Occupational Medicine
Implications of Exposure To
Engineered Nanoscale
Particulate Matter
American Chemical So...
THE
MOLECULAR
FOUNDRY
Nanoscale Science Research
Center and User Facility
Free Engineered Nanoscale
Particulate Matter–“Nanoparticles”
• Not firmly attached to a surface
• Not part of a ...
Primarily Talking About
Inorganic Nanoparticles
Bucky Ball (C60) Nanoflowers Single Wall Carbon...
Goals of Occupational Medicine
1.  Prevent injury and illness
—  Workplace (exposure) monitoring
•  Comparison ...
Why Are We Concerned?
Potential for Novel Toxicity
•  Properties of nanoscale materials may be
fundamentally different from bulk
materia...
Particle Size Dependent Occupational Toxicity
•  Free crystalline silica
—  ost toxic when <10 µm
M
• ...
Nanoparticles Have Been
Produced Commercially for Decades
•  arbon black
C
•  umed silica
F
• ron oxide
I
•  itaniu...
Ambient Ultrafines Are Associated With
Worsening of Disease
•  Ambient fines and ultrafines are associated ...
Nanoparticle Surface Area is Huge!
1 8
...
Surface Area May Be Critical Metric
•  Toxicity of ultrafine
TiO2 appears much
higher than fine TiO2
...
Nanotubes Look A Lot Like
Chrysotile Asbestos
Two simila...
Fiber Toxicology: Dose,
Dimension & Durability
•  Key factors contributing to
toxicity:
• Diameter < 1000...
Distribution Across Anatomical Barriers
•  Nanoparticles may go
where other particles Sally Tinkle, NIEHS
can...
Cardiovascular Toxicity of CNTs
Instilled In The Respiratory Tract
•  Li Zheng of NIOSH,
March 2007
- Intrap...
The Devil Is In The Details!
• Factors shown to influence CNT toxicity
•  Dose
•  SWCNT vs. MWCNT
•  Length/aspect rat...
Pulmonary Toxicity:
All Published Instillation/Aspiration Studies
Year Author Species Granuloma Infla...
Inhalation Studies
• No good published
CNT inhalation studies
to date!
• ...
What is the Real Occupational
Exposure Potential?
Air sampling
...
CNT Clumps In Air Sample
Raw nanotubes consist mostly
of clumps and bundles of
...
Nanotube Exposure Summary
Highest
Nanotube mass concentr...
Are CNTs Just Graphite Toxicologically?
Redacted!
•  ctual MSDS for
...
Anna Shvedova from NIOSH, 2005
“…if workers are exposed to respirable SWCNT
particles at the current PEL (for graphite
p...
Where Do We Stand for Nanoparticles?
1.  Prevent injury and illness
—  Workplace (exposure) monitoring
•  N...
Prudent Approach
1.  Prevent injury and illness
—  Workplace (exposure) monitoring
•  Use simple screening t...
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Nano Occ Med

Published on: Mar 3, 2016
Published in: Technology      Business      
Source: www.slideshare.net


