State of the Science Literature Review: Everything Nanosilver and More

Scientific, Technical, Research,
Engineering and Modeling Support
Final Report

State of the Science
Literature Review:
Everything Nanosilver and More

R E S E A R C H A N D D E V E L O P M E N T

EPA/600/R-10/084
August 2010 www.epa.gov

Scientific, Technical, Research, Engineering and Modeling Support
Final Report

Contract No. EP-C-05-057
Task Order No. 95

State of the Science
Literature Review:
Everything Nanosilver and More

Prepared for

Katrina Varner, Task Order Manager

U.S. Environmental Protection Agency National Exposure Research Laboratory
Environmental Sciences Division
Las Vegas, NV

Submitted by

Jessica Sanford, Task Order Leader, Battelle
Raghuraman Venkatapathy, Project Manager, Pegasus

Prepared by

Amro El-Badawy David Feldhake
Raghuraman Venkatapathy

Although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy. Mention of trade names and commercial products does not constitute endorsement or recommendation for use.

U.S. Environmental Protection Agency Office of Research and Development
Washington, DC 20460

TABLE OF CONTENTS ꢀ
List of Figures............................................................................................................................... iiiꢀꢀ List of Tables................................................................................................................................. vꢀꢀ List of Abbreviations ................................................................................................................... viꢀꢀ Executive Summary.................................................................................................................... xiiꢀꢀ 1. Introduction............................................................................................................................... 1ꢀꢀ 2. Historical and Current Applications of Silver and Silver Nanomaterials........................... 5ꢀꢀ

2.1 Elemental Silver Characteristics and Sources....................................................................... 5 ꢀ 2.2 Chemistry of elemental silver............................................................................................... 5ꢀꢀ 2.3 Historical and Current Applications of Elemental Silver and Silver compounds ................ 7 ꢀ 2.4 Nanosilver: History and Applications................................................................................. 10 ꢀ 2.5 Silver Regulations in the US............................................................................................... 11 ꢀ

3. Uses of Silver Nanomaterials ................................................................................................. 14 ꢀ ꢀ

3.1 Properties of nanosilver ...................................................................................................... 14 ꢀ
3.1.1 Antibacterial properties................................................................................................ 14 ꢀ
3.1.1.1 Antibacterial mode of action................................................................................. 15 ꢀ
3.1.2 Antifungal properties ................................................................................................... 16 ꢀ 3.1.3 Antiviral properties...................................................................................................... 17 ꢀ 3.1.4 Anti-inflammatory properties ...................................................................................... 17 ꢀ 3.1.5 Anti-glycoprotein film properties ................................................................................ 17 ꢀ 3.1.6 Anti-biofilm properties ................................................................................................ 18ꢀꢀ 3.1.7 Surface plasmon resonance properties......................................................................... 18 ꢀ 3.1.8 Plasmonic heating properties....................................................................................... 18 ꢀ 3.1.9 Metal-enhanced fluorescence properties...................................................................... 19 ꢀ 3.1.10 Properties of silver nanomaterials that promote its biosynthesis............................... 19 ꢀ
3.2 Scientific Applications........................................................................................................ 20 ꢀ 3.3 Industrial Applications........................................................................................................ 21 ꢀ
3.3.1 Catalysis....................................................................................................................... 21 ꢀ 3.3.2 Electronics.................................................................................................................... 22 ꢀ 3.3.3 Other Industrial Applications....................................................................................... 22 ꢀ
3.4 Applications in Consumer Products.................................................................................... 22 ꢀ 3.5 Medical Applications.......................................................................................................... 23 ꢀ 3.6 Proposed and Projected Applications ................................................................................. 24 ꢀ

4. Synthesis and Properties of Silver Nanomaterials............................................................... 27ꢀꢀ

4.1 Methods of Synthesis.......................................................................................................... 27 ꢀ
4.1.1 Synthesis Categories.................................................................................................... 27 ꢀ
4.1.1.1 Top-Down versus Bottom-Up............................................................................... 28 ꢀ 4.1.1.2 Synthesis Reactants in Bottom-Up Techniques.................................................... 30 ꢀ
4.1.2 General Discussion on Nanosilver Synthesis .............................................................. 32 ꢀ
4.2 Silver Nanocomposites and Bimetallic Nanoparticles........................................................ 35 ꢀ

