1. Copyright© 2008 TSI Incorporated Nanoparticle Monitoring in Occupational Environments – Comparing and Contrasting Measurement Metrics TSI Incorporated 2008 Nanotechnology and Occupational Health and Safety Education Series

2. Copyright© 2008 TSI Incorporated Agenda Nanoparticle exposure Traditional IH aerosol measurements What is nanotechnology? Filtration mechanisms Engineering controls Current measurement metrics for nanoparticles Working towards best practices Multi-metric sampling and control approaches Summary References Horizontal zinc oxide nanowires on sapphire surface Image credit: Courtesy National Institute of Standards and Technology

3. Copyright© 2008 TSI Incorporated Nanoparticle Exposure Increasing commercial development Worker exposure is a concern Nano-scale materials exhibit new properties –Follow laws of quantum physics –Determines new properties Occupational health risks are not clearly understood “Buckyball” designed for drug delivery Image credit: Courtesy LUNA Innovations

4. Copyright© 2008 TSI Incorporated Nanoparticle Exposure Routes of exposure –Inhalation Most common/efficient Most well understood –Dermal contact Less work done here Just a few studies (e.g., Beryllium, Nano Safe II in Europe) –Ingestion Little interaction between pharmaceutical industry & toxicologists and epidemiologists Questions about adverse health effects and ingestion

5. Copyright© 2008 TSI Incorporated Nanoparticle Exposure Solubility Particle size Particle shape Particle number Surface Area Composition Surface coatings Surface chemistry Others? Properties That Contribute to Nanoparticle Toxicity

6. Copyright© 2008 TSI Incorporated Nanoparticle Exposure Current research indicates that mass and bulk chemistry may be less important than particle size, surface area, and surface chemistry for nanostructured materials (Oberdörster et al. 1992, 1994a,b; Duffin et al. 2002)

7. Copyright© 2008 TSI Incorporated Nanoparticle Exposure Nanoparticle Exposure Studies Dr. Driscoll (1996) and Dr. Oberdörster (2001) have shown that surface area (μm 2 /cc) plays an important role in the toxicity of nanoparticles Surface area is the metric that is highly correlated with particle- induced adverse health effects (Driscoll, 1996; Oberdörster, 2001) Potential for adverse health effects is proportional to particle surface area (Driscoll, 1996; Oberdörster, 2001)

8. Copyright© 2008 TSI Incorporated Nanoparticle Exposure What experts say If nanoparticles can... i.Deposit in the lung and remain there ii.Have active surface chemistry iii.Interact with the body... there is the potential for exposure and dosing

9. Copyright© 2008 TSI Incorporated Nanoparticle Exposure Relatively few occupational studies –Compared to overall money spent on nanotechnology –More are being conducted Most studies in research settings Lack of exposure metrics to compare/contrast –What is a good vs. high number? –Emerging issue for OH&S Monitoring equipment is available –Some not considered IH optimized

10. Copyright© 2008 TSI Incorporated Nanoparticle Exposure Inadequate protection –Engineering controls or PPE Material handling or mixing –Increase chance of fugitive emissions Fugitive emissions –From non-enclosed or controlled production or process systems Maintenance activities Similar to what you already find! Workplace Conditions Likely to Cause Exposure to Nanoparticles

11. Copyright© 2008 TSI Incorporated Traditional IH Aerosol Measurements

12. Copyright© 2008 TSI Incorporated Traditional IH Aerosol Measurements Exposure limits based on mass Size range of ~0.1 – 100 µm Toxicity data Lung deposition models relating to size selective sampling protocols

13. Copyright© 2008 TSI Incorporated Traditional IH Aerosol Measurements OSHA, 2 sizes –Total dust, ≤100 µm Deposits in all areas of the respiratory tract –Respirable dust, ≤4 µm Subset of total dust, deposits in alveolar region of the respiratory tract ACGIH/ISO/CEN, 3 sizes –Inhalable, ≤100 µm Deposits in all areas of the respiratory tract –Thoracic, ≤10 µm Subset of inhalable, deposits in the tracheobronchial and alveolar regions –Respirable, ≤4 µm Subset of thoracic, deposits in the alveolar region Lung deposited size fractions

14. Copyright© 2008 TSI Incorporated Traditional IH Aerosol Measurements Mass measurement methods Gravimetric sampling –Personal air sampling systems Worn by the worker Breathing zone sampling for personal exposure Personal sample pump/inlet conditioner/media –Area air sampling systems Work area sampling For area sampling, baseline screening and trend analysis Pump/inlet conditioner/media Personal or higher volume pump used

15. Copyright© 2008 TSI Incorporated Traditional IH Aerosol Measurements Mass measurement methods Direct-reading instruments –Photometers Incorporate same sampling methodologies as gravimetric –Inlet conditioners –Personal sampling –Area sampling

16. Copyright© 2008 TSI Incorporated Traditional IH Aerosol Measurements Size selective sampling Inhalation and lung deposition –Most common/efficient way for particles to enter Common to sample according to deposition Criteria depends on aerosol being sampled –Mechanisms of lung deposition and dosing Size fractions and examples –Inhalable/total, ≤100 µm > silica –Thoracic, ≤10 µm > cotton dust –Respirable, ≤4 µm > coal dust

17. Copyright© 2008 TSI Incorporated Traditional IH Aerosol Measurements Based on International Commission of Radiological Protection (1994) and U.S. Environmental Protection Agency (1996a). Air Quality Criteria for Particulate matter, 2004, p 6-5. The respiratory tract consists of 3 major regions –Extrathoracic region: uppermost region –Tracheobronchial (TB) region: middle region –Alveolar (A) region: innermost region

