*3.4. Feature Selection Methods*

Feature selection, variable selection, or attribute selection plays an essential role in classification problems. It reduces the number of attributes by excluding the irrelevant and redundant ones to achieve the lower complexity model (see Figure 4). The more uncomplicated and faster models with fewer variables are desirable in machine learning models. Feature selection is an essential part of the machine learning process, leading to overfitting. Overfitting happens when the model learns details and noises made by too many variables, and then the model will not generalize well when presented with new data.

In this research, some feature selections, such as principal component analysis (PCA), particle swarm optimization (PSO), evolutionary search, genetic search, best-first search, and variance inflation factor (VIF), are used.


**1. Introduction**

184 Olive Oil – Constituents, Quality, Health Properties and Bioconversions

Spaniolas, S.; Bazakos, C.; Ntourou, T.; Bihmidine, S.; Georgousakis, A. & Kalaitzis, p.

Tena, N.; Lazzez, A.; Aparicio-Ruiz, R. & Garc´a-Gonz\_alez, D. L. (2007). Volatile

Torres VazFreire, L.; Gomes da Silva, M. D. R. & Costa Freitas, A. M. (2009). Comprehensive

Vos, P.; Hogers, R.; Bleeker, M.; Reijans, M.; Van de Lee, T.; Hornes, M.; Frijters, A.; Pot, J.;

Weissbein, S.( 2006). *Characterization of new olive (Olea europea L.) varieties response to irrigation*

Wiesman, Z. (2009). *Desert Olive oil Cultivation: Advanced Biotechnologies* (first edition),

Williams, J.G.; Kubelik, A.R.; Livak, K.J.; Rafalski, J.A. & Tingey, S.V. (1990). DNA

Zietkiewicz, E.; Rafalski, A. & Labuda, D. (1994). Genome fingerprinting by simple sequence

Wu, S.; Collins, G. & Sedgley, M. (2004). A molecular linkage map of olive (Olea europaea L.) based on RAPD, microsatellite, and SCAR markers, *Genome*. Vol.47, pp. 26–35

storage, *Eue food Res Technol*. Vol. 227, 175-179

*Food Chem. Vol.*55, pp. 7852–7858

profile, *Sci. Hortic.* Vol.118, pp. 139–148

*Nucleic Acids Res*. Vol.18, pp. 6531–6535

Negev, Israel

374257-5

pp. 176–183

fingerprinting, *Nucl. Acids Res.* Vol.23, pp. 4407–4414

(2008b). Use of lambda DNA as a marker to assess DNA stability in olive oil during

compounds characterizing Tunisian Chemlali and Chetouivirgin *olive oil*s, *J. Agric.*

two-dimensional gas chromatography for fingerprint pattern recognition in *olive oil*s produced by two different techniques in Portuguese olive varieties Galega Vulgar, Cobrancosa and Carrasquenha, *Anal. Chim. Acta.* Vol.633, pp. 263–270 Tura, D.; Failla, O.; Bassi, D.; Pedo, S. & Serraiocco, A. (2008) Cultivar influence on virgin

olive (Olea europaea L.) oil flavor based on aromatic compounds and sensorial

Peleman, J.; Kuiper, M.; & Zabeu, M. (1995). AFLP: a new technique for DNA

*with saline water in the Ramat Negev area*. Master thesis. Ben-Gurion University of the

Elsevier Inc.; printed and bounded in United States of America, ISBN: 978-0-12-

polymorphisms amplified by arbitrary primers are useful as genetic markers,

repeat (SSR)-anchored polymerase chain reaction amplification, *Genomics.* Vol.20,

Olive oil is the oil extracted exclusively from the fruit of *Olea europea* L. only by means of mechanical methods or other physical procedures that do not cause any alteration of the glyceric structure of the oil thus preserving its characteristic properties. Olive oil is a highly appreciated edible oil, which is an important component of the Mediterranean diet, and is recognized for its potential health benefits.

The International Olive Council (IOC) establishes the definitions and classes of olive oils, based on methods of production and the free acidity of the oil, as well as the trade standard for their commercialization (International Olive Council, 2011). Much analytical work has been done on the authentication and quality assessment of this high added value agricultural product, as well as on the detection of its adulteration for both economic and health considerations (Frankel, 2010; Guillen & Ruiz, 2001). However, these issues continue to be major analytical challenges. In this context, the European Commission launched the TRACE project (http://www.trace.eu.org/) through the Sixth Framework Program under the Food Quality and Safety Priority with the aim of providing reliable analytical strategies to address this kind of problem.

This chapter reports research work on the use of 1H-NMR fingerprinting, combined with pattern recognition techniques, for the quality assessment of olive oil. Two major issues have been studied, the geographical origin of virgin olive oil (VOO) and the stability of VOO at room temperature.

\* Corresponding Author

The information contained in this chapter reflects the authors' views; the European Commission is not liable for any use of the information contained herein.

Quality Assessment of Olive Oil by 1

origin at the national, regional and/or PDO level.

**1.2 Stability of virgin olive oil**

Ruiz, 2001).

H-NMR Fingerprinting 187

statistical analysis have been used to distinguish olive oils from different types, botanical, geographical origins and pedoclimatic conditions.  PDO olive oils were distinguished using physicochemical parameters of the oils and chemometric class-modeling tools (Federico Marini et al., 2006), sensory parameters and fatty acid profiles of the oils (Ollivier et al., 2006), or the oil sterol composition (Alves et al., 2005). IRMS measurements of the alcohol and sterol fractions of olive oil also proved to be useful for its geographical characterization (Angerosa et al., 1999).  These types of techniques are particularly attractive since they are non selective, require little or no sample pre-treatment; use small amounts of organic solvents or reagents; and the analysis takes only a few minutes per sample. Chemometric analysis of NIR spectra of virgin olive oils allow us to determine its composition and geographical origin (Galtier et al., 2007). 1H, 13C and/or 31P-NMR analysis of the bulk oil (Rosa M. Alonso-Salces et al., 2010b; Rosa M. Alonso-Salces et al., 2011b; Mannina et al., 2010; Petrakis et al., 2008; Rezzi et al., 2005) or the unsaponifiable fraction of olive oil (R. M. Alonso-Salces et al., 2010), in combination with multivariate techniques, have been used to distinguish VOOs from certain geographical origins. In section 3.2., the achievements of 1H-NMR fingerprinting and chemometrics for the geographical characterization of VOO is reported. 1H-NMR fingerprints of a statistically significant number of authentic VOOs from seven countries, namely Italy, Spain, Greece, France, Turkey, Cyprus and Syria and from three different harvests (2004/05, 2005/06 and 2006/07) were analyzed by pattern recognition and classification techniques, such as principal component analysis (PCA), linear discriminant analysis (LDA) and partial least square discriminant analysis (PLS-DA), to evaluate the best approach to identify the geographical

Another matter of major concern regarding the quality of edible oils is their oxidation, not only from the technological and economic point of view but also for safety reasons, due to the undesirable properties of some compounds produced during this process (Guillen &

The high resistance to oxidative deterioration of VOO is due to both its triglyceride composition, which is low in polyunsaturated fatty acids, and its antioxidant constituents, i.e. polyphenols and tocopherols. The oxidative stability of VOO has been evaluated by

#### **1.1 Geographical origin of virgin olive oil**

At present, 75% of the global production of olive oil takes place in the Mediterranean basin, mainly in Spain, Italy and Greece (International Olive Council, 2011). VOO is permitted to be marketed under a Protected Designation of Origin (PDO), Protected Geographical Indication (PGI), or Traditional Specialty Guaranteed (TSG) label, on the basis of its area and method of production [Council Regulations (EC) No 510/2006 and No 509/2006]. In this context, the characterization of the geographical origin of VOO is becoming increasingly important. According to the EU definition, PDO products are most closely linked to the concept of *terroir* — a sense of place discernible in the flavor of the food. PDO products must be produced, processed and prepared in a specific region using traditional production methods. The raw materials must also be from the defined area whose name the product bears. The quality or characteristics of the product must be due essentially or exclusively to its place of origin, i.e., climate, the nature of the soil and local know-how. Food products with a PGI status must have a geographical link in at least one of the stages of production, processing or preparation. The European Commission has already registered in the "Register of protected designations of origin and protected geographical indications" 86 PDO and 15 PGI olive oils, produced in Italy, Greece, Spain, France, Portugal and Slovenia. As can be expected, given the financial benefits associated with these prestigious labels, it is very likely that economic fraud occurs (e.g. labeling a non-PDO product as a PDO one or adulteration with olive oils that do not fulfill the PDO requirements).

Another fraudulent practice is the mislabeling of the geographical origin of olive oils. The EU established new labeling rules that make origin labeling compulsory for virgin and extra virgin labeled olive oil [Commission Regulation (EC) No 182/2009]. So, oil produced from olives from just one EU Member State or third country has to be labeled with the name of the country of origin. VOO produced from olives from more than one EU Member State has to be labeled as a 'blend of Community olive oils', while oil produced using olives from outside the EU would be labeled as a 'blend of non-Community olive oils' or 'blend of Community and non-Community olive oils', or a reference to the EU and/or third countries of origin. Therefore, analytical methods are urgently needed to guarantee the authenticity and traceability of PDO and PGI olive oils, as well as the country of provenance, to help prevent illicit practices in this sector, and to support the antifraud authorities dealing with these issues.

VOO is made up of triglycerides (more than 98%) and minor components (about 1-2%) such as squalene, -tocopherol, phytosterols, phenolic compounds, carotenoids, and aliphatic and terpenic alcohols, which constitute the unsaponifiable fraction of the oil (Bortolomeazzi et al., 2001; Harwood & Aparicio, 2000). The chemical composition of this fraction may vary both qualitatively and quantitatively depending on vegetal species, climatic conditions, extraction and refining procedures and storage conditions (Canabate-Diaz et al., 2007; Harwood & Aparicio, 2000), which also greatly influence the organoleptic quality and stability of the oil. The diversity and interdependence between all these factors makes it highly unlikely that these influences would be the same in different regions. Hence, the geographical characterization of VOO addresses all these agronomic, pedoclimatic and botanical aspects which are unique to the oil of each origin (Aparicio et al., 1994).

