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Registration of NSPW-L30SS 

EPA Response to Comments Received for Docket: EPA-HQ-OPP-2012-0594 

The public comment period was open from August 27 until September 26, 2013 and a total of ten 

public comment submissions were received as of November 8, 2013. All public comments were 

assigned a docket number and are included in this document grouped as follows: 

 Citizens – Two public comment submissions from Citizens 

 Trade Associations – Three public comment submissions from Trade Associations 

(Copper Development Association, Silver Nanotechnology Working Group, Silver 

Task Force North America ) 

 Non-governmental organizations (NGOs) – Five public comment submissions from 

NGOs (Californians for Pesticide Reform, People for the Ethical Treatment of 

Animals (PETA) and Physicians Committee for Responsible Medicine (PCRM), 

The Natural Resources Defense Council (NRDC), Farmworker Association of 

Florida, The International Center for Technology Assessment (ICTA) and Center 

for Food Safety (CFS)) 

Citizens 

Commenter 1: Clean Production Action (EPA-HQ-OPP-2012-0594-0014, Received 

9/26/2013) 

Comment 1.1: There needs to be greater scrutiny, oversight and transparency about 

hazards associated with [NSPW-L30SS] and EPA should be discriminating about specific 

uses. For example, uses that result in discharge to water should be considered differently 

from uses that are unlikely to discharge to water. 

Response 1.1: With respect to concerns about differentiating use sites, EPA considered all 

proposed uses of NSPW-L30SS (including uses that would result in discharges to water 

and uses that are unlikely to discharge to water) when preparing the registration decision. 

As part of problem formulation, EPA groups use sites and assesses the higher exposure use 

sites to screen for risks, separating and refining such grouping as needed during the 

assessment phase to discriminate, for example, between uses or use sites which present no 

risk concern and therefore merit no further assessment or mitigation versus those which 

may present a risk concern and therefore may merit further assessment or potential 

mitigation such as label changes. Since the degree to which each specific use is assessed 

separately from all other uses depends on how refined an assessment is needed, separate 

quantitative risks will not necessarily be calculated for each specific use site. As in this 

case, if a use with the highest possible exposure for a given pathway poses no unacceptable 

adverse effects, no additional refinement and resources are needed by the Agency to 

perform calculations for uses with lower exposure conditions. 

Commenter 2: Joseph S. Hayes (EPA-HQ-OPP-2012-0594-0016, Received 9/26/2013) 

Comment 2.1: It is apparent from the Draft Decision Document that “Nanosilva” is a trade 

name or trademark (which should not be used as a stand-alone noun) and a company name. 

It is not a known chemical name, but the word is also used freely throughout the document 

as a common noun to identify an (allegedly new) chemical substance. This usage is 

confusing and should be rectified. 
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Response 2.1: The decision document has been revised to clarify references to the product 

(NSPW-L30SS), company name (Nanosilva LLC), and substance (nanosilver in NSPWL30SS). 

Comment 2.2: The proposed label describes the active ingredient as “Covalently Bound 

Elemental Silver.” It is proposed that this is somehow new. However it would appear that 

[NSPW-L30SS] consists of metallic silver (PCC 072501) in the shape of nanosilver (PCC 

072599), attached to silica by thiolate bonds and deriving antimicrobial activity by 

production of silver ions (PCC 072501) by oxidation at the surface. There are already 

existing products with similar or comparable structure and function and classified under 

each of the existing PC Codes mentioned. The need for designation of this as a “new” 

chemical, under yet another PC Code, is not apparent. 

Response 2.2: The FIFRA Scientific Advisory Panel (SAP) considered the issue of 

nanosilver toxicity in its November 2009 meeting. In general, the SAP advised that the 

toxicity of nanosilver could differ from and might be higher than other forms of silver. 

While additional research has been conducted and published on intercellular and 

intracellular transport and toxicity of nanomaterials, including different nanosilvers since 

the 2009 SAP, the understanding of how physiochemical properties, such as size, shape, 

surface area, surface chemistry, and reactivity affect behavior and toxicity of nanomaterials 

is still in its infancy. While the Agency has not reviewed all of the research published since 

2009, the research that has been reviewed continues to support the same concerns 

identified in the 2009 SAP, that the hazards of nanosilvers cannot be fully characterized 

using data for the silver ion alone nor by using only data on other nanosilver products. 

Taking into consideration the SAP recommendation, the current understanding of behavior 

and toxicity of different manufactured nanosilvers, especially as it relates to ionic silver, 

and accumulation and toxicity, and in response to Nanosilva LLC’s request for registration 

of a new active ingredient, EPA determined that it would evaluate the manufactured 

nanosilver in NSPW-L30SS in the same manner as a new active ingredient given (i) that 

NSPW-L30SS could not be assessed as containing or releasing ionic silver alone and (ii) 

that the nanosilver in NSPW-L30SS was not similar to the manufactured nanosilver in any 

previously issued registration. Until there is sufficient research defining how the 

characteristics of different nanosilvers affect behavior and toxicity, applications for a 

pesticide product containing a new nanosilver material may need to be assessed as EPA 

would assess a new active ingredient. The Agency also determined it would be appropriate 

to establish a single PC Code to categorize and review all products containing nanosilver 

to recognize that toxicity and behavior of manufactured nanosilvers potentially differs 

from that of metallic silver and silver salts. 

Comment 2.3: Considerable importance is also given to numerous statements along the 

lines that "silver at concentrations greater than the analytical detection limit were not found 

leaching from plastic coupons incorporating [NSPW-L30SS]” (p. v). Much weight is 

clearly placed on “were not found”; however the key phrase here is “greater than the 

analytical detection limit.” 

Response 2.3: EPA agrees with the commenter that the key phrase is “greater than the 

analytical detection limit” and acknowledges that silver at levels below the limit of 

detection (LOD) could have been released. For this reason, EPA calculated risks based on 

one-half the LOD, which as stated in the decision document was in accordance with the 
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OPP Policy Document “Assigning Values to Non-Detected/Non-Quantified Pesticide 

Residues in Human Health Food Exposure Assessment” (U.S. EPA, 2000). This document 

can be found at http://www.epa.gov/pesticides/trac/science/trac3b012.pdf. If EPA believed 

that no silver had been released, EPA would have assumed zero exposure and would not 

have calculated risks. The decision document has been updated to clarify those statements. 

Comment 2.4: I have searched in vain (perhaps with insufficient diligence) for discussion 

in the document of antimicrobial efficacy, but presume that efficacy is a requirement for 

registration. (If not, may I register distilled water?) 

Response 2.4: As explained in 40 CFR §158.2200, each registrant must ensure through 

testing that their product is efficacious when used in accordance with label directions and 

commonly accepted practices. Product performance data must be submitted with any 

application for registration or amended registration for each product that bears a public 

health claim, as described in §158.2204(a). The regulations also make clear that the 

Agency reserves the right to require, on a case-by-case basis, submission of product 

performance data for any pesticide product registered or proposed for registration or 

amendment, for example, to support a benefits assessment where there is some concern for 

risks from use of the pesticide. Because the product does not bear public health claims and 

because there is no risk concern with use of the pesticide during the four year period for 

generation of the data which would otherwise necessitate a closer look at the benefits from 

use of the pesticide, there is no requirement to submit, and no need to review, product 

performance data for this pesticide. 

Comment 2.5: If, ...“All silver-based pesticide products act via the release of a low 

concentration of silver ions that then interact with bacteria,” and if this material is 

effective, then that effectiveness in and of itself should constitute evidence of detection; 

and inhibited or killed bacteria could be examined for the presence of silver (for instance 

by centrifugation, digestion, and ICP-AES). 

Response 2.5: As discussed in Response 2.3, although silver was not detected, the Agency 

did not assume absence of silver in assessing the risk, and used a release rate based on onehalf the LOD in accordance with OPP policy. The commenter’s proposed method for 

detecting silver (i.e., measuring the presence of silver in the bacteria inhibited or killed), 

while an interesting surrogate approach, is not a standard or proven method for 

preconcentrating silver in an aqueous sample in preparation for analytical quantitation and 

would require substantial resources to develop and validate 

(http://www.epa.gov/waste/hazard/testmethods/sw846/online/index.htm ; OCSPP 

850.6100 on the docket at EPA-HQ-OPPT-2009-0154-0008). Moreover, there are 

potentially a number of conventional or standard approaches that can be applied to the 

study design or sample preparation to improve the sample detection limit, if needed, that 

would not require such a surrogate measurement method. For example, inclusion of an 

evaporation step during sample preparation to concentrate the sample. Additionally, 

Nanosilva LLC could have conducted and submitted a method detection limit study to 

support the lower method detection limits given in the plastics leaching study report that 

ranged from 0.8 to 2 μg/L for the non-oil trials over the LOD of 5 μg/L used by the EPA 

for evaluating risk. Comment 2.6 also discusses study design changes to improve detection 

of silver. However, such issues or refinements need not be resolved for this registration at 
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this time because using the higher assumed release rates did not result in a calculation of 

potential human health or environmental risks of concern. 

Comment 2.6: The commenter suggested that the analytical technique used to detect silver 

should be improved and identified a section of the proposed decision document where the 

amount of silver leaching from treated articles might be misconstrued. The commenter also 

recommended specific modifications to the analytical technique for plastic leaching tests. 

These modifications are based on the assumption that neither silver nor silver ions would 

be expected to migrate or diffuse significantly through well-molded LLDPE [Linear Low 

Density Poly Ethylene]. The silver nanoparticles are said to have mean diameters of 

between 6.9 and 10.6 nm, therefore only nanoparticles centered within a surface layer of 

11 nm could be expected to leach silver ions. Based on a coupon surface area and volume, 

the maximum amount that could be leached from the outer 10 nm layer would be 2 ng 

which would be below the LOD for the 50 ml leaching volume that was used in the study. 

The commenter recommended that a smaller amount of leaching fluid be used, that the 

coupons be made much thinner, that multiple coupons be placed in each pouch and that 

NSPW-L30SS loading be increased in order. 

Response 2.6: EPA concurs that some of the modifications recommended by the 

commenter could allow for the measurable detection of an amount of nanosilver or other 

forms of silver released, that when calculated would likely have resulted in lower assumed 

leach rates than those used in the assessment and the risks calculated based on lower 

measured leach rates would also have been lower. These issues will be considered when 

reviewing protocols for future studies. However, these issues need not be resolved for this 

registration at this time, given the very high MOEs in comparison to the target MOEs 

calculated using the assumed release rate. Similarly, the calculated ecological risks are 

below levels of concern even with the assumed release rates. In sum, taking into account 

the low release rates and resulting levels of concern, such refinements to the leaching study 

are not necessary at this time. 

Comment 2.7: If testing of disabled bacteria and improved leaching tests should still fail 

detect any leached silver it might be reasonable to conclude that none appears, although 

even then data on hydrolysis for the agent alone should not be waived. In the (unexpected) 

event that none of these tests, including hydrolysis, show emission of any silver, then 

maybe the extensive discussion of silver and Nano silver in this Draft can be eliminated 

from the final Decision Document and we can think instead about some other mechanism 

of antimicrobial efficacy -- perhaps Einstein’s “spooky action at a distance.” 

Response 2.7: Please see Response 2.5. Also, as explained in Appendix A of the proposed 

decision document, EPA waived the need to conduct a hydrolysis test because metals, 

including nanosilver, do not undergo hydrolytic transformation. 

Trade Associations 

Commenter 3: Harold T. Michels, Copper Development Association (EPA-HQ-OPP-2012-

0594-0017, Received 9/26/2013) 

Comment 3.1: As with other silver-based “antimicrobial” pesticide products already 

registered by EPA, CDA is concerned about the efficacy of and claims made for this 

product which is intended to be incorporated into “treated articles.” There is a long history 

– reflected in EPA enforcement actions and the numerous unaddressed complaints filed by 
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CDA and others with the agency – demonstrating that “treated articles” often are not 

marketed in a manner consistent with the clear requirements for “non-public health” 

products. Rather, these types of products are consistently marketed with implicit and, in 

some cases, explicit public health claims and with advertising and labeling language that 

does not make clear to the consumer that the products do not afford public health 

protection. As a result of such marketing efforts, there is a widespread belief among 

consumers and users that products containing silver-based “materials preservatives” 

provide “public health” benefits. Regardless of the actual label language for [NSPWL30SS] or other silver-based antimicrobial additives, the fact is that there is a general 

association in the mind of the public that a product containing a silver-based additive can 

protect the user against bacteria or other microorganisms that endanger public health. 

Accordingly, CDA urges EPA to require submission of efficacy data, comparable to that 

required for “public health” antimicrobial products, prior to finalizing the [NSPW-L30SS] 

registration. Such data are necessary before EPA can conclude, as it states in the Draft 

Decision Document (at 67), “that use of [NSPW-L30SS] offers the potential for 

conservation of the environment and consumer benefits which contribute to the public 

interest.” 

Response 3.1: 40 CFR 152.25(a) exempts from regulation articles or substances treated 

with, or containing, a registered pesticide to protect the article or substance. Examples of 

this exemption are textiles treated with silver and wood products treated with copper. As 

explained in PR Notice 2000-1, this exemption does not apply to articles or substances 

“bearing implied or explicit public health claims against human pathogens.” Thus, any 

article treated or containing a registered pesticide but bearing implied or explicit public 

health claims must be separately registered. If it is not, distribution of such product is a 

violation under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) section 

12(a)(1)(A), subject to corrective action and penalties under FIFRA section 13 and 14, 

respectively. In addition, under sections 12(a)(1)(E) and 2(q)(1)(A), and 40 CFR 

156.10(b)(2) and 40 CFR 156.10(a)(5), pesticide products with brand names that, in a false 

or misleading manner, state or imply safety, efficacy or comparative claims, or are 

otherwise false or misleading in any particular, are considered to be misbranded and may 

not be sold or distributed. With respect to the comment that efficacy data/product 

performance data are necessary to conclude that use of the pesticide is in the public 

interest, in this case, EPA disagrees. As explained in Response 2.4, product performance 

data that might provide more detailed analysis of the efficacy of the product is not required 

to be submitted here because no public health claims are made as part of the proposed 

registration of this product and because there are no risk concerns with granting this 

registration. However, EPA believes it is appropriate to rely on the following information 

in determining that granting use of the proposed product is in the public interest: (i) clear 

evidence of low release rates of nanosilver and silver when using the proposed product; 

and (ii) lower application rates for the proposed product as compared to higher application 

rates for other silver-based products on the market (see Table 1). Collectively, this 

information supports the conclusion that there will be less exposure to humans and aquatic 

and terrestrial systems to the silver (in the form of nanosilver) in this product as compared 

to exposures from use of traditional silver-based products. Significantly lower releases and 

exposures, where there is no evidence of significantly higher toxicity, is inherently in the 

public interest. 
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Table 1 – Application Rates for Conventional Silver Products Used on Textiles

Product Name 

EPA 

Registration 

Number 

Max. 

Application 

Rate (ppm) 

IRGAGUARD B5000 40810-18 132 

BACTEKILLER AZ 82415-2 525 

ZEOMIC TYPE AV SILVER ZEOLITE A 71227-6 600 

ALPHASAN RC 5000 11631-2 760 

NOVARON AG 300 74079-1 760 

ZEOMIC TYPE AW SILVER ZEOLITE A 71227-5 1180 

ZEOMIC TYPE AJ SILVER ZEOLITE A 71227-1 1250 

ZEOMIC TYPE AC SILVER CU ZEOLITE A 71227-7 1750 

NOVARON AGZ330 74079-2 2000 

ALPHASAN RC 2000 11631-3 2000 

ALPHASAN RC 7000 11631-4 2000 

ZEOMIC TYPE AK SILVER ZEOLITE A 71227-4 2500 

APACIDER - AW 68317-2 4060 

SILVA DUR 707-313 5000 

AGION SILVER ANTIMICROBIAL TYPE AL 88165-2 5000 

AGION SILVER ANTIMICROBIAL TYPE AD 88165-1 11000 

Comment 3.2: Concerns of equity and fairness demand that, instead of allowing silverbased antimicrobial products, including [NSPW-L30SS], to be marketed under the guise of 

the “treated article” exemption, EPA insist that the efficacy of silver-based products be 

supported by meaningful, real world, GLP efficacy data. 

CDA urges EPA to undertake a rigorous review of the label claims and marketing 

materials for all silver-based products, including [NSPW-L30SS] and other “nano-silver” 

products, to address the consumer confusion these products engender by, at minimum, 

implying protection of users from bacteria and other microorganisms. 

Response 3.2: Please refer to Responses 2.4 and 3.1, above. A review of other existing 

registrations is not applicable to the registration in question, and is not addressed in this 

response-to-comments document. 

Comment 3.3: CDA provided the Agency with information (including a journal article) on 

a materials preservative test protocol, Japanese Industrial Standard (“JIS”) Z 2801. 

Response 3.3: The Agency thanks CDA for the information regarding JIS Z 2801. As 

explained in Response 2.4, product performance data that might provide more detailed 

analysis of the efficacy of the product is not required to be submitted here because no 

public health claims are made as part of the proposed registration of this product and 

because no benefits assessment is necessary for this registration. 

Commenter 4: Roslyn Volpe, Silver Nanotechnology Working Group (EPA-HQ-OPP-2012-

0594-0015, Received 9/19/2013) 

Comment 4.1: The Silver Nanotechnology Working Group (SNWG) is extending support 

of the Agency decision to register a second nanosilver-containing product named [NSPWL30SS]. The SNWG feels this is a bold move that gives credibility to efficient, sustainable, 

cost-effective nanotechnology products and encourages further opportunities to prove their 

benefits to society. The SNWG and its membership appreciate the careful risk analysis that 
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the EPA has done on all possible health and exposure endpoints of concern using the most 

current data available and applying conservative estimates of possible risk and responding 

to concerns that have emerged since the last conditional Nanosilver Registration was 

approved. 

The SNWG recognizes the vulnerability of such pioneering efforts. We trust that each of 

these emerging products will be able to withstand the inevitable scrutiny that will occur 

until the ongoing EPA requested research studies are complete. We are confident that the 

research results will provide support and confirmation of EPA's conservative risk 

assessments on these nanosilver products, and will mitigate concerns about the safety of 

Nanosilver products to the public health and the environment. 

The SNWG looks forward to the allowance of the Conditional Registration for [NSPWL30SS], and to all future conditional registrations for safe and effective Nanosilver 

products. 

Commenter 5: Erin M. Tesch, Silver Task Force North America (STFNA) (EPA-HQ-OPP2012-0594-0021, Received 9/26/2013) 

Comment 5.1: The draft decision document acknowledges that the biologically active 

moiety for silver‐based active ingredients is the silver ion. This is the position of the 

STFNA and it is supported by the preponderance of scientific literature. On a practical 

level this acknowledgement will facilitate the Agency’s review of silver‐based actives 

during the current DCI and eliminate the duplication of studies that would result from the 

Agency treating each silver‐based active individually. 

The Agency refers to [NSPW-L30SS] as containing nanosilver as a new active ingredient. 

The STFNA has previously expressed the position that the active component of 

toxicological interest for all silver‐based antimicrobials is the silver ion, and therefore all 

silver‐based antimicrobials should be categorized and reviewed as a group. The Agency’s 

decision to categorize [NSPW-L30SS] as containing a new active is confusing and is a 

departure from the Agency’s longstanding definition of ‘new active ingredient’. 

Specifically, the Pesticide Registration Manual: Chapter 5 ‐ Registration Fees defines a 

“New Active Ingredient” as “An active ingredient that is not currently contained as an 

active ingredient in any registered pesticide product.” This longstanding definition of “new 

active ingredient” is not left to the registrant’s discretion, nor is it dependent upon inert 

ingredients included in the product, but rather is evidence‐based with “new” being derived 

from a comparison to currently registered pesticides. In other words, the Agency has 

historically determined if an active ingredient is new by comparing the chemical structure 

of the active ingredient to the chemical structures of active ingredients of currently 

registered products. Because [NSPW-L30SS]’s active ingredient is silver (and its 

antimicrobial activity is derived from silver ions) STFNA believes that [NSPW-L30SS] 

should be categorized with other metallic silver compounds for the purposes of risk 

assessment. This would be consistent with the conclusion that the active component of 

toxicological interest and the biologically active moiety is the silver ion. This would also 

allow the Agency, the registrant, and other current silver registrants to benefit from the 

efficiency derived from joint review and data generation. 

Response 5.1: As stated in the decision document, the active ingredient addressed by 

much of this assessment is the nanosilver in NSPW-L30SS. The Agency does not agree 
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that the silver ion is the only component of toxicological interest for NSPW-L30SS and 

nanosilver. The Agency is aware that the STFNA suggests that the health and safety 

properties of NSPW-L30SS and nanosilver can be fully characterized using data for the 

silver ion. However, the FIFRA Scientific Advisory Panel (SAP) considered the issue of 

nanosilver toxicity in its November 2009 meeting. In general, the SAP advised that the 

toxicity of nanosilver could differ from and might be higher than other forms of silver 

including the silver ion. The Agency is aware of, and commenters provide, no new data to 

suggest that the SAP review and recommendation is misplaced or that the hazard for the 

nanosilver in or released from use of a pesticide product can be fully characterized using 

only silver ion hazard data. Thus, EPA continues to agree with the SAP concerns discussed 

in 2009. As a result, while silver ions are present and EPA relies in part on the silver ion 

assessment to grant this conditional registration, the nanosilver moiety is present and 

requires review to grant the registration. With respect to the commenter’s concern 

regarding EPA’s determination that the nanosilver in NSPW-L30SS is a new active 

ingredient, EPA’s decision to accept the application for this product and to evaluate the 

nanosilver in NSPW-L30SS in the same manner as any new active ingredient is based on 

the fact that (i) NSPW-L30SS could not be assessed as ionic silver alone and (ii) EPA had 

no information to otherwise demonstrate that the nanosilver in NSPW-L30SS was similar 

to an ingredient in any previously issued registration. Contrary to commenter’s claim, this 

approach is not a significant departure from the advice provided to registrants in the 

Pesticide Registration Manual; consistent with the description for “new active ingredient,” 

EPA considered whether the nanosilver in NSPW-L30SS was found in any previously 

issued registration. While past approaches for determining whether an ingredient is a new 

active ingredient may not have focused on the size, size range or other physiochemical 

properties of the ingredient, the definitions of “active ingredient” and “new active 

ingredient” are not drafted to prescriptively address issues of this specific nature, and thus 

leave with the Agency the necessary discretion to use its scientific judgment on how best 

to classify an ingredient. With respect to Commenter’s suggestion that EPA is referencing 

inert ingredients or properties to justify the “new active” classification, EPA is making the 

determination based on the nanosilver in the product (the nanosilver in NSPW-L30SS has 

a different size range than the nanosilver in other products registered as containing 

nanosilver). 

