UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

 WASHINGTON, DC 20460

 OFFICE OF CHEMICAL SAFETY 

 AND POLLUTION PREVENTION

April 3, 2015 

Erin Tesch, Technical Advisor 

Silver Task Force North America 

c/o Technology Sciences Group, Inc. 

1150 18th Street, NW – Suite 1000 

Washington, DC 20036 

Subject: EPA Response to Silver Task Force North America Position Paper 

 Dated December 12, 2012 

Dear Ms. Tesch: 

Thank you for your October 10, 2012 letter and the Silver Task Force North America (STFNA) 

document titled, “Position Paper on Registration Review of Silver Compounds, December 12, 

2012.” Among other things, the STFNA position paper asserted that, although there are several 

forms of silver active-ingredients under review (Table 1), the active component of toxicological 

interest for risk assessment purposes for all silver-based pesticides is the silver ion. Based on 

that assertion, STFNA recommended that the US Environmental Protection Agency (EPA) 

consolidate the review of all silver-based pesticide products and issue a single data call-in (DCI) 

using the silver ion as the common test substance because the silver ion is the “biologically 

active moiety.” In addition, the STFNA requested that all generic data requirements (i.e., those 

that do not deal with product chemistry) be placed on hold until EPA determines which products 

will be evaluated under which case. 

This letter responds to the “Position Paper on Registration Review of Silver Compounds, 

December 12, 2012.” In our response, EPA affirms the approach of assessing the risk for silver, 

silver ion, silver nitrate, silver chloride, silver oxide, and silver sulfate separately from 

nanosilver, silver zeolite, and silver sodium hydrogen zirconium phosphate as stated in the Silver 

and Compounds Final Work Plan (FWP) on Page 13 “The current PWP [Preliminary Work Plan] 

and this FWP are not intended to examine effects of nanosilver, which will be addressed 

separately...” and on Page 18 “Each silver zeolite compound is thus considered separately for 

hazard and risk assessments....” However, EPA agrees to the STFNA’s request to place certain 

DCI-imposed data requirements (OCSPP guidelines 835, 850, 870, and 875) on hold. The 

registrants who are subject to the affected DCI requirements will be informed by a “DCI Status 

 
2 

letter” about this decision to put the particular data requirements on hold and to impose revised 

deadlines for certain other existing data requirements. 

Background 

EPA is currently reviewing the silver-based pesticides listed in Table 1 to determine whether 

they continue to meet the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard 

for registration. Registration Review was initiated for the Silver and Compounds case in June, 

2009, and a FWP for this case was issued in December, 2009. On February 29, 2012, EPA 

issued DCIs for silver, silver nitrate, silver chloride, silver oxide, and silver sulfate and on July, 

6, 2012, EPA issued a DCI for silver ion. Registration Review for the Nanosilver case was 

initiated in July, 2012 with the posting of the PWP to the Nanosilver docket. 

Table 1. Silver Active Ingredients Currently Undergoing Registration Review 

Case Chemical Name PC Code 

4082 – Silver and Compounds Silver 072501

Silver ion 072501

Silver nitrate 072503

Silver chloride 072506

Silver oxide 129097

Silver sulfate 072511

Silver zeolite 221700

Silver sodium hydrogen zirconium phosphate 072560

5042 – Nanosilver Nanosilver 072599

Risk Assessment Approach 

The STFNA position paper stated that while there were various silver-based materials in 

currently registered products and that these “...materials may differ in their mechanisms of 

action, the common and characteristic element, release of silver ion, should predominate for 

initial risk assessment purposes.” In Attachment 2 of the position paper, STFNA categorized all 

the current registered silver products based on the mechanism of silver ion release, which 

included oxidation, dissolution and elution. Although STFNA provided additional information 

suggesting how pesticide usage relates to release of silver ions, there were no data provided 

quantifying the amount and form of silver released from each of the registrations identified in 

Attachment 2 of the position paper. Notwithstanding the lack of data, but based on its analysis 

STFNA proposed that EPA should issue a single DCI for all silver-based pesticides using silver 

ion alone as the common test substance. 