Transcripts - Nano Occ Med

  • 1. Occupational Medicine Implications of Exposure To Engineered Nanoscale Particulate Matter American Chemical Society Meeting Safety in Nanotechnology Research Rick Kelly, MS, CIH Lawrence Berkeley National Laboratory
  • 2. THE MOLECULAR FOUNDRY Nanoscale Science Research Center and User Facility
  • 3. Free Engineered Nanoscale Particulate Matter–“Nanoparticles” • Not firmly attached to a surface • Not part of a bigger item (e.g., microchip, cell wall) •  an result in exposure via C inhalation, skin absorption or ingestion (or other nanospecific routes of exposure!)
  • 4. Primarily Talking About Inorganic Nanoparticles Bucky Ball (C60) Nanoflowers Single Wall Carbon Nanotube Silica Whiskers Rods, Wires, Shapes Quantum Nanodots
  • 5. Goals of Occupational Medicine 1.  Prevent injury and illness —  Workplace (exposure) monitoring •  Comparison to safe exposure limits —  Engineered, administrative and personal protective controls •  Ventilation, respirators, gloves, training etc. 2.  Detect early signs & symptoms of injury or illness —  Medical surveillance 3.  Intervene in disease process —  Removal from exposure —  Treatment
  • 6. Why Are We Concerned?
  • 7. Potential for Novel Toxicity •  Properties of nanoscale materials may be fundamentally different from bulk materials of same composition •  Among the new properties of nanoscale materials may be: —  ew toxicological N properties not seen in bulk material
  • 8. Particle Size Dependent Occupational Toxicity •  Free crystalline silica —  ost toxic when <10 µm M •  Alveolar deposition •  Probably surface area effect as well http://www4.umdnj.edu/cswaweb/rad_teach/silicosis.html
  • 9. Nanoparticles Have Been Produced Commercially for Decades •  arbon black C •  umed silica F • ron oxide I •  itanium dioxide T •  luminum oxide A •  irconium oxide Z •  sbestos A
  • 10. Ambient Ultrafines Are Associated With Worsening of Disease •  Ambient fines and ultrafines are associated with increased cardiovascular and respiratory events, including death, in susceptible populations Particulate Air Pollution and Risk of ST-Segment Depression During Repeated Submaximal Exercise Tests Among Subjects With Coronary Heart Disease Juha Pekkanen et al 2002 Reflects myocardial ischemia
  • 11. Nanoparticle Surface Area is Huge! 1 8 •  1/2 the size = 2x the surface area and 23 = 8x the number or particles •  Approaches 100% of atoms on the surface 64 512 •  ww.gly.uga.edu/railsback/1121WeatheringArea.jpeg w
  • 12. Surface Area May Be Critical Metric •  Toxicity of ultrafine TiO2 appears much higher than fine TiO2 per unit mass •  Toxicity is equivalent when surface area is the exposure metric Measured polymorphonuclear neutrophils in lung lavage fluid, an index of inflammation Oberdorster, Int Arch Occup Environ Health. 2001 Jan; 74(1):1-8.
  • 13. Nanotubes Look A Lot Like Chrysotile Asbestos Two similar appearing nanofibers •  Chrysotile asbestos (left) •  Multiwall carbon nanotube (above) Similar toxicity? Asbestos and www.gly.uga.edu/schroeder/geol6550/CM07.html macrophage
  • 14. Fiber Toxicology: Dose, Dimension & Durability •  Key factors contributing to toxicity: • Diameter < 1000 nm • Length >5,000 nm: • High biopersistance • Poor pulmonary clearance • Carbon nanotubes can fall into this size range • 80% of raw CNTs retained in lung at 60 days
  • 15. Distribution Across Anatomical Barriers •  Nanoparticles may go where other particles Sally Tinkle, NIEHS can not! — Through intact skin — Through the GI epithelium — Through the respiratory tract epithelium — Through the bloodstream — Up along nerve axons from the nose to brain — Across the placenta — Through the blood-brain barrier?
  • 16. Cardiovascular Toxicity of CNTs Instilled In The Respiratory Tract •  Li Zheng of NIOSH, March 2007 - Intrapharyngeal dosing of SWCNT in mice resulted in oxidative stress in aorta and heart tissue and damaged mtDNA in aorta - Accelerated atherosclerosis
  • 17. The Devil Is In The Details! • Factors shown to influence CNT toxicity •  Dose •  SWCNT vs. MWCNT •  Length/aspect ratio •  Manufacturing method (CVD, HIPCO, laser ablation, carbon arc) •  Catalyst residue (Ni, Y, Co, Fe) •  Degree of aggregation and methods of dispersion •  Oxidation •  Functionalization (increase or decrease toxicity) •  Species, dosing method, cell type •  CNTs may disrupt a number of standard assays of cell viability, stress and function, giving false positive or negative results
  • 18. Pulmonary Toxicity: All Published Instillation/Aspiration Studies Year Author Species Granuloma Inflamm Diffuse Fibrosis 2001 Huczko Guinea pig – No – 2004 Warheit Rat Yesa Yesb No 2004 Lam Rat Yes Yes – 2005 Muller Rat Yes Yes Yes 2005 Huczko Guinea pig Yes Yes Yes (Grubek- Jaworska) 2005 Shvedova Mouse Yes Yesb Yesd 2006 Mangum Rats Yes No Yes 2006 Carrero Mice Yes Yes – Sanchez 2007 Shvedova Mice Yes Yes Yes A = non-uniform, b = transient, c = by choking, d = progressive
  • 19. Inhalation Studies • No good published CNT inhalation studies to date! • NIOSH has completed an inhalation study but has not released the results, pending publication
  • 20. What is the Real Occupational Exposure Potential? Air sampling when handling raw carbon nanotubes Maynard, 2004 Raw single walled carbon nanotube material HiPCO Process
  • 21. CNT Clumps In Air Sample Raw nanotubes consist mostly of clumps and bundles of nanotubes on the micro scale, very few free nanoscale structures
  • 22. Nanotube Exposure Summary Highest Nanotube mass concentration estimated from metals analysis is relatively low So what is an appropriate exposure limit for CNTs?
  • 23. Are CNTs Just Graphite Toxicologically? Redacted! •  ctual MSDS for A CNTs (May, 2007) •  uoted PEL is for Q graphite!
  • 24. Anna Shvedova from NIOSH, 2005 “…if workers are exposed to respirable SWCNT particles at the current PEL (for graphite particles) they may be at risk of developing some lung lesions.” •  ranulomatous lesion G resulting from exposure to CNTs at a level ~ 20 days of inhalation at the permissible exposure limit for graphite.
  • 25. Where Do We Stand for Nanoparticles? 1.  Prevent injury and illness —  Workplace (exposure) monitoring •  No widely accepted methods, tools and analysis expensive and experimental, high background level •  No accepted workplace exposure limits —  Engineered, administrative and personal protective controls •  Ventilation systems, HEPA filters, respirators, gloves all work 2.  Early detection of signs or symptoms of injury or illness —  Medical surveillance •  No accepted protocols specific to nanoparticles •  Technical basis limited 3.  Intervene in disease process —  Removal from exposure •  Might be helpful —  Treatment •  Unknown
  • 26. Prudent Approach 1.  Prevent injury and illness —  Workplace (exposure) monitoring •  Use simple screening tools, control banding approach —  Engineered, administrative and personal protective controls •  Treat all engineered nanoparticles as toxic, use prudent practices to control exposure 2.  Early detection of signs or symptoms of injury or illness —  Medical surveillance •  Implement optional general health awareness exams •  Register and track employees with significant exposure •  Stay abreast of new toxicological findings, implement specific health screening protocols as appropriate, perhaps on an experimental basis 3.  Intervene in disease process —  Removal from exposure •  Very sensitive as it impacts employability —  Treatment •  Unknown

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