18. Copyright© 2008 TSI Incorporated What is Nanotechnology?....technologies, that measure, manipulate, or incorporate material or features with at least one critical dimension between ~ 1 nanometer and 100 nanometers...... whose applications exploit properties, distinct from bulk/macroscopic systems, that arise from their scale/critical dimension... Note: terminology from ASTM Committee E56, definitions are only considerations

19. Copyright© 2008 TSI Incorporated What is Nanotechnology? Nanotechnology “The art and science of building stuff that does stuff at the nanometer scale.” Richard Smalley (1943 – 2005) Nobel Prize Winner, Chemistry (1996)

20. Copyright© 2008 TSI Incorporated What is Nanotechnology? Coarse particle – ≤10 µm Fine particle – ≤2.5 µm Ultrafine particle – ≤0.1 µm (100nm) Nanoparticle Dimensions between 1 and 100 nm in at least one dimension Nanoparticle size may go up to 200 – 300 nm for occupational exposure Note: terminology from ASTM Committee E56, definitions are only considerations

21. Copyright© 2008 TSI Incorporated What is Nanotechnology? Aggregate A group of particles that are strongly bonded together (e.g., fused, sintered, or metallically bonded) Agglomerate A group of particles held together by relatively weak forces (e.g., van der waals, capillary, etc.) that may break apart into smaller agglomerates, aggregates or primary particles upon handling

22. Copyright© 2008 TSI Incorporated What is Nanotechnology? Earth = 12756 km Soccer ball = 0.2264 m –Difference 1.77 x10 -8 Soccer ball = 0.2264 m 10 nm particle = 10x10 -9 m –Difference 4.44 x 10 -8 How small are nanoparticles? Source: Professor David Pui, University of Minnesota

23. Copyright© 2008 TSI Incorporated What is Nanotechnology? Golf ball = playing card 25nm particles = 4 football fields Nanoparticle surface area Source: www.nanohorizons.com

24. The Scale of Things – Nanometers and More Things Natural Things Manmade Ant ~ 5 mm Head of a pin 1 - 2 mm Dust Mite ~ 200 μm Red blood cells with white cell ~ 2 - 5 μm Human Hair ~ 60 - 120 μm wide Carbon nanotube ~ 1.3 nm diameter DNA ~ 2 1/2 nm Diameter Carbon buckyball ~ 1 nm Diameter Micro Electro Mechanical (MEMS) devices 10 - 100 μm wide Adapted from Office of Basic Energy Sciences, Office of Science, U.S. Department of Energy

25. 0.0010.010.1110100 Particle Size Range (micrometers ) Types of Particles Bacteria Virus Oil Smoke Diesel Engine Exhaust Combustion Nuclei Soot Inhalable (Total dust) Respirable Thoracic Pollen Particle Sizes Construction Activities Carbon Black Welding Fume 4 Sea salt Tobacco smoke Coal Dust (mining) Paint Pigment Vacuuming Wind blown dust Volcanic emissions Environmental / Naturally Occurring Particles Workplace / man-made Particles Fly Ash Nanoparticle

26. Copyright© 2008 TSI Incorporated Nanoparticle Sources Nanoparticles and ultrafine particles Capable of depositing in all areas of the lung Essentially the same size range –How they are produced that is different Look at them as one group

27. Copyright© 2008 TSI Incorporated Nanoparticle Sources Naturally Occurring / Biogenic Forest fires Volcanic activity Sea-spray salt Photochemical reactions high in the atmosphere St Helens erupting on May 18, 1980. Source: NASA

28. Copyright© 2008 TSI Incorporated Nanoparticle Sources Manmade / Incidental Unintentionally produced byproducts Products of combustion/high energy operations Produced by chemical reactions Examples Combustion aerosols – many sources! –Welding and cutting –Engine emissions –Heating/furnace emissions –Coal fired power plant emissions –Cooking exhaust –Copiers, faxes and printers

29. Copyright© 2008 TSI Incorporated Nanoparticle Sources Intentionally manufactured from homogeneous materials Examples Carbon nanotubes Carbon nanowires and ropes Buckminster fullerenes Quantum dots Nanocoatings Nanolayers Nanoshells Engineered Nanoparticles Source: AZONANO.com

30. Copyright© 2008 TSI Incorporated Manufacturing Processes Plasma reactors Laser ablation Flame reactors Flame spray pyrolysis Furnace reactors Plasma heating Sputtering Sparking Spray evaporation Spray pyrolysis Nanoparticle Manufacturing Methods

31. Copyright© 2008 TSI Incorporated Nanoparticles vs. Large Particles Relatively little mass –Mass of 1 billion 10 nm particles = mass of 10 µm particle Large surface area Produced in large numbers Quantum effects –Change their physical, chemical, and biological properties Behave like gases –Stay suspended for weeks Disperse quickly –Reach equilibriium (high → low) –Pressure differentials provide transport pathways Tend to agglomerate quickly after production Health effects are not completely understood Nanoparticle Properties and Behavior

32. Copyright© 2008 TSI Incorporated Nanoparticles vs. Large Particles Aerosol researchers have shown worldwide… –86% of the total number of particles in a unit volume of air make up <1% of the mass –14% of the total number of particles make up >99% of the mass

33. Copyright© 2008 TSI Incorporated Present Nanotechnology Nanotechnology is now! US is the largest producer of nanomaterials Material science research focus Intense scientific application study –Chemical, plastics/polymers, optical, electronics, semiconductor, pharmaceutical, biomedical Passive nanotechnology –Enhancement of existing products with new properties/functions –Products are additives/ components Active nanotechnology –Products change state during operation

34. Copyright© 2008 TSI Incorporated Nanotechnology Applications Current applications Longer lasting rubber compounds Plastics (bumpers on cars) Polymers and composites Cement/concrete additives Paints, pigments, inks and coatings Stain- and wrinkle-free clothing Sunscreen and cosmetics Protective and glare reducing coatings Appliances and food storage containers –Silver nanoparticles inhibit the growth of microorganisms www.nanotechproject.org/consumerproducts