Comment 5.2: The data requirements also seem to be inconsistent with those requirements 

of the most recent registrations and associated DCIs. The STFNA believes that the Agency 

has the responsibility to normalize data requirements across all silver compounds not only 

as a matter of fairness, but also to permit efficient review and data generation. 

Response 5.2: The nanosilver data requirements identified as terms and conditions on the 

registration of the current product are based on the data requirements specified in 40 CFR 

Part 158, adapted to address nanoscale silver. To the extent silver is also present or 

released from the current product, the data requirements identified as a term and condition 

on the current product can be cited to satisfy the relevant data required by the recent silver 

DCIs, available at regulations.gov (Docket ID: EPA-HQ-OPP-2009-0334). 

Comment 5.3: On a specific technical level, the STFNA is critical of the leaching study 

reviewed in the document. Due to the small size of the test samples and the corresponding 

small amount of leachable silver present near the surface of the sample, it is questionable if 

there was sufficient silver present to be detected in the leachate. 
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Response 5.3: Leaching studies are used to reveal the release rate of the proposed 

pesticide based on the maximum legal rate of application. The release rate is one factor 

influencing the estimate of potential exposure from use of the proposed pesticide. Per the 

proposed label, the application method for NSPW-L30SS is incorporation, and although 

the leaching study identified no measurable detection of the proposed pesticide from test 

fabric incorporating the pesticide, EPA estimated a release rate based on one-half the LOD 

in accordance with OPP policy (see Response 2.3). While this approach admittedly may 

exaggerate the release rate and therefore the exposure to the pesticide, given the calculated 

MOEs were significantly greater than target MOEs and environmental risks were below 

levels of concern, EPA does not believe it is necessary to consider the types of refinements 

recommended by the commenter. These issues will, however, be considered in future 

applications and with future assessments, as appropriate. 

Comment 5.4: Per EPA guidance, as a federal governmental agency, neither the EPA nor 

its programs can endorse any products of services. However, the Draft Decision Document 

clearly states that, “EPA believes that use of [NSPW-L30SS] offers the potential for 

conservation of the environment and consumer benefits which contribute to the public 

interest.” The STFNA understands that the Agency must articulate a benefit to the public 

interest in order to conditionally register a new active ingredient. The STFNA has no 

information to assess the relative effectiveness of this product compared to other products, 

but in general the STFNA believes that the Agency should refrain from these types of 

apparent endorsements as it can create an unequal competitive landscape based on no 

empirical evidence. 

Response 5.4: Please see Response 3.1 for a discussion of the public interest finding in 

this case. Concluding that granting the registration is in the public interest is not an 

endorsement of the product. Under its authority set forth in FIFRA section 3(c)(7)(C), the 

Agency is making only a public interest finding, which is provided for purposes of this 

finding only and is not to be inferred as any endorsement of a pesticide product. EPA and 

its employees do not endorse any particular product, service or enterprise. If any registrant 

were to include "any statement directly or indirectly implying that the pesticide or device is 

recommended or endorsed by any agency of the Federal Government", then such 

statement, pursuant to 40 CFR 156.10(a)(5)(v), would be false or misleading. 

Comment 5.5: There is no evidence to suggest, as the Agency states, that nanosilver 

particles will retain efficacy for longer periods of time than conventional silver particles, 

nor can the Agency make the claim that nanosilver as an active ingredient is more effective 

than conventional silver at targeting pests. Furthermore, EPA does not require, nor has it 

evaluated, efficacy data for all silver based non‐public health materials preservative 

products. Therefore, the entire discussion of the consumer benefits of the [NSPW-L30SS] 

product are completely unsubstantiated given the fact the Agency has not reviewed 

efficacy data to be able to compare the benefits of the [NSPW-L30SS] product to other 

silver based materials preservative products. 

Response 5.5: The Agency acknowledges the comment concerning the lack of 

comparative efficacy data between conventional silver particles and nanosilver particles 

and has revised the decision document to remove language concerning comparative 

efficacy data. With respect to the comment relating to submission and review of 

efficacy/product performance data, please see Responses 2.4 and 3.1. 
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Non-governmental organizations (NGOs) 

Commenter 6: Patricia L. Bishop, People for the Ethical Treatment of Animals (PETA) and 

Kristie Sullivan, Physicians Committee for Responsible Medicine (PCRM) (EPA-HQ-OPP2012-0594-0020, Received 9/26/2013) 

Comment 6.1: EPA’s State of the Science report on Nanosilver indicates that tests that 

have already been conducted on nanosilver using animals display a considerable lack of 

reproducibility in experimental results. Variations can be traced to the vast differences in 

morphological shape of nanosilver (from rods, to spheres, particles, cubes, truncated 

triangles, wires, and films) and even, more importantly, to the differing animal species 

used in experiments. As the available data also demonstrate, nanosilver properties change 

depending on the exact size/surface area of the nanosilver particles, the carrier used, any 

coatings, and whether the nanosilver has surface modifications, which in turn can have 

effects on its biological activity. These variable properties also can contribute to nanosilver 

behaving differently from bulk silver. 

The bioavailability, fate and transport of nanosilver are dependent upon numerous factors. 

These include particle size, ease of aggregation, surface characteristics, and colloidal 

stability, which in turn is a function of the capping agent, pH, ionic strength, and presence 

of ligands, to name a few. Nanosilver toxicity has been shown to vary with route of 

exposure, oxidation state, and most importantly, physicochemical characteristics. The State 

of the Science report declares “The physicochemical features of the nanoparticles must be 

characterized under the experimental setting so that definitive associations between these 

parameters and any biological responses observed may be identified.” It is also noted in the 

State of the Science report that “...a good dispersion of the silver nanoparticles is required 

for effective toxicological and/or antibacterial activities, and might influence its 

subsequent toxicity. Toxicity determination of nanosilver particles may be dependent on 

the size distribution of the particles.” Thus, for an animal test to have any validity, 

characteristics such as the concentration, diameter and chemical composition of nanosilver 

in the exposure scenario must be identified and mimicked in the experimental setting. Yet, 

the report goes on to say that there are difficulties in accurately measuring and delivering 

doses as well as monitoring nanomaterial behavior, particularly in solution (and in vivo). 

With a potential biological response dependent on numerous factors – and many of these 

factors lacking reliable means of measurement – it is impossible to generate meaningful 

information by conducting the above-mentioned animal tests. For example, it will 

undoubtedly prove technically challenging to deliver representative and appropriate doses 

of nanosilver to rats in the inhalation toxicity test being proposed for this antimicrobial 

pesticide registration review. Therefore, due to the high potential for generating the type of 

equivocal results seen in many other animal studies with nanosilver, it is likely that these 

tests may need to be repeated and so would be a waste of animal lives and resources. 

Response 6.1: Variability between nanosized and conventional-sized chemicals and 

among nanosilver chemicals was addressed in the SAP 2009 Report and is recognized by 

the Agency as an important part of characterizing nanomaterials. With regards to the 

differences between nanosilver and silver ions, please see Responses 2.2 and 5.1. With 

regard to the differences among nanosilver chemicals, because a nanosilver ingredient may 

have different hazards or different degree of hazards as compared to another nanosilver 

ingredient, each nanosilver ingredient may need to receive an assessment that is equivalent 
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in many cases to that provided for new active ingredients. Any potential differences in 

toxicity due to physiochemical differences between the nanosilver in these studies and the 

nanosilver in NPSW-L30SS is covered by an additional 10X database uncertainty factor. 

Please see Response 6.2 for information on the inhalation requirements. These positions 

were summarized in the proposed decision document. Thus, while there may be some 

variations in the toxicity profile of nanosilvers, EPA found that using studies that offered 

the best available data and an additional 10X database uncertainty factor to cover any 

variations between the nanosilvers resulted in calculated MOEs well above the LOC. With 

respect to concerns that data on nanosilver ingredients are not reproducible for the reasons 

noted in the comments, registrants will be required to submit protocols for review to ensure 

that the studies required as a term and condition on the registration will be conducted in a 

fashion to provide meaningful information and so that repetition of a study would not be 

necessary. 

Comment 6.2: In addition to the considerable uncertainty in toxic potential associated 

with the physicochemical variability of nanomaterials, there are many documented 

uncertainties in extrapolating from laboratory animal studies to the human situation 

including: differences in meaningful dosages, variations in responses to chemicals and in 

target organs and tissue effects with different species and strains of animals, as well as 

different toxic thresholds between species including humans. Importantly, biological 

relevance is unlikely with the currently-used rat tests – issues relating to breathing mode, 

physiology, relative sizes of nerve bulbs and the different rate of particle clearance of rats

compared to humans all point to important anatomical and physiological differences that 

preclude clear data extrapolation between species. Certainly, some of these differences will 

make interpretation of the proposed inhalation study results challenging and given the 

likely unrealistic oral dosages and exposure times involved, it seems impossible that the rat 

reproductive/developmental toxicity test being called for in this pesticide registration 

review could provide meaningful data. 

Risk of longer-term exposure to [NSPW-L30SS] would seem to be greatest at the factory 

where workers handle, mix, and load the product. Yet, EPA has issued strict mitigation 

measures to ensure very low exposure potential. These include: 1) closed system loading 

of [NSPW-L30SS] suspensions; 2) NIOSH certified full-face respirators immediately 

available for use in emergency; 3) use of gloves that are chemically resistant to all 

components of [NSPW-L30SS] liquid suspension; 4) use of long-sleeve shirts, long pants, 

and shoes plus socks. It would appear extremely unlikely that any exposures under these 

conditions would result in long-term reproductive and developmental effects in workers, so 

that results of rat reproductive/developmental screening under relatively high dosages are 

unlikely to provide any useful, human-relevant information. 

Response 6.2: As is common in most risk analyses, EPA used a 10X uncertainty factor in 

identifying the target LOC to account for variability between animals and humans 

(interspecies) and another 10X uncertainty factor to account for variability between 

humans (intraspecies). An additional 10X uncertainty factor is used here to account for 

uncertainties in the data base generally, and an additional 3X uncertainty factor was used 

to assess risks for intermediate exposures to account for the absence of a NOAEL in the 

study used for identifying the intermediate POD. The 10X database uncertainty addresses 

potential variations among nanosilver ingredients in the substance tested in the studies 

cited and the nanosilver in NSPW-L30SS. For example, the 10x database uncertainty 
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covers in part how the different physiochemical properties of the nanosilver used in Song 

et al. (2012) and nanosilver in NSPW-L30SS affect inhalational toxicity, and takes into 

consideration (i) the sensitive effects of decreases in physiological measures of lung 

function combined with chronic alveolar inflammation and macrophage accumulation in 

the lungs, and (ii) that the inhalation POD from the Song et al. (2012) study results in a 

MOE that is near the LOC when exposure is assessed with a closed system. In EPA’s 

judgment, while the use of the POD from the Song et al. (2012) study and the 10x database 

uncertainty ensures that the assessment is protective of potential inhalation effects, the 

uncertainty regarding the difference between physiochemical properties for purposes of 

assessing inhalation toxicity, and taking into consider the effects observed in the public 

literature inhalation study, is best addressed by the 90-day Inhalation Study required as a 

term and condition on the registration. Additionally, the Agency has developed protocols 

and programs such as Regional Dose Deposited Ratio (RDDR) which specifically accounts 

for differences in human and rat inhalation mechanisms. The addition of a functional 

observation battery and detailed neuropathology will also help address the uncertainties 

noted above with this route of exposure. 

There are uncertainties based on the study results relating to reproductive and 

developmental effects via any route of exposure. Specifically, there were dose-dependent 

increases in the concentration of silver in the testes of rats after oral ingestion (Kim et al, 

2008), inhalation (Song et al, 2012) and injection (Lee et al. 2012) of nanosilver and, in 

another study, nanosilver was distributed to major maternal organs and extra-embryonic 

tissues although no adverse morphological effects on the developing embryos were 

observed (Austin et al, 2011). However, a paper by Yu et al. (Yu et al, 2013) shows that 

there were no maternal or developmental effects up to 1000 mg/kg bw using a nanosilver 

7.5 nm in size. Thus, although “EPA believes that the inhalation NOAEL of 49 μg/m3

based on the Song et al. (2012) study is expected to be protective of developmental and 

reproductive effects of nanosilver”, and the Yu et al, 2013 study supports this conclusion, 

in EPA’s judgment, the uncertainty with respect to reproductive and development effects 

and with respect to potential variations among nanosilver ingredients is best refined by the 

reproductive/developmental screening study via the inhalation route, and will help 

determine whether a POD for reproductive/developmental toxicity should be used in 

assessing NSPW-L30SS. 

Comment 6.3: Furthermore, there is no clear rationale given in the Draft Decision 

Document for Conditional Registration of [NSPW-L30SS] for conducting a 90-day 

inhalation study. In 2012, EPA was reviewing a similar silica-nanosilver composite 

product, HeiQ AGS-20, which contains nanosilver particle sizes in the 1-10 nm range, 

similar to [NSPW-L30SS]. At that time, EPA required a 90-day inhalation study in rats be 

conducted to confirm findings of cited non-guideline studies submitted for HeiQ AGS-20. 

These same studies (i.e., Sung et al. 2008, 2009) were cited for [NSPW-L30SS] as well as 

a newer inhalation study (Song et al. 2012). Sung et al. (2009) conducted a 90-day 

inhalation study using nanosilver particles that EPA notes were of similar size to the 

pesticide product under review, and a NOAEL of 133 ug/m3

 was determined. Song et al. 

(2012) followed up with a lung-recovery study that indicated lung pathology findings 

similar to Sung et al. (2009) and showed gradual clearing in females, but persistent 

inflammation in high-dose males. A NOAEL of 49 ug/m3

 was derived from this study. In 

addition, two 28-day inhalation studies are available. EPA states in the above document 
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that the Song et al. (2012) study is the most appropriate study for inhalation exposure and 

is using the lower NOAEL of that study as the point of departure (POD) for short- and 

intermediate-term inhalation exposures to the nanosilver in [NSPW-L30SS]. EPA goes on 

to state that the inhalation NOAEL of 49 ug/m3

 is expected to be protective of 

developmental and reproductive effects of nanosilver, as well as neurotoxic effects. 

However, a supplemental DER was issued on 8/1/2013 for the 90-day inhalation toxicity 

test for nanosilver, and indicated that while the Song et al. (2012) study was acceptable and 

both a NOAEL and a LOAEL could be determined, the study still did not satisfy the 

guideline requirements for OCSPP 870.3465. EPA should provide further details on what 

necessary information is lacking and how this information, if gathered, would be used to 

modify labeling and further mitigate the already stringent [NSPW-L30SS] handling 

procedures. EPA should also provide evidence that the two products ([NSPW-L30SS] and 

HeiQ AGS-20) are substantially different in toxicologically-relevant ways that justify 

performing two separate 90-day inhalation studies. Otherwise, the results of the pending 

HeiQ AGS-20 study should be obtained before requiring inhalation studies on [NSPWL30SS]. 

Similarly, requiring a reproduction/developmental toxicity screen for both materials may 

be duplicative. EPA should wait for the results of the testing on HeiQ AGS-20 before 

requiring that hundreds more animals be killed. 

Response 6.3: Please see Response 6.2 for the reason for requiring the inhalation studies. 

The reason that inhalation and reproductive/developmental (via the inhalation route) 

studies are required for both nanosilver pesticides is to reduce the separate database 

uncertainty used in the risk assessment for each, as each nanosilver is considered a new, 

separate active ingredient, their databases are also considered separately. It is unclear 

whether newly generated data will require any modification of the label or further 

mitigation of the registration. Once the data are submitted, however, EPA will determine 

whether any PODs should change, and thus whether the risks are adequately mitigated. 

Finally, as a general matter, EPA does not condition a registration on submission by 

another registrant of data nor may it unilaterally delay a response on the application 

pending submission by another entity of what may be relevant data. However, Nanosilva 

LLC and HeiQ may work together to submit data that may be relevant to both products and 

to both registrations. If Nanosilva LLC and HeiQ choose to jointly pursue generation of the 

required data, EPA recommends that they consult EPA in the process. 

Comment 6.4: Further, when considering the hazard assessment of nanosilver, its 

potential ubiquity in the environment cannot be ignored. Of the more than 250 consumer 

products claiming to contain nanosilver, only a relatively few are being registered as 

pesticide products. Nanosilver is found in food packaging materials, textiles, electronics, 

cosmetics, medical devices, water disinfectants, and room sprays. However, there are very 

little data quantifying its presence or characterizing its forms in the environment or 

describing the amounts to which humans are cumulatively exposed. There are many 

questions regarding the degree to which nanosilver leaches from products, and what forms 

it may take, whether it remains as nanoparticles or aggregates, whether it dissolves or 

converts to ionic silver, and under what conditions these transformations may take place. 

Lacking information on the characterization and presence of nanosilver in the environment, 

data on amounts and forms being released from all types of products, and a clear 
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understanding of the possible interactions with the surrounding environment, it is difficult 

to see how a realistic hazard assessment and exposure scenario can be determined for the 

product subject to this pesticide registration review. 

Response 6.4: Assessing aggregate exposure and cumulative risk is only explicitly 

addressed in the FFDCA and FIFRA for food use pesticides, and are not similarly 

addressed for nonfood use pesticides. See, 21 U.S.C. § 346a(b)(2)(A)(ii) and 7 U.S.C. § 

136(bb). The Agency has reviewed leaching studies (plastics and textiles) that determine 

the amount and form of silver that consumers may be exposed to when in contact with 

plastic and textiles incorporating NSPW-L30SS. These leaching studies were incorporated 

into exposure estimates for the dermal and incidental oral routes of exposure. The 

Agency’s risk assessment also evaluated and is protective for children who may 

simultaneously be exposed to nanosilver via the incidental oral and dermal routes of 

exposure while mouthing toys, contacting flooring, and mouthing textiles incorporating 

NSPW-L30SS. Inhalation exposure to children during laundry drying of textiles 

incorporating NSPW-L30SS is not anticipated and was not considered as part of the 

aggregate exposure. Aggregate assessments may also include other sources of exposure to 

NSPW-L30SS such as in food and drinking water, and exposure to other nanosilvers in the 

market place that are identical to the nanosilver in NSPW-L30SS. However, there is no 

food use for NSPW-L30SS and neither NSPW-L30SS nor the nanosilver that might break 

away from NSPW-L30SS is anticipated to enter drinking water because any particulates 

released to surface water would be removed by gravitational sedimentation and adsorption. 

The only other pesticide product registered as containing nanosilver is HeiQ AGS-20. The 

nanosilver in HeiQ AGS-20 has different size range and surface coatings than the 

nanosilver in NSPW-L30SS, and EPA has not determined that AGS-20 and NSPW-L30SS 

contain the same active ingredient or present exposures that should necessarily be 

aggregated. 

Finally, even if the Agency had concluded that the nanosilver in NSPW-L30SS and the 

nanosilver in HeiQ AGS-20 were the same and exposures to each were to occur 

concurrently (i.e., the markets for each pesticide are separate and therefore exposures to 

each pesticide could be additive), they would not result in MOEs that would be of concern 

(i.e., the Margin of Exposure is large). Therefore the Agency has evaluated the form and 

amount of nanosilver released from NSPW-L30SS treated articles and has determined that 

for the most sensitive subpopulation (children) there are no risks of concern and the margin 

of safety is large. 

With respect to other products (i.e., products that are not registered as pesticides containing 

nanosilver) in the marketplace that are advertised or believed to contain nanosilver the 

Agency has no reliable information to determine whether these products in fact contain 

nanosilver or, if containing nanosilver, whether the nanosilver in these products have the 

same physiochemical properties or toxicity as the nanosilver in NSPW-L30SS. Thus, the 

commenter is correct that EPA does not have reliable information that might allow an 

aggregated exposure assessment with respect to all non-pesticidal products marketed or 

believed to contain nanosilver. 

Nonetheless, the following discussion may be helpful in addressing some of the inherent 

concerns raised by the commenter with respect to products marketed as containing 

nanosilver. First, if a registered pesticide is advertised or marketed as containing 
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nanosilver but has not been registered as containing nanosilver, as part of registration 

review, additional data will be required to address whether any currently registered silverbased pesticides contain nanosilver and have similar physiochemical properties or toxicity, 

and such data will be used to assess any nanosilver component of a pesticide product. In 

contrast, if a product is not registered but makes pesticidal claims relating to nanosilver as 

a component of the product, such product may be an unregistered pesticide subject to 

enforcement if offered for sale or distribution in the United States. While other products 

advertised or marketed as containing nanosilver may be subject to regulation or control 

under other authorities or by other federal agencies, EPA notes that even the Nanotech 

project consumer products inventory (PEN, 2014) indicates that few of the advertising or 

marketing claims for products on the market as containing nanosilver are verified or 

manufacturer supported while the remainder are unsupported. Additional information 

regarding unregistered nanosilver pesticides is included in the EPA Response to the 

International Center for Technology Assessment (ICTA) Petition for Rulemaking 

Requesting EPA to Regulate Nano-Silver Products as Pesticides. The petition and the 

response may be found at www.regulations.gov in Docket ID # EPA-HQ-OPP-0650. 

