Nanomaterial Case Study Workshop:
Developing a Comprehensive Environmental Assessment
Research Strategy for Nanoscale Silver
January 4-7, 2011
Research Triangle Park, North Carolina
Workshop Report
Prepared for EPA/NCEA
December 2011
Prepared by ICF International under
EPA Contract Number EP-C-09-009,
Work Assignment Number 2-12
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Preface
On January 4-7, 2011, ICF International (ICF) organized and coordinated a workshop on nanoscale silver
(Nanomaterial Case Studies Workshop: Developing a Comprehensive Environmental Assessment
Research Strategy for Nanoscale Silver) for the National Center for Environmental Assessment (NCEA) in
the U.S. Environmental Protection Agency's (EPA) Office of Research and Development (ORD). The
workshop was the second in a series that NCEA is conducting to further the development of a research
strategy for completing comprehensive environmental assessments of nanomaterials. The basis of the
workshop was the report Nanomaterial Case Study: Nanoscale Silver in Disinfectant Spray. Prior to and
separate from the workshop, EPA convened a Public Information Exchange to explain the rationale for
the case study approach, the choice of nanomaterials and applications, and the results from a previous
workshop on nanoscale titanium dioxide. In compliance with requirements of the Federal Advisory
Committee Act (5 U.S.C. Appendix 2; see http://www.gsa.gov/portal/content/100916), ICF conducted
the workshop on nanoscale silver and prepared this summary independently of EPA, with EPA funding.
Although this summary is an independent document, it links to and should be viewed in concert with,
EPA's external review draft of Nanomaterial Case Study: Nanoscale Silver in Disinfectant Spray (U.S.
EPA. 2010b).
The outcomes of this and future workshops in the seriesprioritized information gaps and risk
tradeoffswill be used in developing and refining a long-term research strategy to assess potential
human health and ecological risks of nanomaterials and to manage associated risks of specific
nanomaterials.
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Disclaimer
Mention of commercial or trade names does not constitute endorsement by the U.S. Environmental
Protection Agency (EPA). The views expressed in this report are those of the workshop participants and
do not reflect EPA opinions or policy.
ICF International, EPA's contractor, provided logistics and note-taking at the workshop and prepared this
report. This work was conducted under EPA Contract Number EP-C-09-009, Work Assignment Number
2-12.
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Contents
1. Workshop Objectives and Design 1-1
1.1. Workshop Objectives 1-3
1.2. Selection of Participants 1-3
1.3. Pre-Workshop Review and Rankings 1-5
1.4. Workshop Activities 1-7
1.4.1. Information Exchange and Introduction 1-7
1.4.2. Nominal Group Technique 1-7
1.4.3. Breakout Group Reports 1-9
2. Research Questions Proposed During Nominal Group Technique 2-1
2.1. Round 1 2-1
2.2. Round 2 2-6
2.3. Round 3 2-12
2.4. Additional Rounds 2-17
3. Workshop Outcomes 3-1
3.1. Prioritized Research Questions 3-1
3.2. Breakout Group Reports 3-6
3.2.1. Analytical Methods 3-6
3.2.2. Exposure and Susceptibility 3-13
3.2.3. Physical and Chemical Toxicity 3-19
3.2.4. Kinetics and Dissolution 3-24
3.2.5. Surface Characteristics 3-28
3.2.6. Sources and Releases 3-30
3.2.7. Mechanisms of Nanoscale Silver Toxicity 3-34
3.2.8. Ecotoxicity Test Methods 3-37
3.2.9. Is New Nano Unique? 3-42
3.2.10. Biological Effects 3-48
3.2.11. Ecological Effects Required for Risk Assessment 3-51
3.2.12. Communication, Engagement, and Education 3-55
3.2.13. Fate and Transport of Nano-Ag 3-58
4. Other Workshop Documents 4-1
4.1. Workshop Agenda 4-1
4.2. Workshop Participants and Observers 4-3
4.2.1. Participants 4-3
4.2.2. Observers 4-13
4.3. Pre-Workshop Charge to Workshop Participants 4-14
4.4. Research Questions 4-18
4.5. Pre-Workshop Ranking Results 4-29
4.6. Template and Instructions for Breakout Group Reports 4-45
4.6.1. Group Summary 4-45
4.6.2. Group Presentation Slides 4-46
5. References 5-1
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1. Workshop Objectives and Design
Engineered nanoscale materials (nanomaterials) are conventionally described as having at least one
dimension between 1 and 100 nanometers (nm) and possessing unusual, if not unique, properties that
arise from their small size. Like all technological developments, nanomaterials offer the potential for
both benefits and risks. Given the emerging state of nanotechnology, however, much remains to be
learned about the characteristics and effects of nanomaterials before such assessments can be
completed.
In its 2007 Nanotechnology White Paper
(2007). the U.S. Environmental Protection
Agency (EPA) included the recommendations
shown in the text box at the right regarding
the risk assessment of nanomaterials. The
approach the National Center for
Environmental Assessment (NCEA), in EPA's
Office of Research and Development,
adopted is to draft a case study that details
the information currently available to
complete a comprehensive environmental
assessment (CEA) for a selected
nanomaterial in a specific application. The
CEA approach consists of both a framework
and a process. The CEA framework provides
a structure to develop a comprehensive view
of what is known about the nanomaterial
application beginning with the product life
cycle; progressing to its environmental fate
and transport, exposure-dose in ecological
and human populations, and finally, ending
with its human health, ecological, and other
(aesthetic, climate, energy, sustainability, etc.) impacts. This approach enables identification of gaps in
our knowledge and corresponding research topics that could help support a CEA of the nanomaterial.
Compiling the information on what is known about the nanomaterial is the first step in the CEA process
(Figure 1-1). Next, a collective judgment process is used to evaluate and then prioritize this information.
Collective judgment, as has been applied in the CEA process to date, refers to a formal, structured
procedure that enables a diverse group of individuals to be heard individually and represented in a
transparent record of the collectively reached outcomes. In turn, it supports an essential feature of CEA:
the inclusion of diverse technical and stakeholder perspectives to ensure that a holistic evaluation is
achieved (U.S. EPA. 2010c).
The outcomes of the workshopsprioritized information gaps and risk tradeoffswill be used in
developing and refining a long-term research strategy to assess potential human health and ecological
risks of nanomaterials and to manage associated risks of specific nanomaterials.
Recommendations to Address Overarching Risk
Assessment Needs - Case Study
One way to examine how a nanomaterial assessment
would fit within EPA's overall risk assessment paradigm is
to conduct a case study based on publicly available
information on one or several intentionally produced
nanomaterials. ... From such case studies and other
information, information gaps may be identified, which
can then be used to map areas of research that are
directly affiliated with the risk assessment process. This
has been done in the past with research on airborne
particulate matter.
Additionally, a series of workshops involving a substantial
number of experts from several disciplines should be held
to use available information and principles in identifying
data gaps and research needs that will have to be met to
carry out exposure, hazard, and risk assessments.
2007 Nanotechnology White Paper (2007) (p. 89)
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QJ
/ Compile lnformation\
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An important point to emphasize is that
none of the nanomaterial case study
documents and workshops are intended to
be ends in and of themselves, even though
intrinsically they might have value or be of
interest. They are primarily viewed as initial
steps in the development and refinement of
a long-range research strategy to support
CEAs of selected nanomaterials. Full
implementation of such a strategy requires
preparing additional nanomaterial case
studies, and the process is expected to
evolve, reflecting adjustments and
modifications as additional nanomaterials
are considered and new information
becomes available.
This report describes the outcomes of the
2011 nano-Ag workshop. Figure 1-2
illustrates the workshop design. Refer to
the 2010 Workshop Summary for the EPA
Board of Scientific Counselors for more
information on the approach used in
developing the case studies, the rationale in
designing the workshops, and the outcomes
of the 2009 workshop (U.S. EPA, 2010c).
1.1. Workshop Objectives
The goal of this workshop was to prioritize responses to the following question:
What research or information is most needed to
conduct a comprehensive environmental assessment
of nano-Ag used in disinfectant spray?
As discussed in Section 1.4.2, participants were guided through the NGT process, which enabled them to
identify and rank issues in response to the above question using their independent judgments and the
collective judgment of the group. The sections that follow describe the selection of participants, pre-
workshop activities, implementation of NGT for the workshop, and structure of the breakout group
reports.
1.2. Selection of Participants
Securing a multidisciplinary and multistakeholder set of workshop participants involved several steps,
with a goal of achieving a diverse array of technical and stakeholder perspectives to yield insights that
would be useful in defining what is essential to complete a CEA of this emerging nanotechnology. EPA
retained ICF International to help organize and facilitate the workshop.
Day 4
Conclusion and Closing Remarks
Pre-Workshop Rankings
Presentation of Pre-Workshop Rankings
Information Session
Breakout Group Presentations
Day 2
NGT Round Robin Discussions
Day 3
Breakout Group Meetings
Day 1
Figure 1-2. Nano-Ag Workshop Design.
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First, a list of candidate participants was developed based on information EPA provided, Internet
searches, and other investigation. From available biographical information, participants were assigned
to categories based on their sector (academia, consulting, NGO, etc.) and subject matter expertise.
Considerable attention was given to achieving, as much as possible, a balanced representation across
sectors and areas of expertise.
A target number of 25 participants was set. Because the 49 participants in the 2009 nano-Ti02
workshop, working in two NGT groups, independently identified similar research priorities, EPA decided
that 25 participants, working in one NGT group were sufficient to accomplish the 2011 workshop goals.
To ensure a final total of 25 participants, 30 potential participants were initially invited. When a
potential participant declined, an alternate was identified to maintain a balanced distribution of
disciplines and stakeholders. Ultimately, 23 participants, listed in Table 1-1, attended the workshop.
Table 1-2 lists the sector representation, and Section 4.2 presents the biographical sketches each
participant provided.
Table 1-1. Workshop Participant Names and Affiliations
Participant
Affiliation
Sector
Mary Boudreau
U.S. Food and Drug Administration
Government
Mark Chappell
U.S. Army Engineer Research and Development Center
Government
Hongda Chen
USDA National Institute of Food and Agriculture
Government
Mary Jane Cunningham
Nanomics Biosciences
Industry
James Delattre
NanoHorizons
Industry
David Ensor
RTI International
Consulting
Michael Hansen
Consumer's Union
NGO, Labor, Journalism
Carol Henry
Independent Consultant
Consulting
Matthew Hull
NanoSafe Inc.