35. Copyright© 2008 TSI Incorporated Filtration Mechanisms Filtration Used extensively –General / dilution ventilation (HVAC) –Local exhaust ventilation (engineering controls) –Respiratory protection (air purifying respirators and filtering face pieces) Air filters are classified as –Mechanical filters –Electrostatic filters (not ESPs) There are many differences between filters although they all use fibrous media Many different fibers are used –Cotton, fiberglass, polyester, polypropylene

36. Copyright© 2008 TSI Incorporated Filtration Mechanisms Fibrous filters of different design are used for various applications –Flat-panel filters –Pleated filters –Pocket or bag filters –Respirator cartridges

37. Copyright© 2008 TSI Incorporated Filtration Mechanisms Mechanisms There are 4 types of collection mechanisms that govern filter performance –Impaction occurs when a particle due to inertia deviates from the air stream and collides with a fiber –Interception occurs when a particle due to it’s size simply collides with a fiber in the air stream –Diffusion occurs when a particle due to random motion causes it to collide with a fiber in the air stream –Electrostatic attraction occurs when a fiber is contacted by a very small particle and is held in place by a weak electrostatic force

38. Copyright© 2008 TSI Incorporated Filtration Mechanisms Adapted from Guidance for Filtration and Air-Cleaning Systems for Protecting Building Environments, NIOSH

39. Copyright© 2008 TSI Incorporated Filtration Mechanisms Impaction and interception are dominant for collecting particles >0.2 µm Diffusion is dominant for collecting particles <0.2 µm (200 nm) As mechanical filters load with particles their collection efficiency increases The combined effects of these 3 collection mechanisms yields the classic collection efficiency curve

40. Copyright© 2008 TSI Incorporated Filtration Mechanisms This figure is adapted from Lee et al. [1980].

41. Copyright© 2008 TSI Incorporated Filtration Mechanisms Particles from 0.2 – 0.4 µm, most difficult to stop Collection efficiency for nanoparticles by diffusion is as efficient as larger particles by inertial impaction and interception Filter Testing Methods –Photometers, Optical Particle Counters (OPCs), and CPCs are used in filter-testing –CPCs and photometers are used in quantitative respirator fit-testing

42. Copyright© 2008 TSI Incorporated Filtration Mechanisms Testing and current work Current knowledge indicates the well designed exhaust ventilation systems using HEPA filters effectively remove nanoparticles (Hinds 1999) –Apply current ACGIH ventilation design criteria for the “control of particulate matter” for nanoparticles

43. Copyright© 2008 TSI Incorporated Filtration Mechanisms Testing and current work Respiratory protection –No specific recommendations on types of respirators Use P100 filters for highest level of protection –Respirator filters are tested at 300 nm (0.3 µm) size particles Most penetrating particle size (MPPS) –Collection efficiencies for smaller particles should exceed the measured collection efficiency of 300 nm particles (Lee and Liu 1982) –If a respirator works for MPPS, it should work for all particles –NIOSH tested HEPA filters with nanoparticles in 2003 Found that P100 filters good down to at least 2.5 nm –Quantitative CPC fit-testing with particles down to 20 nm for testing respirator fit using HEPA/P100 filter cartridges Uses nanoparticles as the test agent Face seal is the leak/test point

44. Copyright© 2008 TSI Incorporated Filtration Mechanisms Testing and current work For respiratory protection the real question is: –Are the assigned protection factors currently used for respirators good enough for nanotechnology applications –In the absence of exposure limits it is hard to determine if an assigned protection factor is good enough for a given respirator –Be conservative, use full-face APR or SCBA, and use engineering controls to ensure exposure is at a minimum

45. Copyright© 2008 TSI Incorporated Engineering Controls Fundamental Control Assumptions Typically support engineering and maintenance departments –IH’s provide guidance, calculations, and design assistance –Evaluate and validate systems upon start up Five fundamental control assumptions i.All hazards can be controlled to some degree by some method ii.There are alternative approaches to control iii.More than one control may be useful or required iv.Some control methods are more cost-effective than others v.Controls may not completely control the hazard

46. Copyright© 2008 TSI Incorporated Engineering Controls Engineering Control Techniques Ventilation –General/dilution ventilation –Local exhaust ventilation Substitution Enclosure Isolation Process change Process automation Process elimination Other controls Prevention Administrative controls Work practices Personal protective equipment

47. Copyright© 2008 TSI Incorporated Engineering Controls General/Dilution Ventilation Remove air from general area, replace with dilution air Dilution of contaminated air with non-contaminated air in a general area Not as good for health hazard control as local exhaust Limiting factors for general/dilution ventilation –Quantity of contaminant too great to use dilution –Contaminant source too close to worker –Toxicity of contaminant must be low –Contaminant source must be constant

48. Copyright© 2008 TSI Incorporated Engineering Controls General/Dilution Ventilation Typically not good for dusts and fumes –Due to high toxicity, requires more dilution air –Higher concentrations of contaminant produced –In the past hard to measure contaminants Easier to do now with real time monitors

49. Copyright© 2008 TSI Incorporated Engineering Controls Local Exhaust Ventilation Proper design necessary –Capture velocity is dependent on moving air past a contaminant source –Drawing it into an exhaust hood –Using an enclosure to capture particles Negative pressure used to lower exposure Positive pressure used to increase quality and output

50. Copyright© 2008 TSI Incorporated Engineering Controls Particles >10 µm settle very quickly Coarse, fine, and nanoparticles remain airborne –Follow air currents –Health based size range –Same applies to fumes, mists, and smokes Utililze local exhaust –Minimize exposure –Maximize quality and output –Improve housekeeping and maintenance

