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# Nanotechnology White Paper

O f fi c e of t h e S c i e n c e A d v i s o r S c i e n c e P o l i c y C o u n c i lEPA 100/B-07/001 February 2007



# U.S. Environmental Protection Agency

Nanotechnology White Paper

Prepared for the U.S. Envi ro nmental Protection Agency by members of the Nano technology Work group, a group of EPA’s Science Policy Council



## Science Policy Council U.S. En vironmen tal P r otection Agency Washington, DC 20460ii EPA Nanotechnology White Paper



## DISCLAIMER

This document has been reviewed in accordan ce with U.S. Environm ental Protection Agency policy and approved for publicati on and distribution. Mention of trade nam e s or comm ercial products does not constitute e ndorsem ent of recommendation for use. Notwithstanding any use of m a ndatory language such as "m ust" and "require" in this docum e nt with regard to or to reflect scientific practices, this docum ent does not and should not be construed to create any legal rights or requirem e nts.



### Cover Images:

Left : Com p uter im ages of various form s of carbon nanotubes. Im ages courtesy of Center for Nanoscale Materials, Ar gonne National Laboratory

Right : Computer im age of a dendrimer. Im age cour tesy of Dendritic NanoTechnologies, Inc.

Title Pag e I m age : Computer im age of a C-60 Fullere ne. Laurence Libelo, U.S. EPA.iii EPA Nanotechnology White Paper


## Nanotechnology White Paper

Work group Co-Chairs

Jeff Morris Jim Willis Office of Res earch and Development Office of Prevention, Pesticides and Toxic Substances

Science Policy Council Staff

External Coordination Steve Lingle, ORD Dennis Utterback, ORD

EPA Research Strateg y Barbara Karn, ORD Nora Savage, ORD

Risk Assessment Phil Sayre, OPPTS

Physical-C hemical Properties Tracy W illiam s on, OPPTS

Health Effe cts Deborah Burgin, OEI Kevin Dreher, ORD Kathryn Gallagher Office of the Science Ad visor



### Subgroup Co-Chairs

Ecological Effects Anne Fairbrother, ORD

Tala Henry, OPPTS Vince Nabholz, OPPTS

Human Exposures Scott Prothero, OPPT

Environmental Fate Bob Boethling, OPPTS Laurence Libelo, OPPTS John Scalera, OEI

Environmental Detection and Analysis John Scalera, OEI Richard Zepp, ORD

Statutes, Regulations, and Policies Jim Alwood, OPPT Risk Management Flora Chow, OPPT

Converging Technologies Nora Savage, ORD

Pollution P r evention Walter Schoepf, Region 2

Sustainability and Society Diana Bauer, ORD Michael Brody, OCFO

Public Communications and Outrea ch Anita Street, ORDiv EPA Nanotechnology White Paper



### Work group Members

Suzanne Ackerm an, OPA Kent Anapolle, OPPTS Fred Arnold, OPPTS Ayaad Assaad, OPPTS Dan Axelrad, OPEI John Bartlett, OPPTS Sarah Bauer, ORD Nor m an Birchfield, OSA John Blouin, OPPT Jim Blough, Region 5 Pat Bonner, OPEI W illiam Boyes, ORD Gordon Cash, OPPTS Gilber t Castellano s, OIA Tai-Ming Chang, Region 3 Paul Cough, OIA Lynn Delpire, OPPTS John Diam a n te, OIA Christine Dibble, OPA Jerem i ah Duncan, AAAS fellow, OP PTS Thom as Forbes, OEI Conrad Flessner, OPPTS Jack Fowle, ORD Elisabe t h Fr eed, OECA Sarah Furtak, OW Hend Galal-Gorchev, OW David Giamporcaro, OP PTS Michae l Gill, ORD liaison f o r Re gion 9 Collette Hodes, OPPTS Gene Jablonowski, Region 5 Lee Hofm an, OSWER Joe Jarv is, ORD Y’Vonne Jones-Brown, OPPTS Edna Kapust, OPPTS Nagu Keshava, ORD David Lai, OPPTS Skip Laitner, OAR Warren Layne, Region 5 Do Young Lee, OPPTS Virginia Lee, OPPTS Monique Lest er, OARM, on detail to OIA Michael Lewandowski, ORD Bill Linak, ORD David Lynch, OPPTS Tanya Maslak, OSA intern Paul Mattha i, OPPT Carl Mazza, OAR Nhan Nguyen, OPPTS Carlos Nunez, ORD Onye m aechi Nweke, OPEI Marti Otto, OS WER Manisha Patel, OGC Steve Potts, OW Mary Reiley, OW Mary Ross, OAR Bill Russo, ORD Mavis Sanders, OEI Bernie Schorle, Region 5 Paul Solomon, ORD Tim o thy Ta ylor, OSW E R Maggie Theroux-Fieldsteel, Region 1 Stephanie T hornton, OW Alan Van Arsdale, Reg i on 1 W illiam W a llac e , ORD Barb W a lton, ORDv EPA Nanotechnology White Paper



### Table of Contents

FOREW O R D

....................................................................................................................... ............................ VIII

AC KN OWLE DG MENTS

................................................................................................................ .................. I X

AC RO N Y M S

....................................................................................................................... .................................. X

E X E C UTIVE SU M M A R Y

.............................................................................................................. ..................... 1

1. 0 I N TR OD UCTI O N

............................................................................................................... ............................ 4

1. 1 P URPOSE

............................................................................................................................... ......................... 4 1. 2 N ANOTECH NOLO GY D EF IN ED

........................................................................................................................ 5 1. 3 W HY N ANOTECH NOL OGY I S I MPORTA NT TO EPA

....................................................................................... 13 1. 4 N ATIONAL AND I NT ERNA T I ONA L C ON TE XT

................................................................................................. 14 1. 5 W HAT EPA IS D OI NG WI TH R ESP E CT TO N ANOT ECHN OLO G Y

..................................................................... 18 1. 6 O PPORTUNI TIES AN D C HA LL E N GE S

.............................................................................................................. 21

2. 0 EN VI RO NME N TAL B E NEFITS OF N A N O TECH N OLO G Y

................................................................ 22

2. 1 I NTRODUCT I ON

............................................................................................................................... ............. 22 2. 2 B ENEF ITS T HROUGH E NVI RONME N T A L T ECHNO LOG Y A PPLICA T IO NS

......................................................... 22 2. 3 B ENEFITS T H ROUGH O THE R A PPLICAT ION S THA T S UP POR T S UST A IN ABIL ITY

............................................. 24

3. 0 RISK A S S E SSME N T O F N A N O MAT E RIALS

......................................................................................... 29

3. 1 I NTRODUCT I ON

............................................................................................................................... ............. 29 3. 2 C HEMIC A L I DENTI F ICA T IO N AND C HA RACT E R IZ A T I O N OF N ANOM ATER IALS

.............................................. 31 3. 3 E NVIRONM ENTA L F A TE O F N ANOM ATER IALS

.............................................................................................. 32 3. 4 E NVIRONM ENTA L D ET ECT I ON AND A NA L Y SIS OF N ANO MAT E RIA L S

........................................................... 40 3. 5 H UMAN E X P OSURES AN D T HEIR M EAS U REME NT AND C ONTRO L

................................................................ 42 3. 6 H UMAN H E A LTH E FFEC T S OF N ANO MAT E R IALS

.......................................................................................... 52 3. 7 E COLOGIC A L E FF ECTS OF N ANOMA TER I A LS

................................................................................................ 58

4.0 RESPONSIBLE DEVEL O PME N T

.................................................................................................... ......... 63

4. 1 R ESPONS IB LE D EV ELO PM ENT OF N ANO S C ALE M AT ERIA LS

......................................................................... 63 4. 2 P ROGRAM A REAS

............................................................................................................................... .......... 65 4. 3 E NVIRONM ENTA L S T E W A R DSHIP

................................................................................................................. 68

5. 0 EP A’ S RE SEAR CH NE EDS F O R N A N O M ATE R I A LS

.......................................................................... 70

5. 1 R ESEARCH N EEDS FOR E NV I R O N M E NT AL A PPLICAT IONS

............................................................................ 70 5. 2 R ESEARCH N EEDS FOR R IS K A SSESS MEN T

................................................................................................... 72

6. 0 REC O M M EN DATI O NS

............................................................................................................ .................. 82

6. 1 R ESEARCH R ECOM ME NDA TION S FOR E NV IRONM EN TAL A PPLICAT IONS

...................................................... 82 6. 2 R ESEARCH R ECOM ME NDA TION S FOR R IS K A SSESS MEN T

............................................................................. 83 6. 3 R ECOM ME NDAT IONS FOR P OLLU TIO N P RE V E NT IO N AN D E NVIRO NM EN TAL S TE WARD SHIP

......................... 89 6. 4 R ECOM ME NDAT IONS FOR C OLL A BORAT I ONS

............................................................................................... 90 6. 5 R ECOM ME NDAT ION TO C ONVE NE AN I NT RA -A GENCY W ORKGROUP

........................................................... 91 6. 6 R ECOM ME NDAT ION FOR T RAININ G

.............................................................................................................. 91 6. 7 S UMMARY OF R EC OM MEN DATI ONS

............................................................................................................. 92

7. 0 REFERE NCES

................................................................................................................. ............................. 93

APPE NDI X A : GLO S S A R Y OF N A N O TECHN OLOG Y TER MS

............................................................. 107

APPE NDI X B : P R IN CIPLE S OF EN VIR O N M ENT A L STEWA R D S HI P BEH AV I O R

.......................... 110

APPE NDI X C : EPA’S NANOTECHNOL OGY RE SEARCH F R AME W ORK

.......................................... 111

APPE NDI X D : EP A ST AR GR ANTS FO R NA NOTE C H NOL O G Y

.......................................................... 113vi EPA Nanotechnology White Paper

APPE NDI X E : LIST OF N A N O TECH N OLOG Y W H I TE PAPE R E X TE R NAL P EER RE VIE W ERS A N D THEIR AFFI LIATIO NS

............................................................................................................. ..................... 119vii EPA Nanotechnology White Paper



### Table of Figures

F IGURE 1. D IAGRAM I NDICA TING REL A TIV E SCALE OF NA NOSI ZED OBJE CTS

..... ... ... ... ... . .... ... ... ... ... ... ... .. .... ... ... .. 6 F IGURE 2. G ALLIUM P HO SP HI DE (G A P) N ANO TREES

...... .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... . 7 F IGURE 3. C OMPUTER I MAGE O F A C-60 F ULLERENE
..... . .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... 8 F IGURE 4. C OMPUTER I MA GES OF VA RIOU S F O RMS OF C ARBON NA NOT U BES

. ..... ... ... ... .... ... ... ... ... ... ... .. .... ... ... ... . 8 F IGURE 5. “F ORE S T ” OF ALI G NED CARB ON NAN OTUBES

....... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... .. 8 F IGURE 6. Z IN C OX I D E N A N O STRUCTURE S YNTHESI ZED B Y A VAP OR
- S O LID PRO C ESS

....... ... ... ... ... ... ... .. .... ... ... ... 9 F IGURE 7. C OMPUTER IMAGE O F AG ALLIUM ARSENIDE QUANTUM DOT OF 465 ATOMS

.... ... ... ... ... ... ... .. .... ... ... ... 9 F IGURE 8. C OMPUTER IMAGE O F G ENERA T IONS OF A DE NDRIMER
...... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... . 9 F IGURE 9. C OMPUTER IMAGE O F A N ANO
- B I O C O M P OSI T E
. .... ... ... ... ... ... . .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... . 10 F IGURE 10. P ROJECTED S T A GE S OF N ANO T E C HN OL O G Y D EVELO PMENT
.... ... ... ... ... ... ... .... ... ... ... ... ... ... .. .... ... ... .. 13 F IGURE 11. F EDERAL S OURCES TO I NF ORM EPA’ S N ANOT E C HN OL O G Y A CTIVITIES

... .. .... ... ... ... ... ... ... .. .... ... ... 15 F IGURE 12. NN I NSET S UB CO MMITTEE S TRUCTURE

...... .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... .. 16 F IGURE 13. N ANOS CALE ZE RO
- VALENT I R ON E NCA PSUL ATED IN AN E M ULSION DR OPLET

..... ... ... ... .. .... ... ... ... ... 22 F IGURE 14. P IE ZORESISTIVE CANTILEVER SENSOR

..... ... ... .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... . 24 F IGURE 15. EPA’ S R ISK A SSESSMENT A PPRO A C H
...... ... . .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... 29 F IGURE 16. L IFE C YCLE P ERSPECTIVE T O R ISK A SSESSMENT

..... ... ... ... ... .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... 30 F IGURE 17. T RANSMISSION E LECTRO N M ICROSC OPE (TEM) IMAGE OF AEROS O L
- G E NERATED T I O 2 NAN OPA R TICL ES

.... ... ... ... ... ... . .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... . .. ... ... ... .. .... ... .. 32 F IGURE 18. Z I NC OX IDE NAN OSTRU C TURES SYNT HESI ZED BY A V A P O R
- S O LID PRO C ESS

.... ... ... ... ... ... ... .. .... ... ... . 35 F IGURE 19. SEM O F A S C AN NI N G G A TE P R OBE

.... ... ... ... .. ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... .. 42 F IGURE 20. P ARTICLE T OXICO L OG Y C ITATIO NS

....... ... ... ... .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... 53 F IGURE 21. F LUO R ES CENT NANOPARTICLE S IN W A TER FLEA (D APHNI A M A GNA )

....... ... .... ... ... ... ... ... ... .. .... ... ... .. 60 F IGURE 22. EPA O FFICE R O LES

....... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... ... ... ... ... .. .... ... ... .. 64



### Table of Tables

T ABLE 1. E XAMPLES OF P R O DUCTS T H AT U SE N ANOTEC HNOL OGY A ND N ANO MATERI A LS

............................ 11 T ABLE 2. O UTCOMES FOR S USTAINABLE U SE OF M AJOR R ESOURCES A ND R ESOU RCE S YSTEMS

................... 25 T ABLE 3. P O TENTIAL U.S. E NERGY S AVIN G S FR OM E IG H T N ANOT E C HN OL O G Y A PPLI CATION S

.................... 26 T ABLE 4. P O TENTIAL S O URC ES OF O CC UP ATIONAL E XP OSURE F O R V ARIOU S S YNT HESIS M ETHODS

............ 44 T ABLE 5. E XAMPLES OF P O T ENTIAL S O URC ES OF G ENERAL P OP ULATI O N AND / OR C ONSUM E R E XP OSURE F O R S EVERAL P RODUCT T YPES

............................................................................................................................... .... 45 T ABLE 6. S UMMARY OF W ORKG RO UP R ECOMMENDATI O NS R EGAR DIN G N AN OMATE R IALS

........................... 92viii EPA Nanotechnology White Paper



## FOREWORD

Nanotechnology presents opportunities to create new and better products. It also has the potential to improve assessm ent, m a nagem e nt, and prevention of environm ental risks. However, there are unanswered questions about the im pacts of nanom a terials and nanoproducts on hum a n health and the environm ent.

In Decem be r 2004, EPA’s Science Policy Council (SPC) form ed a cross-Agency Nanotechnology W o rkgroup to develop a white paper exam ining potential environm ental applications and im plications of nanotechnology. This document describes the issues that EPA should consider to ensure that society benefits from advances in environm ental protection that nanotechnology m a y offer, and to understand and a ddress any potential risks from environm ental exposure to nanom aterials. Nanotechnology will have an im pact across EPA. Agency m a nagers and staff are working together to develop an approach to nanot echnology that is forward thinking and inform s the risk assessm ent and risk m a na gem e nt activities in our program and regional offices. This docum ent is intended to support that cross-Agency effort.

We would like to acknowledge and th ank the Nanotechnology W o rkgroup subgroup cochairs and mem b ers and for their work in develo ping this docum e nt. W e would especially like to acknowledge the W o rkgroup co-chairs J i m W i llis and Jeff Morris for leading the w o rkgroup and docum e n t developm ent. W e also thank SPC staf f task le ad Kathryn Gallaghe r, a s well as Jim Alwood, Dennis Utterback, and Jerem i ah Duncan for their efforts in assem b ling and refining the docum ent.

It is with pleasure that w e provide th e EPA Nanotechnology White Paper to prom ote the use of this new, exciting technology in a m a nner th at protects hum a n health and the environm ent.

W illiam H. Benson Charles M. Auer Acting Chie f Scientis t Directo r , Of f i ce of Pollution Office of the Science Advisor Prevention and Toxicsix EPA Nanotechnology White Paper



## ACKNOWLEDGMENTS

The Nanotechnology Workgroup would like to acknowledge the Sc ience Policy Council and its Steering Comm ittee for their recomm endat i ons and contributions to this docum ent. W e thank Paul L e slie of TSI Incorporated, and Laura Morlacci, T o m W e bb and Peter McC l ure of Syracuse Research Corporation for their support in developing background inform ation for the docum ent. We also thank the external peer revi ewers (listed in an appen d ix) for their comments and suggestions. Finally

, the workgroup would li ke to thank Bill Farland and Charles Auer for their leadership and vision with respect to nanotechnology.x EPA Nanotechnology White Paper



## ACRONYMS

ADME Absorption, Distribution, Metabolism

, Elim ination ANSI Am erican National Stan dards Ins t itu t e ASTM Am erican Society for T e sting and Materials CAA Clean Air Act CAAA Clean Air Act Am endments CAS Chem ical Abstracts Service CDC Centers for Disease Con t rol and Prevention CERCLA Com p rehensive Environm ental Re sponse, Com p ensation and Liability Act CFCs Chlorofluorocarbons Che m STEER Che m ical Screening Tool for Exposures and Environm ental Releases CNT Carbon nanotubes CPSC Consum er Products Safety Comm ission CW A Clean W a ter Act DfE Design for Environm ent DHHS Departm e nt of Health and Hum a n Se rvices DHS Departm e nt of Hom e land Security DNA Deoxyribonucleic Acid DOC Departm e nt of Commerce DOE Departm e nt of Energy DOI Departm e nt of Interior DOJ Departm e nt of Justice DOS Departm e nt of State DOT Departm e nt of Transportation DOTreas Departm e nt of the Treasury E-FAST Exposure and Fate Assessm e nt Screening Tool EPA Environm ental Protection Agency EPCRA Em ergency Planning and Community Right-to-Know Act FDA Food and Drug Adm i nistration FIFRA Federal Inse ctic ide, Fun g icide and Rodentic ide Act GI Gastrointestinal GST Glutathione-S-Transferase HAPEM Hazardous Air Pollutan t Exposure Model HAPs Hazardous Air Pollutan t s HEPA High Efficiency Particulate Air HPV High Production Volum e IAC Innovation Action Council ISO International Organi zation for Standardization ITIC Intellig ence Technology Inform ation Center Kow Octanol-W ater Partition Coefficient LCA Life Cycle Assessm ent LEDs Light Em itting Diodes MCLGs Maxim u m Contam inant Level Goalsxi EPA Nanotechnology White Paper

MCLs Maxim u m Contam inant Levels MFA Material Flow Analysis MW Molecu lar W e ight NAAQS National A m bient Air Quality Stan dards NASA National Aeronautics an d Space Adm i nistration NCEI National Center for Environm ental Innovation NCER National Center for Environm ental Research NEIC National En f o rcem ent Investig ation s Center NEHI Nanotechnology Environm ental and H ealth Im plications (NNI work group) NERL National Exposure Research Laboratory NHEERL National Health and Environm ental Effects Research Laboratory NHEXAS National Hum a n Exposure Assessm ent Survey NIH National Ins titu tes of Health NIOSH National Ins titu te f o r Oc cupation a l S a f e ty and Health NNAP National Nanotechnology Advisory Panel NNCO National Nanotechnol ogy Coordinating Office NNI National Nanotechnology Initiative NOx Nitrogen oxides NRC National Research Council NRML National Risk Management laboratory NSET NSTC Comm ittee on Technology, S ubcomm ittee on Nanoscale Science, Engineering and Technology NSF National Science Foundation NSTC National Science and Technology Council NTP National Toxicology Program (DHHS) OAR Office of Air and Radiation OARM Office of Adm i nistration and Resource Managem e nt OCFO Off i ce of the Chief Financial Of f i cer OCIR Office of Congressional and Intergovernm ental Relations OECA Office of Enforcem ent and Com p liance Assuran ce OECD Organisation for Econom ic Co-operation and Developm ent OEM Original Equipm ent Manufacturers OEI Office of Environm ental Inform ation OIA Office of International Affairs OLEDs Organic Lig h t Em itting Diodes OPA Office of Public Affairs OPA Oil Pollu tio n Act OPEI Office of Policy, Econom i cs and Innovation OPPT Office of Po lluti on Prevention and T oxics OPPTS Office of Prevention, Pes ticides and Toxic Substances ORD Office of Research and Developm ent OSA Office of the Science Ad visor OSHA Occupational Safety and Health Administration OSTP Office of Science and Technology Polic y (Executive Office of the President) OSWER Office of Solid W a ste and Em ergency Response OW Office of Waterxii EPA Nanotechnology White Paper

PCAST President' s Council of Advi sors on Science and Technology PCBs Polychlorinated Biphenyls PM Particulate Matter PMN Prem anufacture Notice PPE Personal Protective Equip m ent QSAR Quantita tive Structu r e Activ ity Rela tionship RCRA Resource Conservation and Recovery Act SAMMS Self-Assembled Monolayers on Mesoporous Supports SAR Structure Activity Relationship SDWA Safe Drinking W a ter Act SDW I S Safe Drinking W a ter Inform ation System SEM Scanning Electron Microscopy SFA Substance F l ow Analysis SPC Science Policy Council STAR Science To Achieve Res u lts STM Scanning Tunneling Microscope SW CNT Single-W a lled Carbon Nanotubes TOC Total Organic Carbon TRI Toxics Release Inventory TSCA Toxic Substances Control Act USDA US Department of Agriculture USPTO US Patent and Trade Office UST Underground Storage Tank ZVI Zero-Valen t Iron1 EPA Nanotechnology White Paper



## EXECUTIVE S U MMARY

Nanotechnology has potential applications in m a ny sectors of the Am erican econom y, includ ing co nsum er products, health care, tran spo r tation, energy and agriculture. In ad dition, nanotechnology presents new opport unities to improve how we m easure, m onitor, manage, and

m i ni m i ze contam inants in the enviro nm ent. W h ile the U.S. E nvironm ental Protection Agency (EPA, or “th e Agency”) is interes t ed in rese arching and developing the possible benefits of nanotechnology, EPA also has the ob ligation and m a ndate to protec t hum a n health and safeguard the environm ent by better understanding and ad dressing potential risks from exposure to nanoscale materials and products containing nanoscale m a terials (both referred to here as “nanom aterials”).

Since 2001, EPA has played a l eading role in f unding research and setting research directions to develop environm en tal applications f o r, and unders tand the potential hum an health and environm ental im plications of, nanotechnolo gy. That research has already borne f r uit, particularly in the use of nanom aterials fo r environm ental clean-up and in beginning to understand the disposition of nanom a terials in biological system s. Som e e nvironm ental applications using nanotechnology have progressed beyond the research stage. Also, a num b er of specific nanom aterials have com e to the Agency’s attention, whether as novel products intended to prom ote the reduction or rem e diation of pollution or becaus e they have entered one of EPA’s regulatory review processes. For EP A, nanotechnology has evolved from a futuristic idea to wa tc h, to a cur r e n t issue to a ddress.

In Decem be r 2004, EPA’s Science Policy Council created a cross-Agency workgroup charged with describ i ng key scien c e issues EPA should consider to ensu re that society accrues the im portant benefits to environm ental protectio n that nanotechnology m a y offer, as well as to better understand any potential risk s from exposure to nanom aterials in the environm ent. This paper is the product of that workgroup.

The purpose of this paper is to inform EPA managem e nt of t h e science needs associated with nanotechnology, to support related EPA progr am office needs, and to communicate these nanotechnology science issues to stakeholders and the public. The paper begins with an introduction that describes what nanotechnology is, why EPA is interested in it, and what opportunities and challenges exist regarding nanotechnology and the environm ent. It then m oves to a discussion of the poten tial environm ental benefits of nanotechnology, describing environm ental technologies as well as other appl ications that can fost er sustainable use of

resources. The paper next provides an ove rview of existing inform ation on nanomaterials regarding components needed to conduct a risk assessm ent. Following that there is a brief section on responsible developm ent and the Agen cy’s statutory m a ndates. The paper then provides an extensive review of research needs for both en vironm ental applications and im plications of nanotechnology. To help EPA fo cus on priorities for the near term , the paper concludes w ith staff recommendations for addres s i ng science issues and research n eeds

, and includes prioritized research n eeds within m o st risk assessm en t topic areas (e.g., hum a n health ef

f

ects resea r ch, f a te and transpo r t r e search ). In a separ a te f o llow-up ef f

o rt to this W h ite Pape r,2 EPA Nanotechnology White Paper

EPA’s Nanotechnology Research Fram e w ork, attach ed in Appendix C of this paper, was developed by EPA' s Office of Research a nd Developm ent (ORD) Nanotechnology Research Strategy Team. This team is com pos ed of representatives from across ORD. The Nanotechnology Research Fram ewor k outlin es h o w EPA will strateg i cally focus its o w n research program to provide key inf o rm ation on potential environm ental im pacts from hum a n or ecological exposure to nanom aterials in a m a nner that com p lem e nts other federal, academ ic, and priva t e-s ector rese arch a c tiv ities. Addition a l su pplem ental inf o rm ation is provided in a num ber of other appendices.

Key Nanotechnology White Paper recommendations include:

• Environmental Applications Research. The Agency should continue to undertake, collaborate on, and support research to better understand and apply inform ation regarding environm ental applications of nanomaterials.

• Risk Assessment Resea rch. The Agency should continue to undertake, collaborate on, and support research to better understa nd and apply inform ation regarding

nanom aterials’:

o chem ical and physical identif ication and characterization,

o environm ental fate,

o environm ental detection and analysis,

o potential releases and hum a n exposures,

o hum a n health effects ass e ssm ent, and

o ecological effects assess m e nt.

To ensure that research best supports Agency decision m a king, EPA should conduct case stud ies to f u rther id entify unique risk assessm e nt considerations for

nanom aterials.

• Pollution P revention, S t ew ardship, and Sustainability. T h e Agency should engage resources and expertise to encourage, suppor t, and develop approaches that prom ote pollution prevention, sustainable resource use, and good product stewardship in the production, use and end of life m a nagem e nt of nanom aterials . Additionally, the Agency should draw on new, “next generation” na notechnologies to identify ways to support environm entally beneficial approaches such as green energy, green design, green chem istry, and green m a nufacturing.

• Collaboration and Lea d ership. The Agency should continue and expand its collaborations regarding nanom aterial appl ications and potentia l hum an health and environm ental im plications.

• Intra-Agen cy Workgroup. The Agency should convene a standing intra-Agency group to foster inform ation sharing on nano technology science and policy issues.3 EPA Nanotechnology White Paper

• Training. The Agency should continue and expa nd its nanotechnology training activities for scientists and m a nage rs.
Nanotechnology has em e r ged as a growing and rapidly changing fiel d. New generations of nanom a terials will evolve, and with them ne w and possibly unforeseen environm ental issues. It will be crucial that th e Agency’s approaches to leveraging the benefits and assessing the im pacts of nanom aterials continue to evolve in parallel with the expansion of and advances in these new technologies.4 EPA Nanotechnology White Paper



## 1.0 Int r oduction

1.1 Purpose

Nanotechnology presents potential opportunities to create better m a terials and products. Already, nanom a terial-containing products are available in U.S. m a rkets including coatings,

com puters, clothing, cosm etics, sports equipm ent and m e dical devices. A survey by EmTech Research of com p anies working in the field of nanotechnology has identi fied approxim a tely 80

consum er products, and over 600 raw m a terials, interm ediate com ponents and industrial equipm ent item s that are used by m a nufacturers (Sm a ll Tim e s Media, 2005). A second survey by the Project on Em erging Nanotec hnologies at the W oodrow W ils on International Center for Scholars lists over 300 c onsum er products (http:// www.nanotechproject.org/index.php?id=44 or http:// www.nanotechproject.org/consum e rproducts ). Our e c onom y will be incr easin gly af f

ected by nanotechnology as more products containing nanom aterials m ove from research and developm ent into production and commerce.

Nanotechnology also has the potential to im pr ove the environm ent, both through direct applic ation s of nanom a teria l s to detect, prevent, and rem ove pollu tants, as well as indirectly by using nanotechnology to design cl eaner industrial pr ocesses and create environm entally responsible products. H o wever, there are unanswered questions about the im pacts of

nanom aterials and nanoproducts on hum a n hea lth and the environm ent, and the U.S. Environm ental Protection Agency (EPA or “the Agency”) ha s the obligation to ensu re that potential risks are adequately understood to protect hum an health and the environm ent. As products m a de from nanom a terials becom e m o re num e rous and therefore more prevalent in the environm ent, EPA is thus considering how to best leverage advances in nanotechnology to enhance environm ental protection, as well as how the introduction of na nom a terials into the environm ent will im pact the Agency’ s environm ental p r ogra m s, policies, resea r ch ne eds, and approaches to decision making.

In Decem be r 2004, the Agency’s Science Poli cy Council con v ened an in tra-Agency Nanotechnology W o rkgroup and charged the group w ith developing a w h ite paper to exam ine the im plications and applications of nanotec hnology. This docum ent describes key science issues EPA should consider to ensu re that society accrues th e benefits to environm ental protection that nanotechnology m a y offer and that the Agen cy understands and addresses potential risks from environm en tal exposure to nanom aterials.5 EPA Nanotechnology White Paper

The purpose of this paper is to inform EPA managem e nt of t h e science needs associated with nanotechnology, to support related EPA progr am office needs, and to communicate these nanotechnology science issues to stakeholders and the public. The paper begins with an introduction that describes what nanotechnology is, why EPA is interested in it, and what opportunities and challenges exist regarding nanotechnology and the environm ent. It then m oves to a discussion of the poten tial environm ental benefits of nanotechnology, describing environm ental technologies as well as other appl ications that can fost er sustainable use of

resources. The paper next provides an ove rview of existing inform ation on nanomaterials regarding components needed to c onduct a risk assessm ent. Following that is a brief section on responsible developm ent and the Agency’s statut ory m a ndates. The paper then provides an
extens ive review of research needs for both environm ental app lications and im plications of nanotechnology. To help EPA focus on priorities for the near term , the paper concludes with staff recomm endations for addressing science issues and res earch needs, a nd includes prioritized research needs within m o st risk assessm ent topi c areas (e.g., hum a n health effects research, fate and transpo r t research ). In a separate fo llow-up ef f

o rt to this W h ite Paper

, EPA’s Nanotechnology Research Fram ewor k, attached in Appendix C of this paper, was developed by EPA' s Offic e of Research and Developm ent (ORD) Nanotechnology Research Strategy Team

. This team is com posed of representatives from across ORD. The Nanotechnology Research Fram ework outlin es ho w EPA will st ra tegically f o cus its own resea r ch p r ogram to provide key inform ation on potential environm ental im p acts from hum a n or ecological exposure to

nanom aterials in a m a nner that com p lem e nts other federal, academ ic, and private-s ector research activ ities. A ddition a l su pplem ental inf o rm ation is provided in a num ber of additiona l appendices.

A discussion of an entire technological pr ocess or series of processes, as is nanotechno logy, could b e wide rang ing. Howe ver, because EPA operates through specific
programm a tic activities and m a ndates, this doc um ent confines its discussion of nanotechnology science issues within the bounds of EPA’s statutory responsib ilities and authorities. In particula r , th e paper d i sc usses what s c ient if ic inf o rm ation EPA will need to addres s nanotechnology in environm ental decision m a king.



### 1.2 Nanotechnology Defined

A nanom e ter is one billionth of a m e ter (10 -9 m ) —about one hundred thousand tim es

sm aller than the diam eter of a hum a n hair, a thousand tim es sm aller than a red blood cell, or about half the size of the diam et er of DNA. Figure 1 illustrate s the scale of objects in the

nanom eter range. For the purpose of this docum en t, nanotechnology is defined as: research and technology developm ent at the atom ic, m o lecular, or m acromolecular levels using a length scale of approximately one to one hundred nanom eters in any dim e nsion; the creation and use of structures, devices and system s that have novel properties and f unctions because of their sm all size ; and the ability to co ntrol o r m a nipula t e m a tte r on an atom ic scale. This definition is based on part on the definition of nanotechnology used by the Na tional Nanotechnology Initiative (NNI), a U.S. governm e nt initiative launched in 2001 to coordinate na notechnology research and developm ent across the f e deral governm e nt (NNI, 2006a, b, c).6EPA Nanotechnology White PaperFigure 1. Diagram indicating relative scale of nanosized objects.(FromNNI website, courtesyOffice ofBasic EnergySciences, U.S. Departmentof Energy.)7 EPA Nanotechnology White Paper

Nanotechnology is the m a nipulation of m a tter fo r use in particular applications through certain chem ical and / or physical processes to create m a terials wi th specific properties. There are both "bottom

- up" processes (s uc h as self -as s e m b ly) that cr eate nanoscale m a terials from
atom s and molecules, as well as " t op- down" proc e sses (su c h as m illing ) tha t cre a te nano scale

m a terials fro m their m acro-scale coun terparts. F i gure 2 shows an exam ple of a nanom a terial

assem b led through “bottom

- up” processes. Na noscale m a terials that have m acro-scale counterparts frequently display different or enhanced properties com p ared to the m acro-scale for m

. For the rem a inder of this docum ent such enginee r ed or m a nuf actured nanomater ials will be ref e rred to a s “intention a lly produced nanom aterials,” or sim p ly “nanom aterials.” The definition of nanotechnology does not include unintentionally produced nanom a terials, such as diesel exhaust particles or other friction or airbor ne com bustion byproducts, or nanosized m a ter i als tha t occur na tura lly in the environm ent, such as viruses or volcanic ash. W h ere inform ation from incidentally form e d or natural nanosized m a terials (such as ultraf in e particulate m a tter )

m a y aid in the understanding of intentionally produced

nanom ateria ls, this inf o r m ation will be discuss e d

, but the focus of this docum ent is on intentionally produced

nanom aterials. Figure 2. Gallium Phosphide (GaP) Nanotrees. There are many types of intentionally produced
Sem i conductor nanowires produced b y nanom aterials, and a variety of others are expected to controlled seeding, vapor-liquid-solid appear in th e f u ture. For th e purpose of this docum ent, self-as s e m bly

. Bottom

- up processe s use d most current nanom aterials co uld be organized into four to produce materials su ch as these allo w types: for control ov er size and morphol og y. (Im a ge used b y perm issio n , Prof. Lars Sam u elson, Lund Uni v ersity, Sweden. [ D ick et al. 2004] )

(1) Carbon-based materials

. These nanom aterials are com p osed m o stly of carbon, most commonly taking the f o r m of a hollow spheres, e llipso ids, o r tubes. Spher i cal and ellipsoidal carbon nanom a terials are referred to as fullerene s, while cylindrical one s are called nanotubes. These particles have m a ny potential applica tions, including improved film s and coatings, stronger and lighter m a terials, and applications in electronics. Figures 3, 4, and 5 show exam ples of carbon-based nanom aterials.Figure 3. Computer image of a C-60 Fullerene. U.S. EPA

.

