticle Surface Area Monitor EcoChem DC2000 CE Diffusion Charger TEM/SEM

17. Particle Size Measurement TSI 3034 SMPS MSP Corp. Wide-Range Particle Spectrometer Dekati Electrical Low Pressure Impactor (ELPI) Met One HHPC-6 Optical Particle Counter MSP Corp. NanoMOUDI-II

18. Lack of Specificity Process-related or other nanoparticles? –Need for careful data interpretation and/or more specific detection methods (e.g., shape recognition, elemental analysis) From Kuhlbusch et al. (2001)

19. Potential Exposures During Simulated CNT Handling Scenarios Evidence for agglomeration under realistic handling processes; low respirable CNT concentrations Adapted from Maynard et al. (2004), Maynard (2005)

20. Airborne PM in a Fullerene Factory During removal of fullerenes from storage tank for bagging and/or weighing, no elevation in D p 1,000 nm SEM confirmed emission of fullerene aggregates/ agglomerates Consistent with findings from Maynard et al. (2004), observed increase in particle number conc. at D p <50 nm during vacuuming (Fujitani et al., 2008)

21. Airborne Metal Oxide NPs at an Industrial Pilot Plant Results indicate high temperature gas-phase production unit to be main particle source –Average conc. of 59,100 cm -3 and 188  g/m 3 –Direct reactor leaks? Vacuum cleaner increased number conc. but not mass conc. No substantial rise in submicron particles during particle handling and processing (Demou et al., 2008)

22. Airborne Exposures During NP Handling in Fume Hoods Pilot study demonstrates NP exposures when handling dry powders in standard fume hoods –Potential for NP releases: Conventional>by pass>constant velocity –Highly dependent on many variables- e.g., hood design, hood operation, work practices, type and quantity of NPs, etc. Released NPs remained airborne in laboratory air for up to 2 hours Well-designed hoods, operated at a constant face velocity (e.g., constant velocity hoods), shown to be protective under all test conditions Pouring of 100 g Nanoalumina NPs (Tsai et al., 2008)

23. NIOSH Field Investigations Since 2006, NIOSH field team has conducted ~20 site visits –Variety of workplaces- e.g., commercial R&D labs, university labs, manufacturing facilities –Variety of NP types- e.g., carbon nanofibers, metal oxides, QDs Development of Nanoparticle Emission Assessment Technique (NEAT) –Baseline assessment utilizing portable instruments (CPC and HHPC-6) for particle number measurements Are particle number concentrations “higher” with production system on? ~25% increase above background used as subjective decision point If Yes, filter-based samples for TEM and chemical analysis collected –Expanded assessment using less portable, more expensive particle analyzers (e.g., SMPS, surface area analyzers)

24. Preliminary NIOSH Results Available data show measurable particle releases (but generally not NPs!) –Release of >400 nm particles during weighing/ mixing of carbon nanofibers and wet-sawing of composite materials (Methner et al., 2007) –Effectiveness of Local Exhaust Ventilation (LEV) during reactor cleanout operations (Methner, 2008)

25. Exposure to Free NPs from Consumer Products??? Few available data for realistic consumer product use scenarios –For sunscreens, studies show no significant penetration of TiO 2 or ZnO NPs. –For products such as nanocomposite sporting goods, low exposure potential expected due to incorporation into solid, impermeable matrices. –Limited data suggest releases possible during product modification (e.g., sanding, sawing). PNNL Sanding Study of CNT Nanocomposites

26. Categorization Framework for Consumer Products (Hansen et al., 2008) Based on location of nanostructure in product Three broad exposure categories –Expected to cause exposure: “nanoparticles suspended in liquids” and “airborne nanoparticles” –May cause exposure: “surface-bound nanoparticles” –No exposure expected to consumer: “nanoparticles suspended in solids” Applied to Woodrow Wilson Consumer Products Inventory –Categorized 45% of products into the “likely exposure” category, 9% into the category of “no likely exposure,” and 25% as unclassifiable –Highest exposure potential for products in the categories food/ beverages and health/fitness –Highest exposure potential for Ag, TiO 2, and ZnO –Several limitations, including lack of information about location of nanomaterials in many products

27. Effectiveness of Traditional Filter Media (Pui et al., 2008)

28. Conclusions Measurable NP emissions can be released during typical manufacturing and handling processes –Only moderate increases in NP conc. compared to background levels- i.e., uncertain relevance to human health Critical need for additional data representative of real- world exposure conditions –Need for not only more workplace studies, but also studies to determine the likelihood and conditions for potential releases of free NPs from consumer products and end-of-life processes Growing evidence that traditional exposure controls can effectively reduce NP exposure levels –Research indicates that not all fume hoods may be protective

29. Exposure Assessment Needs Field measurements of actual workplace conditions –Need to establish the relationship between basic measurements and research-grade measurements –Need to establish the relevant exposure metric(s) Personal universal aerosol monitor that meets criteria for price, ease of use, and size Real-time instrumentation that can discriminate nano-sized particles of interest Standardized methods and reference materials for assessment of particle size, size distribution, shape, structure, and surface area

30. Need for Collaboration with Nanotech Industries 2006 ICON survey of current practices in the nanotech workplace Only 25 of 78 (32%) respondents indicated that their organization performed monitoring for NPs Of the respondents indicating that their organization performed NP monitoring, most indicated that monitoring occurred on an irregular basis Number concentration and particle size were most commonly measured, generally using hand-held, inexpensive particle counters Four respondents described using monitoring equipment that measures outside of the nanoscale

32. One Final Thought Need for exposure studies to inform toxicity testing Size distributions for SWCNT during handling events (Maynard et al., 2004) Size distribution for SWCNT generated for inhalation toxicity study (Baron et al., 2008)

33. Any Questions? clong@gradientcorp.com (617) 395-5532