51. Copyright© 2008 TSI Incorporated Engineering Controls Examples Point source/capture exhaust systems –Snorkel exhaust –Bench top exhaust –Ventilated cabinets (negative pressure) Lab hoods Process ventilation systems –Push – pull systems –Overhead capture systems –Negative pressure enclosures

52. Copyright© 2008 TSI Incorporated Engineering Controls For most nanotechnology processes and job tasks The control of airborne exposure to nanoparticles can most likely be accomplished using a wide variety of engineering control techniques similar to those used in reducing exposure to general aerosols (Ratherman 1996; Burton 1997) The use of ventilation systems should be designed, tested, and maintained using approaches recommended by ACGIH (ACGIH 2001) In general, control techniques such as source enclosure and local exhaust ventilation systems should be effective for capturing airborne nanoparticles, based on what is known of nanoparticle motion and behavior in air (ACGIH 2001) Using current control techniques based on scientific knowledge of generation, transport, and capture of aerosols, these control techniques should be effective for controlling airborne exposures to nanoscale particles (Seinfeld and Pandis 1998; Hinds 1999)

53. Copyright© 2008 TSI Incorporated Nanoparticle Measurements Applications – back to basics, JHA’s, WAA’s Determining effectiveness of ventilation systems –Mechanical filtering efficiency –Understanding pressure differentials –General/dilution ventilation –Local exhaust ventilation/controls Conduct work area monitoring –Determine specific sources of nanoparticles Point source location Target potential sources and problem areas –Particle mapping/engineering studies Grid out work areas –Determine infiltration of ambient sources into the workplace Transport pathways

54. Copyright© 2008 TSI Incorporated Nanoparticle Measurements Applications – back to basics Assist in characterizing, defining, and validating new production processes Assist with task-specific material handling operations –Minimizing process emissions Selecting and implementing corrective actions –Repair equipment or engineering controls –Remove source –Remediate source –Implement engineering controls –Change worker process interactions –Implement use of PPE Validate corrective actions “ALARA best practice approaches”

55. Copyright© 2008 TSI Incorporated Nanoparticle Measurements General Sampling Practices – back to basics Evaluate and measure outdoor concentrations –Determine external sources –Time of day when concentrations may go up Ventilation system plays a role –Check mechanical filtration efficiency –Local exhaust ventilation –Lack of ventilation Background/baseline measurements of the work area –Before work operations –During and after (if possible) –Can change quickly –Can bias measurements –Ideally would like background, corrected measurement data

56. Copyright© 2008 TSI Incorporated Mass Measurements Why would we want to measure mass for nanoparticles? –It is a well known metric –Established substance-specific exposure limits for larger particles

57. Copyright© 2008 TSI Incorporated Mass Measurements Traditional gravimetric methods may not be effective for nanoparticles –Insignificant mass compared to larger particles –High flow rates and long sampling times required for a quantifiable sample

58. Copyright© 2008 TSI Incorporated Mass Measurements Mass may not be a good indicator for nanoparticle exposure and dosing since it is based on toxicity data for large particles –Quantum chemistry and physics play a role –Do toxicity and pharmacokinetics change? –Size decreases ↔ toxicity increases Mass can be measured –Gravimetrically (discussed) –Photometrically

59. Copyright© 2008 TSI Incorporated Photometry Photometers Photometers measure particle mass in real time Light-scattering effects vary based on –Particle size, size distribution, density, morphology, and refractive index Photometers respond linearly to mass concentration across their detection range Size specific aerosol fractions are measured Size fractions > aerodynamically cut using an inlet conditioner > cyclone or impactor

60. Copyright© 2008 TSI Incorporated Photometry Photometers Typical particle size range: 0.1 – 10 µm Typical concentration range: 0.001 – 100 mg/m 3 Size fractions using inlet conditioners –Respirable, thoracic, PM10, PM2.5 or PM1.0 What types of aerosols will a photometer detect and measure? –Any aerosol within the size range Personal, hand held, table top, and fixed monitor configurations

61. Copyright© 2008 TSI Incorporated Mass Measurements Gravimetric Strengths Area and personal samplers in the nano size range Ability to compare to historical data Relatively inexpensive –Air sampling equipment –Lab analysis Gravimetric Weaknesses Mass measurements for nanoparticles are difficult due to size and sampling constraints Not a real-time measurment Toxicity for nanoparticles unknown –May not have quantitative relevance as an exposure metric No guidelines or standards for nanoparticles

62. Copyright© 2008 TSI Incorporated Mass Measurements Photometer Strengths Qualitative relevance for agglomerated / aggregated nanoparticles: >100 nm Real-time measurement Field portable, battery operated, and easy to use Personal or area sampling Relatively inexpensive ~$3 -10K Photometer Weaknesses Not in the size range for discrete nanoparticles: <100 nm Not size resolved Not a compliance method No guidelines or standards for nanoparticles

63. Copyright© 2008 TSI Incorporated Number Concentration Why measure the number concentration of nanoparticles? –To determine if they are being released from production processes or being re-aerosolized during bulk production use Point source location during production or use Select and validate engineering controls Compare to background/baseline measurements of the work area

64. Copyright© 2008 TSI Incorporated Number Concentration Measure number concentration in real time A CPC uses a method of condensation to grow particles to an optically detectable size CPCs do not size particles, only count them Not a size resolved measurement CPCs require a working fluid –Alcohol or water Condensation Particle Counters - CPC Source: TSI Inc.

65. Copyright© 2008 TSI Incorporated Number Concentration Particle size range: 10 – 1000 nm Concentration range: 0 – 500,000 pt/cc What types of aerosols will a CPC detect and measure? –Any aerosol within the size range Hand held and table top configurations Condensation Particle Counters - CPC Source: TSI Inc.