Final Report dated 07/15/2010

State of the Science – Everything Nanosilver and More

iꢀꢀ

4.3 Environmental Perspective ................................................................................................. 35 ꢀ 4.4 Characteristics of the Silver Nanomaterials Products......................................................... 37 ꢀ 4.5 Characterization Methods, Detection and Speciation......................................................... 54 ꢀ
4.5.1 Methods for Measuring Ionic Silver in Nanosilver Suspensions................................. 56 ꢀ 4.5.2 Methods for Isolating Ionic Silver from Nanosilver Suspensions............................... 56 ꢀ 4.5.3 Novel Detection and Characterization Techniques for Environmental Samples......... 57 ꢀ

5. Potential Magnitude of Silver Nanomaterial Utilization and Environmental Exposure . 67ꢀꢀ

5.1 Inventory of Silver Nanomaterials: Industrial and consumer products .............................. 68 ꢀ 5.2 Routes of Release and Exposure, Ecological...................................................................... 72 ꢀ 5.3 Routes of Exposure, Human ............................................................................................... 77 ꢀ
5.3.1 Exposure via food ........................................................................................................ 80 ꢀ 5.3.2 Exposure via consumer products ................................................................................. 83 ꢀ 5.3.3 Exposure via Medical Applications............................................................................. 88 ꢀ 5.3.4 Exposure via occupation.............................................................................................. 92 ꢀ
5.4 Projected Quantities, Geographic and Demographic Distribution in the US ..................... 94 ꢀ

6. Toxicity and Health Effects.................................................................................................... 98ꢀꢀ

6.1 Silver Toxicity .................................................................................................................... 98 ꢀ 6.2 Nanosilver Toxicity .......................................................................................................... 100 ꢀ
6.2.1 Toxicity of Nanosilver to Organisms......................................................................... 102 ꢀ 6.2.2 Ecological or Multispecies Studies of Nanosilver Toxicity ...................................... 105 ꢀ 6.2.3 Studies Concerning Human Health Including Mammalian Models.......................... 109 ꢀ
6.2.3.1 Respiratory Tract Toxicity.................................................................................. 113 ꢀ 6.2.3.2 Neuronal Uptake................................................................................................. 118 ꢀ 6.2.3.3 Dermal Toxicity.................................................................................................. 118 ꢀ 6.2.3.4 Gastrointestinal Tract Toxicity ........................................................................... 120 ꢀ 6.2.3.5 Other Organ Toxicity.......................................................................................... 121 ꢀ
6.2.3.5.1 Kidney Toxicity ........................................................................................... 122 ꢀ 6.2.3.5.2 Liver Toxicity .............................................................................................. 123 ꢀ 6.2.3.5.3 Immune system Toxicity.............................................................................. 123 ꢀ 6.2.3.5.4 Other blood effects....................................................................................... 124 ꢀ 6.2.3.5.5 Reproductive system Toxicity ..................................................................... 125 ꢀ 6.2.3.5.6 Genotoxicity, carcinogenicity...................................................................... 125 ꢀ
6.2.4 Cell Culture Nanosilver Toxicity............................................................................... 125 ꢀ
6.3 Conclusions on Nanosilver Toxicity................................................................................. 131 ꢀ

7. Life Cycle Analysis for Comprehensive Environmental Assessment .............................. 134ꢀꢀ

7.1 Nanosilver life cycle assessment ...................................................................................... 136 ꢀ 7.2 Nanosilver comprehensive environmental assessment..................................................... 145 ꢀ