Figure 4. Computer images of various forms of carbon nanotubes. (Images courtesy of Center for Nanoscale Materials, Argonne National Laboratory) 8 EPA Nanotechnology White Paper

Figure 5. “Forest” of aligned carbon nanotubes. (Image courtesy David Carnahan of NanoLab, Inc.)

(2) Me tal-based mater i als. These nanom aterials include quantum dots, nanogold, nanosilver and m e tal oxides, such as titanium dioxide. A quantum dot is a closely packed sem i conductor crystal com p rised of hundreds or thousands of atom s, and whos e size is on the order of a few

nanom eters to a few hundred nanometers. Chan ging the size of quant um dots changes their optical properties. Figures 6 and 7 show exa m ples of m e tal-based nanom a terials.9 EPA Nanotechnology White Paper

Figure 6. Zinc oxide nanostructure synthesized by a vapor-solid process. (Image courtesy of Prof. Zhong Lin Wang, Georgia Tech) Figure 7. Computer image of a Gallium arsenide quantum dot of 465 atoms. (Image courtesy of Lin-Wang Wang, Lawrence Berkeley National Laboratory)

(3) Dendrimers

. Thes e nanom aterials are nano sized po lymers built from branched units. The surface of a dendrim er has num erous chain ends, which can b e tailored to perform specific chem ical functions. Th is property could also b e useful for catalys i s. Als o, because threedim e nsional dendrim ers contain interior cavities into which other m o lecules could be placed, they m a y be useful for drug delivery. Fi gure 8 shows an example a dendrim e r.

Figure 8. Computer image of generations of a dendrimer. Dendrimers are nanoscale branched polymers that are grown in a stepwise fashion, which allows for precise control of their size. (Image courtesy of Dendritic NanoTechnologies, Inc.)10 EPA Nanotechnology White Paper

Figure 9. Computer image of a nano-biocomposite. Image of a titanium molecule (center) with DNA strands attached, a bio-inorganic composite. This kind of material has potential for new technologies to treat disease. (Image courtesy of Center for N anoscale Materials, Argonne N ational Lab) (4) Composites com b ine nanoparticles with other nanoparticles or with larger, bulk-type materials. Nanoparticles, such as nanosized clays, are already being added to products ranging from auto parts to packag in g m a terials, to enhance m echanical, therm a l, barrier, and flam e-retardant properties. Figure 9 shows an exam ple of a

com posite.

The unique properties of these various types of intentionally produced nanom ateria ls give them novel electrical, catalytic, m a gnetic, m echanical, ther m a l, or i m aging features that are high ly d e sirab l e for application s in comm ercial, m e dical,

m ilitary, and environm ental s ecto r s. These m a terials m a y als o find their way into m o re com p lex nanostructures and system s as described in Figure 10. As new uses for m a terials with these special properties are identif ied, the num b er of products containing such nanom a t erials a nd their possible applications continues to grow. Table 1 lists som e exam ples of nanotechnology products listed in the W oodrow W ilson Center Consum er Products Inventory ( http://www.nanotechproject.org /44/consum er-nanotechnology ). There are estim a tes that g l obal sales of nan o m a terials could exceed $1 trillion b y 2015 (M. C . Roco, presentation to the Nation a l Research Council, 23 March 2005, presentation available at http://www.nsf.gov/crssprgm /nano/reports/nnipres.jsp ).Table 1. Examples of P r oducts that Use Nanotechnology and Nanomaterials

Health and Fitness Electronics and Computers Home and Garden Food and Beverage Other

Wound dressing

Pregnancy test

Toothpaste

Golf club

Tennis Rack et

Skis

Antibacterial socks

Waste and stain resistan t pan t s

Cosm etics

Air f ilte r

Sunscreen Com puter displays

Ga m e s

Com puter hardware Paint

Antim icrobial pillows

Stain resistant cushions Non-stick coatings for pans

Antim icrobial refrige r ato r

Canola oil Coatings

Lubricants 11 EPA Nanotechnology White Paper

Source: Wo odrow Wilson Center Consumer Products Inventory. ( http://www .nanotechproject.org /44/consumer-nanotech nology )

1.2.1 Converging Technologies

In the long-term , nanotechnology will likely be increasingly discussed within the context of the convergence, integrat ion, and synergy of nanotechno logy, biotechnology, inform ation technology, and cognitive technology. Convergen ce involves the develo pm ent of novel products with enhanced capabilities that incorporate bo ttom

- up asse mbly of m i niature com ponents with

accom p anying biological, com putational and cog n itiv e capab ilities. The convergence of nanotechno logy and biotechnology, alr eady rapid l y progress i n g, will result in the p r odu ction of novel nanoscale m a terials. The convergen ce of nanotechnology a nd biotechnology with inform ation technology and cognitiv e scien ce is expected to rapid l y accelerate in the com i ng decades. Th e increased understand ing of biologi cal system s will prov ide valuable inform ation towards the developm ent of efficient and versatile biom i m etic tools, system s, and architecture.

Generally, biotechnology involves the use of m i croorganisms, or bacterial factories, which contain inherent “bluep rints” encoded in the DNA, an d a m a nu facturing process to produce m o lecules su ch as am ino acids. W ithin these bacterial factories, the organ i zation and12 EPA Nanotechnology White Paper

self -assem b ly of com p lex m o lecules occurs ro utinely. Many “finished” com p lex cellular products are < 100 nanom eters. For this reason, b acterial factories m a y serve as m odels for the organization, assem b ly and transform a tion for other nanoscale m a terials production.

Bacterial factory blueprints are also f l exib le. They can be m o dified to produce novel nanobiotechnology products that have specifi c desired physical-chem i cal (perform ance) characteristics. Using this pr oduction m e thod could be a m o re m a terial and energy ef ficient way
to m a ke new and existing products, in addition to using m o re benign starting m a terials. In this way, the convergence of nano- and biotechnologie s could im prove environm ental protection. As

an exam ple, researchers have extracted photosynth etic proteins from spinach chloroplasts and coated them with nanofilm s that convert sunlight to electrical cu rrent, which one day may lead to energy generating film s and coat ings (Das et al., 2004). The addition of infor m ation and cognitive capabilities will prov ide ad d ition a l features including programm a bility,

m i niaturization, increased power cap acities, ad ap ta bility, and reactive, s e lf -correcting capacities.

Another example of converging technologies is the developm ent of nanom eter-sized biological sensor devices that can detect specific com pounds w ithin the natura l environm ent; store, tabulate, and process the a ccu mulated data; and de ter m ine the import of the d a ta, prov idin g a specific response for the resolv ed conditions would enable rapi d and effective hum a n health and environm ental protection. Resp onses could range from the re lease of a certain am ount of biological or chem ical compound, to the rem oval or transformation of a compound.

The convergence of nanotechnology with bi otechnology and with information and cognitive technologies m a y provide such dram atically different technology products that the

m a nufacture, use and recycling/disposal of thes e novel products, as well as the developm ent of policies and regulations to prot ect hum a n health and the environm ent, m a y prove to be a daunting task.

The Agency is comm itted to keeping abreas t of em erging issues within the environm ental arena, and continues to support critical research, fo r m ulate new policies, and adapt existing policies as needed to achieve its m i ssion. Howeve r, the convergence of these technologies will dem a nd a fl exible, rapid and highly adaptable ap proach within EPA. As t h ese technologies progress and as novel products em erge, increasin gly the Agency will find that m eetin g constan tly changing dem a nds depe nds on taking proactive actions and planning.

We m a y be nearing the end of basic research and developm ent on the first generation of

m a terials resulting from nanotechnologies that include coatings, polym ers, m o re reactive catalysts, etc. (Figure 10). The second generatio n, which we are beginning to enter, involves targeted dru g delivery s y stem s, adaptive s t ructu r es and actuators, and has already provided som e interesting exam ples. The third generation, anticipat ed within the next 10-15 years, is predicted to bring novel robotic devices, three-dim e nsional networks and guided assem b lies. The fourth stage is pred icted to re su lt in m o lecule-by-m o lecule design and self-assem b ly capabilities. Although it is not likely to happen for som e ti m e , this integration of th ese fourth-generation nanotechno logies with infor m ation, biological, a nd cognitive technolog ies will lead to products which can n o w only be im agined. W h ile the A g ency will n o t be able to predic t the f u ture, it needs to prepare for it. Towards that aim

, understanding the unique chal lenges and opportunities13 EPA Nanotechnology White Paper

afforded by converging technologies before they occur will provide the A g ency with the essential tools for the effectiv e and appropriate response to em erging technology and science.

T e ch n o logi c a l Com p le x i t y inc r ea s i ng
First Generation ~2001: Passive nanostructures
Nano-structured coatings, nanoparticles, nanostructured metals, polymers, ceramics, Catalysts, composites, displays

Second Generation ~Now: Active nanostructures
Transistors, amplifiers, targeted drugs and chemicals, actuators, adaptive structures, sensors, diagnostic assays, fuel cells, solar cells, high performance nanocomposites, ceramics, metals

Third Generation ~ 2010: 3-D nanosy stems and systems of nanosystems
Various assembly techniques, networking at the nanoscale and new architectures, Biomimetic materials, novel therapeutics/targeted drug delivery

Fourth Generation ~2015 Molecular Nanosystems

Molecular devices ”by design”, atomic design, emerging functions

Figure 10. Projected Stages of Nanotechnology Development. This analyis of the projected stages of nanotec hnology development was first conceptualized by M.C. Roco.



### 1.3 Why Nanotechnology Is Important to EPA

Nanotechnology holds great prom ise for creati ng new m a terials with enhanced properties and attribu t es. These pro p erties, such as grea ter c a taly tic ef f i ciency, in crea sed ele c tr ica l conductiv ity , and im proved hardness and streng th , ar e a result of nanom a terials’ larg er surface area per unit of volum e and quantum effects that occur at the nanom eter scale (“nanos cale”). Nanom a terials are already being used or tested in a wide range of products such as sunscreens,

com posites, m e dical and electronic devices, and chem ical catalysts. S i m ilar to nanotechnology’s success in consum er products and other sectors, nanom aterials have prom ising environm ental applications. For exam ple, nanosized cerium oxi de has been developed to decrease diesel

em issions, and iron nanoparticles can rem ove contam inants from soil and ground water. Nanosized sensors hold prom ise for im proved detect ion and tracking of contam inants. In these and other w a ys, nanotechnology presents an opport unity to improve how we m easure, m onitor,

m a nage, and reduce con t am inants in the environ m ent.

Som e of the sam e special properties that m a ke nanom a terials useful are also properties that m a y cause som e nanom aterials to pose hazards to hum ans and the environm ent, under14 EPA Nanotechnology White Paper

specific conditions. Som e nanom a t e rials that ente r anim al tissues m a y be able to pass through cell m e m b ranes or cross the blood-bra in barrier. This m a y be a beneficial characteristic for such uses as targeted drug delivery and other dise ase treatm e nts, but coul d result in unintended im pacts in other uses or applications. Inhale d nanoparticles m a y becom e lodged in the lung or be translocated, and the high durability and reactiv ity of som e nanom aterials raise issues of their fate in the environm ent. It m a y be that in m o st cases nanom aterials will not be of human health or ecological concern. However, at this point not enough infor m ation exists to assess environm ental exposure for m o st engineered nano m a terials. This information is im portant because EP A will need a sound scientific bas i s fo r asses s ing and m a naging any unforeseen future im pacts resulting from the introduction of nanopar ticles and nanom a terials into the environm ent.

A challenge for environm ental protection is to h e lp f u lly r ealize th e socie t al ben e f its of nanotechnology while identifying an d m i nim i zing any adverse im pacts to hum a ns or ecosystem s from exposure to nanom aterials. In addition, we need to understa nd how to best apply nanotechnology for pollution prevention in cu rrent m a nufact uring pr ocesses and in the

m a nufacture of new nanom ateria ls and nanoproducts, as well as in environm ental detection, monitoring, and clean -u p. This understand ing will com e from scientific inform ation generated by environm ental research and developm ent activ ities within g overnm e nt agencies, academ i a, and the priv ate sector.



### 1.4 National and International Context

EPA’s role in nanotechnology exists within a range of activities by federal agencies and other groups that have been ongoing for several years. Figure 11 lists examples of federal sources of infor m ation and inte raction to inform EPA’s nanotec hnology activities. Many sectors, includ ing U.S. federal an d state agen cies, academia, the p r ivate-sector, o t h e r national
governm e nts, and international bodies, are consider ing potential environm en tal applications and im plications of nanotechnology. This section descri bes som e of the m a jor pl ayers in this arena, for two principal reasons: to describe EPA’s role regarding nanotechnology and the environm ent, and to identify opportunities fo r collaborative and com p le mentary efforts.

### Understanding Nanotechnology Implications

Characterization

, Properties

DOD DOE EPA NASA NIH NIST NSF Instrumentation, Metrology, Standards

DOD DOE NASA NIH NIST NSF Toxicity

DOD EPA FDA NIH NIOSH NSF EPA

Research

Risk assessment

Risk management

Sustainability

Stewardship Fate, Transport, Transformation, Release, Treatment

DOD DOE EPA NIH NIOSH NSF

Sensors, Devices

DHS DOD DOE EPA NASA NIH NIOSH NIST NSF USDA USGS Pollution Prevention
Green manufacturing Green Engineering

Green Energy

EPA DOD DOE Remediation

EPA DHS DOD NASA NSF Detection, Monitoring

DOD EPA NIH NIOSH NSF USGS 

### Applications Note: NIH includes NIEHS, NCI (NCL), NTP

Figure 11. Federal Sources to Inform EPA’s Nanotechnology Activities. (Based on information in the NNI Supplement to the 2006 and 2007 budget and other information.) 15 EPA Nanotechnology White Paper

1.4.1 Federal Agencies – The Nation al Nanotechnology Initiative

The National Nanotechnology Initiative ( NNI) w a s launched in 2001 to coordinate nanotechnology research and developm ent across the federal governm e nt. Investm e nts into federally funded nanotechnology-re lated activities, coordinate d through the NNI, have grown from $464 m illion in 2 001 to appro x im ately $1.3 billion in 2006.

The NNI supports a broad range of resear ch and developm ent including fundam e ntal research on the unique phenom ena a nd processes that occur at the nano scale, the design and discovery of new nanoscale m a terials, and th e developm ent of nanotechnology-based devices and system s. The NNI also supports research on instrum e ntation, m e tr ology, standards, and nanoscale manufacturing. Most im portant to EP A, the NNI has m a de responsible developm ent of this new technology a prior ity by supporting research on envi ronm ental health and safety im plications

. Twenty-f ive f e deral age n cies cu rren tly pa rticipa t e in the NNI , thir teen of which have budgets which include to nanotechnology research a nd developm ent. The other twelve agencies have m a de nanotechnology relevant to their m i ssions or regulatory roles. Only a sm all part of this federal investm e nt aim s at researching the social and environm ental implications of nanotechnology including its eff ects on hum a n health, the envir onm ent, and society. Nine– 16 EPA Nanotechnology White Paper

f

e deral agen cies a r e inv e sting in im plications r e se arch in cluding the Natio nal Scien c e Foundation, the Nation a l Institutes of Health, th e National Ins titu te for Occupation a l Health and Safety, and the Environm ental Protection Agenc y. These ag encies coord i nate their efforts through th e NNI’s Nanoscale Science, Engineer ing, and Technology Subcomm ittee (NSET) and its Nanotechnology Environm ental Health Im plications workgr oup (NEHI) (Figure 12). The President’s Council of Advisors on Science and Technology (PCAST) has been designated as the national Nanotechnology Advisory Panel called for by the 21 st Century Nanotechnology Research and Development Act of 2003. As su ch, PCAST is responsible for assessing and

m a king recommendations for im proving the NNI

, includ ing its activities to address environm ental and other societal im plica tions. T h e Nationa l Research Council also provides

assessm ents and advice to the NNI.

Work under the NNI can be m onitored through the website http://www.nano.gov.

ECT e a g ue NNCO/ NSE T / NST C NRC Revi ew o f t h e NN I A u g u s t 25- 2 6 , 2005 

## E ubco mitt ee W o rking Leve action NS T S m ee Work ing Lev e l Inter s

NN C O O ffice o f S c ience a n d Te c h n o lo g y P o lic y 24 A g encies Pa rt ic i p a t i n g in NN I

In du s t r y S e c t or s Ho use o f Re p r esent a tives Co mm i ttee o n Sci e nce

Sena t e C o m m it tee o n Co mme rc e, Sc i e nce a n d Tr an s p o r t a ti on Pre s s Na t i o n a l Resea r c h Co u n c i l

Off i c e o f M

a n a g e ment

an d B u d g e t NNA P (P C A S T )

P r of e s

s i on a l So ciet ies In t e r n at i o n a l Org a ni za ti o n s NSET Subco m m

.

Wo r k i n g G r ou ps an d T a s k Fo r c e s o f N S E T Su b c o m m i t t ee GI N WG NE H I WG

Non

- go vern men t a l

Org a ni za ti o n s NI L I WG NP E G WG

R e gi ona l , S t at e , an d L o c a l N a no t e c h no l o g y I n i t i a t i v e s

Figure 12. NNI NSET Subcommittee Structure

1.4.2 Efforts of Other Stakeholders

About $2 billion in annual re search and developm ent investm e nt are being spent by nonfederal U.S. sectors such as states, academ i a, and private industry. State governm e nts collectiv ely spent an es tim a ted $400 m illion on facili ties and research aimed at th e dev e lopm ent of local nanotechnology industr ies in 2004 (Lux Research, 2004).17 EPA Nanotechnology White Paper

Although the industry is relatively new, the private sector is l eading a number of initiatives. Several U.S. nanotechnology trade associations have em erged, including the NanoBusiness Allian ce. The Am erican Chem is try Council also has a co mmittee dev o ted to nanotechnology and is encouraging research into the environm ental health and safety of

nanom aterials. In addition, the Nanoparticle Oc cupational S a fety and Health Consortium has been form ed by industry to investigate occupation al safety and health issues associated with aerosol n a no particles and workplace exposure m o nitoring and protoco l s. A directo r y of nanotechnology industry-related or ganizations can be found at http://www.nanovip.com

.

Environm en tal nongovern m e ntal organizations (NGOs) such as Environm ental Defe nse, Greenpeace UK, ETC Group, and th e Natural Res ources Defense Council are engaged in nanotechnology issues. Also, scient ific organizations such as the National Academ y of Sciences, the Royal S o ciety of the United Kingdom

, and th e Internatio nal Life Sciences Ins t itute are providing important advice on i ssues related to nanotechno logy and the environm ent.

1.4.3 Intern ational Activities

Fully understanding the environm ental applic ations and im plications of nanotechnology will depend on the conce r ted ef f

o rts of scientists and policy m a kers across the glob e. Europe and Asia m a tch or exceed the U.S. federa l nanotechnology research budget. Globally, nanotechnology research and developm ent spe nding is estim a ted at around $9 billion (Lux Research, 2006). Thus, a great opportunity exists for internationally coordinated and integrated efforts toward environm ental research. Other governm e nts have also undertaken efforts to identify research needs for nanom aterials (Uni ted Kingdom (UK) Departm e nt for Environm ent, Food and Rural Affairs, 2005; Euro pean Union Scientific Comm ittee on Em erging and Newly Identified Health Risks (EU SCENIHR), 2005). International organi zations such as the International Standards Orga nization and the Organisation for Econom i c Co-operation and Developm ent (OECD) are engaged in nanotechnol ogy issues. ISO has established a technical

comm ittee to develop in terna tiona l s t andards f o r nanotechnologies. This technical co mmittee, ISO/TC 229 will develo p standard s for term inolo gy and nomenclature, m e tro l ogy and instrum e ntation, including specifications for re ference m a terials, test m e thodologies, modeling and sim u lation, and science-based health, safety and environm ental practices.

The OECD has engaged the topic of the im plications of m a nuf actured nan o m a terials

am ong its mem b ers under the ausp ices of the Jo in t Meeting of the Chem icals Comm ittee and Working Party on Chemicals, Pesticides a nd Biotechnology (Che m i cals Comm ittee). On the basis of an international workshop hosted by EPA in W a shington in December 2005, the Joint Meeting has agreed to establish a subsidiary body to work on the environm ental health and safety im plications of manufactured nanom aterials , with an eye towards enhancing international harm onization and burd e n sharing. In a relate d activ ity, the OECD’s Committee on Scientific and Technology Policy is considering establishing a subsidiary body to address other issues related to realizing comm ercial and public benefits of advances in nanotechnology.

Additionally, the United States and European Union Initiative to Enhance Transatlantic Econom ic Integration and Growth (June 2005) addresses nanotechnology. Specifically, the Initiative s t ates th at th e United States and the Eu ropean Unio n will work together to, am ong18 EPA Nanotechnology White Paper

other things, “support an internat ional dialogue and cooperative activities for the responsible developm ent and use of the em erging field of na notechnology.” EPA is also currently working with the U.S. State Departm e nt, the NNI, and the EU to bring about research partnerships in nanotechnology. Furtherm ore, in the context of environm ental science, the EPA has worked with f o reign resea r ch in s titu tes and a g enci es (e.g. , UK and Taiwan) to he lp inf o rm nanotechnology and related enviro nm ental research programs.

By continuing to actively participa t e in inte rna tio nal sc ientif ic f o ra, EPA will be well position e d to inf o rm both dom e stic a nd inte rnat io nal environ m ental polic y. This will provide essential support for U.S. policy m a kers who work to negotiate inte rnation a l treaties an d trade regim e s. As products m a de from na nom a te rials becom e m o r e common in dom e stic and international channels of trade, policy m a kers will then be able to rely on EPA for the high quality scien ce neces sary to m a ke effectiv e deci sions that could have a sig n ificant im pact, both dom e stically and internationally, on hum a n and environm ental health, and econom ic we ll-being.



### 1.5 What EPA is Doing w i th Respect to Nanotechnology

EPA is actively participating in nanotec hnology developm ent and evaluation. Som e of the activities EPA has undertaken include: 1) actively participa ting in the National Nanotechnology Initiative, which coordinates nano technology research and development across the federal governm e nt, 2) collaborating with sc ie ntists in tern ationa lly in order to shar e the growing body of infor m a tion on nanotechnology, 3) funding nanotechnology research through EPA’s Science To Achieve Results (STAR) grant program and Sm all Business Innovative Research (SBIR) program and perform i ng in-house research in the Office of Research and Developm ent, 4) conducting regi onal nanotechnology research for rem e diation, 5) initiating the developm ent of a voluntary program for the evaluation of nanom a te rials and reviewing

nanom aterial prem anufa c ture notif ic ations in the Off i ce of Pollu tion Prevention and Toxics, 6) reviewing nanom aterial registrati on applic ation s in the Of f i ce of Air and Radiation/Office of Transportation and Air Quality, 7) reviewing potential nanoscale pesticid es in th e Office of Pestic ide Pr ogram s, 8) investig ating the us e of nanoscale m a terials for environm ental

rem e diation in the Office of Solid W a ste and Em ergency Response; and 9) reviewing inform ation and analyzing issues on nanotec hnology in the O ffice of Enforcem ent and Com p liance Assurance.

.
1.5.1 EPA’s Nanotechnology Research Activities

Since 2001, EPA’s ORD STAR grants program has funded 36 research grants nearly 12

m illion in th e applicatio ns of nanotechnology to protect the environm ent, includ ing th e developm ent of: 1) low-cost, rapid, and sim p lifie d m e thods of re m oving toxic contaminants from water, 2) new sensors that are m o re sensitive fo r m easuring pollutants, 3) green m a nufacturing of

nanom ateria ls; and 4 ) more ef f i cient, selec tive ca talys t s. Addition a l app l ication s projects hav e been funded through the SBIR program.

In addition, 14 recen t STAR program projec ts focus on studying the possible harm ful effects, or implications, of engineered nanom ateria ls. EPA has awarded or selected 30 grants to date in this area, to taling approxim a tely $10 m illion. The m o st-recen t res earch so licitations19 EPA Nanotechnology White Paper

include partnerships with the National Sc ience F oundation, the National Institute for Occupational Safety and Health, and the National Institute of Environm ental Health S c iences. Research areas of interest for this proposal in clude the toxicology, fate, release and treatm ent, transpo r t an d transform a tion, bio a vailability, hum an exposure, and life cycle assessm e n t of

nanom aterials. Appendix D lists ST AR grants funded through 2005.

EPA’s own scientists have done research in areas related to nanotechnology, such as on the toxicity of ultrafine partic ulate m a tter (e.g., Dreher, 2004). In addition, EPA scientists have begun to gather inform ation on various environm en tal applications currently under developm ent. ORD has also led developm ent of an Agen cy Nanotechnology Research Fram e w ork for conducting and coordinating intramural and ex tram ural nanotechnology research (Appendix C).

1.5.2 Regional Nanotechnology Research Activities for R e mediation

A pilot study is planned at an EPA Region 5 National Priorities List site in Ohio. The pilot s t udy will in ject zero-valent iron nanoparticles into th e groundwater to tes t its effectivenes s in rem e diating volatile organic com p ounds. The st udy includes sm aller pre-pilot studies and an investigation of the ecol ogical effects of the treatm ent m e tho d. Inform ation on the pilot can be found at http://www.epa.gov/region5/sites/nease /index.htm

. Other EPA Regions (2, 3, 4, 9, and 10) are also considering the use of ze ro-valent iron in site rem e diation.

1.5.3 Office of Pollution Prevention and Toxics Activities Related to Nanoscale Materials

EPA’s Office of Pollution Prevention and T oxics (OPPT) convened a public m eeting in June 2005 regarding a potential voluntary pilot program for na noscale m a terials. (“N a noscale Materials; N o tice of Public Meeting,” 70 Fed. Reg. 24574, May 10, 2005). At the m eeting EPA received comment from a broad spectrum of st akeholders concerning all aspects of a possible stewardship program

. Subsequent ly, OPPT invited the National Pollution Prevention and Toxics Advisory Comm ittee (N PPTAC) to provide its view s. NPPTAC established an Interim Ad Hoc Work Group on Nanoscale Materials which m e t in public to further discuss and receive additional public input on issues pertaini ng to the voluntary pilot program for nanoscale

m a terials. T h e Interim Ad Hoc W o rk Group on Nanoscale Materials developed an overview docum ent describing possible general param e ters of a voluntary pilot program

, which EPA is considering as it m oves forward to develop and implem e nt s u ch a program. OPPT is already reviewing p r em anufacture notifica tions for a number of nanom ateria ls that have been received under the Toxics Substan ces Control Act (TSCA).

1.5.4 Office of Air and Radiation/ Office of Transportation and Air Quality - Nanomaterials Registration Applications

EPA’s Office of Air and Radiation/Office of Transportation and Air Quality has received and is rev i e w ing an applica tion f o r r e gistrati on o f a diesel ad ditiv e conta i ning cer ium oxide. Cerium oxide nanoparticles are being m a rketed in Europe as on- and off-road diesel fuel additives to decrease emissions and som e m a nufa c turers are claim i ng fuel econom y be nefits.20 EPA Nanotechnology White Paper

1.5.5 Office of Pesticide Programs to Re gulate Nano-Pesticide Products

Recently, m e m b ers of the pesticide industr y hav e engaged th e Office of Pesticide Program s (OPP) regarding licensing /registration requirem e nts for pesticide products that m a ke use of nanotechnology. In response to the rapid em ergence of these products, OPP is form ing a largely intra-office workgroup to consider poten tial exposure and risks to hum a n health and the ecological environm ent that m i ght be associated with the use of nano-pest icide s

. Spec if ically, the workgro up will cons ider wheth e r or not ex isting data are s u fficient to s upport licensing/registration or if the unique characteristics asso ciated with nano-pesticides w a rrant additional y e t undefined testing. Th e workgroup will cons ider the exposu r e and hazard profiles associated w ith these new nano-pesticides on a ca se-by-case basis and ensure consistent review and regulation across the program

.
1.5.6 Office of Solid Waste and Emergency Response

The Office of Solid W a ste and Em ergency Re sponse (OSW ER) is inve stigating potential im plications and applications of nanotechnology that m a y affect its program s

. In October 2005, OSWER worked with E P A’s ORD a nd several othe r federal agencies to organize a W o rkshop on Nanotechnology for Site Re m e diation. The m ee ting summary and presentations from that workshop are available at http://www.frtr.gov/nano

. In July 2006, OSWER held a symposium entitled, “Nanotechnology and OSWER: New Oppor tunities and Challenges.” The sym posium featured national and internati onal experts, researchers, and industry leaders who discussed issues relevant to nanotechnol ogy and waste m a nagem e nt practices and focused on the life cycle of nanotech nology prod ucts. Inform ation on the sym posium will be po sted on OSWER’s website. OSWER’s Technology Inn ovation and Fiel d Serv ices Division (TIFSD) is com p iling a databas e of infor m ation on hazardou s waste sites where project m a nagers are cons idering using nanoscale zero-valent iron to addr ess groundwater contam ination. TI FSD is also preparing a fact sheet on the use of nanotechnology for site rem e di ation that will be us eful for site project

m a nagers. In addition, TIFSD has a website with links to relevant inform ation on nanotechnology ( http ://c lu-in.o rg/na n o ).

1.5.7 Office of Enforcement and Compliance Assurance

The Office of Enforce m e n t and Compliance Assurance (OECA) is reviewing Agency inform ation on nanotechnology (e.g., studies, res earch); evaluating ex isting statutory and regulatory fram e works to determ ine the enforcem ent issues associated w ith nanotechnology; evaluating the science issues for regulation/enfor cem ent that are associated with nanotechnology, and; considering what infor m a tion OECA’s National Enf o rc em ent Investigations Center (NEIC)

m a y need to consider to support the Agency.

1.5.7 Communication and Outreach

Gaining and m a intaining public trust and support is im portant to fully realize the societal benefits and clearly com m unicate the im pacts of nanotechnology. Responsible developm ent of nanotechnology should involve and encourage an ope n dialogue with all concerned parties about potential ris k s and benefits. EPA is comm itted to keeping th e public inform ed of the potential environm ental im pacts associated with nanom ateria l develop m ent and applica tions. As an initial21 EPA Nanotechnology White Paper

step, EPA is developing a dedica ted web site to provide com p re hensive infor m ation and enable transparent dialogue concer ning nanotechnology. In addi tion, EPA has been conducting outreach by organizing and sponsor ing sessions at professional society m eetings, speaking at industry, state, and internati onal nanotechnology m eetings.

EPA already has taken steps to obtain public feed back on issu es, alternativ e approach es, and decisions. For example, the previously noted OPPT public m eetings were designed to discuss and receive public inpu t. EPA will c ontinue to work collabo rativ e ly with all stakeholders, including industry, other governm e nt al entities, public in terest groups, and the general public, to identify and assess potential en vironm ental hazards and exposures resulting from nanotechnology, and to discuss EPA’s roles in addressing issues of concern. EP A' s goal is to earn and retain the public’s trust by providing inf o rm ation that is obje c tive, balanced, accurate and tim ely in its presentation, and by using transparent public invol vem e nt processes.



### 1.6 Opportunities and Challenges

For EPA, the rapid developm ent of na notechnology and the in creasing production of

nanom aterials and nanoproducts present both oppor tunities and challenges. Using nanom a terials in applications that advance gr een chem istry and engineering and lead to the developm ent of ne w environm ental sensors and rem e diation technol ogies m a y provide us with new tools for preventing, identifying, and solving environm ental pr oblem s. In addition, at this early juncture in nanotechnology’s developm ent, we have the opport unity to develop approa ches that will allow us to produce, use, recycle, and eventually dis pose of nanom a terials in ways that protect hum an health and safeguard the natural environm ent. The integration and synergy of nanotechnology, biotechno lo gy, inform at ion techno lo gy, and cognitiv e techn o logy will p r esent oppo rtunities as well as challenges to EP A and other regulator y agencies. To take advantage of these opportunities and to m eet the challenge of ensu ring the environm entally safe and sustainable developm ent of nanotechnology, EPA m u st understa nd both the potential benefits and the potential impacts of nanom a teri als and nanoproducts. The followi ng chapters of this docum ent discuss the s c ience issues surround in g how EPA will gain an d apply such understand ing.22 EPA Nanotechnology White Paper



## 2.0 En vironm ental B e nefi ts of Nanotechnology

2.1 Introduction

As applications of nanotechnology develop ove r tim e, they have th e potential to help shrink th e h u m a n footprint on th e en vironm ent. This is im portan t , becaus e over th e n e xt 50 years the world’s population is ex pected to grow 50%, global ec onom ic activity is expected to grow 500%, and global energy and m a terials use is expected to grow 300% (W orld Resources Institute, 2000). So far, increased levels of pr oduction and consum ption have offset our gains in cleaner and more-efficient technolo gies. This has been true fo r m unicipal waste generation, as well as for environm ental im pacts associated with vehicle travel, groundw ater pollution, and agricu ltu ral runoff (OECD, 2001). This chap ter will des c rib e how nanotechnology can create

m a terials and products that will not only directly advance our ab ility to detect, m onitor, and clean-up environm ental contam inants, but also help us avoid creating pollution in the f i rst place. By m o re effectively using m a terials and en ergy throughout a product lif ecycle, nanotechnology

m a y contribute to reducing pollution or energy intensity per unit of econom i c output, reducing the “volum e effect” described by the OECD.



### 2.2 Benefits Through Environmental Technology Applicati o ns

2.2.1 Remediation/Treatment

Environmental remediation includes the degradation, sequestration, or other related approaches that result in reduced risk s to human and environmental receptors posed by chemical and radiological contaminants such as those found at Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), Resource Conservation and Recovery Act (RCRA), the Oil Pollution Act (OPA) or other state and local hazardous waste sites. The benefits from use of nanomaterials for remediation could include more rapid or cost-effective clea nup of wastes relative to current conventional approach es. Such benefits may

Figure 13. Nanoscale zero-valent iron encapsulated in an emulsion droplet. These nanoparticles have been used for remdiation of sites contaminated with variuos organic pollutants. (Image cortesy of Dr. Jacqueline W. Quinn, Kennedy Space Center, NASA) derive from the enhanced reactivity, surface area, subsurface transport, an d/or sequestration characteristics of nanomaterials.