With respect to the suggestion that EPA should consider the cumulative and aggregate 

impact of all the various sources of silver ions loading to the environment. EPA has 

conducted cumulative risk assessments to address human health risks for several pesticide 

groups that share a common mechanism of toxicity, but most human health risk 

assessments for pesticides are typically conducted for single chemicals. Currently, for 

ecological risk assessments, the analytical methodologies and tools are unavailable to 

analyze the ecological risks of multiple sources of a single chemical, mixtures of 

chemicals, and non-chemical stressors. However, at this time, it is not possible for the EPA 

to conduct aggregated or cumulative ecological risk assessments. 

As discussed in Response 2.3, although silver was not detected, the Agency did not assume 

absence of silver in assessing the risk, and used a release rate based on one-half the LOD in 

accordance with OPP policy. While the specific form released from plastics or textiles 

below the LOD is unknown, the Agency has found that use of NSPW-L30SS will not 

cause unreasonable adverse effects to human health or the environment, whether resulting 

in releases of ionic silver or nanosilver. 

Comment 6.5: Due to the physicochemical complexity of nanosilver in the environment, 

EPA must approach its assessment in a comprehensive manner, rather than requiring 

animal tests on individual products. We urge the EPA to first gain an understanding of 

nanosilver’s forms, fate and transport in the environment, characterize the scenarios under 

which it is most bio-active, and determine the variables that influence its toxicity. Much of 

the preliminary toxicity evaluation could be done using in vitro or other non-animal 

methods. There are already a number of promising nanomaterial-specific in vitro 

techniques available and in development that are likely to provide high-throughput and 

reliable data on the cellular toxicity of nanosilver. These techniques will also be of use 

when looking at mechanisms and interactions of nanosilver within human systems, which 

will allow for better predictivity as well as allow assessment of cumulative exposures. 

Once this knowledge is gained, a screening model and other in silico methods could be 

developed to predict toxicity based on characteristics of the particular nanosilver product, 

its use and length of exposure. At that point, specific nanosilver products that show the 

highest potential for toxicity could be identified for further testing. Using such an 
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integrated evaluation and testing approach is more strategic, and more efficient in the long 

run, than testing on animals on a product-by-product basis. Not only will the latter 

approach kill thousands of animals, but the results will be difficult to interpret, particularly 

when so many more non-pesticide-regulated products containing nanosilver go 

uncharacterized and may represent a greater threat. We understand that not all of these 

products are under the Office of Pesticide Programs regulatory purview; even so, a more 

holistic, cooperative approach is essential. 

The EPA’s Nanomaterial Research Strategy focuses on a tiered approach based on in vitro 

toxicity testing methods and recognizes the critical differences in assessing nanomaterials 

and bulk chemicals. We recommend that instead of applying unproven and unvalidated 

animal-based methods used to test bulk chemicals, EPA consider nanosilver as a 

nanomaterial first and foremost and allow for the safety testing of nanosilver using 

available non-animal testing methods. 

Because nanomaterials differ from traditional chemicals and have proven difficult to test 

using some of the animal-based methods used for traditional chemicals, it makes more 

sense to apply an Integrated Testing Strategy (ITS) that takes into account the data 

available for the nanomaterial of interest (in this case, for nanosilver) and provides a 

rational testing strategy to satisfy regulatory needs while minimizing animal testing. 

Methods that have proven most efficient and sensitive to nanomaterials include in vitro 

methods using bacterial, fungal, and algal toxicity tests as well as human cell- and tissuebased toxicity tests to assess human safety for these nanoparticles. Moreover, many of 

EPA’s newer testing designs could be modified slightly to accommodate the robust testing 

of nanomaterials. 

Another promising approach is described in a report focused on elucidating the impact of 

ingesting silver nanoparticles using a novel in vitro digestion model that has been accepted 

to the journal of Nanotoxicology (publication date is to be determined). This study 

assessed nanoparticle effect after coming into contact with artificial saliva, gastric, and 

intestinal solutions. Because of the model’s specificity to nanosilver and its ability to 

assess the nanoparticles as they traverse the digestive system, we request that EPA 

consider this method for further use in risk assessment as well. 

In order to most efficiently regulate nanomaterial-containing pesticides, EPA must require 

manufacturers to further develop and use in vitro and in silico human and environmentallyrelevant methods that are high throughput, efficient and flexible enough to handle the 

infinite variations that are possible with a nanomaterial-based product. If the agency 

decides to require additional registration and testing of products containing true nanosilver 

according to antimicrobial pesticide regulations, then manufacturers should be encouraged 

to assess these risks using a human-relevant intelligent testing scheme that relies on highthroughput, reliable, non-animal methods rather than resorting to the problematic, 

expensive and time-consuming animal-based methods used for traditional pesticides. 

It makes little sense to require animal testing on a product-by-product basis. EPA should 

delay decisions on toxicity testing requirements until nanosilver products can be 

characterized and compared for similarities and differences, and until realistic exposure 

levels can be determined. We disagree with Scientific Advisory Panel recommendations 

that bridging opportunities may be limited among nanosilver products and request that a 

full examination of the physicochemical properties be completed before requiring any 
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animal tests. A recent review of the applicability of QSARs to nanotoxicology highlights 

the promise of computational toxicology methods in evaluating nanomaterials, although 

the article does point out that some major gaps in research required to accelerate the use of 

QSAR methods for regulatory purposes do exist. 

We urge EPA to support human-relevant toxicity test methods for assessing nanosilver. In 

vivo methods are not validated for testing nanomaterials and given the myriad of 

conflicting data from animal studies with nanomaterials, testing nanomaterials in vivo is 

not only subject to the same problems and constraints that plague all animal-based testing, 

but is further confounded by even more practical difficulties than experienced with 

traditional chemicals and pharmaceuticals. 

EPA must employ a more robust and reliable system to assess nanomaterial safety and we 

urge EPA to facilitate the development, implementation, and use of relevant and reliable 

non-animal- based methods. 

Response 6.5: EPA is committed to conducting further research on the form, fate and 

transport of nanomaterials and is constantly examining the scientific literature for new 

information on this topic. See Responses 6.1, 6.2, 7.4, and 7.19 for further discussion on 

the risk assessment and the basis for uncertainty factors and data requirements. While the 

Agency is moving towards encouraging registrants to use more cell-based and other in 

vitro systems, these technologies are largely still in the preliminary stage with the 

exception of certain systems designed for acute toxicity endpoints. The Agency continues 

to use those studies which it thinks will be most effective in determining the hazard and 

risk posed by a given chemical. In regard to QSAR, the Agency has and will continue to 

consider accepting SAR/QSAR to fulfill data requirements on a case-by-case basis, based 

on the quality and completeness of information and supporting rationale provided. 

Registrants are encouraged to submit available information to support SAR/QSAR 

analyses and then work with EPA to provide any additional information needed. With 

regards to a new digestion model, the Agency examines all relevant research and thanks 

the commenter for sharing this paper with the Agency for further review. 

Commenter 7: Jaydee Hanson, The International Center for Technology Assessment (ICTA) 

and Zack Marker, Center for Food Safety (CFS) (EPA-HQ-OPP-2012-0594-0019, Received 

9/26/2013) 

Comment 7.1: We are concerned that crystalline silica is quartz, a highly toxic 

carcinogen. While we doubt that EPA would ever approve quartz, we suggest that [NSPWL30SS] may in fact be attached to synthetic amorphous silica. We wish to flag for EPA 

that the staff reviewing the data on [NSPW-L30SS] have not adequately described the 

nanosilver material in [NSPW-L30SS], whether for lack of the necessary expertise in 

material chemistry or otherwise. 

EPA failed to provide an adequate characterization of the chemistry of [NSPW-L30SS], 

making it impossible for the public, and likely even for EPA staff, to “guesstimate” 

whether or not it would behave like other described nanosilver materials. EPA describes 

[NSPW-L30SS] as, “a liquid suspension containing silica-sulfur-nanosilver particulates 

where the nanosilver active ingredient is attached to crystalline silica via a thiolate bond.” 

First, the description of the silica as crystalline is likely in error; it is likely that the form of 

silica is synthetic amorphous silica. If this is not the case, and it is actually crystalline, then 
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given crystalline silica’s known cancer effects, EPA’s determination of no cancer risk is 

certainly in error. 

Response 7.1: EPA concurs that NSPW-L30SS contains amorphous silica rather than 

crystalline silica. In describing the structure and composition of NSPW-L30SS for the 

purposes of conditional registration, EPA relied heavily on the studies by Lee et al. as cited 

in the proposed decision document. As outlined in Appendix B, Table 1B of the proposed 

decision document, EPA is requiring Product Chemistry and NSPW-L30SS 

characterization data to confirm the composition and structure of NSPW-L30SS.

Comment 7.2: Presuming the error is in the description of the material, this error raises 

red flags about whether or not EPA staff that reviewed [NSPW-L30SS] included material 

chemists, who would have the necessary expertise to characterize the material. [NSPWL30SS] appears to be a single silica particle surrounded by multiple nanoscale PVPcoated-silver particles connected together through weak thiol linkages. However, EPA fails 

to define the thiol linkages adequately and raises significant questions. What is the thiol 

linkage to? Is it to the PVP coating, or to the silver atoms, or to a silver ion that is separate 

from the surface? Research has demonstrated the PVP-coated-nanosilver particles, such as 

those used in the [NSPW-L30SS] product, may be more toxic than uncoated particles. 

Response 7.2: The information EPA is requiring as outlined in Appendix B, Table 1B of 

the proposed decision document, should aid in further characterizing the product. The 

potential difference in toxicity due to variations between nanosilver ingredients (e.g., due 

to coatings) has been accounted for in the database uncertainty factor. See Response 6.2 for 

further discussion on the uncertainty factors. 

Comment 7.3: Nanotechnology is a powerful new set of platform technologies for 

observing, taking apart, and reconstructing nature at the atomic and molecular level. While 

the public generally thinks of nanotechnology in the future tense, consumer products 

containing manufactured nanomaterials have already arrived on market shelves, and 

comprise a product wave spanning many technologies. Nanosilver is the largest sector of 

these products, with hundreds of nanosilver products commercially available, although 

total numbers are unknown, since no labeling is required. These nanosilver products are 

properly defined and should be regulated as pesticides by EPA, since their only intended 

use is as an anti-bacterial, anti-microbial agent, i.e., to kill pests. 

Response 7.3: EPA does not agree with the comment that consumer products containing 

nanosilver are necessarily pesticides. The scope of EPA’s authority to regulate products as 

pesticides is more limited than noted by commenters. For example, EPA’s statutory 

authority extends only to those products that meet the definition of “pesticide” as that term 

is defined under FIFRA and applied in EPA regulations. “Pesticide” is defined, in part, to 

expressly exclude a number of substances, such as liquid chemical sterilants. Thus, 

statutorily excluded substances cannot be classified as a pesticide (FIFRA 2(u)). In 

addition, the statutory definition of “pest” in FIFRA section 2(t) explicitly excludes 

“viruses, bacteria, and other microorganisms on or in living man.” Similarly, if the “pest” 

targeted by the nanosilver is a “fungus” as defined under FIFRA section 2(k), the 

nanosilver is not a pesticide if the targeted fungus is “on or in living man or other animals” 

or “on or in processed food, beverages, or pharmaceuticals.” Under EPA regulations, 40 

CFR 152.5(d), EPA has also extended this statutory exclusion to any fungus “on or in ... 

cosmetics (as defined in FFDCA section 201(i)).” In addition, EPA has, by regulation, 
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identified a set of substances (e.g., deodorizers and cleaning agents), that are not 

considered to be pesticides unless a pesticidal claim is made on the label or in connection 

with the substance’s sale or distribution (40 CFR 152.10). As a result, products that are 

intended solely for uses that fall within the statutory or regulatory exclusions are not 

pesticides and are not subject to the requirements for registration. Please see 40 CFR 152.6 

for a discussion of these and other statutory exclusions, and 40 CFR 152.5 for EPA’s 

regulations on what is a “pest” and 40 CFR 152.8 for a list of products that are deemed not 

for use against a “pest.” 

Further, EPA’s authority to regulate a product as a pesticide extends only to substances or 

mixtures intended for a pesticidal purpose. As commenters note, EPA’s implementing 

regulations at 40 CFR 152.15 state: 

(a) The person who distributes or sells the substance claims, states, or implies (by 

labeling or otherwise): 

i. That the substance (either by itself or in combination with any other 

substance) can or should be used as a pesticide; or 

ii. That the substance consists of or contains an active ingredient and that 

it can be used to manufacture a pesticide; or 

(b) The substance consists of or contains one or more active ingredients and has no 

significant commercially valuable use as distributed or sold other than (1) use 

for pesticide purpose (by itself or in combination with any other substance), (2) 

use for manufacture of a pesticide; or 

(c) The person who distributes or sells the substance has actual or constructive 

knowledge that the substance will be used, or is intended to be used, for a 

pesticidal purpose.” (40 CFR 152.15) 

Only paragraph (b) allows EPA to conclude that a substance has “no significant 

commercially valuable use other than use for pesticide purpose” and that it thus may be 

presumed to have a pesticidal purpose (40 CFR 152.15(b)). As noted in the preamble to the 

final rule adopting these regulations, “EPA acknowledges that a certain degree of judgment 

must be exercised in deciding whether a substance meets this definition. On the other hand, 

the Agency believes that a large percentage, if not the majority, of pesticide active 

ingredients are clearly identifiable either as pesticides or as multi-purpose substances, and 

that the Agency will rarely be compelled to use this criterion alone to judge whether a 

substance is a pesticide” (53 FR 15952, at 15954 - May 4, 1988). This position holds true 

in this case as well. 

While EPA agrees with the commenter that silver and nanosilver ingredients have inherent 

bactericidal properties, that a substance has anti-bacterial properties does not alone address 

the issue; there must be no other significant commercially valuable use. In this case, silver 

and nanosilver have other properties that may instead be the purpose for a substance’s use 

in a product. For example, public literature indicates that silver has many other properties 

that allow uses for other purposes, such as in analytical instrumentation, cloud seeding, 

electroplating, mirrors, photography, and catalysts (Etris, S.F. and Cappel, C.R., Silver 

Compounds. Kirk-Othmer Encyclopedia of Chemical Technology. 16 May 2003). As a 

result, the information before EPA at this time does not allow a general conclusion that 
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nanosilver has no other significant commercially valuable use and that such ingredients 

should therefore be presumed on that basis to be used for a pesticidal purpose. 

In sum, EPA disagrees with commenter that all nanosilver products can be classified as 

pesticides or that any nanosilver product can be classified as a pesticide solely on grounds 

that nanosilver is generally understood to have anti-bacterial properties. EPA does, 

however, agree that it may conclude, on a case-by-case basis, that a particular product is, 

or that certain types of products containing nanosilver are, intended for a pesticidal 

purpose. Additional information can be found in the EPA Response to "Petition for 

Rulemaking Requesting EPA Regulate Nano-Silver Products as Pesticides", available at 

regulations.gov (Docket ID: EPA-HQ-OPP-2008-0650). 

Comment 7.4: The same new properties that so excite industry—tiny size, vastly 

increased surface area to volume ratio, high reactivity—can result in new risks to human 

health and the environment. Swiss insurance giant Swiss Re noted: “Never before have the 

risks and opportunities of a new technology been as closely linked as they are in 

nanotechnology. It is precisely those characteristics which make nanoparticles so valuable 

that give rise to concern regarding hazards to human beings and the environment alike.” 

These risks essentially take two forms: increased potential toxicity and unprecedented 

mobility for a manufactured material. 

First, nanoparticles’ exceptionally large relative surface area creates increased surface 

reactivity and enhanced toxicity potential, which cannot be accurately predicted from 

larger material cousins. As the European Commission’s (EC) Scientific Committee on 

Emerging and Newly Identified Health Risks (SCENIHR) explained: 

“[e]xperts are of unanimous opinion that the adverse effects of nanoparticles 

cannot be predicted (or derived) from the known toxicity of material of 

macroscopic size, which obey the laws of classical physics.” 

It is accepted, therefore, that it is not possible to infer the safety of nanomaterials by using 

information derived from the bulk parent material.” 

Response 7.4: ICTA’s summary matches the EPA’s statements in the decision and 

supporting documents regarding the hazard characterization of nanosilver. EPA established 

points of departure (POD) using whole-animal studies performed using OECD guideline 

studies on nanosilver ingredients, not on the bulk silver parent material. As the final 

decision document states, “As the size of silver particles decreases...the potential for 

releasing silver ions increases, due to the increasing unit of surface area...” However, the 

other factor to consider is release rate. NSPW-L30SS contains nanosilver that is 

complexed to a larger particle that is then embedded into a polymer. The submitted 

leaching studies show that nanosilver is unlikely to be released in quantities above the 

detection limit from this polymer. Absent release from the polymer, the mobility of 

nanosilver in NSPW-L30SS is greatly reduced. As EPA explained in the proposed and 

final decision documents, the available data show release of nanosilver below the level of 

detection. Taking into consideration these low releases, the available toxicity data, use of 

multiple risk uncertainty factors (UFs) and required risk mitigation measures on the 

product label, the calculated margins of exposure (MOEs) and risk quotients (RQs) were 

well above the Agency levels of concern (LOCs). On these grounds, EPA determined that 

there is substantial evidence in the record to conclude that the proposed use of NSPW-
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L30SS during the conditional registration period will not cause unreasonable adverse 

effects on human health or the environment. 

Comment 7.5: Scientists have yet to determine even what physicochemical properties will 

be most important in determining ecological and toxicological properties of nanomaterials. 

Standard toxicological analysis correlates health risks with the mass to which an individual 

is exposed, resulting in an accumulated mass as an internal dose or exposure. However, the 

biological activity of nanoparticles is likely to depend on physicochemical characteristics 

that are not routinely considered in toxicity-screening studies. There are many more factors 

affecting the toxicological potential of nanoscale materials, at least sixteen in fact, 

including: size, surface area, surface charge, solubility, shape or physical dimensions, 

surface coatings, chemical composition, and aggregation potential—a “far cry from the 

two or three usually measured.” Nanotoxicology is an emerging field in its own right, 

requiring new paradigms of predictive toxicology, which are only now being delineated. 

Yet EPA relied solely on mass as its risk metric for [NSPW-L30SS], despite being “aware” 

that “metrics other than mass (such as particle number or surface area) may be more 

suitable for assessing nanoparticle risks.” 

Response 7.5: The Agency is aware of the ongoing debate within the scientific community 

that metrics other than mass (such as particle number or surface area) may be more suitable 

for assessing nanosilver risks and therefore acknowledges the potential for limitations of 

mass-based risk estimates. EPA will be collecting data on such factors during the period 

when newly required data are being developed as outline in appendix B of the decision 

document. However, as EPA explained in the proposed and final decision documents, the 

available data show release of nanosilver below the level of detection. Taking into 

consideration these low releases, the available toxicity data, use of multiple risk 

uncertainty factors (UFs) and required risk mitigation measures on the product label, the 

calculated margins of exposure (MOEs) and risk quotients (RQs) were well above the 

Agency levels of concern (LOCs). On these grounds, EPA determined that there is 

substantial evidence in the record to conclude that the proposed use of NSPW-L30SS 

during the conditional registration period will not cause unreasonable adverse effects on 

human health or the environment. 

Comment 7.6: [D]ue to their tiny size, nanomaterials have unprecedented mobility for a 

manufactured material. They are more easily taken up by the human body and can cross 

biological membranes, cells, tissues, and organs more efficiently than larger particles. 

Once in the blood stream, nanomaterials can circulate throughout the body and can be 

taken up by the organs and tissues including the brain, liver, heart, kidneys, spleen, bone 

marrow, and nervous system. In addition, unlike larger particles, nanoparticles are 

transported within cells and taken up by cell mitochondria and the cell nucleus, where they 

can interfere with cell signaling, induce major structural damage, and result in DNA 

mutation. EPA has, in fact, voiced its concerns regarding nanomaterials’ ability to be 

absorbed into the body and cross the blood-brain barrier, as well as the high durability and 

reactivity of some nanomaterials. 

Response 7.6: The EPA relied on the same toxicity studies to which ICTA referred, and 

concluded that use of NSPW-L30SS will not cause unreasonable adverse effects to human 

health or the environment. Furthermore, NSPW-L30SS contains nanosilver that is 

complexed to a larger particle that is then incorporated into plastics and synthetic textiles 
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and the leaching studies show that nanosilver is unlikely to be released from plastics and 

textiles at levels above detection limit. 

Comment 7.7: As little as is known about nanomaterials’ health impacts, even less is 

known about their environmental impacts. While EPA acknowledged that no fate or 

ecotoxicity studies are available for [NSPW-L30SS], EPA nonetheless proposes granting 

conditional registration of [NSPW-L30SS]. 

