Overview: Health, Safety, and Environmental Issues for Nanotechnology

1. Overview: Health, Safety, and Environmental Issues for Nanotechnology James Yardley May 7, 2004

2. Nanotechnology: Health, Safety, and Environment.

3. Occurance of nanoscale particulate materials. From presentation E. Clayton Teague, NNCO, April 2004.

4. Potential bio-uptake of nanoscale particulates. • Nanoparticles may enter living cells via: • Endocytosis • Receptor activation for initiation • Membrane penetration • Generally occurs with very hydrophobic particles • Transmembrane channels • May be seen with very small nanoparticles (< 5 nm?) Adapted from presentation of Vicki Colvin, Rice University.

5. Potential bio-accumulation of nanoscale particles. • Accumulation of a substance within a species can occur due to lack of degradation or excretion. • Many nanoparticles are not biodegradable. • If nanoparticles enter organisms low in the food web, they may be expected to accumulate in organisms higher in the food web. Very little is understood about possible health effects of nanoparticle exposure! Adapted from presentation of Vicki Colvin, Rice University.

6. Potential human hazards for nanoscale particulates. Inhalation: Inhaled particles induce inflammation in respiratory tract, causing tissue damage. Example: Inhalation of silica particles in industrial workers causes “silicosis”. Dermal exposure: Particles may enter body through the skin. Potential hazards are unknown at present. Ingestion: nanoparticles may cause liver damage. Ingested nanoparticles (i.e. for oral drug delivery) have been found to accumulate in the liver. Excessive immune/inflammatory responses cause permanent liver damage. Other: ocular, …. Adapted from presentation of Vicki Colvin, Rice University.

7. Semiconductor nanoparticules. Red- and green-emitting quantum dots highlight the mitochondria and nuclei, respectively, of human epithelial cells in culture. Although these colorful nanocrystals don't seem to harm the cells, could they pose unforeseen hazards to people or the environment? Silica-coated semiconductor nanocrystals are readily incorporated into a wide variety of eukaryotic cells. In experiments where the quantum dots are deposited on a collagen substrate and then cells are deposited on top of this, the cells incorporate any quantum dots that underlie them When the cells migrate on a substrate, they ingest all the dots they pass over providing a convenient and rapid way for assessing the cells' potential to metastasize, or spread (as a cancer) from one part of the body to another [Adv. Mater., 14, 882 (2002)]. The dots appear to go into cells as "inert spectators." The cells remain healthy and even continue to divide, with each cell division reducing the number of dots in any given cell. The dots have no discernible effect on the cells. ---- A. Paul Alivisatos

8. Wahrheit (Dupont), January 2004. Optical micrograph of lung tissue from a rat exposed to single-wall carbon nanotubes (1 mg/kg) 1 week post exposure. Note the early development of lesions surrounding the instilled SWCNT (arrows) and the nonuniform, diffuse pattern of single-wall carbon nanotube particulate deposition in the lung (X 100). Low-magnification micrograph of lung tissue from a rat exposed to single-wall carbon nanotubes (1 mg/kg) at 1 month postinstillation. Note the diffuse pattern of granulomatous lesions (arrows). It was interesting to note that few lesions existed in some lobes while other lobes contain several granulomatous lesions—and this was likely due to the nonuniform deposition pattern following carbon nanotube instillation. Magnification X 20. Higher magnification optical micrograph of lung tissue from a rat exposed to single-wall carbon nanotubes (1 mg/kg) at 1 month postinstillation exposure. Note the discrete, multifocal mononuclear granuloma centered around the carbon nanotube material (arrows). Magnification X 400. D. B. Wahrheit et. al. Toxilogical Sciences 77, 117-125 (2004)

9. Presentation, ACS, January, 2004 From Lam presentation

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14. Concerns about granulomas and fibers. Granulomas (miscropic nodules), consisting particles, live and dead cells, and debris and could impair cellular and physiological (gas exchange) lung functions and give rise to fibrosis, more defined nodules, and other lesions. Fibers are generally of more health hazard than other forms of particulates. It is well established that the pathogenicity of a fiber in the lungs directly correlates with its biopersistency(Oberdorster 2000). NTs are totally insoluble and probably one of the most biologically nondegradable man-made materials.Determining how the NT-induced granulomas progress would require a longer-duration study with this biopersistent material. From Lam presentation

15. Observations and tentative conclusions. • Granulomas were observed in lungs 7 d or 90 d after an instillation of 0.5 mg NT per mouse (also in some with 0.1 mg); • NT, regardless synthetic methods, types and amounts of residual catalytic metals, produced granulomas; • Lung lesions in the 90-d NT groups, in most cases, more pronounced than those in the 7-d groups. • Our study shows that, on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures. • If fine NT dusts are present in a work environment, exposure protection strategies should be implemented to minimize human exposures. From Lam presentation

16. Governmental regulation - particulate matter. From presentation E. Clayton Teague, NNCO, April 2004.

17. Problem areas for regulation of particulates. From presentation E. Clayton Teague, NNCO, April 2004.

18. NSF Guidelines for Nanocenter Research. • Strong chemical and materials hygiene. • HS&E educational program for all participants. • Protection against inhalation and dermal exposure. • Proper procedures for handling of potentially hazardous materials. • Strict adherence to government and institutional regulations. • Proper disposal of waste materials. • Dissemination of information regarding potential hazards. • Proper reporting of all reportable incidents.