Chloro-orga n ics are a major c l ass of
contam inants at U.S. waste sites, and several

nanom aterials have been applied to a i d in th eir

rem e diation. Zero-valent ir on (Fig. 13) has been used successfully in the past to rem e diate groundwater by construction of a perm eable reactive barrier (iron wall) of zero-valent iron to intercept a nd dechlorinate chlorina ted hydrocarbons such as trichloroethylene in groundwater plum es. Labor atory studies indicate that a wider range of chlorinated hydrocarbons m a y be de chlorina ted using various nanoscale iron particles23 EPA Nanotechnology White Paper

(princ ipa lly by abiotic means, with z e ro-va l ent iron serving as th e bulk reducing agent), including chlorinated m e thanes, ethanes, ben zenes, and polychlorinated biphenyls (E lliot and Zhang, 2001). Nanoscale zero-valent iron m a y not only treat aqueous di ssolved chlorinated solvents in situ, but also m a y re m e di ate the dense nonaqueous phase liqui d (DNAPL) sources of these contam inants within a quifers (Quinn et al., 2005).

In addition to zero-valent iron, other nanosi zed m a terials such as m e talloporphyrinogens have been tested for degradation of tetrach lorethylene, trichlor oethylene, and carbon tetrachloride under anaerobic condi tions (Dror, 2005). Titanium oxi de based nanom aterials have also been developed for potential use in the pho tocatalytic degradation of various chlorinated

com pounds (Chen, 2005).

Enhanced retention or solubi lization of a contam i n ant m a y be helpful in a rem e diation setting. Nanom a terials m a y be useful in decreasing sequestra tion of hydrophobic contam inants, such as polycyclic arom atic hydrocarbons (PAHs), bound to soils and sedim e nts. The release of these con t am inants from sedim e nts and soils co uld m a ke them more accessible to in situ biodegradation. For example, nanom aterials made from pol y(ethylene) glyc ol m odified urethane acrylate have been used to enhance the bioava ilability of phenanthren e (Tungittiplakorn, 2005).

Metal rem e diation has also been proposed, using zero-valent iron and other classes of

nanom aterials. Nanoparticles such as poly(am idoam i ne) dendrim ers can serve as chelating agents, and can be further enhanced f o r ultraf iltr ation of a variety of m e tal i ons (Cu (II), Ag(I), Fe(III), etc.) by attaching f unctional groups such as prim ary am ines, carboxylates, and hydroxym ates (Diallo, 2005). Other research indi cates that arsenite and arsenate m a y be precip itated in the subsu rface using zero-valen t iron, m a king arsenic less mobile (Kan el, 2005). Self-assem b led m onolayers on m e soporous s upports (SAMMS) are nanoporous ceram ic

m a terials that have been developed to rem ove mercury or radionucli des from wastewater (Mattigod, 2003).

Nanom a terials have also been stud ie d f o r their a b ility to re move m e tal contam inants from air. Silica-titania nanocomposites can be used for elem ental m e rcury removal from vapors such as those com i ng from c o m bustion s ources, with silica se rvin g to enhance adsorption and titania to photocatalytically oxidize elem ental m e rcury to the less volatile m e rc uric oxide (Pitoniak, 2005). Other authors have dem onstrated nanostructu red silica can sorb other m e tals generated in

com bustion environm ents, such as lead and cadmium (Lee et al., 2005; Biswas and Zachariah, 1997). Certain nanostructured sorbent proces ses can be used to prevent em ission of nanoparticles and create byproducts that are useful nanom ater ials (Biswas et al., 1998)

2.2.2 Sensors

Sensor developm ent and application ba sed on nanoscale science and technology is growing rapidly due in part to the advancem ents in the m i croelectronics industry and the increasing availability of nanos cale processing and m a nufacturing technologies. In general, nanosensors can be classified in two m a in cate gories: (1) sensors that are used to m easure nanoscale properties (this category com p rises most of the cu rrent m a rket) and (2) sen s ors tha t are them selves nanoscale or have nanoscale com ponents. The second category can eventually result24 EPA Nanotechnology White Paper

in lower m a teria l cos t as well as r e du ced weight and power consum ption of sensors, leading to greater app l icability and enhanced functionality.

One of the near-term research products of nanotechnology for environmental applications is the development of new and enhanced sensors to detect biological and chemical contaminants. Nanotechnology offers the potential to improve exposure assessment by facilitating collection of large numbers of measurements at a lower cost and improved specificity. It soon will be possible to develop micro- and nanoscale sensor arrays that can detect specific sets of harmful agents in the environment at very low concentrations. Provided adequate informatics support, these sensors could be used to monitor agents in real time, and the resulting data can be accessed remotely. The potential also exists to extend these small-scale monitoring systems to the individual level to detect personal exposures and in vivo distributions of toxicants. Figure 14 shows an example of a nanoscale sensor. Figure 14. Piezoresistive cantilever sensor. Devices such as these may be used to detect low levels of a wide range of substances, including pollutants, explosives, and biological or chemical warfare agents. (Image courtesy of Dr. Zhiyu Hu and Dr. Thomas Thundat, Nanoscale Science and Device Group, Oak Ridge National Laboratory)

In the env i ro nm ental app lica tions f i e l d, nanosensor research and developm ent is a relatively uncharted territory. Much of the new generation na noscale sensor developm ent is driven by defense and biom edical fields. Thes e areas possess high-need applications and the resources required to support expl oratory sensor research. On the other hand, the environm ental

m easurem ent field is a cost sens itive arena wi th less available resources for leading-edge developm ent. Therefore, environm ental nanose nsor technology likely wi ll evolve by leveraging the investm e nt in nanosensor research in related f i elds.



### 2.3 Benefi t s through Other Applicatio ns that Support Sustainability

Nanotechnology m a y be able to advance e nvironm ental protection by addressing the long-term sustainability of res ources and resource system s. Li sted in Table 2 are examples describing actual and potential applications re lating to water, energy, and m a terials. Som e applications bridge between se veral resource outcom es. For exam ple, green m a nufacturing using nanotechnology (both top down and bottom up) can improve the m a nufacturing process by increasing m a terials an d energy efficiency, redu cing the need for solvents, and reducing waste products.25 EPA Nanotechnology White Paper

Table 2. Outcomes for Sustainable Use of Major Resources and Resource Systems

Water sustain wa te r resou r ces o f quality and availability f o r desired u s es Energy generate clean energy and use it efficiently Materials use m a terial carefully an d shift to en vironm entally preferable m a terials Ecosystems protect and restore ecosystem functions, goods, and services Land support eco logically sen s itiv e land m a nage m e nt and develop m ent Air sustain clean and health y air

EPA Innovati on Action Co uncil, 20 05

Many of the following applications can a nd should be supported by other agencies. However, EPA has an interest in helping to guide the work in these areas.

2.3.1 Water

Nanotechnology has the potential to contribute to long-term water quality, availability, and viability of water resources, such as through advanced filtration that enables m o re water reuse, recycling, and desalinization. For exam pl e, nanotechnology-based flow-through capacitors (FTC) have been designed that desalt seawater using one-tenth the energy of state-of -the art reverse osmosis and one-hundredth of the energy of distillation system s. The projected capital and operation costs of FTC-based system s are expected to be one -third less than conventional

osm o sis system s (NNI, 2000). Applications potentially extend even more broadly to ecological health. One long-term challenge to water quality in the Gulf of Mexic o, the Chesapeake Bay, an d elsewhere is the bu ild up of nutrients and toxic substanc es due to runoff from agriculture, lawns, and gardens. In general with current practices, about 150% of nitrogen required fo r plant uptake is applied as fertilizer (Frink et al., 1996). Fertilizers a nd pesticides that inco rporate nanotechnology m a y result in less agricu ltural and lawn/garden runoff of nitr ogen, phosphorous, and toxic substances, which is potentially an important em erging appli cation for nanotechnology th at can contribute to sustainability. These potential applications are still in the early resear ch stage (USDA, 2003). Applications involving dispersive uses of nanom a terials in wate r have the potential for wide exposures to aquatic life and hum an s. Therefore, it is im portant to understand the toxicity and environm ental fate of these nanom aterials.

2.3.2 Energy

There is potential for nanotechnology to c ontribute to reductions in energy dem a nd through lighter m a terials for vehicl es, m a terials and geom etries that contribute to m o r e effective
tem p erature control, technologies that im prove manufacturing process efficiency, m a terials that increase the efficiency of elec trical components and transm ission lines, and m a terials that could contribute to a new generation of fuel cells and a potential hydrogen econom y. Howe ver, because the m a nufacture of nanom a te rials can b e energy-intensive, it is important to consider the entire product lifecycle in developi ng and analyzing these technologiesTable 3 illustrates some potential fu ture nanotechnology cont ributions to energy efficiency (adapted from Brown, 2005). Brown (2005a,b) estimates that the eight technologies could result in national energy savings of about 14.5 quadrillion BTU’s (British thermal units, a standard unit of energy) per year, which is about 14.5% of to tal U.S. energy consumption per
year.
Table 3. Potential U.S. Energy Savings fr om Eight Nanotechnology Applications (Adapted from Brown, 2005 a)

Estimated Percent Reduction in Total Nanotechnology Application Annual U.S. Energy Consumption**
Strong, lightweight m a terials in transportation 6.2 * Solid state lighting (such as white light LED’s) 3.5 Self-optim izing m o tor system s (s m a rt sensors) 2.1 Sm art roofs (tem perature-d ependent reflectivity) 1.2 Novel energy-efficient separation mem b ranes 0.8 Energy efficient distillation through supercom puting 0.3 Molecular-level control of industrial catalysis 0.2 Transm ission line conductance 0.2 Total 14.5

* A ssu m in g a 5.15 Millio n BTU / Barrel conversion (correspo n d i ng t o refo rm u l a t ed g a so lin e – fro m EIA m o n t h l y

ener gy re vi ew , Oct o be r 20 0 5

, A ppe n d i x A )

* * Based on U.S. an nu al en erg y con s u m p tio n fro m 2 0 0 4 (99

. 7 4 Qu ad rillion Btu /year) from th e En erg y In fo rm atio n A d m in istr a tio n An nu al En ergy Rev iew 20 04

The items in Table 3 represent many different technology applications . For instance, one of many examples of molecular-le vel control of industrial catalysi s is a nanostructured catalytic converter that is built from nanotubes and has been developed for the chemical process of styrene synthesis. This process revealed a potential of saving 50% of the energy at this process level. Estimated energy savings over the product life cycle for styr ene were 8-9% (Steinfeldt et al., 2004). Nanostructured cataly sts can also increas e yield (and therefore reduce energy and materials use) at the process level. Fo r example, the petroleum industry now uses nanotechnology in zeolite catalysts to crack hyd rocarbons at a significantly improved process yield (NNI, 2000).

There are additional emerging innovative approaches to energy management that could potentially reduce energy consumption. For exam ple, nanomaterials arranged in superlattices could allow the generation of electricity from wa ste heat in consumer appliances, automobiles, and industrial processes. These thermoelectric materials could, for example, further extend the efficiencies of hybrid cars and power generation technologies (Ball, 2005). 26 EPA Nanotechnology White Paper27 EPA Nanotechnology White Paper

In addition to increasing energy efficien cy, nanotechnology also has the potential to contribute to alternative energy tech nologies that are environ m entally cleaner. For ex am ple, nanotechnology is form i ng the basis of a new t ype of highly efficient photovoltaic cell that consists of quantum dots connected by car bon nanotubes (NREL, 2005). Also, gases flowing over carbon nanotubes have been shown to convert to an electrical current, a discovery with im plications for novel distribu ted wind power (Ball, 2004).

While nanotechnology has the potential to cont ribute broadly to energy efficiency and cleaner sources of energ y, it is im portant to consider energy use im plications over the entire product lifecycle, particularly in m a nufacturing nanom aterials. Many of the m a nufacturing processes currently used and be ing developed for nanotechnology are energy intensive (Zhang et al., 2006). In addition, m a ny of the applications di scussed here are projected applications. There are still some technical and econom i c hurdles for these applications.

2.3.3 Materials

Nanotechnology m a y also lead to m o re effici ent and effective use of m a terials. For

exam ple, nanotechnology m a y im prove the functiona lity of catalytic conv erters and reduce by up to 95% the m a ss of platinum group m e tals required. This has overall product lifecycle benefits. Because platinum group m e tals occur in low conc entration in ore, th is red u ction in use m a y reduce ecological im pacts from m i ning (Lloyd et al., 2005). However, manufacturing precise

nanom aterials can be m a terial-intensive.

W ith nanomaterials’ in creased m a terial functi onality, it m a y be possible in som e cases to repla ce tox i c m a terials a nd still ach ie ve the desired functionality (in term s of electrical conductivity, m a terial strength, heat tr ansfer, etc.), often with other life-cycle benefits in term s of

m a terial and energy use. One exam pl e is lead -free conductive adhesive s f o rm ed fromselfassem b led monolayers based on nanotechnology, whic h could eventually s ubstitute for leaded solder. Leaded solder is used broadly in the el ectronics industry; about 3900 tons lead are used per year in the United States alone. In addition to the benefits of redu ced lead use, con ductive adhesives could sim p lify electr onics m a nufacture by elim inati ng several processing steps, including the need for acid fl ux and cleaning with detergent a nd water (Georgia Tech., 2005).

Nanotechnology is also u s ed for Organic Light E m itting Diodes (OLEDs). OLEDs are a display technology substitute for Cathode Ray T ubes, which contain lead

. OLEDs also do not require m e rcury, which is used in conventional F l at Panel Displays (F razer, 2003). The OLED displays have additional benefits of reduced energy use and o v erall m a terial use throu gh the lifecycle (Wang and Ma sciangioli, 2003).

2.3.4 Fuel Additives

Nanom a terials also show potential as fuel additives and autom o tive catalysts and as
cata l ysts f o r utility bo ile r s a nd other energy-producing facilities. For example, cerium oxide nanoparticles are being employed in the United Kingdom as on- and off-road diesel fuel additives to decrease emissions ( http://www.oxonica.com / cm s/pressr eleases/PressR elease-12-03­ 04.pdf and http://www.oxonica.com / cm s/cases tudies/CaseStudyV9SB.pdf ). These manufacturers also claim a more than 5- 10 % decrease in fuel consum ption with an associated decrease in28 EPA Nanotechnology White Paper

vehicle em issions. Such a reduction in fuel cons umption and decrease in em issions would result in obvious environm ental benefits. L i m ited publis hed research and m odel i ng have indicated that the addition of cerium oxide to fuels m a y incr ease levels of specific org a nic chem icals in exhaust, and result in em ission of cerium oxi de (Health Effects Ins titu te, 2001); th e h e alth im pacts asso ciated with s u ch alteratio ns in diesel exhaust were not exam ined.29 EPA Nanotechnology White Paper



## 3.0 Ri sk Ass e ssm ent of Nanom a terials

3.1 Introduction

Occupational and environm ental exposure s to a lim ited num b er of engineered

nanom aterials have been reported (B aron et al., 2003; Maynard et al., 200 4). Uncertainties in health and environm ental effects associated w ith exposure to engineer ed nanom aterials raise questions about potential risks from such expos ures (Dreher, 2004; Sw iss Report Reinsurance Com p any, 2004; UK Royal Soci ety Report, 2004; European Comm ission Report, 2004; European NanoSafe Report 2004; U K H ealth and Safety Executive, 2004)

EPA’s m i ssion and m a ndates call for an unde rstanding of the health and environm ental im plications of intentionally produced nanom ateria ls. A challenge in evaluating risk associated with the m a nufacture and use of na nom a terials is the diversity a nd com p l e xity of the types of

m a terials av ailab l e and b e ing deve lo ped, as well as the se em ingly lim itles s potential u s es of these m a terials. A risk assessm ent is the eval uation of scientific inform ation on the hazardous properties of environm ental agents, the dose-respon se relationship, and the extent of exposure of hum a ns or environm ental receptors to those agen ts. The product of the risk assessm ent is a
statem ent regarding the probability that hum ans (populations or indiv i duals) or o t her environm ental recepto rs so expos ed will be harmed and to what degree (risk characterization).

EPA generally follows the risk assessmentparadigm described by the National Academy of Sciences (NRC, 1983 and 1994), which at this time EPA anticipat es to be appropriate for the assessment of nanomaterials (Figure 15). In ad dition, nanomaterials shou ld be assessed from a life cycle persp ective (Figure 16).

Dos e - Respo ns e

As se ssm en t

Risk Cha r acterizatio n Haz a rd Ident i fica tion

E x posur e A sse s s men t

Figure 15. EPA’s Risk Assessment Approach30 EPA Nanotechnology White Paper

Raw Material

Production Consumer Product Manufacturing Consumer Use End of Life Worker Exposure Consumer Exposure

Recycle

Landfills Incinerators Industrial emissions

Human Population and Ecological Exposure
Figure 16. Life Cycle Perspective to Risk Assessment

The overall risk assessm ent approach used by EPA for conventional chem icals is thought to be generally applicable to na nom ater ials. It is im portant to note that nanom a terials have large surface areas per unit of volum e, as well as novel electron ic prope rties relative to con v entional chem icals. Som e of the special prop erties th at ma ke nanom aterials useful ar e also pro p erties th at

m a y cause som e nanomaterials to pose hazards to hum ans and the environm ent, under specific conditions, as discussed below. Furtherm or e, num erous nanom aterial coatings are being developed to enhance perform a nce for intended a pplications. These coatings m a y i m pact the behavior and effects of the m a teri als, and m a y or m a y not be retain ed in the environm ent. It will be necess a ry to consid er these un ique propertie s and issues, an d their poten tial im pacts on fate, exposure, and toxicity, in developing ri sk assessm ents for nanom a terials.

A num b er of authors have reviewed charac terization, fate, and toxicological inform ation for nanom a terials and proposed research strate gies for safety evalua tion of nanom a terials (Morgan, 2005; Holsapple et al., 2005; Blashaw et al., 2005; Tsuji et al., 2006; Borm et al., 2006; Powers et al., 2006; Thom as and Sayre, 2005). T s uji et al. (2006) proposed a general fra m ework for risk assessm ent of na nom a terials which id entified nanom aterial ch aracteristics, such as particle size, structure/properties, coating, and particle behavior, that are expected be important in developing nanom aterial risk assessm e nts. Thes e issues are sim ilar to those we note herein. Other governm e nts have also undertaken efforts to identify research needs for nanom a terial risk

assessm ent (UK Departm e nt for Environm ent, Food and Rural Affairs, 2005; Borm and31 EPA Nanotechnology White Paper

Kreyling, 20 04). The European Unio n’s Sc ien tific Comm ittee on Em erging and Newly Identified Health Risks (SCENIHR, 2006) has al so overview e d existing data on nanom a terials, data gaps, and issues to be considered in conducting risk assessm ents on nanom aterials.

The purpose of this chapter is to briefly review the state of knowledge regarding the

com ponents needed to conduct a risk assessm ent on nanom at erials. The following key aspects of risk as sessm ent are addressed as they relate to n a nom aterials : chem ical identif ica tion and physical properties characteriza tion, environm ental fate, environm ental detection and analysis, hum a n exposure, hum an health effect s, and ecological effects. Each of these aspects is discussed by providin g a synopsis of key existing inform ation on each topic.



### 3.2 Chemical Identification and Ch aracteri z a tion of Nanomaterials

The identification and characterization of chem ical subs tances and m a terials is an im portant first step in assessing their risk. Understanding the physic al and chem ical properties in particular is necessary in the evaluation of hazard (both tox i co logical and ecological) and exposure (all routes). C h em ical properties that are im portant in the characterization of discrete chem ical substances include, but are not lim ite d to, com position, structure, m o lecular weight,

m e lting point, boiling point, vapor pr essure, octanol-water partition co efficient, water solubility, reactivity, and stability. In addition, inform ati on on a substance’s m a nufa c ture and formulation is im portant in understanding purity, produc t variability, perform a nce, and use.

The diversity and com p l e xity of nanom a terials m a kes chemical identification and characterization not only more im portant but also more difficult. A broader spectrum of properties w ill b e needed to suf f i ciently char acte r ize a given n a nom aterial f o r the purp o ses of evaluating h azard and assessing risk. Che m ical p r operties su ch as those listed above m a y be im portant for som e nanom a terials, but other proper ties such as particle size and size distribution, surface/vo lu m e ratio, shape, electron ic prope rties

, surface characte ristics, state of dispersion/agglom eration and conductiv ity are also expected to be im portant for the m a jority of nanoparticles. Figure 17 provides an illus t ration of different states of aggregation nan oparticles. Powers et al. (2006) provides a discussion of na noparticle properties that m a y be im portant in understanding their effects and m e thods to m easure them

.32 EPA Nanotechnology White Paper



### 20 nm 20 nm

(A) (B) Figure 17. Transmis sion Electron Mic r oscope (TEM) im age of aerosol-generated TiO 2 nanoparticles. (A) Un-aggregated and (2- 5 nm ) (B) an d aggregated (80-12 0 nm ), used in expos ure studies to determ ine the health impacts of m a n u factured nanoparticles. Nanoparticle aggregation m a y p l a y an important role in health and environm enta l im pa cts. (I mages court esy of Vicki Grassian, University of Iowa [Gr assi an, et al., unpu bli s hed results] )

A given nanom a terial can be produced in m a ny cases by several different processes yielding several derivatives of the sam e materi al. For exam ple, single-walled carbon nanotubes can be produced by several different processe s that can generate products with different physical-chem i cal properties (e.g., s i ze, shape, co mposition) and potentially different ecological and toxicological properties (Thom as and Sayre, 2005; Oberdörster et al., 2005a). It is not clear whether existing physical-chem i cal property te st m e thods are adequate for sufficiently characterizing various n a nom aterials in order to evaluate their hazard and exposure an d assess their risk. It is clear that chem ical properties such as boili ng point and vapor pressure are insufficient. Alternative m e thods for m easuri ng properties of nanom aterials m a y need to be developed both quickly and cost effectively.

Because of the current s t ate of deve lopm ent of chem ical identification and characterization, current chem i cal representation and nom enc l ature conventions m a y not be adequate for som e nanom a terials. Nom e ncla ture conventions are im portant to elim inate

am biguity when communicating differences betw een nanomaterials and bulk m a terials and in reporting for regulatory purposes. EP A’s OPPT is participating in new and ongoing workgroup/panel deliberations with the Am eri can National S t andards Ins titu te (ANSI), the Am erican Society for T e sting and Materials (A STM), and the International Organization for Standardization (ISO) concerni ng the developm ent of term inol ogy and chem ical nom enclature f

o r nanosize d substance s , and will a l s o continue with its own nom e nclatu re discu ssio n s with the Chem ical Abstracts Service (CAS).



### 3.3 Environmental Fate of Nanomaterials

As m o re products containing nanomaterials ar e developed, there is greater potential for environm ental exposure. Potential nanom a terial release sources in clude direct a nd/or indirect releases to the environm ent from the m a nufacture and processing of nanom aterials, releases from33 EPA Nanotechnology White Paper

oil refining processes, chem ical and m a terial m a nufacturing processes, chem ical clean up activ ities in c l uding th e re m e diation of contam inated sites, releases of nanom aterials incorporated into m a terials used to fab r icate produ cts for consu m er use including pharm aceutical p r oducts, and releases resulting from the use and dispos al of consum er products containing nanoscale

m a terials (e.g., disposal of screen monitors, computer boards, autom obile tires, clothing and

cosm etics). The funda mental properties concerni ng the environm ental fate of nanom a terials are not well understood (European Comm ission, 2004), as there are few available studies on the environm ental fate of nanom a terials. The fo llowing sections summarize what is known or can be inferred about the fate of nanom a terials in the atm o sphere, in soils, and in water. These summaries are followed by sect ions discussing: 1) biodegr adation, bioavailability, and bioaccum u lation of nano m a terials, 2) the poten tia l for transform a tion of nanom a terials to m o re toxic m e tabolites, 3) possible interactions be tween nanom aterials and other environmental
contam inants; and 4) the applicability of current environm ental fate and transport m odels to

nanom aterials.

3.3.1 Fate of Nanomaterials in Air

Several processes and factors influence the fate of airborne particle s in ad dition to the i r initial d i m e nsional and c h em ical characteristics: th e leng th of tim e the par tic les r e m a in airborn e , the natu re of their interac tion w ith other airborne particles or mo lecules, an d the dis t ance that they m a y travel prior to deposition. The pr ocesses im portant to unde rstanding the potential
atm o spheric transport of particles are diffu sion, agglom eration, wet and dry deposition, and gravitational settling. These processes are rela tively well understood for ultrafine particles and

m a y be applicable to nanom a terials as well (W ie sner et al., 2006). However, in som e cases, intentionally produced nanom ateria ls m a y behave quite differently from incidental ultrafine particles, for exam ple, nanopart icles that are surface coated to prevent agglom eration. In addition, there m a y be differences between fr eshly generated and ag ed nanom a terials.

W ith respect to the length of tim e pa rticle s rem a in airborne, particles with aerodynam i c diam eters in the nanoscale rang e (<100 nm ) m a y follow the laws of gaseous diffusion when released to air. The rate of diffusion is inversely pr oportional to particle diam eter, while the rate of gravitational settling is propor tional to particle diam eter (Aitken et al., 2004). Airborne particles can be classified by size and behavior into three general gr oups: Sm all particles (diam e ters <80 nm ) are described as being in the agglom eration m ode; th ey are sho r t-lived because they rapid l y ag glom erate to for m larg er particles. Large particles (>2000 nm, beyond the discussed <100 nm nanoscale range) are desc ribed as being in the coarse m ode and are subject to gravitational settli ng. Interm ediate-sized partic les (>80 nm and < 2000 nm, which include s par tic le sizes o u tside the discussed <10 0 nm nanoscale range) are described as being in the accum u lation m ode and can rem a in suspend e d in air for the longest tim e , days to weeks, and can be rem oved from air via dry or w e t depos itio n (Bidlem a n, 1988; Preining, 1998; Spurny, 1998; Atkinson, 2000; UK Royal Society, 2004; Denne nkamp et al., 2002). Note that these generalizations apply to environm ental condit ions and do not preclude the possibility that hum a ns and other organism s may be exposed to large as well as sm aller particles by inhalation.

Deposited nanoparticles are typica lly not easily resuspended in the air or re-aerosolized (Colvin 200 3; Aitken et al., 2004). Because phy si cal particle si ze is a critical p r operty of

nanom aterials, m a intaining particle size during the handling and use of nanom a terials is a34 EPA Nanotechnology White Paper

priority. Current research is underway to pr oduce carbon nanotubes that do not form c l um ps either by functionalizing the tubes the m selves, or by trea tm ent with a coating or dispersing agent (UK Royal Society, 2004; Colvin, 2003), so futu re m a terials m a y be more easily dispersed.

Many nanosized particles are reported to be photoactive (Colvin, 2003), but their susceptibility to photodegradation in the atm o sphe re has not been studie d. Nanom a terials are also known to readily adsorb a variety of m a terials (W iesner et al., 2006), and m a ny act as catalysts. H o wever, no studies ar e cu rrently available th at exam in e the interaction of nanosized adsorbants and chem icals sorbed to them , a nd how this interaction m i ght influence their respective atmospheric chem istries.

3.3.2 Fate of Nanomaterials in Soil

The fate of nanom aterials released to soil is likely to vary depending upon the physical and chem ical characteris tics of the n a nom aterial. Nanom a terials released to soil can be strongly sorbed to soil due to their high surface area s and therefore be immobile. On the other hand,

nanom aterials are sm all enough to fit into sm a ller spaces between soil particles, and m i ght therefore travel farther than la rger particles before becom i ng tr apped in the soil m a trix. The streng th of the sorption of any intentionally pr od uced nanoparticle to soil will be dep e ndent on its size, ch em istry, applied particle surface treatm e nt, and the conditions under which it is applied. S t u d ies have d e monstrated the dif f

e re nc es in m obility of a variety of insoluble nanosized m a terials in a porous m e dium (Zhang, 2003; Lecoanet and W i esner, 2004; Lecoanet et al., 2004).

Additionally, the types and prope rties of the soil and environm ent (e.g., clay versus sand) can af f

ect na nom a teria l mobility. F o r exam ple, the m obility of m i neral c o lloids in so ils and sedim e nts is strongly affected by ch arge (W iesner et al., 2006 ). Surface p hotoreaction s provide a pathway for nanom aterial transform a tion on so il surfaces. Hum i c substances, common constituents of natural particle s, are known to photosensitize a va riety of organic photoreactions on soil and other natural surfaces th at are exposed to sunli ght. Studies of nanom aterial transf orm a tions in f i eld situa ti ons are further co mplicated b y the pres en ce of naturally occurring

nanom aterials of sim ilar molecu lar structures and size ranges. Iron oxides are one example.

3.3.3 Fate of Nanomaterials in Water

Fate of nanom aterials in aqueous environm en ts is controlled by aqueous solubility or dispersability, interactions betw een the nanom aterial and natural and anthropogenic chem icals in the system , and biological and ab iotic processes. W a terborne na noparticles generally settle m o re slowly than larger particles of the sam e material. However, due to their h i gh surface-area-tom a ss ratios, nanosized particles have the poten tia l to sorb to s o il and s e dim e nt particles (Oberdörster et al., 2005a). W h ere these soil and sedim e nt particles are subject to sedim e ntation, the sorbed nanoparticles can be m o re readil y rem oved from the water colum n. Som e nanoparticles will be sub j ect to bio tic and abiotic degradation resulting in rem oval from the water column. Abiotic degradation proce sses that m a y occur include hydrolysis and photocatalyzed reaction in surface wa ters. Particles in th e upp er la y e rs of aquatic environm ents, on soil su rfaces, and in water drop lets in th e atm o sphere are exposed to sunlight. L i g h t-indu ced photoreactions often are im portant in determ ining environm ental fate of chem ical substances.35 EPA Nanotechnology White Paper

These reactions m a y alter the physical and chem ical properties of nanom a terials and so alter their behavior in aquatic environm en ts. Certain organic and m e tallic nanom aterials m a y possibly be transform e d under anaerobic conditi ons, such as in aquatic (benth ic) sedim e nts. From past studies, it is known that severa l types of organic com pounds ar e generally susceptible to reduction under such conditions. Complexation by natural organic m a terials such as hum i c collo ids can f acilitate rea c tions that tr ansf orm metals in anaero b ic sed i m e nts (see Nurm i et al., 2005 and references therein).

In contrast to processes that rem ove nanopart icles from the water colum n , som e dispersed insoluble nanoparticles can be stab ilized in aquatic environm ents. For example, researchers at Rice University have reported that although C 60 f u lle rene is initia lly in solu ble in water, it spontaneously form s aqueous colloids containing nanocrystalline aggregates. The concentration of nanom a terials in the s u spensions can be as hig h as 100 parts per m illio n (ppm ), but is m o re typica lly in the range of 10-50 ppm

. The stability of the partic les and susp ensions is se nsitiv e to pH and ionic streng th (CBEN, 2005; Fortner et al., 2005). Sea surface m i crolayers consisting o f lipid, carbohydrate and proteinace ous com ponents along with natu rally-occurring colloids m a de up of hum i c acids, m a y have the potential to so rb nanoparticles and tran sport them in aquatic environm ents over long distances (Moore, 2006, Schwarzenbach et al., 1993). These interactions will also delay nanoparticle rem oval from the water colum n.

Heterogeneous photoreactions on m e tal oxide surfaces are increa singly being used as a

m e thod for drinking water, wastewater and groundwater treatm ent. Figure 18 shows an

exam ple of t h e surface o f a synthesized m e tal oxide nanostructure, Semiconductors such as titanium dioxide and zinc oxide as nanom aterials have been shown to effe ctively catalyze both the reduction of halogenated chem icals and oxidation of various other pollutants, and heterogeneous photocatalysis has been used for water pur if ication in tre a tm ent syste m s.
Nanoparticle photochem i stry is being studied with respec t to it s possible application in
water trea tment. Proces s e s tha t contr o l tr anspor t and rem oval of nanoparticles in water and wastewater are being studied to understand nanoparticle fate (Moore, 2006; W i esner et al., 2 Figure 18. Z i nc oxide nan o structures synthesi z e d by a vapor-solid process. (Im a ge courtesy of Pr of. Z hong Win La ng of Georgia Tech .)

006). The fate of nanosized particles in wastew at er treatm ent plants is not well characterized. Wastewater m a y be subjected to m a ny different types of treatm ent, including physical, chem ical and biological processes, dependi ng on the characteristics of the wa stewater, wheth e r the plan t is a publicly owned treatment work or onsite industr ial facility, etc. Br oadly speaking, nanosized particles are most likely to be affected by sorptio n processes (for exam ple in pr im ary clar if iers ) and chem ical reaction. T h e ability of either of these proces ses to imm obilize or des t ro y the particles will depend on the chem ical and physical nature of the particle and the residence tim es36 EPA Nanotechnology White Paper

in re levant c o m p artm ents of the tre a tm ent plan t. As noted above, sorption, agglom eration and mobility of m i neral colloids are stro ngly af f

ecte d by pH; thus pH is another var i able that m a y affect sorption and settling of nanomaterials. Current res earch in this area includ es th e production of m i crobial granules that are claim e d to rem ove nanoparticles from si m u lated wastewater (Ivanov et al ., 2004). Nanom a terials that escape sorption in prim ary treatm e nt m a y be rem oved from wastewater afte r biological treatm ent via settling in the secondary clarifier. Norm ally th e rate of gra v ita tiona l se ttling of particle s such as nanom aterials in wa ter is dependent on particle diam eter, and sm aller partic les settle more slowly. However, settling of

nanom aterials could be enhanced by entrapm e nt in the m u ch larger sludge flocs, rem o val of which is the objective of secondary clarifiers.

3.3.4 Biodegradation of Nanomaterials

Biodegradation of nanoparticles m a y result in their breakdown as typically seen in biodegrad ation of organic m o lecules, or m a y resu lt in changes in the physical structure or surface characteristics of the m a terial. The p o tential for and possible m e chanis m s of biodegradation of nanosized particles have just begun to be investigated. As is the case for other fate processes, the potential for biodegrad ation will d e p e nd strong ly on the chem ical and physical natu re of the particle. Many of the nanom a teri als in current use are com posed of inherently nonbiodegradable inorgan i c ch em icals, such as ceram ics, m e tals and m e tal oxides, and are not expected to biodegrad e. However, a recen t prelim inary study found that C 60 and C 70 fullerenes were taken up by wood decay fungi after 12 weeks, sugges ting that the fullerene carbon had been

m e tabolized (Filley et al., 2005). For other nanom a terials biodegradability m a y be integral to the

m a terial’s design and function. This is th e case f o r som e biodegradable polym ers being investigated for use in drug transport (Madan et al., 1997; Brzoska et al., 2004), for which biodegradability is m o stly a function of che m ical struct ure and not particle size.