Response 7.7: EPA disagrees that the state of knowledge about NSPW-L30SS is 

insufficient to make a conditional registration finding. Data show the nanosilver in NSPWL30SS leaches out of plastics and textiles below the LOD. While the specific form released 

from plastics or textiles below the LOD is unknown, the Agency has found that use of 

NSPW-L30SS will not cause unreasonable adverse effects to human health or the 

environment, whether resulting in releases of ionic or nano-silver, pending generation of 

the requisite data as a term and condition on the registration. For any portion released as 

ionic silver, this finding is based on the data and analysis in the Reregistration Eligibility 

Decision for silver for these material preservative use patterns. For any portion released as 

nanosilver, this finding is based on the data and analysis discussed in the decision 

document, and further explanations in the current document. More specifically, on the 

exposure analysis, while the specific knowledge of which form is released is desirable and 

is necessary to confirm the identified margin of safety determined in the risk assessment 

(and thus is required as a term and condition on the registration per Appendix B of the 

decision document), the Agency knows identifying which form of silver is released would 

decrease, not increase, the nanosilver exposure estimates provided in the decision 

document, as the risk assessment conservatively assumed all silver was released as 

nanosilver. 

With respect to assessing the acute and intermediate health impacts, see Responses 6.1, 

6.2, 7.4, and 7.19. With respect to assessing the chronic health impacts, although children’s 

short- and intermediate-term exposure durations to plastic toys and textiles treated with 

NSPW-L30SS are expected, children are not anticipated to play with NSPW-L30SStreated toys or contact NSPW-L30SS-treated textiles every day for a period of greater than 

six months, thus long-term exposures are unlikely. Because of the potential for NSPWL30SS to be used in flooring, long-term dermal and incidental oral exposures to children 

contacting flooring are possible. However, EPA does not believe that children will have 

continuous and daily exposure to flooring for a period of greater than 6 months. Even if 

these unlikely long-term exposures were to occur, the calculated MOEs for children’s 

dermal and incidental oral exposure to plastics and textiles incorporating NSPW-L30SS 

are greater than 100,000 indicating that daily exposure to plastics and textiles incorporating 

NSPW-L30SS for greater than 6 months are not of concern. Therefore, the EPA believes 

this chemical does not meet the requirements for triggering the conditional requirement of 

either a chronic or carcinogenicity study as indicated in Part 158W. 

On the ecotoxicity issues, there are sufficient ecotoxicity data on nanosilver to make the 

requisite finding pending generation of data for NSPW-L30SS. First, ecotoxicity data on 

other nanosilver materials provide information on the expected effect range (e.g., 

milligram versus microgram versus nanogram range) for such materials. Second, the 

ecotoxicity data in the decision document use nanoscale particles coated with PVP, similar 

to NSPW-L30SS, and the most sensitive freshwater invertebrate Daphnia magna. Together 
23 of 57

these data show that the ecotoxicity effect range obtained from the different nanosilver 

particles and coatings considered in the decision are protective, taking into account the 

estimated release rates and environmental exposures. Supporting this conclusion is the 

comparison between data on nanosilvers and data on other forms of silver. Specifically, 

even assuming the chronic toxicity of NSPW-L30SS may be more toxic than silver salts, 

the toxicity of silver nanoparticles is not expected to be orders of magnitude more toxic 

than acute values for the more acutely sensitive species and life stages, based on general 

silver nanomaterial toxicity data and the acute-to-chronic ratios (ACRs) seen for silver 

salts. For example, one silver nanomaterial study with a sensitive life stage was identified 

and discussed in the proposed decision document. The 96-hour EC50 Danio rerio embryo 

test results for three different silver nanomaterials (bare, polyvinylpyrrolidone-coated 

(PVP-coated), and bare monodispersed nanoparticles with a dispersant) are not 

significantly different or are less toxic than companion silver nitrate results on a total silver 

basis (Wang et al. 2012b; Tables 17 and 18 of the proposed decision document). Blinova et 

al. (2013) conducted acute and chronic 21-day reproduction tests with D. magna using a 

PVP-coated nanosilver and collargol-coated nanosilver in two natural waters. This study 

was not included in the proposed decision document and while there are several issues 

which limit use of the data quantitatively in a risk assessment, the study does provide 

evidence that the ACRs for silver nanomaterials for D. magna on a total silver basis 

potentially are around or less than 2, which is similar to silver salts. In the case of silver 

salts, acute toxicity values for the most sensitive freshwater species D. magna (unfed 

during duration of acute study per guideline standards) are lower than chronic values on a 

total recoverable silver basis (USEPA Ambient Water Quality Criteria for Copper 1980, 

1987). When daphnids are fed during the silver salt acute tests, acute toxicity has been 

observed to be reduced (2.9 to 40 times less toxic), with resulting ACRs of at least 2 for D. 

magna (USEPA 1980). Similar decreases in acute toxicity have been observed for other 

sensitive cladoceran species (Ceriodaphnia reticulata, Daphnia pulex) when fed (USEPA 

1987). While the Agency has not reviewed more current public literature on acute toxicity 

for silver salts for acceptability for use in a risk assessment, open literature reviews of 

available silver toxicity data based on total recoverable silver demonstrate this pattern has 

also been observed in later studies with D. magna. (Ratte 1999). This difference has been 

attributed to the presence of food providing a mitigating effect (i.e., food binds silver, 

rendering it less bioavailable). There have been limited chronic tests with D. magna where 

the soluble or dissolved concentrations of silver have been measured along with 

companion acute data, but in these cases, the ACR is less than 2. This means if there are no 

acute risks based on the D. magna, unfed, acute value there are definitely no chronic risks 

for this species. Similar effects on acute toxicity of silver nanomaterials have been 

observed. Blinova et al. (2013) discuss how the mortality in chronic tests was lower than 

that observed in acute tests (unfed). One exception to a low silver nitrate ACR for sensitive 

cladocerans is based on acute and chronic results from Bielmyer et al. (2002), cited in the 

EMERGANO review. Bielmyer et al. (2002) conducted acute and chronic testing with 

silver nitrate for the cladoceran Ceriodapnia dubia which results in an ACR of 550 but this 

value is greater than a factor of 10 of all other silver ACRs for cladocerans and is based on 

nominal rather than measured total silver and a dose-space factor of 10 for the chronic 

study. Dose-spacing <3 is standard guidance for acceptable chronic tests with dose-spacing 

of 10 only suitable for range-finding. Bielmyer et al. (2002) reported for C. dubia a 21-d 

NOEC and LOEC of 0.001 and 0.1 ppb, respectively, and an acute value of 0.55 ppb for 
24 of 57

total silver–these results are based on nominal, unmeasured values (note quantitative 

measurements in the study were made only in exposure concentrations >2 ppb—detection 

limit). 

In sum, the general knowledge of the ecotoxicity effect range obtained from the different 

nanosilver particles and coatings considered in the decision provides adequate data to 

determine that, pending generation of newly required data, the proposed uses in this case 

will not cause unreasonable adverse effects, especially given the large difference between 

the LOC and RQs and how much more toxic the nanosilver in NSPW-L30SS would need 

to be to exceed the LOC (see Responses 7.10, 7.14 and 7.15). Tiered fate and ecotoxicity 

data are required as a term and condition on the conditional registration allowing the 

Agency to have additional data points to confirm the margin of safety. 

This analysis is also relevant to the reduced environmental loading basis for the public 

interest finding. Specifically, EPA has registered a number of silver-based antimicrobial 

products for use as materials preservatives in textiles. Most of these antimicrobial silverbased pesticide products currently contain a silver salt (e.g., AgCl or AgNO3). Compared 

to the amount of silver in Nanosilva LLC’s product, most currently registered silver-based 

materials preservative registrations allow far larger application rates than allowed for the 

proposed registration. Therefore, the overall potential environmental loading of silver 

resulting from the lower-volume use of the Nanosilva LLC product should be smaller than 

from a comparable use of currently registered silver-based pesticides. 

Relevant assumptions used by the Agency include the following: 

 Assumed all treated plastic (non-textile) was linear low-density polyethylene 

(LLDPE) which is amongst the most porous of plastics and thus the possibility of 

leaching is higher compared to other available plastics. 

 Assumed all treated in-service plastic lumber would be exposed to water daily, and 

thus leach nanosilver to the environment daily. 

 Assumed 100% of nanosilver in the in-service plastic lumber would leach out 

annually (i.e. 0.274% leaches out daily) even though an estimated <0.042% would 

leach out in 10 days (or <0.0042% daily) based on the LLDPE coupon leaching 

data. The assumption also requires nanosilver to migrate at the same or higher rate 

daily from the interior to the exterior of the plastic product to replenish nanosilver 

for leaching availability the next day. 

 Assumed no removal of nanosilver in run-off from plastic lumber due to adsorption 

to soil (i.e., all released silver goes directly to a stream). 

 Assumed everyone in the U.S. population has a NSPW-L30SS treated t-shirt, and 

washes it weekly. 

 Assumed the nanosilver in the NSPW-L30SS is stable (i.e., does not dissociate into 

ionic silver in the environment) and for aquatic water column organisms none of 

the nanosilver discharged from a WWTP is removed from the water column. 

 For assessing acute risks to aquatic species, total silver results from an acute test 

where daphnids were not fed during testing were used. When food is present in 

acute tests with D. magna, reduction of acute toxicity in terms of total silver by 

about a factor of 10 has been observed. 
25 of 57

Comment 7.8: EPA cannot show that [NSPW-L30SS] will not cause “unreasonable 

adverse effects on the environment” as required by FIFRA for conditional registration. 

Before granting a pesticide registration, EPA must determine that the pesticide will not 

cause any “unreasonable adverse effect on the environment.” The term “unreasonable 

adverse effects on the environment” means “any unreasonable risk to man or the 

environment, taking into account the economic, social, and environmental costs and 

benefits of the use of any pesticide.” 

EPA’s conditional registration of [NSPW-L30SS] is unlawful because nanosilver poses 

unreasonable risks to man and the environment. The unreasonableness of the risks posed 

by nanosilver pesticides are further underscored by the dearth of health and safety data in 

the record. 

Response 7.8: Please refer to Response 6.1, 7.7, 7.14, 7.15, 7.27, and 7.28 

Comment 7.9: EPA applies the wrong standard in making its determination to 

conditionally register [NSPW-L30SS]. EPA states that it “has determined that there is a 

low probability of adverse risk to human health and the environment from plastics and 

textiles incorporating [NSPW-L30SS].” Applying this “low probability of adverse risk” 

standard in granting [NSPW-L30SS] conditional registration not only puts human health 

and the environment at risk, but is also indicative that EPA failed to consider the proper 

factors, and thus is arbitrary and capricious agency action on behalf of EPA. 

Response 7.9: ICTA ignores the sentence that follows: 

“...there is a low probability of adverse risk to human health and the environment from 

plastics and textiles incorporating NSPW-L30SS. Thus, the Agency concludes that use of 

NSPW-L30SS will not cause unreasonable adverse effects on the environment during the 

period when newly required data are being developed.” The calculated MOEs are well 

above the target MOEs, and thus EPA concluded the proposed use of the pesticide will not 

cause unreasonable adverse effects on human health. Similar findings were made for 

ecotoxicity risks. 

Thus, EPA made the statutorily required finding and used the correct legal standard. 

Comment 7.10: EPA lacks adequate data to make its decision. As with nanomaterials 

more generally, there is a lack of research on the human health and environmental safety of 

nanosilver, and especially with a composite product like [NSPW-L30SS] that the company 

plans to use more extensively than any existing nanosilver products. Indeed, it plans more 

extensive use than even any existing bulk silver products. Among other things, proposed 

incorporation of [NSPW-L30SS] includes textiles, plastic films, sheets, slabs, and molded 

parts, as well as consumer products such as footwear, sportswear, uniforms, and auto parts, 

floor coverings, outdoor furniture, decking, and house siding. To our knowledge, no other 

silver pesticide product registrations cover floor coverings, plastic films, slabs, and molded 

parts, such as those that would be found in outdoor furniture, decking and house siding. 

SAP specifically acknowledged that “data gaps about potential exposures and hazards 

related to nanosilver are broad,” noting that “there is very little information about 

nanosilver in the environment related to fate, transport, and transformation.” Further, 

EPA’s Draft Decision Document admits that there are “no fate or ecotoxicity studies 
26 of 57

available for [NSPW-L30SS],” which required EPA to estimate the fate and ecotoxicity 

using existing studies in the scientific literature. 

EPA acknowledged the existence of many gaps in scientific knowledge with regard to 

nanosilver’s effects on health and the environment. These gaps include: 

 no intermediate- or long-term human or environmental toxicity studies 

available for [NSPW-L30SS] or for the nano-sliver released from products 

incorporating [NSPW-L30SS] 

 no studies on environmental fate and transport 

 no studies in the scientific literature that investigate mutagenicity or 

carcinogenicity of nanosilver 

 no subchronic or chronic oral or dermal toxicity studies available for [NSPWL30SS] or on the nanosilver that might break away from products 

incorporating [NSPW-L30SS] 

 no acceptable studies on the reproductive and developmental toxicity for 

nanosilver 

 inadequate information to assess mutagenic and carcinogenic potential of 

nanosilver due to differences in results between in vitro studies and in vivo 

studies, and limitations of the only available in vivo study 

 insufficient information on aggregate exposures to other nanosilvers currently 

in the market place. 

Yet the absence of data cannot replace the agency’s burden to show, based on substantial 

evidence, that there will be no unreasonable impacts on the environment. 

Response 7.10: The Agency disagrees that it lacks adequate data to determine that the 

proposed uses, during generation of required data, will not cause unreasonable adverse 

effects on the environment. While data on the nanosilver in NPSW-L30SS or on NPSWL30SS specifically do not exist for the listed pathways/toxicities there is adequate data on 

nanosilvers sufficient to determine that the proposed uses in this case will not cause 

unreasonable adverse effects, especially given the large difference between the LOC and 

MOE for most routes of exposure. For those routes where the difference is smaller 

(inhalation) or there are areas of additional interest (e.g., reproduction/fertility), data are 

being required (90 day inhalation study with a functional observation battery, motor 

activity and detailed neuropathology, modified reproduction/developmental toxicity via the 

inhalation route and a Tier 2 non-guideline peri- and post natal developmental study) to 

reduce the 10X database uncertainty factor applied and to determine whether any other 

POD should be used in the risk assessment. For similar reasons, tiered fate and ecotoxicity 

data are being called in for the duration of the conditional registration at which point the 

Agency will have additional data points to confirm the margin of safety. In regard to the 

comment that no other silver-based registrations cover the range of the uses that are 

covered by the NSPW-L30SS application, the commenter is incorrect. The Agency has 

registered silver-based products for use in plastics including such uses as floor coverings, 

plastic films, slabs, molded parts, sidings, furniture, etc. In regards to mutagenicity, as 

noted in the decision document, available in vitro studies suggest that nanosilver is 

equivocal to mutagenic potential. However, the lack of mutagenicity in several wellconducted in vivo studies, showing cytotoxicity and evidence that the nanoparticles 

reached the target tissue, suggests that the in vitro mutagenic potential observed in some of 
27 of 57

the in vitro studies may be intrinsic to nanoparticles, but is not expressed in whole animals. 

There is evidence that silver nanoparticles are genotoxic, expressing DNA damage in 

cultured human lung cells and in the lungs and liver of intact animals (comet assay) via 

intracellular generation of ROS. These findings are supported by the inflammatory 

processes observed in the lungs. However, since initiation of ROS-induced oxidative DNA 

damage can be blocked by ROS scavengers, there is not a concern for mutagenicity or 

genotoxicity. Furthermore, EPA believes that the short-term oral NOAEL and 

intermediate-term oral LOAEL of 30 mg/kg/day and inhalation NOAEL of 49 μg/m3

 are 

expected to be protective of mutagenicity. In regards to chronic toxicity, including 

carcinogenicity, the potential exposure to NSPW-L30SS is not likely to result in significant 

human exposure over a considerable portion of the human life span which is significant in 

terms of frequency, time, duration, and/or magnitude of exposure. The release rate based 

on the leaching study from the use of NSPW-L30SS is so small and the resulting MOEs so 

high that the EPA has determined that the chronic/carcinogenicity toxicity studies are not 

triggered as conditionally required as part of 158W. For more information on 

environmental fate, transport and toxicity, see Response 7.7. For more information on 

reproductive and developmental toxicity, see Response 7.28. For more information on 

subchronic toxicity, see Response 6.2. For more information on aggregate exposure, see 

Response 6.4. 

Comment 7.11: Nanoscale particles including nanosilver have been shown to be capable 

of penetrating biological barriers such as cell membranes and can enter into the cells 

themselves. Nanoparticles are able to attach to cell membranes, producing changes in 

membrane permeability, redox cycling in the cytosol, intracellular radical accumulation, 

and dissipation of the proton motive force for ATP synthesis. Each of these has been 

reported as a possible mechanism for nanoparticle toxicity. Evidence from scanning 

transmission electron microscopy also shows that smaller particles (< 10 nm) may enter the 

cell directly to inhibit microbial growth. 

Response 7.11: While the studies have shown the above effects, these studies are in vitro

studies. These studies have not been characterized to represent in vivo effects as they do 

not account for the complexities of biological systems, including things as varied as first 

pass effects and blood protein binding. Furthermore, the other factor to consider is release 

rate. NSPW-L30SS contains nanosilver that is complexed to a larger particle that is then 

embedded into a polymer. The submitted leaching studies show that nanosilver is unlikely 

to be released in quantities above the detection limit from this polymer. Absent release 

from the polymer, the mobility of nanosilver in NSPW-L30SS is greatly reduced. As EPA 

explained in the proposed and final decision documents, the available data show release of 

nanosilver below the level of detection. Taking into consideration these low releases, the 

available toxicity data, use of multiple risk uncertainty factors (UFs) and required risk 

mitigation measures on the product label, the calculated margins of exposure (MOEs) and 

risk quotients (RQs) were well above the Agency levels of concern (LOCs). On these 

grounds, EPA determined that there is substantial evidence in the record to conclude that 

the proposed use of NSPW-L30SS during the conditional registration period will not cause 

unreasonable adverse effects on human health or the environment. 

Comment 7.12: Among documented potential harms to human health, in vitro (test tube) 

studies demonstrate that nanosilver is toxic to mammalian liver cells, stem cells and even 

brain cells. One 2009 study discovered that absorption of nanosilver may interfere with the 
28 of 57

replication of DNA molecules, potentially creating genetic mutations. Two other studies 

have demonstrated that exposure to nanosilver can reduce mitochondrial function. The 

number of diseases associated with mitochondrial malfunction is increasing and includes 

Parkinson’s, Alzheimer’s, and Huntington’s disease. 

Response 7.12: Again, the studies listed above are in vitro studies. These studies have not 

been characterized to represent in vivo effects as they do not account for the complexities 

of biological systems, such as first pass effects and blood protein binding. The Agency 

recognizes the potential risks associated with nanosilver products. However, as EPA 

explained in the proposed and final decision documents, the available data show release of 

nanosilver below the level of detection. Taking into consideration these low releases, the 

available toxicity data, use of multiple risk uncertainty factors (UFs) and required risk 

mitigation measures on the product label, the calculated margins of exposure (MOEs) and 

risk quotients (RQs) were well above the Agency levels of concern (LOCs). On these 

grounds, EPA determined that there is substantial evidence in the record to conclude that 

the proposed use of NSPW-L30SS during the conditional registration period will not cause 

unreasonable adverse effects on human health or the environment. For further information 

on how the current risk assessment addresses neurotoxicity, and on why certain studies are 

required, please refer to Responses 6.1 and 6.2. 

Comment 7.13: Beyond the issue of toxicity, nanosilver may also create a public health 

burden by producing antimicrobial resistance. The Centers for Disease Control and 

Prevention (CDC) recently acknowledged antimicrobial resistance as one of the world’s 

most serious health threats, in part because of the use and overuse of antibiotics in 

medicine and food production. As with antibiotics, the use and overuse of nanosilver may 

promote resistance to important antimicrobials, which must be addressed before it is too 

late. 

Response 7.13: As explained in the decision document, while development of antibacterial 

resistance due to the use of nanosilver in NSPW-L30SS is possible, the Agency concluded 

that the likelihood is low that the levels used in NSPW-L30SS treated articles will lead to 

the development of silver resistant microbes which will spread throughout the environment 

resulting in widespread bacterial resistance to silver. For example, in terms of 

environmental impact, a recent study involved releasing 1 mg/L of nanosilver into 

microcosms containing estuary water overlying estuarine sediment cores (Bradford et al., 

2009). The study found no impact to the microbial community over a 30 day monitoring 

period. Evidence for antibacterial resistance was also evaluated during this study and no 

increase in antibiotic resistance to the bacterial population in the sediment was found 

(Mühling et al. 2010). Wigginton et al. (2010) suggested that the lack of antimicrobial 

effect in the microcosm was expected given that bacterial proteins efficiently bind to 

nanosilver. The commenter does not specifically respond to this detail in our proposed 

decision document. Nor does the commenter provide any additional detail to better 

understand the comment or to allow the EPA to engage on the substantive issue. 

Comment 7.14: Nanosilver is also toxic to a variety of aquatic and terrestrial organisms. 

EPA acknowledges that, even in its bulk form, silver is extremely toxic to fish and other 

aquatic species. EPA ignores that, at the nano-scale, nanosilver can be many times more 

toxic. Swiss researchers recently modeled the environmental concentrations of several 
29 of 57

commercially available nanomaterials and predicted that nanosilver emissions may already 

pose risks to aquatic organisms. 

