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Taking Stock of the OSH Challenges of Nanotechnology: 2000 - 2015


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The slide deck review the occupational health and safety hazards and risks associated with the scientific construct of nanotechnology. It provides a basic understanding of how nanotechnology is very important aspect in pulmonary disease and toxicity other potential medical disorders and the need for hierarchy of controls, medical surveillance, and epidemiology to reduce risk of exposure during manufacture and breakdown of products containing nano particles. The life cycle analysis provides perspectives into the types of workers who maybe exposed.

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Taking Stock of the OSH Challenges of Nanotechnology: 2000 - 2015

  1. 1. Taking Stock of the Occupational Safety and Health Challenges of Nanotechnology: 2000-2015 Schulte, PA, Hodson LL, Murashov V, Hoover MD, Zumwalde RD, Castranova V, Kuempel ED, Geraci CL, Roth GA, Stefaniak AB, Howard J National Institute for Occupational Safety and Health, USA Disclaimer: The findings and conclusions in this report are those of the author and do not necessarily represent the views of the National Institute for Occupational Safety and Health.
  2. 2. Presentation Objectives  Describe nanotechnology  Summarize the last 15 years of progress since the inception of commercial nanotechnology  Describe the efforts of the occupational safety and health community  Identify what still needs to be accomplished
  3. 3. A New Technology  Illustrates the challenges to society of a new technology  Beneficial properties  Potential hazard  What to do when information is lacking or uncertain
  4. 4. Workers  Workers generally the first people in society exposed to a new technology  Nanotechnology is not an exception  More than 1,000 nano-enabled products in commerce  Workers make and use them
  5. 5. Transport Commercial Academic Research Laboratories Warehousing/Maintenance Waste Handling Start Up/Scale Up Operations Transport Warehousing/Maintenance Manufacturing/Production Warehousing/Maintenance Transport Waste Handling Incorporation in Products Maintenance of Products Manipulation of Products Application of Products - Medical Delivery Disposal / End of Life Recycling
  6. 6. Nanotechnology  Development of materials at the atomic, molecular, or macromolecular levels with at least one dimension in the range of 1-100 nanometers  Creating and using structures, devices, and systems that have novel properties and functions because of their small and/or intermediate size  Ability to control or manipulate matter on the atomic scale
  7. 7. How little is “nano?” If the diameter of the Earth represented 1 meter… …1 nanometer would be the size of a dime.
  8. 8. Size of Nanoparticles Relative to Microorganisms and Cells Influenza virus 75-100 nm Tuberculosis bacteria 2,000 nm Red blood cells 8,000 nm
  9. 9. From Milli to Nano… “Nano” is less than 100 nm Welding fume 1.4 nm Single-walled carbon nanotubes 1 nm 10 nm 1 µm 10 µm100 nm Dust collected 5 miles from Mt. St. Helens 100 µm 1 mm Respirable crystalline silica Human Hair ~70 µm
  10. 10. Nanoparticles: Some Old, Some New Naturally occurring Man-made by-product Engineered Nanomaterials (ENM)
  11. 11. Not only smaller, but different • Lower melting point • Useful as catalyst • Different color • Different conductivity Same Properties 60 nm bar New Properties 30 nm bar
  12. 12. New Properties of Matter Based on Size and Surface Area ¼m 1nm 1m GOLD Each side = 1 meter Mass ≈ 43,000 lb Surface Area (SA) = 6 m2 ≈ 8 ft x 8 ft room Each side = 1/4 meter Mass ≈ 43,000 lb SA = 24 m2 Each side = 1 nanometer Mass ≈ 43,000 lb SA = 6 billion m2 ≈ 2500 miles2 Area of Delaware = 2490 miles2 ScalingcomparisoncourtesyofKristenKulinowski, Ph.D.
  13. 13. Why are nanomaterials potentially dangerous? 1 10 1,000 10,000100 Diameter (nm) 60 40 20 0 %SurfaceMolecules Source:Kelly[2009]
  14. 14. What could a “nanoparticle” be? Source:Dr.A. Maynard:WoodrowWilsonInternationalCenterfor Scholars
  15. 15. Nanoparticles: Many shapes, many chemistries Not all nanoparticles are the same
  16. 16. Same Composition—Different Shape Zinc oxide nanoparticles Source:MaterialsTodayJune2004.ZhongLinWang,GeorgiaInstituteof Technology
  17. 17. Parameters That Could Affect Nanoparticle Toxicity  Size  Shape  Composition  Solubility  Crystalline structure  Charge  Surface characteristic  Agglomeration  Impurities  Attached functional groups
  18. 18. Nanomaterial Science: Opening the 3rd Dimension of the Periodic Table ”Carbon just isn’t carbon anymore”
  19. 19. Why is nanotechnology of great interest?  Imparts useful properties to materials  Stronger  Lighter  More durable  Different melting temperatures  Enhanced electrical conductivity  More transistors on integrated chip  Enhanced chemical reactivity All of these point to the possibility of creating new and very powerfulapplications.