A considerable number of sensorial (Pardo et al., 2007), physical (F. Marini et al., 2004; Federico Marini et al., 2006) and chemical (Aguilera et al., 2005; Boggia et al., 2002; Lanteri et al., 2002; Federico Marini et al., 2006; Federico Marini et al., 2007) approaches combined with

At present, 75% of the global production of olive oil takes place in the Mediterranean basin, mainly in Spain, Italy and Greece (International Olive Council, 2011). VOO is permitted to be marketed under a Protected Designation of Origin (PDO), Protected Geographical Indication (PGI), or Traditional Specialty Guaranteed (TSG) label, on the basis of its area and method of production [Council Regulations (EC) No 510/2006 and No 509/2006]. In this context, the characterization of the geographical origin of VOO is becoming increasingly important. According to the EU definition, PDO products are most closely linked to the concept of *terroir* — a sense of place discernible in the flavor of the food. PDO products must be produced, processed and prepared in a specific region using traditional production methods. The raw materials must also be from the defined area whose name the product bears. The quality or characteristics of the product must be due essentially or exclusively to its place of origin, i.e., climate, the nature of the soil and local know-how. Food products with a PGI status must have a geographical link in at least one of the stages of production, processing or preparation. The European Commission has already registered in the "Register of protected designations of origin and protected geographical indications" 86 PDO and 15 PGI olive oils, produced in Italy, Greece, Spain, France, Portugal and Slovenia. As can be expected, given the financial benefits associated with these prestigious labels, it is very likely that economic fraud occurs (e.g. labeling a non-PDO product as a PDO one or

Another fraudulent practice is the mislabeling of the geographical origin of olive oils. The EU established new labeling rules that make origin labeling compulsory for virgin and extra virgin labeled olive oil [Commission Regulation (EC) No 182/2009]. So, oil produced from olives from just one EU Member State or third country has to be labeled with the name of the country of origin. VOO produced from olives from more than one EU Member State has to be labeled as a 'blend of Community olive oils', while oil produced using olives from outside the EU would be labeled as a 'blend of non-Community olive oils' or 'blend of Community and non-Community olive oils', or a reference to the EU and/or third countries of origin. Therefore, analytical methods are urgently needed to guarantee the authenticity and traceability of PDO and PGI olive oils, as well as the country of provenance, to help prevent illicit practices in this sector, and to support the antifraud authorities dealing with these issues. VOO is made up of triglycerides (more than 98%) and minor components (about 1-2%) such as squalene, -tocopherol, phytosterols, phenolic compounds, carotenoids, and aliphatic and terpenic alcohols, which constitute the unsaponifiable fraction of the oil (Bortolomeazzi et al., 2001; Harwood & Aparicio, 2000). The chemical composition of this fraction may vary both qualitatively and quantitatively depending on vegetal species, climatic conditions, extraction and refining procedures and storage conditions (Canabate-Diaz et al., 2007; Harwood & Aparicio, 2000), which also greatly influence the organoleptic quality and stability of the oil. The diversity and interdependence between all these factors makes it highly unlikely that these influences would be the same in different regions. Hence, the geographical characterization of VOO addresses all these agronomic, pedoclimatic and

botanical aspects which are unique to the oil of each origin (Aparicio et al., 1994).

A considerable number of sensorial (Pardo et al., 2007), physical (F. Marini et al., 2004; Federico Marini et al., 2006) and chemical (Aguilera et al., 2005; Boggia et al., 2002; Lanteri et al., 2002; Federico Marini et al., 2006; Federico Marini et al., 2007) approaches combined with

adulteration with olive oils that do not fulfill the PDO requirements).

**1.1 Geographical origin of virgin olive oil**

statistical analysis have been used to distinguish olive oils from different types, botanical, geographical origins and pedoclimatic conditions.  PDO olive oils were distinguished using physicochemical parameters of the oils and chemometric class-modeling tools (Federico Marini et al., 2006), sensory parameters and fatty acid profiles of the oils (Ollivier et al., 2006), or the oil sterol composition (Alves et al., 2005). IRMS measurements of the alcohol and sterol fractions of olive oil also proved to be useful for its geographical characterization (Angerosa et al., 1999).

 These types of techniques are particularly attractive since they are non selective, require little or no sample pre-treatment; use small amounts of organic solvents or reagents; and the analysis takes only a few minutes per sample. Chemometric analysis of NIR spectra of virgin olive oils allow us to determine its composition and geographical origin (Galtier et al., 2007). 1H, 13C and/or 31P-NMR analysis of the bulk oil (Rosa M. Alonso-Salces et al., 2010b; Rosa M. Alonso-Salces et al., 2011b; Mannina et al., 2010; Petrakis et al., 2008; Rezzi et al., 2005) or the unsaponifiable fraction of olive oil (R. M. Alonso-Salces et al., 2010), in combination with multivariate techniques, have been used to distinguish VOOs from certain geographical origins. In section 3.2., the achievements of 1H-NMR fingerprinting and chemometrics for the geographical characterization of VOO is reported. 1H-NMR fingerprints of a statistically significant number of authentic VOOs from seven countries, namely Italy, Spain, Greece, France, Turkey, Cyprus and Syria and from three different harvests (2004/05, 2005/06 and 2006/07) were analyzed by pattern recognition and classification techniques, such as principal component analysis (PCA), linear discriminant analysis (LDA) and partial least square discriminant analysis (PLS-DA), to evaluate the best approach to identify the geographical origin at the national, regional and/or PDO level.

#### **1.2 Stability of virgin olive oil**

Another matter of major concern regarding the quality of edible oils is their oxidation, not only from the technological and economic point of view but also for safety reasons, due to the undesirable properties of some compounds produced during this process (Guillen & Ruiz, 2001).

The high resistance to oxidative deterioration of VOO is due to both its triglyceride composition, which is low in polyunsaturated fatty acids, and its antioxidant constituents, i.e. polyphenols and tocopherols. The oxidative stability of VOO has been evaluated by

Quality Assessment of Olive Oil by 1

**2.1 Chemicals and plant material**

Chemie (Steinheim, Germany).

**2. Experimental**

**2.2 NMR analysis**

H-NMR Fingerprinting 189

Deuterated chloroform for NMR analysis (99.8 atom %D) was provided by Sigma-Aldrich

Virgin olive oils (963 samples) from seven countries of the Mediterranean basin, namely Italy (661 VOOs), Spain (144 VOOs), Greece (97 VOOs), France (39 VOOs), Turkey (14 VOOs), Cyprus (6 VOOs) and Syria (2 VOOs), were collected directly from the producers (olive oil mills) from most of the main producing regions of these countries during three harvests (2004/05, 2005/06 and 2006/2007). The sample collection was carried out with the collaboration of Dipartimento di Chimica e Technologie Farmaceutiche ed Alimentari - Università degli Studi di Genova (Italia), Laboratorio Arbitral Agroalimentario (Ministry of Agriculture and Fishery, Spain), General Chemical State Laboratory D'xy Athinon (Greece), General State Laboratory (Ministry of Health, Cyprus), Departamento de Química Orgánica - Universidad de Córdoba (Spain), Istituto di Metodologie Chimiche - Laboratorio di Risonanza Magnetica Annalaura Segre – CNR (Italy), Fondazione Edmund Mach - Istituto San Michele all'Adige (Italy), and Eurofins Scientific Analytics (France), in the framework of the EU TRACE project. The true type (virgin or extra virgin) and origin of the olive oils at the national, regional and PDO level were assured. The Italian samples were representative of the olive oil producing areas, which are markedly influenced by

For the study of VOO stability, about a liter of VOO was divided into aliquots contained in dark glass 40mL-vials completely filled and kept at -20ºC in a freezer. Each month, over a period of more than 3 and half years (samples for the months 20th, 32nd, 38th and 42nd are missing), one vial was taken from the freezer and stored at room temperature (r.t.) in a closed box. A preliminary supposition was made; this considered that the degradation of VOO at -20ºC is not significant and thus the last aliquot taken out of the freezer was time 0. All aliquots were analyzed by 1H-NMR once the last sample was taken from the freezer.

Aliquots of 40 µL of each VOO were dissolved in 200 µL of deuterated chloroform, shaken in a vortex, and placed in a 2 mm NMR capillary. The 1H-NMR experiments were performed at 300K on a Bruker (Rheinstetten, Germany) Avance 500 (nominal frequency 500.13 MHz) equipped with a 2.5 mm broadband inverse probe. The spectra of the samples used for the study of the geographical origin of VOOs were recorded using a 7.5 µs pulse (90°), an acquisition time of 3.0 s (32k data points) and a total recycling time of 4.0 s, a spectral width of 5500 Hz (11 ppm), 64 scans (+ 4 dummy scans), with no sample rotation. The spectra of the samples used for the VOO stability study were recorded using a 6.7 µs pulse (90°), an acquisition time of 3.5 s (50k data points) and a total recycling time of 7.0 s, a spectral width of 7100 Hz (14 ppm), 32 scans (+ 4 dummy scans), with no sample rotation. Prior to Fourier transformation, the free induction decays (FIDs) were zero-filled to 64k and a 0.3 Hz linebroadening factor was applied. The chemical shifts are expressed in scale (ppm), referenced to the residual signal of chloroform (7.26 ppm) (Hoffman, 2006). The spectra were phase- and baseline-corrected manually, binned with 0.02 ppm-wide buckets, and normalized to total intensity over the region 4.10-4.26 ppm (glycerol signal).

Most of the studies on the oxidative stability of olive oil employed questionably hightemperatures which, unfortunately, cannot be considered reliable to predict the stability of olive oils at room temperature (Frankel, 2010), i.e. under normal storage conditions. This is due to the fact that the mechanism of lipid oxidation changes at the elevated temperatures at which these experiments were run. In this sense, the rate of lipid oxidation is independent of O2 pressure at ambient temperatures; whereas it does become dependent on O2 pressures at elevated temperatures due to the decrease in solubility of O2. This causes the O2 concentration to become a significant limiting factor that increases with the degree of oxidation. For this reason, in oxidative stability studies the use of several temperatures, in a range as low as practical, preferably at or below 60 ºC, is an important consideration. Moreover, polymerization and cyclization of PUFA, which mainly occurs at elevated temperatures, are not significant at room temperature. Furthermore, volatile acids that are measured by the Rancimat and OSI methods are produced only at elevated temperatures (Frankel, 2010). For all these reasons, the results of the studies on the oxidative stability of olive oil at high temperatures are neither relevant nor can be extrapolated to normal storage conditions at room temperature. Olive oil stability at room temperature is of great interest, for instance, to know its storage shelf-life. Because VOO is relatively stable to oxidation due to its particular chemical composition, there has been apparently little or no control of its stability under normal storage conditions in the past. To provide some knowledge on this issue, the stability of olive oil at room temperature while protected from light by 1H-NMR fingerprinting was studied (Alonso-Salces et al., 2011a). The 1H-NMR spectra of the VOO aliquots kept under these conditions, over a certain period of time, were analyzed by principal component analysis (PCA).