Response 7.14: EPA agrees that there is evidence in the literature that nano-scale silver 

can potentially be more toxic than ionic silver alone, but not sufficiently more toxic to 

raise risk concerns when taking into account leaching rates for the proposed uses. For the 

plastic screening scenario, the scale of the increase in toxicity over ionic silver, or other 

nano-scale ecotoxicity data used in this assessment would need to be on the order of 5 to 

53 times more toxic to raise any potential concern with respect to nanosilver ecotoxicity or 

causing any potential for refining the risk assessment. Moreover, given that at a minimum 

exposure due to leaching is highly likely to be overestimated (e.g., 0.00042 fraction 

leached / 10 days x 365 days/year = 0.015 fraction leached/year or 1.5% leached/year not 

100%/year; for a surface water concentration of 0.00021 ppb for the 10th percentile 1Q10 

stream flow) the order of sensitivity of aquatic organisms to this particular nanosilver 

would need to be 360 to 3600 times greater. For the textile scenario, the scale of the 

increase in toxicity over ionic silver, or other nano-scale silver ecotoxicity data used in this 

assessment would need to be on the order of 19 to 190 times more toxic, which, while a 

narrower margin, is still not likely. The order for both textiles and plastics would 

additionally increase by about a factor of 10 (i.e., 3600 to 36,000 and 190 to 1,900 times, 

respectively), if taking into account that in the presence of food the acute value on a total 

silver basis is expected to be at least a factor of 10 higher (see Response 7.7). 

Comment 7.15: Further, the same property that makes these nanoparticles attractive to 

manufacturers—their highly enhanced antimicrobial properties—can be highly destructive 

to ecosystems, by threatening the bacteria-dependent processes that underpin natural 

systems. Microorganisms are the foundation of all ecosystems and provide key 

environmental services ranging from primary productivity to nutrient cycling and waste 

decomposition. Early studies show that nanosilver can reduce the activities of microbes 

employed in treating wastewater. Widespread use of household products that release 

nanosilver into the sewage system could adversely affect waterways, exacerbated by the 

inability of public utilities and water treatment plants to properly treat the substance. 

Response 7.15: While there are reports suggesting the potential for nanosilver to impact 

wastewater treatment operations, the Agency does not anticipate that proposed use of 

NSPW-L30SS will cause unreasonable adverse effects to the environment during the 

period for generation of the data. Estimated concentration in influent from the decision 

document would be on the order of 0.03 ppb (e.g., from Table 19 of the decision 

document – 0.004 ppb effluent ÷ (1-0.85 fraction removed) = 0.03 ppb). Based on general 

nano-scale silver toxicity data as discussed in the decision document, toxicity of nano-scale 

silver to wastewater microorganisms is on the order of 500 to 1,000 ppb or higher. The 

nanosilver in NSPW-L30SS would need to be >18,000 times more toxic than ionic silver 

or the general nano-scale silver data in Section 6.1.3 of the decision document for there to 

be a concern with impacts to wastewater treatment operations. 

Comment 7.16: In 2009, as a result of these and other potential adverse impacts on the 

environment, EMERGNANO, the first global review of environmental, health, and safety 

studies examining the risks of nanotechnology exposure, found that there is “sufficient 

evidence to suggest that silver nanoparticles may be harmful to the environment and 

therefore the use of the precautionary principle should be considered in this case.” 
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Response 7.16: Commenters do not explain how use of the precautionary principle here 

would change the Agency’s assessment or decision. However, EMERGNANO states that 

the reason to apply the precautionary principle in the case of silver nanoparticles is that 

“[t]he RO [research reports] present indicative evidence of the harm of silver nanoparticles 

at low concentrations on aquatic invertebrates, which suggest that the environmental 

release of silver nanoparticles should consider taking the necessary steps to reduce or 

eliminate the potential exposure of the environment to these nanoparticles.” In the 

Executive Summary, the report also states that in the case of silver “In these specific cases 

further investigation as to the need to invoke the precautionary principle is required, taking 

into consideration all available data.” Thus, the report does not necessarily call for 

application of the precautionary principle. Moreover, to the extent that comments are 

calling for a delay in a registration decision pending receipt of additional data, EPA 

disagrees. For the reasons discussed throughout the decision document and this responseto-comments document, it is appropriate to grant the registration in this case because the 

requisite statutory findings can be made. Finally, while silver nanoparticles may be toxic at 

low concentrations on aquatic invertebrates, some evidence of toxicity alone does not 

define the appropriate steps the Agency may take. In this case, the low release rates 

contribute significantly to a determination that, notwithstanding data showing some aquatic 

toxicity, use of the active ingredient will not cause unreasonable adverse effects on the 

environment. This is similar to the case of other antimicrobial pesticides, like silver salts, 

and other conventional pesticides that are toxic to aquatic invertebrates, also at low 

concentrations. Like these other active ingredients, the Agency considered all available 

information in the decision and compared exposure levels to toxicity levels to evaluate the 

potential risk for registration of the proposed uses. 

Comment 7.17: Given the improper standard that EPA applies to its decision, the 

acknowledged data gaps about potential exposures and hazards, significant red flags raised 

by existing data, and new broad uses proposed for [NSPW-L30SS], EPA has failed to 

show that conditional registration of [NSPW-L30SS] will not cause unreasonable adverse 

effects on the environment. 

Response 7.17: Please refer to Responses 6.1, 6.2, 7.7, 7.14, 7.15, 7.23, 7.27, and 7.28.

Comment 7.18: Nanosilva [LLC] has had sufficient time to generate and submit required 

data. 

FIFRA allows EPA to grant conditional registrations of active ingredients not contained in 

any currently registered pesticides to allow registrants to generate and submit required 

data. However, only when a data requirement is “first imposed” so recently that a registrant 

is unable to generate the data in time for the registration application may EPA grant a 

conditional registration. 

For example, EPA may require additional information from a registrant because those data 

specified in the regulations are insufficient for EPA to properly evaluate the product. Upon 

such a request, the registrant should be given sufficient time to generate that data, and a 

conditional registration may be applicable. However, that is not the case here. 

Nanosilva LLC applied in August 2009 to register this product. EPA concluded that 

because it had not yet reached a final decision as to which types of data would be required 

for [NSPW-L30SS], in part to apply the advice provided by SAP, that insufficient time had 
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elapsed from the point at which EPA determined and informed Nanosilva LLC of the data 

requirements needed to assess Nanosilva LLC’s application for Nanosilva LLC to have 

generated the data. Nearly four years have passed since SAP convened in November 2009 

and identified what would be needed to make a decision on [NSPW-L30SS]’s application. 

EPA now proposes to grant another three years to develop the newly required studies. 

More than sufficient time has elapsed for the company to perform adequate toxicological 

testing of its product. 

Response 7.18: While it has been several years since the SAP convened in 2009, the SAP 

did not make specific recommendations on the data needed to assess a nanosilver 

ingredient or how to adapt existing data requirements and guidelines to assess nanosilver. 

Rather it is the Agency that needed to take the steps to address these and other issues in the 

course of its consideration of applications it had already received. In response to and 

consistent with the SAP advice and after a review of the data available at that time, the 

Agency first determined that it cannot rely on data for macrosilver alone when assessing 

the risks from products containing nanosilver and that it needed to cautiously approach 

general use of nanosilver data to evaluate specific nanosilver ingredients given the stated 

concerns from the SAP that the toxicity of different nanosilver ingredients could differ. 

Then, the Agency took steps to assess the risks from use of nanosilver in the subject 

product based on a review the existing data available on nanosilver. From that assessment, 

the Agency considered what data would still be needed to more fully assess use of the 

current product, and whether or how to adapt the existing data requirements and guidelines 

to address any additional data needs or concerns. Generally, EPA determined that the 

existing data requirements would be a good starting point, but that those requirements 

needed to be refined or new data would be needed to more specifically address the unique 

nanosilver issues or concerns. Thus, in some cases, for example, EPA determined a study 

not currently required by the regulations would be needed (e.g., additional leaching data). 

In other cases, for example, EPA determined that adapting the regulatory data requirements 

and/or guideline references through combining elements of existing data requirements and 

other guideline references (e.g., developmental/reproductive) or tiering data (i.e., all Tier II 

data) would be needed to assess the product and to avoid doing additional/unnecessary 

studies. These specific data requirements and adaptations of existing requirements are not 

captured by the existing regulatory data tables, and had not previously been communicated 

to or required of the applicant. Taking into consideration the uniqueness of this registration 

and the notice and comment process, the decision about what data would be required for 

this nanosilver product was not made final until after EPA heard from commenters on the 

proposed decision, considered the comments and prepared the final decision. However, the 

decision made on this product will inform how to approach future applications for 

pesticide products containing nanosilver, and thus EPA expects the time for generation of 

data post-application or post registration will narrow over time. Thus, for the reasons noted 

above, EPA disagrees with the commenter that Nanosilva LLC had a reasonable period of 

time within which to generate and submit required data to the Agency. With respect to this 

registration action, EPA notes that the required studies must be completed within four 

years after issuing the registration. This time period was chosen to allow time for protocol 

reviews prior to initiation of the studies, completion of the studies, and Agency review of 

the study results. The Agency will evaluate these data as they are submitted to confirm 

elements of the risk assessment supporting the Agency’s determination that the use of 

NSPW-L30SS will not cause unreasonable adverse effects to human health and the 
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environment. If Nanosilva LLC fails to take appropriate steps to initiate the required 

studies, or if Nanosilva LLC fails to submit the protocols or data, EPA will issue a notice 

of intent to cancel NSPW-L30SS’s registration under FIFRA section 6(e). In addition, the 

conditional registration for NSPW-L30SS will automatically expire four years after being 

issued. Nanosilva LLC should request an amendment to remove the expiration date once 

they have submitted the required data if they wish to continue to sell and distribute NSPWL30SS in the United States. 

Comment 7.19: To grant a conditional registration, EPA must determine that the use of 

the pesticide is in the public interest. EPA believes that the registration of this product 

benefits the public based on the following points: 1) conservation of the environment, 2) 

consumer benefits, and 3) innovation. 

For the first claim, EPA notes that a number of silver-based pesticide products are 

registered for use as materials preservatives, and that the use of [NSPW-L30SS] could 

result in less environmental loading of silver than from currently registered silver-based 

pesticides. However, because nanosilver is a more potent pesticide than traditional silverbased pesticides – that is, less nanosilver kills more microbes – even if [NSPW-L30SS] 

results in a reduction in the overall mass of silver released into the environment, the 

potential for environmental damage and non-target impacts may still be greater than that 

resulting from currently registered silver-based pesticides. In fact, SAP noted that the rate 

and concentration of silver ions released from nanosilver will likely affect the acute or 

chronic toxicity of nanosilver compared with silver. 

EPA ignores the fact that there is no silver pesticide product on the market right now that is 

used as a material preservative in plastic for products like decking and plastic lumber, 

which have not previously relied on silver-based pesticides. Thus [NSPW-L30SS] will be 

in addition to, rather than in place of other silver-embedded products in the environment. 

Therefore, conditional registration of [NSPW-L30SS] will necessarily increase, not reduce, 

the amount of silver ions that will be released into the environment 

SAP noted that nanosilver, but not silver, can penetrate cell membranes and deliver toxic 

ions directly inside of cells; the toxicity of silver nanoparticles appear to be much higher 

than that of silver nitrate; and that because of these differences in chemical properties, 

there are likely differences in exposure and environmental fate of nanosilver that should be 

considered. Thus, in the case of [NSPW-L30SS] replacing silver-based pesticides in 

commerce, any reduction in environmental loading of silver is not likely to result in 

conservation of the environment. 

Response 7.19: With respect to the public interest finding, please refer to Response 3.1. 

For more detailed information on why reduced environmental loading is in the public 

interest, even assuming nanosilver is more toxic than silver, please refer to Response 7.7. 

With respect to existing uses of silver based products in plastics, see Response 7.10. As 

EPA explained in the proposed and final decision documents, the available data show 

release of nanosilver below the level of detection. Taking into consideration these low 

releases, the available toxicity data, use of multiple risk uncertainty factors (UFs) and 

required risk mitigation measures on the product label, the calculated margins of exposure 

(MOEs) and risk quotients (RQs) were well above the Agency levels of concern (LOCs). 

On these grounds, EPA determined that there is substantial evidence in the record to 
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conclude that the proposed use of NSPW-L30SS during the conditional registration period 

will not cause unreasonable adverse effects on human health or the environment. 

Comment 7.20: In its second claim, EPA asserts that conditional registration of [NSPWL30SS] will lead to consumer benefits, such that “plastics or textiles incorporating 

nanosilver may have longer-term ability to reduce the number of odor and stain causing 

bacteria as compared to other similar products on the market that contain conventional 

silvers.” However, EPA has failed to explain why consumers need antimicrobial plastics or 

textiles in the first case. 

Response 7.20: EPA agrees that the potential for consumer benefits does not address the 

need for the pesticide. See Response 3.1 for further discussion of the public interest 

finding. 

Comment 7.21: EPA claims that it sees the emergence of nanotechnology as offering 

benefits for society including pest control products, and seeks to encourage innovative 

work to realize those benefits. However, EPA does not provide any supporting data that 

suggests how or why it believes that nanotechnology “may allow for more effective 

targeting of pests and use of smaller quantities of pesticide.” Moreover EPA fails to assert 

how conditional registration of [NSPW-L30SS] will encourage such innovative work, or in 

the alternative, how requiring sufficient data and studies of [NSPW-L30SS] would 

discourage such innovative work. 

Response 7.21: Based on the review as detailed in the decision document, EPA believes 

the registration of NSPW-L30SS has the potential to reduce environmental loading of 

silver. EPA has registered a number of silver-based antimicrobial products for use as 

materials preservatives in textiles. Most antimicrobial silver-based pesticide products 

currently contain a silver salt (e.g., AgCl or AgNO3). Compared to the amount of silver in 

Nanosilva LLC’s product, most currently registered silver-based materials preservative 

registrations allow far larger application rates than allowed for the conditional registration 

of NSPW-L30SS. Therefore, the overall potential environmental loading of silver resulting 

from the lower-volume use of the Nanosilva LLC product should be smaller than from a 

comparable use of currently registered silver-based pesticides. 

The White House has specifically identified nanotechnology as an emerging field 

(http://www.whitehouse.gov/sites/default/files/omb/inforeg/for-agencies/nanotechnologyregulation-and-oversight-principles.pdf and 

http://www.whitehouse.gov/assets/documents/SEPT_20__Innovation_Whitepaper_FINAL

.pdf - Released September 21, 2009). EPA supports innovation when its review shows the 

product developed under innovative technologies meets the statutory standards. Granting 

the registration of NSPW-L30SS provides industry with a second example of EPA’s 

assessment of a nanosilver pesticide while also providing increased certainty for data 

needs, which contributes to a more efficient registration process and thus encourages 

innovation in pesticides. 

See Response 7.14 for a discussion of how most currently registered silver-based materials 

preservative registrations allow for larger application rates than NSPW-L30SS. 

Comment 7.22: Given the potential harm to human health and the environment, 

significant scientific unknowns, and lack of support for alleged benefits of [NSPWL30SS], the conditional registration of [NSPW-L30SS] is not in the public interest. 
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Response 7.22: Please refer to Responses 3.1, 6.1, 7.4, 7.7, 7.14, and 7.15. 

Comment 7.23: CFS/ICTA is opposed to conditional registration generally and to that of 

[NSPW-L30SS] specifically. Conditional registrations of pesticides have been overused by 

EPA and the management of EPA’s conditional registration program raises significant red 

flags about its ability to protect the American public while allowing products with known 

risks to remain on the market while undergoing further study. 

Section 3(c)(7) of FIFRA provides EPA the authority to grant a “conditional registration” 

for a pesticide product under certain circumstances, even though some necessary data have 

not been provided by the registrant in the application. By doing so, EPA allows pesticides 

into the marketplace without complete data, such as toxicity tests and studies that 

demonstrate the pesticides’ impact on the environment. EPA’s Office of Pesticide 

Programs (OPP) has overused conditional registrations, not in keeping with their original 

intent – to be used only in limited circumstances where a public need was established. 

In March 2011, an internal review conducted by OPP determined that of 16,156 active 

pesticide registrations, 11,205 (69 percent) were conditionally registered. Of those, over 

3,200 pesticides had been in conditional status since 1995, and 2,100 pesticides had been 

in conditional status since 1990. OPP officials allege that these numbers are inaccurate as a 

result of misclassifications and that the basis for many registration decisions was 

mischaracterized as conditional. 

The high numbers of products registrations that remain conditionally registered after so 

many years raises several concerns. 

At best, EPA has poorly overseen its registration program to the point that its tracking 

system cannot even identify the status of conditionally registered pesticides to ensure that 

registrants submitted, and EPA reviewed, the required additional data upon which 

registration is conditioned, in a timely manner. As currently construed, the conditional 

registration program calls into question EPA’s assertion that it will evaluate the additional 

required data “to confirm the Agency’s risk assessment.” 

More importantly, OPP may be failing to meet its requirements under FIFRA to review 

each chemical every 15 years, allowing products to stay on the market despite lacking the 

data required by law. 

The Government Accountability Office (GAO) addressed these issues, amongst others, in a 

2013 report entitled, “PESTICIDES: EPA Should Take Steps to Improve Its Oversight of 

Conditional Registrations.” GAO made several conclusions regarding EPA’s improper 

handling of conditional registration, including: 

EPA lacks a reliable system to track key information related to conditional registrations, 

including whether companies have submitted the additional data required by conditional 

registration within the required time frames. Thus, EPA lacks an important registration 

management tool and cannot ensure that companies submit the required data, which may 

allow pesticides to remain on the market for years without EPA’s receipt and review of 

these data. 

GAO has well documented OPP’s problems with data management, with studies dating 

back to 1980, 1986, 1991, and 1992 noting problems with OPP data systems used to track 

the status of pesticide registrations. 
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GAO was unable to verify OPP officials’ assertion that all actions mistakenly categorized 

as conditional registrations were legitimate program actions which were lawful under other 

sections of FIFRA. EPA needs to correct misclassifications to ensure the accuracy and 

integrity of its data and make clear the statutory basis for these actions. 

OPP’s use of conditional registrations for actions other than those that meet the criteria 

outlined in FIFRA Section 3(c)(7) has created confusion for its staff. OPP lacks written 

guidance or a consistent methodology for maintaining its pesticide registration files, 

resulting in difficulty developing summary information about the status of pesticide 

registrations, and managing the pesticide registration program. 

Given the mishandling of EPA’s conditional registration program, its usage here is 

troublesome. Specifically, because EPA cannot adequately track conditional registrations 

and assure that the requested data is timely submitted, the public cannot be assured what 

will happen upon the expiration of the four years which EPA has granted Nanosilva [LLC] 

to supply the required data. EPA provides no clue as to what will happen upon expiration 

of this four year time period, such as [NSPW-L30SS] products being removed from the 

market, or prosecution for continued production of [NSPW-L30SS] incorporated products. 

Thus, even if [NSPW-L30SS]’s conditional registration expires in four years there is no 

guarantee that EPA will take proper action to protect environmental safety and ensure that 

[NSPW-L30SS] products are removed from the market or prevented from entering the 

market. 

EPA has overused conditional registrations generally, failed to adequately oversee its 

conditional registration program allowing pesticide products to remain on the market 

without adequate and required studies, and should curtail its use of conditional registration 

to adhere to its original intent. Specifically, EPA’s proposed conditional registration for 

[NSPW-L30SS] is not supported by necessary elements as required by FIFRA. 

Response 7.23: The Agency’s Conditional Registration web page 

(http://www.epa.gov/pesticides/regulating/conditional-registration.html) addresses many of 

these issues in great detail. 

EPA project managers are assigned with reviewing and monitoring the progress registrants 

make in meeting the required deadlines for submission of protocols and studies for 

conditional registrations including this registration. The Conditional Registration Status 

table (available at: http://www2.epa.gov/pesticide-registration/conditional-registrationstatus-2000-2014), also provides information regarding pesticide active ingredients 

initially registered under the conditional registration authority in FIFRA sec. 3(c)(7)(C) 

from FY2000 to the present. 

The expiration date on a conditionally registered product is an effective tool because it 

makes sales or distribution of such product after the expiration date a violation and subject 

to corrective action and penalties under FIFRA. The expiration date requires that the 

registration be amended to authorize continued sale and distribution of the pesticide by the 

end of the expiration period, or that a new registration be issued. In either case, whether the 

data have been timely submitted and reviewed and what submitted data show will be taken 

into consideration in determining whether an amended or new registration may be 

authorized and under what conditions. If Nanosilva LLC fails to take appropriate steps to 

initiate the required studies, or if Nanosilva LLC fails to submit the protocols or data, EPA 
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will issue a notice of intent to cancel the registration of NSPW-L30SS under FIFRA 

section 6(e) even before the expiration of the registration. If the registration is allowed to 

expire, EPA will issue an order under section 6(a) to address existing stocks requirements. 

Through the registration review program, the EPA is reevaluating all registered pesticides 

to ensure that they continue to satisfy statutory standard for registration – that is, these 

pesticide registrations are based on current scientific and other knowledge and can still be 

used without unreasonable adverse effects on human health and the environment. 

Nanosilver is currently undergoing registration review by the EPA’s Office of Pesticide 

Programs. The Preliminary Registration Review Work Plan for nanosilver, available at 

regulations.gov (Docket ID: EPA-HQ-OPP-2011-0370), explains the next steps the 

Agency is proposing in the review process. More information about the Registration 

Review Process is available at: http://www2.epa.gov/pesticide-reevaluation/registrationreview-process#program status. 

Comment 7.24: Proceeding with a conditional registration based on the rationale provided 

in the Draft Decision Document would be an arbitrary and capricious action by EPA, and 

contrary to law. Agency action must be set aside if it is arbitrary and capricious, an abuse 

of discretion, otherwise not in accordance with law, or without observance of procedure 

required by law. Agency action is arbitrary and capricious if the agency relied on factors 

Congress has not intended it to consider, entirely failed to consider an important aspect of 

the problem, offered an explanation for its decision that runs counter to the evidence before 

the agency, or is so implausible that it could not be ascribed to a difference in view or the 

product of agency expertise. EPA’s Draft Decision Document overlooked important gaps 

in scientific data, applied faulty science to determine possible risks to conditional 

registration of [NSPW-L30SS], and if approved would be arbitrary and capricious agency 

action. 