  20. 20. Applications of Nanotechnology Agriculture More efficient, targeted delivery of plant nutrients, pesticides Automotive Lighter, stronger, self-healing materials Biomedical Targeted therapeutics, enhanced detection, new structural materials Energy More efficient fuel cells, solar collectors Environmental New pollution control and remediation tools, sensors Food New safety sensors, food preservatives, nutrient additives Materials Self-cleaning glass, stain resistant, stronger materials, body armor Water New purification approaches
  21. 21. Early Nano-Enabled Consumer Products are on the Market Now [Gibbs 2006] Eddie Bauer Ruston Fit Nano- Care khakis Wilson Double Core tennis balls Kodak EasyShare LS633 camera Laufen Gallery washbasin with Wondergliss Smith & Nephew Acticoat 7 antimicrobial wound dressing Samsung Nano SilverSeal Refrigerator
  22. 22. Nanoparticulate fuel additives = 10% better fuel economy Nanocomposite body moldings = 20% lighter Nanoscale catalysts = 20% reduction in emissions Source:Gibbs[2006]
  23. 23. Picturesource:Burnham Institute Nanotechnology: Turning Fiction to Reality • Potential for: – Disease sensing – Diagnosis – Targeted therapy Cancer treatment (
  24. 24. Potential Revolution in Manufacturing • See and manipulate one atom at a time – building molecular tools – Using 35 Xenon atoms to spell out a logo • Copy nature – mimic self replication Source:IBMResearch
  25. 25. $0.0 $3.0 $3.5 2000 2020 (estimate TRILLIONSOFU.S.D. World US 2008 2015 (estimate) YEAR Adapted from Savolainen et al. (2013) $2.5 $2.0 $1.5 $1 Trillion $1.0 $0.5 $3 Trillion Market Incorporating Nanotechnology
  26. 26. Where We Were
  27. 27. Background for Concerns  Ultrafines in air pollution epidemiology  Health effects of diesel and welding fumes  Metal fume fever  Fumed silica—acute pulmonary inflammation  Nanogold travel from nasal mucosa to brain (DeLorenzo 1970)  Animal pulmonary studies of ultrafine zinc respiratory effects (Amdur et al. 1988)
  28. 28. National Science Foundation Workshop September 28-29, 2000 Futuristic safety concerns were envisioned early: “As currently envisioned, nano-mechanisms are likely to possess at least three properties that will generate novel safety and governance challenges: invisibility, micro-locomotion, and self-replication.” Page 214
  29. 29. “Presumably nanoparticles must be handled with the same care given to bio-organisms or radioactive substances.” (p34) (Swiss Re, 2004)
  30. 30. The Royal Society & Royal Academy of Engineering (2004) “There are uncertainties about this risk of nanoparticulates currently in production that need to be addressed immediately to safeguard workers and consumers and support regulatory decisions.”
  31. 31. The Royal Society & Royal Academy of Engineering (2004) “The evidence that we have reviewed suggests that manufactured nanoparticles and nanotubes are likely to be more toxic per unit mass than particles of the same chemical at larger size and will therefore present a greater hazard.”
  32. 32. The Royal Society & Royal Academy of Engineering (2004) “Free particles in the nanometer size range do raise health, environmental and safety concerns and their toxicology cannot be inferred from that of particles of the same chemical at larger size.” (p42)
  33. 33. Conceptual Timeline for Growth of Nanomaterial Products and Workforce NumberofProductsonEmerging NanotechnologyInventoryasSurrogatesfor VolumeofENMinCommerceandNumberof Workers 1959 Feynman’s Vision 1974 Taneguchi “Nanotech- nology” 1986 AFM Invented 1990 First Nanotech- nology Journal 2004 First NanOEH Conference (Buxton) 2010 2015 2020 272 1300 (est.) Initial calls for precautions 1814 (est.) Beginning of epidemiologic surveillance and assessment of precautionary guidance in use More specific precautionary guidance 3400
  34. 34. Buxton 2004 Minneapolis 2005 Taipei 2007 Helsinki 2009 Boston 2011 Nagoya 2013 Limpopo 2015 NanOEH Conferences
  35. 35. Hazard Identification “Is there reason to believe this could be harmful?” Risk Management “Develop procedures to minimize exposures.” ExposureAssessment “Will there be exposure in real- world conditions?” Risk Characterization “Is substance hazardous and will there be exposure?” Key Elements in Worker Protection
  36. 36. Hazard Identification “Is there reason to believe this could be harmful?” Risk Management “Develop procedures to minimize exposures.” ExposureAssessment “Will there be exposure in real- world conditions?” Risk Characterization “Is substance hazardous and will there be exposure?” Hazard Nanotoxicology What do we know? Are there “trends?” Key Elements in Worker Protection
  37. 37. Othersites (e.g.,muscle,placenta) Injection Inhalation IngestionDeposition Exposuremedia Uptake pathways Translocation &distribution Excretory pathways CNS PNS Lymph Bonemarrow Kidney Spleen Heart GItract Sweat/ exfoliation Urine Breastmilk Feces Source: Oberdörster, et al. [2005] Blood (platelets,monocytes, endothelialcells) AirDrugdelivery Food,waterAir,water,clothes Skin Respiratorytract Nasal Tracheo- bronchial Alveolar Liver Lymph Confirmedroutes Potentialroutes