Corresponding Author

**1. Introduction**

**Nanosilver in Consumer Products –**

**Its Impact on the Eco-Product**

**Design for Public Health**

*1Department of Physics, MTSE Program, New Jersey Institute of Technology, NJ,*

K. W. Lem1,7 et al.\*

*7Nanobiz, LLC, NJ,*

*USA*

### **Waste Minimization for the Safe Use of Nanosilver in Consumer Products – Its Impact on the Eco-Product Design for Public Health**

K. W. Lem1,7 et al.\* *1Department of Physics, MTSE Program, New Jersey Institute of Technology, NJ, 7Nanobiz, LLC, NJ, USA*

#### **1. Introduction**

216 Public Health – Methodology, Environmental and Systems Issues

Xu, H.S., Roberts, N., Singleton, F.L., Attwell, R.W., Grimes, D.J. & Colwell, R.R. (1982).

Yaron, S. & Matthews, K. (2002). A Reverse Transcriptase-polymerase Chain Reaction Assay

Zimmerman, A.M., Rebarchik, D.M., Flowers, A.R., Williams, J.L. & Grimes, D.J. (2009).

*Microbiology*, Vol.49, No.4, (October 2009), pp. 478–483, ISSN 0266-8254

1982), pp. 313-323, ISSN: 0095-3628

1364-5072

Survival and Viability of Nonculturable *Escherichia coli* and *Vibrio cholerae* in the Estuarine and Marine Environment. *Microbial Ecology*, Vol.8, No.4, (December

for Detection of Viable *Escherichia coli* O157:H7: Investigation of Specific Target Genes. *Journal of Applied Microbiology*, Vol.92, No.4, (April 2002), pp. 633-640, ISSN

*Escherichia coli* Detection Using mTEC Agar and Fluorescent Antibody Direct Viable Counting on Coastal Recreational Water Samples. *Letters in Applied*

> Winslow (1920) has defined the meaning of public health as "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Thus, the focus of public health intervention is the improvement of health and quality of life through the prevention and treatment of disease, and promotion of healthy behaviors. Promotion of hand washing is a typical common public health practice to prevent the spread of "unwanted" diseases (Samuel et al., 2005).

> With the rapid increase on applications for nanoparticle silver, its potential impact on public health has become a critical issue. Nanosized silver can be made with different shapes such as particles, wires, and rods. Silver nanoparticles (AgNPs; many other names such as nanosilver (nAg) and colloidal silver) have already been used in everyday consumer

\* S-H. Hsu2, D. S. Lee3, Z. Iqbal4, S. Sund5, S. Curran6, C. Brumlik7, A. Choudhury7, D. S-G. Hu8, N. Chiu9, R. C. Lem10 and J. R. Haw11,#

*1 Department of Physics, MTSE Program, New Jersey Institute of Technology, NJ, USA,*

*2 Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan,*

*3 Department of Chemical Engineering, Chonbuk National University, Chonju, Korea,*

*4 Department of Chemistry and Environ Science, New Jersey Institute of Technology, NJ, USA,*

*5 Nygard Consulting, LLC, NJ, USA,*

*6 Boston Scientific, MA, USA,*

*7 Nanobiz, LLC, NJ, USA,*

*8 Dept of Mat Sci and Eng, National Taiwan University Science and Technology, Taipei, Taiwan,*

*9 UMDNJ-New Jersey Medical School, Newark, NJ, USA,*

*10 Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA,*

*11 Department of Materials Chemistry and Engineering, Konkuk University, Seoul, Korea.*

# Corresponding Author

Waste Minimization for the Safe Use of Nanosilver

applications in nanoproduct development and manufacture.

in Consumer Products – Its Impact on the Eco-Product Design for Public Health 219

Figure 1 gives a roadmap of top-down and bottom-up development of nanoproducts under a value chain of "material – properties – processing – structure – performance – applications". This roadmap helps to identify the unmet needs from materials to/from

Fig. 1. Top-Down and Bottom-Up Development [Lem et al., 2009; Brauer et al., 2009)]

(polishing and grinding) are used as physical methods to produce nanoparticles.

or personal care products.

and spin coating (Koecher et al., 2009).

Commercial AgNPs products are typically produced via a bottom-up process, while analysis of environmental impact by AgNPs products is a top-down process (Tolaymat et al., 2010).

In order to use nanosilver for different applications, various chemical and physical methods are used to synthesize the nanosilver. One of the best recent overviews is the U.S. EPA's report by EI-Badawy et al. (2010). Chemical methods usually require a silver salt precursor, a reducing agent (formaldehyde, glucose or hydrogen peroxide.), a solvent, a stabilizer and a capping agent. Silver nitrate is a commonly used precursor to produce silver nanoparticles (Mousa & Linhart, 2010). Alternatively, the wet/dry electroplating method (Yang et al, 2006), electric spark bombardment (Koecher et al., 2009), and other mechanical techniques

Fabrication of nanosilver in the nanofiber form is usually done by electro spinning techniques. Other methods are being explored in applications to wound dressing and textile

Coatings have been used to employ the antibacterial property of nanosilver in biomedical devices or electronic devices. The nanosilver coating techniques include technologies such as spraying , chemical vapor deposition, dipping, printing knife-coating, transfer coating,

products requiring broad spectrum antibiotic performance because of their enormous surface area and reactivity. Faunce & Watal (2010) recently analyzed international regulatory issues for medical and domestic use in the United States, European Union, United Kingdom, and Australia. They found that despite the numerous studies reported in recent decades, many scientists are still uncertain of its safety. Very recently, Powers (2010) showed positive that Ag+ and AgNPs are developmental neurotoxicants in vitro and in vivo. Therefore, there is a need to conduct a study to identify a global landscape of AgNPs, their products, and their manufacturers. A market-based intellectual property (IP) study has been conducted to examine the current global patent landscape of companies using AgNPs in their consumer product development and production from 1980 to 2010 (Lem et al., 2012). Information on materials, compositions, formulation, manufacturing processes, and ultimate application were extracted using a "two-stage" stage-gate process using the IP activity in the use of nanosilver in consumer products. The two stages studied were commercial and consumer products. In the first stage for AgNPs and AgNPs-based commercial products, Lem et al. (2012) reported that there were 7,422 patent families from January 1, 1980 to December 31, 2010. In the second stage for AgNPs-based consumer products, 932 patent families from January 1, 1980 for to December 31, 2010 were found.

Korea, China and the USA were found to be the major players in AgNPs and AgNPs-based commercial and consumer products. Korea has been the leader and consumer products containing nanosilver are even sold on the streets. Due to its enormous surface reactivity, nanosilver has already found utility in everyday products that require antibiotic performance, such as materials that contact food, textiles and fabrics, appliances, consumer products, children's toys, infant products, 'health' supplements, cosmetics and pharmaceuticals (Chaloupka et al., 2010). Thus, safety has become a potentially critical issue for companies that make products containing nanosilver. For product stewardship to their customers, suppliers must address environmental health and safety issues in terms of real risks, perceptual risks, and government regulation.

In this chapter, we evaluate consumer products containing nanosilver especially in Korea using an IP landscaping study. We examine the recent literature regarding the effect of silver and nanosilver on public health from a clinical medicine perspective. We then evaluate the concept of waste generation and waste minimization in the material life cycle. We examine the flow of silver and nanosilver in the life cycle of food metabolism to identify ways to minimize potential adverse effects of nanosilver and to provide concepts of ecoproducts to minimize exposure to nanosilver for public health. Coupling the recent literature and the IP landscaping study, together with Design for Lean Six Sigma – Green (DFLSS-G) and TRIZ, we demonstrate the concept of waste minimization by controlling the release of nanosilver (Lem et al., 2011; Liu JG et al., 2010) in eco-product design.

#### **2. Manufacturing commercial AgNPs products**

Nanoproducts can be produced in two ways: top-down or bottom-up. A top-down approach is essentially tearing down of a device to gain insight into its components, materials and compositions (e.g., ball milling). A bottom-up approach is the piecing together of materials to give rise to components and finally to build a device (e.g., chemical precipitation).

products requiring broad spectrum antibiotic performance because of their enormous surface area and reactivity. Faunce & Watal (2010) recently analyzed international regulatory issues for medical and domestic use in the United States, European Union, United Kingdom, and Australia. They found that despite the numerous studies reported in recent decades, many scientists are still uncertain of its safety. Very recently, Powers (2010) showed positive that Ag+ and AgNPs are developmental neurotoxicants in vitro and in vivo. Therefore, there is a need to conduct a study to identify a global landscape of AgNPs, their products, and their manufacturers. A market-based intellectual property (IP) study has been conducted to examine the current global patent landscape of companies using AgNPs in their consumer product development and production from 1980 to 2010 (Lem et al., 2012). Information on materials, compositions, formulation, manufacturing processes, and ultimate application were extracted using a "two-stage" stage-gate process using the IP activity in the use of nanosilver in consumer products. The two stages studied were commercial and consumer products. In the first stage for AgNPs and AgNPs-based commercial products, Lem et al. (2012) reported that there were 7,422 patent families from January 1, 1980 to December 31, 2010. In the second stage for AgNPs-based consumer products, 932 patent

Korea, China and the USA were found to be the major players in AgNPs and AgNPs-based commercial and consumer products. Korea has been the leader and consumer products containing nanosilver are even sold on the streets. Due to its enormous surface reactivity, nanosilver has already found utility in everyday products that require antibiotic performance, such as materials that contact food, textiles and fabrics, appliances, consumer products, children's toys, infant products, 'health' supplements, cosmetics and pharmaceuticals (Chaloupka et al., 2010). Thus, safety has become a potentially critical issue for companies that make products containing nanosilver. For product stewardship to their customers, suppliers must address environmental health and safety issues in terms of real

In this chapter, we evaluate consumer products containing nanosilver especially in Korea using an IP landscaping study. We examine the recent literature regarding the effect of silver and nanosilver on public health from a clinical medicine perspective. We then evaluate the concept of waste generation and waste minimization in the material life cycle. We examine the flow of silver and nanosilver in the life cycle of food metabolism to identify ways to minimize potential adverse effects of nanosilver and to provide concepts of ecoproducts to minimize exposure to nanosilver for public health. Coupling the recent literature and the IP landscaping study, together with Design for Lean Six Sigma – Green (DFLSS-G) and TRIZ, we demonstrate the concept of waste minimization by controlling the

Nanoproducts can be produced in two ways: top-down or bottom-up. A top-down approach is essentially tearing down of a device to gain insight into its components, materials and compositions (e.g., ball milling). A bottom-up approach is the piecing together of materials to give rise to components and finally to build a device (e.g., chemical

release of nanosilver (Lem et al., 2011; Liu JG et al., 2010) in eco-product design.

families from January 1, 1980 for to December 31, 2010 were found.

risks, perceptual risks, and government regulation.