Response 7.24: FIFRA authorizes EPA to issue registrations under Section 3(c)(5) or 

“conditional” registrations under Section 3(c)(7). 7 U.S.C. §§ 136a(c)(5), (c)(7). To 

support either type of registration, applicants must submit studies intended to identify 

potential effects on human health and the environment. 7 U.S.C. § 136a(c); 40 C.F.R. Parts 

158, 161. While a conditional registration provides a registrant with the same rights as a 

registration under Section 3(c)(5), EPA is authorized to issue a conditional registration 

even where it has not yet received certain required data concerning the risks associated 

with a pesticide, so long as EPA has sufficient information to determine that use of the 

pesticide “will not cause any unreasonable adverse effect on the environment” while the 

required data are being generated, that there has been insufficient time to submit the 

required data since the Administrator first imposed the data requirement, and that the “use 

of the pesticide is in the public interest.” 7 U.S.C. § 136a(c)(7)(C). 

Commenters suggest that in the absence of all required data, EPA cannot make the 

determination that the proposed use of the pesticide “will not cause any unreasonable 

adverse effect on the environment” while the newly required data are being generated. 

Such an argument reduces the authority in FIFRA section 3(c)(7)(C) to a nullity. Congress 

contemplated that there would be an absence of required data when it authorized issuance 

of conditional registrations. In this case, there are data still needed to assess the nanosilver 

in NSPW-L30SS. The data are required as a condition of the registration and are a 

combination of (i) data not yet required by the regulatory data requirements (e.g., leaching 
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studies), (ii) data that are nanosilver-specific adaptations of the regulatory data 

requirements for antimicrobials (e.g., 90-day inhalation toxicity study, 

reproduction/developmental toxicity screening test) and (iii) regulatory data requirements 

determined by EPA to be unnecessary unless Tier 1 data results trigger the need for the 

data. These data are required for this product because the Agency determined that it cannot 

rely on data for macrosilver alone when assessing the risks from products containing 

nanosilver and yet determined that the existing regulatory data requirements and guidelines 

generally needed to be adapted to address the needs specific to review of nanosilver. In 

some cases, for example, this means requiring a study not currently required by the 

regulations. In other cases, for example, this means adapting the regulatory data 

requirements for this case to avoid requiring unnecessary data or to focus the study on a 

narrow need, known only after assessing the pesticide. With respect to concerns that the 

absence of these data means the Agency’s decision is arbitrary and capricious, as EPA 

explained in the proposed and final decision documents and throughout this document, the 

available data show release of nanosilver below the level of detection. Taking into 

consideration these low releases, available toxicity data, multiple risk uncertainty factors 

(UFs) into the risk assessment, which included an additional 10x to account for missing 

data that will be submitted in response to the condition on the registration, and required 

risk mitigation measures on the product label, the calculated margins of exposure (MOEs) 

and risk quotients (RQs) were well above the Agency levels of concern (LOCs). On these 

grounds, EPA determined that there is substantial evidence in the record to conclude that 

the proposed use of NSPW-L30SS during the conditional registration period will not cause 

unreasonable adverse effects on human health or the environment, even absent some of the 

data that EPA is requiring as a condition on the registration. Thus, this case is a clear 

example of circumstances that support finding that use of the pesticide will not cause 

unreasonable adverse effects, notwithstanding the need for additional data. 

Comment 7.25: EPA’s cursory look at aggregate effects is insufficient and fails to 

consider the other nano-scale antimicrobials which are on the market without having 

undergone a full chemical risk assessment on the nano-scale material. 

EPA’s proposed conditional registration of [NSPW-L30SS] while turning a blind eye to 

other nanosilver pesticides currently on the market is contrary to its obligations under 

FIFRA. The agency is legally obligated to adopt a consistent policy with regard to 

nanosilver products, because nanosilver is a pesticide requiring registration. These other 

nanosilver products, like [NSPW-L30SS], are properly classified as “pesticides” since the 

only purpose of the infused nanosilver is to fight bacteria, i.e., prevent pests. Nanosilver 

thus meets the definition of a pesticide. 

EPA argues that, because Congress specifically required consideration of aggregate 

exposures for registration under FIFRA for food-use pesticides, but not for non food-use 

pesticides, that such studies are not required to determine whether registration of [NSPWL30SS] will cause any unreasonable adverse effects on the environment. 

Thus, for the sake of “transparency,” the extent of EPA’s consideration of aggregate 

exposures involved [NSPW-L30SS] and HeiQ AGS-20, “the only other pesticide which 

was knowingly registered as containing nanosilver.” In so doing, EPA concluded that if 

exposures to the two active nanosilver ingredients in [NSPW-L30SS] and HeiQ AGS-20, 

were to occur concurrently, they would not result in margins of exposure that “would be of 
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concern.” However, this fails to account for aggregate human and environmental exposures 

from other sources of nanosilver, which are many. Given that EPA’s rationale for 

approving a conditional registration for this product is the purported environmental benefit 

to the environment from the release of silver ions, EPA must consider the cumulative and 

aggregate impact of all the various sources of silver ions in the environment. 

According to the Woodrow Wilson International Center for Scholars, Project on Emerging 

Nanotechnologies (PEN), which maintains a registry of self-labeled products containing 

nanomaterials, there are over 300 nanosilver products already on the market. Since no 

labeling or government registration is currently required, these self-labeled products are 

likely only the tip of the iceberg. PEN estimates that there are three to four new nanotech 

products hitting the market every week. 

EPA has acknowledged that it suspects it already approved the registrations of some likesituated products on the market that contain nanosilver as the active ingredient without 

knowledge that these products may contain nanosilver and without assessing any potential 

risks that might be associated with nanosilver. Though EPA intends to seek more data from 

those products, such an admission should call for more caution, not less. 

Response 7.25: With respect to comments stating that all products containing nanosilver 

or advertised to contain nanosilver can be classified as a pesticide, please see Response 

7.3. With respect to comments that EPA is obligated to consider all exposures to 

nanosilver in products on the market, please see Response 6.4. 

Comment 7.26: EPA acknowledged that it lacks the necessary information required to 

conduct an adequate aggregate risk assessment as to exposure to other nanosilver products 

in the market place. Not only does EPA not have sufficient information to conduct an 

aggregate risk assessment, EPA asserts that it lacks adequate information on the 

composition of the nanosilver or potential nanosilver in other silver based pesticides to 

determine if all nanosilver should be treated as a single chemical. Yet, EPA claims it had 

sufficient information to determine that [NSPW-L30SS] would not pose unreasonable 

adverse effects on the environment. Without including such increased aggregate exposure 

and cumulative risk, the agency’s determination failed to ensure that the registration will 

not cause any “unreasonable adverse effects” on the environment or health, and is plainly 

contrary to the public interest. 

Response 7.26: Please refer to Responses 6.4 and 7.25. 

Comment 7.27: EPA’s reliance on available studies on the effect of nanosilver is 

misplaced because [NSPW-L30SS] is unique as a nanosilver and nanosilicon based 

combination nano-particle, a combination for which there is no public data. 

[NSPW-L30SS] is a silica-sulfur-nanosilver complex where the nanosilver activeingredient is attached to crystalline silica via a thiolate bond. This configuration presents a 

more than substantial alteration to existing nanosilver combinations. Minimal public data 

exists on the unique combination of nanosilver and nanosilicon, such that any reliance on 

available studies on the effect of nanosilver by EPA is misplaced and inadequate in 

evaluating the risk to human health and the environment. 

EPA acknowledged that SAP “cautioned about extrapolating from one nanosilver 

formulation to another when assessing hazards because differences in particle formulation 

(e.g., coating and inert ingredients) are likely to affect biological activity, among other 
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things.” Yet, EPA has done exactly that. For example, because no repeated-dose 

subchronic or chronic toxicity studies exist for [NSPW-L30SS] or the nanosilver in 

[NSPW-L30SS], the Agency relied on studies in the scientific literature on nanosilver 

toxicity based on the belief that they would be sufficient for assessing the risks of the 

unique [NSPW-L30SS] complex. 

Response 7.27: Please refer to Responses 6.1, 6.2, 7.7, 7.10, 7.14, 7.15, and 7.28. While 

the Agency acknowledges the points addressed by the SAP, it feels the cited existing data 

are sufficient for assessing the risks in this case because, in addition to those data 

addressing the significant routes of exposures and identifying hazards, EPA accounts for 

any variation between the nanosilvers through use of the additional 10X database 

uncertainty factor and the resulting MOEs are well above any risk concern. For further 

information on why specific studies are required, please refer to Responses 6.1 and 6.2. As 

EPA explained in the proposed and final decision documents, the available data show 

release of nanosilver below the level of detection. Taking into consideration these low 

releases, the available toxicity data, use of multiple risk uncertainty factors (UFs) and 

required risk mitigation measures on the product label, the calculated margins of exposure 

(MOEs) and risk quotients (RQs) were well above the Agency levels of concern (LOCs). 

On these grounds, EPA determined that there is substantial evidence in the record to 

conclude that the proposed use of NSPW-L30SS during the conditional registration period 

will not cause unreasonable adverse effects on human health or the environment. 

Comment 7.28: Until EPA has data which shows that [NSPW-L30SS] is not a 

reproductive or development toxicant, a carcinogen, an endocrine disrupter, and that it is 

not toxic to the aquatic environment, EPA cannot allow this product to enter the market. 

Without these data, EPA cannot show that there are no unreasonable adverse effects to the 

environment and human health associated with the use of [NSPW-L30SS], and as such, 

cannot conditionally register this pesticide product. 

Response 7.28: The Agency disagrees with commenters’ premise that data showing no 

toxicity is required to grant the pesticide registration request. FIFRA section 3(c)(7)(C) 

requires EPA to find that use of the pesticide will not cause unreasonable adverse effects, 

and that finding takes into account both toxicity and exposure information. In this case, 

there is sufficient information on the endpoints noted above and to make this finding. With 

respect to data on reproductive or developmental toxicity, as explained in both the 

proposed and final decision documents, the Agency disagrees that there is no information 

sufficient to make the requisite statutory finding. Please see Responses 6.1 and 6.2. 

There is a paper by Yu et al. (Yu et al, 2013) supporting these conclusions which shows 

that there were no maternal or developmental effects up to 1000 mg/kg bw using a 

nanosilver 7.5 nm in size. These levels at which no effects were observed support the 

Agency’s conclusion that PODs chosen to assess the risks from the use of NSPW-L30SS 

are protective of any potential developmental or reproductive effect. Finally, as noted in 

the Proposed Decision Document, the Agency is also requiring the registrant to complete a 

modified reproductive/developmental assay. The additional 10X database uncertainty 

factor is sufficient and health protective until these additional data are submitted to the 

Agency and incorporated in the assessment. 

In regards to carcinogenicity, a cancer study is conditionally required for “all other 

nonfood uses” under 158W. Additionally, test note 21i states the cancer study is required if 
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“the use of the pesticide is likely to result in significant human exposure over a 

considerable portion of the human lifespan which is significant in terms of frequency, time, 

duration, and/or magnitude of exposure.” Although children’s short- and intermediate-term 

exposure durations to plastic toys and textiles treated with NSPW-L30SS are expected, 

children are not anticipated to play with NSPW-L30SS-treated toys or contact NSPWL30SS-treated textiles every day for a period of greater than six months, thus chronic 

exposures are unlikely. The EPA also does not believe that children will have continuous 

and daily exposure to NSPW-L30SS treated flooring for a period greater than 6 months. 

Based on the lack of chronic exposure, a carcinogenicity study is not required for NSPWL30SS. Furthermore, the in vitro mutagenicity data are equivocal and the available in vivo

micronucleus rat assay of oral administration of nanosilver at concentrations of up to 1,000 

mg/kg/day (Kim, et al, 2008) is neither clastogenic nor aneugenic. Therefore there is no 

concern for mutagenicity or genotoxicity. 

In regards to endocrine disruption, the EPA has developed the EDSP to determine whether 

certain substances (including pesticide active and other ingredients) may have an effect in 

humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or 

other such endocrine effects as the Administrator may designate.” The EDSP employs a 

two-tiered approach to making the statutorily required determinations. Tier 1 consists of a 

battery of 11 screening assays to identify the potential of a chemical substance to interact 

with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go 

through Tier 1 screening and are found to have the potential to interact with E, A, or T 

hormonal systems will proceed to the next stage of the EDSP where EPA will determine 

which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is 

designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. In the 

case of NSPW-L30SS, the Tier 2 test for mammals (Extended One-Generation 

Reproduction Study with modifications) is required upon registration. This route 

appropriate study will provide endocrine related endpoints and will be used by the Agency 

to determine if further endocrine testing is warranted. Regardless, the current points of 

departure and total uncertainty factors are health protective for endocrine effects. 

Comment 7.29: EPA’s reliance on available studies on the effect of silver is misplaced 

because it is not possible to infer the safety of nanomaterials by using information derived 

from the bulk parent material. 

In its Draft Decision Document, EPA acknowledged the conclusions of SAP that: 

“existing information on conventional silver could be useful but would not 

necessarily be sufficient in assessing potential nanosilver risks. SAP 

recommended that the Agency treat nanosilver differently from its 

conventional silver counterpart in evaluating proposed nanosilver product 

applications (in terms of both data requirements and the conduct of risk 

assessments). Moreover, the Panel recommended that EPA require additional 

data on the physical chemistry, exposure potential, and the potential hazard to 

human health and the environment.” 

Yet, EPA’s conclusion that human health or ecological risk from exposure to silver ions 

derived from products incorporating [NSPW-L30SS] are not of concern, “relied on the 

existing reregistration decision for silver.” Similarly, despite known risks of silver’s 
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toxicity to aquatic life, Nanosilva [LLC] did not submit any tests with aquatic organisms. 

However, after mentioning the concentrations of silver in surface waters, EPA summarily 

concluded that it does not expect any unreasonable adverse effects to the environment by 

citing a twenty year old assessment of conventional silver, from 1993, with no further 

explanation. Such reliance is misplaced and fails to adequately assess the risk exposure 

from granting [NSPW-L30SS] conditional registration. 

Response 7.29: The Agency did not infer the safety of nanosilver by using information on 

bulk silver. For more detailed discussion of the assessment, including on both nanosilver 

and silver ions, please refer to Responses 6.1, 6.2, 7.7, 7.14, 7.15, 7.27, and 7.28. With 

respect to reliance on the 1993 RED for assessment of silver ions, comments do not 

provide enough detail for the Agency to understand why it should not be relying on the 

1993 Silver RED for the portion of the NSPW-L30SS risk assessment relating to silver 

ions. 

Comment 7.30: EPA’s proposed conditional registration of [NSPW-L30SS] would be an 

arbitrary and capricious agency action contrary to law and in violation of FIFRA. Given 

significant unknowns about nanotechnology generally, and [NSPW-L30SS] specifically, 

EPA’s proposed conditional registration would expose the environment to unreasonable 

adverse effects. These significant known and unknown risks provide all the more reason 

that EPA should require more testing before allowing [NSPW-L30SS] on the market. EPA 

has overused and misused its authority under FIFRA in its use of conditional registrations, 

allowing untested products on the market while relying on improper science and ignoring 

significant data gaps about their effects. EPA must withdraw its proposal to conditionally 

register [NSPW-L30SS] so as to act in accordance with its duties under FIFRA and to 

protect human health and the environment. 

Response 7.30: Please refer to Response 7.25. 

Commenter 8: Mae Wu and Jennifer Sass, The Natural Resources Defense Council (NRDC) 

(EPA-HQ-OPP-2012-0594-0022, Received 9/26/2013) 

Comment 8.1: We are concerned that crystalline silica is quartz, which is highly toxic 

carcinogen. We doubt that EPA would ever approve quartz, and suggest that [NSPWL30SS] is in fact attached to synthetic amorphous silica. We will address the issue of the 

poorly defined material later in these comments, but here wish to flag for EPA that the 

staff reviewing the data on [NSPW-L30SS] seem not to have the necessary expertise in 

material chemistry required to adequately describe the Nanosilver material. This is not the 

training of toxicologists. 

Response 8.1: Please refer to Response 7.1.

Comment 8.2: The FIFRA Scientific Advisory Panel (“SAP”) reported in 2010 that 

several major differences between silver and nanosilver were likely to result in a distinct 

hazard profile for nanosilver. However, the SAP noted that there are no studies that are 

definitive regarding a comparison of silver and nanosilver toxicity, and more research is 

required. These findings showcase the problem with EPA’s proposal to put nanosilver on 

the market essentially untested, with an inadequate hazard database, while knowing that it 

is likely to be more hazardous than silver. 

Response 8.2: Please refer to Responses 6.1, 6.2, 7.7, 7.14, 7.15, 7.27, and 7.28. 
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Comment 8.3: At this time, EPA has so many unsolved problems with conditional 

registrations that it should not grant any conditional registration of a new pesticide active 

ingredient. EPA is inappropriately using the conditional registration process and should not 

do so until it can fix the problems and ensure that it is protecting the environment and 

public health from dangerous pesticides. 

In March, 2013, NRDC released its report “Superficial Safeguards: Most Pesticides are 

approved by a flawed EPA process.” The report indicates that the majority of pesticides 

registered by EPA were conditionally registered. In fact, NRDC’s review of the EPA 

database showed that 65 percent of all registered pesticides were done so through the 

conditional registration process. In addition to the misuse of conditional registrations, 

NRDC also found that EPA’s database to track these conditional registrations was a mess. 

EPA was unable to tell whether requested data had been submitted in a timely manner, 

whether the data had been reviewed by the agency, or whether any review of the data 

resulted in changes to the pesticides registration designation. NRDC further highlighted 

two specific examples of pesticides that were improperly registered conditionally, 

including AGS-20, which is also a nanosilver pesticide product that EPA conditionally 

registered in 2011. In response to news articles about this report, EPA stated “We will 

continue to work on improving record-keeping and have developed a plan to update the IT 

(information technology) systems to address that need.” 

On September 9, 2013, the U.S. Government Accountability Office (“GAO”) released its 

report, “PESTICIDES: EPA Should Take Steps to Improve Its Oversight of Conditional 

Registrations” (hereinafter referred to as the “GAO Report.”) Similar to NRDC’s report, 

the GAO found that EPA had inaccurate data on the total number of conditional 

registrations that have been granted due to “insufficient guidance and training, 

management oversight, and data management.” 

The GAO found that EPA does not have a way to track the status of conditional 

registrations. Although EPA officials believed that routine program operations would 

provide a suitable quality control check, the GAO found that “they fall short of what is 

needed because they are neither comprehensive nor do they ensure the timely submission 

of these data.” 

For example, EPA believed that “good faith submissions” by registrants would satisfy the 

data requirement, despite the fact that EPA had found cases where “required data were not 

submitted or were submitted late.” EPA also relied on individual product managers to 

develop their own tracking systems, including “electronic spreadsheets or reminder 

notices, handwritten notes, and memory,” which opens up to many problems especially 

when managers retire, resign, or take extended absences. 

The GAO further explained that “without a reliable tracking system, [EPA] may miss 

conditional pesticides where, had the additional required data been submitted and 

reviewed, [EPA] might have altered the terms of a registration.” “[W]ithout the ability to 

systematically track conditional registrations, [EPA] is not well-positioned to produce 

summary data to enable it to easily identify situations for priority follow-up; enforce 

FIFRA and its implementing regulations; and report to Congress and others on program 

status.” 
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GAO recommended three major changes that EPA should undertake to improve this 

program. The most important of the three was the first: “Complete plans to automate data 

related to conditional registrations to more readily track the status of these registrations and 

related registrant and agency actions and identify potential problems requiring 

management attention....” 

While EPA responds that it is taking some steps to achieve this goal, it hedges its bets by 

saying “it plans to develop a more comprehensive system for tracking conditional 

registrations; however, the agency’s ability to do so depends on the availability of funding 

and the complexity of incorporating changes in the databases.” 

In the Draft Decision Document, EPA states that [NSPW-L30SS]’s registration will 

automatically expire after four years and that Nanosilva [LLC] will have to submit another 

application to obtain an unconditional registration. If this is EPA’s weak attempt to 

circumvent the systemic problems with its conditional registration program, it is not 

enough. There is no indication that [NSPW-L30SS] products will automatically be 

removed from the market at expiration of the four year time period. While EPA may argue 

that any [NSPW-L30SS] products still on the market after four years would be there 

illegally, this argument is not comforting. As EPA acknowledged in conditionally 

registering AGS-20, there are many nanosilver products illegally on the market. Hei-Q was 

merely the first company to take steps to legally register its product. To our knowledge, 

EPA has never prosecuted or taken any other actions to ensure that illegal nanosilver 

products are removed from the market. Therefore, even if the [NSPW-L30SS] registration 

were to expire in four years, there is no guarantee that EPA would take any action to 

ensure that all [NSPW-L30SS] products are actually removed from the market. 

Response 8.3: With respect to general concerns with issuing conditional registrations, 

please refer to Response 7.23. With respect to claims that there are illegal nanosilver 

products, nanosilver products that have been identified as unregistered pesticides are being 

addressed through various administrative and enforcement actions. Additional information 

can be found in the EPA Response to "Petition for Rulemaking Requesting EPA Regulate 

Nano-Silver Products as Pesticides", available at regulations.gov (Docket ID: EPA-HQOPP-2008-0650). 

Comment 8.4: Early in the Draft Decision Document, EPA explains its decision to 

conditionally register [NSPW-L30SS]. It states “EPA has determined that there is a low 

probability of adverse risk to human health and the environment from plastics and textiles 

incorporating [NSPW-L30SS]...” This is the wrong standard. FIFRA allows a pesticide to 

be conditionally registered only if the Administrator has determined that “use of the 

pesticide will not cause any unreasonable adverse effect on the environment...” 7 U.S.C. 