The STFNA approach of classifying certain silver-based pesticides based on the silver ion is 

consistent with EPA’s current risk assessment approach. For certain silver-based pesticides, the 

Antimicrobials Division Toxicity Endpoint Committee met in 2004 and determined that once 

internalized in the body, the compound of interest is ionic silver, which is common to the silver 

salts, and that therefore, one toxicology dataset can represent the hazard for the silver salts. This 

was the basis for combining silver, silver nitrate, silver chloride, silver oxide, silver sulfate, and 

silver ion as “Silver and Silver Salts” in the FWP for Silver and Compounds. However, for the 
3 

reasons discussed in the following paragraphs, EPA has not concluded that the hazard of 

nanosilver or silver-based zeolites can be fully characterized using only data for the silver ion. 

EPA issued the Nanosilver case separately from the Silver and Compounds case because the 

agency believes that because of the unique characteristics of nanosilver, products containing 

nanosilver may have different toxicity and / or fate profiles than products containing only macroscaled silver or other silver ingredients. Thus, additional and different data are needed to 

determine whether the FIFRA standard for maintaining registrations containing nanosilver are 

met. This view on nanosilver is consistent with the 2009 FIFRA Scientific Advisory Panel (SAP) 

report on this issue, in which the SAP concluded that nanosilver has unique physical and 

chemical properties and that the toxicity of nanosilver could differ from other forms of silver 

including the silver ion.1 Notwithstanding this background, the STFNA position paper provided 

EPA with new and different journal articles than were considered by the 2009 SAP, and the 

STFNA position paper suggests that if the EPA were to consider the findings of these journal 

articles that the health and safety properties of nanosilver would be fully characterized using data 

for the silver ion alone. The agency is aware of no new data to suggest that the SAP concerns are 

misplaced or that the hazard for the nanosilver in or released from use of a pesticide product can 

be fully characterized using silver ion hazard data only. 

The EPA has determined that each zeolite-based silver compound (silver zinc zeolite, silver 

copper zeolite and silver sodium hydrogen zirconium phosphate) will be considered separately 

for antimicrobial pesticide hazard and risk assessments. As stated in the STFNA proposal, EPA 

issued a letter to Gary Burin of Technology Sciences Group on December 7, 2010 stating that it 

intends to bridge available toxicity data among antimicrobial zeolites manufactured from zeolite 

A instead of requiring toxicity data separately for each product containing zeolite A. However, 

there is no final conclusion regarding extending this determination to bridge toxicity data for 

products containing zeolite X. At this time, the agency lacks sufficient information to determine 

if ionic silver is the only material of toxicological interest for silver-based zeolites. Therefore, the 

agency has not determined if the hazard of silver-based zeolites can be fully characterized using 

data for ionic silver alone. Because of this uncertainty, as stated in the Silver and Compounds 

FWP, EPA is requiring studies for silver-based zeolites that are separate from silver salts. A DCI 

for silver-based zeolites has not been issued because EPA believes many silver-based zeolites 

may be incorrectly classified under the silver PC Code 072501 and therefore may need to be 

reclassified. 

Re-Classification of the Form of Silver in Each Registration 

EPA greatly appreciates STFNA’s efforts regarding classifying silver-based pesticides by type 

(Attachment 2 of STFNA’s Position Paper) and plans to use this information in guiding the reclassification process. In the event that EPA re-classifies a product, EPA will provide written 

notification to the registrant of each affected product and will post the information in the Silver 

Compounds and Nanosilver registration review public dockets. EPA will use the product 

chemistry data that were required in the DCIs issued in February and July, 2012 for assessment 

and to ensure that the form or forms of silver contained in each silver product is classified 

correctly. 

 

1

 FIFRA SAP. November 3-6, 2009: Assessment of Hazard and Exposure Associated with Nanosilver and other 

Nanometal Pesticide Products: A Consultation. http://www.epa.gov/scipoly/sap/. 
4 

All product-specific data requirements, including, but not limited to, particle size (OCSPP 

guideline 830.7520), must be submitted. The agency notes that many companies are deficient in 

responding to portions of the DCI, specifically the particle size data requirement. To avoid EPA 

issuance of a Notice of Intent to Suspend the affected products pursuant to FIFRA section 

3(c)(2)(B)(iv), the agency will request to receive from registrants within 90 calendar days 

measured from receipt of their “DCI Status letter,” information that the agency determines will 

satisfy the overdue data requirements identified in Tables 3 through 8. 