**2. Manufacturing commercial AgNPs products**

precipitation).

Figure 1 gives a roadmap of top-down and bottom-up development of nanoproducts under a value chain of "material – properties – processing – structure – performance – applications". This roadmap helps to identify the unmet needs from materials to/from applications in nanoproduct development and manufacture.

Fig. 1. Top-Down and Bottom-Up Development [Lem et al., 2009; Brauer et al., 2009)]

Commercial AgNPs products are typically produced via a bottom-up process, while analysis of environmental impact by AgNPs products is a top-down process (Tolaymat et al., 2010).

In order to use nanosilver for different applications, various chemical and physical methods are used to synthesize the nanosilver. One of the best recent overviews is the U.S. EPA's report by EI-Badawy et al. (2010). Chemical methods usually require a silver salt precursor, a reducing agent (formaldehyde, glucose or hydrogen peroxide.), a solvent, a stabilizer and a capping agent. Silver nitrate is a commonly used precursor to produce silver nanoparticles (Mousa & Linhart, 2010). Alternatively, the wet/dry electroplating method (Yang et al, 2006), electric spark bombardment (Koecher et al., 2009), and other mechanical techniques (polishing and grinding) are used as physical methods to produce nanoparticles.

Fabrication of nanosilver in the nanofiber form is usually done by electro spinning techniques. Other methods are being explored in applications to wound dressing and textile or personal care products.

Coatings have been used to employ the antibacterial property of nanosilver in biomedical devices or electronic devices. The nanosilver coating techniques include technologies such as spraying , chemical vapor deposition, dipping, printing knife-coating, transfer coating, and spin coating (Koecher et al., 2009).

Waste Minimization for the Safe Use of Nanosilver

space of pharma and consumer goods patents.

1. Nanosilver size or percentage loading,

2. Nanosilver form or geometry, 3. Material composition, and 4. Application area and products.

1. Trace dose, less than 0.01 wt. %. 2. Low dose, 0.01 to 1.0 wt. %. 3. Medium dose, 1.0 to 10 wt. %. 4. High dose, greater than 10 wt. %.

on these applications:

publications were reviewed to distil information with respect to:

more than 70% of the application areas as shown in Figure 3.

in Consumer Products – Its Impact on the Eco-Product Design for Public Health 221

The details of the search methodology and results are not the subjects of this article. They have been reported recently by Lem et al. (2012). Figure 2 shows the countries researching AgNPs. Figure 2 shows that out of all the major patenting authorities, South Korea is leading with 2087 publications. The U.S. is second and China is third. These three countries have about 80% of the total patent publications. It is important to note that Chinese patent numbers are over-weighted by their Chinese Utility Model Patents that only protect the shape and/or structure of a product for 10 years and are not subject to substantive examination. The International Bureau or WIPO's Patent Cooperation Treaty (PCT) is a

Due to its antiseptic and biocidal nature, more than 50% patenting activity of AgNPs is seen in the area of pharmaceuticals, healthcare, consumer goods, preservatives, sterilization, and water treatment. Using the patent landscape analysis, we identified relevant patents for pharmaceutical, healthcare, and consumer goods patents. Intensive IP analysis, such as broadness of claims, details of office actions can help in identifying the share of the market that can be attributed to current and future technology. Active companies in the technology space were identified as they can influence the market. For example, LG Household and Health Care Ltd (health care) and L'Oreal (cosmetics) are amongst the major assignees in the

Several observations were found in the 932 patent families from January 1, 1980 to December 31st, 2010 that was related to AgNP in consumer products. These 932 patent

Among these 932 publications, cosmetics, personal care, medical, and health care occupy

In order to analyze the data in more detail, we defined four different classes of formulation to examine the role of the concentration of nanosilver (e.g., dose) used in the formulations

Clearly trace dose formulation found applications in foods, drinking water, drugs, facial mask, cream, wound care, gel, and textiles (Lem et al., 2012). At low and medium doses, the formulations found applications in household products materials, medical, personal care and cosmetics. Typical medical applications include catheter, endotracheal tube, and subcutaneous central venous port; pacemakers, prosthetic heart valves, prosthetic joints, voice prostheses, contact lenses, stents, heart valves, penile implants, small or temporary joint replacement, urinary dilators, cannulae, and intrauterine devices; catheter lock, needle, luer-lok (medical device) connectors, needleless connectors, clamps, forceps, scissors, skin hooks, tubing, needles, retractors, sealer, drills, chisel, rasps, surgical instruments, dental instruments, intravenous tubes, breathing tubes, dental water line, dental drain tubes, feeding tubes, bandages, wound dressings, orthopedic implants, and saws (Lem et al., 2012).

parallel patenting route that covers most of the world's patenting countries.

Furthermore it is known that functionalizing the nanosilver with different functional groups/moieties can make nanosilver suitable for specific applications like biomedical devices, dye-doped particles, biomedical imaging, *etc.* One interesting example uses glycosaminoglycan conjugated nanosilver particles for biomedical devices (Mousa & Linhart, 2010). Anti-coagulation is another active area for research where a core of metal silver is coated with a surface layer of silver oxide (Zhu et al., 2002; Zhu & Zhu, 2004). One method of increasing sterilizing power and antibacterial property of nanosilver is by mixing it with nanosulfur compounds (Oh, 2002). Coated nanoparticles are produced by precipitating nanoparticle cores from two aqueous reactant solutions in a microemulsion, and adding a coating agent to coat the cores (Tan, 2003).

#### **3. The landscaping of consumer products containing nanosilver**

To have a better global picture of nanosilver in commercial and consumer products, Lem et al. (2012) have conducted an exhaustive intellectual property (IP) search study using a "two stages" stage-gate process. This search is divided into three parts based on timelines.

Fig. 2. AgNPs Patent Filing Countries (Adopted from Lem et al., 2012)

The details of the search methodology and results are not the subjects of this article. They have been reported recently by Lem et al. (2012). Figure 2 shows the countries researching AgNPs. Figure 2 shows that out of all the major patenting authorities, South Korea is leading with 2087 publications. The U.S. is second and China is third. These three countries have about 80% of the total patent publications. It is important to note that Chinese patent numbers are over-weighted by their Chinese Utility Model Patents that only protect the shape and/or structure of a product for 10 years and are not subject to substantive examination. The International Bureau or WIPO's Patent Cooperation Treaty (PCT) is a parallel patenting route that covers most of the world's patenting countries.

Due to its antiseptic and biocidal nature, more than 50% patenting activity of AgNPs is seen in the area of pharmaceuticals, healthcare, consumer goods, preservatives, sterilization, and water treatment. Using the patent landscape analysis, we identified relevant patents for pharmaceutical, healthcare, and consumer goods patents. Intensive IP analysis, such as broadness of claims, details of office actions can help in identifying the share of the market that can be attributed to current and future technology. Active companies in the technology space were identified as they can influence the market. For example, LG Household and Health Care Ltd (health care) and L'Oreal (cosmetics) are amongst the major assignees in the space of pharma and consumer goods patents.

Several observations were found in the 932 patent families from January 1, 1980 to December 31st, 2010 that was related to AgNP in consumer products. These 932 patent publications were reviewed to distil information with respect to:

220 Public Health – Methodology, Environmental and Systems Issues

Furthermore it is known that functionalizing the nanosilver with different functional groups/moieties can make nanosilver suitable for specific applications like biomedical devices, dye-doped particles, biomedical imaging, *etc.* One interesting example uses glycosaminoglycan conjugated nanosilver particles for biomedical devices (Mousa & Linhart, 2010). Anti-coagulation is another active area for research where a core of metal silver is coated with a surface layer of silver oxide (Zhu et al., 2002; Zhu & Zhu, 2004). One method of increasing sterilizing power and antibacterial property of nanosilver is by mixing it with nanosulfur compounds (Oh, 2002). Coated nanoparticles are produced by precipitating nanoparticle cores from two aqueous reactant solutions in a microemulsion,

To have a better global picture of nanosilver in commercial and consumer products, Lem et al. (2012) have conducted an exhaustive intellectual property (IP) search study using a "two

Part A. Before 1980 "pre nano": In this the search is done to identify patent documents which have a mention of nano sized silver material before nanotechnology became an

Part B: Jan 1980 to Jul 2008: Time prior to EPA expressing their concern about toxicological

Part C: Aug 2008 to Dec 2010: This is the time after the EPA has started showing concern towards toxicological uncertainties as a consequence of using nano scale silver. The search is terminated 2010 to avoid complications of handling data for the incomplete

stages" stage-gate process. This search is divided into three parts based on timelines.

and adding a coating agent to coat the cores (Tan, 2003).

establish field of science and technology.

year 2011.

**3. The landscaping of consumer products containing nanosilver**

uncertainty as a consequence of using nano scale silver.

Fig. 2. AgNPs Patent Filing Countries (Adopted from Lem et al., 2012)

4. Application area and products.

Among these 932 publications, cosmetics, personal care, medical, and health care occupy more than 70% of the application areas as shown in Figure 3.

In order to analyze the data in more detail, we defined four different classes of formulation to examine the role of the concentration of nanosilver (e.g., dose) used in the formulations on these applications:

Clearly trace dose formulation found applications in foods, drinking water, drugs, facial mask, cream, wound care, gel, and textiles (Lem et al., 2012). At low and medium doses, the formulations found applications in household products materials, medical, personal care and cosmetics. Typical medical applications include catheter, endotracheal tube, and subcutaneous central venous port; pacemakers, prosthetic heart valves, prosthetic joints, voice prostheses, contact lenses, stents, heart valves, penile implants, small or temporary joint replacement, urinary dilators, cannulae, and intrauterine devices; catheter lock, needle, luer-lok (medical device) connectors, needleless connectors, clamps, forceps, scissors, skin hooks, tubing, needles, retractors, sealer, drills, chisel, rasps, surgical instruments, dental instruments, intravenous tubes, breathing tubes, dental water line, dental drain tubes, feeding tubes, bandages, wound dressings, orthopedic implants, and saws (Lem et al., 2012).

Waste Minimization for the Safe Use of Nanosilver

(January 1, 1980 to December 31, 2010)

capital – Seoul as illustrated in Figure 5.

products actually contained AgNPs.