§136a(c)(7)(C). The standard is not “low probability” of adverse risk – it is no 

unreasonable adverse effect. EPA’s finding of “low probability of adverse risk” weakens 

the statutory standard and is impermissible. 

Response 8.4: Please refer to Response 7.9. 

Comment 8.5: In August 2009, Nanosilva [LLC] applied to register [NSPW-L30SS] as a 

new active ingredient. EPA may only conditionally register a new active ingredient for a 

period of time to allow the registrant to generate required data because “a period 

reasonably sufficient for generation of the data has not elapsed since the Administrator first 
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imposed the data requirement....” 7 U.S.C. §136a(c)(7)(C). EPA relies on the fact that it 

had to consult with its SAP to determine the data requirements needed to assess Nanosilva 

[LLC]’s application. The SAP convened in November, 2009 meaning that almost four 

years have passed since EPA would have identified the data requirements that would be 

needed to make a decision on Nanosilva [LLC]’s application. EPA is now granting 

Nanosilva [LLC] another three years to develop the requisite health effects studies 

including the health effects toxicity tests, the ecological effects tests, and the 

environmental fate studies. The time that has transpired between the SAP meeting when 

EPA developed the list of tests that are necessary and now does provide a reasonably 

sufficient period of time for generation of the data, and argues against granting a 

conditional registration. 

Response 8.5: Please refer to Response 7.18. 

Comment 8.6: The conditional registration of [NSPW-L30SS] is not in the public interest. 

It provides no measurable medical or health benefits to consumers, but puts them in harm’s 

way. There seems to be little doubt that consumers will come in direct contact with the 

pesticide while wearing treated clothing, and that children have a high likelihood of 

ingesting the pesticide while mouthing the clothing in addition to direct dermal contact. It 

is also possible that nanosilver that breaks away from the [NSPW-L30SS] product will be 

another source of exposure – potentially from floor coverings, outdoor furniture, or other 

uses. Because the proposed application is to treat textiles and plastics that consumers will 

come into direct contact with, exposure will be unavoidable. The potential harm from such 

contact is poorly understood and untested, which is a direct violation of FIFRA’s 

requirement for a safety finding. 

Response 8.6: EPA agrees that NSPW-L30SS is not proposed to have any medical or 

health benefits. However, EPA disagrees that NSPW-L30SS puts the public in harm’s way 

and that exposures in this case are poorly understood or untested. EPA’s exposure analysis 

was thorough. The analysis of use of NSPW-L30SS to treat textiles takes into 

consideration exposure scenarios, such as dermal exposures while wearing clothing and 

potential ingestion by children from mouthing textiles. EPA’s exposure analysis also takes 

into consideration the potential exposures from use of NSPW-L30SS to treat plastics. This 

analysis is driven by the low release rates from NSPW-L30SS treated textiles and plastics 

that yield low exposures, which, when compared to effects seen in toxicological studies, 

support the finding that the proposed use will not cause unreasonable adverse effects. 

Thus, EPA disagrees with the commenter’s conclusions. For additional information on 

EPA’s public interest finding, please see Response 3.1. 

Comment 8.7: To grant a conditional registration for a new active ingredient, EPA must 

show that use of the pesticide is in the public interest. The legislative history of the 

conditional registration process is clear that the “public interest” encompasses a narrow, 

not broad, range of interests, such as when there “is a significant pest control problem 

which cannot satisfactorily be handled by use of products which have been fully 

registered.” As explained by the then-EPA Administrator, the conditional registration 

would be important when “there may be a real need for use of the pesticide to avoid pest 

outbreaks.” Furthermore, he noted that “[a]lthough we think that the exercise of this 

conditional registration authority for new chemicals would be rare, we feel that it should be 

available in appropriate cases. 
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To ensure that conditional registration for new chemicals only occurred in the limited 

situations when the public interest was at stake, the House of Representatives agreed 

during conference to adopt a version of the amendment similar to the Senate’s that would 

require the Administrator to “determine as a condition to granting the registration that use 

of the pesticide is in the public interest.” 

In the GAO report on EPA’s use of conditional registrations, EPA also acknowledges that 

the conditional registration is to be used sparingly. EPA explains that in creating the 

conditional registration process, “Congress also recognized that it would be appropriate to 

give EPA discretionary authority, in very narrow circumstances, to approve the registration 

of a product containing a new active ingredient for which EPA requires additional data.” 

Despite the requirements that the conditional registration not be overused, EPA is 

proposing to conditionally register this pesticide product using an improperly generic and 

broad definition of public interest. Furthermore, some of the conclusions that EPA makes 

about the benefits associated with [NSPW-L30SS] are wrong. 

Response 8.7: Please see Response 3.1 for a discussion of the public interest finding in 

this case. The Agency disagrees that conditional registrations for new active ingredients 

are only authorized in such narrow cases as when there is a need to avoid pest outbreaks. 

Although the “public interest” may clearly be served in granting a registration request to 

address such a situation, EPA does not believe that Congress intended such a narrow 

interpretation of the “public interest” finding. This is evident from the fact that the early 

Senate bill referring to the pest outbreak example permitted a conditional registration for a 

new active ingredient only when “required in the public interest.” See, S. Report No. 95-

334, at 21 (1977). However, while the House companion had no such public interest 

requirement, the Conference Committee adopted a public interest finding, but without 

reference to “required.” This compromise between the position of the House and Senate 

indicates an intent to allow public interest findings for new active conditional registrations 

even when the pesticide use is not needed or required, but when the pesticide use would 

nonetheless be in the public interest. As discussed in EPA’s 1986 statement on the public 

interest finding considerations other than “need” are important in determining whether use 

of a pesticide is in the public interest. 51 Fed. Reg. at 7632 (“... EPA will consider a 

variety of factors pertaining to the need for the chemical, its comparative benefits, risks, 

and costs.”) Although this narrow circumstance is one that extends beyond the public 

interest finding typically offered in past conditional registration actions because here, for 

example, there is no comparative risk analysis that reviews each of the alternative silverbased pesticides, it is nonetheless consistent with the purposes of FIFRA. This is because, 

in this case, the already-registered silver-based pesticides with similar textile and plastic 

use patterns allow greater amounts of silver to be used, thus allowing greater amounts of 

silver to be released to the environment. Taking this information into consideration and 

based on the available data reviewed in the context of this registration request, there is a 

strong basis to believe that releases through use of this product will result in a lesser risk to 

the environment than might result from similar silver-based registrations. Because of the 

very low release rates, the nanosilver in NSPW-L30SS would need to be orders of 

magnitude more toxic than the comparable silver pesticide products on the market for the 

risks as between NSPW-L30SS and silver-based pesticides to be comparable, and, as noted 

in Response 7.7, that is simply not expected in light of the available data. 
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Comment 8.8: EPA contends that one of the public interest benefits of [NSPW-L30SS] is 

“Conservation of the Environment.” However, EPA’s explanation actually points to a 

greater adverse impact on the environment from [NSPW-L30SS], not lower. 

EPA states that because a smaller mass of silver is used in [NSPW-L30SS] than in other 

products, “the overall potential environmental loading of silver from the lower-volume use 

of [NSPW-L30SS] “should be smaller than from a comparable use of currently registered 

silver-based pesticides.” However, EPA ignores the fact is that there is no silver pesticide 

product on the market right now that is used as a material preservative in plastic for 

products like decking and plastic lumber. The [NSPW-L30SS] will be incorporated into 

wholly new products, not taking the place of other silver-embedded products. Therefore, 

the introduction of [NSPW-L30SS] into commerce – no matter the amount – will 

necessarily increase, not reduce, the amount of silver ions that will be released into the 

environment. 

More problematically, EPA acknowledges that more silver ions will be released because 

the nanosilver particles are smaller and therefore have higher surface area per unit mass of 

silver. Since nanosilver is much more potent (effective) than conventional sized silver, less 

nanosilver kills more microbes. While [NSPW-L30SS] may possibly lead to a reduction in 

the overall mass of silver released into the environment, its killing potential is greater and 

therefore the potential for environmental damage and non-target impacts is greater. In fact, 

the SAP noted that the rate and concentration of deadly silver ions released from 

nanosilver is different and will likely affect the acute or chronic toxicity of nanosilver 

compared with silver. The data referenced by SAP show that nanosilver, but not silver, can 

penetrate cell membranes and deliver toxic ions directly inside of cells and that this may be 

its mechanism for killing microbes so effectively. The SAP also noted that “when 

compared as a function the Ag+ concentration, toxicity of silver nanoparticles appeared to 

be much higher than that of silver nitrate.” Moreover, the SAP noted that because of these 

differences in chemical properties, there are likely to be differences in exposure and 

environmental fate of nanosilver that should be considered. 

Silver is highly toxic to aquatic organisms. Increasing the amount of silver ions that will 

enter rivers and streams through our wastewater system or from run-off during rainstorms 

will only harm the environment. It does not conserve the environment. 

Response 8.8: Please refer to Response 6.1, 6.2, 7.7, 7.10, 7.14, 7.15, 7.27, and 7.28. 

Regarding the concern expressed for higher release rates of ionic silver, the commenter is 

incorrect in their interpretation of the proposed decision document. The Agency did not 

state that nanosilver particles result in a greater release of silver ions because the particles 

are smaller than conventional silver salt active ingredients. Rather, the discussion in the 

decision document referenced by commenters compares the release rate between different 

sizes of particles composed of the same active ingredient. 

Comment 8.9: EPA contends that benefits inured to consumers by [NSPW-L30SS] 

contribute to the public interest enough to warrant a conditional registration of a product 

missing critical toxicity data. Part of this argument is grounded in EPA’s assumption that 

[NSPW-L30SS] products “are reported to retain the ability to reduce the number of odor 

and stain causing bacteria.” EPA also assumes that [NSPW-L30SS] “should be able to 

maintain its ability to reduce” bacteria longer than other silver active ingredients. EPA 
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assumes that products using nanosilver “may have longer-term ability” to reduce the 

bacteria compared to conventional silver embedded products. 

EPA’s contention that nanosilver provides a consumer benefit is grounded in assuming 

nanosilver’s efficacy. EPA provides no evidence and does not indicate that any data 

regarding [NSPW-L30SS]’s efficacy exist. Without such evidence, EPA’s claim that 

consumers benefit from the presence of [NSPW-L30SS] on the market is mere conjecture 

and is an inappropriate basis for making a regulatory determination. 

Response 8.9: Please see Response 2.4 relating to efficacy data, and Response 3.1 relating 

to presumed efficacy and other aspects of the Agency’s public interest finding. EPA 

disagrees that efficacy data is necessary to make a determination that consumers benefit 

from the presence of a product on the market. 

Comment 8.10: EPA wishes to encourage innovation in nanotechnology, but allowing 

untested pesticides into products to be used in ways that are potentially harmful is not the 

appropriate way to do so. EPA’s mission is to ensure that products that are brought to 

market will be used in ways that will not harm the environment or public health. But in this 

case, EPA is turning a blind eye to all the possible environmental and health hazards 

associated with [NSPW-L30SS] in an effort to encourage broadly the field of 

nanotechnology. EPA has many other opportunities to actually encourage innovation 

through supporting research and through its existing programs to ease market access for 

pesticide products that are adequately tested and shown to be reduced risk. EPA has even 

established criteria for determining that pesticides are reduced risk, which include 

compatibility with Integrated Pest Management (IPM) strategies. Ironically, the pivotal 

principle of IPM is to avoid using pesticides if they are not necessary – an approach 

undermined by this prophylactic integration of nanosilver into consumer products. By EPA 

allowing an untested product like [NSPW-L30SS] on the market where consumers learn 

after-the-fact that it might cause unreasonable health or environmental effects will only 

stifle real innovation, undermine desirable IPM strategies, pose unknown environmental 

risks, and undermine consumer confidence. 

Response 8.10: Please refer to Response 3.1, 6.1, 7.4, 7.7, 7.14, 7.15, 7.21, 7.27, and 7.28.

Comment 8.11: To conditionally register a new active ingredient, EPA must determine 

that that use of the pesticide during the period of the conditions will not cause any 

unreasonable adverse effect on the environment. 7 U.S.C. §136a(7)(C). In the case of 

nanosilver (and specifically [NSPW-L30SS]), the flaws in the studies relied on by EPA 

and the critical data gaps especially on reproductive toxicity, carcinogenicity, and 

endocrine disruption (among many others) mean that, scientifically, EPA cannot make that 

determination. 

Response 8.11: Please refer to Response 6.1, 7.4, 7.7, 7.14, 7.15, 7.27, and 7.28.

Comment 8.12: EPA failed to provide an adequate characterization of the chemistry of 

[NSPW-L30SS], making it impossible for the public, and likely even for EPA staff, to 

“guesstimate” whether or not it would behave like other (equally poorly) described 

nanosilver materials. EPA describes [NSPW-L30SS] as “a liquid suspension containing 

silica-sulfur-nanosilver particulates where the nanosilver active ingredient is attached to 

crystalline silica via a thiolate bond.” 
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First, the description of the silica as crystalline is likely in error; it is likely that the form of 

silica is synthetic amorphous silica. If EPA did not make an error, and the silica is actually 

crystalline, then given crystalline silica’s known cancer effects, EPA’s determination of no 

cancer risk is in error. If EPA did make an error in describing the material, then it raises 

red flags about whether or not EPA staff that reviewed [NSPW-L30SS] included material 

chemists, who would have the necessary expertise to characterize the material. 

Response 8.12: Please see Response 7.1. 

Comment 8.13: Furthermore, [NSPW-L30SS] appears to be a single silica particle 

surrounded by multiple nanoscale PVP-coated-silver particles connected through weak 

thiol linkages. The thiol linkages have not been defined in the sense of “linkage to what?” 

Is it to the PVP coating or to the silver atoms or to a silver ion that is separate from the 

surface? In a product, these may be in some sort of equilibrium relationship, but in a 

realistic environmental exposure scenario, one is likely to dominate. This would mean that 

the chemistry – and therefore the toxicology – depends on the route of exposure. 

Response 8.13: Please refer to Response 7.2.

Comment 8.14: Moreover, Lee et al. (2006) (referenced by EPA) describes [NSPWL30SS] as a material with 4% PVP, only 0.1% silica, and even less thiol. This means that 

there is a much greater chance of nanosilver reacting with PVP than silica particles. It is 

arguably much more likely that the PVP outnumbers the number of thiol groups on the 

silica surface. EPA’s description of a nanosilver active ingredient coated with PVP and 

sulfur is wholly unsupported, unlikely, unscientific, and inadequate to predict the behavior 

of the material under real-world conditions relevant to a hazard assessment. 

Response 8.14: Please refer to Response 7.2.

Comment 8.15: There is no scientific evidence to support statement that “the resulting 

liquid suspension contains 1% nanosilver by weight where the nanosilver surface is coated 

with sulfur and PVP, and is attached to silica.” First, for that to be true, the sulfur 

connected to a thiol connected to a silica particle would need to surround the silver 

particles (instead of silver particles surrounding the silicon dioxide particle). Second, that 

would mean the sulfur has disengaged from the thiol, meaning disengaged from the silicon 

dioxide. It is unknown if the above complex would survive the temperature and chemical 

conditions of a master batch. If disengaged (broken at the point of contact with the silicon 

dioxide or chemically attacked and “corroded” through at a neck point) then the silver and 

silicon dioxide may migrate to separate locations within the fiber. 

Response 8.15: Please refer to Response 7.2. Additionally, Nanosilva product has been 

characterized by the registrants through the use of techniques like TEM as: “sulfur is 

bonded to the nanosilica particles. Nanosilver cluster (consisting of ten atoms of nAg) is 

covalently bonded to sulfur.” Thus sulfur acts as a tie for nanosilver particles. Nanosilver 

particles are then capped with PVC. The release of nanosilver to the surface is restricted. 

Thiol (SH) was used to generate a silica/sulfur/nanosilver bond. 

Comment 8.16: In short, the [NSPW-L30SS] is not characterized well enough to 

determine with confidence that data on other nanosilver materials can be used to predict 

the toxicology of [NSPW-L30SS]. Scientific support for extrapolating from one nanosilver 

to another is lacking. EPA should use science, not speculation, to evaluate pesticide 

hazards. 
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Response 8.16: Please refer to Response 6.1, 7.4, 7.7, 7.14, 7.15, 7.27, and 7.28.

Comment 8.17: It is unreasonable to rely on data on nanosilver particles that are not 

[NSPW-L30SS]. 

In August 2009, EPA turned to its SAP regarding some open questions about the hazard of 

and exposure to nanosilver. The SAP “cautioned about extrapolating from one nanosilver 

formulation to another when assessing hazards because differences in particle formulation 

(e.g., coating and inert ingredients) are likely to affect biological activity, among other 

things.” Despite the warnings from the SAP, EPA appears to rely on studies of different 

nanosilver formulations to make the determination that [NSPW-L30SS] could be used 

without any adverse effects on the environment or on human health. 

The SAP also noted that “not enough literature is available to draw any firm conclusions 

regarding human (occupational or consumer) and environmental exposures to nanosilver 

under realistic use scenarios.” 

Response 8.17: Please refer to Responses 6.1, 6.2, 7.4, 7.7, 7.14, 7.15, 7.27, and 7.28. 

Comment 8.18: EPA identifies five studies in the scientific literature that investigate the 

oral toxicity of nanosilver in rodents. Three of the most robust studies are not complete 

enough to determine regulatory limits. The other two are even less well described, and 

therefore less useful for supporting regulatory decisions. As such, EPA does not have a 

reliable study that addresses the oral toxicity of [NSPW-L30SS]. 

In December 2011, EPA conditionally registered HeiQ AGS-20 containing nanosilver as a 

materials preservative in textiles. As part of its final decision to register the product, EPA 

relied on Park et al. (2010) for the point of departure (“POD”) of 0.5 mg/kg-day to 

calculate the oral and dermal POD for the nanosilver in HeiQ AGS-20. 

In this proposed conditional registration of [NSPW-L30SS], EPA has determined that Park 

et al. (2010) is no longer reliable for calculating a POD. EPA states that in its recent review 

of the study for this assessment of [NSPW-L30SS], EPA reversed its reliance on the study, 

and now finds that it lacks enough analysis of the cellular changes to draw conclusions 

with confidence. EPA says, “In the absence of histopathological findings, the clinical 

chemistry changes observed [in Park et al. 2010] are insufficient evidence of an adverse 

effect.” 

Response 8.18: EPA disagrees with the comment that there is no reliable study to address 

oral toxicity of [NSPW-L30SS]. The Agency has determined that the combined 

toxicological database of the Kim 2008 and Kim 2010 studies (both of which are rated by 

the Agency as Acceptable/Non-guideline) are sufficient for fulfilling the requirement for a 

90 day subchronic oral study. As explained in the decision document, these studies 

“identified histopathological patterns in the liver that were indicative of distinct adverse 

effects.” A 3X uncertainty factor was added to the Kim 2010 study to account for the 

LOAEL to NOAEL conversion, as is typically done in the absence of a NOAEL in a study. 

Since the Kim 2008 and Kim 2010 were conducted by OECD guidelines, they present a 

more robust understanding of the toxicity of nanosilver. With respect to Park et al. (2010), 

it was previously used to assess the nanosilver in another product, HeiQ AGS-20. 

However, it has since been determined by the Agency that the Kim et al studies were a 

more robust series of studies, including histopathology of a larger number of organs in 

addition to a longer dosing regimen, and thus are more appropriate for a baseline 
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assessment of nanosilver generally. Finally, the Hadrup (2012) study did not determine a 

LOAEL and thus was not acceptable for deriving a quantitative POD, though information 

is used in a WOE approach toward risk assessment. 

Comment 8.19: EPA calculated a POD from Park et al. (2010) of 0.5 mg/kg/day for oral 

and dermal toxicity, based on effects observed in mice that ingested nanosilver for 28 days. 

After discarding that study for this current assessment of [NSPW-L30SS], EPA calculated 

a POD of 30 mg/kg/day, based on the 28-day oral toxicity study by Kim et al. (2008). This 

result weakened oral and dermal exposure limits by 60-fold. 

The scientific community has identified Kim et al. (2008) as not useful for derivation of a 

POD. The study provides no information on the form or shape of the silver nanoparticles in 

the solution that was used to dose the animals. Further, the study misstated that it was 

performed in accordance with OECD 407 study guidelines. In fact, no neurotoxicity 

endpoints were investigated, and the histopathology (observation of cellular damage) failed 

examine the spinal cord, peripheral nerve, bone marrow, lymph nodes, stomach or small or 

large intestines. 

EPA moved away from the more protective POD from Park et al. (2010) claiming that the 

histopathology analysis was too weak, and unjustifiably proposes to rely on this lessprotective study by Kim et al. (2008) that lacks any histopathology analysis on so many 

critical organs and tissues. 

Importantly, Kim et al. (2008) reported a dose-dependent accumulation of silver content in 

a broad range of tissues including blood, liver, lungs, kidneys, stomach, testes and brain. 

Cellular damage in the liver of male and female rats included dose-dependent bile-duct 

hyperplasia, dilation of the central veins, and inflammation. However, the authors failed to 

specify which dose groups had these effects. Silver concentrations were dose-dependent in 

blood and all examined tissues, with the kidney concentrations in females being 2-fold 

higher than males. 

That ingested nanosilver is accumulating in many critical organs, where its antimicrobial 

activity may lead to significant cellular damage that has not been adequately studied, is 

evidence that EPA cannot determine that there are no unreasonable adverse effects 

associated with the use of [NSPW-L30SS]. 