  38. 38. 0.001 0.01 6% 12% 18% 24% Lungtumor proportion 0.1 1 Particle surface area dose (m2 /g lung) TiO 2 Carbon Black Talc Toner Coal Dust Diesel Eshaust particulate 30% 36% Lung Tumor Response is Associated with Particle Surface AreaDose of Fine Poorly Soluble Low Toxicity Particles (PSLT) or Ultrafine PSLT NIOSH (2011) Driscoll (1996) Oberdörster and Yu(1990)
  39. 39. Nel et al. (2006) Hierarchical Oxidative Stress Model
  40. 40. Nel et al. (2006) Possible Mechanisms by which Nanomaterials Interact with Biological Tissues
  41. 41. OECD Testing Program
  42. 42. Toxicology  Particle and fiber toxicity paradigms underpin the majority of toxicological investigations of ENMS  Confirmed that particle size is generally an important factor in toxicity but other physico-chemical factors may play major roles  Confirmed that nanoparticles could reach the alveoli and could enter the interstitium and blood stream
  43. 43. Toxicology  Pulmonary exposure to carbon nanotubes (CNTs) causes alveolar interstitial fibrosis, which develops rapidly and is persistent. Fibrotic potency appears related to the physicochemical properties of the CNT  Pulmonary exposure to nanoparticles can cause cardiovascular effects (alteration of heart rate and blood pressure, and microvascular dysfunction)
  44. 44. Toxicology  Multi-walled carbon nanotubes (MWCNTs) (Mitsui-7) are a promoter of lung cancer  Nanoparticles deposited in the lung can translocate to distal sites  Insoluble nanoparticles do not appear to rapidly cross intact skin or the GI tract  Nanoparticle penetration through intact skin is not likely but exposure to sensitizers and irritants still a concern
  45. 45. A single MWCNT penetrating from the subpleural tissue through the visceral pleura intothe pleural space of a mouse is shown in the FESEM image of 7 D (80 μg dose, 56 day post- aspiration). Mercer et al. Particle and Fibre Toxicology 2010 7:28 doi:10.1186/1743-8977-7-28
  46. 46. Two dividing control cells with normal centrosome morphology Courtesy Linda Sargent
  47. 47. Tripolar mitosis following exposure to .024 g/cm2 SWCNT
  48. 48. Four polar mitosis, nanotube association 24 hours following exposure to .024 g/cm2 SWCNT
  49. 49. Mitotic Spindle Damage 24 Hours Following Exposure to .024- 24 g/cm2 SWCNT
  50. 50. Mitotic Spindle Aberrations  Following acute and chronic exposure to carbon nanotubes  SWCNT enter the nucleus, are integrated with microtubules and centrosomes, are within the bridge separating dividing cells • Fragment the centrosome • Disrupt the mitotic spindle • Induce aneuploidy • Chemicals and fibers that induce centrosome damage, mitotic spindle damage and aneuploidy increase risk of cancer Linda Sargent, Ph.D. Molecular Genetics Laboratory, NIOSH
  51. 51. H. F.Krttg if@Md 001: 10.1(0l/a.rce,2014(•J;(i1 anosafety Research - A r c We on the Right Track ? Hamid F.Krug
  52. 52. Physical Hazards  Explosive potential  Flammability
  53. 53. Hazard Identification “Is there reason to believe this could be harmful?” Risk Management “Develop procedures to minimize exposures.” ExposureAssessment “Will there be exposure in real- world conditions?” Risk Characterization “Is substance hazardous and will there be exposure?” Exposure Can it be measured? Where is it occurring? Metric? Key Elements in Worker Protection
  54. 54. Multiple Metrics Can Be Used to Assess Exposure  Mass: Links to historical data; lacks sensitivity and specificity  Size distribution: More information not always easy, not specific  Number concentration: Fairly simple with monitors, not specific to particles, recent correlation of number in ambient air to biomarkers of coronary heart disease  Surface area: Some relevance based on toxicology and technology is available “Each one may be right”
  55. 55. Stefaniak et al. (2013)
  56. 56. .eport of JJn.&.estigation Reference Material® 8013 Gold Nanopa1ticles, Nominal 60 n1nDiameter This Reference Material (RM) is intended primarily to evaluate and qualify methodology and/or instrument performance related biomedical research. to the physical/dimensional characterization of nanoscale particles used in pre-clinical The RM may also be useful in the development and evaluation of in vitro assays designed to assess the biological response (e.g., cytotoxity, hemolysis) of nanomaterials, and for use in interlaborato 1y test comparisons. RM 8013 consists of nominally 5 mL of citrate-stabilized Au nanopanicles in an aqueous suspension, supplied in hermetical ly sealed pre-scored glass ampou les steri lized by gamma irradiation. A unit of RM8013 consists of two 5 mL ampoules. The suspension contains primary particles (monomers) and a small percentage of clusters of primary pa,ticlcs. Expiration of Value Assignment: The reference values for RM 8013 are valid, Vithin the measurement uncenainty specified, until 25 October 2018, provided the RM is handled and stored in accordance with the instructions given in th is rcpori (sec "Notice and Warni ng to lJscrs"). This report is nul l ified if the R M is damaged, conlamfoaled, or olherwise mod ified. Maintenance of RM: NIST ,viii monitor this RM over the period of its validity. Ifsubstantive technical changes occur thal affect lhe reference values before the expiration of this report, N lST will nolify lhe purchaser. Registration (see attached sheet or register online) will facilitate notificatfon.