Guidance Concerning the Particle Size Distribution Data Requirement (GLN 830.7520) 

Because existing data indicate that particle size distribution may affect the hazard profile of 

metals as pesticide ingredients, EPA required information about the particle size distribution of 

the silver-based active ingredient in these products. The agency intends to use particle size 

distribution data along with other product chemistry information to determine if each product(s) 

should be moved to the Nanosilver Registration Review (Case No. 5042) or if the product(s) 

should remain in the case where they are currently included. 

In response to requests for EPA guidance on determining the appropriate test method(s) to be 

used to fulfill this data requirement, EPA is providing the guidance below. EPA notes that there 

is no single method that is most appropriate for determining the particle size distribution of 

pesticide ingredients. The appropriate method depends, among other things, on the particle sizes 

of the ingredient and whether the ingredient is suspended in liquid, present as a dry powder, or 

contained within a solid matrix. The registrant must test the TGAI or MUP. Also, additional 

testing may be appropriate for nanomaterials. Refer to the discussion that follows on 

nanomaterial standards. 

For liquid (and possibly solid powder) products: 

a. If the material is in solution as a colloid, use the Dynamic Light Scattering (DLS) 

technique for screening level size and size distribution. The identity of the capping 

agent used to limit the size of the nanomaterial should be submitted to the agency. 

b. If the material is produced as a solid powder, use Dynamic Light Scattering (DLS) 

technique for screening level size and size distribution. 

c. If the material is in solution as a colloid or produced as a solid powder and DLS is not 

sufficient, use Scanning Electron Microscopy (SEM) or Transmission Electron 

Microscopy (TEM). 

For matrix composite products: 

a. If the material produced is incorporated into a silica matrix or any other polymeric 

matrix (to form a nanocomposite), use the X-Ray diffraction Method (XRD) to 

provide information on the structure of the entire material and a detailed position of 

each atom in the material. If more well-defined particle size distribution data is 

needed, use SEM or TEM. 

Standards Developed by ASTM and ISO for Nanomaterials 

Registrants are required to submit data which identify and characterize their product. The 

analytical techniques used for the characterization of materials with larger particles are not 
5 

sufficient for the characterization of nanomaterials. Literature on nanomaterials indicates that 

one analytical technique may not suffice to identify and characterize a nanomaterial depending 

on the individual makeup of the product. The American Society for Testing Materials (ASTM) 

and the International Standards Organization (ISO) have developed a number of standards for 

nanomaterials. OPP recommends the methods in Table 2. 

Table 2: Methods Relevant to Nanometals (metal oxides) 

Standard Method ID/ 

Organization 

Information obtained from the Standard 

ISO/TR 11360: 2010 Nanotechnologies guidance for the classification and 

characterization of nanomaterials 

ISO/TS 11937: 2012 Nanotechnologies nanoscale titanium dioxide in powder 

form-characteristics and measurements 

ISO/TR 13329: 2012 Nanomaterials preparation of material safety data sheet 

(MSDS) 

ISO/TS 17200-2013 Nanotechnologies nanoparticles in powder formcharacteristics and measurements 

ISO/NP TS 19590 Nanoparticles detection and characterization using singleparticle ICP-MS 

ASTM E2490-09 Standard Guideline for measurement of particle size 

distribution of nanomaterials in suspension by photon 

correlation spectroscopy 

ASTM E2834-12 Standard guide for measurement of particle size 

distribution of nanomaterials in suspension by nanoparticle 

tracing analysis (NTA) 

ASTM E2578-07(2012) Standard practice for calculation of mean sizes/diameters 

and standard deviations of particle size distributions 

ASTM E2859-11 Standard Guide for size and size measurement of 

nanoparticles using atomic force microscopy (AFM) 

DCI Status 

Because proper product classification is essential to determine which products are subject to 

which data requirements, the agency is placing the generic data requirements guidelines 835, 

850, 870 and 875 imposed by the referenced DCIs on hold until further notice. The specific data 

requirements affected by the hold are identified as such in Tables 3-8. These holds do not affect 

the product chemistry data requirements which still must be satisfied as stated in the referenced 

DCIs. Since, it is well past the initial due date for fulfilling product chemistry data requirements 

in the DCI, any required information is due 90 calendar days after a letter is received by the 

registrant. 