Biodegradab ility in was t e tre a tm ent and the environm ent m a y be influenced by a variety of factors. Recent labo ratory s t udies on C 60 fullerenes have indicated the developm ent of stable colloid structures in water that dem o nstrate to xicity to bacteria under aerobic and anaerobic conditions (CBEN, 2005; Fortner et al., 2005). Further studies ar e needed to determine whether fullerenes may be toxic to m i croorganism s unde r environm ental conditions. One m u st also consider the potential of photorea ctions and other abiotic processe s to alter the bioavailability and thus biodegradation rates of nanom a terials. In summ ary, not enough is known to enable

m eaningful predictions on the bi odegradation of nanom aterials in th e env i ronm ent and m u ch further testing and research are needed.

3.3.5 Bioavailability an d Bioaccumulation of N a nomaterials

Bacteria and living cells can take up nanosized p a rticle s, pro v iding th e b a sis f o r pote n tia l bioaccum u lation in the food chain (Biswass and W u, 2005). Aquatic and m a rine filter feeders near the base of the food chain f eed on sm all particles, even partic les down to the nanom e ter size fraction. Th e bioavailab ility of specific nanom at er ials in the environm ent will depend in part on the particle. Environm e n tal fate processes m a y be too slow for effective rem oval of persistent

nanom aterials before they can be taken up by an organism

. In the previous section, it was noted that som e physical rem oval processes, such as gravitational settling, ar e slower for nanosized particle s tha n f o r m i croparticle s. This would lead to an increased potential for inhalation37 EPA Nanotechnology White Paper

exposure to terrestrial organism s and for increa sed exposure of aquatic organism s to aqueous colloids. Not enough infor m ation has been gene rated on rates of depos ition of nanomaterials from the atmosphere an d surface water, or of sorption to s u sp ended soils and sedim e nts in th e water column, to determ ine whether these proc ess e s could effectively sequ ester specific nanoparticles before they are taken up by organism s.

Com p lexation of m e tallic nanom aterials m a y have im portant interactive effects on biological availab i lity and photochem i cal reactivity. For ex am ple, the biological av ailab i lity of iron depends on its free ion concentr ations in water and the free i on concentrations are affected by com p lexation. Complexation reduces bio l og ical availability by reducing free m e tal ion concentrations and dissolved iron is quantitat ively com p lexed by organic ligands. Solar UV radiation can interact with thes e processes through photor eactions of the com p lexes. Further, iron and iron oxides can participate in enzym a tic redo x reactions that change the oxidation state, physical chem ical properties and bioavailabi lity of the m e tal (Reguera et al., 2005).

3.3.6 Potential for Toxic Transformati on Products from Nanomaterials

Ce r t a i n na no ma t e r i al s ar e be i ng designed for release as reacta nts in the environm ent, and therefore are expected to under go chem ical transform a tion. One exam ple of this is iron (Fe 0 ) nanoparticles em ployed as reactants for the dechlo rination of organic poll utants (Zhang, 2003). As the reaction progresses, the iron is oxidized to iron oxide. Other m e tal particle s are also converted to oxides in the presen ce of air and water. W h ether the oxides are m o re or less toxic than the free m e tals depends on the m e tal. Un der the right conditions, certain m e tal com pounds could be converted to m o re m obile compounds. In these cases, sm all particle size would m o st likely enhance this inherent reactivity. Som e t ypes of quantum dots have been shown to degrade under photolytic and oxidative conditions, and furtherm ore, com p rom i se of quantum dot coatings can reveal the m e talloid core, whic h may be toxic (Hardm an, 2006). Degradation products from carbon nanom a terial s (fullerenes and nanotubes) ha ve not yet been reported.

3.3.7 Interactions Betw een Nanomaterials and Or ganic or Inorganic Contaminants: Effects and the Potential for P r actical Applicat ions

The exam ples cited in th is sec tion illustra t e how nanom aterials have been dem onstrated to alter the p a rtition i ng b e havior of c h em i cals between enviro nm ental co mpartm ents and between the environm ent and living organism s. Furtherm ore, several nano m a terials are reactive toward chem icals in the environm ent, generate reactive spec ies, or cata ly ze reaction s of other chem icals. These properties are currently under study for use in waste rem e diation operations. It should be noted that the potenti al also exists for nanom aterials to effect unforseen changes, if rele ased to the environm ent in large quantities.

Two types of effects under study for possible exploitation are sorpti on and reaction. T h e high surface area of nanosized pa rticles provides enha nced ability to sorb both organic and inorganic chem icals from environmental m a trices com p ared to conventional form s of the sam e

m a terials. T h is property can pot en tia lly be u tilize d to bind pollutan t s to en hance envir o nm ental

rem e diation. Many examples of immobilized nanom aterials for use in pollution control or environm ental rem e diation have been described in the literature. Th ese include nanosponges or
nanoporous ceram ics, large particulate or bead m a terials with nanosized pores or crevasses38 EPA Nanotechnology White Paper

(Christen, 2004), and solid support m a terials with coatings of nanoparticles (for exam ple, see Com p arelli et al., 2004 ). This sectio n will ins t ead focus on releas es of free nanoparticles and effects on chem icals in th e environm ent. The rem a inder of this section will be organized into known changes in the mobility of chem icals caused by their sorption to nanoparticles, and known instances of reactivity and catalytic activity towa rd chem icals m e diated by nanoparticles.

No single overall effect can be described fo r the sorption of chem icals to nanom aterials based on their size or chem ical m a keup alone. In air, aerosolized nanoparticles can adsorb gaseous or particulate pollutant s. In soil or sedim e nts, na nom aterials m i ght increase the bioavailability of pollutants, thereby increasing the pollutant = s availability for biodegradation (UK Royal Society, 2004). Depending on the conditions, nanosized carbon such as C 60 or nanotubes could either enhance or inhibit the m o bility of organic pollutants (Cheng et al., 2004). Stable colloids of hydrophobic na nom a terials in an aqueous environm ent could provide a hydrophobic m i croenvironm ent that suspends hydrophobi c contam inants and re tards their rate of deposition onto soils and sedim e nts. Sim ila r effe cts are known to happen with naturally occurring colloids m a de up of hum i c acids and su spended sedim e nt particles (Schwarzenbach et al., 1993). Nanoparticles can be altered to op tim i ze their affinities for particular pollutan t s by modifying the chem ical identity of the polym er.

Several s t ud ies inv e stiga ting th e sorption of organic pollutants a nd m e tals in air, soil, and
water to n a n o sized m a ter i als h a ve re c e ntly be en r e ported in th e litera tu re. The sorption of naphthalene to C 60 from aqueous solution was compared to sorption to activated carbon (Cheng et al., 2004). The investigators observed a correl ation between the surface area of the particles and the am ount of naphthalene adsorbed from solu tion. In other studies, nanoparticles m a de of

an am phiphilic po lym e r have been s hown to m o bilize phenanthrolene from contam i n ated sandy soil and increase its bioavailability (Tungittiplakorn et al., 2004, 2005)

. It has been reported that

m a gnetite crystals adsorb arsenic an d chrom i um (CrVI) from water (CBEN, 2005; Hu et al., 2004), suggesting potential purif ication techniques for m e tal-laden drinking water (C BEN, 2005). The adsorption and desorption of vol atile organic compounds from am bient air by fullerenes has been investigated (Chen et al., 2000). Inhalation exposures of benzo(a)pyrene sorbed to u l trafine aeros o ls of Ga 2 O 3 (Sun et al., 1982) and diesel exhaust (140 nm ) (Sun et al., 1984) were studied in rats. The studies showed that when compared to inhalation of pure benzo(a)pyrene aerosols, m a terial sorbed to th e gallium oxide had increased retention in the respirato r y tract, and increased expo sure to the stom ach, liver, and kidney.

Nanoscale m a terials a r e typic a lly more reac tiv e than large r particle s of the sam e m a ter i al. This is true especially f o r m e tals and certain m e tal oxides. In the environm ent, nanom aterials have the potential to react with a variety of chemicals; their in creased or novel reactivity coupled with their so rptiv e properties allo ws for accelerated rem oval of chem icals from the environm ent. Many groups are currently investigat ing the use of nanom a terials for the destruction of persistent pollutants in the environm ent.

Nanoscale iron particles have been dem onstrated to be effective in the in s itu rem e diation of soil contam inated with tetrachlo ro ethylen e. A wide variety of a dditiona l pollu tants are claim e d to be transform e d by iron nanopartic les in laboratory experim e nts, including halogenated (Cl, Br) m e thanes, chlorinated benzenes, certain pe sticides, chlorinated ethanes,39 EPA Nanotechnology White Paper

polychlorinated hydrocarbons, TNT, dyes, and inorga nic anions such as nitrate, perchlorate, dichrom a te, and arsenate. Furt her investigations are underway with bim e tallic nanoparticles (iron nanoparticles with Pt, P d, Ag, Ni, Co, or Cu deposits) and m e tals deposited on nanoscale support m a terials such as nanoscale carbon platel ets and nanoscale polyacrylic acid (Zhang, 2003). Nanosized clusters of C 60 have been sho w n to generate reactive oxygen species in water under UV and polychrom atic light. Sim ilar colloi ds have been reported to degrade organic
contam inants and act as bacterio cides (Boyd et al., 2005). Fullerol (C 60 (O H) 24 ) has als o been dem onstrated to produce reactive oxygen speci es under sim i lar conditions (Pickering and W i esner, 2005).

3.3.8 Applicability o f Current Environmental Fate and Transport Mo dels to Nanomaterials

When perform i ng expos ure assessments on m a te rials for which there are no experim e ntal data, m odels are often used to generate estim ated data, whic h can provide a basis for m a king regulatory decisions. It would be advantageous if such m ode ls could be applied to provide estim ated properties for nanom ateria ls, sinc e the r e is very little experim e ntal data available for these m a terials. The m o dels used by EPA’s Of fice of Pollution Prevention and Toxics (OPPT) to assess environm ental fate and exposure, are, for the m o st part, designed to provide estim ates for organic molecules w ith defined and discrete structures. T h ese m odels are not designed for use on inorganic m a terials; therefore, they canno t be applied to inorga nic nanom aterials. Many models derive their estim a tes from structural infor m ation and requi re that a precise structure of the m a teria l of interes t b e pr ovided. Since m a ny of the nanom ater ials in curren t use, such as quantum dots, ceram ics and m e tals, are solids wit hout discrete m o lecular structures, it is not possible to provide the precise ch em ical s t ructures that these m odels need . W h ile it is usually possible to d e term ine dis tinc t structu r es f o r f u llere nes, the m odels ca nnot accept the complex fused-ring structures of the fullerenes. Also, the tra i ning se ts of chem icals with which the quantitative structure-activity re lationships (QS A R) in the models were developed do not include fullerene-type m a terials. Fullerenes are uniqu e m a terials with unusual properties, and they cannot be reliably m odeled by QS ARs developed for other substa ntially dif f

erent types of

ma t e r i a l s

. In general, models used to assess the e nvironm ental fate and exposure to chem icals are not applicable to inte ntionally produced nanom aterials. Depending on the relevance of the chem ical property or transfor m a ti on process, new m odels may have to be developed to provide estim ations for these m a terials; however, m odels cannot be developed without the experim e ntal data needed to design and va lida t e th em

. Bef o re the environ m ental f a te, transpo r t an d multim edia partition i ng of nanom a teria l s can be e f f

ectively modeled, reliable exper i m e ntal data must be acquired for a variety of in tentionally produced nanom a terials.

However, models are also used which focu s on the fate and distri bution of particulate

m a tter (air models) and / or co lloid al m a terial s (s oil, water, landfill leachates, ground water), rather than discrete organics. For exam ple, fate of atm o sphe ric particulate m a tter (e.g., PM 10 ) has been the subject of substantia l re search inte re st and is a pr incipal regulatory focus of EPA = s Office of Air and Radiation. Si nce intentionally produced nanom a terials are expected to be rele ased to a nd exist in the envi ronm ent as particles in m o st cases, it is wise to investigate applic ability of these oth e r m odels

. In fact it can be reasoned th at the m o s t useful m o deling tools for exposure assessm ent of nanom a terials are likely to be found not in the area of environm ental40 EPA Nanotechnology White Paper

fate of specific organic com pounds (more pr ecisely, prediction of their transport and transform a tion), rather in fields in w h ich the f o c u s is on m e dia-or ien t ed p o llution is su es: a i r pollution, water quality, ground water contam ination, etc. A survey of such tools should be

m a de and their potential util ity for nanom a terials assessed.



### 3.4 Environmental Detection and Analysis of Nanomaterials

The challenge in detecting nanom at erials in the environm ent is com pounded not only by the extrem ely sm all size of the particles, but also by their unique physic al structure and physicochem ical characteristics. Th e varying of physical and chem i cal properties can significantly im pact the extraction an d analytical techniqu es th at can be u s ed for the analysis of a specific

nanom aterial. As noted above, the chem ical prope rties of particles at the nanom eter size can significan tly differ from the chem ical properties of larger particles c onsisting of the sam e chem ical composition. Independent of the chal lenges brought on by the intrinsic chem ical and physical characteristics of nanom a terials, the in teractions of nanom a te rials with and in the environm ent, including agglom eration, also prov ide significant analy tical challenges. Som e

nanom aterials are b e ing developed w ith chem ical surface treatm ents that m a intain nanoparticle properties in various environm ents. These surfac e tre a tm ents can also co mplicate the detec tion and analysis of nanom a terials.

In characterizing an env i ronm ental sam p le fo r intentionally produced nanom a terials, one must be able to distinguish between the nanopartic les of interest and other ultra-fine particles, such as nano scale p a rticles in th e atm o sphere gen e rated from coal com bustion or forest fires, or nanoscale p a rticle s in aq uatic e nvironm ents derived from soil runoff, sewage treatm ent, or sedim e nt resuspension. Infor m ation used to he lp characterize nanom aterials includes particle size, m o rphology, surface area and chem ical composition. Other inform ation taken into consider atio n in iden tif ying the source of nanomaterials includes observed particle concentrations m a pped over an area along with transport conditions (e .g., m e teorology, currents) at the tim e of sa m p ling. For nanom aterials with unique chem ical com position as found in som e quantum dots containing heavy m e tals, chem ical characterization (qualitat ive and quan titativ e) can play an important role in thei r detection and sour ce identif ication.

The level of ef f

o rt neede d and costs to perf orm analysis f o r n a nom aterials will depend on which environm ental co mpartm ent sam p les are bei ng taken from , as well as the type of desired analytical infor m ation. The anal ysis of nanom a terials from a n air m a trix requires significantly less (if any) “sam ple” preparation th an sam p les ta ken f r om a soil m a trix where it is n ecessa ry to

em ploy greater efforts for sam p le extraction and/or particle isolation. Analytical costs also depend on the degree of inform ation being acquired. Analyzing sam p les for num b er concentration (i.e., the num b er and size distribution of nanopart icles per unit volum e) requires significantly less effort than broadening such anal yses to include charac te riza tion of p a rticle types (fullerenes, quantum dots, nanowires, etc.). The level of effort als o increases f o r elem ental

com position analyses.

Although significant advances in aerosol particle m easure m ent technology have been

m a de over the past two decades in response to National A m bient Air Quality Stan dards (U.S. EPA, 2004), m a ny of these technologies were de signed to effectively function on m i cron sized particles, particles hundreds to a thousand tim es larger than nanopa rticles, and ar e not effective41 EPA Nanotechnology White Paper

in the separation or analysis of particles at the nanom e ter scale. However, som e of these technologies have advanced so that they are eff ective in providing separa tion and analytical data relevant to nanoparticles.

The inform ation availab l e from the bulk anal ysis of nanom a terial s from environm ental

sam p les has lim itations when one is trying to id entify a specific nanom at erial. As stated previously, nanoscale particles ge nerated by natural and other an thropogenic sources cannot be separated from nanom a terials of interest using sampling m e thodologies based upon particle size. During analysis, detected signals generated by na noscale par tic les th at a r e not of interest can

m a sk or augm ent the signals of nanom aterials of inte rest, resu lting in in adequate or erroneous data. W h ere procedures are availab l e for the se lective extraction of nanom aterials of inte rest, one can avoid interfering signals from other nano scale particles obtained during sam p ling. In the case of inseparable m i xtures of natural and engi neered/m anufactured nanom a terials, the use of single p a rticle analysis m e thodologies m a y be n ecessary to provide definitiv e analy s is for the engineered/m anufactured nanom aterials.

Even given all the challenge s presented in analyzing for specific nanom aterials of interest, m e thods and technologies are available that have demonstr ated success. For aerosols, multi-s t age impactor sa mplers ar e a v ailab l e co mmercially that can s e pa rate and collect nanoparticle size fractions for subsequent analys is. These technologies provide nanoparticle fraction s e p a ration based upon the aerodynam i c mobility p r o p erties of th e particles. Aerodynam i c m obility-b ased ins t rum e nts in clude m i cro-orifice uniform deposit im pactors (MOUDIs), and electrical low-pressure im pactor s (ELPIs) (McMurry, 2000). There are also aerosol fractionation and collection technologi es based upon the electrody nam i c m obility of particles. These technologies use th e m obility properties of charged nan oparticles in an electrical field to obtain particle size fractionation and collection. Instrum e nts e m pl oying this technology include d i f f

e rential m obility analyz er s (DMAs) a nd scanning mobility pa r tic le sizers ( S MPSs) (McMurry, 2000).

Available technologies for the size fractiona tion and collection of nanoparticle fractions in liquid m e dium s include size-exclusion ch rom a tography, ultrafiltra tion and field flow fractionation (Powers et al., 2006; R o cha et al ., 2 000; W illis, 2002; Chen and Selegue, 2002). On-line particle size analysis in liquid m e dium s c a n be done using vari ous techniques including dynam i c light scattering (DLS) to obtain a part icle size distribution (Bisw a s and W u, 2005) and inductively-coupled m a ss spectrom e try (ICP-MS ), a technique that provides chem ical characterization inform ation (Chen and Beckett, 2001). For more definiti ve analytical data, single-particle analytical tec hniques can be em ployed. Single- particle laser m i croprobe m a ss spectrom e try (LAMMS) can provid e chem ical composition data on single particles from a collected fraction (McMurry, 2000)

. Electron m i croscopy techni ques [e.g., transm ission electron

m i croscopy (TEM), scanning electron m i cros copy (SEM)] can provide particle size, morphological and chem ical com position inform ation on collected single nanoparticles in a

vacuum environm ent. Figure 19 shows an SEM of a scanning gate probe, which is an exam ple of an instrum e nt that can be used to analy ze n a n o m a terials. Atom ic Force Micro s cop y, a relatively new technology, can provide particle size and m o rphological inf o rm ation on single nanoparticles in liquid, gas, and vacuum environm ents (Maynard, 2000)42 EPA Nanotechnology White Paper

Figure 19. S E M of a scanning gate p r obe. The large tip is the probe f o r a scanning tunnelin g microscope, a nd the sm all e r is a gate that allows sharper i m agi ng of the sa mple. Instrum e nts such as these c a n be used to analy ze nanom ate r ials. (Im a ge courtesy of Prof. Le o Kouwehnh oven, Delft University of Technology . Reprint e d with
p er m i ssion from Gur e vich, L., et al., 2000) (Copy r ight 2000, Am erican Institute of Phy s ics.)



### 3.5 Human Exposures and Their Measurement and Control

As the use of nanom a terials in society increa ses, it is rea s ona ble to a ssume that their presence in environm ental m e dia will increase p r oportion a tely, with cons equences for hum a n and environm ental exposure. Potential hum an exposures to nanom aterials, or m i xtures of

nanom aterials, include w o rkers exposed during th e production, use, recycling and disposal of

nanom aterials, general population exposure from releases to the environm ent as a result of the production, use, recy clin g and disposal in the workplace, and direct general populatio n exposure during the use of comm e r cially available produ cts containing nanom aterials. This section identifies potential sources, pathways, and rout es of exposure, discusses potential m eans for

m itigating o rm i nim i zing worker ex posure, desc ribe s po tential too l s and models that m a y be used to estim a te exposures, and identifies pot ential data sources for these m odels.

3.5.1 Exposure to Nanomaterials

The exposure parad i gm accounts for a series of events beg i nn ing from when external

m echanis m s (e.g., releases or handling of che m ical s) m a ke a chem ical available for absorption or other m ode of entry at the outer bod y boundary to when the chem ical or its m e tabolite is delivered to the target organ. Between outer bod y contact with the ch em i cal and deliv ery to the target organ, a chem ical is absorbed and dist ributed. Depending on the nature of the chem ical and the route of exposure, the chem ical m a y be m e tabolized. For the purposes of this section, we will lim it th e discuss i on to the types of resour ces that a r e need ed (and ava i lable ) to a s s e ss exposure up to the point where it is distributed to the target organ.

3.5.2 Populations and Sources of Exposure

The potential for intentionally produced nanom aterials to be released into the environm ent or used in quantities that raise hum an exposure concerns are num e rous given their43 EPA Nanotechnology White Paper

predicted widespread applications in products. T h is section di scusses som e of the potential sources and pathways by which humans m a y be exposed to nanom aterials.

3.5.2.1 Occupational Exposure

Workers m a y be exposed to nanoscale m a te rials during m a nufacturin g/synthesis of the nanoscale materials, during for m ulation or end us e of products containing the nanoscale m a terial, or during d i sposal or recycling of the products co ntain i ng the nanoscale materials. Because higher concentrations and am ount s of nanoscale m a terials and hi gher frequencies and exposures

are m o re lik ely in workp l ace settings, occupati on al exposures warrant p a rticular atten t ion.

Table 4 presents the potential sources of occupational exposure during the common

m e thods for nanoscale material synth e sis: g a s phase synthes i s, vapor depos ition, collo id al, and attrition m e thods.44 EPA Nanotechnology White Paper

Table 4. Potentia l Sources of Occu pational Exposure for Various Synthesis Methods (adapted from Aitken, 2004) Syn t hesis Process Pa rticle Form ati o n Exposure Source or Wor k e r Ac tivity Primary Exposure Route

Gas P h ase in air Direct leaka g e from reactor, e s pecially if the reactor is op erated at po sitiv e p r essure. In hal a t i on

Product rec o ve ry from bag filters in react ors. Inhalation / De rm al

Pr ocessing and p a ck ag i n g of d r y po wd er. I n h a latio n / D e r m al

Equipm ent cleaning/m a intena nce (including reactor

ev acu ati o n and sp en t filters). Derm al (and I n hal a t i on d u ri ng reactor evacuat ion)

V a por Depo sitio n on su bst r at e Product rec o ve ry from react or/dry c ontam ination of workplace. In hal a t i on

Pr ocessing and p a ck ag i n g of d r y po wd er. I n h a latio n / D e r m al

Equipm ent cleaning/m a intena nce (including reactor evacuati o n). Derm al (and I n hal a t i on d u ri ng reactor evacuat ion)

Co llo id al/ Attritio n l i qui d

sus p ensi on I f liqu i d su sp en sion is pr o cessed i n to a powd e r, pot e n t i a l ex pos ure d u ri ng s p ra y dry i n g t o cre a t e a p o wd er, an d the pr o cessing an d p a ck ag ing of th e dr y po w d er

. Inh a latio n / Derm al

Equipm ent cleaning/m a intenance. Derm al

No te: Ing e stion wou l d b e a seco nd ary ro u t e of ex po su re fro m all so u r ces/ activ ities fro m d e po sition o f nan o m aterials

on f o od o r m u cous t h at i s su bs eque nt l y swal l o we d ( p ri m a ry ex po su re ro ut e i nhal a t i o n) a n d f r om han d

- t o -m out h
cont act (p ri m a r y exp o s u re r o u t e derm al ). O c ul ar e x pos u r e wo ul d be an ad di t i onal ro ut e o f e x p o s u re f r o m so m e

so urces/activ ities fro m d e po si tio n o f airborne po wd ers o r mists in th e ey es or fro m sp lash ing o f liq u i ds

.

While there are sev e ral p o tential exp o su re sources for each manufacturing process, packaging, transfer, and cleani ng operations m a y provide the gr eatest potential for airborne levels of nanom a terials and result ant occupational exposures. “The risk of particle release during production seem s to be low, because m o st produc tion p r ocesses take p l ace in clo s ed system s with appropriate filterin g system s. Contam ination and exposure to workers is m o re likely to happen during handling and bagging of the m a te rial and also during cleaning operations.” (Luther, 2004).

During the form ulation of the nanom aterials into products (e.g., coatings and com p osite

m a terials), workplace releases and exposures m a y be m o st likely to occur during th e transfer/unloading of nanoscale m a terial from sh ipping containers and dur ing cleaning of process equipm ent and vessels. During the use of som e of these products in workplace settings, releases of and exposures to nanoscale m a terial are highl y dependent upon the application. For exam ple, workers who m a nually apply spray coatings often ha ve higher levels of occupational exposure. Alternately, com ponents of com posites are usua lly bound in the com posite m a trix, and workers handling the com posites would generally have lowe r levels of occupational exposure. Exposure45 EPA Nanotechnology White Paper

could also occur during product m achining (e .g., cutting, drilling a nd grinding), repair, destruc tion and recyc lin g [ N ational I n stitu te f o r Occupationa l Health and Saf e ty (NIOSH), 2005a]. NIOSH (2004, 2005b) has issued a dditional documents on nanotechnology and workplace s a fety and as sociated res earch needs.

3.5.2.2 Release and General Population Exposure

General population exposure m a y occur from environm ental releases from the production and use of nanom aterials and from direct use of products containing nanom a terials. During the production of nanom a terials, there are several potential sources for environm ental releases includ ing th e evacuation of production cham bers , filter res i d u es, losses d u ring spray drying,

em issions from filter or scrubber b r eak-thr ough, and wastes from equipment cleaning and product handling. No data have been identified quantifying the releases of nanom a terials from industrial processes or of the fate of nanom aterials after release in to the environm ent. However, due to the sm all size of nanom aterials, they will likely stay airborne fo r a substantially longer tim e than other types of particulate. The m o st likely pathway for general population exposure from releases from industrial processes is direct inhalation of m a terials released into the air during m a nufacturing (UK Royal So ciety, 2004). Releases from industrial or transportation acciden t s, n a tural dis a sters, or m a levolent activ ity such as a terro ris t a ttack m a y also lead to exposure of workers or the general public.

Nanoscale m a terials have potential applicatio ns in m a ny consum er products resulting in potential general population exposure. Electr onics, m e dicine, cosm etics, chem istry, and catalysis are potential be neficiaries of nanotechnology. W i desp read exposure via direct contact with products from these sectors is expected. Table 5 presents severa l examples of potential sources of general population and co nsum er exposure associates with the use of such products.

Table 5. Examples of P o tentia l Sources of Gen eral Popula t ion and/or Consumer Exposure for Several Product Types

Prod uct T y pe Release and/ or Exposure Source Exposed Pop u l ation P o t e n t ia l Ex po s u re Ro ut e Sunscree n cont ai ni ng nanoscale
mater i al Pro d u ct a ppl i c at i on by co ns u m er t o s k i n C ons um er Derm al
Release by consum er (e.g., wa shing with

so ap an d w a ter) to w a ter su pply Gene ral po p u l a t i on In gest i o n

Di sp osal of su nscree n c o nt ai ner ( w i t h residu al su n s creen ) after u s e (to land fill or in cin e ration) Gene ral po p u l a t i on In hal a t i o n o r I nge st i on

Metal catalysts in
g a so lin e for reducing ve hicle exha ust * R e l ease fr om vehi cl e ex ha ust t o ai r (t he n deposition to surface water) Gene ral po p u l a t i on In hal a t i o n o r I nge st i on

Pain ts an d C o at i ngs Weathe ring, di sposal C ons um ers, ge neral
p opu latio n , Derm al , In hal a t i on or In gest i o n

C l ot hi n g Wear
, washi n g , di s p osal C ons um ers, ge neral
p opu latio n Derm al , i nhal a t i on, i nge st i o n fr om surface o r gr ou n d wate rProd uct T y pe Release and/ or Exposure Source Exposed Pop u l ation P o t e n t ia l Ex po s u re Ro ut e Electronics Release at end of life or recyc ling sta g e C ons um ers, ge neral
p opu latio n Derm al , i ngest i on fr om surface or groundwater
Sporting goods Release at end of life or recyc ling sta g e C ons um ers, ge neral
p opu latio n Derm al , i nhal a t i on, i nge st i o n fr om surface o r gr ou n d wate r 46 EPA Nanotechnology White Paper

NOTE: Th is is n o t an exh a ustiv e list of co nsumer p r od u c ts or ex po su r e scen ar i o s. Ing e stion wou l d b e a second ary ro u t e of ex po sure fro m so me so urces from d e p o s itio n of n a no m a terial s on food o r

m u cous t h at i s sub s eq ue nt l y swal l o we d ( p ri m a ry exp o s u re r out e i nhal a t i o n) an d fr om hand -t o

- m out h c ont act (p ri m a ry expos ure r out e de rm al ). Ocu l ar exp o s ure wou l d b e an ad d itio n a l rou t e o f exp o su re fro m so me

so urces/activ ities fro m d e po si tio n o f ai rborne po wd ers o r mists in th e ey es or fro m sp lash ing o f liq u i ds.

* Metal catalysts are no t curren tly b e ing u s ed in g a so l i n e i n t h e U.S

. C e ri um oxi de na no part i c l e s are be i ng mark eted i n Europ e as on and o f f-ro ad d i esel fu el add itiv es.

3.5.3 Exposure Routes

Much rem a ins to be scien tifically demonstrated about the m echanism s by which hum an exposure to nanom aterials can oc cur. Intentionally produced na nom aterials share a number of characteristics, such as size and dim e nsions, with other substances (e.g., ul trafine particles) for which a large body of infor m ation exists on how th ey access the hum an body to cause toxicity. The data from these other substances focus prim arily on inhalation as the route of exposure. However, as the range of applications of nanom a terials expands, other routes of exposure, such as derm al, ocular, and oral, m a y also be found to be significant in hum ans.

3.5.3.1 Inhalation Exposure

A UK Health and Safety Executive reference suggests that aerosol science would be applicable to airborne nanoparticle behavior. A e rosol behavior is prim arily affected by particle size and the forces of inertia, gravity, and diffusion. Other factors affecting nanoparticle airborne concentrations are agglom eration, de position, and re-suspens ion. (UK Health and Safety Executive, 2004) All of these issues, which are discussed in m o re detail in the reference, are relevant for understanding, predicting, and controlling ai rborne concentrations of

nanom aterials.

One reference study was found to have investigat ed issues involved with aerosol release of a single-walled carbon nanotube (SW C NT) m a terial. T h is study noted that while laboratory studies indicate th at sufficient agitation can re lea s e f i ne par t icles into th e air, a e roso l concentrations of SWCNT generate d while handling unrefined m a teri al in the field at th e work loads and rates observed were very low on a m a ss basis (Maynard et al., 2004). The study suggests that m o re research wi ll be needed in this area.

3.5.3.2 Ingestion Exposure

Inform ation on exposure to nanoscale envir onm ental particles via oral exposure is lacking. In addition to traditional in gesti on of food, food additiv es, m e dicines and d i etary supplem ents, dust and soil (particula rly in the case of children), inge stion of inhaled particles can47 EPA Nanotechnology White Paper

also occu r (s uch as throu gh the ac tivities of the m u cocillia ry e s cal ator). The quantity ingested is antic ipated to be relativ e l y sm all in term s of mass.

3.5.3.3 Derm al Exposure

Derm al exposure to nanom a terials has received much attention, perhaps due to concerns with occupational exposure and th e introduction of nanom a terials such as nanosized titanium dioxide into cosm etic and drug products. One re ference study was found to have investigated issues involved with potential de rm al exposure to a SW CNT m a terial. T h e study suggests that more research will be n eeded in this area. Th is s t udy noted that airbor ne particles of SW CNT

m a y contribute to po tential derm al exposure alo ng with surface deposits due to m a terial handling. S u rface deposits on glo v es were estim a ted to be b e tween 0.2 mg and 6 m g per hand. (Maynard et al., 2004)

There is an ongoing debate over the potenti al for penetration through “healthy/intact” versus dam a ged skin. Hart (2004) highlights phys iological characteristics of the skin that m a y perm it the absorption of nanosized m a terials. In particular the review hig h lights a con ceivab l e route for the absorption of nanoparticles as be ing through interstices formed by stacking and layering of the calloused cells of the top layer of skin (Hart, 2004). Movem e nt through these inte rstices w ill sub s eque ntly lead to the skin bene ath, f r om which substan ces can be a b sorbed into the blood stream

. Nanom ateria ls also have a greater risk of being absorbed through the skin than m acro-sized particles (Tink l e, 2003). Reports of toxicity to hum an e p iderm a l keratinocytes in culture following exposure to carbon nanot ubes have been m a de (Shvedova et al., 2003; Monteiro-Riviere et al., 2005). A significant am ount of intrad erm a lly injected nanoscale quantum dots were found to disperse into the su rrounding viable subcutis and to draining lym ph nodes via su bcutaneous lym phatics (Roberts, D.W. et al., 20 05). It has recently been reported that quantum dots with different physicochem i cal properties (size, shapes, coatings) penetrated the stratum corneum and localized within th e e p iderm a l and derm al layers of intact porcine skin within a m a xim u m 24 hours of exposure (Rym a n -R asm u sse n et al., 2006). Drug delivery studies using m odel wax nanoparticles h a ve provided ev id ence that n a noparticle surface charg e alters blood-brain barrier integ r ity and perm eability (L ockm an et al., 2004).

3.5.3.4 Ocular Exposure

Ocular exposure to nanom a teri als ha s rece ived little a tten ti on. However, the potential for ocular expos ure to nano m a terials fro m depositio n of airborn e powders o rm i sts in th e eyes or from splashing of liquids m u st also be considered.

3.5.4 Exposure Mitigation

Approaches exist to m itigate exposu r e to fine and ultrafine particulates. S o m e approaches such as engineering controls are app l icable to th e work place and m a y m i t i gate environm ental releases while others such as pe rso n al pro t ectiv e equipm ent (PPE) are p r im arily applicable to the workplace. NIOSH suggests c onsidering the range of contro l tech nologies and personal protective equipm ent dem o nstrated to be e ffective with other fine and ultrafine particles (NIOSH, 2005a). In the hier archy of exposure reduction m e t hods, engineering controls are preferred over PPE.48 EPA Nanotechnology White Paper

3.5.4.1 Engineering Controls

Engineering controls, and particularly those us ed for aerosol control, should generally be effective for controlling exposures to airborne nanoscale m a teri als (NIOS H , 2005a). Depending on particle size, nanoparticles m a y diffuse rapidl y and readily find leakag e paths in engineering control system s in which containm ent is not comp lete (Aitken et al., 2004). However, a welldesigned ex haust ven tilation sys t em with a high efficiency p a rticulate air (HEPA) filter should effectively rem ove nanoparticles (Hinds, 1999). As with all f ilter s, the filter m u st be properly seated to prevent nanoparticles from bypassing th e filter, decreasing the filter efficiency (NIOSH, 2003). Aitken et al. (2004) recomm ends that engineer ing controls (e.g., enclosures, local exhaust ventilation, fum e hoods ) used to control exposure to nanoparticles need to be of sim ilar quality and specification as those typically used for gases. However, the report also notes that no research has been identified evaluating th e effectiven ess of engin eering controls for nanoparticles.