Industry
Ian llluminato
Friends of the Earth
NGO, Labor, Journalism
Larry Kapustka
LK Consultancy
Consulting
Bojeong Kim
Virginia Tech University
Academia
Kristen Kulinowski
Rice University CBEN
Academia
Debbie Lander
DuPont
Industry
Paul Lioy
EOHSI / Rutgers University - UMDNJ-RWJMS
Academia
Brian O'Connor
FPInnovations - PAPRICAN
Industry
Maria Powell
Nanotechnology Citizen Engagement Organization
NGO, Labor, Journalism
Gurumurthy Ramachandran
University of Minnesota
Academia
Christie Sayes
Texas A&M University
Academia
Maria Sepulveda
Purdue University
Academia
Brian Strohmeier
RJ Lee Group
Consulting
Michael Tolocka
University of North Carolina - Chapel Hill
Academia
Dik van de Meent
RIVM Laboratory for Ecological Risk Assessment
Government
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Table 1-2. Participant Sector Representation
Upon acceptance of the
invitation, each participant
received a conflict of interest
disclosure form to complete;
no conflicts were identified.
Generally, a written
agreement was executed with
each nonfederal-government
participant for
reimbursement of travel
expenses and payment of an
honorarium of $2,000 for
services. A purchase order
agreement and honorarium were used to help ensure that participants would understand that a
commitment of their time and attention was expected and that their services were not being offered
gratis.
Sector
Total
Participants
Academia
7
B, F, L, 0, U, V, W
Industry
5
D, H, R, S, T
NGO, Labor, Journalism
3
A, K, N
Consulting
4
C, F, G, M
Government
4
1, J, P, 0
Total
23
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1.3. Pre-Workshop Review and Rankings
Confirmed participants were asked to review the nano-Ag case study document in advance of the
workshop and, using an Excel-based form, submit their preliminary rankings of research questions listed
in the case study. They also were invited to submit review comments on the case study, to be
considered in revising the case study document prior to final publication. The objective of having the
participants rank the questions and review the draft case study document prior to the workshop was
both to help ensure that participants actively read the document and to prepare them to provide final
ranking of the issues in priority order. Essentially, this pre-workshop exercise was intended to substitute
for the brainstorming aspect of NGT (Van de Ven and Delbecq, 1972).
Participants were asked to determine their rankings of research questions by selecting: (1) the 10 most
important questions identified in the draft case study document in rank order from 1 to 10; (2) 15
additional questionsin no particular orderthat were also of high but lesser importance; and (3) up to
10 questions of lowest priority in laying the foundation for a CEA of nano-Ag. Participants also were
invited to submit modifications of existing questions from the case study and new questions not
included in the document. All revised and new questions were compiled and distributed to the
workshop participants via email one week before the workshop, and the questions were included in the
folders of materials provided to the participants at the workshop. During the initial plenary session at
the workshop, the facilitators presented the results of the pre-workshop ranking of the questions.
Figure 1-3 presents the pre-workshop ranking results for the top ten ranked questions. The instructions
to participants detailing the pre-workshop ranking procedure are presented in Section 4.3 of this report;
lists of new and revised questions are included in Section 4.4; and the pre-workshop ranking results for
all questions and the methodology used to analyze the results are presented in Section 4.5.
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Ranking Results (1-10)
Shown in ranked order beginning with the question awarded the most total points (Question 5.3.).
Number of Participants Selecting Question
Question
5.3. What effect, if any, do surface treatments of nano-Ag particles have on: a. uptake?
b. biopersistence? c. bioaccumulation? d. biomagnifi cation?
6.1 To what extent do particle properties (e.g., size, shape, chemical composition,
surtacetreatments) determine biological responses to nano-Ag?
3.6. What changes occurto the physicochemical properties ofnano-Ag throughout the
material life cycle stages, either as a function of process and product engineering or as
afunction of incidental encounters with other substances andthe environment?
5.1. Are available methods adequate to characterize nano-Ag concentrations and
associated exposurevia relevant matrices such as: a. air? b. water? c. food?
3.7. What are the potential exposure vectors by which nano-Ag or nano-Ag by-products
couldbe releasedto the environment at the various life-cycle stages?
2.6. What physicochemical properties ofnano-Ag can be usedto: a. predict fate and
transport in environmental media? b. predict toxicity to humans or biota?
2.5. How does surface coating affect: a. the physicochemical properties ofnano-Ag?
b. toxicity to humans or biota?
3.2 What data regarding the physicochemical properties, concentrations, and
formulations in nano-Ag spray disinfectants are appropriate for assessing their
behaviors in and impacts on the environment?
2.7 Which physicochemical properties of nano-Ag are most essential to characterize
before and during toxicity experiments?
4.7 How does nano-Ag partition among soil, water, sediment, and air, andwhat are the
key parameters determining this partitioning behavior?
CO
CO
5
cn
ฆ
CO
CO
16
I Ranked
] High
]Low
Figure 1-3. Pre-workshop ranking results for the top ten research questions posed in the nanosilver case study document.
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1.4. Workshop Activities
This section describes several key workshop-related activities, including an EPA Public Information
Exchange, the NGT process, and development of reports by participants.
1.4.1. Information Exchange and Introduction
Prior to and separate from the workshop, EPA convened a Public Information Exchange to explain the
rationale for the case study approach, the choice of nanomaterials and applications, and the results
from the 2009 workshop on nano-Ti02. During the exchange, EPA clarified that ICF would conduct the
Nanomaterial Case Study Workshop on Nano-Ag independently of EPA, with EPA funding, in compliance
with requirements of the Federal Advisory Committee Act (5 U.S.C. Appendix 2; see
http://www.gsa.gov/portal/content/100916).
1.4.2. Nomina! Group Technique
A description of the NGT process was provided to participants in advance of the workshop (see text box
on the following page). The workshop agenda (Section 4.1) provides further detail about how the
meeting was conducted.
The workshop was structured to introduce participants to NGT in the opening plenary session, when the
pre-workshop ranking results also were presented and discussed to stimulate further thought about the
relative importance of the various questions. At the end of the session, participants were asked to
carefully consider and then select the top research priorities, along with rationales, for presentation
during the NGT round robin.
The round-robin procedure allowed individuals up to 3 minutes each to present to the group a single
high priority research/information need and a rationale for selecting that issue in relation to conducting
a CEA. Participants also were allowed to present an entirely new question or to modify the phrasing or
content of an existing research question. Each high priority research need was written on a flip-chart to
enable consideration by the group. After each participant had spoken, the procedure was repeated for
two more rounds, until all research priorities were posted on the wall. Altogether, participants
identified 78 research issues as information needs during this stage: 58 unique issues and 20 issues that
more than one participant proposed (see Section 2).
The second part of the NGT process involved consolidating similar or overlapping research needs into
related research topic areas. Participants were given the opportunity to propose consolidating two or
more research needs into a research theme, subject to approval by those participants who had
nominated the respective research needs in question. Participants indicated that consolidation into
research themes would be easier if the research questions were grouped by topic. Participants then
divided those topics into research themes according to instruction by the facilitator that the themes
should be amenable to being addressed in a single request for proposals or applications. The facilitator
also reiterated the need to consolidate individual research needs into research themes to allow the
participants to develop breakout group reports to ultimately guide future research prioritization.
The individual research questions were retained for later reference. Altogether, 56 of the 58 unique
research needs were categorized into 23 consolidated research needs. Ten of the unique research
needs were assigned to two consolidated research needs: 2.5, 2.6, 4.6, 4.10, 5.17, 6.8, 6.10, 6.16, N.9,
and N.12.
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Description of Nominal Group Technique
This summary was distributed to workshop participants and observers prior to the workshop.
Nominal Group Technique (NGT) is a structured process for a set of individuals to identify and rank a
number of choices. Typically, several individuals (nominally a group) are convened and each person is
afforded an equal opportunity to offer his or her view(s) about which choices are highest priority.
When a large number of choices are under consideration, they may be grouped or consolidated into a
more manageable number. A multi-voting process is then used to rank the choices. In the January
2011 Nanomaterial Case Studies Workshop, the participants will form one NGT group of approximately
25 individuals. This brief document provides an overview of NGT as it will be implemented at this
workshop.
Round Robin Discussions. Each participant will be asked to state and provide justification for the
research question they believe embodies the most important research or information need with
respect to nano-Ag. This brief oral presentation (to be conducted without visual aids) must be
completed within a 3-minute period (strictly enforced). Each presentation should include a statement
or description of the research question and an explanation of why it is a high priority in relation to a
comprehensive environmental assessment of nanoscale silver (nano-Ag). As time permits, additional
priorities will be presented in subsequent rounds of presentations. If another participant precedes you
and speaks to the issue you intended to present, you may use your time in support of the same issue or
you may raise a different issue that you consider to also be a high priority.
Consolidation and Multi-Voting. Each research question will be noted on a large sheet of paper and
displayed for the group. A facilitator will work with the group to determine which questions can be
consolidated into major research areas, thereby consolidating the total number of questions to around
20-30 themes. The consolidation process will be followed by multi-voting, during which participants
will assign weighted votes to the research questions they deem most important for supporting a
comprehensive environmental assessment of nano-Ag. The pre-workshop ranking process used multi-
voting to develop a preliminary list of the top 10 questions, and essentially the same process will be
used during the workshop.
Breakout Group Discussions and Summaries. After the group has prioritized the research questions
through multi-voting, the participants will convene to discuss the ranking results. The participants will
then be divided into breakout groups (each comprising 3 to 4 individuals), with each group assigned one
of the top priorities. The breakout groups will discuss their assigned areas and prepare short written
summaries in a standardized format that describe the research question of interest, explain what
additional data are needed and why, and present other related information (including, as appropriate,
alternate viewpoints). Then, the group will reconvene, review the next set of research questions based
on the multi-voting results, and divide into new breakout groups to discuss the next set of priorities and
develop another set of written summaries.
Plenary Discussion. Finally, the participants will reconvene in plenary and each of the summaries from
the two sets of breakout groups will be presented. A primary objective of this final session will be to
identify linkages among most highly ranked research areas.
The result of the workshop will be the set of the research questions selected through the NGT process
as most important by the group. These questions and the summary information developed by the
breakout groups will be incorporated into a workshop report.
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The third part of the NGT involved a multi-
voting exercise to develop a ranking of the
consolidated research needs in terms of their
importance for conducting a CEA. Each
participant was given 10 Sticky Notes, labeled
1 to 10 with an identifying letter. The
participants were then asked to rank their
top 10 research priorities by giving 10 points
to the research need they deemed most
important for conducting the CEA, 9 points to
their next highest priority, and so on, down to
1 point. Only 10 research topics could be
ranked by an individual, and each topic could
receive only one ranking per individual. After
the voting process, the results were tallied
and the ranked research priorities were
identified. The ranking of research priorities
is listed in Section 3.1.
1.4.3. Breakout Group Reports
The agenda was structured to allow for two
separate breakout group sessions so that
participants joined one breakout group in the
morning and the other in the afternoon. At
the 2009 workshop, only one breakout
session was included for the most highly
ranked themes (ranked 1 through 8). By
scheduling two separate breakout group
sessions for the 2011 workshop, participants
could create reports for the most highly
ranked themes (ranked 1 through 7) and also
for the middle tier themes (ranked 8 through
14). This approach enabled participants
equal opportunity to contribute to one highly
ranked theme and one middle tier theme,
rather than some participants contributing to
two highly ranked themes and other
participants contributing to two middle tier
themes. It also expanded the number of
consolidated themes on which participants
created reports from 8 in the 2009 workshop
to 13 (with one research topic omitted) in the
3,5,3.
