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February 8, 2010

EPA SAP Releases Report on Nanosilver and Other Nanometal Pesticide Products

The ACTA Group

The U.S. Environmental Protection Agency (EPA) Scientific Advisory Panel (SAP) has released the minutes of its November 3-5, 2009, meeting regarding evaluation of the hazard and exposure associated with nanosilver and other nanometal pesticide products.

Before summarizing the SAP’s primary conclusions and recommendations, we note a few general observations. First, the SAP final recommendations address nanosilver almost entirely, and little or no mention is made of “nanometal pesticide products.” Second, the Panel stated that existing models “are not appropriate” for use with silver nanomaterials and “will not accurately predict nanosilver exposure scenarios.” The Panel stated that it “strongly believe[s] that in addition to current data requirements under [the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)], additional assays which compared nanoscale and bulk materials would be most beneficial in addressing” differences in toxicokinetics and toxicodynamics for nanoscale materials. This conclusion alone poses formidable challenges for nanosilver pesticide applicants wishing to obtain registration status under FIFRA. Third, the Panel agreed that pesticide products should be tested on a “case-by-case basis,” EPA should use a meta-analysis on the products to understand better trends in life cycle analyses, and “close attention” should be given to products that claim a non-ionic mode of action as an antimicrobial agent. Fourth, the Panel outlined detailed research needs that EPA should consider. The outline will discourage even the most optimistic potential FIFRA registrant for a nanopesticide as the research needs are extensive and likely costly. The Panel also identified the “most useful short-term information needs,” of which stakeholders should be aware. Finally, the Panel stated that a “critical issue” that “must be clarified is the use of [the] terminology ‘nano'” and that for standardization, “the unique property for nanosilver should be established.”

As some may be aware, and as discussed in our prior communications on the matter, EPA is reportedly poised to announce soon that it is adopting a policy that would require any pesticide registrant that is aware that some constituent of a registered pesticide product is nanosized (i.e., presumably that has particles or structures with a diameter less than 100 nanometers) to submit the information to EPA pursuant to FIFRA Section 6(a)(2). EPA is expected to announce this new interpretation of Section 6(a)(2) reporting requirements in a Federal Register notice, either in the form of a Pesticide Registration (PR) notice or as a formal policy statement or regulatory interpretation. In addition, this notice is expected to confirm EPA’s view that substitution of a nanoscale active or inert ingredient for a conventionally-sized active or inert ingredient in a product currently registered under FIFRA requires that the registrant submit an application to amend that registration. In light of the conclusions and recommendations of the SAP, EPA’s soon to be announced policy under Section 6(a)(2) can be expected to be all the more difficult to oppose.

EPA requested advice and recommendations on the following issues:

  1. Scientific evidence that nanosilver and other nanometals/nanometal oxides with dimensions in the range of 1 – ~100 nm have unique behavior under conditions relevant to human and environmental risk assessment and other properties (in addition to size) that may influence this behavior;
  2. Recommendations regarding the types of data that the Office of Pesticide Programs (OPP) should require to evaluate the risks to humans and the environment for products containing free nanosilver and/or nanometals or nanometal oxides and products with incorporated nanosilver and/or nanometals or nanometal oxides with variable potential to leach and the relative priorities for obtaining recommended types of data; and
  3. Recommendations regarding how OPP should conduct risk assessments of pesticide products containing nanosilver and/or nanometals or nanometal oxides.

SAP’s summary of its discussions and recommendations includes the following:

  • SAP was not aware of any information that suggested that silver ions released from silver nanomaterials would behave differently than silver ions generated by any other source. SAP believed, however, that the rate of silver ion production, as well as the distribution of silver in tissue, may differ substantially between silver nanomaterials and other forms of silver.
  • SAP agreed that particle size has a substantial impact on particle properties, including rate and concentration of silver ion release, reactivity and catalytic efficiency, plasmon resonance, and quantum effects. The effects of silver nanoparticle size on biological responses are less defined, however. SAP suggested that an appropriate set of metrics that incorporated size in conjunction with physicochemical or biological parameters, such as surface area or polydispersity, may be appropriate in bridging exercises, but appropriate physical or multi-criteria decision models should be developed. SAP suggested that available data on existing colloidal silver materials should be investigated.
  • SAP indicated that it was not aware of studies that definitively answered the question whether agglomerated silver nanoparticles in the range of 100 nm to 1,000 nm pose different hazards than larger sized particles. SAP identified the following three factors that may influence the response of agglomerates relative to larger single particles: (1) differences in density and aerodynamic (hydrodynamic) parameters that are likely to influence airway deposition and environmental distribution; (2) agglomerates may have increased activity due to higher accessible surface area; and (3) agglomerates may deagglomerate leading to exposure to dispersed smaller sized nanomaterials.
  • Regarding exposure from “realistic use” scenarios, SAP indicated that there are limited data available. SAP agreed that virtually all uses of nanosilver will result in some release of silver, as ionic, nanoparticulate, or composites. Human exposure is likely to occur by inhalation, oral ingestion, and dermal exposure routes, and will vary with the product used.
  • Environmental fate of silver nanomaterials remains unclear, though SAP again suggested evaluation of existing data on fate of products containing colloidal silver, including those used in photography.
  • SAP stated that most existing models are not appropriate for use with silver nanomaterials and will not accurately predict nanosilver exposure scenarios. New models implementing novel approaches to predict environmental exposures to nanoparticles should be created. SAP discussed two approaches: (1) developing very simplified exposure models using tools of multi-criteria decision analysis to allow classification of different nanomaterials (including nanosilver products with different properties) in different risk groups; and (2) developing complex mechanistic models using the best knowledge on mechanisms governing nanomaterial behavior, including additional metrics for dose and exposure, particle size, surface area, and number and mass concentration, as well as additional parameters such as particle size/distribution, particle shape, agglomeration state and rate of agglomeration/de-agglomeration or stabilization in application environments, surface chemistry of nanoparticles, and rate of dissolution.
  • SAP reiterated some of the existing data that suggest differences in toxicokinetics and toxicodynamics for nanoscale materials. SAP “strongly believed that in addition to current data requirements under FIFRA, additional assays which compared nanoscale and bulk materials would be most beneficial in addressing this question.” According to SAP, it is also necessary to know chemical composition and hazard properties of end-use products, including inert ingredients, to account for possible synergistic effects. Studies should be conducted with relevant forms of materials under relevant exposure conditions as defined by exposure characterization.
  • SAP believed that the lack of existing data suggests that it would be necessary to conduct research on a case-by-case basis to evaluate whether silver nanomaterials remain associated with a substrate. SAP indicated that “current data requirements for antimicrobial pesticide products are a starting point, but the general use patterns and test guidelines require adjusting to accommodate the novel properties and novel uses that will likely evolve through the application of nanotechnology.” SAP discussed the need for studies that provide information about the degradation of substrates containing nanomaterials; metabolism and the transformation of dislodged nanomaterials; and fate information related to leaching, dissipation, and bioaccumulation. SAP recommended that a system of metrics for environmental exposures be developed, including mass, particle number, and surface area concentrations. According to SAP, a life cycle analysis is needed to determine stability of nanosilver products over time.
  • SAP disagreed that nanosilver applied to a substrate will permanently bind with the substrate, and concluded that, given the state of science and measurement standards currently available, “it will be especially challenging to determine that there is no release of nanomaterials from a substrate.” SAP suggested use of tests to simulate realistic use of products and potential nanosilver release with subsequent quantitative life cycle assessment and risk assessment.
  • SAP agreed that additional data are needed before the scientific community can conclude whether particles at the smaller end of the size scale are likely to behave like particles at the larger end of the scale. SAP noted at least two observations that could lend credence to the existence of a relationship between particle size and potential hazard: (1) biological activity and penetration through biological barriers depends on particle size; and (2) particle dynamics, which affect transport and exposure, depend on size. SAP suggested considering concentrations of particular particle sizes falling within specific ranges of sizes within a product when assessing hazard.
  • SAP cautioned about extrapolating from one nanosilver formulation to another when assessing hazards. Moreover, according to SAP, “extrapolations between nanomaterials based on different metals could be of particular concern.”
  • SAP believed that environmental conditions can affect the properties of nanoparticles, including silver. SAP suggested that each nanomaterial should be characterized in the primary phase (pristine dry state), secondary phase (aqueous solution), and tertiary phase (in vitro or in vivo fluid, cells, or tissues) on a case-by-case basis.
  • SAP acknowledged that data gaps about potential exposures and hazards related to nanosilver are broad and there is very little information about nanosilver in the environment related to fate, transport, and transformation. SAP provided a detailed framework to help guide the assessment of nanosilver products in two areas: (1) environmental fate, transport, and transformation needs; and (2) toxicity assessment. In addition, SAP provided recommendations on scientific studies in support of an integrated risk-based decision framework for regulatory decision making.

SAP’s report is available online.