Efficient ultrafine particle control devices (e.g., soft x -ray enhanced electrostatic precipitation system s) may have applicability to nanoparticles control (K ulkarni et al., 2002). HEPA f ilter s m a y be effectiv e, and v a lida tion of their ef f

ectiv eness is curr ently be ing s t udied (NIOSH, 2005a). Magnetic filte r system s in welding processe s have proven effective in capturing magnetic oxides and the use of nanostructu red sorbents in sm elter exhausts to prepare ferroelectric m a terials may also have applicability (Biswas et al., 1998).

3.5.4.2 Personal Protective Equipm e n t (PPE)

Properly f i tted respira t or s with a HEPA f ilter m a y be ef f

ectiv e at r e m oving

nanom ateria ls. Contra ry to intu ition, f i brous f ilte rs tr ap sm aller and large r particle s more effectively than m i d-sized particles. Sm all particles (<100 nm ) tend to m a ke random Brownian motions due to the i r in te raction with gas m o lecule s. The inc r eased m o tion causes th e particle to “zig-zag aro und” and have a grea ter chance of hitting and sticking to the fiber filter (Luther, 2004). Interm ediate-sized particles (>80 nm and < 2000 nm ) can rem a in suspended in air for the longest tim e. (Bidlem a n, 1988; Preining, 1998; S purny, 1998; Atkinson, 2000; UK Royal Society, 2004; Dennenkamp et al., 2002)

NIOSH certifies particulate respirato r s by chal lenging them with sodium chloride (NaCl) aerosols with a count median diam e t er 75 nm or dioctyl phthalate (DOP) aerosols with a count

m e dian diam eter of 185 nm [ 42 CFR Part 84.181(g)], which have been found to be in the m o st penetrating particle size range (S tevens and Moyer, 1989). H o wever, as with all respirators, the greatest factor in determ ining th eir e f f

ectiveness is not pen e tr ation through the f ilter, but rather the face-s eal leakage byp assing th e d e vice. Due to size and m obility of nanom a terials in the air, leakage m a y be m o re prevalent although no m o re than expected for a gas (Aitken, 2004). Only lim ited data on face-seal leakage h a s been iden tified. W o rk done by researchers at the U.S. Ar m y RDECOM on a headform showed that m a sk leakag e (i.e., sim u lated respirato r fit factor)

m easured using subm icron aerosol challenges (0.72 μm polystyrene latex spheres) was representative of vapor challenges such as sulf ur hexafluoride (SF6) and isoam y l acetate (IAA) (Gardner et al., 2004).49 EPA Nanotechnology White Paper

PPE m a y not be as effective at m itigating derm al exposure. P P E is likely to be less effective against derm al exposure to nanom aterials than m a c r o-sized part icles from both hum an causes (e.g., touching face with contam inated fingers) and PP E penetration (Aitken, 2004). However, no studies were identified that discu ss the efficiency of PPE at preventing d i rect penetration of nanom a terial s through PPE or from failu re due to hum an causes.

3.5.5 Quantifying Exposure to Nanomaterials

There is broad consensus that m a ss dose alone is insufficient to char acterize exposure to

nanom aterials (Oberdörster et al ., 2005a, b; NIOSH, 2005a, b). Ma ny studies have indicated that toxicity in creases with d ecreased particle size an d that particle su rface area is a better m e tric for

m easuring exposures (A itken, 2004). This is of particular concern fo r nanom a terials, which typically have very high surface-area-to-m a ss ratios. Additionally, there curren tly are no convenien t m e thods for monitoring the surface area of particles in a work er’s b r eathin g zone or

am bient air. W h ile there could be a correlati on between m a ss and surface area, large v a riations in particle weight and su rface ar ea can occur with in a given b a tch. The average particle weigh t and averag e particle surface area of the nanom aterials being asse ssed wou l d also b e required for
any assessm ents based o n surface area. (Maynard and Kue m pel, 2005). It has also been

recomm ended that m a ss, surface area, and partic le num ber all be m easured for nanomaterials (Oberdörster et al., 2005b).

3.5.6 Tools for Exposure Assessment

Several tools exist for perform i ng expos ure assessm ents including m onitoring data, exposure models, and the use of analogous data fr om existing chem icals. The following sections discuss these tools and their pote ntial usefulness in assessing expos ure to nanoscale materials.

3.5.6.1 Monitoring Data

Types of m o nitoring data that can be used in exposure assessm e nt include biological monitoring, personal sampling, am bient air m onito ring, worker health m o nitoring and m e dical surveillance. Although monitori ng and m easurem ent are discusse d earlier in section3.4, the discussion below includes cove rage of som e issues direct ly pertinent to exposure.

Biological Monitoring

Biom onitoring data, whe n perm itted and applied corre ctly, p r ovides th e b e st inf o rm ation on the dose and levels of a chem ical in the hum an body. Examples of bi o-m onitoring include the Centers for Disease Con t rol and Prevention (C DC) national monitoring program and sm aller surveys such as the EP A’s National Hum a n Exposure Assessm ent Survey (NHEXAS). Biom onitoring can be the best tool for unders tanding the degree and spread of exposure, inform ation that cannot be captured through m o n itoring concentrations in am bient media. Biom onitoring, however, is potentia lly lim ited in its application to nanotechnology because it is a science that is m u ch dependent on knowledge of biom arkers, and its benefits are highest when there is background knowledge on what nanom aterials should be m onitored. Given the current lim ited knowledge on nanoscale m a terials in comme rce, their uses, and their fate in the environm ent and in the hum a n body, it is difficult to identify or priori tize nanom aterials for biom onitoring. Should biom onitoring becom e more feasible in the future, it presents an50 EPA Nanotechnology White Paper

opportunity to assess the spatial and tem poral distribution of na nom aterials in workers and the general population.

Personal Sampling

Personal sampling data provide an estim ate of the exposure experien ced by an individual, and can be an im portant indicator of exposure in occupational settings. It is lim ited in that it does not account for changes to the dose rece ived by the target organ after the biological processes of absorption, distribution, m e tabolis m and excretion. Generally, for cost and feasibility reasons, personal and biomonitoring data are not availa ble for all ch em icals on a scale that is m eaningful to policym akers. Als o, the ap plicab ility o f personal sa mpling to

nanom aterials is dep e nd ent on the d e velopm ent of tools for accurately d e tecting and m easuring such m a terials in am bient m e dia.

Ambient Monitoring

Am bient m e dia m onitoring m easures concentr ations in la rger spaces such as in workplaces, hom e s or th e general en vironm ent. Am bient data are us ed as assum e d exposure concentrations of che m icals in popu lations when it is not feasible or practical to conduct personal

sam p ling for individuals in the populations. Typica lly, these data are used in m odels in addition to other assumptions regarding exposure pa ram e ters, including popul ation activities and dem ographics such as age.

Challenges of Monitoring

As discussed in Section 3.4, there are m a ny challenges to de tecting and characterizing nanoscale materials, including the ex trem ely sm all size of the analyte, as well as the n e ed to distinguish the m a terial of in terest from other sim ilarly-size d m a teria l s, the tend ency f o r nanoparticles to agglom erate, and the cost of anal ysis. Additionally, as discussed in above, it is not always clear what the m o st appropriate m e tr ic is to m easure. Mass m a y not be the m o st appropriate dose m e tric; therefor e, techniques m a y be required fo r m easuring particle counts and surface area, or other p a ram e ters. These probl ems are com pounded when there is a need for monitoring data to be used in exposure assessm e n t. Monitoring equipm e n t should be not only sensitive an d specific, b u t also easy to use, durab le, able to operate in a range of environm ents, and affordable. Additionally, data som e ti m e s need s to be collected contin uously and analyzed in real-tim e. Further, the n a nom aterials m a y need to be m easured in a variety of m e dia and several properties m a y need to be m easured in parall el. All of the current m easuring m e thods and instrum e nts individually fall short of ad equately addressing all of these needs.

3.5.6.2 Exposure Modeling

A recent use of a m bient monitoring data to es timate th e expo sure of a population is the

cum u lative exposure project for air toxics recen tl y com p leted for hazard ous air toxics using the Hazardous Air Pollutan t Exposure Model (HAPEM) ( http://www.epa.gov/ttn/fera/hum an_hapem .ht m l ). This m ode l predicts inhalation exposure concentrations of air toxics from all outdoor sources, based on am bient concentrations from modeling or monitor data for specific ai r toxics at the census tract level.51 EPA Nanotechnology White Paper

Other EPA screening level m odels include the Chem ical Screening Tool for Exposures and Environm ental Releases (ChemSTEER) (http://www.epa.gov/oppt/exposure/docs/chem steer.ht m ) and the Exposure and Fate A ssessm ent Screening Tool (E-FAST) (http://www.epa .gov/oppt/exposure/docs/efast.htm )

. Che m STEE R estim ates po tential dos e rates for workers and en v i ronm ental releas es from workplaces. E-FAST uses the workplace releases to estim ate poten tia l dose rates for the gen e ral population. E-FAST also estim ates potential dose ra tes for consum ers in the general public. However, whether Chem STEER and E-FAST will be u s ef ul f o r ass e ssm ents of nanoscale mater i als is no t cle a r because of the significantly differen t chem i cal and physical properties of nanom aterials.

Challenges of Using Models with Nanoscale Materials

There ar e se veral m odels that sp an multiple lev e ls of com p lexity and ar e designed to estim ate exposure at several points in the exposur e paradigm

. The effectiveness of these m odels at pred icting hum a n exposure will d e pend on the param e ters and assum p tions of each model. For m odels that are based on assum p tions specif ic to the chem ical such as the physical and chem ical properties, and interactions in hum an s and the environm ent based on these properties, much substance-specific data m a y be required.

Data Sets for Modeling

The availability of am bient data is clearly cr itical to m odeling exposure, an d there are a

num b er of resources within EPA for this type of data. In som e cases such as f o r pes tic ides, th e exposure can be anticipated based on the quantity of the substance that is proposed to be applied and the anticipated residue on a food item as an exam ple. Som e ti m e s there are data collected under statutory obligations, such as data collected for the Toxi cs Release Inventory (TRI) under the Em ergency Planning and Comm unity Right to Know Act (EPC RA). For contam inants in drinking water, the data m a y be reported to the S a fe Drinking W a ter Inform ation System (SDW IS). Generating data for nanom a terials nece ssita tes the identif i ca ti on of nanom a terials as separate and different from other chem icals of id entical nomenclature, an d their classification as toxic substances, or in a m a nner that adds nanomaterials to th e lis t of repo rtab le releases/contam i nants.

Though not fully representative of population exp o sure, work place data h a ve frequently provided the foundation for understa nding exposure and toxicity for m a ny chem icals in industrial production. A recent stu dy in the Un ited States, in which ambient air con centration s and glove deposit levels were m easured, identif ied a c oncern for exposure during handling of nanotubes (Maynard et al., 2004). In the work environm ent, data on workplace exposure is frequently collected under the purview of Occupational Safety and H ealth Adm i nistration (OSHA)­

m a ndated program s to assess worker exposur e and assure compliance with workplace regulations and worker protection. Em ployers, however, are not requir ed to report these data. In addition, OSHA standards are typica lly airborne exposure levels that are based on health or

econom ic criteria or both, and typically only defined exceedences of these standards are docum ented. To understand nanotechnology risk s in the workplace, the National Ins titu te of Occupational Safety and Health (NIO SH) is advancing initiatives to investigate am ongst other issues, nanoparticle exposure and w a ys of c ontrolling exposure in the workplace (NIOSH, 2004).52 EPA Nanotechnology White Paper



### 3.6 Human Health Effects of Nanomaterials

There is a significant gap in our knowledge of the environm ental, health, and ecological im plications associated with nanotechnology (D reher, 2004; Swiss Report, 2004; UK Royal Society, 2004; European NanoSafe, 2004; UK He alth and Saf e ty Executive, 2004). This section provides an overview of currently available inform ation on the toxicity of nanoparticles; m u ch of the inf o rm ation is f o r na tural or inc i d e ntally f o rm ed nanosized m a terials, and is presented to aid in the understanding of intenti onally produced nanom a terials.

3.6.1 Adequacy of Current Toxicological Data base

The Agency’s datab a ses on the health effects of particulate m a tter (P M), asbestos, silica, or other toxicological databases of sim ilar or larg er siz e d par t icle s of iden tica l chem ical

com position (U.S. EPA, 1986, 1996, 2004) should be evaluated for their potential use in conducting toxicological assessm ents of intentio nally produced nanom aterials. The toxicology chapter of the recen t Air Quality Criteria for Par t icula t e Ma tter docum ent cites hundreds of references describing the health effects of am bient air particu l ate m a tter including u l trafine

am bient air (PM 0. 1 ), silica, carbon, and titanium dioxide pa rticles (U.S. EPA, 2004). However, it is im portant to note that am bien t air ultrafine pa rticles are distinct from intentionally produced

nanom aterials since they are not pu rp osely eng i neered and rep r esent a phy sicochem ical and dynam i c complex m i xture of particles derived from a variety of natural and com bustion sources. In addition, only approxim ately five percent of the refere nces cited in the current Air Quality Criteria for Particu l ate Matter docum ent describe the toxicity of chem ic ally defined ultrafine particles, recently review ed by Oberdörster et al. (2005a) and D onaldson et al. (2006).

A search of the literature on particle toxicity studies published up to 2005 confirm s the paucity of data describing the toxicity of che m i cally defined ultrafine pa rticles and, to an even greater extent, that of intentionally produced nano m a terials (Figure 20). The ability to assess the toxicity of intentionally produced carbon nanot ubes by extrapolating from the current carbonparticle toxicological database was exam ined by Lam et al. (2004) and Warheit et al. (2004). Their findings dem onstrate that graphite is not an appropriate safety reference standard for carbon nanotubes, since carbon na notubes displayed very dif f

erent m a ss-based dose-response relationships and lung histopathology when directly com p ared with graphite.53 EPA Nanotechnology White Paper

Figure 20. Particle Toxicology Citations . Results depict the number of toxicological
p ublications for each type of particle obtained from a PubMed search of the literature up to 2005 using the indicated descriptors and the term “toxicity.” Uf denotes ultrafine size (<100nm) particles.

These initial findings indicate a high degree of un certainty in the ability of curren t particle toxicological databases to assess or predict the toxicity of intentionally produced carbonbased nanom a terials displaying novel physicoche m i cal properties. Additional com p arative toxico logical studies are needed to as sess the u t ility of the current particle toxicological databases in assessing the toxi city of other classes or t ypes of intentionally produced

nanom ateria ls, as well as to re late the i r hea lth ef f

ects to n a tur a l or an throp ogenic ultraf ine particle s

.54 EPA Nanotechnology White Paper

3.6.2 Toxicity and Hazard Identification of E n gineered/Manufactu red Nanomateria l s
Studies assessing the role of particle size on toxicity have generally found that ultrafine or nanosize range (<100 nm ) pa rticles are m o re toxic on a mass-based exposure m e tric when

com p ared to larger particles of identical chem ical com position (Oberdörster et al., 1994; Li et al., 1999; Höhr et al., 2002). Other studies have sh own that particle surface area dose is a better predictor of the toxic and pathol ogic responses to inhaled partic les than is particle m a ss dose (Oberdörster et al., 1992; Drisco ll, 1996; Lison et al., 1997; D ona ldson et al., 1998; Tran et al., 2000; Brown et al., 2001; Duffin et al., 2002). S t udies exam ining the pulmonary toxicity of carbon nanotubes have provided evidence that inte ntionally produced nanom a terials can display unique toxicity that cannot be explained by differe nces in particle size alone (Lam et al., 2004; Warheit et al., 2004). F o r exam ple, Lam re ported single walled carbon nanotubes displayed greater pulm onary toxicity than carbon black nano particles. Sim ilar results have been obtained from com p arative in v itr o cytotoxicity studies (Jia et al., 2005). Muller et al. (2005) reported multi-walled carbon nan o tubes to b e more proinfla mmatory and profibrog e nic when com p ared to ultrafine carbon black particles on an equivalent m a ss dose metr ic. Shvedova et al. (2005) reported unusual inflam m a tory and fibrogenic pu lm onary responses to specific nanom a terials, suggesting that they m a y injure the lung by ne w m echanis m s

. Exposure of hum a n epiderm a l keratinocyte cells in culture to single-walled carbon nanotubes was repor ted to cause derm al toxicity, in cluding oxidative stress an d loss of cell viability (S hvedova et al., 2003). T h e

com b ination of sm all particle size, large surf ace area, and ability to generate reactive ox ygen species have been suggested as key factors in induction of lung injury following exposure to

som e incidentally produced nanom aterials (Nel et al., 2006).

Contrary to other reports, Uchino et al. (2002), Warheit et al. (2006) and Sayes et al. (2006) have reported nanoscale titanium dioxide toxicity wa s not found to be dependent on particle size and surface area. Th es e authors repo rted that sp ec ific cry s tal structure an d the ability to generate reactive oxygen species are important factors to c onsider in evaluating

nanom aterial toxicity. S i m ilar to other reports, W a rheit de monstrated that nanom ateria l coa ting im pacted toxicity (W arheit et al., 2005).

Studies hav e dem onstrated that n a no partic le toxicity is extre m ely com p lex and m u ltifactorial, potentially be ing regulated by a variety of physicoc hem i cal properties such as size and shape, as well as su rface properties such as charg e , area, and reactivity (S ay es et al., 2 004; Cai et al., 1992; Sclafani and H e rrm ann, 1996; Nemma r et al., 2003; Derfus et al., 2004). The properties of carbon nan o tubes in relation to pulm onary toxicology have recen tly been reviewed (Donaldson et al., 2006).

Toxicological assessm e n t of intentiona lly produced nanom aterials will require inform ation on the route (inhalation, oral, derm al) th at carries the greatest risk for exposure to these m a terials, as well as com p rehensive physic ochem i cal characterization of them in order to provide inform ation on size, shap e, as well as su rface properties such as charge, a r ea, and reactivity. Establishm e n t of dos e-response relationships linki ng physicochem i cal properties of inten tiona lly produced n a nom aterials to the i r tox i cities will id entif y the ap propria te ex posure

m e trics that best correlate w ith adverse health effects.55 EPA Nanotechnology White Paper

One of the most striking findings regarding pa rticle h ealth e f f

ects is the ability of particle s to genera te loc a l tox i c ef f

ects a t the s i te of initial deposition as well as very significant system ic tox i c respon ses (U.S. EPA, 2004). Pu lmonary deposition of po lystyrene nanoparticles was found to not only elicit pulm onary inflamm a tion but also to induce vascular thrombosis (Nemmar et al., 2003). P u lm onary deposition of carbon black nanoparticles was found to decrease heart rate variabili ty in rats and prolonged cardi ac repolarization in young healthy individu als in recen t toxicological an d clin ical stu d ies (Hard e r et al., 2005 ; Fram pton et al., 2004). Extrapulm onary translocation follo wing pulm onary deposition of carbon black nanoparticles was reported by Ober dörster et al. (2004a, 2005a) S ubm icron particles have been shown to penetrate the stratum corneum of hum a n skin following derm al application, suggesting a potential route by which the imm u ne system may be affected by derm al exposure to nanoparticles (Tinkle et al., 2003; R y m a n-Rasmusse n et al., 2006). Zhao et al. (2005) have reported that in m o lecular dynam i c com puter sim u lations C 60 fullerenes bind to double and single-stranded DNA an d note that th ese sim u lations suggest that C 60 m a y negatively im pact the structure, stability, and biological functions of DNA. It is clear that toxicological assessm ent of inten tiona lly produced n a nom aterials will r e quir e consider ation of both local and sys t em ic toxic responses (e.g., immune, cardi ovascular, neurological toxicities) in order to ensure that that we identify the health effects of concern from these m a terials.

3.6.3 Adequacy of Toxicity Test Methods for Nanomaterials

A challenge f acing the to xicolog i cal assessm ent of intention a lly produ ced nanom aterials is the wide diversity and com p lexity of the types of m a terials that are av ailable commercially o r are under developm ent. In m a ny cases, the sam e type of nanom aterial can be produced by several different processes, giving rise to a num ber of versions of the same type of nanom a terial. For exam ple, single-walled carbon nanotubes can be m a ss produced by four different processes, each of which generates products of different si ze, shape, co mposition, and potentially different toxicological propert ies (Bekyarova, 2005 )

. It is not known whet her the toxicological

assessm ent of one type and source of nanom a terial will be su fficient to as sess the toxicity of the

sam e class/type of nanom aterial produced by a di fferent process. Manufactured m a terials m a y also be treated with coatings, or oth e r surface m odifications, in order to g e nerate m ono-dispersed suspensions that extend and enhance their unique properties. The extent to which surface modifications of intentionally produced nanom ateria ls affect their toxic ity is not know n. Other testing issues include the possibi lity of physicochem i cal changes in the m a terial before and after adm i nistration in a test s y stem , presenting a ch al lenge in id en tif ying the c h arac ter i za tion criter ia for nanom a terial tox i city

. Test m e thods that d e term ine the to xicity and h azardous physicochem i cal properties of in tentionally prod uced nanomaterials in an accepted, tim e ly and cost effectiv e m a nner are needed in order prov id e health risk assessm ent inf o rm ation f o r the diversity of such nanomaterials that are currently available (Oberdörster et al., 2005b).

3.6.4 Dosimetry and Fate of Intent ionally Prod uced Nanomaterials

Much of what is known regarding particle dosimetry and fate has been derived from pulm onary exposure studies using ultrafine m e ta l oxide and carbon black studies (U.S. EPA, 2004; Oberdörster, 1996; Oberdörster et al., 2005a, b; Oberdörster et al., 2004a; Kreyling et al., 2002)

. Ultrafine carbon black and m e ta l oxide particles display di fferential deposition patterns within the lung when compared to larger sized pa rticles of identical chem ical com position. For56 EPA Nanotechnology White Paper

exam ple, 1 nm particles are pr eferentially deposited in the nasopharyngeal region while 5nm particles are deposited th roughout the lung and 20 nm particles are preferentially deposited in the distal lung within the alveolar gas exchange region (Oberdörster et al., 2005a). Host susceptibility factors such as pre-existing l ung disease significantly affect the am ount and location of particles deposited wi thin the lung. For exam ple, indi viduals with chronic obstructive pulm onary disease have 4-fold higher levels of particles deposited in their upper bronchioles when com p ared to health indivi duals exposed to the sam e concen tration of particles (U .S. EPA, 2004). Also, pulm onary deposited ultrafine par ticles can evade the norm a l pulm onary clearance

m echanis m s and translocate by a variety of pathwa ys to distal organs (O berdörster et al. 2004a, 2005a; Krey ling et al., 2 002; Renwick et al., 200 1). Additio nal stud ies that prov ide infor m ation on the deposition and fate of inhaled nanom aterials include s t udies in anim als (Takenaka et al., 2001; Oberdörster et al., 2002) and st udies in hum a ns (Brown et al., 2002; Chalupa et al., 2004).

The deposition and fate of the class of nanom a terials called dendrim ers have been

exam ined to som e degree due to their potential drug de livery applications (Malik et al 2000; Nigavekar et al., 2004. ). Both studies dem onstrat ed the critical ro le which surface ch arge and chem istry play in regulating the deposition and clearance of dendrim ers in rodents.

A significant am ount of intr aderm a lly injected nanoscale quantum dots were found to disperse into the surrounding vi able subcutis and to draini ng lymph nodes via subcutaneous lym phatics (Roberts, D.W. et al., 2005). Othe r s t udies (Tink l e et al., 2003) have shown enhanced penetration of subm icron fluorosphere s into the stratum corneum of hum a n s k in following derm al application and m echanical stimulation. D r ug delivery studies using m odel wax nanoparticles h a ve provided ev idence that n a noparticle surface charg e alters b l oo d-brain barrier integ r ity and perm eability (L ockm an et al ., 2004). It has recently been repo rted that quantum dots with different physicochem i cal propert ies (size, shapes, coat ings) penetrated the
stra tum corneum and localiz ed within the epid er m a l and derm al layers o f intact po rcine skin within a m a xim u m 24 hours of exposure (Rym a n -Rasm u sse n et al., 2006). A recent review noted that quantum dots cannot be considered a uniform group of substances, and that size, charge, concentration, coating, and oxidative, photolytic, and m e ch anical stability are determ ining factors in quantum dot toxicity as well as their absorption, distribution, m e tabolism and excretion (Hardm an, 2006). Toxicological st udies have dem onstrated the direct cellular uptake of multi-walled carbon nanotubes by human ep iderm a l keratinocytes (Monteiro-Riviere et al., 2005).

Very little is known regarding th e deposition and fate of other types o rclasses of intentionally produced nanom aterials following inhalation, ingestion, or derm al exposures. Knowledge of tissue and cell specific depositi on, fate and persisten ce of engineered or

m a nufactured nanom aterials, as well as factors such as host susceptibi lity and nanoparticle physicochem i cal properties regulati ng their dep o sition and fate, is needed to determ ine exposuredose-response relationships associ ated with various routes of e xposures. Infor m ation on the fate of nanom a terials is needed to assess their persistence in b i ol ogical system s, a property that regulates accum ulation of these particles to le vels that m a y produce adverse health ef fects following long-term exposures to low c oncentrations of these particles.57 EPA Nanotechnology White Paper

At a 2004 nanotoxicology workshop at the Univ ersity of Florida (Roberts, S.M., 2005), concerns were expressed about the ability of existing technologies to detect and quantify intentionally produced nanom ater ials in biological system s. New detection m e thods or approaches, such as the use of labeled or tagge d nanom aterials, m a y have to be developed in order to analyze and quantify nanomat er ials with in biolog ica l system s.

3.6.5 Susceptible Subpopulations

Particle toxicology research has shown that not all individuals in the population respond to particle exposures in the sam e wa y or to the sam e degree (U.S. EPA, 2004). Host susceptibility factors that influe nce the toxicity, deposition, fate and persistence of intentionally produced nanom a terials are largely unknown, al though a study regardi ng the deposition of nanoparticles in the respiratory tr act of asthm a tics has been pub lished (Chalupa et al., 2004). More inform ation is critically needed to unders tand the exposure-dose-re sponse relationships of intentionally produced nanom aterials in order to recomm end s a fe e xposure levels that protect the most susceptible subpopulations.

3.6.6 Health Effects of Environmental T echnologies That Use Nanomaterials

The potential for adverse health effects m a y arise from direct expos ure to intentionallyproduced nanom a terials and/or bypr oducts associated with their applications. Nanotechnology is being em ployed to develop pollution control and re m e diation applic ation s

. Reactive z e ro-va l ent iron nanoparticles are being used to treat soil and aquifers co ntam inated with halogenated hydrocarbons, such as T C E (trichloroethylene) or DCE (dichloroethylen e), and heavy m e tals ( www.bioxtech.com ). However, the production of biphe nyl and benzene associated w ith nanoscale zero-valent iron degrad ation of m o re complex polychlor inated hydrocarbons has been reported (Elliott et al., 2005).

Photocatalytic titanium di oxide nanoparticles (nano-TiO 2 ) are being incorporated into building m a terials such as cem ent and surface co a tings in ord e r to reduce am bient air nitrog en oxides (NOx) levels. T h e European Union Photo catalytic Innovative Coveri ngs Applications for Depollution Assessm ent has evaluated the e ffectiveness of photocatalytic nano-TiO 2 to decrease

am bient air NOx levels and has co ncluded that this technology repr esents a viable approach to attain 21 ppb am bient air NOx levels in Europe by 2010 ( www.picada-p r oject. c om ). However, the extent to which nano-TiO 2 reacts with other ambient air co-pollutants and alters their corresponding health ef fects is not known.

Cerium oxide nanoparticles are being em pl oyed in the United Kingdomas on- and offroad dies el f u el additives to decrease em i ssions and som e m a nufacturers are claim i ng fuel

econom y be nefits. However, one s t u dy em ploying a cerium a dditiv e with a particulate trap has shown ceriu m to significantly alter th e physicoch e m i stry of diesel exh a ust em issions resulting in increased levels of air to xic chem icals such as benzene, 1,3-b u tadien e, an d acetaldehy de. Modeling estim ates have predicted th at use of a cerium additive in diesel fuel would significantly increase the am bient air levels of cerium (Health Effects Institut e, 2001). The health impacts associated w ith th ese alterations in d i esel exh a ust have not been exam in ed and are cu rrently no t known.58 EPA Nanotechnology White Paper

Environm ental technolo g ies using n a notechno lo gy lead to d i rect interactions of reactive, inten tiona lly produced n a nom aterials with chem ica lly com p l e x m i xtures present within a variety of environmental m e dia such as soil, water, am bient air, and com bustion em issions. The health effects associated with these in teractions are unknown. Research will be needed to assess the health and environm ental risks associated w ith environm ental applic ations of nanotechnology.



### 3.7 Ecological Effects of Nanomaterials

Nanom a terials m a y af f

e ct aqua tic o r terr estria l o r ganism s dif f

e rently than large rpar tic les of the sam e m a terials. As noted above, assess ing nanom at erial tox i city is extrem ely com p lex and m u lti-factorial, and is potentially influenced by a variety of physicochem i cal properties such as size and s h ape, and su rface properties su ch as charge, area, and reactiv ity. Furthermore, use of nanom a terials in the environm ent m a y result in novel byproducts or degradates that also m a y pose risk s. The following section s u mm arizes available inform ation and considerations regarding the potential ecologica l effects of nanom a terials.

3.7.1 Uptake and Accumulation of Nanomaterials

Based on analogy to physical-chem ical propert ies of larger m o lecules of the sam e

m a terial, it m a y be poss i ble to estimate the te ndency of nanom aterials to cross cell m e m b ranes and bioaccu mulate. However, current studies have been lim i ted to a v e ry sm all num b er of

nanom aterials and target organism s. Sim ilarly, existing knowledge could lead us to predict a

m itigating effect of natural m a terials in the en v i ronm ent (e.g. , organic carbon); howev er, th is last concept would need to be tested for a wide range of intentionally produced nanom aterials.

Molecu lar w e ight (MW ) and effectiv e cross

- se ctional diam eter are im portant facto r s in uptake of materials across the gill m e m b ranes of aquatic organism s or the GI tract of both aquatic and terrestrial organism s. Uptake via pa ssive diffusion of neutral particles is low, but still m easurable within a range of small m o lecular weights (600-900) (Zitko, 1981; Opperhuizen et al., 1985; Niim i and Oliver, 1988; McKim et al., 1985). The m o lecular weight of som e

nanom aterials falls within this range. For exam ple, the MW of n-C 60 fullerene is about 720, although the M W of a C 84 carbon nan o tube is g r eater than 100 0. Passive d i ffusion thro ugh gill

m e mbranes or the GI tract also depends on the cr oss section a l diam eter of particles (Opperhuizen et al., 1985; Zitko, 1981). Existi ng evidence indicates that th e absolute lim it for passive diffusion through gills is in the nano m e ter range (between 0. 95 and 1.5 nm ), which suggests th at passive diffusion m a y be possible for nanom aterials within this range, but not for nanom a terials with la rger e f f

ective cr os s-sectional d i am eters.

Charge is also an im portant characteristic to consider for nanom a terial uptake and distribution. For exam ple, as noted above, drug delivery studies using m o del wax nanoparticles have provid e d evidence that nanop article surface charge alters blood-brai n barrier integrity and
perm eability in m a mmals (Lockm an et al., 2004 ).

Other chem ical and b i otic characteris tics m a y need to be considered when predicting

accum u latio n and toxicity of nanoparticles in aqu a tic system s. For exam ple, the Office of W a ter uses several specific character istics, including water chem istr y (e.g., dissolved organic carbon and particulate organic carbon) and biotic (lipid content and trophic level) characteristics, when59 EPA Nanotechnology White Paper

calcu lating national bio accum u latio n factors for highly hydrophobic neu t ral organ i c com pounds (U.S. EPA, 2003).

Because the properties of som e nanom a teri als are likely to result in up tak e and distribution phenom ena different from m a ny conventi ona l ch em icals, it is critica lly importan t to conduct studies that will provi de a solid understanding of thes e phenom e n a with a range of

nanom aterials and species. Studi es related to human health eff ects as sessm ent will prov ide an im portant foundation for understanding m a mm alian exposures and som e cross-species processes (e.g., ability to penetrate endotheli um and m ove out of the gut and into the organism ). However, other phys io logy differs am ong ani m al classes, m o st notab ly respiratory p hysiology (e.g., gills in aquatic organism s and air sacs and unidirecti onal air flow in bird s), while plants and invertebrates (terrestrial and a quatic) have even g r eater physiological differences. Because of their size, the uptake and distribution of nano m a terials m a y fol l ow pathways not normally considered in the context of conventional m a te rials (e.g., pinocytosis, facilitated uptake, and phagocytosis).

3.7.2 Aquatic Ecosystem Effects

To date, very few ecotoxicity studies with nanom a terials have been conducted. Studies have been conducted on a lim ited number of na noscale m a terials, and in a lim ited number of aquatic species. There h a ve been no chr onic or full life-cycle studies reported.

For exam ple, Oberdörster (2004b) studied effect s of fullerenes in the brain of juvenile largem outh bass and concluded that C 60 fullerenes induce oxidative stress, based on their observations that (a) ther e was a tr en d f o r reduce d lipid p e rox i dation in th e live rand g ill, (b) significant lipid peroxidation was found in brains , and (c) the m e tabolic enzym e glutathione-Stransferease (GST) was m a rginally depleted in the gill. Howe ver, no concentration-response relationsh i p was evident as effects ob served at a low dose were not observed at the single higher dose and no changes in fish behavior were obser ved; effects could have been due to random variation in individual fish.