2008).

in Consumer Products – Its Impact on the Eco-Product Design for Public Health 223

3.  Male Korean life

4. The younger populace is looking for general skin care and hair care products while the

5. There is a clear trend of the market heading towards premium cosmetic products that

Fig. 4. Nanosilver in Different Application Areas in Korea (Adopted from Lem et al., 2012)

Recently, nanosilver has also found use in everyday products such as antimicrobial products, consumer products, and electronic products. Consumer products containing nanosilver have been selling everywhere in South Korea, especially on the streets of her

At this juncture, it should be pointed out that not all the consumer products claimed to contain AgNPs indeed have AgNPs. Using energy dispersive X-ray spectroscopy (EDS) analysis (Yang et al., 2011), we have found that not all the commercial products sold in Korea claimed to have AgNPs indeed contain AgNPs (Kim et al., 2011; Yang et al., 2011). These experimental results are not unusual, though negative results can also be due to washing away over time. However, it appears that marketing (especially by street vendors) of AgNPs is not always directly tied to science. Even with a sophisticate Cloud Point Extraction-Based Separation together with EDS, SEM, TEM, and UV analyses, Chao et al., (2011) reported that only three out of six tested antibacterial AgNPs containing commercial

expectancy has increased from 59 in 1970 to 79 in 2006 (Shin, 2008).

need new technology, especially nanotechnology.

older generation has more specific needs for their cosmetics products.

life expectancy of female Korean has increased from 66 in 1970 to 82 in 1986 (Shin,

Fig. 3. Nanosilver in Various Application of Consumer Products (Adopted from Lem et al., 2012) (January 1, 1980 to December 31, 2010)

High dose formulation applications were in antimicrobial pharmaceuticals, hair mousse, biocides, disinfectants, electronic chemicals, silver conductive ink, medical applications, solar panels, smart glass, and suppository (Lem et al., 2012).

#### **4. The landscaping of consumer products containing nanosilver in Korea**

As indicated earlier, Korea is a leader in patent publications for use of nanosilver in consumer products. Cosmetics and personal care, medical, and health care occupy 65% of the Korean applications shown in Figure 4. This is a similar percentage as the global consumer products shown in Figure 3. Comparing Figure 3 and Figure 4 illustrates some of the Asian cultural and societal differences. While the world is spending more (40%) on medical/ health care and little less (32%) on cosmetics/ personal care, Korea invested more than twice in cosmetic/personal care (47%) than in medical /health care (18%) (Lem et al., 2012).

Koreans spent about \$130 per person in 2008 on makeup and skin care products and use in plastic surgery clinics doubled to about 1,000 facilities between 2004 and 2007 (Shin, 2008; Barry, 2002; U.S. Commercial Service, 2011; Consumer Demand Beneficiaries in Korea, 2008). Several reasons accounted for the strong growth of cosmetics in the Korean market.

Fig. 3. Nanosilver in Various Application of Consumer Products (Adopted from Lem et al., 2012)

High dose formulation applications were in antimicrobial pharmaceuticals, hair mousse, biocides, disinfectants, electronic chemicals, silver conductive ink, medical applications,

As indicated earlier, Korea is a leader in patent publications for use of nanosilver in consumer products. Cosmetics and personal care, medical, and health care occupy 65% of the Korean applications shown in Figure 4. This is a similar percentage as the global consumer products shown in Figure 3. Comparing Figure 3 and Figure 4 illustrates some of the Asian cultural and societal differences. While the world is spending more (40%) on medical/ health care and little less (32%) on cosmetics/ personal care, Korea invested more than twice in cosmetic/personal

Koreans spent about \$130 per person in 2008 on makeup and skin care products and use in plastic surgery clinics doubled to about 1,000 facilities between 2004 and 2007 (Shin, 2008; Barry, 2002; U.S. Commercial Service, 2011; Consumer Demand Beneficiaries in Korea, 2008). Several reasons accounted for the strong growth of cosmetics in the Korean market. 1. Life expectancy of Koreans has increased from 62 in 1970 to 79 years in 2006 (Shin,

2. Korea's rapidly aging population and increasing female workforce are now driving the demand for beauty and personal cares products in the domestic market. Also the

**4. The landscaping of consumer products containing nanosilver in Korea**

(January 1, 1980 to December 31, 2010)

2008).

solar panels, smart glass, and suppository (Lem et al., 2012).

care (47%) than in medical /health care (18%) (Lem et al., 2012).

life expectancy of female Korean has increased from 66 in 1970 to 82 in 1986 (Shin, 2008).

Fig. 4. Nanosilver in Different Application Areas in Korea (Adopted from Lem et al., 2012) (January 1, 1980 to December 31, 2010)

Recently, nanosilver has also found use in everyday products such as antimicrobial products, consumer products, and electronic products. Consumer products containing nanosilver have been selling everywhere in South Korea, especially on the streets of her capital – Seoul as illustrated in Figure 5.

At this juncture, it should be pointed out that not all the consumer products claimed to contain AgNPs indeed have AgNPs. Using energy dispersive X-ray spectroscopy (EDS) analysis (Yang et al., 2011), we have found that not all the commercial products sold in Korea claimed to have AgNPs indeed contain AgNPs (Kim et al., 2011; Yang et al., 2011). These experimental results are not unusual, though negative results can also be due to washing away over time. However, it appears that marketing (especially by street vendors) of AgNPs is not always directly tied to science. Even with a sophisticate Cloud Point Extraction-Based Separation together with EDS, SEM, TEM, and UV analyses, Chao et al., (2011) reported that only three out of six tested antibacterial AgNPs containing commercial products actually contained AgNPs.

Waste Minimization for the Safe Use of Nanosilver

effect of size of particles on public health.

in Consumer Products – Its Impact on the Eco-Product Design for Public Health 225

With this rapid growth of nanotechnology, it is only natural that the next major wave of applications for silver would include nanoscale particles. However, the safety of nanosilver (AgNPs) in public health is a potential "Nano-Titanic" possibly preventing a sustainable nanosilver industry. As with macroscale silver, nanosilver effectively kills bacteria and is

At the nanoscale, materials have different properties as a function of size compared with the same materials at a larger size. The size range of greatest interest is typically from 100 nm down to approximately 0.2 nm, because in this size range properties of the materials become tunable (Sun, 2007; Lem et al., 2010). This tuneability requires a better understanding of

Given the explosive growth in applications of nanosilver, certain authors have expressed misgivings about potential public health effects. Senjen and Illuminato (2007; 2009) of Friends of the Earth claimed that nanosilver was an extreme germ killer which presents a growing threat to public health. Chaloupka et al. (2010) discussed a number of medical uses of Ag and AgNPs in human prophylactic antibacterial effects such as bone cement, implants, and coating for neurosurgical shunts and catheters. In their literature citation, Wijnhoven et al. (2010) and Chao et al. (2010) found that AgNPs were toxic to rat and human cells. They further noted that these silver nanoparticles could enter the human skin via textile and dressing contact, via release from medical devices ingressing into the female gentile tract, forming protein-silver complexes that can deposit in human vital organs such as the liver, lungs, and kidneys. Recently, silver has found use in everyday products such as

Even with the urgent need to specify the nanotechnology that could be the most assist the developing world, Faunce & Watal (2010) reported that the role of AgNPs was not specifically mentioned in water purification due to their potential environmental toxicity. Very recently, Powers (2010) mentioned in her dissertation that her results showed positive that Ag+ and AgNPs are developmental neurotoxicants in vitro and in vivo. Furthermore, the discharge, emission, and disposal of AgNPs and their products to the environment during their entire products life cycle are also a major concern (Rebitzera et al., 2004; Ross et al., 2002; Panyala et al., 2008; Hansen, 2009; Danscher & Locht, 2010; Nowack, 2010). In recent years, the uncertainty of safety has increasingly made nanosilver a concern of potential threats to public health. Despite the fact that silver and nanosilver has been used for many centuries in applications pertinent to our daily life because silver has an antiseptic

effect. In ancient times, many Greeks used silver vessels for drinking water storage.

In contrast, Volpe (2010) and Height (2009) of The Silver Nanotechnology Working Group (SNWG) argued that AgNPs used in antimicrobial applications are identical to all the EPAregistered silver products that were used for decades. Very recently, Nowack et al. (2011) urged the policy regulators should not hastily declare nanosilver materials as new chemicals in their study on the 120+ years of nanosilver history. However, Schäfer et al. (2011) rebuked Nowack et al. (2011) by questioning the difference between the scientific definition of "colloid silver" and nanosilver. They further raised five pertinent questions regarding the

therefore biocidal, but many scientists are still uncertain of its safety.

antimicrobial products, consumer products, and electronic products.

safety of nanosilver in consumer products that need to be clarified: 1. Is the toxic potential of nanosilver identical to "classical" silver? 2. Since when has it been possible to analyze silver at the nanoscale?

Fig. 5. Selling AgNPs Consumer Products on the Street in Seoul, Korea

### **5. Silver/nanosilver and public health**

Today, about 320 tons/year of AgNPs are produced and used worldwide in industrial products (Nowack et al., 2011). Stensberg et al. (2011) reported that an estimate of 1,120 tons of AgNPs will be used in 2015. They also reported that the number of products that contain AgNPs has increased from 30 in 2006 to over 300 at the beginning of 2011. In any event, the assumption that silver is benign to humans or that health effects are relatively mild cannot be made without further research to confirm these views. The existence of previous studies show, if anything, that there are potentially very real and severe side-effects which must be addressed prior to increasing the use of silver and especially nanosilver in health, consumer, and professional settings. Therefore, whether it is an old or new problem, we must deal with it seriously.

The growth in investment in nanoscience and nanotechnology has been astounding. Among the \$12.4B spent in 2006 worldwide nanotechnology research funding (Mamikunian, 2007), at least 50 %, that is >\$6B, was spent on the effect of size on the development of nanomaterials and devices.

Nanotechnology application focuses on exploitation of the size effects to create structures, devices and systems with novel properties and functions. The focus of nanoscience research is the understanding of the effect of size and its influence on the properties of nano-material.

Fig. 5. Selling AgNPs Consumer Products on the Street in Seoul, Korea

Today, about 320 tons/year of AgNPs are produced and used worldwide in industrial products (Nowack et al., 2011). Stensberg et al. (2011) reported that an estimate of 1,120 tons of AgNPs will be used in 2015. They also reported that the number of products that contain AgNPs has increased from 30 in 2006 to over 300 at the beginning of 2011. In any event, the assumption that silver is benign to humans or that health effects are relatively mild cannot be made without further research to confirm these views. The existence of previous studies show, if anything, that there are potentially very real and severe side-effects which must be addressed prior to increasing the use of silver and especially nanosilver in health, consumer, and professional settings. Therefore, whether it is an old or new problem, we must deal with

The growth in investment in nanoscience and nanotechnology has been astounding. Among the \$12.4B spent in 2006 worldwide nanotechnology research funding (Mamikunian, 2007), at least 50 %, that is >\$6B, was spent on the effect of size on the development of

Nanotechnology application focuses on exploitation of the size effects to create structures, devices and systems with novel properties and functions. The focus of nanoscience research is the understanding of the effect of size and its influence on the properties of nano-material.

