1. Nanotechnology What about safety, is there a risk? Evaluation of risk Wim de Jong

2. Increase in consumer products with nanoclaim Number of total products listed, by date of inventory update, with regression analysis. August 2009 Nanotechnology Consumer Products Inventory, Woodrow Wilson International Center for Scholars, Washington, USA

3. Most commonly used nanomaterials in consumer products Nanotechnology Consumer Products Inventory, August 2009, Woodrow Wilson International Center for Scholars, Washington, USA

4. Consumer products with nanoclaim

5. Why are we concerned? Nanomaterials (nanoparticles) can have sizes similar to structures at subcellular level. Reminder, chemicals (molecules) also do this. nanopore, dendrimer, nanoshell, fullerene, nanotube, nanowire, nanocrystalls cantilevers, microneedles Nanotechnology lab-on-a-chip erythrocyte apple water molecule virus DNA Nature Nanometres 10 -1 1 10 1 10 2 10 3 10 4 10 5 10 6 10 7 10 8

6. Increase in reactivity due to increase in surface All: 1 x 1 cm Decrease in size results in (enormous) increase in surface area 6,000cm 2 1 x 10 12 1 µm 60.000.000 cm 2 (600km 2 ) 1 x 10 21 1 nm 60 cm 2 1,000 1 mm 6 cm 2 1 1 cm Total Surface area number size

8. Problems with dispersion in toxicity testing Gold nanoparticles in PBS, A and B 10 nm, C 50 nm, and D 100 nm diamater) De Jong et al., Biomaterials 29, 1912, 2008

10. Is nano more toxic than micro material? Depends on the dose metric used for particle toxicity Oberd ö rster et al., Environ Health Perspect 113, 823, 2005 This was demonstrated for local effects in the lung after inhalation exposure. What about other routes of exposure (oral, dermal, intravenous)?

11. Risk Assessment Risk characterization Hazard characterization Internal dose Hazard identification Dose response assessment Exposure assessment

14. Some issues/problems associated with engineered nanomaterials

15. Nanofibres, issue on CNT versus asbestos Scientific publications on possible cancer risk Sakamoto Y, Nakae D, Fukumori N, Tayama K, Maekawa A, Imai K, Hirose A, Nishimura T, Ohashi N, Ogata A. Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fisher 344 rats. The Journal of Toxicological Sciences, 34, 65-76, 2009 nature nanotechnology | VOL 3 | JULY 2008 | 423

16. Poland et al 2008 MWCNT induce chronic inflammation Takagi et al 2008, Sakamoto et 2009 MWCNT induce tumors in P53 mice and F344 rats Muller et al 2009 MWCNT do NOT induce tumors in 2 year study Nygaard et al 2009 CNT act as adjuvant

20. Nanostructures in pleural fluid and in pulmonary epithelial cell Song et al, Eur Resp J 34, 559-567, 2009 Bar represents 200 nm