Oberdörster (2004c) tested uncoated, wa ter soluble, colloidal fullerenes (nC 60 ) and estim ated a Daphnid 48-hour LC 50 (forty-eight-hour c oncen tr ation that w a s lethal for 50 percent of the anim a l s in the test) at 800 parts per billion (ppb) , using standard EP A protocols. Lovern and Klaper (2006) tested titanium dioxide (TiO 2 ) and uncoated C 60 f u llere nes in an EP A standard, 48-hour acute toxici ty test using Daphnia m a gna. Toxicity of titanium dioxide particles and fullerenes differed by an order of m a gnitude, with fullerene particle solutions (particle clumps m easured as 10-20 nm diam eter) having an LC50 of 460 ppb and titanium dioxide (10-20 nm ) with an LC50 of 5.5 parts per m illion (pp m ). Particle preparation im pacted toxicity: filtering solutions to rem ove particles larger than 100 nm resu lted in LC50 of 7.9 ppm

, while la rger titanium dioxide clum ps yielded no m easurable toxicity. Lar g e particles of titanium dioxide (the kind found in sunbloc k, paint, and toothpaste) did not cause toxicity. Figure 21 shows nanoparticles in the gut and lipid storage droplets of Daphnia magna following uptake fro m wat e r.60 EPA Nanotechnology White Paper

Additionally, in behavior tests with f ilte red f u llerene s, Daphnia exhibited behavioral responses, with juveniles showing an apparent inability to swim down from the surface and adults dem o nstrating sporadic swimming and disorientation (Lovern and Klaper, 2005). Further research on ecological s p ecies is clearly needed.

Toxicity studies and structureactivity relationship predictions for carbon black and suspended clay particles, based on analyses by EPA’s OPPT, suggest that som e suspended
natura l nano sized pa rticles in th e aqu a tic environm ent will have lo w toxicity to Figure 21. Fluorescent nanoparticles in water flea ( Daphnia magna ). Adult and neonate Daphnia were exposed to 20nm and 1000nm fluorescently tagged carboxylated nanospheres for up to 24 hours. Nanoparticles were observed in gut and fatty lipid storage droplets using laser scanning confocal microscopy. (Image courtesy of Teresa Fernandes and Philipp Rosenkranz, Copyright Napier University. Research funded by CSL [DEFRA, UK]) aquatic organisms, with effects thresholds ranging from tens to thousands of parts per m illion. L i m ited prelim inary work with engineered/m anufactured nanom aterials

seem s to substantiate this conclusion. For exam ple, Cheng and Cheng (2005) reported that aggregat es of single-walled carbon nanotubes (SW C NT) added to zebrafish embryos reduced hatching rate at 72 hr s, but by 77 hrs post ferti liza tion a ll e m bryos in the treated group had hatched. However, when evaluating a lim ited data set of nanoscale

m a terials (i.e., carbon black and clay only), avai lable inform ation on differences in toxicity observed between natural and engineered or m a nuf actured nanom a terials should be considered. For exam ple, as noted previously, S W CNTs di splayed greater pulm onary toxicity than carbon black nanoparticles (Lam et al., 2004). Shvedova et al. (2005) reported unusual inflammatory responses to specific nanom a terial s in m a mm als, suggesting that som e nanom a terials m a y injure organs by novel m echanism s

. Recent repo rts suggest that nanom aterials m a y be effective b actericidal agents against both gram positiv e and n e gativ e bacteria in growth m e dia (Fo r tner et al., 2 005). The ability of these “n ano-C 60 ” aggreg ates to inhib it th e growth and respiration of m i crobes needs to be dem onstrated under m o r e realis tic co nditions. Fo r exam ple, effects on m i crobes in sewage sludge effluent and natu ral comm unities of bacter ia in natu ral waters shou ld be exam ined.

3.7.3 Terrestria l Ecosystem Effects

To date, very few studies have successfully been conducted to assess potential toxicity of

nanom ateria ls to e c ological terr estria l tes t spec ies (plan t s, wildlif e, soil in verteb rates, or soil

m i croorganism s).61 EPA Nanotechnology White Paper

For ter r estrial m a mmals, toxic ity test data on rats and m i ce obtained for hum a n health risk assessm ents should be considered. For ex ample, studies describe d above indicate that ultrafine or nanosize range part icles are m o re toxic on a m a ss-based exposure m e tric when

com p ared to larger particles of identical ch em ical com position in studies of lung toxicity (Oberdörster et al., 1994; Li et al., 1999; Höhr et al., 2002), and som e nanom aterials can display unique toxicity that cannot be explained by differe nces in particle size alone (Lam et al., 2004; Warheit et al., 2004). T oxicity to mammalian epid erm a l cell in culture has also been reported (Shvedova et al., 2003).

The sam e properties of nanom aterials that regulate uptake in aquatic organism s m a y lim it uptake of nanoparticles by plant roots or transport through plan t leaves and stom ata (i.e., reducing p a s s ive transpo r t at lower MW or size)

. Additionally, becaus e m a ny nanom a terials are designed to have strong ly reactive su rfaces, it is q u ite poss i ble that s i gnificant pathway s for toxicity m a y exist without uptake (e.g., disruption of respiratory ep ithelium structure/function or other surface cell struct ure/function). In a recent study of nanom a terial effects on plants, Yang and W a tts (2005), reported that al umina nanoparticles (13 nm) slowed root growth in a soil-free
exposure m e dium

. Species tested included comme rcially im portant specie s used in ecological risk assessm ents of pesticides: corn (Zea m a ys), cucum b er (Cucum is sativus), soybean (Glycine

m a x), cabbage (Brass ica oleracea), and carro t (D aucu s coro ta). The autho r s repo rted that coating the alum ina nanoparticles with an organic com pound (phenanthrene), reduced the nanom a terial’s effect of root elongation inhibi tion. Larger alumina particles (200-300 nm ) did not slow root growth, indicating that the alum ina itself was not causing the toxi city. The authors hypothesized that the surf ace charge o n the alum ina nanopartic les m a y have played a role in the decreased plant root growth. It should be noted that these studies were conducted in Petri dishes without soil, so environm ental relevance is uncertain. Further, Murashov (2006) noted som e lim itations of this report including lack of discussion of known phytotoxicity of al umina, and that the increased solubility of nanoscale alum ina m a y ha ve resu lted in inc r eased concentrations of alum ina species, which m a y have contributed to the observed phytotoxicity, as opposed to the nanoscale properties of the alum ina.

Funda m e ntally, our ability to extrapolate toxicity inform ation from conventional substances to nanom aterials will require knowle dge about uptake, distribution, and excretion rates as well as m odes of toxic action, and m a y be inform ed by existing structure-activity relationships (SARs), such as SARs for polyc ationic polym ers, published in Boethling and Nabholz (1997). Synthesis of radio-labeled na nom a terials (e.g., carbon-14 labeled nanotubes)

m a y be a us eful tool, along with advanced m i croscopy (e.g., com p arable to techniques used for asbestos quantification) f o r developing info rm ation on sites of toxic action and m e tabolic distribution.

3.7.4 Ecological Testin g Issues

Because nan o m a terials are often engineered to have very specific properties, it s eem s reasonable to presum e that they m a y end up havi ng unusual toxicological effects. E xperiences with conventional chem icals suggest that in these cases, chronic effects of exposure are often a more im portant com ponent of understanding ecological risk than acute lethality. As such, initial studies should include longer-term exposures m easuring m u ltiple, sub-lethal endpoints. They should be co nducted (us i ng appropriate form s and routes of ex posure) in a m a nner that will62 EPA Nanotechnology White Paper

elucidate key taxonom ic groups (i.e., highly sens itive organism s that m a y becom e indicator species) and endpoints that m a y be of greatest im portance to determ ining ecological risk. These studies m u st also include careful tracking of uptake and dispositi on to understand toxicity as a function of dose at th e site of action.

A num b er of existing test procedures that assess long-term survival, growth, developm ent, and reproductive endpoints (b oth whole organism and physiological or biochem i cal) for invertebrates, fish, am phibians, birds, and plants (including algae, rooted

m acrophytes, and terrestrial plants) should be adaptable to nanom a teri als. These tests are able to

exam ine a wide range of species and endpoints to help pinpoint the t ypes of effects most significant to the evaluation of nanom aterials, an d have a strong foundation relative to projecting likely ecological effects. Both pilot toxicity testing protocols and definitive protocols should be evalua ted with respe c t to their applic ability to n a nom a teria l s. In addition, field studies or

m e socos m s t udies m i ght be conducted in system s known to be exposed to nanom aterials to screen for food chain bio accum u latio n and unanticipated effects or endpo ints.63 EPA Nanotechnology White Paper



## 4.0 Resp onsible Devel o p m ent

One of the stated goals of the Natio nal Nanotechnology Initiative is to support responsible developm ent of nanotechnology. EPA ad m i nisters a statutory fra m ework laid out in this chapter that support s responsible developm ent. EPA also funds and conducts research, and identifies research n eeds within th e context of its programm a tic statutory m a ndates. The ways that risks are characterized and decis i ons are m a de vary based on the program area (air, water, chem ical substances, etc.) and also the specific s t atu t e invo lv ed (for example, Clean A i r Act, Clean W a ter Act, Toxic Substances Control Ac t). Supporting responsible developm ent at EPA is inform ed by an understanding of the risk from e xposure to potential hazar d. Section 4 of this paper discusses the risk assessm ent process and th e types of inform ation that EPA could need to inform its decisions. F i gure 22 identifies EPA o ffice roles, statutory auth o r ities, and ca tegor ies of research needs related to na notechnology. As illu strated in Figur e 22 and describ e d in greater detail in Chapter 5, an understanding of envi ronmental applications, chem i cal identification, potential environm ental release, environm en tal fate and transport, hum an exposure and

m itigation, h u m a n and environm ental effects, ri sk assessm ents, and pollu tio n prevention is needed to provide sound scientific inf o rm ation that inform s the responsible developm ent of nanotechnology.


### 4.1 Responsible Development of Nanoscale Materials

EPA recognizes the potential bene fits of nanomaterials. To fully realize that potential, the responsible development of su ch products is in the interest of EPA, state environmental protection agencies, producers, their suppliers, as well as user s of nanotechnology, and society as a whole. EPA believes that a proactive approach is appropriate in res ponsible development. EPA believes that partnerships with industrial sect ors will ensure that responsible development is part of initial decision making. Working in part nership with producers, th eir suppliers, and users of nanomaterials to develop best practices a nd standards in the workplace, throughout the supply chain, as well as other environmental programs, would help ensure the responsible development of the production, use, and end of life management of nanomaterials.Office ofOffice of SolidOffice ofOffice ofOffice ofPrevention,Office of Air andWaste andEnforcementOffice of WaterEnvironmentalResearch andPesticides, andRadiationEmergencyand ComplianceResponseInformationDevelopmentAssuranceToxicSubstancesToxic SubstanceControl Act:Review/Oversight ofIndustrial ChemicalComprehensiveToxic ReleaseCoordinateEnforcementClean Air Act:ChemicalIdentificationand AnalysisEnvironmentalFateReleases andHumanExposureHealth andEcologicalEffectsRiskAssessmentEnvironmentalDetection andAnalysisRemediationApplicationsEnvironmentalInventory:Researchof all federalReporting ofStrategyenvironmentalResponse,Criteria airchemicalConductlaws eg TSCA,Compensation, andpollutants,releasesResearch forCWA, RCRA,Liability Act andHazardous airall of thoseOPA, CERCLApollutants,Resource ConservationneedsRegistration of fuelsFederalInsecticide,Fungicide,Rodenticide Act:Registration ofPesticidesand Recovery Act:and fuel additivesHazardous substancesor wastes,Solid WasteEvaluationof existingstatutory/regulatoryframeworkregardingenforcementissuesScience tosupportenforcementChemicalIdentificationand AnalysisEnvironmentalFate andTreatmentChemicalIdentification andAnalysisEnvironmentalFateReleases andHuman ExposureHealth andEcological EffectsRisk AssessmentEnvironmentalDetection andAnalysisChemical Identificationand AnalysisEnvironmental Fateand TreatmentReleases and HumanExposureHealth and EcologicalEffectsRisk AssessmentEnvironmentalDetection andAnalysisRemediationApplicationsKeyClean Water Act:Effluent Guidelines,Water qualityguidelines orstandardsSafe DrinkingWater Act:Contaminants indrinking water,cleaning upcontaminantsOfficeStatuteand RolesResearchNeedsChemicalIdentification andAnalysisEnvironmentalFate andTreatmentReleases andHuman ExposureHealth andEcological EffectsRisk AssessmentEnvironmentalDetection andAnalysisChemicalIdentificationand AnalysisEnvironmentalFate andTreatmentPollution PreventionAct: Incorporate P2into all aspects ofchemical oversightChemical Identificationand AnalysisEnvironmental Fateand Treatment64EPA Nanotechnology White PaperFigure 22. EPA Office Roles, Statutory Authorities, and Categories of ResearchNeeds Related to Nanotechnology.65 EPA Nanotechnology White Paper

Responsible developm ent of nanomaterials m a y present issues that are not easily characterized because of the breadth of categorie s of such substances. S o m e nanoscale m a terials are produced under established industrial hygiene practices based on their history of

m a nufacturing processes and use. Hum a n and environm ental exposure inf o rm ation for these particular substances likely woul d already be available to inform responsible developm ent. For

som e other nanoscale materials, there is less und erstanding of expected exposure and potential hazard. The uncertainty m a y be greater wh ere new industrial m e thods are em ployed.

EPA intends to review as appropriate new nanotechnology products and processes as they are introduced, under E P A’s product review authorit ies, such as TSCA, FIFRA, and the Clean Air Act. EPA intends to work with producers an d users of nanom a terial s to develop protocols and approaches that ensure responsible developm ent. As ne w knowledge becom e s increm entally available through the research needs identified in this white paper, refinem e nt of approaches m a y be needed.



### 4.2 Program Areas

EPA adm i nisters a wide range of environm ental statutes, som e of which m a y apply to

nanom aterials depending on the specif ic m e dia of application or rel ease, s u ch as air or water. Other statutes m a y apply to certain nanom aterials depending on their specif ic uses, applications, and processes and m a y require EPA to evaluate the nanom aterials before they enter into commerce ( s uch as pes t icides, f u el a dditiv es, etc. ). Som e risk m a nagem e nt activities c a rried out under these statutes could also utilize nanom ater ials as products for environm ental rem e diation or pollu tion prevention technologies. The statu t es adm i nistered by EPA outlin ed belo w are a starting point for evalua ting and m a na ging risks and benefits from nanom a terials. Some current EPA policies and regulations m a y require m odi fications to address this new technology.

Nanoscale m a terials will present other novel risk assessm ent/m anage m ent challenges. Standards that need to be developed in clude term inology/nomenclature, m a terial characterization, m e trology, testing procedures, and detection m e thodology. There is also a need
to rev i ew co nventional h azard, expo s u re, and risk assessm ent tools for th eir applicability to

nanom ateria ls, as well as developm ent of risk m itiga tion options that are tailored to n a noscale

m a terials. T h ere m a y also be a need to review and m odify reporting tool s under various statutes to best cover nanoscale m a terials.

4.2.1 Chemical Substances

Generally, n a noscale m a terials that m eet th e definition of “chem i cal substances” under the Toxic Substances Control Act (T SCA), but wh ich are not on the TSCA Inventory, m u st be reported to EPA according to section 5(a) of the Act, which provides for pre-m a nufacture review. The prem anufac ture review process serv es as a gatekeeper to identify concerns and exercise appropriate regulatory oversight. For exam ple, use re strictions, occupational exposure lim its/contro ls, lim its on rele ases to the environm ent and lim its on m a nufa cture m a y be required until toxic i ty and f a te d a ta a r e deve loped to better inf o rm a risk asse ssm ent of the che m ical. As previously noted EPA already is reviewing prem anufacture notifications f o r som e nanom aterials that have been received under TSCA. EPA al so m a y review under section 5(a) of TSCA

nanom ateria ls tha t rep r es ent sign if ica n t new us es of chem icals alrea dy on the TSCA Inventory.66 EPA Nanotechnology White Paper

Under TSCA, EPA has the authority, by rule, to prohibit or lim it th e m a nufacture, im port, processing, distribution in comm er c e , use, or disposal of a chem ical substance; require developm ent of test data; and/or require reporting of health and safety stud ies, categories of use, production volum e , byproducts, an estim ate of the num ber of individuals potentially exposed, and duration of such exposures, if th e necessary findings or d e term ination s are m a de. Nanom a terials that m eet the defi nition of a chem i cal substance under TSCA could be subject to

som e or all of these provisions and program s.

4.2.2 Pesticides

Under the F e dera l Inse cticide, Fung icide and Ro dentic ide Ac t (FIFRA) , EPA is responsible for registering pestic ide products for distribution or sa le in the United States. An application f o r registration under FIFRA must di sclose to E P A the specific chem icals in the pesticide formulation. P e sticide registration deci sions are based on a detailed assessment of the potential effects of a product on human health an d the enviro nm ent, when used acco rding to label directions. FIFRA requires EPA and states to establish program s to protect workers, and to provide training and certificati on for applicators. Pesticide products containing nanom a terials will be sub j ect to FIFRA’s rev i ew an d regis t ratio n requirem e nts. In add i tion, to th e extent that the use of pesticide products containing nanom at er ials results in residues in food, the resulting residue s req u ire the es ta blishm ent of a tole ra nce (m axim um allowed res i d u e lim it) un der the Federal Food, Drug, and Cos m etic Act.

4.2.3 Air

The Clean Air Act (CAA) governs, among othe r things, the establishm ent, review and revision of national am bient air qua lity standards and identification of criteria air pollutants. As

am ended in 1990, it also identified 1 90 Hazardo us Air Pollu tants (HAPs) for regulation (the list currently includes 187 HAPs) and provides EPA with authority to identif y additional HAPs. The CAA also contains requ irem ents that address acc idental releases of hazardous substances from stationary so urces th at potentially can have serious advers e effects to hum an health o r the environm ent. Use or m a nufacture of nanom aterials could result in em issi ons of pollutants that are or possibly could be listed as criteria ai r pollutants or HAPs.

Under the CAA, EPA has issued health eff ects testing requirem e nt s for fu el s and fuel additives. G a solin e and diese l f u els and their ad ditiv es ar e s ubject to the regula tions issued by EPA. These fuels and ad ditiv es for u s e in on-road applicatio ns m a y not be introduced into commerce until they hav e been reg i stered by EPA. As previo usly noted E P A has received and is reviewing an application for registration of a diesel addi tive containing cerium oxide.

4.2.4 Pollution Prevention

The Pollution Prevention Act of 1990 was c onsidered a turning point in how the nation looks at the control of pollution. Instead of focusing on waste m a nage m e nt and pollution control, Congress declared a national policy for the United States to a ddress pollution based on "source reduction." The policy esta blished a hierarchy of m easures to protect hum an health and the environ m ent, where m u lti-m e dia approach es would be anticipated : (1) pollu tion should be67 EPA Nanotechnology White Paper

prevented or reduced at the source; (2) pollution that cannot be prevented should be recycled in an environm entally safe m a nner; (3) pollution th at cannot be prevented or recycled should be treated in an environm entally safe m a nner; and (4) disposal or ot her r e le as e into the en vironm ent should be employed only as a last resort and shou ld be conducted in an environm entally safe

m a nner.
As a result of the Act, two program s were initia te d, with two dif f

e rent approaches, to

m eet the spirit of the new national policy: the D e sign for the Environm e n t (DfE) Program and the Green C h em istry Program

. Under DfE, EPA wo rks in partnership with industry sectors to im prove perfor m a nce of commercial processes wh ile reducing risks to hum a n health and the environm ent. The Green Che m istry Program prom otes research to design chem ical products and processes th at redu ce or elim inate th e use a nd generation of toxic chem ical substances. In 1998, EPA com p lim e n ted these two programs w ith the G r een Engineering Program, which applies approaches and tools for evaluating and reducing the environm ental im pacts of processes and products (see http://www.epa.go v/opp t/greenengineering ). Nanotechnology offers an opportunity to im ple m ent pollution prevention pr inciples into the design of a new technology.

4.2.5 Water

The stated goals of the C l ean W a ter Act (CW A ) are to protect the chem ical, physical, and biological integrity of th e nation ’ s waters as well as to ensu re the hea lth a nd welf are o f the environm ent, fish, shellfish, other aquatic organi sm s, wildlif e, and hum a n s that live in, recreate
on, or com e in contact w ith waters of the United States. Depending on the toxicity of

nanom aterials to aquatic life, aquatic dependent w ildlife, and hum a n health, as well as the potential for exposure, nanom ateria ls m a y be regulated under the CW A. A variety of approaches are available under the C W A to provide protec tion, including effluentlim itation guidelines, water quality standards (aquatic life, hum a n health, biological), best m a nagem e nt practices, NPDES per m its, and whole effluent toxicity test ing. Sim u ltaneously, nano m a terials m a y provide an effective and efficient m echanism to reso lv e water quality contam ination and its impacts on aquatic life, aquatic dependent w ildlife, and human health. Both scenarios m u st be explored to determ ine how and when to regulate these potent ially hazardous additions to the nation’s waters.

The Safe Drinking W a ter Act (SDWA), as am en ded in 1996, is the m a in federal law that protects pub lic health by regulating h azardous co nt am inants in drinking w a ter. SDWA authorizes the Agency to estab lish n on-enforceable he a lth-b ased Maxim u m Contam inant Level Goals (MCLGs) and enforceable Max i m u m Contam inan t Levels (MCLs) or required treatm ent techniqu es, as close as feasib le to th e MCLGs, taking in to c onsidera tion costs and a v ailab l e analytical and treatm ent technol ogy. Nanotechnology has the potential to influence the setting of MCLs through im provem e nts in analyti cal m e thodology or treatm e nt techniques. Nanotechnology has the potential to contribute to better and more cost-effective rem o val of drinking water contam inants, such as m e tals (e .g. arsenic or chrom i um ), toxic halogenated organic chem icals, suspended particulate m a tter and pathogenic m i croorganism s. If nanoparticles enter drinking water, such as throu gh their use in water treatm e nt, then exposure to

nanom aterials m a y occur through drinking water i ngestion or inhalation (e .g. from showering). Based on their toxicity and occu rrence in drinking water supp lies, nanom a t erials could be regulated under the SD WA.68 EPA Nanotechnology White Paper

4.2.6 Solid Waste

The Com p rehensive Environm ental Res ponse, Com p ensation, and Liability Act (CERCLA) addresses contam inati on at closed and abandoned wast e sites. CERCLA gives EPA the authority to respond to actual or threatened releases of hazardous substances to the environm ent and to actual or threatened releases of pollutants or contam inants that m a y present an imm i nent and substantial dange r to the public health or welfar e. Nanom a terials that m eet these criteria potentially would be subject to this authority.

The Resource Conservation and Recovery Act (R CRA), whic h am ended the Solid W a ste Disposal Act, regulates, from the point of generation, the m a nagem e nt of s o lid and hazardous wastes, underground storage tanks, and m e dical wastes. Subtitle D of RCRA covers m unicipal and other non-hazardous wastes

. Subtitle C of RCRA covers the storage, transportation,
treatm ent, disposal, and cleanup of h azardous wastes

. Nano m a terials th at m e et one or m o re of the definitio ns of a hazardous waste (i.e., a waste th at is specifically list ed in the regulations and/or that exhibits a defini ng cha r ac ter i stic) po te ntia lly w ould be subject to subtitle C regulations. Subtitle I covers underground storag e tanks, and Subtitle J covers m e dical waste incineration.

The 1990 Oil Pollution Act (OPA) am ended th e Clean W a ter Act (CW A ) to address the harmful environm ental impacts of oil spills. EP A responsibilities under the Oil Pollution Act include response (cleanup/containm e n t/prevention action ) an d enforcem ent actions related to discharges and threatened discharg es of oil or hazardous substanc es in the inland waters of the Uni t e d St at es.

4.2.7 Toxics Release In ventory Program

In 1986, Congress passed the Emergency Planning and Community Right to Know Act (EPCRA) and the Toxics Release Inventory (T RI) was established. The TRI is a publicly available database containing information on toxic chemical releases and other waste management activities that are reported annually by manufacturing facilities and facilities in certain other sectors, as well as federal facilities. Some produc ers of nanomaterials containing materials listed in the TRI may be subj ect to reporting under the TRI Program ( www.epa.gov/tri/ ). Facilities required to report TR I chemical releases and other waste management quantities are those that met or exceeded the minimum criteria of number of employees and total mass of chemical manufactur ed, processed, or otherwise used in a calendar year. Of the nearly 650 toxic chemicals a nd chemical compounds on the TRI, a number are metals and compounds containing these metals, including cadmium, chromium, copper, cobalt and antimony. Such compounds may be produced as nanomaterials, and some are commonly used in quantum dots.



### 4.3 Environmental Stew a rdship

Nanotechnology provides an opportunity for EPA a nd other stakeholders to develop best practices for preventing pollution at its source and conserving natural res ources when ever possible. For exam ple, EPA and ot hers are supporting research into green nanotechnology , to identify applications of nanotec hnology that reduce pollu tion from industrial processes as well as69 EPA Nanotechnology White Paper

to develop m a nufacturing proce ss that fabricate nanom aterials in an environm entally friendly

m a nner. Appendix B provides a fuller discussi on of stewardship principles. Many diverse industrial organizations a nd their suppliers have the opportunity at this early stage of technology developm ent and use to be lead ing environm ental stewards.

At EPA, in addition to our support for green nanotechnology research, there are a num ber of program s already in place that are based upon environm ental stewardsh i p prin ciples. These
program s address processes, including inputs; wa ste stream s; and the design, use, disposal, and stewardship of products consistent w ith th e goal of pollution prevention. Inform ation on nanotechnologies and m a terials could be provi ded through existing inform ation networks, and EPA could pursue additional volun tary initiatives or integr ate nanotechnology and nanoscale

m a terials into already existi ng voluntary programs to ensure responsible developm ent.70 EPA Nanotechnology White Paper



## 5.0 EP A’ s Res e arch Needs for Nan o mat e rials

Research is needed to in for m EPA’s actio ns related to the benefits and impacts of

nanom aterials. However, there are s i gnificant ch alleng es to addressing research n e eds for nanotechnology and the environm ent. The sheer va riety of nanom a terials and nanoproducts adds to the difficulty of developing research needs. E ach stag e in their lifecy cle, from extraction to

m a nufacturing to use and then to ultim a te disposal, will present separate research challenges. Nanom a terials also pres ent a particu l ar research challenge over their m acro for m s in that we have a very lim ited understandi ng of nanoparticles’ physicochem i cal properties. Research should be designed from the beginn ing to identify beneficial app lications and to inform risk

assessm ent, pollution prevention, an d potential ri sk m a nage ment m e thods. Such research will

com e from m a ny sources, includ ing academ ia , industry, EPA, and other agencies and organizations. Other governm e nt and internationa l in itiatives have also undertaken efforts to identify research need s for nanom aterials and ha ve com e to sim ilar conclusions (UK Departm e nt for Environm ent, Food and Rural Affairs, 2005; NNI, 2006c ).

An overarching, guiding principl e for all testing, both hum an h ealth and ecological, is the determ ination of which nanom aterials are m o st used and/or have potential to be released to, and interact with , the environ m ent. These nanom ateria ls shou ld b e sele cted from each of the broader classes of nanom a terials (carbon -based, m e tal-based, dendrim ers, or composites) to serve as representative particles for testing/evaluation purposes.



### 5.1 Resea rch Needs for En vironmental Applications

The Agency recognizes the benefits of using nanom aterials in environm ental technologies. Research is need ed to develop and test the efficacy of appl ications that detect, prevent and clean up con t am inants. EPA also has the responsibility for determ ining the ecological and hum a n health im pli cations of these technologies.

5.1.1 Green Manufactu ring Research Needs

Nanotechnology offers the possibility of cha nging m a nufacturing pro cesses in at least two ways: (1) by using less m a terials and (2) using nanom at erials for catalysts and separations to increase efficiency in current m a nufacturi ng processes. Nanom a terial and nanoproduct

m a nufacturing offers the opportunity to em pl oy the principles of green chem istry and engineering to prevent pollution from currently known harmful chem icals. Research enabling this bottom

- up m a nufacturing of chem icals and m a te rials is one of the most im portant areas in pollution prevention in the long term. Resear ch questions regarding green m a nufacturing include :

• How can nanotechnology be used to redu ce waste products during m a nufacturing?

• How can nanom a terials be m a de using benign starting m a terials?

• How can nanotechnology be used to reduce th e resources needed for m a nufacturing (both

m a terials an d energy)?71 EPA Nanotechnology White Paper

• What is the life cycle of various types of nanom a terial s and nanoproducts under a variety of m a nufacturing and en vironm ental conditions?

5.1.2 Green Energy Research Needs

Developing green ene r g y approache s will inv o lv e rese arch in m a ny areas, includ ing s o lar energy, hydrogen, power transm ission, diesel, pollu tion control devices, and lighting. These areas have either direct or indirect impact s on environm ental protection. In solar energy,

nanom aterials m a y m a ke solar cells more e fficient and m o re affordable. In addition, nanocatalysts m a y e fficiently create hydrogen from water using solar energy. Research questions for green energy include:

• What research is needed for incentives to encourage nanotechnology to enable green
energy ?

• How can nanotechnology assist “green” en ergy production, distri bution, and use?

5.1.3 Environmental R e mediation/ Treatment Research Needs

The research questions in th is area revolve around the effect iveness and risk param e ters of nanom a terials to be used in site rem e diation. Materials such as zero -valent iron are expected to be useful in rep l acing curren t pump-and-treat or off site treat m e nt m e thods. In ad dition, o t her

nanorem ediation approaches can involve the m e thods of coating biological particles, determ ining the effect on the particles (enzym e or bact eriophage) following coating, and application technologies. This is an area th at has not been exam ined in any great detail. Therefore, research is needed to develop technologi es using nanocoated biological particles for environm ental decontam ination or prophylactic treatm ent to prevent contamination. The products of this research would be technologies utilizing innocuous biological en tities treated with nanoparticles to decontaminate or prevent bacterial growth. In an age of antibio tic res i s t ance and av ersion to chem ical decontam ination, enzym e and bacteriopha ge technologies offer an attractive option. Rem e diation and tre a tm ent rese arch q u estions inc l ude:

• Which nanom aterials are m o st effective for remediation and treatm ent?

• What are the fate and effects of nanom a teri als used in rem e diation applications? W h e n

nanom aterials are placed in groundwater treatm ent, how do th ey behave over tim e ? Do they m ove in groundwater? W h at is their pot ential for m i grating to drinking water wells?

• How can we im prove m e thods for detecti ng and monitoring nanom aterials used in

rem e diation and treatm ent?

• To what extent are these m a terials and thei r byproducts persistent, bioaccum ulative, and toxic and w h at organ i s m s are affected ?

• If toxic byproducts are produce d, how can these be reduced?72 EPA Nanotechnology White Paper

• What is needed to enhan ce the efficiency and co st-effectiv en ess of rem e diation and
treatm ent technology?

5.1.4 Sensors

In general, nanosensors can be classif i ed in two main categories: (1) senso r s that are us ed
to m easure nanoscale pro p erties (this catego r y co mprises m o s t of the current m a rket) and (2) sensors that are them selves na noscale or have nanoscale com p onents. The second category can
eventua lly r e sult in lowe r m a terial co st as we ll as reduced weight and power consum ption of sensors, leading to greater appli cability, and is the subject of th is section. Research needs for sensors to detect nanomaterials in the environm ent are d i scus sed in th e Environm ental Detec tion section below.

• How can nanom a terials be em ployed in the deve lopm ent of sensors to detect biological and chem ical contam inants ?

• How can sensor systems be developed to m on itor agents in r eal tim e and the resu ltin g data ac cesse d rem o tely?

• How these sm all-scale monitoring system s be developed to detect personal exposures and in vivo distributions of toxicants.



### 5.2 Resea rch Needs for Risk Assessment

5.2.1 Chemical Identification and Characteriz a tion

Research th at can be rep licated depe nds on agreem ent on the identification and characterization of nanom aterials. In addi tion, understanding the physical and chem ical properties in particular is necessary in the ev aluation of hazard (both human and ecolo gical) and exposure (all routes). It is not clear whether existing physical -chem i cal property test m e thods are adequate for sufficiently characterizing vari ous nanom aterials. Alternative m e thods m a y be needed. Research questions include:

• What are the unique chem ical and physical characteristics of nanom aterials? How do these characteristics vary am ong different classes of m a te rials (e.g., carbon based, metal based) and among the individual m e mbers of a class (e.g., fullerenes, nanotubes)?

• How do these properties affect the material’s r e a c tiv ity, tox i c ity and other attributes?

• To what extent will it be necessary to tailor research protocols to th e specific type and use pattern of each nanom aterial? Can properties and effects be ex trapo l ated w ithin a class of

nanom aterials?73 EPA Nanotechnology White Paper

• Are there adequate m easurem ent m e thods/te chnology available to fully characterize

nanom aterials, to distinguish am ong different ty pes of nanomaterials, and to distinguish intentionally produced nanom ater ials f r om ultraf ine partic les or naturally occurring nanosized particles?

• Are current test m e thods for characterizing nanom aterials adequate for the evaluation hazard and exposure data?

• Do nanom a terial characteristics vary from their pure form in the laboratory to their form

as com pone nts of products and eventually to the for m in which they occur in the environm ent?

• What intentionally produced nanom aterials ar e now on the m a rket and what new types of

m a terials can be expected to be developed?

• How will manufacturing processes, form ulations

, and incorpo r ations in en d products alter the characteristics of nanom a terials ?

5.2.2 Environmental F a te and Treatment Research Needs

EPA needs to ascertain the fate of nanom a teria l s in the env i ro nm ent to un derstand the availability of these m a terials for ex posure to hum a ns and other life for m s. Research on the transpo r t an d potential transfor m a tion of nanom a terials in soil , subsurface, surface waters, wastewater, drinking water, a nd the atm o sphere is essentia l as nanom aterials are u s ed increasingly in products. To support these investigations, exis ting m e thods should be evaluated and if necessary, they sh ould be m o dified or ne w m e thods should be developed. Research is needed to ad dress th e following high-priority questions.

5.2.2.1 Transport Research Questions

• What are the physicochemical factors that influence the transport and deposition of intentionally produced nanomaterials in the environment? How do nanomaterials move through these media? Can existing informati on on soil colloidal fate and transport and atmospheric ultrafine particulate fate and transport inform our thinking?

• How are nanomaterials transported in the at mosphere? What nanomaterial properties and atmospheric conditions control the a tmospheric fate of nanomaterials?

• To what extent are nanomaterials mobile in soils and in groundwater? What is the potential for these materials, if released to soil or landfills, to mi grate to groundwater and within aquifers, with potential exposur e to general populations via groundwater ingestion?

• What is the potential for these materials to be transported bound to particulate matter, sediments, or sludge in surface waters?74 EPA Nanotechnology White Paper

• How do the aggregation, sorption and agglom eration of nanopart icle s af f

ect th eir transpo r t?