 
6 

Table 3 - Silver (GDCI-072501-1129) 

February 29, 2012 

Guideline 

Requirement 

Number Study Title Due Date 

830.1600 Description of materials used to produce the product 90 days from receipt of 

letter 

830.1620 Description of production process 90 days from receipt of 

letter 

830.1650 Description of formulation process 90 days from receipt of 

letter 

830.1670 Discussion of formation of impurities 90 days from receipt of 

letter 

830.1700 Preliminary analysis 90 days from receipt of 

letter 

830.1750 Certified limits 90 days from receipt of 

letter 

830.1800 Enforcement analytical method 90 days from receipt of 

letter 

830.1900 Submittal of samples 90 days from receipt of 

letter 

830.6314 Oxidizing or reducing action 90 days from receipt of 

letter 

830.6315 Flammability 90 days from receipt of 

letter 

830.6316 Explodability 90 days from receipt of 

letter 

830.6317 Storage stability of product 90 days from receipt of 

letter 

830.6319 Miscibility 90 days from receipt of 

letter 

830.6320 Corrosion characteristics 90 days from receipt of 

letter 

830.6321 Dielectric breakdown voltage 90 days from receipt of 

letter 

830.7520 Particle size, fiber length, and diameter distribution 90 days from receipt of 

letter 

830.7840 Water solubility: Column elution method, shake flask 

method 

90 days from receipt of 

letter 
7 

835.1100 Activated sludge sorption isotherm On hold 

850.1350 Mysid chronic toxicity test On hold 

850.1400 Fish early-life stage toxicity test On hold 

850.1735 Whole sediment: acute freshwater invertebrates On hold 

850.1740 Whole sediment: acute marine invertebrates On hold 

850.1850 Aquatic food chain transfer On hold 

850.4225 Seedling emergence, Tier II On hold 

850.4250 Vegetative vigor, Tier II On hold 

850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II On hold 

850.5400 Algal toxicity, Tiers I and II On hold 

850.6800 Modified Activated Sludge Respiration Inhibition On hold 

870.3465 90-day inhalation toxicity On hold 

875.1400 Inhalation exposure - indoor On hold 

875.1700 Product Use Information On hold 

875.2300 Indoor surface residue dissipation On hold 

875.2700 Product Use Information On hold 

875.3000 Non-dietary ingestion exposure On hold 

Table 4 - Silver Sulfate (GDCI-072511-1130) 

February 29, 2012 

Guideline 

Requirement 

Number Study Title Due Date 

830.7520 Particle size, fiber length, and diameter distribution 90 days from receipt of 

letter 

830.7840 Water solubility: Column elution method, shake flask 

method 

90 days from receipt of 

letter 

835.1100 Activated sludge sorption isotherm On hold 

850.1350 Mysid chronic toxicity test On hold 

850.1400 Fish early-life stage toxicity test On hold 

850.1735 Whole sediment: acute freshwater invertebrates On hold 

850.1740 Whole sediment: acute marine invertebrates On hold 

850.1850 Aquatic food chain transfer On hold 

850.4225 Seedling emergence, Tier II On hold 

850.4250 Vegetative vigor, Tier II On hold 

850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II On hold 

850.5400 Algal toxicity, Tiers I and II On hold 

850.6800 Modified Activated Sludge Respiration Inhibition On hold 

870.3465 90-day inhalation toxicity On hold 
8 

875.1400 Inhalation exposure - indoor On hold 

875.1700 Product Use Information On hold 

875.2300 Indoor surface residue dissipation On hold 

875.2700 Product Use Information On hold 

875.3000 Non-dietary ingestion exposure On hold 

Table 5 - Silver Nitrate (GDCI-072503-1131) 