66. Copyright© 2008 TSI Incorporated Number Concentration CPC Strengths CPCs are well suited to measuring nanoparticles in the workplace –Good qualitative measurements –Based on relative changes in concentration Field portable, battery operated, and easy to use Handheld models relatively inexpensive ~ $5 – 8K CPC Weaknesses CPCs are not a size resolved measurement –Cannot determine particle size –Cannot account for agglomeration No guidelines or standards exist for number concentration of nanoparticles

67. Copyright© 2008 TSI Incorporated Size Distribution Why measure size distribution of nanoparticles? –To know the size and number of nanoparticles produced Exposure information Quality control purposes (maximize output and minimize loss) –To determine if they are being released from production processes or being re-aerosolized during bulk production use Point source location Select and validate engineering controls Compare to background/baseline measurements of the work area –To determine if nanoparticles are agglomerating or aggregating after production

68. Copyright© 2008 TSI Incorporated Size Distribution Size distribution can be measured in a number of ways –Scanning Mobility Particle Sizer (SMPS), <1 µm –Optical Particle Counter (OPC), >0.3 µm

69. Copyright© 2008 TSI Incorporated SMPS Technology A SMPS uses a Differential Mobility Analyzer (DMA) and a CPC to measure size and number concentration of nanopaticles DMA separates particles according to charge and electrical mobility for size classification CPC grows the particles to a detectible size for counting

70. Copyright© 2008 TSI Incorporated SMPS Technology High resolution and accuracy Wide size and concentration range Fast response time What type of aerosols can be detected with a SMPS? –Any aerosols within the detection range

71. Copyright© 2008 TSI Incorporated SMPS Technology Size ranges vary –2.5 – 1000 nm –10 – 487 nm Multiple size bins Fast continuous scanning

72. Copyright© 2008 TSI Incorporated OPC Technology Measures the size and number concentration of particles in real time –Counts individual flashes of scattered light and the intensity of each flash OPCs may be able to measure nanoparticles in the workplace –Nanoparticles must have agglomerated or aggregated to ≥0.3 µm Typically have multiple size bins that can be arranged to simultaneously measure size fractions –Respirable, thoracic, >10 µm, PM1.0, PM2.5 and PM10 –Eliminating the need for inlet conditioners like cyclones and impactors

73. Copyright© 2008 TSI Incorporated OPC Technology Typical particle size range: 0.3 µm – ~15 µm Concentration range: 2x10 6 particles/ft 3 (70 pt/cc) What types of aerosols will a OPC detect and measure? –Any aerosol within the size range Hand held, table top and fixed instruments

74. Copyright© 2008 TSI Incorporated Size Distribution SMPS Strengths Particle size range –2 to 1000 nm Real-time measurement Size resolved, quantitative measurement –For nanoparticle production process applications –Determine if nanoparticles are agglomerating Qualitative area sampling –Locate point sources –Select and validate engineering controls for nanoparticles SMPS Weaknesses No guidelines or standards for nanoparticles Limited field portability Computer controlled Expensive $60 – 80K

75. Copyright© 2008 TSI Incorporated Size Distribution OPC Strengths For agglomerated/aggregated nanoparticles, >300 nm Size-resolved measurement Real time measurement Qualitative area sampling –Relative changes in number concentration –Locate point sources –Select and validate engineering controls Field portable, battery operated, and easy to use Relatively inexpensive ~$3 -10K OPC Weaknesses Not in the size range for discrete nanoparticles, <300 nm No guidelines or standards for nanoparticles

76. Copyright© 2008 TSI Incorporated Surface Area Measurements Why measure the surface area of nanoparticles? To obtain exposure information based on lung deposited surface area To determine if they are being released from production processes or being re-aerosolized during bulk production use Point source location Select and validate engineering controls Compare to background/baseline measurements of the work area

77. Copyright© 2008 TSI Incorporated Surface Area Measurements Nanoparticles vs. large particles –Have relatively little mass –Have large surface area –Produced in large numbers –Quantum effects change physical, chemical, and biological properties Nanoparticle exposure studies –Drs. Driscoll (1996) and Oberdörster (2001) have shown that surface area (μm 2 /cc) plays an important role in the toxicity of nanoparticles

78. Copyright© 2008 TSI Incorporated Surface Area Measurements Surface area is the metric that is highly correlated with particle-induced adverse health effects (Driscoll, 1996; Oberdörster, 2001) Potential for adverse health effects is proportional to particle surface area (Driscoll, 1996; Oberdörster, 2001) Emerging need to assess workplace exposure to nanoparticles based on surface area

79. Copyright© 2008 TSI Incorporated Surface Area Measurements Lung Deposition Inhalation is primary exposure route Most common/efficient way for particles to enter the body The respiratory tract consists of 3 major regions –Extrathoracic region: uppermost region –Tracheobronchial (TB) region: middle region –Alveolar (A) region: innermost region Uptake of inhaled particles according to deposition in respiratory tract

80. Copyright© 2008 TSI Incorporated Lung Deposition Based on International Commission of Radiological Protection (1994) and U.S. Environmental Protection Agency (1996a). Air Quality Criteria for Particulate matter, 2004, p 6-5.