What are (he associated
feedstocks and by-productฎ?
Of these feedstocks and by
products, which might be
ro,'eased, in what quantities,
and via which pathways'.*
^ 3,7.
What are the potential
exposure vectors By which
nano-Ag or nano-Ag by.
products could be released to
the environment at the various
lifa-eyde stages?
4.10.
How eflectivety is naix>.Ag
removed from sewag# and
industrial process water by
wastewater treatment technology,
and can information on the
removal of convwtwfll silver be
applied to nano-Ag wnovai?
^ A W ^ fc
^ jOUfcES 5 t , r
5 antk i release rates or
Minolta ftto M
roteased, in what quantities,
a,,d via which pathways''
^ 3,7.
What are the potential
exposure vectors by which
nano-Ag of nano-Ag by-
products could be released to
the environment at the various
lite-cycle stages?
4.10.
Hew effectively is nano-Ag
removed from sewage and
industrial process water by
wastewater treatment technology,
ami can information on the
removal of conwribonal siivei be
applied to nano-Ag removal?
*5^
~ ' i release rates of
Pitleaฃ& t fMOTta ftto iit,
-" rfWtfotTrywf ?
Example of four questions consolidated into a research
theme with multi-vote results.
2011 workshop.
Participants volunteered to work on an issue of their choice (with guidance to limit group sizes to 3 or 4
people), resulting in 13 breakout groups corresponding to the top 14 research topics. Participants
omitted one research topic (human and mammalian test methods) for a breakout group presentation,
but the 13 remaining breakout groups were instructed to reference this topic in their reports. The
groups were given around 3 hours for each breakout group session (including lunch) to develop a short
report fleshing out descriptions of the research topic areas using an MS Word document template
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(Section 4.6). The facilitator observed the breakout groups, offering guidance when appropriate. The
written reports are presented in full in Section 3.2 of this report. On the last day of the workshop, a
spokesperson from each breakout group gave a 5-minute presentation to the plenary group, using a
provided PowerPoint template (Section 5). These presentations were meant to summarize each
breakout group's written report, with particular emphasis on the topic's connections to other priority
areas. Time was allowed for the plenary group to respond to these presentations, especially for the
purpose of pointing out additional connections or relationships among research topic areas. The
presentations and discussion points are also presented in Section 3.2 of this report.
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2, Research Questions Proposed During Nomina! Group Technique
2.1. Round 1
2.7 Which physicochemical properties of nano-Ag are most essential to characterize before and
during toxicity experiments?
Participant A1
From the viewpoint of consumers, I want to represent what the personal health impact will be.
There are both exposure and health questions; it was a toss-up for me.
It is important to know what you are looking at and why before you conduct a health
assessment.
When you come to conclusions, you need to understand whether a certain harmful effect is due
to a particular characteristic.
You must understand what physicochemical properties are important vis-a-vis toxicity of
nanoparticles.
2.10 Do adequate analytical methods exist to detect and characterize nano-Ag in environmental
compartments and in biota?
Participant B
Once nano-Ag is released to the environment, the biggest challenge we have is to distinguish
nano-Ag from incidental and naturally occurring particles.
The difference between nano-Ag and incidental or naturally occurring particles is not like
quantum dots or nanotubes, which are obviously manmade.
It is difficult to know the source of nano-Ag in environmental compartments.
For a CEA framework, we need to have a methodology to identify what they are and how much
they are in the environmental matrix, so we can address which questions are important.
6.1 To what extent do particle properties (e.g., size, shape, chemical composition, surface
treatments) determine biological responses to nano-Ag?
Participant C
There are several others questions that say the same thing in a different way, so it was difficult
to pick this one.
I agreed with everything Michael Hansen said about physicochemical properties determining
effects.
You must make sure you are measuring the right thing (e.g., single particles, clusters) if you want
to find the best analytical method.
6.3 Are the effects observed for exposure to nano-Ag due to silver ion release or the presence of
nanoparticles? Can this be distinguished?
Participant D
There is a multitude of hazardous tests that can be done, but you need to know what the hazard
is to begin with (e.g., nano-Ag or ions).
We know silver ions are toxic, so that is important to address.
It is important to know whether nano-Ag is acting as a vector for the ions.
If nano-Ag is a vector, you make it a different threshold as it is providing ions at a point of
exposure, rather than diffused.
1 Participants' names were coded to so that individuals could openly express ideas during the workshop.
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We need to know whether silver nanoparticles act differently in people, due to the oxidation of
nano-Ag.
2.10 Do adequate analytical methods exist to detect and characterize nano-Ag in environmental
compartments and in biota?
Participant E
I am coming from the public health and environmental policy perspective.
New technologies are invented for benefits, but there are also dangers and opportunities.
It is clear that these technologies (e.g., nano-Ag sprays) are going to be produced, marketed,
and sold and will become part of the environment.
Do we have rapid, routine, and cheap systems to detect nano-Ag in the environment? I do not
think we are close.
If we cannot detect it, we cannot measure it, and we cannot be sure what is happening.
6.3 Are the effects observed for exposure to nano-Ag due to silver ion release or the presence of
nanoparticles? Can this be distinguished?
Participant F
The physicochemical properties, route of exposure, and health effects are the main three
themes.
Is the function of the nano-Ag in this spray as an antimicrobial going to kill the bacteria?
Nano-Ag kills bacteria over a longer time according to the literature.
The literature also shows that particles act differently than ions.
It all comes back to dose and the concentration. Will we be spraying it more often because it is
not as effective as ions only?
There is a fundamental difference in toxicology between a low dose and a high dose. The
literature is filled with overdose, not low-dose exposures.
We must determine if the spray is a low-dose or high-dose scenario.
N.3 What is the half-life of nano-Ag in the environment?
Participant G
What are the basic mechanisms?
If you released 20-nm particles, they would rapidly coagulate and ultimately be 0.5 micron. Will
it last a week or a year?
What is the reactivity in various media?
There is a definitional problem that will be solved in the courts.
Based on work done in Paul Lioy's lab, it is hard to determine how much nano-Ag in a particle
makes it a nano-Ag particle.
A nano-Ag particle has a very low mass compared to the whole particle.
What makes it a nanomaterial? How many nanoparticles make a nanomaterial?
N.3 What is the half-life of nano-Ag in the environment?
Participant H
If it has a short lifetime, it is much easier to understand the fate.
If it becomes an ion, we can establish fate and transport. If it is a particle, we know what
happens.
If it keeps moving, releasing over time, we do not know how to think about it and it is more
difficult to model.
Persistence is vague. I prefer half-life.
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N.4 What are the release rates of all sources of nano-Ag into the environment?
Participant I
No effects, no exposure; no release, no exposure.
Many questions ask how something influences nano-Ag. The important thing we need to
understand is how readily something influences.
6.1 To what extent do particle properties (e.g., size, shape, chemical composition, surface
treatments) determine biological responses to nano-Ag?
Participant J
It is important to ensure safety of the product to the consumer and environment.
Particle properties pose a threat to me as a consumer or to the environment.
6.16 Are the current tests for regulatory acceptance relevant to nano-Ag?
Participant K
The consumer is our priority.
As we settle into research priorities, I question whether we are allowing products on the market
that should not be allowed.
If human health is a priority, should we make a precautionary gesture toward the public and
hold off on further market entry until we know more?
6.5 Is the available ecological effects evidence adequate to support ecological risk assessment for
nano-Ag? If no, what research is needed to make an assessment possible?
Participant L
Do we have the available information, which encompasses the rest of the Chapter 6 questions?
6.27 Are there sufficient data to develop concentration- or dose-response relationships instead of
the current emphasis on point estimates or narratives of relative effects?
Participant M
This would apply to ecological issues as well as human health issues.
This is related directly to the behavior of the particles, so many other things get folded into it.
Nanomaterials function as colloidal products producing an odd bathtub-shaped dose-response
(partly due to different exposure routes).
When we start at low concentrations, we get effects, but when we move to high concentrations,
the effect goes away.
Until we do good characterization of what is in the test system, we will fail.
It is going to be difficult to tell the public how little we know.
This is the way to improve eco-tox.
3.7 What are the potential exposure vectors by which nano-Ag or nano-Ag by-products could be
released to the environment at the various life-cycle stages?
Participant N
I work with citizens and state government agencies, and we work to understand and prevent
health and environmental exposures.
I want to call attention to the top of the CEA diagram.
We tend to find out something is bad after it is released and then try to go back and determine
the sources, but I would like to see us avoid that with nano-Ag.
As we know, nano-Ag is already in products and silver is the second most toxic to aquatic
organisms.
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We need to understand the potential pathways, where the releases will be, what types of
releases, what organisms and humans will be exposed, etc.
From the standpoint of risk management, if we do not understand where the releases are, we
cannot shut off the valve.
5.21 What information exists on the temporal changes in the release of ionic silver by nano-Ag in
relation to particle physicochemical and environmental characteristics?
Participant O
We know these particles release ionic silver, but in my opinion, we do not understand how
different environmental chemistry conditions (e.g., pH, ionic strength) affect the particles,
especially over time.
4.1 Do the properties of nano-Ag that differ from those of well-characterized colloidal and bulk
silver, if any, cause them to behave differently in aquatic, terrestrial, and atmospheric
environmental compartments?
a. If they do differ, how do they differ?
b. Can information about how colloidal silver behaves in these environments be used to
understand how nano-Ag behaves?
Participant P
Is there any real difference between nano-Ag and bulk silver in the environment over time?
Soils are mostly rich in calcium, so you have a strong flocculent there.
Electrostabilized nanoparticles are not thermodynamically stable.
Those sterically stable, coated by organics are typically consumable by microorganisms.
There is not a good chance of persistence after digestion.
I do not think there is a lot of chance for nano-Ag to stay dispersed (high van der Waals force).
Because we are moving through a solid, we are talking about filtration. Clay particles do not
have enough separation to move these small particles.
2.1 What information could be provided about the nano-Ag contained in spray disinfectants to
enable adequate characterization of exposure routes and toxic effects?
Participant Q
This probably encompasses everything we have discussed so far.
In studies we have conducted looking at toxicity in vivo in rats, we found that particle size when
injected (i.v. or by gavage), in relation to silver acetate, the area under the curve decreased as
particle size increased.
We saw an inverse relationship and sex differences.
We need to know what sized particles are actually contained in the disinfectant sprays.
Do manufacturers have sufficient data to provide to EPA?
Are these particles are going to agglomerate like bulk particles? If they agglomerate, they are
no longer nano-sized.
Will the agglomerates fall out of the spray onto surfaces?
What surface treatments are done to the nano-Ag included in the sprays?
How are they held in dispersion?
