1. ONAMI’s - Safer Nanomaterials and Nanomanufacturing Initiative Recommendations for the FDA Nanotechnology Task Force Stacey Harper

2. Issues for Nanotechnology Growing concerns about ecotoxicity, human health effects and safety Chemistry and physics different at nanoscale size Biological interactions largely unstudied Lack of data: Impossible to assess risk without data Potentially large-scale application (and thus large-scale impact) Trillion dollar industry by 2015 (NSF Report Societal Implications of Nanoscience and Nanotechnology, 2001) Importance of public acceptance Perceptual risks may be a barrier to commercialization Activists already making the case that untested nanomaterials are being forced on the public

3. Better, safer nanoparticles Less wasteful nanomanufacturing High performance nanodevices Safer Nanomaterials and Nanomanufacturing Initiative (SNNI) http://www.greennano.org/

4. Designing safer nanoparticles Nanomaterial synthesis Test Properties Redesign Material Nanoparticles have widely tunable properties - the key is to enhance performance and safety at the same time Structure/Property Relationships: Physicochemical properties and hazards

5. Testing the biological impacts of engineered nanoparticles Tier 1: Toxicity Screening Toxicity testing in cells, tissues and whole organisms –In vitro (human cells, tissue cultures) –In vivo (vertebrate models) Tier 2: Cellular Targets and Distribution Defined in vivo –Fluorescent nanomaterials –Targeted assays Tier 3: Molecular Expression Molecular (genetic) response –Whole animal gene expression profiles Vertebrates Nanomaterial Effects Database Feed data back into design scheme heart eye

6. A diverse family of functionalized nanoparticles has been prepared for 1.5-nm and 0.8-nm core sizes R = -(CH 2 ) 17 CH 3 -(CH 2 ) 15 CH 3 -(CH 2 ) 11 CH 3 -(CH 2 ) 9 CH 3 -(CH 2 ) 8 CH 3 -(CH 2 ) 7 CH 3 -(CH 2 ) 5 CH 3 -(CH 2 ) 2 CH 3 -(CH 2 ) 2 Si(OMe) 3 -(CH 2 ) 2 SO 3 - Na + -(CH 2 ) 3 SO 3 - Na + -(CH 2 ) 2 N + HMe 2 Cl - -(CH 2 ) 2 N + Me 3 Cl - -(CH 2 ) 2 O(CH 2 ) 2 N + Me 3 - OTs -(CH 2 ) 2 O(CH 2 ) 2 O(CH 2 ) 2 N + Me 3 - OTs -(CH 2 ) 2 O(CH 2 ) 2 O(CH 2 ) 2 N + Et 3 - OTs -CH 2 COO - Na + -(CH 2 ) 2 COOH -(CH 2 ) 11 COOH -(CH 2 ) 2 OH -(CH 2 ) 2 PO(OH) 2 -[(CH 2 ) 2 O] 2 (CH 2 ) 2 OH -(CH 2 ) 2 O(CH 2 ) 2 OH -[(CH 2 ) 2 O] 2 CH 2 COOH -(CH2)2COGlyGlyOH -(CH 2 ) 2 CONH(CH 2 ) 14 CH 3 Nanomaterial synthesis Test Properties Redesign Material

7. Example: Toxicity affected by size and surface functionalization Positive Charge (N,N,N-trimethylammoniumethanethiol) 0.8 nm Negative Charge (2-mercaptoethanesulfonate) 1.5 nm

8. Recommendations Identify environmental impacts Identify biological impacts Incorporate toxicological evaluations into research and development schemes Characterization and purification done carefully

9. Bettye LS Maddux, PhD Assistant Director ONAMI Safer Nanomaterials and Nanomanufacturing Initiative bettye@greennano.org 541.713.1330 http://greennano.org/ Contact Information Jim Hutchison, PhD Director ONAMI Safer Nanomaterials and Nanomanufacturing Initiative hutch@uoregon.edu 541.346.4228 http://greenchem.uoregon.edu Stacey Lynn Harper, PhD NIEHS Research Fellow Environmental Health Sciences Center Oregon State University harpers@science.oregonstate.edu 541.737.2791 http://www.onami.us/NanoNet/researchers Robert Tanguay, PhD Associate Professor Environmental and Molecular Toxicology Oregon State University robert.tanguay@oregonstate.edu 541.737.6514 http://emt.oregonstate.edu/faculty/tanguay.htm