  57. 57. International Attention Needed to Resolve  Consensus on prioritization of RM needs  Harmonization of terminology  Poorly defined or qualitative measurements and lack of metrological traceability  Better understanding of measurement process  When RMs are not available, clarify when test materials can be useful for hypothesis testing Stefaniak et al.(2013)
  58. 58. Exposure Assessment  Exposure to ENMs is:  Occurring, often episodic or task-based  Measurable  Many ENM emissions form agglomerates  Growing body of published exposure data  Importance of measuring background  International harmonization is occurring
  59. 59. Small Literature on Exposure  Relative newness of exposure scenarios  Uncertainties of what metric to use  Difficult getting entrance to worksites  Not a wide range of operations assessed  Little information on downstream users
  60. 60. (Maynard et al. 2004)
  61. 61. Exposure Scenarios Evaluated
  62. 62. Nanoparticle Emission Assessment Technique (NEAT) for the Identification and Measurement of Potential Inhalation Exposure to Engineered Nanomaterials — PartA and Part B: Results from 12 Field Studies M. Methner, L. Hodson, C. Geraci National Institute for Occupational Safety and Health (NIOSH), Nanotechnology Research Center, Cincinnati, Ohio Recent Published Summary of Field Exposure Assessments JournalofOccupationaland EnvironmentalHygieneMarch 2010
  63. 63. Graded Approach to Measurement • Step 1 – Particle counters and simple size analyzers to screen the area and process • Step 2 – Filter based samples for electron microscopy and elemental analysis, collected at Source • Step 3 – Filter based samples for electron microscopy and elemental analysis, collected at Personal Breathing Zone • Step 4 – Less portable aerosol sizing equipment
  64. 64. Brouwer (2010) Brouwer (2010)
  65. 65. Am,.Oc.:"up. llJg.,2015, VoL59, No.6,70$-i23 doi:10.1093iannl,yu•l'v020 Adv;in<eAe<esspubl i tion7ApriJ 2015 •-.c(,,;r,')l"!Q(')(t x-c :o, w..1,'CfhOO<lhFror-ccrhn Carbon Nanotube and Nanofiber Exposure Assessments:An Analysis of 14Site Visits Matthew M. Dahm' Mary K. Schubauer-Berigan1, DouglasE..Evans2, M. Eileen Birchi,Joseph E. Fernbackl and JamesA.Deddens' 1. lndcn:rywid<' S:udiM6un< or. NSorv('t.llMl r<'.Hurd Ev.afo11ti(lr,.u1d Pi<'ldStUdi<'S. N.AtiClll lMtitutt fo•Om1r.1tlon.1J 1i;:1fi'1rand Hc-..!tl.1; 1091)Tu'4"1"1.1A,,:, MS•R14,C111u111ut1,OH Sl:26,US.; l.Chnnlr.aJ Exposu:'t'ar.d MC'oitoting 8r.anch1UM.5ionofApplioo Rt.5Nrch ilndT«hnolcgy, N.nio:Wttu1itlt(' fo, Occll(Mtional Safl'ly nd I l<'.ulb, l090il1,culU1r1Axt:.Cincinn:11i,OJ I4116,t.:S1 't,',d]u,;IV wlmm c.u;rt':,pvr.Jt'nu::.l1uu J bt .:JJ1 sed.TI: +l·Sl3..fS8·7l36;(.u.: +151J·84J ·+t86;t:·rnll :1n,hhm(.llcdc.g,;,¥ Submlrrtd 3!it"ptcmbrr 2014;mi$00 23J.amury2015: t t ist'd v,milOnacc.-:p1td2.2Ftbru.uy201S, AJISTIUC.T Recent evidence l.l$ suggc...tedthepoten tial For widc·r,mging llcaJth effect couJdrcsuh fromupo· sure to crhon n:inotubcc; (CNT) and c:arbn nanc)6hcr (CNF). In rc poMe, the Nationa.l ln.tt1tutt for Om,p•tio<1al S..fel)' and He-1th (NIOSH) ,et•recomm<n d,Jcrposurc Limit (REL) fO<CNTand CNF: l 1;1,gm 'a$;i,n S·h limt weighted aver.1ge (TWA) ofclcmcntal carbon (EC) forrht spirable siu fr1<tion. The purpose o( thjs study w;1s to conduct 1 l l indtrywide exposure .i.SS-essment among US CNT and CNF users. Fourteen toul sites "';ere viiited to 1sseu exposott-s toC. n ( D sites) ,nd CNF (I site). Person,!breathing ion• (POZ) ,r.d aruiamples wm, col!tcted for both the inhd1ble ,nd r,spirable r.1ass concentrotion of EC, using NIOSH Method SO.JO. lnhabble P8Z s:timplcs were collcctc<I u ninesi:cs while !lt the remaining five s i t both respirablc and inhJ1:able, l'HZ samples were collected siJc b;·-:;idc. TraNmi.$sion electron microscvpy (TEA,() PBZ an<l area· pies were alsocollected at the inhakibk sh.c fraction and analyzed to quantify andsi1.c CNT an<l CNF agglomcntc :md fibrous cxpo5urcs.Rc-spira.blc EC PSZ concentrations ranged from 0.02 lo 2 94 pg m·>with agcomctnc mean (GM) of0.34 gm·)and an 8-h TV/A o(O.l6 pg m l. PBZ s.uuJ1lts ;a1thP inhabblcs1zc fraction for EC ranged (rom0.01 to 79.!,7 F&m >witha G·lo( 111t•gm..J. PBZsarnpls :amlr«d byTEM )hawed co11cc;:1trations ranging from 0.0001lo 1.613CNT or CNF structm'S cml with GM o(0.008 and an $-h TWA concentration of 0.003.The most comnum Ct-:T n1ct1.l.l'e site$,re found tobe hrgcragglomcrates in the2-Slllll nngc ;iswdlas agslomcr.,tcs >S 1,m.Ast:.tisti· c:illy signifkant correlation was ol>Krvcd bctwc"-n the lnh.a ablc samples for the ma s of EC an<lstru<· turc cou:n,br TEM (Sporman p•0 . 3 , . f' <0.000 1).O,,crnU, EC PBZand area rv.:snmplC!ii w·.-e bc:lowthe NIOSH REL {96% wen: -<J g m >at thercspirabl,c iit'e fraction), while 3 0 of the inhal,1ble P.82ECsampJeswerefound to be >l pgm·l. Untilmore information is known abuut healthdT'.1.lS .U50('i.m:d with larger agglomt"ratcs. 11seems prurlcnl to :.11s::,t';SSworker cxpo:.urc tomrborne CNT anJ CNFmaterialsby monitoring £C:itboth th, rl'Spir.ible an(I mhafable sin fr.actions. Concurrent TF.M sJmplcs should be,oJlcc-wd toconfirm the prcsen<e ofCNT .ind CNF. l(EYWOROS : carbo1, 1ianofibc1-s;(.l1bon o..notub..-s;cxp(});mc a :.cs:,u1cnt;no1nu11,.1 1.i1!s
  66. 66. (Bekker et al. 2015)
  67. 67. ISSN 0 0 0 3 -4S 7S (.:>Al"-T> ISSN 147;;;-3162(ONLINE) The Annals Of .''.l JTCRN:TIONiL SCll'.:NTII'JC J>URNAL 01 IHI- C A U A I I O I AND CON IKOL O r WORK-RE..ATED JLL-HE.'U,TH Occupational Hygiene Volume S+ Number 6 August 2010
  68. 68. Images from field air samples. Complex nanomaterial shapes in a complex matrix.