• How do nanom aterials b i oaccum u late? Do th eir unique character is tics affect their bioavailability ? Do nanom a terials b i oaccum u la te to a greater or lesser extent than macroscale o r bulk m a terials ?

5.2.2.2 Transformation Research Questions

• How do nanoparticles react differently in th e environm ent than their bulk counterparts?

• What are the physicochem i cal factors that aff ect the persistence of intentionally produced

nanom aterials in the environm ent? What data are available on the physicochem i cal factors that affect the pers istence of unintentionally pr oduced nanom aterials (e.g., carbonbased com b ustion products) that m a y provi de infor m ation rega rding inte ntiona lly produced nanom a terials?

• Do particular nanom aterials persist in the e nvironm ent, or undergo degradation via biotic or abiotic processes? If they degrade, what are the byproducts and their characteristics? Is the nanom a terial likely to be in th e environm ent, and thus be available for bioaccum u lation/b i om agnification ?

• How are the physicochem i cal and biological pr operties of nanom a terials altered in

com p lex environm ental m e dia such as air, water, and soil? How do redox processes influence en vironm ental tran sform a tion of nanomaterials? To what exten t are

nanom aterials photoreactive in th e atmosphere, in water, or o n environm ental su rfaces?

• How do the aggregation, sorption and aggl om eration of nanoparticles affect transform a tion?

• In what am ounts and in what for m s m a y nanopa rticles be released from m a terials that contain them, as a result of environm ental fo rces (rain, sunlight, et c.) or through use, reuse, and disposal.

5.2.2.3 Chemical Interaction Research Questions

• How do nanosized adso rbants and ch em icals sorb ed to them influence their respective environm ental in tera ctio ns? Can the s e m a terial s alter the m obility of other substances in the environ m ent? Can these m a terials alter the reactivity of othe r subs tances in the environm ent?

5.2.2.4 Treatment Research Questions

• What is the potential for these m a terials to b i nd to soil, subsu r face m a terials, sed i m e nt or wastewater sludge, or binding agents in waste treatm ent facilities?• Are these m a terials effectively rem oved from wa stewater using conventional wastew ater treatm ent methods and, if so, by wha t m echanism?

• Do these m a terials h a ve an im pact on the treat ability of other substances in waste stream s (e.g., wastewater, hazardous and nonhazardous so lid wastes ), or on treatm ent facilities perform a nce?

• Are these m a terials effectively rem oved in drinking water treatm ent and, if so, by what

m echanism ?

• Do these m a terials h a ve an im pact on the rem oval of other substances during drinking water treatment, or on drinking water treatm ent facilities perfo r m a nce?

• How effective are existing treatm ent m e thods (e.g., carbon adsorption, filtration, coagulation and settling, or incine ration/air pollution control system sequestration/stabilization) for treating nanom at erials?

5.2.2.5. Assessment Ap proaches and Tools Questions

• Can existing inform ation on soil colloidal fa te an d transpo r t, as well as atmospheric ultr af ine par ticu l ate f a te and transpo r t, inf o rm our thinking? Do the current databases of ultr af ines/f ibers shed lig ht on any of these questions?

• Do the different nanom aterials act sim ilarly enough to be able to create classes of like

com pounds? Can these classes be used to pr edict structure-activity relationships for f u ture m a terials ?

• Should current fate and transport m odels be m odified to incorporate the unique characteristics of nanomaterials ?

5.2.3 Environmental D e tection and Analysis Research Needs

While there are a variety of m e thods curre ntly available to m easure nanoparticle

m a ss/ m a ss concentration s , surface area, particle count, size, p hysical structure (m orphology), and chem ical com positio n in the labo ratory, the c h alleng e re m a ins to detect nanom ateria ls in the environm ent. Research is needed to a ddress the following high-priority questions:

5.2.3.1 Existing Methods and Technologies Research Questions

• Are existing methods and technologies capable of de tecting, characterizing, and quantifying intentionally produced nanomaterials by meas uring particle number, size, shape, surface properties (e.g., reactivity, charge, and area), etc.? Can they distinguish between intentionally produced nanomaterials of interest a nd other ultrafine particles? Can they distinguish between individual particle s of interest and particles that may have agglomerated or attached to larger particles?

• Are standard procedures available for both sample preparation and analysis? 75 EPA Nanotechnology White Paper76 EPA Nanotechnology White Paper

• Are quality assurance an d c ontro l ref e rence m a te ria l s a nd procedures available?

• How would nanom aterials in waste m e dia be m e asured and evaluated?

5.2.3.2 Ne w Methods and Technologies Research Needs

• What low-cost, portable, and easy-to-use technologies can detect , characterize, and quantify nanom a terials of interest in e nvironm ental m e dia and for personal exposure monitoring.

5.2.4 Human Exposures, Their Measurement and Control

Potential sources of hum an exposure to na nom aterials include workers exposed during the production and use of nanom a terials, gene ral population exposure from releases to the environm ent during the production or use in th e workplace, and direct general population exposure during the use of comm ercially available products c ontaining nanoscale m a terials. Releases fro m industrial acciden t s, n a tural disast ers, or m a levolent activ ity such as a terro rist attack should also be considered. R e search is ne eded to identify potential sources, pathways, and routes of exposure, potential t ools and m odels that m a y be used to estim a te exposures, and potential da ta sources f o r

these m odels, as well a s approache s f o r m easuring and m itigating
exposure. N I OSH has also exam ined research ne eds regarding risks to workers and developed a strategic plan to address these needs (NIOSH 2005a, b). Resear ch is needed to address the following high-priority questions.

5.2.4.1. Risk and Exposure Assessment Research Questions

• Is the current expos ure assessment process adequate for assessing exposures to nanomaterials? Is mass dose an effective metric for measuring exposure? What alternative metric (e.g., particle count, surface area) should be used to measure exposure? Are sensitive populations’ (e.g., endangered spec ies, children, asthmatic s, etc.) exposure patterns included?

• How do physical and chemical properties of nanomaterials affect re leases and exposures?

• How do variations in manufacturing and subseq uent processing, and the use of particle surface modifications affect exposure characteristics?

5.2.4.2 Release and Exposure Quantification Research Questions

• W h at inf o rm ation is availab l e abou t uni que release and exposure patterns of

nanom ateria ls ? W h at addition a l inf o rm ation is n eeded ?

• What tools/resources currently exist for a ssessing releases and exposures w ithin EPA (chem i cal release information/m onitoring system s (e.g., TRI), m easure m ent tools,77 EPA Nanotechnology White Paper

models, etc)? Are thes e tools/re sources adequate to m easure, estim ate, an d assess releases and exposures to nanom aterials? Is degr adation of nanom a terials accoun ted for?

• What research is needed to develop sensor s that can detect nano m a terials, including personal exposure m onitoring?

5.2.4.3 Release and Exposure Reduction a nd Mitigation Research Questions

• What tools/resources exist for lim itin g rele ase an d/or exposu r e during m a nufacture, u s e or following release via waste stream s? Are these tools / reso urces ad equ a te for

nanom aterials?

• Are curren t respirato r s, filters, g l oves , and other P P E capable of reducing or elim inating exposure from nanom a terials?

• Are current engineering contro ls and pollution prevention devices capable of m i ni m i zing releases and exposures to nanom aterials?

• Are technologies and procedures for c ontrolling spills during m a nufacture and use adequate for nanom aterials? Can current conventional technologies (i.e., for nonnanom aterials) be adapted to control nanom ateria l spills ?

• In the case of an unintentional spill, what are the appropriate em ergency actions? How are wastes from response actions disposed of properly?

• Do existing m e thods using vacuum c l eaners with HEPA filters work to clean up a spill of solid nanom aterials? If not, would a wet vacuum system wor k ?

• W h at PPEs would be suitable f o r us e by operato r s during sp ill m itigation ?

5.2.5 Human Health Effects As sessment Research Needs

Adverse health effects of in tentionally produced nanom ateria ls m a y result f r om either direct exposure resulting from inadvertent re lease of these novel m a terials or unintentional byproducts produced by their intenti onal release into the environm ent. Very little data exist on the tox i city, hazardous p r operties, d e position and fate , as well as suscep tib ility asso ciated with exposure to inten tionally produced n a nom aterials , their application byp rod u cts, decom position products o rproduction waste stream s. Finally, it is un certain whether s t andard tes t m e thods will be capable of identifying toxic ities associated with the unique physical chem ical properties of intentionally produced nanom aterials.

It will be im portant for nanom aterial health effects risk assessm e nt research to also estab lish wh ether current particle and fiber toxico logical databases have th e ability to predic t or assess the toxicity of intentionally produced nanom a terial s displaying unique physicochem i cal properties. The lim ited studies c onducted to date indicate that the toxicological assessm e nt of78 EPA Nanotechnology White Paper

specif i c inte ntiona lly pr oduced nano m a terials will be d i f f i cult to ex trapo l ate f r om existing databases. The toxic ef fects of nanoscale m a terial s have not been fully characterized, but it is generally believed that nanoparticles can have toxi cological properties that differ from their bulk

m a terial. A num b er of studies have dem onstrat ed that nanoparticle toxicity is com p lex and multifactorial, poten tially being re gu lated by a variety of physiochem ical properties s u ch as size, chem ical composition, and shape, as well as su rface properties such as ch arge, area an d reactivity. As the size of partic les decreases, a resulting larger surface-to-volum e ratio per unit weight for nanoparticles correlate s with increased toxicity as com p ared with bulk m a terial toxicity. Also as a result of their smaller size, nanopa rticles m a y pass into cells directly through cell m e m b ranes or penetrate the skin and distribute throughout the body once tr anslocated to the circulatory system

. W h i l e the effects of shape on toxicity of nanopartic les appears unclear, the results of a recent in vitr o cytotoxicity study appear to sugge st that single-wall carbon nanotubes

are m o re toxic than m u lti-wall carbon nanotubes. Therefore, with respect to nanoparticles, there is concern for system ic effects (e .g., target organs, cardiovascular, and neurological toxicities) in addition to portal-of-entry (e.g. lung, skin, intestine) toxicity.

Initially, it will be im portan t to be s p ecifi c with respec t to th e nature of the surface

m a terial/coating, the application fo r which the material is used, th e likely route of exposure, the presence of other exposures which m a y a ffect toxicity (e.g., UV radiation) and not rely on inform ation derived from a study conducted under one set of conditions to predict outcom e s that

m a y occur under another set of conditions. Ho wever, past experience with conventional chem icals suggests that toxico logy research on nanom aterials should be designed from the beginning w ith an eye towards devel oping hypothesis-based predictive testing.

Research is also need ed to exam ine health im pa cts of highly disp ersive nanotechnologies that a r e em ployed f o r site rem e diatio n, m onitorin g, and pollu tion control s t ra tegie s . It will be necessary to determ ine both th e im pa cts these types of nanot echnologies have on regulated pollutants in air, soil, or water, as well as their corre sponding potential health effects. Research should be conducted in the following areas:

A. Determ ining the adequacy of current test ing schem e s, hazard protoco l s, and dose

m e trics. B. Identifying the properties of nanom a terials th at are m o st predicti ve of toxicity to
recep tors an d their sensitive subpopu lations. C. Identifying those nanomaterials with hi gh commercial potential with dispersive applications, and their most probable exposure pathways.

These areas lead to the following res earch questions:

• What are the health effects (lo cal and system ic; acute and chronic) from either direct exposure to nanom aterials, or to their bypr oducts, associated with those nanotechnology applications that are m o st likely to have potential for exposure? (Addresses area C, above)• Are there specific toxicological endpoints th at are of higher concern for nanomaterials, such as neurological, cardiovascular, re spiratory, or immunologi cal effects, etc.? (Addresses area C, above)

• Are current testing methods (organisms, exposure regimes, media, analytical methods, testing schemes) applicable to testing nanomaterials in standardized agency toxicity tests ( http://www.epa.gov/opptsfrs/OPPTS_Harmonized/ )? (Addresses area A, above) 79 EPA Nanotechnology White Paper

• Are current test m e thods, for exam ple OECD and EPA har m onized test guidelines, capable of d e term ining the toxic ity o f th e wide variety of intentionally produced

nanom aterials and byproducts associated with their producti on and applications? (Addresses area A, abov e)

• Are current analytical methods capable of analyzing and quan tifying intentionally produced nanom a terials to generate dose-re sponse relationships? (Addresses area A, above)

• What physicochem i cal properties regulate nanomaterial absorption, distribution,

m e tabolism

, and excretion (ADM E)? (Addresses area A, ab ove)

• What physicochem i cal properties and dose m e trics best correlate with the toxicity (local and system ic; acute and chronic) of inte ntionally produced na nom a terials following various routes of exposure? (Addresses area A, above)

• How do variations in m a nufacturing and subseq uent processing, and the use of particle surface m o difications affect nanom ater ial hazard ? (Addre sses area B, ab ove

• Are there subpopulations that m a y be at in creased risk of adve rse health effects associated w ith exposure to intentionally produced nanom aterials? (Addresses area B, above)

• What are the best approaches to build eff ective predictive m o dels of toxicity (SAR, PBPK, “om i cs”, etc.)? (Addre sses areas A and B, above)

• Are there approaches to grouping particles into classes relative to their toxicity potencies, in a m a nner that links in vitro
, in vivo , and in silic o data?

5.2.6 Ecological Effects Research Needs

Ecosystem s m a y be affe cted through inadvert ent or intentional rel eases of intentionally produced nanom a terials. Drug and ge ne delivery system s, for exam pl e, are not likely to be used directly in the environm ent but m a y contam inat e soils or surface waters through waste water
treatm ent plants (from hum an use) or m o re direc tly as runoff from concentrated anim al feeding operations (CAFOs) or from aquaculture. Direct applications m a y include nanoscale monitoring system s, control or clean-up system s for conve ntional pollutants, and desalination or other80 EPA Nanotechnology White Paper

chem ical modifications of soil or water. Nanoscale particles m a y af f

ect aquatic o r te r r estria l organism s differently than larg er particles due to their extr eme hydrophobicity, their ability to cross and/or dam a ge cell m e mbranes, and differen ces in electrostatic charge. Furtherm ore, use of nanom a terials in the environm ent m a y result in novel byproducts or degradates that also m a y pose significant risks.

Im portant considerations for prioritizing and de f i ning the scope of the research needs include determ ining which nanom aterials are m o st used (vol um e), are likely to be used in the near future (imm inence of use), and/or have m o st potential to be released into the environm ent (dispersive applic ation s ). Another c onsidera tion is the n eed to test representative m a terials from e ach of the four classes of nanom a teri als (carbon-based, m e tal-based, dendrim e rs, composites).

The sam e ge neral research areas used for prio ritizing hum an health e ffects research needs were used to prioritize ecological research need s. Using these areas as a gu ide, the follo w ing research questions were identified:

• Are current testing schem e s and m e t hods (organism s , endpoi nts, exposure regim e s,

m e dia, analytical m e thods) applicable to tes ting nanom aterials in standardized toxicity
tests ? Both pilot tes ting protoco l s an d de f i nitiv e protoco l s sh ould be eva l uated with
respec t to th eir app lic ability to nano m a terials.

• What is the distribution of nanom a terials in ecosystem s ? Research on m odel ecosystem s studies (m icro, m e socosm s) is needed to assist in determ ining the distribution of

nanom aterials in ecosystem s and potentially affected com p artm ents and species.

• What are the effects (local and system ic; acute and chronic) from e ither direct exposure
to nanom aterials, or to their byproducts, associated with those nanotechnology applications that are m o st likely to have potential for exposure?

• What are the absorption, dist ribution, m e tabolism

, elim ination (ADME) param e ters for various nanom a terials for ecologi cal receptors? This topic addr esses the uptake, trans port, bioaccum u lation relevan t to a rang e o f species (fis h, invertebrates, birds, amphibians, reptiles, plants, m i crobes).

• How do variations in m a nufacturing and subseq uent processing, and the use of particle surface m o difications affect nanom ateria l tox i city to ecolog i cal species ?

• What research is need ed to exam ine the in teraction of nanomateri als with m i crobes in sewage tr eatm e nt plants, in sewage e f f l uent, and in natu ral co mmunities o f m i crobes in
natura l soil and natur a l water ?

• What research is needed to develop stru c t ure a c tivity r e la tion s hips (SARs) f o r

nanom aterials for aquatic organism s?

• What are the m odes of action (MOAs) for various nanom aterials for ec ol ogi c a l s p e c ie s? Are the MO As different or sim ilar across eco logical species ?81 EPA Nanotechnology White Paper

5.2.7 Risk Assessment Rese arch - Case Study

The overall risk assessm ent approach used by EPA for conventional chem icals is thought to be generally applicable to nanom aterials. It will be necessa ry to consider nanom aterials’ special properties and their pote ntial im pacts on fate, exposure, a nd toxicity in developing risk

assessm ents for nanom a terials. It m a y be usef ul to consider a tiered- testin g schem e in the developm ent of testing a nd risk as ses s m e nt approaches to n a n o m a teria l s. Also, decis i ons will need to be m a de even as prelim inary data a r e be ing gener a te d, m eaning that dec i sion m a king will occur in an environm ent of si gnificant uncertain ty. Decision -support too l s will n e ed to be developed and applied to inform ass e ssm ents of potential hazard and exposure.

Case studies could be conducted based on publicly available in form ation on several intentionally produced nanom ateria ls. Such case studies would be useful in further identifying unique considerations that should be focused in conducting risk a ssessm ents for various types of

nanom aterials. From such case studies and other inform ation, inform ation gaps m a y be identif i ed, which can the n be used to m a p areas of resea r ch th a t are d i re ctly af f iliated with the risk assessm ent process and the us e of standard EPA tools such as tiered testing schem e s. EPA frequently u s es tiered tes ting sch e m e s for specifi c risk assessm e nt applications. A series of workshops involving a substantial num b er of expert s from relevant disciplin es could be held to

use case s t u d ies and o t h e r inform ation for the id entification of any unique considerations for

nanom aterials not previously iden tified, testing schem e s, and associ ated research needs that will have to be m e t to carry out exposur e, hazard an d risk assessm e nts.82 EPA Nanotechnology White Paper



## 6.0 Recommendations

This section provides st aff recomm e ndations for Ag ency actions related to nanotechnology. These staff recomm endations are based on the discussion of nanotechnology environm ental applications and im plications disc ussed in this paper, a nd are presented to the Agency as proposals for EPA actions for sc ience and regulatory policy, research and developm ent, collaboration and communication, and other A g ency in itiatives. Included below are staff recomm endations for research that EPA should conduct or otherwise fund to address the Agency’s decision-m aking needs. When possible, relative priorities have been given to these needs. Clearly, the ability of EPA to addre ss thes e research n eeds will depend on available resources and com p eting priorities. Potential lead offices in the Agency have been identified for each recomm endation. It m a y be appropriate for other EPA offices to co llabo rate with the identified leads for specific recomm e ndations. E P A should also collaborate with outside groups to avoid duplication and leverage research by others. Identified research recomm endat i ons were used as a point of departure for Agency disc ussion and developm ent of the EPA Nanot echnology Research Fram e w ork, attached as Appendix C.



### 6.1 Research Recommendations fo r Environmental Applications

6.1.1 Research Recommendations for Green Manufactu ring

• ORD and OPPT should take the lead in i nvestigating and promoting ways to apply nanotechnology to reduce waste products generated, and energy used, during

m a nufacturing of conventional m a te rials as well as nanom aterials.

6.1.2 Research Recommendations for Green Energy

• ORD and OPPT should prom ote research into applications of nano m a terials green energy approaches, including sola r energy, hydrogen, power transm ission, diesel, pollution control devices, and lighting.

6.1.3 Environmental R e mediation/ Treatment Research Needs

• ORD should support research on im proving polluta nt capture or dest ruction by exploiting novel nanoscale structure-propert y relations for nanom aterials used in environm ental control and rem e diation applications.

6.1.4 Research Needs for Sensors

• ORD should support developm ent of nanotechno logy-enabled devices for m easuring and monitoring contam inants and other com pounds of interest, including nanom a terials. For

exam ple, ORD should lead developm ent of ne w nanoscale sensors for the rapid detection of virulent bacteria, viruses, and protozoa in aquatic environm ents83 EPA Nanotechnology White Paper

6.1.5 Research Needs for Other E n vironmental Applications

• ORD should work with industrial partners to verify the perform a nce of na nom a terials and nanoproducts used for environm ental applications.

• ORD should develop rapid screening m e thods that keep pace with rapid technological change for nanom aterials and nanoproducts building on existing Life Cycle Analysis

m e thods. OPPTS, OW and OAR should collab orate with stakeholde rs developing rapid screening methods.

• ORD and OPPT should collaborate with NIOSH a nd others to evaluate the application of nanotechnology for exposure reduction; e.g., nano-enabled PPE, respirators containing

nanom aterials, and nanoscale e nd-of-life sensors, sensors th at indicate when a product has reached the end of its useful life.



### 6.2 Resea rch Recommendati ons for Ris k Ass e ssment

A m u ltidisciplinary approach is need ed th at involves physics, biology, and chem istry to understand nanom aterials at a basic level and how they inte ract with the environm ent. This calls for a cross-m e dia approach and one that involves collaboration w ith other federal agencies, and the private and non-profit sectors. T h is incl udes exam ining the im plications (risks) of the environm ental applications of nanotechnology.

6.2.1 Research Recommendations for Chemical Identification and Characterization

• ORD should lead research on the unique chemical and physical characteristics of nanomaterials and how these properties affect the material’s reactivity, toxicity and other attributes.

• ORD should lead research on how nanomaterial characteristics vary from their pure form in the laboratory to their form as components of products, and eventually to the form in which they occur in the environment.

• ORD should determine if there are adequa te measurement methods/technology available to fully characterize nanomaterials, to distinguish among different type s of nanomaterials, and to distinguish intentionally produced na nomaterials from ultrafine particles or naturally occurring na nosized particles.

6.2.2 Research Recommendations for Environmental Fate and Treatment

The following are recommendations, in order of priority, in support of the environm ental fate and treatm ent research needs id e n tif ied as p r iorities in Chapter 5.

Fate,Treatm e nt and Transport84 EPA Nanotechnology White Paper

• OS WER an d ORD shou ld lead re search on the fate of nanomaterials, such as zero-valent iron, used in the rem e diation of chemically contam inated sites. This research should also address the impacts of such nanom aterials on the f a te of other contam inants at

rem e diation sites. These offices should co llaborate with state environm ental program s and academ ia on this research. Based upon avai lable field activities where nanom aterials are being used for site rem e diation, this re search could be con ducted within the few
years.

• ORD and OAR should lead res earch on the stab ility of vario u s types of intentionally produced nanoparticles in the atm o sphere. This effort should involve both theoretically derived inform ation as well as som e laboratory testing.

• ORD, OPPT, OPP, OSWER and OW should le ad research on the biotic and abiotic transport and degradation of na nom a ter i als wa ter s , soils and s e dim e nt that are relevant to environm ental conditions.

• ORD should lead research that defines th e physical and chem ical properties of

nanom ateria ls tha t im pact the i r env i r o nm ental f a te.

• ORD, OSW and OW should collaboratively le ad research on treatm e nt m e thods used for

rem oving nanom a terials from wastewater. Research should include analysis of the specific types of nanom a terials that are likely to end up in large quantities in sewage
treatm ent plants, the efficiency of removing nanoparticles from the effluent, the fate of

nanom aterials after rem o val, m e thods for di sposal of sludges cont aining nanom a terials, and the im pact nanom aterials m a y have on the rem oval or degradation of other substances in sewage during the treatm e nt process. EPA should collaborate with municipal s e wage treatment faciliti es and academ ia on th is res earch.

• ORD, OPPT and OW should shar e the lead on research on the fate of nanom a terials used in the purification of drinki ng water. Research w ould be based on actual field and/or laboratory findings and recomm endat i ons w ould be provided on how to improve the

nanom aterial rem oval process where hum a n heal th issues a r e a concern. This research should also evaluate individual processe s; i.e., w h ether m e thods such as carbon adsorption, filtration, and coagulation a nd settling are effectiv e for treatin g

nanom aterials.

• ORD, OS W and OAR sh ould lead research on the fate of na nom aterials in incineration and other therm a l treatm e nt processes, including the efficiency of destroying

nanom aterials, the efficiency of various air pollution control de vices (e.g., baghouses, liquid scrubbers, and electrostatic precipitato rs) at rem oving entrained nanom a terials, the fate of nanom aterials after rem oval, m e thods for disposal of ash containing

nanom aterials, and the impact nanom a terials ma y have on the rem oval or degradation of other substances during the treatm e nt process.

• ORD and OSW should lead research on the fate of nanom a terials in other waste treatm ent processes (e.g. chem ical oxidati on, stabilization). Research w ould identify relevant w a ste85 EPA Nanotechnology White Paper

stream s, the efficiency of curren t treatm e nt regim e s at addressing nanom at erials, the fate of nanom a terials after treatm ent, m e thods for disposal of treat m e nt output containing

nanom aterials, and the impact nanom a terials may have on the treatm ent of other toxic constituents in the waste stream

. EPA shoul d collaborate with treatm ent, storage, and disposal facilities (TSDFs) a nd academ ia on this research.

• ORD and OSW should lead research on the fate of nanom a terials in m unicipal, industrial, and hazardo us waste (i.e., Subtitle C) landf ills, an d other land-based waste m a nagem e nt scenarios (e. g., surface impoundm e nts). Research would identify relevan t waste stream s, the efficiency of current containm ent tec hnologies (e.g., various cap and liner types, leachate co llection system s) at preventi ng th e leaching of nanom a terials into groundwater, the fate of nanom aterials after disposal, and the im p act nanom a terials m a y have on the containm ent of other tox i c cons titu en ts in th e was t e stream

. EPA should collaborate with m unicipal a nd industrial stakeholders, a nd academ ia on this research.

6.2.3 Research Recommendations for Environmental Detection and Analysis

Where applicable, the in itial focus of e nvironm ental detection and analysis related research should be on nanom a teri als or types of nanom aterials th at have demonstrated potential hum a n or ecological toxicity. The following is a prioritized list of research needs for environm ental detection and analysis.

• ORD should lead the developm ent of a report on the assessm ent of available environm ental detection m e thods and technol ogies for nanomaterials in environm ental

m e dia and for personal exposure monitoring. ORD could collaborate with NIOSH, DOD, industry and academ ia in developing this report.

• ORD should collaborate with NIST, NIOSH, DOD, nanom a terial m a nufac turers and
governm e nt and private s ector o r ganization s in th e developm ent of quality contro l reference m a terials for analytical m e thods for nanom a terials.

• ORD should lead developm ent of a set of standard m e thods for the sam p ling and analysis for nanom a terials of interest in various e nvironm ental m e dia. ORD shoul d collaborate with NIOSH, DOD, indu stry, academia, the Am erican Society for Testing Materials (ASTM) and the Am erican Nationa l Standa rds I n stitu te (ANSI) in deve loping thes e

m e thods.

6.2.4 Research Recommendation Human Exposures, their Measurement and Control

The following is a prioritized list of re search needs for hum a n exposures, their

m easure m ent and control.

• OPPT should conduct a literature search to evaluate the effects of nanom aterial physical/chem i cal properties on releases and exposures.

• ORD and OPPT should lead research to dete rm ine what dose m e trics (e. g. m a ss, surface area, particle count, etc.) ar e appropriate for m e a s uring exposure to nanom a terials.86 EPA Nanotechnology White Paper

• OPPT and ORD should evaluate sources of in form ation for assessing chem ical releases and exposures for their appli cability to nanom aterials. Th ese sources, including release and exposure tools and models, would be evaluated to determ ine whether they would be applicable to assessing releases and exposures to nanom aterials. If found applicable, the sources would be evaluated to determine wh ether additional data or m e thods would be needed for assessing n a n o m a terials. Issues su ch as degrad ation would be considered also.

• OSWER, ORD, and OPPT should evaluate th e proper em ergency response actions and

rem e diation in case of a nanom at erial spill, and the proper dis posal of wastes from such response actions.

• OPPT should define risk assessm ent needs for various types of nanom a terials in consultation with other stakeholders.

• OPPT should consider approaches f o r perform i ng exposure assessm ents for

nanom aterials for hum an and environm ental species, including sensitive populations (e.g., endangered species, children, asthm a tics, etc.), in consultation with other offices and stakeholders.

Som e parts of the rem a ining exposure a nd release research in itiatives below are contingent upon com p letion of the risk and exposure assessment guidance docum ents noted in the two paragr aphs ab ove. Until this conti nge ncy is m e t, m a ny of the rem a ining re search needs cannot be fully completed.

• OPPT should lead developm ent of exposure a nd release scenarios for nanom a terials in

m a nufacturing and use operations. T h is effort should be conducted by OPPT in consultation with industry, NIOSH, a nd ORD, as appropriate.

• OPPT and ORD should evaluate and test equ i pm e n t for contro lling and red u cing chem ical releases and ex posures for th eir app lic a b ility to nan o m a teria l s.

• OPPT, ORD, OSWER, a nd OPP should evalua te and test personal protective equipm ent for controlling and reducing chem ical exposures for their applicabil ity to nanom aterials, in collaboration with NIOS H and other external groups.

• ORD should lead developm ent of sensor s for m o nitoring personal exposures to nanoparticles

6.2.5 Research Recommendations for Human Health Effects Assessment

The f o llowing is a pr ior i tized lis t of health effects research n eeds:

Test Methods87 EPA Nanotechnology White Paper

• ORD and OPPTS should determ ine the appl icability of current testing m e thods (organism s , exposure regim e s, m e di a, analytical m e thods, testing schem e s) (http://www.epa.gov/opptsfrs/hom e/testm e t h.htm ) for evaluating nanoparticles in standardized agency toxicity tests. These offices shoul d consider whether OECD and EPA har m onized test gu idelines are capable of determ ining the toxicity of the wide variety of intentionally produced nanom a teri als and waste byproducts associated with their production. In this effort ORD should lead research evaluating whether current analytical methods are capable of analyz ing and quantifying in tentionally produced

nanom aterials to generate dose-response relationships.

Nanotoxicology

• ORD should lead research to determ ine the he alth effects (local a nd system ic; acute and chronic) resulting from either direct exposure to nanom ater ials, or to their byproducts, associated w ith dispersive nanotechnology appl ications such as rem e diation, pesticides, and air pollution control tec hnologies. Research should determ ine whether there are specific toxicological endpoint s that are of high concern for nanoparticles, such as neurological, cardiovascular, respiratory, or i mmunological effects, etc. Research in this area should also provide inform ation as to th e ad equacy of ex isting toxicological databas e s to predic t or ex trapo l ate the toxic ity of intentionally pr oduced nanom a terials. The Agency should also collaborate with st akeholders in cataly zing this research.

Hazard Iden tification an d Dosimetry & Fate

• ORD should lead research to determ ine what physicochem i cal properties and dose

m e trics (m ass, surface area, particle num b er, et c. ) best co rrelate with the toxicity (local and system ic; acute and chronic) of intentionally produced nanom a terials.

• ORD should lead research on the absorpti on, distribution, m e tabolism

, and excretion (ADME) of intentiona lly produced nanom aterials followi ng various routes of exposure. This research m u st also include determ in ing what physicochem i cal properties regulate intentionally produced nanom aterial ADME. ORD should collaborate with OPPTS on this r e sea r ch

. Susceptibility

• ORD should lead research to identify subpopula tions that m a y be at increased risk for adverse health effects associated with expos ure to intentionally produced nanom aterials. This is a need that cannot be established until inform ation from earlier res earch needs have been collected.

Computational Nanotoxicology

• ORD should lead research to determ ine what approaches are most effective to build predic tive to xicity asse ssm e nt m odel s (SAR, PBPK, “om i cs”, etc.).88 EPA Nanotechnology White Paper

Research into the hum an health eff ects assessm ent of in tentionally produced

nanom ateria ls will b e ex trem ely challenging and the ability to inte ract with other f e der a l, international, academ ic, and private activ ities in this area wo uld be m o st beneficial. A num b er of organizations are engaged in health effects re search. Collaboration with NAS A, NIOSH, FDA, NCI, NTP, DOD/MURI , NIST, NE HI, DOE, th e European Union, EPA grantees, academ ic institutions, and others w ill leve rage r e sources in gaining kno wledge on the potential health effects of nanom a terials.

6.2.6 Ecological Exposure and Effects

It is critical that research be focused specifically upon th e fate, and subsequent exposure and effects, of nanom a terials on invertebrates, fish, and wildlife associated with ecosystem s. What is the behavior of nano m a terials in aquatic and terrest rial environm ents? How can environm ental exposures be sim u lated in the labo ratory? W h at are the acute and chronic toxic effects? There is a need for developm ent and validation of analytical m e thodologies for

m easuring nanoscale substances (both parent m a teria l s and m e tabolite s/co mplexes) in environm ental m a trices, including ti ssues of organism s. In term s of toxicity, a critical challenge in the area o f ecosystem effects lies in determ inin g the im pacts of m a terials whose cumulative toxicity is likely to be a m a ni festation of both physical and chem i cal interactions with biological system s. The following is a prioritized list of ecological research needs:

Test Methods

• ORD should collaborate with other EPA offices in research on the applicability of current testing schem e s and m e t hods (organism s , endpoi nts, exposure regim e s, m e dia, analytical

m e thods) for testing nanom a terials in standard ized toxicity tests. Both pilot testing protoco l s an d def i nitiv e protoco l s sh ould be ev a l uated with r e spect to the i r app licab ility
to nanom aterials.

Environmental Fate/Distribution of Nanomaterials in Ecosystems

• ORD shoul d lead on research on the distri bution of nanom a terials in ecosystem s

. Nanotoxicology and Dosimetry

• ORD should determ ine the effects of dire ct exposure to nanom a terials or their byproducts, associated w ith dispersive na notechnology uses, on a range of ecological species (fish, inverts, birds, am phibians, rept iles, plants, m i crobes). This research should be focused on organism s residing in ecologica l co mpartm ents that the nan o m a teria l s in question preferentially distribute to, if any, as identified above. This research should include evaluation of the uptake, tran sport, and b i oaccum u lation of these m a terials.

• ORD, OW a nd OPPT should lead research on the inte ractions of nanom a teria l s with

m i crobes in sewage treatm e nt plants in se wage ef fluent and natural communities of

m i crobes in natura l soil and natur a l water.89 EPA Nanotechnology White Paper

• ORD should lead research aim e d at developing structure-activity rela tionships (SARs) for

nanom aterials for aquatic organism s.

• ORD should lead research on the m o des of ac tion for various nanom aterials for a range of ecological species.

