1.0 Introduction

This risk assessment was prepared to support the registration of HeiQ AGS-20 for use in treating textiles. HeiQ AGS-20 is a novel silver-silica nanocomposite material (Egger et al., 2009) that contains silver nanoparticles embedded in a matrix of amorphous silica which prevents agglomeration of the silver particles. The silver nanoparticles have a typical diameter of 1 to 10 nm and the silver-silica composite material has an average diameter of approximately one micron. This material will be formulated as a powder which will be used as a materials preservative to treat textiles either by application as a coating or by incorporation into the starting materials during fiber manufacture.

2.0 HeiQ Risk Assessment Assumptions and Agency Response

The HeiQ risk assessment contains a number of assumptions that support their conclusion that the registration of AGS-20 will not cause unreasonable risk to human or the environment. A discussion of these assumptions is included below:

2.1 The potential for leaching from AGS-20 in use has been demonstrated to be extremely low.

HieQ Rationale for the Assumption

HeiQ asserts that the nanoscale silver particles are trapped within an inert matrix which is subsequently further embedded in a treated article . They also point out that their leaching study confirmed that the silver nanoparticles did not separate from the treated article and leach out or otherwise become physically separated into wash water. They also mention that this no leaching finding was confirmed on the same test materials by an independent study published in a peer reviewed journal.

Agency Response

AD reviewed the leaching study conducted by HeiQ (MRID 477287-01) and the independent study (Geranio et al. 2009) in memo D369399 of April 15, 2010. With respect to the HeiQ leaching study, AD determined that it cannot be conc luded that very few if any nanoparticles of silver were released. This is because the magnification used, which was at the micron scale, was insufficient to detect the nanosilver particles which are 1-10 nm in diameter. It is also not known if the silver nanoparticles would have aggregated and become visible at lowermagnifications and there are issues associated with the sensitivity of the Energy Dispersive Xray (EDX) method. AD also reviewed the Gerani o et al. study and concluded that HeiQ treated textiles that were subjected to machine washing with detergents and bleach released silver in the form of coarse particulate, but it is not known if this particulate consists of nanosilver particles in fiber fragments, aggregates of silver nanopar ticles or precipitates of ionic silver. AD recommends that an additional leaching study be done in the manner of Geranio et al. with the

Page 2 of 6addition of electron microscopy to characterize the pa rticulate. The characterization is needed to determine if nanoparticles could be released from the particulate.

2.2 The risk assessment for occupational expo sure indicates that the risks are not of

concern.

HieQ Rationale for the Assumption

Although HeiQ asserts there are no dietary, drinki ng water or residential exposures for the use pattern proposed, they do acknowledge that there might be occupational exposure during the handling of the AGS-20 powder. They provide a risk assessment for these exposures which is based on the assumption of adding a 1 kg container of AGS-20 per day into a mixing vessel with no ventilation. To calculate exposures, they use unit exposure values of 10.2 mg/kg ai handled (5.1 mg/lb ai handled) for dermal exposure and 0.66 mg/kg ai handled (0.30 mg/lb ai) for inhalation exposure from the Technical Notes for Guidance on Human Exposure (European Commission, 2008). They compare these exposures to the “EPA weight of Evidence limit” for ionic silver (US EPA, 2009) and conclude that the risks are not of concern if gloves are worn to minimize dermal exposures and full face respirators are worn to minimize inhalation exposures.

Agency Response

The Agency does not concur with the HieQ rationale for the occupational risk assessment because of the following reasons:

• It is not known if the unit exposure values from guidance document are from materials that have the same properties, such as particle size, as AGS-20. It is highly possible that these unit exposure values are based on materials that have larger particle sizes than AGS-20 which would lead to the underestimation of exposure. These values are similar to the wettable powder values (3.7 mg/lb ai handled for dermal exposures with no gloves and 0.043 mg/lb ai handled for inhalation exposures) from the Pesticide Handlers Exposure Database (PHED) which are based on conventional pesticide formulations that were in use prior to 1995.

• Is not known if a mass based comparison would be appropriate for nanosilver. It is possible that an alternate metric such as surface area would be more appropriate.

• The endpoint for assessing exposure, which is based on ionic silver, is not appropriate for assessing exposures to nanoparticles of silver. This point is discussed further in Section

2.3.

Page 3 of 62.3 Nanoscale colloidal silver algaecides have been EPA registered with an established record of safe use for over 50 years.

HeiQ Rationale

HeiQ asserts that swimming pool algaecide products such as Silver Algaedyn (68161-1, registered in 1954) and nu-clo Silvercide (7124-101, registered in 1993) contain silver nanoparticles. In the Silver Nano Working Group (SNWG) presentation to the FIFRA Scientific Advisory Panel (SAP), particle size data was included which indicated that Silver Algaedyn contains particles in the range of 20-100 nm and nu-clo Silvercide contains particles in the range of 20-110 nm (SNWG, 2009). They also mention some other colloidal products such as Cary Lea colloidal silver and ASAP-AGX-32. In the risk assessment they claim that: “The toxicology database for ionic silver contains data on colloidal (nano) products, which potentially are the same in terms of size as many currently registered silver antimicrobials, suggesting that uses of discrete nanoscale (colloidal) silver products have been successfully regulated based on the same conservative endpoint as has been established for ionic silver”.