  69. 69. Exposure Data Conclusions/Challenges  Exposure metrics and approaches need to be harmonized  Mass is still the primary metric  Mass and particle number might be a good association  Direct-reading approaches have a place  Agglomeration is a reality  Confirmatory methods are needed
  70. 70. Hazard Identification “Is there reason to believe this could be harmful?” Risk Management “Develop procedures to minimize exposures.” ExposureAssessment “Will there be exposure in real- world conditions?” Risk Characterization “Is substance hazardous and will there be exposure?” Risk Hazard x Exposure Key Elements in Worker Protection
  71. 71. Quantitative Risk Assessment (QRA)  The estimation of the severity and likelihood of adverse responses associated with exposure to a hazardous agent  Can be used to estimate the exposure concentrations that are likely—or unlikely—to cause adverse health effects in workers  Two sources for prediction  Animal data  Human (epidemiologic) data
  72. 72. Assume equal response to equivalent dose Rat Dose-response model (particle surface area dose in lungs) Calculate lung tissue benchmark dose Working lifetime exposure concentration* Equivalent tissue dose Estimated lung deposition fraction Recommended exposure limit Technical feasibility of measurement and control Extrapolate (Adjust for species differences in lung surface area) *Comparerat-basedriskestimateswithconfidenceintervalsfromhuman studies Quantitative Risk Assessment in Developing Recommended Exposure Limits for Nanoparticles Human
  73. 73.
  74. 74. Risk Assessment: Ultrafine (Nano) TiO2 • NIOSH draft recommended exposure limits (RELs) – 2.4 mg/m3 fine TiO2 – 0.3 mg/m3 ultrafine TiO2 – Reflects greater inflammation & tumor risk of ultrafine on mass basis • Key message: The OEL for a material in its “large” form may not be appropriate for the nano form.
  75. 75.
  76. 76. Risk Assessment: Carbon Nanotubes • Use data from Ma-Hock (2009) – Wistar rats exposed 0.1, 0.5, 2.5 mg/m3 multiwall carbon nanotubes (6 hr/day, 5 days/wk, 15 wks) • OEL for a risk of pulmonary fibrosis at less than 1/1000 over a working lifetime • Likely to be less than the limit of quantitation for organic carbon i.e., < 7 g/m3
  77. 77. Nadonal tnsdnoteforPublicHealth and thennvironment ltitusuyo{Hea1ck,Wel(arew,dSpon Grouping nanomaterials Astrategytowards groupingandread-across
  78. 78. Stone et al. (2014)
  79. 79. Hazard Identification “Is there reason to believe this could be harmful?” Risk Management “Develop procedures to minimize exposures.” ExposureAssessment “Will there be exposure in real- world conditions?” Risk Characterization “Is substance hazardous and will there be exposure?” Recognize and Manage Risk What works? What has been used? What can be reapplied? Key Elements in Worker Protection
  80. 80. Risk Management  Follow hierarchy of controls  Establish OELs  Utilize Prevention through Design  Institute medical surveillance  Conduct epidemiological studies
  81. 81. Societal Level  Ethical principles  Workers have a right to safe and healthy workplace and a right to know hazards  Employers have responsibility to provide safe and healthy workplaces  Uncertainty and precaution
  82. 82. When hazard is uncertain, precaution should be high Schulte & Salamanca-Buentello [2007] Hazard Identification Risk Assessment and Characterization More Precautionary Risk Communication and Management Less Precautionary Less Certain More Certain
  83. 83. Hierarchy of Controls
  84. 84. Pieces in the Big Picture
  85. 85. Conventional controls should work Exhaust Ventilation Capture Inertia Dominants Diffusion Dominates No Capture Air Stream About 1 nm Most Fine Dusts Micro Scale 200 to 300 nm
  86. 86. Controls have been applied in research and pilot development work
  87. 87. Air Air Concentration m air concentration Concentration "With" due to use ofLEV "Without" LEV LEV ('Yo)* Manganese (Mn) Reactor c1eanout 3619 150 96 Silver (Ag) Reactor cleanout 6667 L714 74 Iron (Fe) Reactor clcanoul 714 41 94 Background (Reactor area Prior to cleanout) ND ND NIA
  88. 88. Manufacturing Containment Courtesyof NanocompTechnologies, Inc.
  89. 89. Manufacturing Containment Courtesyof NanocompTechnologies, Inc.