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2.6 What physicochemical properties of nano-Ag can be used to:
a. predict fate and transport in environmental media?
b. predict toxicity to humans or biota?
Participant R
Want to combine with 2.5; what physicochemical properties can be used to predict fate and
transport and effects and what are the surface effects?
The manufacturers are not concerned because they put the nanomaterial in a matrix or
composite, and it will never break down from their perspective.
Will the use cause it to break down?
Physicochemical properties and surface effects are important to this question.
6.14 What are the biological responses observed at current nano-Ag occupational exposure levels?
Participant S
All of the questions so far require somebody to test the material in a lab, and we can be
somewhat reckless win the lab with how we handle them.
I do not think the material is a huge concern for consumers at this point.
It is a concern to those who are manufacturing and handling the material in the lab.
We should measure nano-Ag levels in facilities or total silver levels in production facilities and
focus on acute and chronic exposure at those levels.
N.7 What are the phys-chem properties of currently available and historic silver products?
Participant T
The evolution of terminology has been obscured.
The case study mentions the historical uses of silver but does not integrate them into the
discussion.
Cary Lee particles (chosen by OECD as reference materials for nano-Ag studies underway which
tells us something about the value of historical data) were used in the 1800s.
In the 1950s, the first product registered by FIFRA was a silver product.
Registration under FIFRA is important because there are production data and an incidence
database.
If you go to the conventional silver data, there are nano-Ag data there that should be leveraged
for risk assessment.
For the avian toxicity studies referenced in the case study, it is 7-nm algaecide particles.
These data have been applied to nano-Ag incorrectly.
N.3 What is the half-life of nano-Ag in the environment?
Participant U
Kinetics, or what happens when nano-Ag when it is released into the environment, matter most
when determining properties.
This ties in to exposure and ultimately toxicity.
If you release the 7-nm particles into the atmosphere, and data show 5-nm particles are toxic,
there will eventually be solubilization that will change the 7-nm particles to 5-nm particles. At
what point this happens is important.
This is also dependent on how quickly the surface coating dissolves.
Temperature is crucial in kinetics; there is an exponential dependence.
This is also important for wastewater.
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5.18 What is the distribution of exposure intensities and frequencies of such exposures among
workers, homemakers, children, and maintenance personnel, and are these of concern for acute
and or chronic health effects?
Participant V
This is supported by 5.17 and is a legally logical question.
There is no need to have a question as to whether people are exposed (there are releases into
the environment), but what are the intensities of exposure and do these exposures lead to
harmful effects?
You cannot do a meaningful risk assessment without this information.
Determining the chemical, physical, and particle-size characteristics at the time of exposure is
critical.
There is an ecological question and I can frame it in the same way: What exposures occur to fish
and other benthic and nonbenthic organisms?
Without exposure, there is no dose, with no dose, there are no effects.
We need to know quantitatively whether particles should be taken off the market and whether
new products should be on the market.
Understanding exposure is the bottom line and all of the rest can be derived from that.
This question should be expanded to include occupational setting, rather than just the
consumer, although the most highly exposed might not be the most sensitive.
Companies choose the material they are spraying, but the user has no choice. The various
contexts for exposure are relevant.
5.17 How should dose and exposure be characterized for human exposures and how do the following
parameters affect it: (1) physiological characteristics, (2) behavior, (3) lifestage, (4) susceptibility
factors?
Participant W
We need to determine who is exposed, at what levels, and in what contexts to assess exposure.
If you look at 6.14, the response depends on what exposure metric is being used. Depending on
the metric, you may or may not observe a dose-response relationship.
Is it mass, surface area, surface chemistry, or number of particles?
With population and stage of their lifecycle, it is difficult to determine which subgroup of the
population is most highly exposed.
Occupational populations might be most highly exposed, but once you look at consumers, it is
not easy to determine which parts of the population will be most sensitive or susceptible.
Which populations are we talking about and how do we measure exposures?
2.2. Round 2
5.14 Many effects of emerging substances are not known until many years after their introduction
and use in commerce. What are the chronic and subchronic effects of nano-Ag, and how can we
accelerate our understanding of them? Can nano-Ag have an impact on F-l generation via
changes in gene expression patterns?
Participant A
For regulatory purposes, we have a set group of toxicity studies that should be done for various
acute, subchronic, and chronic exposures, but for all of the products on the market, we do not
think about if it would affect the next generation behaviorally or in another way.
We now have the technology to start screening and looking at gene expression arrays to
determine effects on the next generation.
Are there things that current toxicity tests might not pick up that would be important?
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If there is not enough exposure the effect will not be there, but we need to look at it.
3.6 What changes occur to the physicochemical properties of nano-Ag throughout the material
lifecycle stages, either as a function of process and product engineering or as a function of
incidental encounters with other substances and the environment?
Participant B
Transformation after release to the environment is not available because we still need data on
the parent compound.
This is in line with the half-life of nano-Ag particles, but is it losing antibacterial properties or
nano characteristics?
2.12 Do adequate analytical methods exist to detect and characterize exposure to nano-Ag via soil,
water, and air?
Participant C
Methods is the key word, because it implies more than instrumentation.
We have the instrumentation in existence (e.g., SEM, TEM, STEM, to 1-2 million times).
The problem is determining which method to use with the instrumentation.
If I have a product with nano-Ag at some small percentage, we can know a little about the
nanoparticles, but in a gallon of river water, it becomes problematic.
I do not know how to approach characterization in water, soil, and air samples.
6.10 At a minimum, what assays could be considered in a harmonized test guideline for
determination of the human health effects of nano-Ag?
Participant D
As a company that is producing a new nanomaterial, it is up to us to make sure there is no
hazard to exposure.
When it comes to human tests, it would be nice to have some guidelines from EPA and
Environment Canada.
You have to take into account what needs to be done and what has to be done.
We need to know which procedures should be used to test what things from regulators.
What needs to be done is more important than what can be done.
4.10 How effectively is nano-Ag removed from sewage and industrial process water by wastewater
treatment technology, and can information on the removal of conventional silver be applied to
nano-Ag removal? Is the nano-Ag harmful to the beneficial organisms in wastewater
treatment?
Participant E
This is part of characterizing the ecological impacts. Yes, it is out there but how can we detect
it?
The potential of nano-Ag particles is to do the beneficial antimicrobial activities but also they
could knock out the beneficial things.
What is the bacterial resistance?
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4.1 Do the properties of nano-Ag that differ from those of well-characterized colloidal silver, if any,
cause them to behave differently in aquatic, terrestrial, and atmospheric environmental
compartments?
a. If they do differ, how do they differ?
b. Can information about how colloidal silver behaves in these environments be used to
understand how nano-Ag behaves?
Participant F
"Is nano-Ag different from colloidal silver?" is a research question that needs to be addressed.
The literature has a debate as to whether or not people are seeing that nano-Ag particles are
more efficient than any other antimicrobials we have out there (including metal salts).
Can we characterize efficacy for killing bacteria and understand that a little bit more?
If it does, what about the beneficial bacteria in our gut. If it is indeed killing bacteria, either by
slow release or by ionic silver, are we killing the bacteria in our gut? What is the bacterial
resistance?
2.9 Are there standard nano-Ag reference materials that can be used in exposure and effects testing
to aid in comparison of results among investigators?
Participant G
The methods that we have talked about need validation.
We need round-robin testing and references for that.
It depends on the media the particles are dispersed in (e.g., surfactant, powder, aerosol).
Mary Boudreau mentioned OECD has reference materials and two different coatings in liquid
form.
4.12 How could existing models applicable to conventional silver be used to adequately predict the
transport and fate of nano-Ag through environmental compartments, or how could they be
modified to do so?
Participant H
I do not see a great concern for humans, but rather a focus on the environment.
We are going to need modeling, because these questions will take years to answer.
We think a lot can be done with models we have used for REACH and we can modify them to get
in the ballpark.
We can use a tiered approach using the worst case to hone in on where we need to go and what
tests we will need to get the answer.
For nano-Ag, I am going to do a different risk approach for the spray than I am for an industrial
use.
You can follow up with what is really going on after you get the guidance from the models.
N.ll What are the rates of dissolution of nano-Ag into the environment?
Participant I
I am talking about the dissolution of nano-Ag to silver ions.
From an environmental risk assessment and ecosystem exposure, the answer is going to be it is
the ions that do the job.
I need to ask for release rates of silver ions from materials, specifically, the rate of dissolution of
nano-Ag.
If dissolution occurs on a short timescale, we might not be interested in how rapidly it occurs
from an ecological perspective.
We can assume it is being transformed into ionic silver all at once.
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If dissolution is slow, we would then need to know at what rate this dissolution occurs.
From the perspective of the nanoparticle, this may not be different from half life.
From the perspective of toxicity of silver ions in water, it would mean that you ask for a rate of
entry into the environment.
5.1 Are available methods adequate to characterize nano-Ag concentrations and associated
exposure via relevant matrices such as:
a. air?
b. water?
c. food?
Participant J
Safety implementation to industry, consumer, and regulation are important.
This is a daunting task.
How do you isolate and characterize the nanoparticles?
N.l Does the release of nano-Ag contribute to climate change?
Participant K
This is an interdisciplinary question.
Nano-Ag when exposed to sludge releases 4x the amount of nitrous oxide, which is a potent
GHG.
N. How can we incentivize researchers to focus in on the most critical questions and best methods
for CEA?
Participant L
There are a lot of data out there on nano-Ag, but applicability of existing data to risk assessors is
a problem.
Anything we can do to improve research quality needs to be done, such as reference materials.
If we design a good research experiment, we need pristine materials varied in a very precise
way, but this might have little relevance to the state of nano-Ag in life-cycle stages associated
with actual exposures.
6.26 Is there evidence of adaptive tolerance developing in microorganisms to Ag and to nano-Ag that
would render the products useless, especially as the products gain widespread use?
Participant M
When we get to the point of regulation, there will be an efficacy component to the final
decision.
If we do not anticipate the possibility of resistant strains developing and becoming infective, we
will overestimate the benefits the product might give us.
This has a ripple effect, especially through ecological consequences.
We do not what happens when we stir the pot in a complex ecological system. It could trigger
an unknown response.
We need to know whether resistance is a concern.
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5.18 What is the distribution of exposure intensities and frequencies of such exposures among
homemakers, children, and maintenance personnel, and are these of concern for acute and or
chronic health effects?
Participant N
These products are already on the market and people are using them and being exposed.
At the State level, consumers and public health workers are concerned about whether these
products are safe.
Ethically, the most important thing is to understand the exposures right now as soon as possible.
Methods need to be worked out, but we have most of the instrumentation we need.
People are exposed before it is released into the environment, so we need to focus our
attention there.
In the past, we have waited until people become sick or die before we do anything, but we need
to reverse that.
2.10 Do adequate analytical methods exist to detect and characterize nano-Ag in environmental
compartments and in biota?