Response 8.19: With respect to comments on the reevaluation of the Park study and the 

use of the Kim studies (both 2008 and 2010) in determining the POD for NSPW-L30SS, 

see Response 8.18. With respect to accumulation of nanosilver in critical organs, the 

presence of silver in the varied organs is not considered adverse in the absence of 

histopathology indicating an effect. Thus in the absence of histopathology indicating an 

effect, the presence of silver was not used to identify a NOAEL or LOAEL. As explained 

throughout the decision document and this response-to-comments document, the PODs 

chosen are protective at the levels at which effects are observed in the studies available. In 

any case, given the low release rate, the calculated MOEs are protective, 310,000 for the 

subchronic oral route for the most sensitive population (with an aggregate MOE for 

incidental oral of 110,000 for the most sensitive population) and take into account the 

differences between the chemical composition of the studied chemical and NSPW-L30SS 

and database gaps through use of an additional 10X uncertainty factor. Finally, although 

Kim et al. (2008) did not investigate neurotoxicity endpoints, EPA believes there is 
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adequate data on neurotoxicity to find that use of [NSPW-L30SS] will not cause 

unreasonable adverse effects on human health, pending generation of the required 90-day 

inhalation study. As noted in the proposed decision document, the “currently available oral 

toxicity studies indicate that nanosilver causes liver and kidney toxicity in laboratory 

animals where silver is distributed to all organs and tissues with accumulation of silver in 

the brain and male animal testes. ... There were potential neurotoxic effects identified with 

increases in neurotransmitter concentrations and loss of spatial cognition; however, these 

same effects were not observed in a follow-on study. As explained in the Proposed 

Decision Document, EPA believes that these neurotoxicity studies are inadequate in their 

assessment of behavioral effects and do not use optimal methods to evaluate the potential 

toxicity to the nervous tissue structure and function.” EPA also stated that it believes “the 

short-term oral NOAEL and intermediate-term LOAEL of 30 mg/kg/day are expected to be 

protective of neurotoxic effects” of [NSPW-L30SS] based on the “study by Liu et al. 

(2013) [which] reported no effects on the spatial cognition or hippocampal activity of mice 

after injecting nanosilver into the body cavity (i.e., intraperitoneal injection) at 

concentrations of up to 50 mg/kg.” “The effects on spatial cognition and hippocampal 

activity observed by Liu et al. (2012) after administering nasal drops containing nanosilver 

at concentrations of 3 and 30 mg/kg to rats suggest possible neurotoxic effects from the 

inhalation of nanosilver. However, EPA believes that the doses used in the Liu et al. 

(2012) study were greater than the maximum dose used in the inhalation toxicity study by 

Song et al. (2012). Therefore, EPA believes that the inhalation NOAEL of 49 μg/m3 based 

on the Song et al. (2012) study is expected to be protective of neurotoxic effects of 

nanosilver. (Proposed Decision Document at 24). Commenters do not address EPA’s 

analysis on this issue. Further, the subchronic inhalation study will include a functional 

observation battery, motor activity and detailed neuropathology, as it is the route of 

greatest exposure and should confirm that the existing analysis is protective of neurotoxic 

effects. 

Comment 8.20: EPA identified Hadrup et al. (2012) as another study that investigates the 

oral toxicity of nanosilver in rats. 

First, EPA itself determined that the study lacked histological support for determining a 

POD. Second, the nanoparticles studied by Hadrup et al. are silver nanoparticles stabilized 

with polyvinylpyrrolidone (PVP), whereas the particles in [NSPW-L30SS] are very 

different, formed of a composite of silica-sulfur-nanosilver particles. The PVP-coated 

nanosilver particles are likely to disengage and transport separately from the silica. This is 

also significantly different from the HeiQ product that EPA recently conditionally 

approved, which probably transports in the environment more like a silica particle carrying 

along the silver. In short, the scientific support for extrapolating from one nanosilver 

composite type to another is lacking. EPA should use science, not speculation, to evaluate 

pesticide hazards. 

Response 8.20: While the Hadrup study is not being used to determine a POD due to the 

inability to establish a NOAEL/LOAEL, the toxicity data are being included in the 

proposed decision document because the results, while not sufficient to come to a risk 

conclusion on their own, contribute to the knowledge base on nanosilvers by increasing the 

understanding of distribution of nanosilver and the changes in hematology and clinical 

chemistry. This knowledge base forms the weight of evidence in the Agency’s approval 

process for this chemical. 
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Comment 8.21: Critical data gaps for nanosilver prevent a finding of no unreasonable 

adverse effects 

EPA acknowledges that it is missing data on entire categories of hazards. These missing 

studies are essential to a complete assessment of the potential adverse effects associated 

with the proposed uses of [NSPW-L30SS]. Therefore, because EPA lacked essential data, 

its determination that [NSPW-L30SS] will not have unreasonable adverse effects on the 

environment is unreasonable, unsupported, and arbitrary and capricious. 

Response 8.21: Please refer to Response 6.1, 6.2, 7.4, 7.7, 7.14, 7.15, 7.27, and 7.28.

Comment 8.22: EPA has no acceptable studies on reproductive and developmental 

toxicity 

Reproductive and developmental toxicity are essential components of a full human health 

risk assessment, and without information about that hazard, EPA cannot determine whether 

a pesticide will have unreasonable adverse impacts on human health. (“Disorders of 

reproduction and hazards to reproductive health have become prominent public health 

issues.” Developmental toxicity is manifested as “death, structural abnormality, altered 

growth, and functional deficit,” all critical to a complete human health risk assessment.) 

Information about the hazard characterization is a crucial component to a complete risk 

assessment. “A statement of the potential for human risk and the consequences of exposure 

can come only from integrating the hazard characterization and quantitative dose-response 

analysis with human exposure estimates in the risk characterization.” 

In proposing to conditionally register [NSPW-L30SS], EPA states that it has enough 

information to determine that [NSPW-L30SS] will not have any unreasonable adverse 

impacts on human health. However, EPA highlights the critical data gaps on reproductive 

and development toxicity in its assessment of nanosilver. Specifically, EPA states, 

 There are studies showing significant, dose-dependent increases in the 

concentration of silver in the testes of rats after oral ingestion, inhalation, and 

injection of nanosilver...; however there are few studies available on the 

reproductive and development toxicity of nanosilver. 

To counter this data gap, EPA is requiring Nanosilva [LLC] to submit the results of a 

Modified Reproduction/ Development Toxicity Screening Test 37 months after the 

conditional registration is issued. EPA’s rationale is that this test “will provide initial 

information on possible effects on reproduction and/or development.” To make a first 

determination whether [NSPW-L30SS] has any unreasonable adverse impacts on human 

health, EPA needs to be able to assess whether there are any reproductive or 

developmental toxicity concerns. Reproduction and development are essential components 

of human health, and therefore, without even basic “initial” information about reproductive 

and developmental toxicity, EPA cannot complete its safety determination of [NSPWL30SS]. 

Response 8.22: EPA agrees that the reference to needing “initial information” is not 

accurate and the Final Decision Document has been edited to be more precise on this issue. 

Further the Agency disagrees that there is no information on the 

developmental/reproductive toxicity of nanosilvers sufficient to find that use of NSPW-
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L30SS will not cause unreasonable adverse effects pending generation of the required data. 

Please see Response 7.28. 

Comment 8.23: For the mutagenicity of nanosilver, EPA states that “there are no studies

in the scientific literature that investigate the potential of nanosilver to cause cancer....” 

After reviewing the in vitro studies that exist, EPA concludes that “there is inadequate 

information to assess mutagenic (and hence carcinogenic) potential of nanosilver due to 

differences in results between the in vitro studies and in vivo studies, and the limitations of 

the only available in vivo study.” Without a full suite of mutagenicity tests on the material 

of interest, [NSPW-L30SS], EPA cannot determine with scientific confidence whether or 

not [NSPW-L30SS] may be mutagenic to DNA, and therefore pose a risk of cancer, 

intergenerational effects, disease, birth defects, or other severe adverse health endpoints 

related to mutagenicity. 

Response 8.23: Please see Response 7.10 for information on mutagenicity. 

Comment 8.24: According to EPA, Nanosilva [LLC] “has not conducted any studies to 

characterize the environmental fate of [NSPW-L30SS] or the other particles that could be 

released during leaching or disposal of plastics and textiles incorporating [NSPW-L30SS]” 

and “has not conducted any studies to characterize the ecotoxicity of [NSPW-L30SS] or 

other particles that could be released during leaching or disposal of plastics incorporating 

[NSPW-L30SS]” These are critical components of an environmental assessment to 

determine where the [NSPW-L30SS] goes into the environment and what harm it causes 

when it is there. As a result, EPA is left to rely on studies of conventional silver and 

nanosilver particles that are different from [NSPW-L30SS]. 

Furthermore, EPA acknowledges that silver “may become toxic to aquatic life at elevated 

concentrations.” However, after mentioning the concentrations of silver in surface waters, 

EPA concludes that it does not expect any unreasonable adverse effects to the 

environment, citing a twenty year old assessment of conventional silver from 1993. That 

old assessment never contemplated the presence of nanoscale silver particles – 

nanotechnology had barely begun as a scientific endeavor at that point. Therefore, EPA’s 

reliance on the old assessment is wholly improper, and EPA has failed to provide any 

explanation for its determination at the nanoscale. 

Nanosilva [LLC] did not submit any tests with aquatic organisms, and EPA is left to assess 

the scientific literature addressing aquatic organisms and other nanosilver particles – 

despite the SAP’s admonition that the differences in particle sizes cannot be 

underestimated. After identifying six studies in the scientific literature on aquatic animals, 

EPA concludes that the data “do not characterize the effects from longer-term exposure to 

nanosilver.” One study (Wu and Zhou, 2013) looked at long term effects, and while it did 

not show lethal effects, the authors reported non-lethal effects at all nanosilver 

concentrations tested. Non-lethal effects can also reflect an unreasonable impact on the 

environment and cannot be summarily dismissed. EPA fails to address this finding in 

discussing the environmental toxicity of [NSPW-L30SS]. 

Response 8.24: Please refer to Responses 7.4, 7.7, 7.14 and 7.15.

Comment 8.25: The GreenscreenTM for Safer Chemicals (GS) is a comparative chemical 

hazard assessment framework. It builds on the EPA Design for the Environment (DfE) 

approach, along with the OECD Globally Harmonized System (GHS) and other accepted 
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systems. It is being used by industry, government and non-governmental organizations 

(“NGOs”) to support product design and development, materials procurement, and as part 

of alternatives assessment to meet regulatory requirements. 

A GS assessment of a chemical looks at eighteen hazard endpoints (including chronic and 

acute toxicity, ecotoxicity, and physical characteristics such as flammability and 

reactivity), scores each endpoint according to the available data or lack thereof (i.e. a data 

gap), and assigns a Benchmark score (BM) from 1 to 4, with 1 being the most hazardous. 

Where there are no data for an endpoint, GS can use analogues, modeled data, or other 

available reasonable substitutes to inform that endpoint. Confidence in the score is 

identified as high (bold), low (italics), or very poor (“DG” for data gap). Chemicals that are 

carcinogens, mutagens, reproductive and/or developmental toxicants, endocrine disruptors, 

and PBTs (persistent, bioaccumulative, and toxic) are considered substances of high 

concern and receive a BM of 1. 

Nanosilver, silver, and the silver-silica composite AGS-20 were put through the GS and 

those assessments compared. The three GS assessments were all conducted by independent 

scientists at NSF International, which is an approved GS profiler. They found an extensive 

lack of data on critical endpoints for nanosilver, and by extension for [NSPW-L30SS]. 

The specific materials evaluated for the silver case study were nanoscale metallic silver, a 

silicasilver nanocomposite, and conventional low-solubility dispersed silver and silver 

salts. Both silver and nanoscale silver scored a benchmark of 1(high concern), based on 

high aquatic toxicity, high persistence, and acute inhalation toxicity. The identified data 

gaps for nanoscale silver include reactivity, flammability, carcinogenicity, reproductive 

toxicity, and endocrine disruption. 

The HeiQ AGS-20 silica-nanosilver composite received a BM of U (unspecified) due to 

the large number of data gaps. Unfortunately, EPA approved the AGS-20 for textiles in 

2011, on the assumption that hazard data on silver nitrate and other soluble salts could be 

used as analogues to fill data gaps. It was not scientifically justifiable for EPA to substitute 

data on other nanosilver particles in its AGS-20 assessment. The SAP noted that “when 

compared as a function of Ag+ [ion] concentration, toxicity of silver nanoparticles 

appeared to be much higher than that of silver nitrate.” Because of these differences in 

chemical properties, there are likely to be differences in exposure and environmental fate. 

For this reason, the GS assessment did not use silver nitrate or other soluble silver salts as 

analogs to fill data gaps, because the screen sought to examine particle size-specific 

hazards. 

The results of these three GS assessments demonstrates that there are numerous critical 

areas of information that EPA lacks knowledge about regarding the potential health and 

safety impacts of [NSPW-L30SS] for people and the environment. 

Altogether, these critical health endpoints and environmental impacts are essential to 

making a determination about registering this pesticide. Until EPA has data specific to 

[NSPW-L30SS] on reproductive and developmental toxicity, carcinogenicity, endocrine 

disruption, and environmental toxicity, EPA cannot allow this product to enter the market. 

In the absence of these data, EPA cannot show that there are no unreasonable adverse 

impacts to the environment and human health associated with the use of [NSPW-L30SS], 

and as such, cannot register this pesticide product. 
55 of 57

Response 8.25: Please refer to Responses 6.1, 6.2, 7.4, 7.7, 7.14, 7.15, 7.27 and 7.28. 

While GS is a hazard screening analysis, the EPA performed a more robust analysis, 

considering more information, when conducting the risk assessment for the nanosilver in 

AGS-20. EPA approved AGS-20 for textiles based on bridging data from open literature 

studies on nanosilver materials, not only on assumptions of hazard data from silver nitrate 

and other silver salts. 

For NSPW-L30SS, as EPA explained in the proposed and final decision documents, the 

available data show release of nanosilver below the level of detection. Taking into 

consideration these low releases, the available toxicity data, use of multiple risk 

uncertainty factors (UFs) and required risk mitigation measures on the product label, the 

calculated margins of exposure (MOEs) and risk quotients (RQs) were well above the 

Agency levels of concern (LOCs). On these grounds, EPA determined that there is 

substantial evidence in the record to conclude that the proposed use of NSPW-L30SS 

during the conditional registration period will not cause unreasonable adverse effects on 

human health or the environment. 

Comment 8.26: In the aquatic risk portion of the risk assessment, EPA states that it “only 

considers silver that could be released by [NSPW-L30SS] and does not include other 

sources of silver which will contribute to the environmental loading of silver.” Given that 

part of EPA’s rationale for conditionally registering this product is the purported benefit to 

the environment from the release of silver ions, EPA should consider the cumulative and 

aggregate impact of all the various sources of silver ions loading to the environment. 

Response 8.26: Please refer to Response 6.4.

Comment 8.27: EPA relies on Song et al. (2012) for the short- and intermediate-term 

inhalation No Observable Adverse Effect Level (“NOAEL”). The study by Song et al. 

(2013) exposed six week old male and female Sprague Dawley rats with either no dose 

(control group) or one of three dose groups (49, 117, and 381 μg/m3

; each group consisted 

of 17 male rats and 12 female rats) with silver nanoparticles 14-15 nm in diameter in an 

inhalation chamber for 6 hours per day over 12 weeks. 

The authors report a statistically significant decrease in various measurements of lung 

function in the male rats – but not females – in the middle and high dose groups throughout 

both the exposure period and the recovery period. Moreover, the authors report that the 

female rats gradually recovered from lung inflammation, whereas the males in the high 

dose group showed persistent inflammation throughout the 12 week recovery period. Sex 

differences were also observed for the distribution of silver across organs, with five times 

more silver accumulated in the kidneys of females compared with males in the same 

treatment group. There was a statistically significant dose-dependent increase in lung tissue 

silver concentration in both males and females after the exposure period, which was not 

completely cleared by the end of the 12 week study. The authors also reported that signs of 

inflammation were present in the middle-dose group after 12 weeks of exposure. 

Statistically significant accumulation of silver compared to the control group was reported 

in the liver and spleen in male rats after 12 weeks of recovery, and the kidneys in female 

rats contained five times more accumulated silver than the male kidneys. 

Maybe most important, the male rats in the high-dose group showed persistent 

inflammation throughout the 12 week study period. Because the males did not completely 
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recover during the study period, and because gender differences remain unexplained by 

either the authors or EPA, this study seems to raise more questions than it answers, and 

lacks confidence in the ability to rely on it to determine a POD. 

Importantly, the nanoparticles studied by Song et al. are uncoated silver nanoparticles, 

whereas the particles in [NSPW-L30SS] are very different, formed of a composite of 

silica-sulfur-nanosilver particles. It is not clear how the rate of ion release may differ 

between these two markedly different materials. The scientific support for extrapolating 

from a nanosilver composite to an uncoated nanosilver particle is lacking. EPA should use 

science, not speculation, to evaluate pesticide hazards. 

NRDC does not support using Song et al. to determine a POD. However, if EPA is going 

to rely on Song et al. to determine a POD, an uncertainty factor must be applied to adjust 

for the lack of a NOAEL. An uncertainty factor of at least 10X should be incorporated 

because EPA has neither pharmacokinetic nor pharmacodynamic information to warrant 

lowering the default 10x factor in adjusting for the lack of a NOAEL. 

Response 8.27: The Agency notes that the Song et al. study did establish a NOAEL at the 

low dose. The effects were only observed at the mid and high doses. Therefore a LOAEL 

to NOAEL factor of 10x is not warranted and 49 μg/m3

 is an appropriate point of departure 

for short- and intermediate-term inhalation risk assessment. The target MOE is 1,000 based 

on 10x intraspecies, 10x interspecies, and 10x database uncertainty factors. For 

information on uncertainty factors and inhalation MOEs, please refer to Responses 6.1 and 

6.2. For more information regarding release rates, please refer to Responses 2.3 and 2.5. 

For additional information with respect to concerns of utilizing data from more than one 

form of nanosilver, please refer to Responses 6.1, 6.2, 7.4, 7.7, 7.14, 7.15, 7.27, and 7.28. 

Comment 8.28: Over the years, EPA has abused the conditional registration provision in 

FIFRA and allowed pesticides to market that are inadequately tested and have wreaked 

havoc on the environment. Imprelis reportedly caused billions of dollars of damage in dead 

trees. Clothianidin is part the family of neonicotinoid pesticides that are partly implicated 

in the massive bee death crisis. Examples of other pesticides allowed to enter the market 

based on flawed or insufficient data continue to emerge. 

Separate reports by NRDC and the GAO exposed the flaws in the EPA conditional 

registration to the public’s scrutiny for the first time. Pesticides littering the market have 

been fast-tracked through the conditional registration process and EPA has not developed a 

method for properly tracking them. Despite the outcry against this misuse of conditional 

registrations, EPA once again turns to this fast track system to let another pesticide to 

market where many consumers will become unknowing guinea pigs for the benefit of one 

company whose only duty is to its financial bottomline. 

Because EPA does not have an established program in place at this time, granting this 

conditional registration means that [NSPW-L30SS] could become the next poster child for 

a conditional registration system gone seriously wrong. The only unknown at that point 

will be the extent of the damage that ensues. If EPA continues down this path, the public 

confidence in the safety of pesticide products will erode further. EPA must fix its program 

before it can go forward with this – or any other – conditional registration. For this, and the 

other reasons stated above, NRDC strongly opposes the conditional registration of 

[NSPW-L30SS]. 
57 of 57

Response 8.28: Please refer to Responses 6.1, 6.2, 7.7, 7.14, 7.15, 7.23, 7.27, and 7.28.

Commenter 9: Jeannie Economos, Farmworker Association of Florida (EPA-HQ-OPP-2012-

0594-0018, Received 9/26/2013) 

Comment 9.1: The Farmworker Association of Florida is opposed to the conditional 

registration of [NSPW-L30SS]. Our concern is both for the environmental and human 

health potential impacts of a product whose long term fate and short term implications are 

not yet fully understood nor tested. Farmworkers are one of the most vulnerable members 

of the population in the United States. In the course of their daily work, they are exposed to 

a multitude of various pesticides and fertilizer chemical compounds. In addition, a recent 

study indicated that families in low-income, agricultural areas were prone to higher levels 

of body burden of flame retardents (sic). This does not include their exposure to other 

household, occupational and environmental chemicals. Farmworkers are the least likely to 

be educated about the risks of chemicals in the products that they use and are more likely 

to purchase the least expensive, and possibly more risky, consumer items. This puts them 

at increased risk for additive, cumulative and synergistic impacts of chemical exposures. 

While we are not scientists, we are a community based organization which daily sees the 

human health impacts - both acute and chronic – of occupational exposure to pesticides on 

a community of people who are struggling to survive and raise healthy children and to 

provide them with an education. We, also, represent a community of people who were 

exposed generationally to organochlorine pesticides at a time when they were deemed to 

be safe. We now know otherwise, and, yet, an entire group of people are suffering chronic 

health problems likely related to such exposures. We do not need any more inadequately 

understood or tested chemicals to add to the current impacts on our society. 

We support the comments submitted earlier by the Natural Resources Defense Council and 

call upon the EPA to be true to its mission to protect the environment, and, in so doing, to 

be protective of human health. 

Response 9.1: In regards to comments submitted by NRDC, please see Responses 8.1 – 

8.28. 

Commenter 10: Tracey Brieger and Sarah Aird, Californians for Pesticide Reform (EPA-HQOPP-2012-0594-0013, Received 9/26/2013) 

Comment 10.1: Californians for Pesticide Reform is a statewide coalition with over 185 

member organizations. On behalf of our members, we are writing to support the comment 

letter submitted to this docket by the Natural Resources Defense Council (NRDC). 

Response 10.1: In regards to comments submitted by NRDC, please see Responses 8.1 – 

8.28.