81. Copyright© 2008 TSI Incorporated Diffusion Charger Technology A Diffusion Charger measures the charge of the particles and calculates the surface area deposited in the TB or A regions of the lung Particle size range: 10 nm – 1000 nm Measurement ranges: TB = 1 – 2,500 µm 2 /cc A = 1 – 10,000 µm 2 /cc What types of aerosols will a diffusion charger detect and measure? –Any aerosol within the size range Desk top and hand held instruments

82. Copyright© 2008 TSI Incorporated Surface Area Measurements Diffusion Charger Strengths Surface area is highly correlated with observed toxic effects Nano size range, 10 - 1000 nm Real time measurement Quantitative area sampling –Surface area dosing information Qualitative area sampling –Data correlates well with CPC and SMPS measurement trends Field portable, battery operated, and easy to use Relatively inexpensive, ~ $10 - 16K Diffusion Charger Weaknesses Not size resolved –Cannot determine size of particle –Does not account for agglomeration No guidelines or standards for nanoparticles –What’s a good number vs. a bad number

83. Copyright© 2008 TSI Incorporated Working Towards Best Practices What can be done? A Proactive Approach – to managing risk To minimize the risk of exposure, implement a risk management program Develop a health hazard surveillance program for workers in nanotechnology operations Continual reassessment of potential hazards and exposures based on information gained is necessary to maintain the surveillance program

84. Copyright© 2008 TSI Incorporated Working Towards Best Practices Program Elements 1.Hazard surveillance monitoring 2.Guidelines for installing and evaluating engineering controls 3.Work practices Education and training of workers Establishing safe production processes and material handling procedures 4.Procedures for selection and use of PPE (e.g., respirators, clothing and gloves)

85. Copyright© 2008 TSI Incorporated Working Towards Best Practices Hazard Surveillance Monitoring Conduct a job hazard analysis Determine need for sampling –Based on potential exposure areas Leads to a decision to measure nanoparticles, keep in mind several factors –Mass and bulk chemistry for exposure may be less important than particle size, surface area and surface chemistry –Currently, there is no single sampling method to use to characterize nanoparticle exposure (Brower et al., 2004) –Therefore, use a multi-metric sampling and measurement approach to characterize workplace exposure to nanoparticles (Brower et al., 2004)

86. Copyright© 2008 TSI Incorporated Working Towards Best Practices Hazard Surveillance Monitoring 1.Identify source(s) of nanoparticle emissions Critical to get ambient background / baseline measurements regardless of monitoring metric used Compare against measurements taken during and after work processes Area, point source, and personal sampling locations 2.Once point source location(s) are identified continue using multi-metric sampling approach Select engineering control techniques to use Conduct dosing and exposure measurements Goal is to achieve ALARA conditions

87. Copyright© 2008 TSI Incorporated Working Towards Best Practices Hazard Surveillance Monitoring 3.Implement and validate engineering controls using same multi-metric sampling approach To achieve ALARA conditions 4.Continue with hazard surveillance monitoring program on a regular basis Ensure engineering controls functioning Verify process and workplace conditions have not changed

88. Copyright© 2008 TSI Incorporated Working Towards Best Practices Health Hazard Monitoring Using a multi-metric sampling approach, assessment of worker exposure to nanoparticles can be conducted This multi-metric approach: –Determines presence and identification of nanopaticles –Assists in selecting, implementing, and validating engineering controls –Assists in characterizing the aerosol measurement metrics Since most nanoparticle measurements rely primarily on area sampling, some uncertainty will exist in estimating worker exposures

89. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Nanotechnology Applications 1. Nanoparticle manufacturing –Bulk production of engineered nanoparticles 2.Industrial manufacturing using nanoscale materials –Utilizing bulk nanoscale materials in products –Bulk nanoscale material handling

90. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Nanoparticle Manufacturing Process Manufucturing nanoparticles in bulk May be a well characterized and defined production process or not May be a clean room manufacturing environment (R&D Lab) or, a “dirty” environment –May or may not have general/dilution ventilation

91. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Hazard Surveillance Monitoring Do a job hazard analysis –Determine need and make decision to sample What do you measure to determine sources? –Size distribution using a SMPS Know what size of nanoparticle being produced Want to see if it is getting into ambient air to determine if you have process leaks Quality control measurement (minimize loss and maximize output) Comparing against background measurements –Number concentration using a CPC for locating point sources Qualitatively locating point sources using changes in relative nanoparticle concentration Comparing against background measurements

92. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Hazard Surveillance Monitoring Located sources now what do you measure? –Size distribution using a SMPS Know what size of nanoparticle being produced Want to see if it is producing the same size particle Quality control measurement (minimize loss and maximize output) Comparing against background measurements –Number concentration using a CPC for selecting, implementing, and validating engineering controls Qualitatively using relative changes in number concentration to achieve ALARA conditions Comparing against background measurements –Surface area concentration using a diffusion charger Conduct work area dosing and exposure measurements Before, during, and after implementation of engineering controls Compare against background measurements

93. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Hazard Surveillance Monitoring Continue with monitoring on a regular basis to ensure that ALARA conditions are maintained Reassess hazard surveillance plan periodically

94. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Manufacturing Using Bulk Nanoscale Material Not well characterized or defined manufacturing process –Utilizing bulk nanomaterials in products –Bulk nanoscale material handling processes –May be dealing with agglomerates and or aggregates, >100 to 300 nm Typically a dirty production environment –May or may not have general/dilution ventilation –Other processes may contribute aerosol contaminants

95. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Hazard Surveillance Monitoring Do a job hazard analysis –Determine need and make decision to sample What do you measure to determine sources? –Mass using a photometer, particles >100 nm –Size distribution using a OPC, particles >300 nm –Number conentration using a CPC, particles >10 nm –Surface area using a diffusion charger, particles >10 nm Qualitatively locate point sources using relative changes in concentrations for all measurements Locate and ruling out other contributing contaminant processes Use any measurement that works to locate point sources Compare against background measurements

96. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Hazard Surveillance Monitoring Located sources now what do you measure? –Use any point source location measurement that works for selecting, implementing, and validating engineering controls Qualitatively using relative changes in number concentration to achieve ALARA conditions Comparing against background measurements –Surface area concentration using a diffusion charger Conduct work area dosing and exposure measurements –Before, during, and after implementation of engineering controls Compare against background measurements