Participant O
A lot of us have addressed methodological issues, especially related to exposure, in the second
round.
It is easy to measure these particles in simple matrices, but if you have a whole organism, it is
difficult to determine how much exposure has taken place.
We can measure total silver, but we do not know how relevant that is to nano-Ag.
4.6 Does nano-Ag form the same strong complexes with anions as conventional and dissolved silver,
and if so, is it also effectively immobilized in aquatic environments?
Participant P
Environmental fate is the low-hanging fruit in terms of nano-Ag research.
We know nano-Ag is not inherently soluble and the surface must be oxidized.
What are the release kinetics of nano-Ag in the environment?
Do humics increase or decrease dissolution?
Iron oxides are where all the heavy metals are. Do we expect iron oxides to accumulate all of
the silver in the soil?
What is the differential activity of iron oxides or free moving silver?
There is the question of species and distribution with respect to the complexes silver can form in
the environment.
Do these complexes have the same toxicity and antimicrobial activity? Typically, no.
4.2 Does the particle size or source or agglomeration state of nano-Ag affect the rate of release of
silver ions in environmental compartments?
Participant Q
Silver was characteristically used as an antibiotic in history.
Does the particle size affect the release of ions into the environment?
We need to talk about what the toxic substance is.
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2.5 How does surface coating affect:
a. the physicochemical properties of nano-Ag?
b. toxicity to humans or biota?
Participant R
There are a lot of surface coatings that are biocompatible.
Are these coatings adequate enough to neutralize adverse effect?
N.6 How urgent is the need for the benefits offered by the candidate application/material?
Participant S
If you look at the use of silver in wound creams, it addresses a need that is not addressed by
other products.
Do we have alternatives to using nano-Ag?
This may be a philosophical question. We do not want to intrude on the free market or inhibit
entrepreneurs.
We should compare efficacy of nano-enhanced products to other products.
N.3 What is the half-life of nano-Ag in the environment?
Participant T
There have been new findings since the case study (e.g., publications by Bojeong Kim and Bernd
Nowack).
If half-lives are sufficiently short, we have a massively simplified risk assessment in terms of
environmental fate.
If so, consumer products might be indistinguishable from other naturally occurring or known
(e.g., mining, photography) silver releases.
Understanding speciation that follows half-life is important.
How does the particle size of silver sulfides change?
How likely is it that we will see silver sulfides? Publications by Choi and Hu discuss this.
Entrained in municipal waste stream, there are four orders of magnitude more silver sulfide;
excess silver sulfide is very stable.
Historically, these silver sulfides are the reason that silver algaecides have been deemed less of
an environmental risk.
5.1 Are available methods adequate to characterize nano-Ag concentrations and associated
exposure via relevant matrices such as:
a. air?
b. water?
c. food?
Participant U
It might be easy to determine the dose, because there is so much material in the environment.
Nanomaterial, in general, might be considered at the pictogram level and smaller and what type
of health effects that small amount might cause.
For some techniques, I am uncertain about efficacy toward unraveling surface coating that
might be carbonaceous.
There have been issues with microscopy and ICP agreement.
N.7 What are the phys-chem properties of currently available and historic silver products? What are
the properties of those chemicals in terms of exposure?
Participant V
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We are dealing with near-field, intermediate, or far-field inhalation or ingestions.
We will have to deal with agglomerates.
The toxicity tests that will be necessary to determine whether the efficacy in terms of product
remain the same.
Does the transformed product have the same potential for human health effects?
5.16 What effect, if any, do surface treatments of nano-Ag particles have on human exposures and
uptake?
Participant W
This is a rewording of 5.3.
It affects half-life, exposure, and if you unbundle those properties, the most important part is
surface properties.
The surface effects are the most important in my opinion.
We need to know how it affects human exposure.
2,3. Round 3
N.9 Do nano-Ag products actually offer more efficacy than products on the market?
Participant A
EPA does not require efficacy data.
What is the real antimicrobial effect of the silver that is in the sprays or in some of the other
products?
Does it really have an effect? You do not need efficacy information to get it on the market.
There should be a requirement of efficacy of these products and there should be a benefit
analysis compared to something already out there.
6.8 What are the most sensitive ecological endpoints to nano-Ag exposure? Are there sufficient
data/analytical techniques to determine how sensitive specific endpoints and organisms are to
nano-Ag exposure, including:
a. benthic invertebrates;
b. marine invertebrates; and
c. freshwater invertebrates?
Participant B
This is related to 6.22.
From a regulatory standpoint, it is important to know what the human and environmental risks
are for these materials.
Developing a protocol to measure ecological toxicity is very important.
5.3 What effect, if any, do surface compositions of nano-Ag particles have on:
a. uptake?
b. biopersistence?
c. bioaccumulation?
d. biomagnification?
Participant C
The treatment that the manufacturers put on nano-Ag might be completely gone.
The surface is where the interaction with tissue, bacteria, biota, and people occurs, not the bulk
of the material.
I have never seen a material where the surface is the same as the bulk material, even in small
particles.
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It is important to understand the surface composition of the particles as they are manufactured
as well as once they are in the environment.
6.15 Do current publications describing the health effects of nano-Ag particles and laboratory-
generated nano-Ag particles accurately depict the toxicity of commercially available nano-Ag
materials?
Participant D
In doing a CEA, it is critical to look at the literature, but sometimes bad apples get in there.
We need to determine how the materials in the lab compare to the hundreds of products on the
market.
What you start with sometimes dictates what you end with, so we need to test the actual
products.
6.33 Can we predict whether widespread resistance to silver ions may develop and if so, are silver
and/or nanosilver likely to be useful antimicrobials in the future?
Participant E
How we used silver through the 40s and 50s is different from how we use it now.
The current approach is some is good, more is better.
Historical medicinal use and FIFRA-approved products have been limited and will be different
from how we use them now.
Information in the literature or from FDA might demonstrate that there is no antibiotic
resistance.
This is an important issue as nano-Ag products penetrate markets.
2.16 Do nanoparticles react with materials (i.e. organic matter, other metals, polymers) and alter
properties such as REDOX potential or leached metal ion rates?
Participant F
We recently published a series of papers on redox chemistries of nano mixtures.
We need to think about it being reduced, as well as the reducing agent, and if it changes.
We need to determine whether the reducing agent goes from a passive to an active material.
Redox properties need to be added to the minimal characterization data reported for
nanomaterials.
5.22 Which sources, pathways, and routes offer the greatest exposure potential to nano-Ag for
humans?
Participant G
We are primarily talking about consumer chemicals.
If a carpet is treated with nano-Ag, dust might be resuspended with nano-Ag, which we might
inhale.
We have to look for unexplained and unintended consequences.
Could there be synergy between previous chemical applications and nano-Ag?
4.10 How effectively is nano-Ag removed from sewage and industrial process water by wastewater
treatment technology, and can information on the removal of conventional silver be applied to
nano-Ag removal?
Participant H
Ions are bad, particularly to fish.
Where does nano-Ag go? If it does not go the aqueous route, but settles out, it will not affect
the fish.
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We have a lot of history from colloidal silver used in the photographic industry.
There is probably a lot of removal going on, based on this historic data.
We need to look into this from a nano-Ag perspective.
Effective removal reduces releases to aqueous environments.
If we have effective removal through wastewater treatment, the nano-Ag should settle out,
which would cut out a route of exposure.
N.3 What is the half-life of nano-Ag in the environment?
Participant I
This combines all of the other questions.
We can work out sedimentation that removes nano-Ag from water.
This more effectively gets to the knowledge we need to know rather than going through all of
the research.
N.12 What are the relevant susceptibility factors in terms of exposure?
Participant J
Each person will have a different degree of susceptibility.
We need to address human nutrition. New genomic study on the future of foods is needed.
We need a map of the susceptibility in order to map it to populations of interest.
2.8 What standardized test methods or characterization protocols are necessary to ensure that
research results generated in multiple laboratories are consistent, reproducible, and reliable?
Participant K
With 6.15.
Studies I might use would differ from others. It would be interesting to work together to
identify those priorities in terms of studies that would be used in reports.
When we work at this scale, we are tapping into a new wavelength.
We need to think beyond our own experience and take a big-picture perspective.
From a quantum perspective, we do not understand the effects on the future.
5.22 Which sources, pathways, and routes offer the greatest exposure potential to nano-Ag for
humans?
Participant L
We are overweighted on hazard studies and underweighted on exposure studies.
This leads to a skewed perception of risk without understanding of exposure.
Hazard papers outweigh exposure papers by about 5:1.
Mining the publications is not a substitute for a CEA.
We need more information about sources and potential exposures to enable a CEA.
N.5 We need an integrated holistic approach to nano risk assessment. How can we do this?
Participant M
The CEA process can be more than just workshops.
I want to call for the use of integrative holistic assessments.
In 1946, the WHO talked about health as being more than the absence of disease and toxic
materials.
Nanomaterials are going to expand into ethics and bioethics.
I see the framework as a complex matrix with a lot of empty boxes that need to be filled so that
somebody later can do a proper risk assessment.
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We need to make a dedicated effort to develop conceptual models and focus on exposure in
order to improve efficiency.
Exposure is currently the most ignored aspect. An integrated holistic approach would break
down the artificial barrier between human and ecological effects.
We need one coherent message that can be communicated to the general public.
5.5 Do particular species of biota and particular human populations have greater potential for
exposure to nano-Ag?
Participant N
What humans will be exposed to is closely tied to what ends up in the environment and
accumulated in animals.
There will be particular populations that are more likely to be exposed.
This will help us to prioritize where we will go first for exposure assessments.
The most exposed (e.g., janitors, maintenance workers) are often the least thought of. This
introduces social science questions.
There needs to be a greater focus on exposure.
6.13 What are the fundamental biological responses to and associated mechanisms of nano-Ag
exposure at the cell, organ, and whole-animal levels?
Participant O
We have not talked about mechanisms of toxicity at the cellular level.
We need to relate this to the physicochemical properties as well.
2.7 Which physicochemical properties of nano-Ag are most essential to characterize before and
during toxicity experiments and post-exposure?
Participant P
Most of the papers do not show post-exposure characterization data.
The ones that do are highly aggregated, indicating that exposures are not associated with
nanomaterials at all.
If we are talking about chronic exposures, this is very important.
5.5 Do particular species of biota and particular human populations have greater potential for
exposure to nano-Ag?
Participant Q
We need to know which human or environmental groups are exposed.
Antibacterial sprays might be used more around children (e.g., daycare centers spraying toys
and food trays).
Even if the particles settle out in the water, we need to think about ground feeders.
3.5A What are the associated feedstocks and by-products; of these feedstocks and by-products,
which might be released, in what quantities, and via which pathways?
Participant R
We need to know the starting material we are working with.
Several toxicity case studies show that people measured a contaminant instead of the test
product.
There are earlier studies where people used investigative nanomaterials, but they were actually
investigating the byproducts.
Some of the results were released to media.