**5. Silver/nanosilver and public health**

it seriously.

nanomaterials and devices.

With this rapid growth of nanotechnology, it is only natural that the next major wave of applications for silver would include nanoscale particles. However, the safety of nanosilver (AgNPs) in public health is a potential "Nano-Titanic" possibly preventing a sustainable nanosilver industry. As with macroscale silver, nanosilver effectively kills bacteria and is therefore biocidal, but many scientists are still uncertain of its safety.

At the nanoscale, materials have different properties as a function of size compared with the same materials at a larger size. The size range of greatest interest is typically from 100 nm down to approximately 0.2 nm, because in this size range properties of the materials become tunable (Sun, 2007; Lem et al., 2010). This tuneability requires a better understanding of effect of size of particles on public health.

Given the explosive growth in applications of nanosilver, certain authors have expressed misgivings about potential public health effects. Senjen and Illuminato (2007; 2009) of Friends of the Earth claimed that nanosilver was an extreme germ killer which presents a growing threat to public health. Chaloupka et al. (2010) discussed a number of medical uses of Ag and AgNPs in human prophylactic antibacterial effects such as bone cement, implants, and coating for neurosurgical shunts and catheters. In their literature citation, Wijnhoven et al. (2010) and Chao et al. (2010) found that AgNPs were toxic to rat and human cells. They further noted that these silver nanoparticles could enter the human skin via textile and dressing contact, via release from medical devices ingressing into the female gentile tract, forming protein-silver complexes that can deposit in human vital organs such as the liver, lungs, and kidneys. Recently, silver has found use in everyday products such as antimicrobial products, consumer products, and electronic products.

Even with the urgent need to specify the nanotechnology that could be the most assist the developing world, Faunce & Watal (2010) reported that the role of AgNPs was not specifically mentioned in water purification due to their potential environmental toxicity. Very recently, Powers (2010) mentioned in her dissertation that her results showed positive that Ag+ and AgNPs are developmental neurotoxicants in vitro and in vivo. Furthermore, the discharge, emission, and disposal of AgNPs and their products to the environment during their entire products life cycle are also a major concern (Rebitzera et al., 2004; Ross et al., 2002; Panyala et al., 2008; Hansen, 2009; Danscher & Locht, 2010; Nowack, 2010). In recent years, the uncertainty of safety has increasingly made nanosilver a concern of potential threats to public health. Despite the fact that silver and nanosilver has been used for many centuries in applications pertinent to our daily life because silver has an antiseptic effect. In ancient times, many Greeks used silver vessels for drinking water storage.

In contrast, Volpe (2010) and Height (2009) of The Silver Nanotechnology Working Group (SNWG) argued that AgNPs used in antimicrobial applications are identical to all the EPAregistered silver products that were used for decades. Very recently, Nowack et al. (2011) urged the policy regulators should not hastily declare nanosilver materials as new chemicals in their study on the 120+ years of nanosilver history. However, Schäfer et al. (2011) rebuked Nowack et al. (2011) by questioning the difference between the scientific definition of "colloid silver" and nanosilver. They further raised five pertinent questions regarding the safety of nanosilver in consumer products that need to be clarified:

Waste Minimization for the Safe Use of Nanosilver

decrease the body's cell count (Powell, 2011).

binding prokaryotic and non-mammalian organisms (Power, 2011).

and suggests deeper pathophysiological effects in the body.

developmental abnormalities (Powell, 2011).

in Consumer Products – Its Impact on the Eco-Product Design for Public Health 227

biochemical chain reaction which eventually leads to the destruction of cellular metabolism, structures, and DNA (Faunce & Watal, 2010). Oxidative stress can disrupt cell membranes or cell walls, leading to cell destruction (Powell, 2011). In vitro studies have shown that silver can increase the rate of cell death, inhibit cell growth, decrease DNA and protein synthesis, disrupt DNA replication, affect cell membrane ion transport and integrity, cause cell swelling and toxicity, cause cell death, inhibit neutrophil and lymphocyte activity, and

Environmental concerns surrounding nanosilver have also entered the public health arena (Yu, 2008). Nanosilver production can lead to bulk form release of silver and nanosilver into waste streams, which have previously led to major environmental toxicities (Faunce & Watal, 2010). Such pollution can lead to not only deleterious effects to the ecosystem as a whole, but also cause direct poisoning of humans and animals. In fact, ionic silver is considered to be the second most toxic metal after mercury, in part because of its efficacy in

One common condition linked to increased silver deposits in the skin is argyria, a permanent blue-gray discoloration of the skin, and the related argyrosis, a similar discoloration in the eye (Atiyeh et al., 2007; Powell, 2011). The presence of silver is thought to increase melanin production, therefore leading to the color change, particularly in the presence of sun exposure (Powell, 2011). Though long thought to be a harmless cosmetic change, the finding of argyria is a proxy for increased systemic contamination with silver

Medically, well-documented effects have suggested that silver harms the renal and hepatological systems (Powell, 2011). Deposits of silver in the glomerular subunits of the kidney have led to its classification as a nephrotoxin (Powell, 2011). In the cardiovascular system, case reports have noted an association with arteriosclerosis, a precursor of coronary artery disease (Powell, 2011). The inhalation of silver in the respiratory system has also been linked to inflammation, emphysema, reduction of lung volume, and straining of the tissues in the lung (Powell, 2011). As a result, patients have complained of sometimes daily upper respiratory tract irritation, cough, wheezing, and chest tightness (Powell, 2011). Silver has also been used as an abortifacient and sterilizing agent, suggesting its intrinsic damage to the reproductive tract (Powell, 2011). In pregnant women, silver has also been show to cross the placental barrier, allowing it to enter the fetus as well (Powell, 2011). One case-control study also suggested an association between the presence of silver in drinking water and

Delayed wound healing and decreased white cell count has been found to be a result of silver-enhanced wound dressings (Powell, 2011). In patients with argyrosis, discoloration of the eyes with decreased night visual acuity has also been reported (Powell, 2011). Neurological effects include deposits in the central nervous system, glial changes, and cellular gliosis (Powell, 2011). Clinical manifestations may include seizures, vertigo, weakness, gait disturbance, and decreased sensation (Powell, 2011). Finally, studies in mouse embryonic stem cells have shown a rise in levels of p53, one of the main tumor suppressor proteins which help prevent cancer in the body, which inevitably leads to the question of whether nanosilver use can potentially contribute to greater likelihoods of cancer (Faunce & Watal, 2010). On the other hand, enhanced efficiency of wound healing has also been reported by application of AgNPs on skin wounds in mice (Liu X et al., 2010).

In her exhaustive study, Powell (2011) clearly concluded that, "I propose that enough is known already about the toxicity of silver as a metal to begin taking strong steps to prevent human exposures and environmental releases now, rather than waiting till silver becomes the next mercury."

Recently, the German Federal Institute for Risk Assessment (BfR) has conducted the Delphi study (Bartels, 2010) regarding nanoscale silver compounds in food products, cosmetics and every day products. To ensure that products are safe for consumer health, BfR recently recommended that German manufacturers not use nanoscale silver or nanoscale silver compounds in foods and everyday products until the data are available and comprehensive enough to allow a conclusive risk assessment (Bartels, 2010). Faunce & Watal (2010) noted further the uncertainty of the safety may be compounded by lack of toxicological data and lifecycle studies of acceptable environmental exposure limits.

#### **6. A clinical medicine perspective of silver and nanosilver**

In view of the many applications in Asian countries like Korea, the importance of a clinical medicine perspective of silver and nanosilver needs to be emphasized. Silver has long been used as an antimicrobial agent in medicine to keep wounds clean since the days of ancient Greece, Egypt, and Rome (Chen & Schluesener, 2008; Lansdown, 2010). This is because of the efficacy of thiol group reactions which inactivate bacterial enzymatic activity (Faunce & Watal, 2010). Colloidal silver was introduced as long ago as 1884 by German physician Dr. C.S.F. Crede, to prevent transmission of maternal gonorrhea to newborns and thus preventing blindness. This is still a practice used in nurseries today (Feder, 2005). Silver was used as a wound dressing and disinfectant during World War I until the advent of penicillin, but the combination of silver with the antibiotic sulfonamide into silver sulfadiazine cream is still the first-line treatment for burns (Atiyeh et al., 2007; Ahamed et al., 2008; Faunce & Watal, 2010).

Nanosilver, or nano-particle sized silver provide a greater surface area of silver and theoretically a more efficacious product. It has also been used extensively in medical applications, from the impregnation and coating of surgical mesh, indwelling catheters, ports, stents, tubes, scopes, and cuffs to other devices to prevent the growth of bacterial biofilms which can precipitate infection. (Faunce & Watal, 2010) Additionally, the use of nanosilver has extended into the public health arena, where it is being used to coat food and agricultural facilities in an effort to prevent bacterial outbreaks in the general population (Powell, 2011).

