Carbon NanoTubes   Human Health Risks   Oxford University Begbroke Science Park Nasrin McGuire 2009
Carbon nanotubes, and fullerenes Unique characteristics <ul><li>CNTs display unique structural and electronic properties d...
Comprehensive exposure assessment <ul><li>Exposure Characterisation : due to physico-chemical characteristics, crystallini...
toxicological endpoints for human or animal exposing to UFPs <ul><li>cell counts,  </li></ul><ul><li>enzymes,  </li></ul><...
CNTs Dosimetry ~ 70% of studies are in vitro <ul><li>Physicochemical properties, CNTs suspension, deposited mass, media do...
Asbestos like Inflammatory response?? Wick P et al, The degree and kind of agglomeration affect carbon nanotube cytotoxici...
Whether exposure to long straight CNTs will occur? Whether these fine fibres will reach the mesothelium surrounding the lu...
Insufficient evidence yet to approve toxicity or emergence of any common disease (NIOSH) <ul><li>Flow cytometry was used t...
Genotoxicity <ul><li>Pathways to affect DNA and histones:  </li></ul><ul><li>Indirectly due to inflammatory effects,  </li...
Risks against benefits <ul><li>There is no chronic inhalation study to date, only inhalation-testing on animals.  </li></u...
Great need for fundamental research, and standardisation <ul><li>Need for applied research </li></ul><ul><li>Hazard assess...
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Cnts Human Health Risks

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Review of literature on carbon nanotubes exposure risks to human health, and hypes involved in exageration of risks and raising issues regarding research carried out in unrealistic laboratory environment that exhibit excess of human uptake.