2-15
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3.3 What are realistic strategies for collecting data on production quantities and product
characteristics given that much of this information is proprietary, and how can this information
help prioritize research needs?
Participant S
Interesting assumptions are made in the White Paper about global production.
This is extremely difficult to get, but we can do a bit more to get more information on these
materials.
It is good to make estimates in the absence of hard data, but we do need more data.
What is possible to conceive as being a nanoparticle effect in the environment cannot
necessarily be realized given current manufacturing techniques?
We need to distinguish between what is possible and what can actually be realized.
Different surface chemistries or article characterizations might cause health effects, but
manufacturers can only test so many.
It is important to link health effects to what is actually possible by manufacturers.
0.4 Have the database and risk assessment methodology used by FDA during approval of nano-Ag
medical devices been integrated with EPA's database and risk assessment processes?
Participant T
We need to make sure we know what we know before we set research priorities.
There are areas of deep knowledge of silver in medical devices and at EPA.
We might accept a greater risk in a clinical setting than in a consumer population.
Nano-Ag is standard care for infected wounds and we might be able to get more information
about dermal risk from this.
FDA's view on antibiotic resistance is that it is of great concern.
Based on the frequency with which they are approving new nano-Ag devices, we can assume
FDA thinks it is a manageable risk in the medical devices realm.
FDA might be able to say something about growing risk of staph infections and application on
the consumer market.
What happens in the consumer world can affect what happens in the medical world.
There may be a potential to integrate materials for public health applications, such as treatment
of food supplies (e.g., eggs).
EPA disinfectant testing on commercially available disinfectants found that a number of them
are inadequate and do not meet their marketing claims.
We cannot assume that products currently on the market live up to their claims.
N.8 What kinds of exposure do these populations have, including physicochemical characteristics?
Participant U
What kinds of exposures do these populations have?
The exposure leads to dose.
The type of exposure will guide the toxicology studies to focus on the right materials and the
right properties.
N.13 How can the CEA framework be improved to ensure passive or active consumer/occupational
exposure research is completed for nano-Ag and for other nanomaterials?
Participant V
This encompasses what we have all been saying.
2-16
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6.14 What are the short-term and long-term biological responses observed at current nano-Ag
occupational exposure levels as well as consumer exposure levels?
Participant W
We are not just looking at occupational exposure and its health effects, but rather all exposures.
Biological effects capture more subtle effects as well.
2.4. Additional Rounds
The round robin was repeated for additional rounds until all research priorities that participants valued
were posted on the wall.
5.5 Do particular species of biota and particular human populations have greater potential for
exposure to nano-Ag throughout the entire lifecvcle?
Participant A
Recycling and disposal workers might be exposed.
6.33 Can we predict whether widespread resistance to silver ions may develop and if so, are silver
and/or nanosilver likely to be useful antimicrobials in the future?
Participant E
There are advanced methods that should be easily used, readably available, portable, and
cheap.
For the carpet example mentioned earlier, we could have a sniffer that monitors.
Equipment, detection, and monitoring all get back to exposure.
How we measure this outside of the laboratory is really going to be important.
Exposure is the wasteland of risk assessment partly because it is so expensive.
One of the issues I have heard is exposure to academic lab workers.
There is an educational component to the nano issue, and the safety of the researchers is
important.
6.6 At a minimum, what assays could be considered in a harmonized test guideline for
determination of the ecological effects of nano-Ag?
Participant D
This is the same as 6.10, except it is ecological instead of human.
N.14 How do we effectively communicate risk/benefit information for nano-Ag to the general public?
Participant J
The knowledge gap between this group and the general public who will use this knowledge is
huge.
If the public has the perception that ingestion of nano-Ag only leads to discoloration of the skin,
we are not doing our job.
N.5 We need an integrated holistic approach to nano risk assessment. How can we do this?
Participant K
We have plenty of knowledge to pull from (e.g., Chinese traditional medicine).
Experimenting with a holistic approach could be useful.
Western science is a minority in this world, so we could learn from other perspectives.
2-17
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2.21 For the purpose of assessing potential risk, what metrics are most informative for quantifying
exposure and dose of nano-Ag?
Participant L
There might be a misunderstanding that CEA does not encompass exposure.
CEA takes a broad perspective on exposure.
Everyone's exposure needs to be considered and controlled.
N.15 How do we engage citizens and workers in discussions about how nano-Ag sprays are being
used?
Participant N
There is a lack of social science here.
How can we engage citizens and consumers in discussions and decisions about why they are
buying the products and how they are actually using them, which is important to exposure?
Use is often not as intended.
Consumers are a valuable source of information.
The only way to figure that out is to communicate with these people who actually use them.
N.10 How do we educate people about the risks, benefits, and safety related to nano products?
Participant F
Communication, engagement, and education are critical.
When I talk to students in engineering about toxicology, I get resistance.
We need to integrate education and exposure students to safety at the college level.
Comment
Participant M
The term exposure should be clarified, unless exposure is bringing a dose or concentration that
is biologically relevant.
We often tend to speak in shorthand, and we get into trouble with the public.
If there is exposure, that is problematic. Unless that exposure is giving us a dose or exposure
that is biologically relevant, we should avoid scaring people. People already think that because
there is exposure, there is a risk.
Comment
Participant E
Safety in academic laboratories is a big deal.
If a document from EPA to send a message to the research community existed, it would be
helpful.
If we cannot detect it, then we do not know what we are doing.
3.9 Do explosion risks exist for dried nano-Ag powders or nano-Ag powders modified with certain
types of surface coatings?
Participant S
I am concerned about the explosive potential of nano-Ag.
It is a potential acute risk.
2-18
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Comment
Participant V
The way we treat products is pedestrian. People use products and they do not know anything
about them.
We need to get back to the basics and educate our audience. The audience is the consumer and
many are ignorant to the dangers posed.
2-19
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3, Workshop Outcomes
3.1. Prioritized Research Questions
The questions presented in this section are the prioritized research themes resulting from the multi-
voting at the end of the NGT session. These questions were presented in the round robin sessions and
subsumed during the consolidation process. The research/information needs for conducting a CEA of
nano-Ag in disinfectant spray are posed as questions at the end of Chapters 2-6 in the draft case study
(U.S. EPA. 2010b). New questions posed by participants before the workshop were numbered either
sequentially in each chapter following the last original question or, for new questions corresponding to
multiple issues, sequentially beginning with 0.1. New questions posed by participants at the workshop
were numbered sequentially beginning with N.l, based on the position of the flip-chart paper on the
wall, not based on the order in which they were posed. Modifications to existing questions were
designated by underlining edited text. Participants divided into breakout groups prepared 13 reports
(presented in Section 3.2) on the research themes in the list below.
1 - Analytical Methods (120 points, 19 votes)
2.12. Do adequate analytical methods exist to detect and characterize exposure to nano-Ag via soil,
water, and air?
2.10. Do adequate analytical methods exist to detect and characterize nano-Ag in environmental
compartments and in biota?
2.9. Are there standard nano-Ag reference materials that can be used in exposure and effects
testing to aid in comparison of results among investigators?
5.1. Are available methods adequate to characterize nano-Ag concentrations and associated
exposure via relevant matrices such as:
a. air?
b. water?
c. food?
6.10. At a minimum, what assays could be considered in a harmonized test guideline for
determination of the human health effects of nano-Ag?
2 - Exposure and Susceptibility (120 points, 17 votes)
5.17. How do the following parameters affect (1) physiological characteristics, (2) behavior, (3)
lifestages, and (4) susceptibility factors?
N.12. What are the relevant susceptibility factors in terms of exposure?
N.8. What kinds of exposure do these populations have, including physicochemical characteristics?
5.5. Do particular species of biota and particular human populations have greater potential for
exposure to nano-Ag through the life cycle?
5.22. Which source, pathways, and routes offer the greatest exposure potential to nano-Ag for
humans?
3-1
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5.18. What is the distribution of exposure intensities and frequencies of such exposures among
homemakers, children, and maintenance personnel, and are these of concern for acute and or
chronic health effects?
3 - Physical and Chemical Toxicity (115 points, 16 votes)
2.6.b. What physicochemical properties of nano-Ag can be used to: predict toxicity to humans or
biota?
2.5.b. How does surface coating affect toxicity to humans or biota?
6.1. To what extent do particle properties (e.g., size, shape, chemical composition, surface
treatments) determine biological responses to nano-Ag?
2.7. Which physicochemical properties of nano-Ag are most essential to characterize before, during,
and after toxicity experiments?
4- Kinetics and Dissolution (98 points, 15 votes)
N.3. What is the half life of nano-Ag in the environment?
5 - Surface Characteristics (81 points, 14 votes)
2.5.a. How does surface coating affect: the physicochemical properties of nano-Ag?
3.9. Do explosion risks exist for dried nano-Ag powders or nano-Ag powders modified with certain
types of surface coatings?
5.3. What effect, if any, do surface treatments of nano-Ag particles have on:
a. uptake?
b. biopersistence?
c. bioaccumulation?
d. biomagnification?
5.16. What effect, if any, do surface treatments of nano-Ag particles have on human exposures and
uptake?
6 - Sources and Release (76 points, 15 votes)
4.10. How effectively is nano-Ag removed from sewage and industrial process water by wastewater
treatment technology, and can information on the removal of conventional silver be applied to
nano-Ag removal?
3.7. What are the potential exposure vectors by which nano-Ag or nano-Ag by-products could be
released to the environment at the various life-cycle stages?
3.5.a. What are the associated feedstocks and by-products; of these feedstocks and by-products,
which might be released, in what quantities, and via which pathways?
N.4. What are the release rates of all sources of nano-Ag into the environment?
3-2
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7 - Mechanisms of Nanoscale Silver Toxicity (72 points, 11 votes)
6.13. What are the fundamental biological responses to and associated mechanisms of nano-Ag
exposure at the cell, organ, and whole-animal levels?
6.3. Are the effects observed for exposure to nano-Ag due to silver ion release or the presence of
nanoparticles? Can this be distinguished?
8 - Test Methods - Mammals/Humans (67 points, 11 votes)
6.10. At a minimum, what assays could be considered in a harmonized test guideline for
determination of the human health effects of nano-Ag?
2.8. What standardized test methods or characterization protocols are necessary to ensure that
research results generated in multiple laboratories are consistent, reproducible, and reliable?
6.16. Are the current tests for regulatory acceptance relevant to nano-Ag?
Can nano-Ag have impacts on the F-l (next) generation via changes in gene expression
patterns?
9 - Ecotoxicity Test Methods (59 points, 10 votes)
6.6. At a minimum, what assays could be considered in a harmonized test guideline for
determination of the ecological effects of nano-Ag?
2.8. What standardized test methods or characterization protocols are necessary to ensure that
research results generated in multiple laboratories are consistent, reproducible, and reliable?
6.16. Are the current tests for regulatory acceptance relevant to nano-Ag?
Can nano-Ag have impacts on the F-l (next) generation via changes in gene expression
patterns?