  90. 90. Filtration Performance of an Example NIOSH Approved N95 Filtering Facepiece Respirator n=5; error bars represent standard deviations TSI 3160; Flow rate 85 L/min
  91. 91. Task Duration Quantity milligrams kilograms 15 minutes 8 hours slurry/suspension highlydisperseagglomerated Physical Form Factors Influencing Control Selection Engineered Local Exhaust Ventilation Closed Systems Occupational Health Hazard mild / reversible severe / irreversible Courtesy Donna Heidel, formerly atNIOSH
  92. 92. Exposure Management Control Banding—Concept Low Dustiness Medium Dustiness High Dustiness Hazard Group A Small 1 1 1 Medium 1 1 2 Large 1 2 2 Hazard Group B Small 1 1 1 Medium 1 2 2 Large 1 3 3 Hazard Group C Small 1 1 2 Medium 2 3 3 Large 2 4 4 Hazard Group D Small 2 2 3 Medium 3 4 4 Large 3 4 4 Hazard Group E For all hazard group E substances, choose control approach 4 Parameters Amount Used Dustiness Hazard Group (R-Phrase) ilo.orgSource:T.J.Lentz, NIOSH ControlApproach 1. General Ventilation 2. Engineering Control 3. Containment 4. SpecialistAdvice
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  94. 94. Establishment of OELs  No officially promulgated OELs  16 “unofficial” proposed OELs
  95. 95. Pauluhn 4 5 3 0 1 5 5000 MWCNT 2.5 µg/m3 CNT & CNF 7 µg/m3 MWCNT 30 µg/m3* OELs for Carbon Nanotubes OSHA Carbon black PEL 3500 Baytubes MWCNT 50 µg/m3 OSHA Graphite PEL(respirable) *Period-limited (15-yr) Nanocyl NIOSH Japan BSI—0.01 f/ml [benchmark exposure limit-BEL] high aspect ratio nanomaterials –established at 1/10 asbestos OEL OEL(µg/m3)
  96. 96. Anticipatory international consensus standards established at the introductory stage of nanotechnology could potentially hinder the “race to the bottom” where nations compete for jobs by lowering national workplace safety standards. Murashov et al. [2012]
  97. 97. Prevention through Design (PtD) Design molecule Nanotechnology Design process
  98. 98. Functionality Health Safety
  99. 99. Parameters that could affect nanoparticle toxicity Size Shape Composition Solubility Crystalline structure Charge Surface characteristic Agglomeration Impurities Attached functional groups
  100. 100. Occupational Health Surveillance GROUP Medical Surveillance INDIVIDUAL Medical Screening
  101. 101. Issues in Medical Surveillance for Workers in Nanotechnology NeedsAssessment Is there a hazard? Is there exposure? What is the risk? Decisions on Medical Surveillance Medical Screening Systematic Data Collection Exposure Registry Hazard Surveillance
  102. 102. Medical Surveillance  Insufficient scientific and medical evidence to recommend the specific medical screening of workers potentially exposed to engineered nanoparticles  If nanoparticles are composed of chemical or bulk material, for which medical screening recommendations exist, these would apply to nanomaterial workers  Analysis of change in frequency of adverse effects in worker groups is warranted  Exposure registries may be useful in some situations
  103. 103.  Value of medical screening  Lack of specific health end point  Hazard surveillance  Potential for exposure registry Interim Guidance Issued by NIOSH
  104. 104. Medical Screening Health Council of the Netherlands [2012]  No screening programmes are currently available, anywhere in the world, for individuals who work with nanoparticles
  105. 105. NIOSH Recommendations for Surveillance among Nano-workers: Specific Cases  Ultrafine titanium dioxide  Current Intelligence Bulletin (CIB) recommends following general guidance for nanomaterials (NIOSH 2009) Difference based on toxicological hazard (pulmonary fibrosis for CNT) at occupationally relevant exposure levels  Carbon nanotubes & nanofibers  CIB recommends employers consider implementing medical monitoring for workers exposed to CNT or CNF at levels above the recommended exposure limit  Baseline evaluation, spirometry, chest x-rays, others
  106. 106. Epidemiology  Few epidemiological studies have been conducted  Difficult to identify workers exposed to specific nanomaterials  Difficult to form cohorts  Cross-sectional biomarkers studies have been initiated  Most biomarkers have not be validated for their positive predictive value
  107. 107. etc. Sector:Food Sector:Electronics Sector:Medicine Sector:Energy Sector:Materials Workplaces NanomaterialType Carbon Nanotubes Graphene Metal Oxides Dendrimers Fullerenes Metal Nanomaterials Nanowires Nanostructured Metals Nanoporous Materials Nanoscale Encapsulation Laboratory Research Start up/Pilot Manufacturing Production Disposal
  108. 108. RTI Contract Report [2014] Flowchart of the uses of iron oxide nanoparticles within key industries
  109. 109. First Wave of Epidemiological Studies of Nanomaterials Workers 16 Studies Completed or Issued Abstracts  11 cross-sectional  5 longitudinal (panel studies)  Generally used biomarkers as dependent variables  Generally had limited exposure assessment  Small sample size  Exposures:  Carbon nanotubes  Nanosilver  Titanium dioxide  Iron oxide  Calcium carbonate  Nanogold  Carbon black