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Cnts Human Health Risks

  1. 1. Carbon NanoTubes Human Health Risks Oxford University Begbroke Science Park Nasrin McGuire 2009
  2. 2. Carbon nanotubes, and fullerenes Unique characteristics <ul><li>CNTs display unique structural and electronic properties due to: </li></ul><ul><li>Size range (length) ~ <100 nm </li></ul><ul><li>High aspect ratio </li></ul><ul><li>Surface chemistry </li></ul><ul><li>Shape (spherical fullerene), (cylindrical SWNTs, MWNTs) </li></ul><ul><li>Synthesized or engineered through nanotechnologies </li></ul><ul><li>Aggregation and agglomeration state </li></ul><ul><li>Inherent electronic properties (fullerenes act as radical sponges activating against ROS) </li></ul><ul><li>Potential pharmaceutical applications are anticipated for water-soluble fullerene derivatives </li></ul><ul><li>http://www.springerlink.com/content/xvg0885j2x12412k/fulltext.pdf?page=1 </li></ul>
  3. 3. Comprehensive exposure assessment <ul><li>Exposure Characterisation : due to physico-chemical characteristics, crystallinity and in connection to different metal traces CNTs canvas diverse biological activities and toxicities </li></ul><ul><li>Dose rate, dose response: Cell/ tissue uptake measures (manufactured or ambient - need for proper standardisation), different pathways particularly passing through BBB </li></ul><ul><li>Exposure extent and duration (screening and monitoring) </li></ul><ul><li>Biopersistent, rigidity, and High aspect ratio </li></ul><ul><li>Reaction dynamics and energy, such as quenching reactive oxygen species ROS (within biological fluid environment protein coating may affect CNT behaviour) </li></ul>
  4. 4. toxicological endpoints for human or animal exposing to UFPs <ul><li>cell counts, </li></ul><ul><li>enzymes, </li></ul><ul><li>cytokines, </li></ul><ul><li>bronchoalveola lavage fluid (BALF), </li></ul><ul><li>DNA damage. </li></ul><ul><li>Chow and Watson (2006) </li></ul><ul><li>Oxidant stress and inflammation as marker of toxicity (Nel et al 2006) </li></ul>
  5. 5. CNTs Dosimetry ~ 70% of studies are in vitro <ul><li>Physicochemical properties, CNTs suspension, deposited mass, media dose, media mass, cell dose and density affect settling rate and magnitude of response, </li></ul><ul><li>Challenges to extrapolate animal study to human doses, normal vs. disease </li></ul><ul><li>Challenges to measure CNTs characteristics </li></ul><ul><li>Measurements need Comparative observations and repeatable methods </li></ul><ul><li>(SCENIHR 2006) </li></ul><ul><li>http://www.dtsc.ca.gov/TechnologyDevelopment/Nanotechnology/upload/04_teeguarden.pdf </li></ul>
  6. 6. Asbestos like Inflammatory response?? Wick P et al, The degree and kind of agglomeration affect carbon nanotube cytotoxicity, toxicology Letters, vol 168, Issue 2, 30 Jan 2007, p 121 <ul><li>Inhalation of SWCNTs causing lung inflammation and lesions and dose-dependent oxidative damage to the DNA of mice’s heart (Li et al. 2005, 2006). </li></ul><ul><li>Muller et al. 2005 claiming about MWCNT to be highly fibrogenic and inflammogenic, “roughly equivalent to a chrysotile asbestos control.” </li></ul><ul><li>Shvedova et al. (2005) found that SWCNT induces a “robust acute inflammatory reaction”. In a 24 day study </li></ul><ul><li>Li et al. (2007) ) compared intratracheal instillation with inhalation exposure of mice to MWCNTs. </li></ul><ul><li>Donaldson et al. (2006), Jain et al. (2007), Lam et al. (2006), Muller et al. (2006), Oberdörster et al. (2007) </li></ul>
  7. 7. Whether exposure to long straight CNTs will occur? Whether these fine fibres will reach the mesothelium surrounding the lungs, and go on to cause mesothelioma. (Maynard, 2008) <ul><li>This study demonstrates carbon nanotubes that physically resemble harmful asbestos fibres, can also behave like harmful asbestos fibres. (Poland et al. 2008; and Takagi et al. 2008) </li></ul><ul><li>Carbon nanotubes were taken up by cell nuclei in an in vitro study where they caused dose-dependent cell death (Porter et al. 2007) </li></ul><ul><li>Multi-walled carbon nanotubes localised within skin cells in in vitro studies. They caused irritation, impaired protein function and decreased cell viability. The authors warn this could cause skin disease (Monteiro-Riviere et al. 2005; Witzmann and Monteiro-Riviere 2006) </li></ul><ul><li>Cardiovascular risks due to nanoparticulate air pollution both directly and indirectly was observed (Mills et al. 2009) </li></ul><ul><li>Accelerate platelet aggregation (in vitro), and vascular thrombosis (in vivo, rat) </li></ul><ul><li>Funcitonalised (C60(OH)24) exposed risk but not in its pure form (Niwa and Iwai 2007). </li></ul>
  8. 8. Insufficient evidence yet to approve toxicity or emergence of any common disease (NIOSH) <ul><li>Flow cytometry was used to show that the fluorescence from MitoSOX™ Red, a selective indicator of superoxide in mitochondria, was statistically similar in both control cells and cells incubated in SWNTs. The combined results indicate that under our sample preparation protocols and assay conditions, CoMoCAT DM-SWNT dispersions are not inherently cytotoxic to HeLa cells. http://www.jnanobiotechnology.com/content/5/1/8 </li></ul><ul><li>Only long thin fibrous forms (length >20 micrometer), rigidity, and non-degradability (biopersistence). Inflammation and granulomas were only found in the case of the long straight nanotubes whilst the short/tangled nanotubes had no effect. (Davis et al. 1986) </li></ul><ul><li>It needs sufficient long straight CNTs to get airborne in workplaces to reach a threshold dose followed by translocation to the pleural mesothelium. </li></ul><ul><li>Risk Assessment of Products of Nanotechnologies (SCENIHR) </li></ul><ul><li>http://www.flex-news-food.com/files/EFSA.nonotechnologies.18.02.09.pdf </li></ul>
  9. 9. Genotoxicity <ul><li>Pathways to affect DNA and histones: </li></ul><ul><li>Indirectly due to inflammatory effects, </li></ul><ul><li>through oxidative stress due to entry to cells and direct activity in mitochondria and the nucleus affects during cell divisions </li></ul><ul><li>Other paths, eg. metal released activity </li></ul><ul><li>Shown increase risks for SWNCT, SiO2, CoCr, TiO2, V2O3, Carbon black, Diesel Exhaust particles </li></ul><ul><li>Studies’ conditions questionable, poor characteristics of particles, increasing possibilities of contaminants </li></ul><ul><li>The genotoxicity of C60 proved contradictory, but often shown weak risk </li></ul><ul><li>Unacceptable high dose are used both in vivo and in vitro </li></ul>
  10. 10. Risks against benefits <ul><li>There is no chronic inhalation study to date, only inhalation-testing on animals. </li></ul><ul><li>Investigations on CNTs are not longitudinal studies to be valid for extrapolation. </li></ul><ul><li>There is no specific risk of physicochemical issue yet under scrutiny to investigate hazard across particle types. </li></ul><ul><li>CNTs used for drug synthesis and delivery, and tissue regeneration and replacement, but they can enter cells, hence, risks should be balanced against benefits. (Roco 2006) </li></ul><ul><li>Functionalised CNTs able to pass the cell membrane with no toxicity upto 10 μ m, and are biocompatible (Pantarotto 2003). </li></ul><ul><li>dry and wet abrasive machining of CNTs shown that wet-work with engineered CNTs did not produce exposure risk, while dry-work without emission control was the worst case (Bello 2009) </li></ul>
  11. 11. Great need for fundamental research, and standardisation <ul><li>Need for applied research </li></ul><ul><li>Hazard assessment </li></ul><ul><li>Bridging research </li></ul><ul><li>Integrated assessment </li></ul><ul><li>Dosimetry </li></ul><ul><li>Material characteristics </li></ul>
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