10 - Is New Nano Unique? (59 points, 10 votes)
4.6. Does nano-Ag form the same strong complexes with anions as conventional silver, and if so, is it
also effectively mobilized in aquatic environments?
N.7. What are the phys-chem properties of currently available and historic silver products?
N.9. Do nano-Ag products actually offer more efficacy than products currently on the market?
4.1. Do the properties of nano-Ag that differ from those of well-characterized colloidal silver, if any,
cause them to behave differently in aquatic, terrestrial, and atmospheric environmental
compartments?
a. If they do differ, how do they differ?
b. Can information about how colloidal silver behaves in these environments be used to
understand how nano-Ag behaves?
11 - Biological Effects (56 points, 10 votes)
6.8. What are the most sensitive ecological endpoints to nano-Ag exposure?
N.12. What are relevant susceptibility factors (for biological response)?
3-3
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6.14. What are the short-term and long-term biological responses observed at current nano-Ag
occupational exposure levels as well as consumer exposure levels?
5.14. Many effects of emerging substances are not known until many years after their introduction
and use in commerce. What are the chronic and subchronic effects of nano-Ag, and how can
we accelerate our understanding of them? Can nano-Ag have impact on F-l (next) generation
via changes in gene expression patterns?
12- Ecological Effects Required for Risk Assessment (43 points, 9 votes)
6.8. What are the most sensitive ecological endpoints to nano-Ag exposure? Are there sufficient
data/analytical techniques to determine how sensitive specific endpoints and organisms are to
nano-Ag exposure, including:
a. Benthic invertebrates;
b. Marine invertebrates; and
c. Freshwater invertebrates?
6.5. Is the available ecological effects evidence adequate to support ecological risk assessment for
nano-Ag? If no, what research is needed to make an assessment possible?
12- Communication, Engagement, and Education (43 points, 9 votes)
N.14. How do we effectively communicate risk/benefit information for nano-Ag to the general public?
N.15. How do we engage citizens and workers in discussions about how nano-Ag sprays are being
used?
N.10. How do we educate people about the risks, benefits, and safety related to nano products?
N.5. We need an integrated holistic approach to nano risk assessment. How can we do this?
14 - Fate and Transport of Nano-Ag (39 points, 12 votes)
2.6.a. What physicochemical properties of nano-Ag can be used to predict fate and transport in
environmental media?
4.12. How could existing models applicable to conventional silver be used to adequately predict the
transport and fate of nano-Ag through environmental compartments, or how could they be
modified to do so?
14 - Adequacy of Current Data (39 points, 6 votes)
6.15. Do current publications describing the health effects of nano-Ag particles and laboratory-
generated nano-Ag particles accurately depict the toxicity of commercially available nano-Ag
materials?
6.27. Are there any parallels between health effects of conventional silver and those in emerging
studies on nanosilver?
3-4
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16 - Dissolution (36 points, 9 votes)
5.2. What information exists on the temporal changes in the release of ionic silver by nanoparticles
physicochemical and environmental characteristics?
N.ll. What are the rates of dissolution of nano-Ag into the environment?
4.2. Does particle size of nano-Ag affect the rate of release of silver ions in environmental
compartments?
17 - Information from Manufacturers (35 points, 10 votes)
0.4. Has the database and risk assessment methodology used by FDA during approval of nano-Ag
medical devices been integrated with EPA's database and risk assessment processes?
3.3. What are realistic strategies for collecting data on production quantities and product
characteristics given that much of this information is proprietary?
17 - Adaptive Tolerance / Resistance (35 points, 8 votes)
6.33. The majority of toxicity studies with conventional silver were conducted over a decade ago. Are
more studies needed that utilize state-of-the-art technology for comparing its mode of toxicity
to that of nano-Ag? In other words, can we accurately say that nano-Ag and conventional silver
have different modes of toxicity if most of the studies available for conventional silver were not
conducted using current methods?
4.10. Is the nano-Ag harmful to the beneficial organisms in wastewater treatment?
19 - Metrics (33 points, 7 votes)
5.17. How should dose and exposure be characterized for human exposures?
2.21. For the purpose of assessing potential risk, what metrics are most informative for quantifying
exposure and dose of nano-Ag?
20 - Kinetics II (22 points, 5 votes)
2.16. Does nano-Ag react with materials (i.e., organic matter, other metals, polymers) and alter
properties such as REDOX potential or leached metal ion rates?
3.6. What changes occur to the physicochemical properties of nano-Ag throughout the life-cycle
stages, either as a function of process and product engineering or as a function of incidental
encounters with other substances and the environment?
N.l. Does the release of nano-Ag contribute to climate change?
21 - Benefits (9 points, 5 votes)
N.9. Do nano-Ag products actually offer more efficacy than products on the market?
22 - Incentivize Research for CEA (8 points, 1 vote)
N.2. How can we incentivize researchers to focus in on the most critical questions and best methods
for CEA?
3-5
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N.6. How urgent is the need for the benefits offered by the candidate application/material?
23 - CEA Framework (1 point, 1 vote)
N.13. How can CEA framework be improved to ensure passive or active consumer/occupational
exposure research is completed for nano-Ag and for other nanomaterials?
3.2. Breakout Group Reports
Each section below includes the breakout group report for each of the top 13 ranked research priorities,
followed by the group's PowerPoint presentation, and a summary of the plenary discussion that
followed the presentation. Note that the plenary discussion took place after the collective judgment
portion of the workshop and thus served strictly to clarify information or allow observers of the
workshop to express their individual viewpoints. The views expressed in this discussion are those of
each individual and do not necessarily represent the views or policies of the U.S. Environmental
Protection. In addition, because participants incorporated the research priority on human and
mammalian test methods (ranked 8) into the reports for the other priorities, a separate report is not
presented below.
3.2.1. Analytical Methods
Group Members: Participants B, C, and S
3.2.1.1 Group Summary
Original Questions
2.9. Are there standard nano-Ag reference materials that can be used in exposure and effects
testing to aid in comparison of results among investigators?
2.10. Do adequate analytical methods exist to detect and characterize nano-Ag in
environmental compartments and in biota?
2.12. Do adequate analytical methods exist to detect and characterize exposure to nano-Ag via
soil, water, and air?
5.1. Are available methods adequate to characterize nano-Ag concentrations and associated
exposure via relevant matrices such as: a) air?, b) water?, and c) food?
Ideas Discussed
Instrumentation vs. methods vs. ensemble techniques.
Methods to measure exposure vs. concentration in tissue.
Stress the need for broad availability of "reference materials."
Nowhere in the above questions is the word "properties" mentioned (need to know what the
properties are to develop analytical methods).
Analytical methods for surfaces of nanoparticles are very limited; this is worrisome given the
importance of the surface in so many of the other areas discussed; current methods focus on
characterization of bulk surfaces or sufficiently large "clusters" of nanoparticles.
Reference materialsavailability of standard methods for analysis of reference materials
(tolerance levels have not been not established)
3-6
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Other questions to consider:
2.6. Which physicochemical properties of nano-Ag can be used to:
a. predict fate and transport in environmental media?
b. predict toxicity to humans or biota?
2.7. Which physicochemical properties of nano-Ag are most essential to characterize before and
during toxicity experiments?
2.8. What standardized test methods or characterization protocols are necessary to ensure that
research results generated in multiple laboratories are consistent, reproducible, and reliable?
2.13. What new analytical methods would enhance characterization of nano-Ag particles?
2.17. How can engineered nano-Ag particles be routinely, inexpensively detected, monitored, or
distinguished from incidental, background, or naturally occurring nano-Ag particles?
Viewpoints:
We need to know the metrics in order to focus on developing/refining the analytical methods.
Near-term - integration of existing techniques and instrumentation into
standardized/verifiable/reproducible methods for characterization of nanoparticles in diverse
media (e.g., air, suspension, complex waters, biological tissue, soils/sediments).
Long-term/high-risk research area - continue focus on developing rapid, inexpensive, routine
analysis.
Quantitative vs. qualitative for all metrics, not just concentration.
General techniques applicable to a range of materials are possible, but will require tuning for
specific materials.
Why is this research theme of high importance?
Without analytical methods, one cannot:
Measure/determine exposure.
Determine sources of release.
Establish linkages between properties and toxicological or other effects.
Evaluate fate/transport.
Adequately characterize products (maybe more on the manufacturer side?).
Accurately track/compare historic, current, and future levels in various biological/environmental
compartments.
Where does this research theme fit within the CEA process?
Note: Measurement and Characterization bar spans all sections (vertically)
Lifecycle Stages - for example, comparison of product changes (e.g., leaching) throughout life
cycle.
3-7
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External Factors - for example, changes in properties under varying environmental, biological
conditions; changes in surface characteristics attributable to co-occurring substances.
Environmental Compartments and Gateways - enables determination of presence and form in
varying compartments including wastewater.
Organisms - evaluation of uptake, toxicity, partitioning.
Ecosystems - partitioning in aquatic/terrestrial compartments, potential for bioaccumulation,
etc.
Effects - there is no way to arrive at accurate evaluation of effects without the above.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
Enable the generation and verification of accurate data on, for example, lifecycle effects and
interactions of nanoparticles with external environmental factors, organisms, and ecosystems,
to inform the determination of effects and ultimately the estimation of risks.
Need analytical methods to link properties to outcomes.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
In general, each question under this theme is relevant to 1, 2, and 3. One major area of distinction,
however, is that the adequacy of existing analytical techniques varies based on the composition of the
particular material:
1. Metal-based nanoparticles (e.g., certain quantum dots, Ag, Au, rare metallic)
2. Ubiquitous metal-based nanoparticles (e.g., iron oxide, zinc oxide)
3. Carbon-based nanoparticles (e.g., fullerenes, tubes)
Applications dictate the extent to which multiple techniques and analytical approaches must be
integrated. For example, additional extraction/preparation techniques might be required depending on
the nature of the matrix in which nano-Ag is incorporated.
Major question: How do preparation techniques alter nano-Ag properties? For example, preparation of
biological tissue for transmission electron microscopic analysis requires many steps, chemical reagents,
that can interact/alter nanoparticle properties.
Major need: techniques to characterize particles in their native state and minimize artifacts.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Limitations of instrumentation
Surface analysis of nanoparticles
"Rapid, field-portable" is nice, but not really in the lexicon right now (or in the near future).
Cost of equipment, analysis, availability of funding for under-represented groups (e.g., social
groups)
3-8
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Training of personnel to operate equipment, perform measurements
Agreement on properties to measure
Maintenance expense - "$1M dollar paperweight" (non-functioning equipment)
Need for grants to provide:
Analytical equipment/training to those who need them
Maintenance/support of analytical equipment
Training/support of personnel
Accessibility of instruments/time
Availability of reference materials
Cost
Dissemination
Objectivity (when given commercial suppliers)
Long-term availability of reference material
Chicken/egg scenario - need field studies to inform analytical methods; need analytical methods
to conduct field studies
Practicality of regulations - Policy decisions, threshold limit values, and water quality criteria will
be developed based on the capabilities and results of analytical methods
Asbestos example - "no particles." Can we measure that? (no analytical method to reach
0%)
Perchlorate - measurements are more sensitive than where effects have been shown
How are the research questions under this theme related to other top priority themes or questions?