6.2.7 Recommendations to Address Overarching Risk A ssessment Needs - Case Study

One way to exam ine how a nanom a terial assess m e nt would fit within EP A’s overall risk

assessm ent paradigm is to conduct a case study ba sed on publicly available inform ation on one or several intentionally produced nanom a terials. In the past , such case studies have proven useful to the Agency in adjusting the chem ical risk assessm ent process for stressors su ch as bacteria. For exam ple, assessm ents of recom b in ant bacteria need to account for reproduction, and other factors no t co nsidered with chem ical risk assessm e n ts. From s u ch case studies and other information, inform ation gaps m a y be identif ied, which can then be used to m a p areas of

resea r ch th at are direc tly af f ilia ted with the risk a s sessm ent process. This has been do ne in the past with research on ai rborne particulate m a tter

. Additionally, a series of wo rkshops involving a substantial num b er of experts from several disciplines should be held to use availabl e inform ation and principles in identifying data gaps and research needs that will have to be m e t to carry out exposure, hazard and risk

assessm ents.



### 6.3 Recommendations for Pollution Prevention and Environmental Stew a rdship

Opportunities exist to advance pollution prevention as nanotechnology industries form and develop. EPA has the capability to support research into nanotechno logy applications of pollution prevention and environm ental stewardshi p principles that have been developed for green energy, green chem istry, green engineerin g, and environm entally benign m a nufacturing. EPA is well-position e d to work with stakeho l ders on pollution prevention and product stewardship approaches for producing nanom aterials in a green m a nner, as well as for identifying areas where nanom aterials m a y be cleaner alte rnatives to exisiting i ndustrial inputs. The following are the prim ary recomm endations for pollution prevention and environm ental stewardship:

• EPA should support research into approaches that encourage environm ental stewardship throughout the com p lete life cycle of nanom aterials and products.

• OPPT, ORD, and other stakeholders should encourage product stewardship, design for the environm ent, green engineering and green chem istry principles and approaches to

nanom aterials and nanoproducts.

Other recomm endations for pollution prev ention and environm ental stewardship:90 EPA Nanotechnology White Paper

• NCEI and OECA should research nanotechnolog y sectors, supply chains, analytical and design tools, and applications in order to inform pollution prevention approaches. OECA should collaborate with other Agency progr am s, such as OPPT’s Green S upply Chain Network to identify nanotechnol ogy sectors, supply chains, an alytical and design tools, and applications.

• OCIR and OCFO should encourage research w ithin organizations such as the Ecological Council of the States (E COS), state tec hnology assistance organizations, and other technology transfer groups to further the unde rstanding of how to integrate environm ental stewardship for nanotechnology into their ongoing assistance efforts.

• OPEI, OPPT, and ORD should support research on econom i c incentives for environm ental stewardship behavior associ ated w ith nanom aterials and nanoproducts.

• ORD should continue to support research to promote clean producti on of nanom aterials and nanoproducts..



### 6.4 Recommendations for Collaborations

In addition to the Agency’s current co llaborations on nanotechnology issues and our ongoing co mmunication activ ities, we recomme nd the follo wing additio nal actions. These collabo ratio n s will r e du ce resou r ce burdens on EPA’s scien ce program s and will f a c ilitate communication with stakeholders.

• ORD should collaborate with other groups on research into the environm ental applications and im plications of nanot echnology. ORD’s laboratories should put a special em phasis on establishing Cooperative Research and Developm ent Agreem ents (CRADAs) to leverage non-federal resources to develop environm ental applications of nanotechnology (CRADAs are established betwee n the EPA and research partners to leverage personnel, equipm ent, services, and expertise for a specific research project.)

• EPA should collaborate with other countries (e.g., through the OECD) on research on potential hum a n health and envi ronm ental im pacts of nanotechnology.

• OCIR should lead efforts to investigate the possibilities for co llaboration with and through state and local governm e nt econom ic de velopm ent, environm ental and public health officials and organizations.

• OPA and program offic e s, as appropriate, shoul d lead an Agency effort to im ple m ent the communication strategy for nanotechnology.

• OPEI’s Sm all Business Om sbuds m a n should engage in inform ation exchange with sm all businesses, which com p rise a larg e percen tage of U.S. nanom a terial producers.91 EPA Nanotechnology White Paper



### 6.5 Recommendation to Convene an Intra-Agency Workgroup

The Agency should convene a standing intra- Agency group to foster inform ation sharing regarding risk assessm ent, and regulatory ac tiv itie s , as well a s pollution prevention and stewardsh i p-orien t ed activities regarding nanom aterials across program offices and regions.



### 6.6 Recommendation for Training

EPA has begun educating itself about nanot echnology through sem i nars in the program and regional offices, an internal cross-Agen cy workgroup (NanoMeeters) with an extensive databas e , an d a Milleniu m lecture series cov e ri ng both the adm i nistrative and technical aspects of nanotechnology. The SPC Nanot echnology Wor kgroup also held a “prim e r” session on nanotechnology to help infor m its m e mbers during the early stages of developm ent of this paper. While this w h ite paper also provides infor m ati on for Agency m a nagers and scientists, there should be ongoing education and tr aining as well as expert suppor t for EPA m a nagers and staff to assist in the understanding of nanotechnol ogy, its potential applic ations, regulatory and environm ental im plications, as well as unique co nsiderations when conducting risk assessm ents

on nanom at erials relative to m acro-sized m a terials.

### 6.7 Summary of Recommendations

EPA should begin tak i ng steps to h e lp ensure both that so ciety accrues th e im portant benefits to environm ental protection that nanotechnology m a y offer and that the Agency understands potential risks from human and environm ental exposure to nanom a terials. Table 6 summarizes the staff recomm e ndations identified above.

Table 6. Summary of Workgroup Recomme n d ations Regarding Nanomaterials

6.1 Research for Environmental A pplications. EPA should undertake, collaborate on, and support research on the various types of nanom a terials to better understand and apply inf o rm ation regard ing th eir env i ron m ental appli cations. Specific research recomm endations for each area are identified in the tex t

. 6.2 Research for Risk Assessment. EPA should undertake, co llaborate on, and support research on the various types of nanom aterials and nanotechnologies to better understand and apply inform ation regarding: i) chem ical identificat ion and characterization, ii) environm ental fate and treatm ent m e thods, iii) environm ental detection and analysis, iv) potential hum a n exposures, their m easurem e n t and control, v) hum an health effects assessm ent, vi) eco logical effects ass e ssm ent, and vii) conducting case studies to furt her identify unique risk assessm ent considerations for nanom aterials. Specific res earch recomm endations for each area are identified in the tex t

. 6.3 Pollution Prevention, Stew ards hip and Sus tainability. EPA should engage resources and expertise as nanotechnology industries form and develop to encourage, develop and support nanom a terial pollution pr evention at its source and an approach of stewardship. Detailed pollution prevention recomm endations ar e id entif ie d in the text. Additiona lly, the Agency should draw on the “next generation” nanotechnologies for applications that support environm ental stewardship and sustainability, such as green energy and green m a nufac turing. 6.4 Collaboration

. EPA should continue and expa nd its collaborations regarding

nanom aterial applications and potential hum an and environm ental health implications.
6.5 Intra-A g ency Workgroup. EPA should convene a standing intra-A g ency group to foster inform ation sharing regarding risk assessm ent or regulatory activities fo r nanom aterials across
program offices and regions. 6.6 Training. EPA should continue and expand its a c tiv ities aim e d at tra i ning Agency scien tis ts an d m a nagers regarding potential environm enta l applications and environm ental im plications of nanotechnology. 92 EPA Nanotechnology White Paper93 EPA Nanotechnology White Paper



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## Appendix A: Glossary of Nanotechnology Terms

Aerosol : A cloud of solid or liqui d particles in a gas.

Array : An arrangem e nt of sensing elem ents in rep eating or non-repeating units that are arranged f

o r increa se d sensitiv ity or selectivity.

Biomimetic : Im itating nature and applying th ose techniques to technology.

Buckyball/C 60 : see Fullerenes , of which “buckyballs” is a subset. The term “buckyball” refers only to the spherical fullerenes and is derived from the word “Buckm insterfullerene,” which is the geodesic dom e / soccer ball-shaped C 60 m o lecule. C 60 w a s the first buckyball to be discovered and rem a ins the m o st common and easy to produce.

Catalyst : A substance, usually used in sm all a m ounts re lative to the reac tant s, that modifies and incre a ses th e rate of a re action witho u t bei ng consum ed or changed in the process..

Dendrimers : artificially engineered or m a nufactured m o lecules built up f r om branched units called m onom e rs. Technically, a den d rim e r is a b r anched po lym e r, which is a large m o lecule

com p rised of m a ny s m al ler ones linked together.

Diamondoid : Nanom e ter-sizes structures derived from the diam ond crystal structure.

Electron beam lithography : Lithographic patterning using an electron beam , usually to induce a change in solubility in polym er f ilm s. The resulting p a tter ns can be subsequently transferred to other m e tallic, sem i conductor, or insulating film s

. Engineered/manufactu red nanomateria l s : Nanosized m a terials are purposefully m a de. These are in contrast to incidental and natu rally occurring nanosized m a terials. Engineering/m a nufacturing m a y be done through certain chem ical a nd / or physical processes to

crea te m a ter i als with spe c if ic prope rties. Th ere are both "bottom

- up" pr ocesses (such as selfassem b ly) th at create n a n o scale m a terials from atom s and molecules, as well as "top-down"
processe s (s uch as m illing) tha t cre a t e nanosc a le m a teria l s f r o m their m acro-sc ale co unterpa rts. Nanoscale m a terials th at have m acro-scale coun terp arts frequently display different or enhanced properties com p ared to the m acro-scale form

. Exposure assessment : The determ ination o r estim a tion (qua litativ e or qu antitative) o f the

m a gnitude, frequency, duration, route, and extent ( num ber of people) of exposure to a chem ical,

m a terial, or m i croorganism

.

Fullerenes : Pure carbon, cage-like m o lecules composed of a t least 20 atom s of carbon. The word ‘f uller e ne’ is d e r i v e d f r om the word “Buckm insterf u lle rene,” which ref e rs spec if ically to the C 60 m o lecule and is nam e d after Buckm i nster Fu ller, an architect w ho described and m a de fa m ous the geodesic dom e

. C 60 and C 70 are the most common and easy to produce f u llerenes.108 EPA Nanotechnology White Paper

Incidental nanosi z e d materials: Nanom a terials that are the bypr oducts of hum a n activity, such

as com bustion, welding, or grinding.

Intentionally produced nanomaterials : See Eng i neered/ma nufactured nanoscale mater i als.

Manufacturing processes : General term used to identify the variety of processes used in the production of the part. Processes m a y include plastic injection molding, vacuum for m i ng,

m illing, stamping, casting, extrud in g, die-cu ttin g, sewing, printing, pack aging, polis hing, grinding, m e tal spinning, welding, and so forth.

Nano-: a prefix m eaning one billionth.

Nanobiology : A field of study com b ining biology and physics which looks at how nature works on the nanom e ter scale, particularly how tran sport takes place in biological system s. The interaction between the body and nanodevices are st udied, for exam ple, to develop processes for the body to regenerate bone, ski n, and other dam a ged tissues.

Nanochemistry : A discipline focusing on the unique propert ies asso cia t e d with the a s sem b ly of
atom s or m o lecules on a nanom eter scale. At th is scale, new m e thods of carrying out chem ical reactions are possible. A ltern atively, it is the developm ent of new tools, technologies and

m e thodologies for doing chem istry in the nanolitre to fem t olitre dom ains.

Nanoelectronics : Electronics on a n a nom eter scale, whether by current techniques or nanotechnology; includes both m o lecular electron ics and nanoscale devices resem b ling today' s

sem i conductor devices.

Nanomaterial : See Engineered/man ufactured n a noscale materia l s

Nanometer : one billionth of a m e ter.

Nanoparticle : Free standing nanosized m a terial, consis ting of between tens to thousands of
atom s.

Nanoscale : having dim e nsions m easured in nanom e ters.

Nanoscience : the inte rdisciplinary f i eld of scie nce devoted to the advancem ent of nanotechnology.

Nanostructures : structures at the nanoscale; that is, stru ctures of an interm ediate size between molecular and m i crosco pic (m icrometer-sized) s t ructures.

Nanotechnology : Research and technology developm ent at the atom ic, molecular or

m acrom olecular levels, in the length scale of approxim a tely 1 - 100 nanometer range; creating and using structures, devices and system s that have novel properties and functions because of their sm all and/or in term ediate siz e ; and the ab ility to control or m a nipulate on the atom ic scale.109 EPA Nanotechnology White Paper

Nanotube : Tubular structure, carbon and non-carbon based, with dim e nsions in nanom e ter regim e.

Nano wire : High aspect ratio structu r es with nan o m e te r diam eters tha t ca n be f illed ( n anorods) o r hollow (nanotubes).

PM 0. 1 : Particulate m a tter less than 0. 1 m i crom eters in diam eter

PM 2. 5 : Particulate m a tter less than 2. 5 m i crom eters in diam eter

PM 10 : Particulate Matter less th an 10 m i crom eters in diam eter

Quantum dot : A quantum dot is a closely packed sem i conductor crystal com p rised of hundreds or thousands of atom s, a nd whose size is on th e order of a few nanom e ters to a few hundred

nanom eters. Changing the size of quantum dots changes their optical properties

Self-Assembled Monolayers on Mesoporous Supports (SAMMS) : nanoporous ceram i c

m a terials that have been developed to rem ove contam inants from environm ental m e dia.

Self-as s emb l y : The ab ility of objects to assem b le them selv es into an orderly structure. Routinely seen in living cells, this is a property that nanotechnology m a y extend to inanim ate matter.

Self-r eplica tion : The ab ility of an en tity su ch as a liv ing cell to m a ke a copy of itself.

Superlattice : nanom aterials com posed of thin crys tal layers. The properties (thickness,

com position) of these laye rs repeat periodically.

Unintentionally produced nanomaterials : See Incidental nanosi z e d materials110 EPA Nanotechnology White Paper



## Appendix B: Principles of Envi ronmental Stewardship Behavior

What does a good environmental stew ard do? (based on statem ents by environm ental stewards and others)

Exceeds req u ired compliance. An environm ental steward views environm ental regulations only as a floor, not a target.

Protects natural systems and uses natura l resources effecti vely and efficiently. An environm ental steward considers and reduces the household, comm unity, farm or com p any’s entire environm ental foot print. A steward safeguards and restor es nature at hom e and elsewhere. A steward follows the pollution prevention hierarchy of acting first to prevent pollution at its

source. A steward uses less toxic, more enviro nm entally benign m a terials, uses local resources and conserves natural resources wh enever poss i b l e. A steward reuses and recycles m a terials and wastes and seeks sustainability.

Makes en vir onment a key part of internal priorities, values a nd ethics, and leads by example. Environm ental stewards m a ke d ecisions through their own volition that will prevent or m i nim i ze environm ental harm

. They anticipate, plan for

, an d take responsibility for econom ic, environm ental and social consequences of acti ons. A steward approach es business strategies, policy planning, and life as an integrated dynam i c with the environm ent

. A steward a c ts in innovative ways, using all availa ble tools and creating or addi ng value. A steward adopts holistic, sy stem s approaches.

Holds oneself accountable. An environm ental steward m easures the effects of behavior on the environm ent and seeks progress. A steward applies an understa nding of carrying capacity to

m easure progress and update objectives to ach ieve continuous im provem e nt, often using indicators, environm ental assessm e nts, a nd environm ental managem e nt system s.

Believes in shared respo n sibility. An environm ental steward recognizes obligations and connections to all stak eh olders - shar eholders, cu stom ers, communities a t hom e and elsewher e. For a com p a ny, this m eans being concerned with the full life cycle of products and services, beyond company boundaries, up and down the supply chain (including consum ers and end-oflife). For a community, this m eans to protec t the environm ent f o r all m e mbers and ta kes responsibility for effects on downstream air pollution, and effects of wastes disposed elsewhere. A steward o p erates with transparency

. They enco urage others to be collaborative stewards.

Invests in th e futur e

. An environm ental steward anticipat es the needs of future generations while serv in g the needs of the prese n t gener a tio n. Their actions reflec t p o ssible chan ges in population, the econom y and technology. A stewar d guides the developm ent of technology to

m i nim i ze negative envir o nm ental im plica ti ons and m a xim i ze potential environm ental stewardsh i p application s

. A stew ard values and protects natural and social capital. Th ey seek preventative and long-term solutions in comm uni t y development, busines s strategy, agricultural strategy, and household plans.111 EPA Nanotechnology White Paper



## Appendix C: EPA’s Nanotechno logy Research Framework

Nanotechnology has the potential to provide benefits to society a nd to improve the environm ent, both through direct applications to detect, preven t, and rem ove pollutants, the design of cleaner industrial processes and the creat ion of environmentally friendly products. However, som e of the sam e unique properties that m a ke m a nufactured nanoparticles beneficial also raise questions about the potential im pa cts of nanoparticles on hum a n health and the environm ent.

Based on th e fiscal year 2007 Presid ent’s budget request of $ 8.6 m illion, EPA is developing a nanotechnology research strategy for fiscal years 2007-2012 that is problem -driven, focused on addressing the Agency' s needs. The fra m ework for this strategy, as outlined here, involves conducting research to understand w h ether nanopart icles, in particular those with the greatest potential to be released into the env i ronm ent and/or trigger a hazard con c ern, pose s i g n ificant risks to human health or ecosyst em s, considering the entire lif e cycle. EP A also will conduct research to identify approaches for detecting and m easuring nanoparticles. This research fra m ework is based on the recomm e ndations from the EPA Nanotechnology White P aper and is consistent w ith the research needs id entified by the Interagency W o rking Group on Nanotechnology Environm ental and Health Im pli cations, one of the working groups of the Nanoscale S c ience Eng i neering and Technology Subcomm ittee of the National Scien c e and Technology Council.

While som e studies have been done to determ ine potential toxicity of certain nanoparticles to hum a ns and other organism s (both in vivo and in vitro ), very little research has been perform e d on environm ental fate and transport, transform a tion, and exposure potential. Research also is lacking on technologies and m e thods to dete ct and quantify nanom aterials in various environm ental m e dia. In addition, studies ind i cate that the to xicity of the nanom aterial will v a ry with size, su rface charg e , coating, state of agglom eration, etc. Therefore, in fiscal years 2007 and 2008, EPA will focus o n the following high prio rity areas: environm ental fate, transp ort, transform a tion and exposure; and m onitoring an d de tection m e thods. Resulting data will be us ed to inform and develop ef fects and exposure asse ssm e nt m e thods and identify im portant points of releases for potential m a nagem e nt. Specific activities will in clude:

 Identifying, adapting, and, where necessary, de veloping m e thods and techniques to m easure

nanom aterials from sour ces and in the environm ent

 Enhancing the understanding of the physic al, chem ical, and bi ological reactions

nanom aterials undergo and the re sulting transform a tions and pe rsistence in air, soil and
water

 Characterizing nanom at eria ls th roug h their lif e c y cle in the e nvironm ent

 Providing the capability to predict si gnificant exposure pathway scenarios

 Providing data to inform hum a n he alth a nd ecological toxicity studies, as well as

com putational tox i colog i cal app r oach es, and ai d in the developm ent of the m o st relevant testing m e thods/protocols

Having laid a foundation for understanding possi ble m a terial alterations under various conditions, EPA will direct a g r eat er share of fiscal year 200 9 and 2010 resources to exploring112 EPA Nanotechnology White Paper

the effects, s p ecifically toxicity of the altered m a ter i als as ide n tif ied in the f i rst two ye ars. This approach will be informed and refined by case st udies, initiating in fisc al year 2007, designed to elicit information on how EPA can address high-exposure-potential nanoparticles/na nom a terials. By 2011-2012, sufficient knowledge will result in the develo pm ent of system atic and integ r ated approaches to assess, m a nage and communicate ri sks asso cia t ed with engineered nano m a terials in the env i ro nm ent.

To com p le ment its own research program

, EPA is working with other federal agencies to develop research portfolios that address environm ental and hum a n h ealth needs. In addition, the Agency is collabo rating with academ ia and indu stry to fill kno wledge gaps in thes e areas. Finally, the Agency is working in ter n ationa lly and is part of the Organization of Econom ic Cooperation and Developm ent’s efforts on the to pic of the im plications of m a nufactured

nanom aterials.113EPA Nanotechnology White PaperAppendix D: EPA STAR Grants for NanotechnologyThrough Science to Achieve Results (STAR) programin EPA’s Office of Research and Development/National Center forEnvironmental Research, a number of nanotechnology research grants have been awarded.The table below shows nanotechnologygrants funded though 2005.Additional grants focusing on implications of nanomaterials for the2006 solicitation are in the process offinal selection and funding by EPA, the National Science Foundation (NSF), the National Institutefor Occupational Safety and Health(NIOSH), and the National Institute of Environmental Health Sciences (NIEHS).Information onfunded grants, including abstractsand progress reports is available online atwww.epa.gov/ncer/nano.Grant #PrincipalInvestigator (PI)TitleInstitutionYearAmountRD829621Bhattacharyya,DibakarMembrane-BasedNanostructured MetalsforReductive Degradation of Hazardous Organicat Room TemperatureUniversity ofKentucky2002$345,000RD829606Chen,WilfredNanoscale Biopolymerswith TunableProperties for Improved Decontamination andRecycling of Heavy MetalsUniversity ofCalifornia, Riverside2002$390,000RD829603Chumanov,GeorgePlasmon SensitizedTiO2Nanoparticles as aNovel Photocatalyst for Solar ApplicationsClemson University2002$320,000RD829626Diallo,MamadouDendritic Nanoscale ChelatingAgents:Synthesis, Characterization, MolecularModeling andEnvironmental ApplicationsHowardUniversity2002$400,000RD829599Gawley,RobertNanosensors for Detectionof Aquatic ToxinsUniversity ofArkansas2002$350,000RD829622Johnston,MurrayElemental Composition of Freshly NucleatedParticlesUniversity ofDelaware2002$390,000RD829600Larsen,SarahDevelopmentof Nanocrystalline ZeoliteMaterialsasEnvironmental Catalysts:FromEnvironmentally Benign SynthesisEmissionAbatementUniversity of Iowa2002$350,000RD829620McMurry,PeterIon-Induced Nucleation of AtmosphericAerosolsUniversity ofMinnesota2002$400,000114EPA Nanotechnology White PaperGrant #PrincipalInvestigator (PI)TitleInstitutionYearAmountRD829624Shah, S. IsmatSynthesis, Characterizationand CatalyticStudies of Transition Metal CarbideNanoparticles as Environmental NanocatalystsUniversity ofDelaware2002$350,000RD829604Shih,WanUltrasensitivePathogen Quantification inDrinkingWater UsingHighly PiezoelectricPMN-PT MicrocantileversDrexel University2002$400,000RD829602Sigmund,WolfgangSimultaneous Environmental MonitoringandPurification through SmartParticlesUniversity of Florida2002$390,000RD829601Strongin,DanielA Bioengineering Approach to NanoparticleBased Environmental RemediationTemple University2002$399,979RD829623Tao,NongjianA Nanocontact Sensor forHeavy Metal IonDetectionArizona StateUniversity2002$375,000RD829619Trogler,WilliamNanostructured Porous Silicon andLuminescentPolysiloles as Chemical Sensorsfor Carcinogenic Chromium(VI) and Arsenic(V)University ofCalifornia, San Diego2002$400,000RD829605Velegol,DarrellGreen Engineering of DispersedNanoparticles:Measuring and Modeling NanoparticlesForcesPennsylvaniaStateUniversity2002$370,000RD829625Zhang,Wei-xianNanoscale Bimetallic Particles for In SituRemediationLehighUniversity2002$300,000RD830907Anderson,AnneMetal Biosensors: Development andEnvironmental TestingUtah State University2003$336,000RD830910Beaver,EarlImplicationsofNanomaterials Manufacture andUse: Development of a Methodology forScreening SustainabilityBRIDGES toSustainability2003$99,741RD830904Drzal,LawrenceSustainable BiodegradableGreenNanocomposites from Bacterial Bioplastic forAutomotive ApplicationsMichigan StateUniversity2003$369,000RD830902Kan,EdwinNeuromorphicApproach to Molecular Sensingwith Chemoreceptive Neuron MOS Transistors(CnMOS)Cornell University2003$354,000115EPA Nanotechnology White PaperGrant #PrincipalInvestigator (PI)TitleInstitutionYearAmountRD830909Kilduff,JamesGraft Polymerizationas aRoute to ControlNanofiltrationMembrane Surface Properties toManage Riskof EPA Candidate Contaminantsand ReduceNOM FoulingRensselaerPolytechnic Institute2003$349,000RD830905Lave, LesterEnvironmental Implicationsof NanotechnologyCarnegie MellonUniversity2003$100,000RD830911Lavine,BarryCompound SpecificImprinted Nanospheres forOptical SensingOklahoma StateUniversity2003$323,000RD830898Lowry,GregoryFunctional Fe(0)-BasedNanoparticles forInSituDegradation of DNAPLChlorinatedOrganic SolventsCarnegie MellonUniversity2003$358,000RD830908Masten,SusanUse of Ozonation in Combination withNanocomposite Ceramic Membranes forControlling DisinfectionBy-ProductsMichigan StateUniversity2003$353,959RD830901Mitra,SomenathMicro-Integrated Sensing System (μ-ISS) byControlled Assembly of CarbonNanotubes onMEMS StructuresNew Jersey Instituteof Technology2003$346,000RD830903Sabatini,DavidNanostructured Microemulsions asAlternativeSolvents to VOCs in Cleaning Technologiesand VegetableOil ExtractionUniversity ofOklahoma, Norman2003$315,000RD830906Sadik,OmowunmiAdvancedNanosensors for ContinuousMonitoring of Heavy MetalsState University ofNew York,Binghamton2003$351,000RD830896Senkan,SelimNanostructured CatalyticMaterials forNOxReduction Using Combinatorial MethodologiesUniversity ofCalifornia, LosAngeles2003$356,000RD830899Subramanian,VivekLowCost Organic Gas Sensors on Plastic forDistributed EnvironmentalMonitoringUniversity ofCalifornia, Berkeley2003$328,000RD830900Wang,JosephNanomaterial-Based Microchip AssaysforContinuous EnvironmentalMonitoringArizona StateUniversity2003$341,000RD830897Winter,WilliamEcocomposites Reinforcedwith CelluloseNanoparticles: An Alternative to ExistingPetroleum-Based Polymer CompositesState University ofNew York, Syracuse2003$320,000116EPA Nanotechnology White PaperGrant #PrincipalInvestigator (PI)TitleInstitutionYearAmountRD831722Elder,AlisonIron Oxide Nanoparticle-Induced OxidativeStress and InflammationUniversity ofRochester2004$350,000RD831716Ferguson, P. LeeChemical andBiological Behavior of CarbonNanotubes inEstuarine Sedimentary SystemsUniversity of SouthCarolina2004$349,740RD831717Grassian,VickiA Focus on NanoparticulateAerosol andAtmospherically ProcessedNanoparticulateAerosolUniversity of Iowa2004$350,000RD831712Holden,PatriciaTransformations of Biologically ConjugatedCdSe QuantumDotsReleased Into Water andBiofilmsUniversity ofCalifornia, SantaBarbara2004$343,853RD831721Huang,Chin-paoShort-TermChronic Toxicity of PhotocatalyticNanoparticles to Bacteria, Algae, andZooplanktonUniversity ofDelaware2004$349,876RD831719Hurt,RobertPhysicaland Chemical DeterminantsofNanofiber/Nanotube ToxicityBrown University2004$350,000Monteiro-Riviere,North CarolinaStateRD831715NancyEvaluated Nanoparticle InteractionswithSkinUniversity2004$340,596RD831714Pinkerton,KentHealthEffects of InhaledNanomaterialsUniversity ofCalifornia, Davis2004$349,998RD831718Tomson,MasonAbsorption and Release ofContaminants ontoEngineered NanoparticlesRiceUniversity2004$348,747RD832531Turco,RonaldRepercussionof CarbonBased ManufacturedNanoparticles on MicrobialProcesses inEnvironmental SystemsPurdueUniversity2004$350,000RD831723Veranth,JohnResponses ofLung Cells toMetals inManufacturedNanoparticlesUniversity of Utah2004$344,748RD831713Westerhoff,PaulThe Fate, Transport, Transformation andToxicity of Manufactured Nanomaterials inDrinkingWaterArizona StateUniversity2004$349,881GR832225\Zhang,Wei-xianTransformation of Halogenated PBTswithNanoscale Bimetallic ParticlesLehighUniversity2004$325,000William Marsh RiceRD832534Alvarez, PedroMicrobial Impacts of EngineeredNanoparticlesUniversity2005$375,000117EPA Nanotechnology White PaperGrant #PrincipalInvestigator (PI)TitleInstitutionYearAmountRD832531Asgharian,BahmanMechanisticDosimetry Models of NanomaterialDepositionintheRespiratory TractCIIT CentersforHealth Research2005$375,000RD832532Bakshi,BhavikEvaluating the Impactsof Nanomanufacturingvia Thermodynamic and LifeCycle AnalysisOhio State University2005$375,000Barber, DavidUptake and Toxicity of Metallic NanoparticlesinFreshwater FishUniversity of Florida2005NSFRD832530Bertsch,PaulThe Bioavailability, Toxicity, and TrophicTransferof Manufactured ZnO2Nanoparticles:A View from the BottomUniversity of Georgia2005$363,680RD832635Bonzongo, JeanClaudeAssessment of the Environmental Impacts ofNanotechnology on Organisms andEcosystemsUniversity of Florida2005$375,000RD832536Colvin,VickiStructure-Function Relationships in EngineeredNanomaterial ToxicityWilliam Marsh RiceUnibersity2005$375,000Cunningham,MaryJaneGene Expression Profiling ofSingle-WalledCarbonNanotubes: A Unique SafetyAssessment ApproachHouston AdvancedResearchCenter2005NSFRD832525Diallo,MamadouCellular Uptake and Toxicity of DendriticNanomaterials: An Integrated Physicochemicaland Toxicogenomics StudyCalifornia Institute ofTechnology2005$375,000GR832382Gawley, RobertNanosensors for Detectionof SaxitoxinUniversity ofArkansas2005$340,000RD832528Gordon,TerryRole of Particle Agglomeration in NanoparticleToxicityNew YorkUniversitySchool of Medicine2005$375,000GR832371Heiden, PatriciaA Novel Approach to Prevent Biocide LeachingMichiganTechnologicalUniversity2005$333,130RD832529Kibbey,TohrenHysteretic Accumulation and Release ofNanomaterials in the Vadose ZoneUniversity ofOklahoma2005$375,000RD832526Kim,JaehongFate and Transformation ofC60 Nanoparticlesin Water Treatment ProcessesGeorgia Institute ofTechnology2005$375,000GR832372Kit,KevinNanostructuredMembranesforFiltration,Disinfectionand Remediation of Aqueous andGaseous SystemsUniversity ofTennessee2005$349,200118EPA Nanotechnology White PaperGrant #PrincipalInvestigator (PI)TitleInstitutionYearAmountGR832374Lu,YunfengNovel NanostructuredCatalysts forEnvironmental Remediation of ChlorinatedCompoundsTulaneUniversity2005$320,000Marr, LinseyCross-Media EnvironmentalTransport,Transformation, and Fateof ManufacturedCarbonaceous NanomaterialsVirginia PolytechnicInstitute andStateUniversity2005NSFRD832527McDonald,JacobChemical Fate, Biopersistence, and Toxicologyof Inhaled Metal Oxide Nanoscale MaterialsLovelace Biomedical& EnvironmentalResearch Institute2005$375,000GR832375Mulchandani,AshokConducting-Polymer Nanowire ImmunosensorArraysfor Microbial PathogensUniversity ofCalifornia, Riverside2005$320,000R01OH8806O'Shaughnessy,PatrickAssessment Methods forNanoparticles in theWorkplaceUniversity of Iowa2005NIOSHRD832535Pennell,KurtFate and Transport of C60Nanomaterials inUnsaturatedand Saturated SoilsGeorgia Institute ofTechnology2005$375,000RD832537Perrotta,PeterEffects of NanomaterialsonHuman BloodCoagulationWest VirginiaUniversity2005$375,000RD832533Theodorakis,ChrisAcute andDevelopmentalToxicity of MetalOxide Nanoparticlesto Fish and FrogsSouthern IllinoisUniversity2005$375,000R01OH8807Xiong,JudyMonitoring and Characterizing AirborneCarbonNanotube ParticlesNew YorkUniversitySchool of Medicine2005NIOSHGR832373Zhao,DongyeSynthesis andApplication of a NewClass ofStabilized NanoscaleIron Particlesfor RapidDestructionof ChlorinatedHydrocarbonsinSoiland GroundwaterAuburnUniversity2005$280,215TotalEPA$22,613,34370 TOTAL -65 STAR, 3 NSF, 2 NIOSH119 EPA Nanotechnology White Paper



## Appendix E: List of Nanotechnolo gy Whit e P a per Ext ern al Peer Reviewers and their Affiliations

Pratim Biswas, Ph.D. Departm e nts of Che m ical and Civil Engineering Environm ental Engineering Science Program Washington University in St. Louis

Richard A. Denison, Ph.D. Senior Scientist Environm ental Defense

Rebecca D. Klaper, Ph. D

. Great Lakes W A TER Institu te University of W i sconsin, Milwaukee

Igor Linkov, Ph.D. Senior Scientist Ca m b ridge Environm ental Inc Current Af f ilia tion: Man a ging Scien t ist, INTERTOX, Inc.

Andrew D. Maynard, P h.D. Chief Science Advisor Project on Em erging Na notechnologies Woodrow W ilson International Center for Scholars

Vladam ir V. Murashov, Ph.D. Special Ass i stant to the Directo r National Ins titu te f o r Oc cupation a l S a f ety and Health

Stephen S. Olin, Ph.D. Deputy Director International Life Sciences In stitute (ILSI) Research Foundation

Jennifer B. Sass, Ph.D. Senior Scientist, Health and Environm ent Natural Resources Defense Council

Donald A. Tom a lia, Ph.D. Presiden t & Chief Technical Officer Dendritic Nanotechnologies, Inc.

Nigel J. W a lker, Ph.D. National Ins titu te of Environm ental Health Scie nces National Ins titu tes of Health120 EPA Nanotechnology White Paper

David B. Warheit, Ph.D Senior Research Toxicologi st, Inhalation Toxicology E.I. du Pont de Ne m ours & Co., Inc. Haskell Lab o ratoryPRESOR TED ST ANDARD POST AGE & FEES P AID EP A PERMIT NO. G-35

O f fi c e o f t h e S c i e n c e A d v i s o r ( 8 1 0 5 R ) W a s h i n g t o n , D C 2 0 4 6 0

O f fi c i a l B u s i n e s s P e n a l t y f o r P r i v a t e U s e $ 3 0 0