97. Copyright© 2008 TSI Incorporated Multi-metric Sampling & Control Approaches Hazard Surveillance Monitoring Continue monitoring on a regular basis to ensure that ALARA conditions are maintained Reassess hazard surveillance plan periodically

98. Copyright© 2008 TSI Incorporated Summary Nanoparticle exposures are not clearly understood... mass and bulk chemistry may be less important than particle size, surface area, and surface chemistry (or activity) for nanostructured materials... Primary route of exposure is inhalation and lung deposition No established exposure metrics Filtration and engineering controls can be effective Use multi-metric approach to assess nanotechnology workplaces

99. Copyright© 2008 TSI Incorporated Gregory M. Olson, Jr., M.S. Product Manager Health and Safety Instruments TSI Incorporated USA (651) 490-4042 greg.olson@tsi.com

100. 0.0010.010.1110100 Particle Size Range (micrometers ) Inhalable (Total dust) TSP Respirable Thoracic Particle Size Range for Aerosol Instruments Photometer CPC-alcohol OPC Diffusion Charger 4 OPC: Optical Particle Counter CPC: Condensation Particle Counter SMPS: Scanning Mobility Particle Sizer CPC - Water SMPS Nanoparticle

101. Photometer OPCCPCSMPS Diffusion Charger Typical Size Range0.1 to 10 um0.3 to 20 um 0.0025 to 3.0 um 0.0025 to 1 um 0.02 to 0.1 um Measures Particle Mass (estimate)YesNo (Yes)No Typical Mass Concentration Range0.01 to 100 mg/m3 N/A Measures Particle SizeNoYesNoYesNo Detects Single ParticlesNoYes No Typical Number Concentration Range (Particles / cc) N/A2 x 10 6 1.5 x 10 10 1 x 10 8 N/A Upper Limit, number concentration (particles/cc) N/A70500,0001 x 10 8 N/A Measures Lung-Deposited Surface AreaNo No 1 Yes OPC = Optical Particle Counter CPC = Condensation Particle Counter SMPS = Scanning Mobility Particle Sizer 1 Surface area can be calculated using SPMS size distribution data. Aerosol Technology Comparisons

102. Application Comparison PhotometerOPCCPC Diffusion charger Indoor Air Quality - Conventional StudiesGood N/A Indoor Air Quality - Ultrafine Particle TrackingPoorN/AExcellentN/A Industrial Workplace Monitoring (Conventional)ExcellentPoorN/A Industrial Workplace Monitoring (Nano-Materials)Poor 1 /Good 2 Excellent 3 Outdoor Environmental MonitoringGood Excellent 3 Emissions MonitoringExcellentPoorGoodExcellent Respirator Fit Testing ExcellentPoorExcellentN/A Filter Testing Excellent N/A Clean Room MonitoringPoorExcellent N/A 1 Engineered nano particles of homogenous material less than 0.1 micron (100 nm) in diameter. 2 Agglomerated and aggregated nano particles greater than 0.1 microns (100 nm) diameter for photometers and greater than 0.3 microns (300nm) for OPC’s. 3 The Health effects of engineered nano particles and ultrafine particles below 0.1 micron (100 nm) in diameter are not completely understood. Research suggests these ultrafine particles may cause the greatest harm. There are currently no established exposure limits or governmental regulations specifically addressing ultrafine or nano particles exposure.

103. Copyright© 2008 TSI Incorporated References Nanotechnology Consensus Workplace Safety Guidelines –http://www.orc-dc.com/ National Nanotechnology Initiative (NNI) –http://www.nano.govhttp://www.nano.gov USEPA – “Nanotechnology White Paper” –http://www.epa.gov/osa/nanotech.htm NIOSH - “Approaches to Safe Nanotechnology” –www.cdc.gov/niosh/topics/nanotech/www.cdc.gov/niosh/topics/nanotech/ UK Health & Safety Executive – “Nanoparticles: Occupational Hygiene Review” –http://www.hse.gov.uk/RESEARCH/rrhtm/rr274.htmhttp://www.hse.gov.uk/RESEARCH/rrhtm/rr274.htm

104. Copyright© 2008 TSI Incorporated References National Nanotechnology Initiative (NNI) – US Gov’t. –Started in 2000 –Over $2 Billion spent on nanotechnology research since 2000 –$1 Billion allocated in FY 2006 –Predicting annual investment of $15 Billion per year by 2015 –Estimated that 50% of all products produced will be affected by nanotechnology within 10 years –Employment in nanotechnology is expected to grow to 2 million workers in next 10 years (US Department of Labor)

105. Copyright© 2008 TSI Incorporated References NIOSH – US –Taking a leadership role for nanotechnology and OH&S Research to Practice –Comprehensive nanotechnology website, including the “Nanoparticle Information Library” –“Approaches to Safe Nanotechnologies” Formulate guidance relevant to occupational health surveillance for nanotechnology Provide information that can be used to create appropriate occupational health surveillance to fit the needs of those involved with nanotechnology –Nanotechnology industry field studies –Research projects for nanopaticle toxicity

106. Copyright© 2008 TSI Incorporated References US Environmental Protection Agency –Traffic related particle exposure and risk assessment studies Mass, number concentration, size distribution, and surface area –Investigating whether or not nanomaterials should be classified as new chemicals (e.g., new CAS numbers) under TSCA, or will it be a classified as a “new use” for an existing chemical under TSCA ASTM, ANSI, and ISO –Working on consensus nomenclature terminology –ISO developed and released a document on information and guidance for monitoring for nanoparticle exposures in workplace atmospheres (2006)

107. Copyright© 2008 TSI Incorporated References Federal OSHA –Participating in NNI as a federal agency –Working with NIOSH as they conduct research –Future plans to develop guidance documents for nanotech companies Health and Safety Laboratory (HSL/HSE) – UK –Nanotechnology industry field studies –Workplace sampling and control strategies using control banding techniques