  110. 110. ? ? ? ? Estimated number of workers actually exposed to engineered nanoparticles 2000 2010 2015 2025 1000 10,000 100,000 1,000,000 10,000,000 NumberofWorkersExposed Dilemmas in Identifying Workers Exposed to Engineered Nanoparticles 1959 Feynman’s vision 1990’s Beginning of commercialization Source: Schulte[2009] Global employment estimated USA employment estimated [Roco & Bainbridge, 2005]
  111. 111. Conceptual Illustration of a Nanomaterials Worker Health Study Continued exposure assessment • Register workers • Characterize exposure • Baseline health assessment • Epidemiologic investigations • Specimen banking Prospective studies of sub-cohorts Biomarker cross-sectional (CS) studies CS CS Periodic medical monitoring Timeline Components
  112. 112. Registry of NOAA exposure CNT exposed workers cohort Specific TiO2 exposed workers cohort Worker inclusion questionnaire Prevalence & incidence morbidity cross-sectional & panelstudies Mortality data Generalist CMR job-exposure matrices (JEM) Generalist PM & fibers JEM (MatPUF, Ev@lutil) Research & expertise institutions: INRS, INERIS, INSERM, CEA, … Data on associated exposures and potential confounders data Health care and drug prescription database (SNIIRAM) Hospital discharge summary (PMSI) International collaborative studies Perimeter of the integrated system for epi-surveillance and research on NOAA InVS abilities in data gathering andabstracting Collaborative actions Measurement of ENM exposure & biomarker studies Epi-surveillance & descriptive statistics General prospective follow-up Causes of death register (CépiDC) Declaration R-nano Worker follow-up questionnaire Guseva Canu (2010)
  113. 113. Potential Objectives for Future Epidemiological Research  Legacy nanomaterials  Carbon black  Nano-titanium dioxide  Harmonized global approach to epidemiologic studies of engineered nanomaterials (ENMs)  Prospective studies
  114. 114. Riediker et al. 2012
  115. 115. J N:inopart Res (2014) 16:2302 DOI 10.1007/s11051-014-2302-9 REVlEV Biomarkers of nanomaterial exposure and effect: current status Jvo lavicoli ·Veruscka Leso ·Mau1izio Manno · Pa.ul A. Schulte Received: 30 July 201:3/Accepted: 27 January 2011 /Published online: 22 februa.ry 201'1 © Springer Science+Business fedia Dordreht 2014 Abstract Recent advances in nanoteclmology have induced a prnduction rutd application of nanomaterials. As a consequem.:e, an increasing num her of worker.s are expected to undergo exposure to the&c xenobiotics, while the possible hazards to their health remain nol being rnmpkldy understood. InLhis context, hiological mon itoring may play a key rolenot only to identify potential hazards from .:'Indto evaluate but also metallic content in blood or urine or other biological materials, whereas spc:cific mole;culc.smay becarefully evaluated in Lurgel tissues as possible biomarkers oi hiologically effective dose. Oxiclat.ive stres.s hiomark ers, such as 8-hydroxy-dc0xy-guruto&ine, gcnotoxicity biomurkers, andinllmrumrlory responseindic.:alors may also he useful, although not speci fic, as hiomarkers of nanomaterial early adverse health effects. Finally, polcnlial from
  116. 116. Exposure Disease
  117. 117. Source ----...__...........--..-......-- "E x p o s u r e ) Internal dose;> . / Amb ient environment
  118. 118. Rothman et al. [2012]
  119. 119. Lung Blood MWCNT Lung RXN Blood Produced Complex Signal Minimal transport of MWCNT into blood MWCNT act in lung and induce “serome” response. MWCNT Modest Transport Courtesy of Andrew Ottens, VCU; Matthew Campen, UNM; Aaron Erdely, NIOSH; Unpublished Findings
  120. 120. 10ug MWCN T 40ug MWCN T 10ug MWCNT 40ug MWCNT 2,507 Responsive Factors, Kruskal-Wallis; FDR 5% Factors on/off with MWCNT No dose effect Log(2) Log(2) Courtesy of Andrew Ottens, VCU; Matthew Campen, UNM; Aaron Erdely, NIOSH; Unpublished Findings
  121. 121. To what extent are nanomaterial workers being protected?
  122. 122. Adherence to Precautionary Guidance
  123. 123. Examples of Government Guidance Documents NIOSH IRSST BAuA UK HSE METI JNIOSH Safe Work Australia IRSST, Institut de Recherche Robert-Sauvé en Santé et en Sécuritédu Travail BAuA, (German) Federal Institute for Occupational Safety and Health HSE, Health and Safety Executive METI, Ministry of Economy, Trade and Industry (Japan) JNIOSH, Japanese National Institute for Occupational Safety and Health
  124. 124. Is risk management guidance being followed? What is known? What is not known?  Guidance has been followed in some cases  The extent of awareness and adherence with exposure controls and precautionary guidance needs to be assessed  The effectiveness of adherence with guidance needs to be assessed – what works and what doesn’t work  Additional targeting of guidance may be needed for specific workplaces and workforces where adherence is low
  125. 125. Advanced Manufacturing
  126. 126. Image source: United States Government Accountability Office, 2015.
  127. 127. Fused Filament Fabrication Operation: 1. Thermoplastic heated in print head. 2. Print head scans platform, deposits plastic. 3. Thermoplastic cools and solidifies. 4. Platform lowers or print head raises. Subsequent layers add height. KeyAspects: • Inexpensive (< $1,000) • Poor resolution • Thermoplastics only; additives (including nanomaterials) are being explored • Most common consumer 3D printing technology Image source: Eva Wolf,2012.