Despite the wide ranging applications of silver and nanosilver in medicine, it is not clear that enough regulation exists or that there is sufficient research on the potential toxicity of silver to the human body and environment at large. Not only is there evidence for the potential toxicity of nanosilver, there is evidence to suggest that nanosilver is uniquely harmful to the human body when compared to silver compounds because of its ability to generate reactive oxygen species (ROS). ROS, also known as free radicals, cause a

5. Is our current knowledge on nanosilver in consumer products sufficient to account for

In her exhaustive study, Powell (2011) clearly concluded that, "I propose that enough is known already about the toxicity of silver as a metal to begin taking strong steps to prevent human exposures and environmental releases now, rather than waiting till silver becomes

Recently, the German Federal Institute for Risk Assessment (BfR) has conducted the Delphi study (Bartels, 2010) regarding nanoscale silver compounds in food products, cosmetics and every day products. To ensure that products are safe for consumer health, BfR recently recommended that German manufacturers not use nanoscale silver or nanoscale silver compounds in foods and everyday products until the data are available and comprehensive enough to allow a conclusive risk assessment (Bartels, 2010). Faunce & Watal (2010) noted further the uncertainty of the safety may be compounded by lack of toxicological data and

In view of the many applications in Asian countries like Korea, the importance of a clinical medicine perspective of silver and nanosilver needs to be emphasized. Silver has long been used as an antimicrobial agent in medicine to keep wounds clean since the days of ancient Greece, Egypt, and Rome (Chen & Schluesener, 2008; Lansdown, 2010). This is because of the efficacy of thiol group reactions which inactivate bacterial enzymatic activity (Faunce & Watal, 2010). Colloidal silver was introduced as long ago as 1884 by German physician Dr. C.S.F. Crede, to prevent transmission of maternal gonorrhea to newborns and thus preventing blindness. This is still a practice used in nurseries today (Feder, 2005). Silver was used as a wound dressing and disinfectant during World War I until the advent of penicillin, but the combination of silver with the antibiotic sulfonamide into silver sulfadiazine cream is still the first-line treatment for burns (Atiyeh et al., 2007; Ahamed et

Nanosilver, or nano-particle sized silver provide a greater surface area of silver and theoretically a more efficacious product. It has also been used extensively in medical applications, from the impregnation and coating of surgical mesh, indwelling catheters, ports, stents, tubes, scopes, and cuffs to other devices to prevent the growth of bacterial biofilms which can precipitate infection. (Faunce & Watal, 2010) Additionally, the use of nanosilver has extended into the public health arena, where it is being used to coat food and agricultural facilities in an effort to prevent bacterial outbreaks in the general population

Despite the wide ranging applications of silver and nanosilver in medicine, it is not clear that enough regulation exists or that there is sufficient research on the potential toxicity of silver to the human body and environment at large. Not only is there evidence for the potential toxicity of nanosilver, there is evidence to suggest that nanosilver is uniquely harmful to the human body when compared to silver compounds because of its ability to generate reactive oxygen species (ROS). ROS, also known as free radicals, cause a

3. Does nanosilver enter the body in the same way as "classical" silver? 4. Do we know enough about the environmental spread of silver resistance?

lifecycle studies of acceptable environmental exposure limits.

**6. A clinical medicine perspective of silver and nanosilver**

safe use?

the next mercury."

al., 2008; Faunce & Watal, 2010).

(Powell, 2011).

biochemical chain reaction which eventually leads to the destruction of cellular metabolism, structures, and DNA (Faunce & Watal, 2010). Oxidative stress can disrupt cell membranes or cell walls, leading to cell destruction (Powell, 2011). In vitro studies have shown that silver can increase the rate of cell death, inhibit cell growth, decrease DNA and protein synthesis, disrupt DNA replication, affect cell membrane ion transport and integrity, cause cell swelling and toxicity, cause cell death, inhibit neutrophil and lymphocyte activity, and decrease the body's cell count (Powell, 2011).

Environmental concerns surrounding nanosilver have also entered the public health arena (Yu, 2008). Nanosilver production can lead to bulk form release of silver and nanosilver into waste streams, which have previously led to major environmental toxicities (Faunce & Watal, 2010). Such pollution can lead to not only deleterious effects to the ecosystem as a whole, but also cause direct poisoning of humans and animals. In fact, ionic silver is considered to be the second most toxic metal after mercury, in part because of its efficacy in binding prokaryotic and non-mammalian organisms (Power, 2011).

One common condition linked to increased silver deposits in the skin is argyria, a permanent blue-gray discoloration of the skin, and the related argyrosis, a similar discoloration in the eye (Atiyeh et al., 2007; Powell, 2011). The presence of silver is thought to increase melanin production, therefore leading to the color change, particularly in the presence of sun exposure (Powell, 2011). Though long thought to be a harmless cosmetic change, the finding of argyria is a proxy for increased systemic contamination with silver and suggests deeper pathophysiological effects in the body.

Medically, well-documented effects have suggested that silver harms the renal and hepatological systems (Powell, 2011). Deposits of silver in the glomerular subunits of the kidney have led to its classification as a nephrotoxin (Powell, 2011). In the cardiovascular system, case reports have noted an association with arteriosclerosis, a precursor of coronary artery disease (Powell, 2011). The inhalation of silver in the respiratory system has also been linked to inflammation, emphysema, reduction of lung volume, and straining of the tissues in the lung (Powell, 2011). As a result, patients have complained of sometimes daily upper respiratory tract irritation, cough, wheezing, and chest tightness (Powell, 2011). Silver has also been used as an abortifacient and sterilizing agent, suggesting its intrinsic damage to the reproductive tract (Powell, 2011). In pregnant women, silver has also been show to cross the placental barrier, allowing it to enter the fetus as well (Powell, 2011). One case-control study also suggested an association between the presence of silver in drinking water and developmental abnormalities (Powell, 2011).

Delayed wound healing and decreased white cell count has been found to be a result of silver-enhanced wound dressings (Powell, 2011). In patients with argyrosis, discoloration of the eyes with decreased night visual acuity has also been reported (Powell, 2011). Neurological effects include deposits in the central nervous system, glial changes, and cellular gliosis (Powell, 2011). Clinical manifestations may include seizures, vertigo, weakness, gait disturbance, and decreased sensation (Powell, 2011). Finally, studies in mouse embryonic stem cells have shown a rise in levels of p53, one of the main tumor suppressor proteins which help prevent cancer in the body, which inevitably leads to the question of whether nanosilver use can potentially contribute to greater likelihoods of cancer (Faunce & Watal, 2010). On the other hand, enhanced efficiency of wound healing has also been reported by application of AgNPs on skin wounds in mice (Liu X et al., 2010).

Waste Minimization for the Safe Use of Nanosilver

less than 100% (Berglund and Snyder, 1990).

(c) re-manufacturing, recycle, and compositing.

Eqn 1.

and 2 into Eqn 3

(Adopted from Lem et al., 2006)

in Consumer Products – Its Impact on the Eco-Product Design for Public Health 229

The actual performance is often lower than the theoretical because the efficiency is always

Elimination and minimization of waste have been making great progress in industries and businesses using advanced methodologies such as Lean Six Sigma (Curran et al., 2006; EPA, 2009). For instance, in polymer composite manufacturing, the total waste generated from these processes could be as high as 25% based on the theoretical yield of raw materials (Lem et al., 2006). Figure 6 gives a typical schematic of a materials processing value chain. The steps of the process include component selection, processing, structure, product, and performance. Each step can generate waste only if the waste cannot be recycle back to the start or inputs. Gutowski (2002) has examined the product induced material flows through the product manufacturing system, and has suggested several research strategies to reduce material related environmental loads. This can be accomplished by focusing on three key aspects of the manufacturing process: (a) resource productivity, (b) cleaning products, and

A simple mass balance of the net flow performance balance in Figure 6 can be described by

( )

= +

–

( )

*Performance af critical component selection its wastes*

– –

*Performance af critical component selection bf process*

= − λ

constants. ). The variation of V (xj), W(xj), λj , and ωj greatly affects the value of P(x).

Where a, b, c, d are constants. In term of a continuous flow process, we can rewrite Eqns 1

Where, P(x) is a value performance function, V(xj) is the value generating function at component xj stage or phase j, and W(xj) is the waste generating function at component xj, and λj , and ωj are

Fig. 6. Relationship of Component Selection–Processing-Structure-Product-Performance

( ) ( )

( )() ( ) ( ) ( ) = + + + −

*all sources*

 ω

*bf process its wastes cf structure its wastes df products its wastes performance wastes*

– –

+ +

*cf structure df products wastes* (2)

() ( ) ( ) *P x V x dx W x dx j jj j j* (3)

(1)

Novel research done recently by Powers (2010) has shown that monovalent silver impairs mechanisms of neuronal development in vitro, but also causes disruption of neurodevelopmental mechanisms in vivo, which persists as lasting changes in adult neurochemistry and behavior (Powers, 2010). Working with the model organism, zebrafish (Danio rerio), Powers was the first to show that while lower levels of silver ion did not affect morphology or embryonic viability, they do nevertheless negatively impact swimming performance and thus long-term mortality. Higher concentrations of ionic silver resulted in clear embryonic problems such as delayed hatching, decreased survival, and dysmorphology, suggesting a concentration-dependent effect (Powers, 2010). Powers also provides evidence for the teratogenic effect of silver nanoparticles and of note, shows that the toxicity of nanoparticles was through a distinct mechanism from ionic silver. Some of these biological effects can be explained through differing toxicokinetic and toxicodynamic effects, which elicited unique developmental and neurobehavioral pathologies (Powers, 2010).

Another study conducted by Seoul National University showed that nanosilver enhances platelet activation and procoagulant activity (Jun et al., 2009). Nanosilver worked synergistically with thrombin, a native blood protein which precipitates platelet activation and aggregation, to amplify thrombotic effects. Jun et al. (2009) found that nanosilver works in separate ways to enhance both the activation of platelets as well as facilitate platelet aggregation, or clumping. Intracellular calcium levels were increased by more than two fold in the presence of nanosilver, which is directly related to the activation of GPIIb/IIIa, a protein found on platelet surfaces which aids in platelet activation and binding to fibrinogen. By potentiating these platelet activation and aggregation pathways, nanosilver exposure can theoretically lead to increased thrombotic events. Thrombosis can lead to decreased blood flow or infarction in the circulatory system, particularly in individuals already predisposed to blood clots. Potential complications include venous thromboembolism, deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction, underscoring the importance of understanding the thrombotic effects of nanosilver (Jun et al., 2009)..

Despite the plethora of studies which suggest certain harmful effects of silver, the data are incomplete. The links between in vitro and animals studies to humans are in dispute, and the existing data on humans are largely through case reports, case-control studies, or retrospective analyses. There is a lack of high-quality, randomized controlled trials (RCTs) which can increase statistical power while minimizing biases. Obvious ethical concerns limit the amount and type research that can be done on human subjects, though longer-term, broader retrospective studies of patients exposed to silver may prove to be more helpful (Powell, 2011). In any event, the assumption that silver is benign to human begins or that health effects are relatively mild cannot be made without further research to confirm these views. The existence of previous studies show, if anything, that there are potentially very real and severe side-effects which must be addressed prior to increasing the use of silver and especially nanosilver in the health, consumer, and professional settings.

#### **7. Concept of waste generation**

Waste generation is a critical limitation for any sustainable industrial system (Evens et al., 2009). Waste is an important part of our life. Humans are not perfect and thus create wastes.