108. Copyright© 2008 TSI Incorporated References Woodrow Wilson Institute for Scholars –Project on Emerging Nanotechnologies, started 2005 –Dedicated to helping ensure that as nanotechnologies advance, 1.Possible risks are minimized 2.Public and consumer engagement remains strong 3.The potential benefits of these new technologies are realized –Philosophy of “responsible nanotechnology”

109. Copyright© 2008 TSI Incorporated References US Food and Drug Administration (FDA) –Regulates a wide range of products, including foods, cosmetics, drugs, devices, and veterinary products, which may utilize nanotechnology or contain nanomaterials –Formed a task force in August 2006 “Charged with determining regulatory approaches that encourage the continued development of innovative, safe and effective FDA-regulated products that use nanotechnology materials”

110. Copyright© 2008 TSI Incorporated References Research Work In chronic rat inhalation studies: –Inflammatory response induced by different particle types was found best correlated with surface area of particles retained in the alveolar space (Oberdörster, 1996) -Total surface area of retained particles was found best dose parameter for a correlation when the endpoint was lung tumor (Driscoll, 1996)

111. Copyright© 2008 TSI Incorporated References Research Work Nano-sized TiO 2 induce tumor in rats (Lee et al., 1985; Heinrich et al. 1995) –Chronic inhalation studies with nano-scale ( ~ 20 nm) and fine TiO2 (~ 250 nm) have shown that more than ten times lower inhaled concentrations of the aggregated ultrafine particles, compared with fine particles, are sufficient to produce the same amount of tumor-induction in rats Nano-sized Teflon fumes (count median particle size~18nm) result in severe pulmonary inflammation and hemorrhage in rats. No toxicity observed for 100 nm particles of same material (Oberdörster et al., 1995)

112. Copyright© 2008 TSI Incorporated References Research Work Carbon black nanoparticles cause mutations and cancer –Large enough dosage of nano-sized carbon black capable of causing pulmonary inflammation, particle overload, lung tumors and mutations in rats (Driscoll et al.,1996) –Similar results seen with nano-sized quartz and TiO2 (Driscoll et al., 1995; Heinrich et al., 1995)

113. Copyright© 2008 TSI Incorporated References Research Work Intratracheally induced carbon nanotubes cause pulmonary toxicity in mice and rats (Warheit et al., 2004; Lam et al., 2004) In hamsters, inhaled nanoparticles translocate into blood (Nemmar et al., 2001) In humans, inhaled nanoparticles translocate into blood thus influence cardiovascular endpoints directly (Nemmar et al., 2002)

114. Copyright© 2008 TSI Incorporated References 1.Donaldson, K. et al. Ultrafine (Nanometer) Particle Mediated Lung Injury, J. Aerosol Sci. 29(5/6):553-560. (1998) 2.Driscoll K.E. Role of inflammation in the development of rat lung tumors in response to chronic particle exposure. Inhal. Toxicol. 8 [suppl1: 85-98] (1996) 3.Driscoll K.E. et al. Pulmonary inflammatory, chemokine, and mutagenic responses in rats after subchronic inhalation of carbon-black. Toxicol. Appl. Pharmacol. 136, 372-380 (1996) 4.Driscoll K.E. et al. Characterizing mutagenesis in the hprt gene of rat alveolar epithelial-cells. Exp. Lung Res. 21, 941-956 (1995). 5.Heinrich et al. Chronic inhalation exposure of Wistar rats and two different strains of mice to diesel engine exhaust, carbon black, and titanium dioxide. Inhal. Toxicol. 7: 533-556 (1995) 6.Lam C.W. et al. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation, Toxicol. Sci. 77 (1): 126-134 (2004)Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation 7.Lee K.P. et al. Pulmonary response of rats exposed to titanium dioxide by inhalation for two years. Toxicol. Appl. Pharmacol. 79: 179-192 (1985) 8.Li N. et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage, Environ. Health Persp. 111:455-460 (2003) 9.Nemmar A. et al. Passage of inhaled particles into the blood circulation in humans, Circulation 105:411-414 (2002) 10.Nemmar A. et al. Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am J Respir Crit Care Med (164) 1665-1668 (2001)

115. Copyright© 2008 TSI Incorporated References 11. Oberdörster E. Manufactured nanomaterials (Fullerenes, C-60) induce oxidative stress in the brain of juvenile largemouth bass, Environ. Health Persp. 112 (10): 1058-1062 (2004)Manufactured nanomaterials (Fullerenes, C-60) induce oxidative stress in the brain of juvenile largemouth bass 12. Oberdörster G. Pulmonary effects of inhaled ultrafine particles. Int. Arch. Occup. Environ. Health 74:1-8 (2001) 13. Oberdörster, G. Significance of Particle Parameters in the Evaluation of Exposure-Dose- Response Relationships of Inhaled Particles, Particulate Sci. Technol. 14(2):135-151 (1996). 14. Oberdörster G. et al Association of particulate air pollution and acute mortality: involvement of ultrafine particles? Inhal. Toxicol. 7:111-124 (1995) 15. Penttinen P. et al. Number concentration and size of particles in urban air: effects on spirometric lung function in adult asthmatic subjects, Environ. Health Persp. 109:319-323 (2001) 16. Shanbhag, A. S. et al. Macrophage/Particle Interactions: Effect of Size, Composition and Surface Area, J. Biomed. Mat. Res. 28(1):81-90 (1994). 17. Utell M.J. et al. Acute health effects of ambient air pollution: the ultrafine particle hypothesis. J. Aerosol Med. 13:355-359 (2000). 18. Warheit D. B. et al. Comparative Pulmonary Toxicity Assessment of Single-wall Carbon Nanotubes in Rats, Toxicol. Sci. 77 (1): 117-125 (2004)