8. Data Gaps .............................................................................................................................. 147ꢀꢀ 9. Bibliography.......................................................................................................................... 150ꢀꢀ Appendix A – List of US Companies Producing Nanosilver Containing Compounds....... 198 ꢀ Appendix B – Woodrow Wilson Database Containing Nanosilver Products...................... 207 ꢀ Appendix C – List of Companies Producing Raw Nanosilver in the US............................. 355 ꢀ

ii

List of Figures

Figure 2.1: Nanomaterials dimensions on the metric scale (in nm)............................................. 11ꢀꢀ Figure 2.2: Analysis of FIFRA registered products containing nanosilver for the period 1950- 2010............................................................................................................................................... 12ꢀꢀ Figure 4.1: Top-down and Bottom-up synthesis approaches....................................................... 30ꢀꢀ Figure 4.2: Schematic for an organometallic approach of synthesis of silver nanoparticles....... 34ꢀꢀ Figure 4.3: Schematic of a spinning disc processor for synthesis of silver nanoparticles........... 36ꢀꢀ Figure 4.4: Characterization of silver nanoparticle size and morphology with scanning electron ꢀ microscopy (SEM)........................................................................................................................ 38ꢀꢀ Figure 4.5: Schematic diagram of the Electrospray-Scanning Mobility Particle Sizer (ES-SMPS) ꢀ system ........................................................................................................................................... 58ꢀꢀ Figure 4.6: Cross section of a small part of the FlFFF channel................................................... 59ꢀꢀ Figure 5.1: Forms of nanosilver incorporated in consumer products. ......................................... 69ꢀꢀ Figure 5.2: Categories of nanosilver-containing products........................................................... 70ꢀꢀ Figure 5.3: Overview of silver flows triggered by biocidal plastics and textiles......................... 75ꢀꢀ Figure 5.4: Process simulated in the model developed by Blaser et al. (2008) ........................... 76ꢀꢀ Figure 5.5: Routes of exposure, uptake, distribution, and degradation of nanomaterials in the ꢀ environment .................................................................................................................................. 78ꢀꢀ Figure 5.6: Fresh Box, manufactured by FinePolymer, Inc. (South Korea), is a nanosilver ꢀ antimicrobial food container......................................................................................................... 81ꢀꢀ Figure 5.7: The Nano Tea Pot – Aroma manufactured by Top Nano Technology Co., Ltd ꢀ (Taiwan)........................................................................................................................................ 81ꢀꢀ Figure 5.8: Samsung’s Silver Wash washing machine................................................................ 85ꢀꢀ Figure 5.9: Illustration showing production flow process and measurement locations in the ꢀ Korean silver nanoparticle manufacturing facility ....................................................................... 88ꢀꢀ Figure 5.10: Anti-microbial burn dressing manufactured by Anson Nano-Biotechnology ꢀ (Zhuhai) Co., Ltd., China.............................................................................................................. 91ꢀꢀ Figure 5.11: Conjuctival-corneal argyrosis in the craftsman occupationally exposed to silver .. 93ꢀꢀ Figure 5.12: Number of companies, universities, laboratories and/or organization working in ꢀ nanotechnology across the US...................................................................................................... 95ꢀꢀ Figure 5.13: Nanosilver flows during high emission scenarios................................................... 96ꢀꢀ Figure 6.1: Systemic argyria of the skin from ingestion of colloidal silver................................. 99ꢀꢀ Figure 6.2: HAADF image of an HIV-1 virus........................................................................... 104ꢀꢀ Figure 6.3: A schematic of the human body with pathways of exposure to nanoparticles........ 110ꢀꢀ Figure 6.4: Deposition of particles in the respiratory tract as a function of their size............... 114ꢀꢀ Figure 6.5: A simplified depiction of potential factors that may influence the effects of ꢀ engineered nanoparticles on the respiratory system ................................................................... 115ꢀꢀ Figure 6.6: The proposed mechanism of nanosilver toxicity based on the experimental data .. 131ꢀꢀ Figure 7.1: Comprehensive environmental assessment (CEA) ................................................. 136ꢀꢀ Figure 7.2: Choices associated with a nanotechnology throughout its life cycle as proposed by ꢀ Meyer et al. (2009)...................................................................................................................... 137ꢀꢀ Figure 7.3: Choices associated with a nanotechnology throughout its life cycle as proposed by ꢀ Gill (2007)................................................................................................................................... 138ꢀꢀ Figure 7.4: The Nanomaterial Database maintained by Nanowerk........................................... 142ꢀꢀ