Novel research done recently by Powers (2010) has shown that monovalent silver impairs mechanisms of neuronal development in vitro, but also causes disruption of neurodevelopmental mechanisms in vivo, which persists as lasting changes in adult neurochemistry and behavior (Powers, 2010). Working with the model organism, zebrafish (Danio rerio), Powers was the first to show that while lower levels of silver ion did not affect morphology or embryonic viability, they do nevertheless negatively impact swimming performance and thus long-term mortality. Higher concentrations of ionic silver resulted in clear embryonic problems such as delayed hatching, decreased survival, and dysmorphology, suggesting a concentration-dependent effect (Powers, 2010). Powers also provides evidence for the teratogenic effect of silver nanoparticles and of note, shows that the toxicity of nanoparticles was through a distinct mechanism from ionic silver. Some of these biological effects can be explained through differing toxicokinetic and toxicodynamic effects, which elicited unique developmental and neurobehavioral pathologies (Powers,

Another study conducted by Seoul National University showed that nanosilver enhances platelet activation and procoagulant activity (Jun et al., 2009). Nanosilver worked synergistically with thrombin, a native blood protein which precipitates platelet activation and aggregation, to amplify thrombotic effects. Jun et al. (2009) found that nanosilver works in separate ways to enhance both the activation of platelets as well as facilitate platelet aggregation, or clumping. Intracellular calcium levels were increased by more than two fold in the presence of nanosilver, which is directly related to the activation of GPIIb/IIIa, a protein found on platelet surfaces which aids in platelet activation and binding to fibrinogen. By potentiating these platelet activation and aggregation pathways, nanosilver exposure can theoretically lead to increased thrombotic events. Thrombosis can lead to decreased blood flow or infarction in the circulatory system, particularly in individuals already predisposed to blood clots. Potential complications include venous thromboembolism, deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction, underscoring the importance of understanding the thrombotic effects of

Despite the plethora of studies which suggest certain harmful effects of silver, the data are incomplete. The links between in vitro and animals studies to humans are in dispute, and the existing data on humans are largely through case reports, case-control studies, or retrospective analyses. There is a lack of high-quality, randomized controlled trials (RCTs) which can increase statistical power while minimizing biases. Obvious ethical concerns limit the amount and type research that can be done on human subjects, though longer-term, broader retrospective studies of patients exposed to silver may prove to be more helpful (Powell, 2011). In any event, the assumption that silver is benign to human begins or that health effects are relatively mild cannot be made without further research to confirm these views. The existence of previous studies show, if anything, that there are potentially very real and severe side-effects which must be addressed prior to increasing the use of silver

Waste generation is a critical limitation for any sustainable industrial system (Evens et al., 2009). Waste is an important part of our life. Humans are not perfect and thus create wastes.

and especially nanosilver in the health, consumer, and professional settings.

2010).

nanosilver (Jun et al., 2009)..

**7. Concept of waste generation**

The actual performance is often lower than the theoretical because the efficiency is always less than 100% (Berglund and Snyder, 1990).

Elimination and minimization of waste have been making great progress in industries and businesses using advanced methodologies such as Lean Six Sigma (Curran et al., 2006; EPA, 2009). For instance, in polymer composite manufacturing, the total waste generated from these processes could be as high as 25% based on the theoretical yield of raw materials (Lem et al., 2006). Figure 6 gives a typical schematic of a materials processing value chain. The steps of the process include component selection, processing, structure, product, and performance. Each step can generate waste only if the waste cannot be recycle back to the start or inputs. Gutowski (2002) has examined the product induced material flows through the product manufacturing system, and has suggested several research strategies to reduce material related environmental loads. This can be accomplished by focusing on three key aspects of the manufacturing process: (a) resource productivity, (b) cleaning products, and (c) re-manufacturing, recycle, and compositing.

A simple mass balance of the net flow performance balance in Figure 6 can be described by Eqn 1.

$$\begin{aligned} \text{Performance} &= af \text{ (critical component selection -- its waste)} + \\ bf \text{ (process -- its waste)} &+ cf \text{ (structure -- its waste)} + \\ df \text{ (products -- its vastes)} &- \text{ performance} \,\text{wates} \end{aligned} \tag{1}$$

$$\begin{aligned} \text{Performance} &= af \text{ (critical component selection)} + bf \text{ (process)} + \\ &\text{cf (structure)} + df \text{ (products)} - \sum \text{(waste)}\_{\text{all sources}} \end{aligned} \tag{2}$$

Where a, b, c, d are constants. In term of a continuous flow process, we can rewrite Eqns 1 and 2 into Eqn 3

$$P(\mathbf{x}) = \int \mathcal{J}\_j V(\mathbf{x}\_j) d\mathbf{x}\_j - \int a\rho\_j \mathcal{W}(\mathbf{x}\_j) d\mathbf{x} \tag{3}$$

Where, P(x) is a value performance function, V(xj) is the value generating function at component xj stage or phase j, and W(xj) is the waste generating function at component xj, and λj , and ωj are constants. ). The variation of V (xj), W(xj), λj , and ωj greatly affects the value of P(x).

Fig. 6. Relationship of Component Selection–Processing-Structure-Product-Performance (Adopted from Lem et al., 2006)

Waste Minimization for the Safe Use of Nanosilver

**Real Process**

**Exergy**

**Efficiency**

Exergyin

Resources

emission.

plastics.

in Consumer Products – Its Impact on the Eco-Product Design for Public Health 231

(Adopted from Dewulf et al, 2008)

Fig. 7. Waste Generation and Exergy Loss (Dewulf et al., 2008, Lem et al., 2009, 2010)

**9. Flow of Ag and AgNPs as a food metabolism process in material life cycle**  Using a material flow analysis (MFA), Johnson et al. (2006) in their "anthropogenic cycling of silver in 1997" study have found that North America and Europe have the biggest share of use of silver products on a per capita basis. They found that global silver discards are approximately 57% of the silver mined and only 57% of the silver entering waste management globally is recycled. The amount of silver entering landfills globally is comparable to the amount found in silver mining tailings. Eckelman and Graedel (2007) reported that more than 13 Gg of silver are emitted annually to the environment globally. The tailings and landfills make up almost three-fourths of the total

Resources = Products **+ [ByProducts + Heat + Wastes]+ [Exergy Loss]**

Exergyin = Exergyout + Exergy Loss

**Exergy Loss**

**Waste Generation**

**By-Products**

**Products**

**Wastes**

**Heat**

Exergyout

Figure 8 gives an overview of a silver/nanosilver product's life cycle as food and waste in industrial metabolism. The metabolization of resources should be optimized with respect to exergy. Dewulfn and Van Langenhove (2002, 2004) have previously applied exergy analysis as a quantitative tool in the thermodynamic optimization of the life cycle of

The expression in Eqn 3 has found uses in many applications in science and engineering. An example of such is the tensile modulus of several ordered polymers (Lem et al., 2006) in Table 1, in which the actual value [P(x)] is substantially lower than the theoretical value [V(x)]. V (xj) is not restricted with any limitations in Eqn 3 and it is valid to include the feedback loops (as in a recycling process) in Figure 6 except with different forms of V (xj) and W (xj), and different values of λj and ωj.

Table 1. Tensile Modulus of Several Ordered Polymers (Adapted from Lem et al., 2006)

#### **8. Waste minimization in flow of materials as a food metabolism process in a material life cycle**

The quality of our life is improved by our industrial system, but the current system is creating unintended and serious consequences for the environment and public health at a global scale. For nanotechnology, to minimize these consequences, one must be able to transform all sources of waste and toxicity into "technical" or "biological nutrients". We can then reuse them indefinitely without harm to living systems.

Senge and Carstedt (2001) offered a view of why industry produces waste and suggested that a synthetic process can emulate nature to reduce the waste using a cyclic industrial system. One example of this approach is recycling of nylon 6 carpets (Sifniades et al., 1999; Lem et al., 2001, 2002). This type of cyclic process has addressed and overcome the economic, technical, and logistical barriers to commercialize a closed loop recycling process and recover caprolactam from waste nylon 6 materials (Lem et al., 2010). Based on the exergy analysis by Dewulf et al. (2002-2007), in Figure 7, Lem et al. (2010; 2011) have shown that waste generation in a real process is more than just exergy loss (destroyed) in industrial metabolism. Waste generation is unavoidable so waste minimization becomes a fundamental requirement for economic feasibility. The energy and exergy concepts can be formulated in the laws of thermodynamics. Energy is motion or ability to produce motion. It is always conserved in a process (1st law). Exergy is work or ability to produce work. It is always conserved in a reversible process, but is always consumed in an irreversible process (2nd law, the law of exergy) (Wall, 1988; Sciubba & Wall, 2007))

The expression in Eqn 3 has found uses in many applications in science and engineering. An example of such is the tensile modulus of several ordered polymers (Lem et al., 2006) in Table 1, in which the actual value [P(x)] is substantially lower than the theoretical value [V(x)]. V (xj) is not restricted with any limitations in Eqn 3 and it is valid to include the feedback loops (as in a recycling process) in Figure 6 except with different forms of V (xj)

> Theoretical [V(x)] [value generating function at component x]

GPa GPa GPa %

Cis 730-670

Cis 610-600

Actual [P(x)] [Value performance function]

360

325

Trans 707-620 347 – 260 60 - 37

Trans 605-525 280 – 200 53 – 33

Gap [W(x)] [Waste Generating Function]

370 – 310 55 – 43

285 – 275 48 – 45

Table 1. Tensile Modulus of Several Ordered Polymers (Adapted from Lem et al., 2006)

3 Polyethylene 360 – 320 172 – 117 243 – 148 76 – 41

4 Graphite 1500 600 – 70 1430 – 900 95 – 60

then reuse them indefinitely without harm to living systems.

(2nd law, the law of exergy) (Wall, 1988; Sciubba & Wall, 2007))

**8. Waste minimization in flow of materials as a food metabolism process in a**

The quality of our life is improved by our industrial system, but the current system is creating unintended and serious consequences for the environment and public health at a global scale. For nanotechnology, to minimize these consequences, one must be able to transform all sources of waste and toxicity into "technical" or "biological nutrients". We can

Senge and Carstedt (2001) offered a view of why industry produces waste and suggested that a synthetic process can emulate nature to reduce the waste using a cyclic industrial system. One example of this approach is recycling of nylon 6 carpets (Sifniades et al., 1999; Lem et al., 2001, 2002). This type of cyclic process has addressed and overcome the economic, technical, and logistical barriers to commercialize a closed loop recycling process and recover caprolactam from waste nylon 6 materials (Lem et al., 2010). Based on the exergy analysis by Dewulf et al. (2002-2007), in Figure 7, Lem et al. (2010; 2011) have shown that waste generation in a real process is more than just exergy loss (destroyed) in industrial metabolism. Waste generation is unavoidable so waste minimization becomes a fundamental requirement for economic feasibility. The energy and exergy concepts can be formulated in the laws of thermodynamics. Energy is motion or ability to produce motion. It is always conserved in a process (1st law). Exergy is work or ability to produce work. It is always conserved in a reversible process, but is always consumed in an irreversible process

and W (xj), and different values of λj and ωj.

Structure