Agency Response

The Agency has very limited data on the physical and chemical properties of the colloidal products and is therefore unable at this time to determine if they are similar to AGS-20. Although some particle size data was included in the SNWG presentation, the details of how these data were collected were not included and it is not known if sample preparation methods, such as ultrasonication, were used which would have affected the particle size distribution. It is also not known if the silver in the colloidal produc ts is primarily particulate or if also includes ions. The FIFRA SAP report (US EPA, 2010) also mentions colloidal silver and suggested that available data on existing colloidal silver materials be investigated.

Another area of concern is that the silver nanoparticles in AGS-20, which range in size from 1 to 10 nm, are an order of magnitude smaller than the reported sizes of the particles in the colloidal products such as Algaedyne and nu-clo Silverci de. According to the FIFRA SAP report: “the literature does suggest that silver nanoparticles in the range of about 1 to 20 nm do possess the greatest quantum properties, are the most optically active and may have the potential to induce the greatest toxicities”.

2.4 HeiQ ® AGS-20 is not a “nanopesticide” that exhibits novel “size-related” properties and/or toxicity.

HeiQ Rational

HeiQ ® AGS-20 is not a “nanotechnology” product by NNI’s definition because the particles are micron sized (1-3 μm). The product has identical physical and chemical properties to bulk metallic silver and exhibits no novel size-related properties. There is no indication of any novel toxicity for the particles. The product is not a “nanopesticide”, i.e., it is not different from other registered pesticides that contain silver.

Page 4 of 6Agency Response

Egger et al. (2009) characterized the HeiQ AGS-20 silver-silica nanocomposite and determined that it contains silver nanoparticles that have a typical diameter of 1 to 10 nm. They also detailed the production process and the results of the comparison in efficacies among HeiQ AGS-20, conventional silver (AgNO 3 ; 63.5%) and silver zeolite (38% Ag bound to type A zeolite). They concluded that “a silver-silica nanocomposite material with a novel structure and composition exhibited very good antimicrobial activity against a wide range of microorganisms.”

The current OPP working definition defines nanom aterials as “an ingredient that contains particles that have been intentionally produced to have at least one dimension that measures between approximately 1 and 100 nanometers” with novel properties. Based on this working definition and the published article, the active ingredient of HeiQ ® AGS-20 is nanosilver particles with novel properties.

The FIFRA SAP report (EPA, 2010) recommends that:

(1) Both “nano-sized particles of silver (Ag)” as well as “ionic silver (Ag + )” contribute to toxic effects of silver nanoparticles. The rate of silver ion production, as well as the distribution of silver nanoparticles in tissues and environment, may differ substantially between silver nanomaterials and other forms of silver, as nanomaterials can deliver ions directly to specific tissues, cell membranes or inside cells – places where other forms of silver compounds cannot reach. Therefore, the hazard profile of silver nanomaterials may differ from other forms of silver. (2) Particle size substantially impact particles properties, such as rate and concentration of silver ion release, reactivity and catalytic efficiency, plasmon resonance, and quantum effects. Smaller sized-particles are easier to be taken by organisms and distributed more widely. Other physicochemical properties, such as shape, surface area, surface charge or coating, are also likely to impact biological response and environmental fate. (3) The Panel “disagreed that nanosilver applied to a substrate will permanently bind with the substrate”. It is “especially challenging to determine that there is no release of nanomaterials from a substrate”, under current state of science and available measurement standards. It is suggested to use tests that simulate realistic use of products and potential nanosilver release along with quantitative life cycle analysis and risk

assessment. (4) Caution should be taken when extrapolating from one nanosilver formulation to another when assessing hazards, as differences in particle formulation (e.g., coating and inert ingredients) are likely to affect particle properties and associated biological activity. (5) A case-by-case approach, based on the use pattern, is used when evaluating products that

contain silver nanomaterials.

Page 5 of 6Page 6 of 6 References:

Egger et al., 2009. Antimicrobial Properties of a Novel Silver-Silica Nanocomposite Material, Applied and Environmental Microbiology, May 2009, p. 2973-2976.

Geranio et al., 2009. The Behavior of Silver Nanoparticles during Washing. Environmental Science and Technology. Published online September 24, 2009.

SNWG, 2009. “Evaluation of Hazard and Exposure Associated with Nanosilver and Other Nanometal Oxide Pesticide Products”, Presentation to the Scientific Advisory Panel, November

4, 2009.

US EPA, 2009. Ionic silver: Toxicity and Weight of Evidence, US Environmental Protection Agency, Office of Pesticide Programs, Antimicrobials Division, May 11, 2009.

US EPA, 2010. Transmittal of Meeting Minutes of the FIFRA Scientific Advisory Panel Meeting Held November 3-5, 2009 on the Evaluation of Hazard and Exposure Associated with

Nanosilver and Other Nanometal Pesticide Pr oducts, SAP Minutes No. 2010-01, EPA Office of Science Coordination and Policy, January 26, 2010.