  128. 128. Occupational Safety and Health Concerns • Materials – Nanomaterials (powders, additives) – Heavy metals – Organic chemicals (polymers/binders) • Energy – Thermal sources – Lasers & electron beams • Emissions – Releases during operation – Cleanliness of products – Machine maintenance • IH Practices – Return of “cottage industry” – New material testing
  129. 129. Advanced Nanomaterials
  130. 130. Generations of Nanomaterials  1st generation  2nd generation  3rd generation  4th generation Passive nanomaterials Active nanomaterials Integrated system Nano systems
  131. 131. The Long Run Trajectory in nanotechnology Development  Shift from passive to active nanostructures [Subramanian et al. 2010]  An active nanostructure—“changes or evolves its state during operation” [NSF 2006]  Structure, state, and/or properties change during their use  “…Build stuff that does stuff” [Smalley quoted in Maynard 2009]
  132. 132. .htm Molecular Car
  133. 133. 5 Types of Active Nanomaterials 1. Remote actuated active nanostructure: Nanotechnology whose active principle is remotely activated or sensed. 2. Environmentally responsive active nanostructure: Nanotechnology that is sensitive to stimuli like pH, temperature, light, oxidation-reduction, certain chemicals etc. 3. Miniaturized active nanostructure: Nanotechnology which is a conceptual scaling down of larger devices and technologies to the nanoscale.
  134. 134. 5 Types of Active Nanomaterials (cont’d) 4. Hybrid active nanostructures: Nanotechnology that involves uncommon combinations (biotic- abiotic, organic-inorganic) of materials. 5. Transforming active nanostructures: Nanotechnology that changes irreversibly during some stage of its use or life.
  135. 135. Extrinsic Properties  Beginning to create materials that are unique  Have properties never before available to scientists
  136. 136. Extrinsic Properties (cont’d)  Could have human health and environmental risks never before encountered  Functionality associated with carefully engineered collection of chemicals and components (what it does)  Becomes more than just the sum of its parts
  137. 137. Extrinsic Properties (cont’d)  We are moving to a world where knowing what something is made of is no guarantee of how to handle it safely  When does engineering a substance at nanoscale lead to deviation in its conventionally established risk profile?
  138. 138. Most regulations focus on the intrinsic properties of materials instead of extrinsic
  139. 139. Increasingly Sophisticated Nanomaterials  Since materials change during their use successive changes may have unforeseen and unintended consequences  Challenges to re-think exposure scenarios  Could have unique risk profiles  Could have the potential to stress and force change in existing regulatory frameworks  How do we anticipate the stresses?
  140. 140. leturnal of Oc.cupatiett!i.·ll ani E,i·.,•ironmen,.a,,9: D12 D:22 ISSN: 1545-9624 print J1545-9632 onlioc DOT: 10.1080il 545%24.2012.6ll2 l i Commentary Progression of Occupational Risk Management with Advances in Nanomaterials Vladimir Murashov, Paul Schulte, and John Howard National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Washington, D.C. INTRODUCTION anotedrnulogy h;1sbt',cm Louted as a lransfonualiv tt'.(;h Nnology lhal wou ld encompass a broad rnngc of protlucls am] applicalion are,as ancl improvt', urnny aspe,cls of human life. As rnmolcdrnolugy urntures, lhc crnupkxiLy of iLs main product. nano111aterials. increa!'-e. Four generations of nano mat.erial!- have heen rletinecl by a Worlcl Technology Evalua tion Center (WTEC) Report,('J namely, passive nanomaterials, active nanomaterials. integrated nanosystems, and molecular nanosystems. According to the Woodrow Wilson Nanotech nology Consumer Product Inventory, V• there are over 1000 self-identified nano-enabled consumer products on the market. Mosl of Lht'.se, proclui.;ls art bai:;e,tl on fi.ri:;l-gt',nt',ralion "passive'. nanomaterials." Limited understanding of passive nanoma krial has challcng,xl trndilional occupalional heallh ri:-k asscssrn(.111.arnl rnanagclllcnl. approaches. New approaches including rmg,gest.ions for rhe development and adopt.ion of proaeLiw approaches l.o nanolcchnology risk assesslllcnL and control have heen propoerl(:;, I.Jnl ike reactive approache!-, where risk control measures are applied to well characte1ized hazards, proactive or anticipatory approaches aim at minimiz- .'.'Ind nanosystems m.'ly present more compkx health risks th.·m p;1ssivc nanomal,:rials,(10> risk asi:;,:ss1m:nt i:;tudies i:;pccifi.illy directed at. these mater ials in the workplace need to he funded anrlconducted. ltwas recognized tlutnanotechnology and advanced nano materia Jr; raise isr;uer; that are more compleir anrl far-reaching than many other iimovations.'1 1 '•111erefore, approaches to the overall risk governance of emerging tedmologies, which can be defined as a comprehensive oversight framework encom passing re.gulaLory and non-rt',gulalory approache,i:; lo rii:;k as sessment and risk management, may need to be validated and rnotlified as appropriaLe,. Inlhis Cmmn..:nlary, soui..:of lhc compkx. issu,:spertaining to the occupational safety anrl health risk i111plicat.io11sofactivc ials anrl nanoyst.ems are explored. NANOMATERIAL COMPLEXITY Generations of Nanomaterials Aclvancemc".nL of rnnoltdnmlogy can bt eharaclc" by a number of factors, such as the narnre of the manufacturing proc,:sscs used Lopnx.lucc nanolilaLeriali:;, bn:.aclLhofnanoL,:ch-
  141. 141. Future Needs • More standardized toxicological studies with better particle characterization • Develop refined metrological approaches • More collection, collation, publication and meta-analysis of exposure data • More attention to toxicity and exposure to advanced ENMs • Further development of categorical approaches for risk assessment and management • Refined medical surveillance guidance • More epidemiologic studies • Global assessment of compliance to risk management guidance
  142. 142. Thank You!