February 29, 2012 

Guideline 

Requirement 

Number Study Title Due Date 

830.1600 Description of materials used to produce the product 90 days from receipt of 

letter 

830.1620 Description of production process 90 days from receipt of 

letter 

830.1700 Preliminary analysis 90 days from receipt of 

letter 

830.1800 Enforcement analytical method 90 days from receipt of 

letter 

830.1900 Submittal of samples 90 days from receipt of 

letter 

830.7520 Particle size, fiber length, and diameter distribution 90 days from receipt of 

letter 

830.7840 Water solubility: Column elution method, shake flask 

method 

90 days from receipt of 

letter 

835.1100 Activated sludge sorption isotherm On hold 

850.1350 Mysid chronic toxicity test On hold 

850.1400 Fish early-life stage toxicity test On hold 

850.1735 Whole sediment: acute freshwater invertebrates On hold 

850.1740 Whole sediment: acute marine invertebrates On hold 

850.1850 Aquatic food chain transfer On hold 

850.4225 Seedling emergence, Tier II On hold 

850.4250 Vegetative vigor, Tier II On hold 

850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II On hold 

850.5400 Algal toxicity, Tiers I and II On hold 

850.6800 Modified Activated Sludge Respiration Inhibition On hold 

870.3465 90-day inhalation toxicity On hold 

875.1400 Inhalation exposure - indoor On hold 

875.1700 Product Use Information On hold 
9 

875.2300 Indoor surface residue dissipation On hold 

875.2700 Product Use Information On hold 

875.3000 Non-dietary ingestion exposure On hold 

Table 6 - Silver Chloride (GDCI-072506-1132) 

February 29, 2012 

Guideline 

Requirement 

Number Study Title Due Date 

830.7520 Particle size, fiber length, and diameter distribution 90 days from receipt of 

letter 

830.7840 Water solubility: Column elution method, shake flask 

method 

90 days from receipt of 

letter 

835.1100 Activated sludge sorption isotherm On hold 

850.1350 Mysid chronic toxicity test On hold 

850.1400 Fish early-life stage toxicity test On hold 

850.1735 Whole sediment: acute freshwater invertebrates On hold 

850.1740 Whole sediment: acute marine invertebrates On hold 

850.1850 Aquatic food chain transfer On hold 

850.4225 Seedling emergence, Tier II On hold 

850.4250 Vegetative vigor, Tier II On hold 

850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II On hold 

850.5400 Algal toxicity, Tiers I and II On hold 

850.6800 Modified Activated Sludge Respiration Inhibition On hold 

870.3465 90-day inhalation toxicity On hold 

875.1400 Inhalation exposure - indoor On hold 

875.1700 Product Use Information On hold 

875.2300 Indoor surface residue dissipation On hold 

875.2700 Product Use Information On hold 

875.3000 Non-dietary ingestion exposure On hold 

Table 7 - Silver Oxide (GDCI-129097-1133) 