iii
Figure 7.5: Quantified mass flows of silver triggered by the use of biocidal products and by other silver uses........................................................................................................................... 144 Figure 7.6: Nanosilver flows from the nanomaterial containing products to various environmental compartments...................................................................................................... 145

iv

List of Tables

Table 3.1: Emerging applications of nanosilver in medical products.......................................... 26 ꢀ Table 4.1: Description of Evidence for Silver Nanoparticle Synthesis for General Applications39 ꢀ Table 4.2: Description of Evidence for Silver Nanoparticles Synthesis for Specific Applicationsꢀꢀ ....................................................................................................................................................... 45 ꢀ Table 4.3: Description of Evidence for Silver Nanocomposites.................................................. 49 ꢀ Table 4.4: Description of Evidence for Bimetallic Silver Nanoparticles..................................... 51 ꢀ Table 4.5: List of Acronyms used in Tables 4.1 to 4.4 ................................................................ 52 ꢀ Table 4.6: Possible Conventional Characterization and Detection Techniques for Nanosilver .. 62 ꢀ Table 5.1: Main characteristics for human exposure to nanomaterials from food, consumer and ꢀ medical products........................................................................................................................... 78 ꢀ Table 5.2: Ranking of potential human exposures to nanosilver................................................. 79 ꢀ Table 5.3: Summary of applications of nanotechnology in the food production chain .............. 82 ꢀ Table 5.4: Product categories with examples of products containing nanosilver........................ 86 ꢀ Table 5.5: Medical devices containing nanosilver....................................................................... 90 ꢀ Table 5.6: Emerging applications of nanosilver in medical products.......................................... 91 ꢀ Table 5.7: Predicted environmental concentrations in Rhine River............................................. 96 ꢀ Table 7.1: Companies selling nanosilver as listed in the Nanowerk database........................... 139 ꢀ

v

List of Abbreviations ꢀ

-CN

Cyano group

-COOH -NH₂
Carboxyl Group Amine Group

-SH

Thiol Group

AAS

Atomic Absorption Spectroscopy

American Conference of Governmental Industrial Hygienists Atomic Force Microscopy Silver Isotopes
ACGIH AFM ¹⁰⁷Ag, ¹⁰⁹Ag

Ag

Elemental Silver

Ag⁺, Ag²⁺, Ag³⁺Ag₂O AgBr
Ionic Silver Silver Oxide Silver Bromide

AgCl

Silver Chloride

AgF

Silver Fluoride

AgI

Silver Iodide

AgNO₃AgCN AgN₃AgNP AgOH AgONC AgS
Silver Nitrate Silver Cyanide Complex Silver Azide Silver nanoparticle Silver Hydroxide Silver Fulminate Silver Sulfide

ALP

Alkaline Phosphatase

American Society for Testing and Materials Adenosine Triphosphate Agency for Toxic Substances and Disease Registry Gold
ASTM ATP ATSDR Au

BBB

Blood Brain Barrier

Before Christ

B.C.

BET

Brunauer-Emmett-Teller Analysis

vi

BPEI BSA
Branched Polyethyleneimine Bovine Serum Albumin

Ethyl Alcohol

C₂H₅OH

Ca

Calcium

CA

California

Cal/EPA CE
California Environmental Protection Agency Capillary Electrophoresis Comprehensive Environmental Assessment Chloride Ion
CEA Cl^-

cm

Centimeter

CNT CO
Carbon Nanotube Carbon Monoxide
CTAB Cu
Cetyltrimethylammonium Bromide Copper
Cu(NO₃)₂DI
Cupric Nitrate Deionized

DLS

Dynamic Light Scattering

Differential Mobility Analyzer N,N-Dimethyl Formamide Deoxyribonucleic Acid
DMA DMF DNA DOC DPR
Dissolved Organic Carbon Department of Pesticide Registration California Department of Toxic Substances Control