February 29, 2012 

Guideline 

Requirement 

Number Study Title Due Date 
10 

830.1600 Description of materials used to produce the product 90 days from receipt of 

letter 

830.1620 Description of production process 90 days from receipt of 

letter 

830.1650 Description of formulation process 90 days from receipt of 

letter 

830.1670 Discussion of formation of impurities 90 days from receipt of 

letter 

830.1700 Preliminary analysis 90 days from receipt of 

letter 

830.1750 Certified limits 90 days from receipt of 

letter 

830.1800 Enforcement analytical method 90 days from receipt of 

letter 

830.1900 Submittal of samples 90 days from receipt of 

letter 

830.6314 Oxidizing or reducing action 90 days from receipt of 

letter 

830.6315 Flammability 90 days from receipt of 

letter 

830.6316 Explodability 90 days from receipt of 

letter 

830.6317 Storage stability of product 90 days from receipt of 

letter 

830.6319 Miscibility 90 days from receipt of 

letter 

830.6320 Corrosion characteristics 90 days from receipt of 

letter 

830.6321 Dielectric breakdown voltage 90 days from receipt of 

letter 

830.7000 pH of water solutions or suspensions 90 days from receipt of 

letter 

830.7100 Viscosity 90 days from receipt of 

letter 

830.7200 Melting point/melting range 90 days from receipt of 

letter 

830.7520 Particle size, fiber length, and diameter distribution 90 days from receipt of 

letter 

835.1100 Activated sludge sorption isotherm On hold 

850.1350 Mysid chronic toxicity test On hold 
11 

850.1400 Fish early-life stage toxicity test On hold 

850.1735 Whole sediment: acute freshwater invertebrates On hold 

850.1740 Whole sediment: acute marine invertebrates On hold 

850.1850 Aquatic food chain transfer On hold 

850.4225 Seedling emergence, Tier II On hold 

850.4250 Vegetative vigor, Tier II On hold 

850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II On hold 

850.5400 Algal toxicity, Tiers I and II On hold 

850.6800 Modified Activated Sludge Respiration Inhibition On hold 

870.3465 90-day inhalation toxicity On hold 

875.1400 Inhalation exposure - indoor On hold 

875.1700 Product Use Information On hold 

875.2300 Indoor surface residue dissipation On hold 

875.2700 Product Use Information On hold 

875.3000 Non-dietary ingestion exposure On hold 

Table 8 - Silver Ion (GDCI-072500-1194) 

July 6, 2012 

Guideline 

Requirement 

Number Study Title Due Date 

830.1600 Description of materials used to produce the product 90 days from receipt of 

letter 

830.1620 Description of production process 90 days from receipt of 

letter 

830.1650 Description of formulation process 90 days from receipt of 

letter 

830.1670 Discussion of formation of impurities 90 days from receipt of 

letter 

830.1700 Preliminary analysis 90 days from receipt of 

letter 

830.1750 Certified limits 90 days from receipt of 

letter 

830.1800 Enforcement analytical method 90 days from receipt of 

letter 

830.1900 Submittal of samples 90 days from receipt of 

letter 

830.6314 Oxidizing or reducing action 90 days from receipt of 

letter 
12 

830.6315 Flammability 90 days from receipt of 

letter 

830.6316 Explodability 90 days from receipt of 

letter 

830.6317 Storage stability of product 90 days from receipt of 

letter 

830.6319 Miscibility 90 days from receipt of 

letter 

830.6320 Corrosion characteristics 90 days from receipt of 

letter 

830.6321 Dielectric breakdown voltage 90 days from receipt of 

letter 

830.7520 Particle size, fiber length, and diameter distribution 90 days from receipt of 

letter 

830.7840 Water solubility: Column elution method, shake flask 

method 

90 days from receipt of 

letter 

835.1100 Activated sludge sorption isotherm On hold 

850.1350 Mysid chronic toxicity test On hold 

850.1400 Fish early-life stage toxicity test On hold 

850.1735 Whole sediment: acute freshwater invertebrates On hold 

850.1740 Whole sediment: acute marine invertebrates On hold 

850.1850 Aquatic food chain transfer On hold 

850.4225 Seedling emergence, Tier II On hold 

850.4250 Vegetative vigor, Tier II On hold 

850.4400 Aquatic plant toxicity test using Lemna spp. Tiers I and II On hold 

850.5400 Algal toxicity, Tiers I and II On hold 

850.6800 Modified Activated Sludge Respiration Inhibition On hold 

870.3465 90-day inhalation toxicity On hold 

875.1400 Inhalation exposure - indoor On hold 

875.1700 Product Use Information On hold 

875.2300 Indoor surface residue dissipation On hold 

875.2700 Product Use Information On hold 

875.3000 Non-dietary ingestion exposure On hold 

A copy of this letter will be placed in the Silver Compounds and Nanosilver registration review 

public dockets (EPA-HQ-OPP-2009-0334 and EPA-HQ-OPP-2011-0370, respectively). If you 

have any questions regarding this letter, please contact SanYvette Williams, DVM, the chemical 

review manager (CRM) of these cases. Any questions should be directed to her in writing either 

by email at williams.sanyvette@epa.gov or by USPS letter. 
13 

 

CC: Lance Wormell, Chief, Regulatory Management Branch II, Antimicrobials Division 

 John Hebert, Chief, Regulatory Management Branch I, Antimicrobials Division 

 Rose Kyprianou, Reevaluation Team Leader, Antimicrobials Division 

 Seiichi Murasaki, Acting Product Manager 33, Antimicrobials Division 

 SanYvette Williams, Chemical Review Manager, Antimicrobials Division 

 

Sincerely, 

Jennifer L McLain, Acting Director 

Antimicrobials Division (7510P) 

Office of Pesticide Programs