Theme
No.
Theme/Question
Does Theme Relate
to Analytical
Methods?
Example of How Analytical Methods
Relate to Other Theme
2
Exposure and Susceptibility
yes
e.g., allows us to quantify exposure
3
Phys Chem Tox
yes
e.g., allows the establishment of linkages
between properties and tox
4
Kinetics
yes
e.g., permits determination of time-
dependent changes in particle properties
5
Surface Characteristics
yes
e.g., evaluate changes in surface
composition
6
Sources and Release
yes
e.g., identify sources and chemical form,
and transformations of chemical form
7
Mechanisms
yes
e.g., particle vs. ionic species
8
Test Methods (Humans)
no
9
Test Methods (Ecological)
no
10
Is new nano unique?
yes
e.g., determination of novel properties for
nano-Ag relative to bulk or ionic forms
3-9
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Theme
No.
Theme/Question
Does Theme Relate
to Analytical
Methods?
Example of How Analytical Methods
Relate to Other Theme
11
Biological Effects
yes
e.g., determination of bio exposure levels;
quantification of concentration
12
Eco Tox
yes
e.g., determination of eco exposure levels;
quantification of concentration
13
Communication, Engagement,
and Education
yes
e.g., training personnel to perform a
methods appropriately
14
Fate and Transport
yes
e.g., determine changes in form, chemical
interactions
15
Adequacy of Current Data
yes
e.g., must be able to compare the
appropriateness of methods used
16
Dissolution
yes
e.g., evaluate release of ions, changes in
particle structure
17
Info from Manufacturers
yes
e.g., must know what properties to
measure and how to measure them
appropriately; could reduce disconnect
between supplier and independently
determined specs
18
Adaptive
Tolerance/Resistance
no
19
Metrics
yes
e.g., quantify dosimetry
20
Kinetics II
yes
e.g., evaluate interactions and changes
occurring at various stages of the product
lifecycle
21
Benefit
no
22
Incentivize research for CEA
no
23
CEA framework
no
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Allow us to identify and quantify what is present in a particular compartment
Quantify exposure
Permit monitoring over time
Identify potential sources of release
Facilitate management (e.g., wastewater treatment, recovery from certain processes)
Improve accuracy of risk assessments
Identify byproducts and transformation products (if we know how it looks now, we can better
identify how it has changed through a particular process).
3-10
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3.2.1.2 Group Presentation Slides
Short Description of Priority Theme:
Accurate, reliable, and verifiable analytical methods are needed for the determination of
physicochemical properties of nano-Ag in a range of environmental matrices and at varying
points throughout the lifecycle of nano-Ag.
These methods are essential to investigate all of the themes/elements of the CEA framework
and their linkages (Exposure/Dose -> Effects).
Why is this research theme of high importance?
Without accurate, reliable, and verifiable analytical methods, we cannot:
Characterize products (e.g., manufacturer specifications)
Make comparisons among different investigators, labs
Measure/determine exposure
Determine sources of release
Establish linkages between properties and effects
Evaluate fate/transport
Accurately track and compare historic, current, and future levels in various
biological/environmental compartments.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Allow us to identify and quantify what is present in a particular compartment
Quantify exposure
Permit monitoring over time
Enable identification of potential sources of release
Facilitate management (e.g., wastewater treatment, recovery)
Improve accuracy of risk assessments
Identify byproducts and transformation products.
3.2.1.3 Presentation Motes
Presenter: Participant S
Establish linkages between different aspects of the CEA and physicochemical properties
Establish accuracy of physicochemical characterization
Without these methods, cannot characterize products
Determine sources of release
Need well developed methods
3-11
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Evaluate fate/transport
Need to characterize particles at one point in transport chain or else we do not know how it
might transform
Developing analytical methods allows us to go back to previous studies where methods were
not as robust
Monitoring over time - so we know how levels are changing over time
3.2.1.4 Questions and Answers
Participant G: Reference materials fell off the table - even though OECD has some reference
materials, there is a role for reference materials in different matrices.
Answer: Comes back to verifiability. NIST provides some reference materials, but
availability and awareness of those materials needs to improve.
Participant E: Routine availability of these systems and methods and mobilizing them into the
field is critical. If we don't have that, we won't be able to test these materials.
Answer: I wonder if these techniques or devices will be available in my lifetime because
geochemistry has been using TEM and EDX for many years and they've never progressed to
where they can be used in the field. A couple can, like Raman scattering, are hand held.
Question: Geochemistry has a timeline that doesn't suit commercially available products.
Consumer products push the technology. If we don't explicitly ask for cheaper, more reliable,
portable technologies, we won't get it.
Answer: We feel there is value in ensemble techniques. We laid out near-and long-term
priorities. Long term would be innovative development for small research grants.
Participant G: There may be someone who can develop something affordable for silver, but
until that need is articulated, we will not get it.
Participant B: Our plans and projects have a timeline. Technical difficulties of analyzing and
estimating nano-Ag in consumer products are that there is the matrix. We need a method
of simple preparation to remove the nano-Ag from the matrix. We need less about the
instrumentation and more about the preparation of samples. Accessibility to
instrumentation is one thing, but we also need a protocol of what we want to see in those
products.
Participant R: The equipment to do this would take up a quarter of the room and they want it to
be much smaller. There has to be another revolution in technology to do this for nanomaterials
and we are not ready to do that. They can do it on a large scale, but smaller scale, no.
Participant P: I work a lot in this. It is not always necessary to have portable technologies.
This large technology is very effective. You can successfully transport samples to the lab and
to these instruments. We have the technology to do this stuff, but they are not field
portable.
3-12
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3,2.2. Exposure and Susceptibility
Group Members: Participants L, N, V, and W
3,2.2.1 Group Summary
Short Description of Priority Theme:
Based on our theme, exposure and susceptibility, the following questions were deemed necessary to
answer before completing a CEA:
What is the distribution of exposure intensities and frequencies of such exposures among
occupational and consumer populations and susceptible groups such as women of childbearing
age, children, maintenance workers, and other groups for acute and chronic health effects?
How do the parameters of physiological characteristics, behavior, lifestage, and genetic factors
influence the design and the hypotheses to be tested for nano-Ag exposure?
How do the physical and chemical properties of nano-Ag influence the kinds of exposures
experienced by individuals or populations?
What are the appropriate measurement and modeling metrics that should be used to
characterize exposure?
Which sources, pathways, and routes throughout the lifecycle offer the greatest exposure
potential to nano-Ag for humans?
Why is this research theme of high importance?
Production and use of more than 500,000 kg of nano-Ag-containing materials per year can lead
to human contact with nano-Ag across lifecycle stages. Thus, many human populations will be
exposed to nano-Ag throughout their lifetimes.
Because few research studies and occupational measurements have been conducted and
published, little is known about which populations are exposed, the magnitudes of these
exposures, and the factors that affect the exposures.
The lack of exposure information, especially in light of the growing hazard knowledge base, is
limiting the ability of the Agency to complete a balanced CEA for eventual application to risk
assessment.
Where does this research theme fit within the CEA process?
At the present time, the characterization of human environmental and occupational exposure is not
explicitly mentioned within the CEA framework. This must change because the topic of exposure and
the routes of exposure (inhalation, dermal, and ingestion) are central to the CEA. To accomplish this,
the current CEA Framework needs a box below environmental compartments and gateways, and above
organisms that explicitly define exposure characterization.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
Answering these questions will provide information for half of the equation required to complete a
quantitative assessment of human risk. Because risk, in its simplest terms, is equal to hazard x
exposure, and most of the currently available knowledge relates to hazard, the quantitative
3-13
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characterization of exposure among susceptible populations and the general public is required
immediately.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
As we now envision the uses of nano-Ag and other nanomaterials within commerce and manufacturing
and the remaining components of a product's lifecycle, the characterization of human exposure is
required. For all nanomaterials, however, the spectrum of potential human exposure can change based
on application, use, and lifecycle stage. Thus, the characterization of the distribution and intensity of
exposure is required for nanomaterials in general.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Technical challenges:
Personal sampling (i.e., inhalation, dermal, and ingestion) and microenvironmental sampling
tools are needed for appropriate metrics for nano-Ag (e.g., size, number, shape, surface, mass).
Tools are needed for conducting biological marker measurements of exposure to the skin and
eye, and for bioaccumulation or transport in the blood and urine. These markers should
include, where necessary, the inhalation, dermal, or ingestion routes of exposure.
The susceptible and user populations that would make up the pool of subjects for a quantitative
exposure characterization need to be defined.
Social:
Gaining access to workplaces to conduct workforce identification and exposure measurements.
Gaining access to information on parent and product nano-Ag characteristics to design an
exposure study properly.
Focusing the manufacturers and the commercial interests on the value and benefits of
completing quantitative exposure assessments for products that contain nano-Ag before they
are:
generally distributed to the public (consumer and users)
produced, that is, during the design of a production process
released and then placed in a waste stream.
Policy:
The lack of clear regulatory guidance on workplace or personal product exposure limits for
exposure management.
Provide public health and environmental agencies with the resources and capacity to assess
consumer and environment exposures to nano-Ag.
Provide occupational health agencies with the resources and capacity to assess consumer and
environment exposures to nano-Ag.
Provide the mechanisms for funding exposure characterization projects on nano-Ag.
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How are the research questions under this theme related to other top priority themes or questions?
For Highest priority Topics 1-7: Analytical Methods, Surface Characteristics, Sources and
Release.
Biological Effect, Communication, Engagement and Education, Fate and Transport.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
The characterization and assessment of exposure are necessary prerequisites to the implementation of
exposure controls or application of techniques to prevent consumer contact with nano-Ag that could
result in relevant health effects. Once workers are handling nano-Ag-containing materials and products
are released into commerce, exposures will occur. If exposures are high in intensity, duration, or
frequency, they could lead to health effects that are not traditionally covered in conventional toxicology
studies. Thus, minimizing the potential for exposures early in product development will minimize the
potential for unintended consequences.
3.2.2.2 Group Presentation Slides
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3-15
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Exposure distributions among occupational and consumer populations and susceptible groups
Effects of physiological characteristics, behavior, lifestage, and genetic factors.
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Effects of physical and chemical properties of nano-Ag on exposure.
Appropriate measurement and modeling metrics.
Sources, pathways, and routes throughout the lifecycle that lead to the greatest exposure
potential?
Importance of Research Theme
Many human populations will be exposed to nano-Ag-containing materials throughout their
lifetimes.
Because few research studies and occupational measurements have been conducted and
published, little is known about which populations are exposed, the exposure magnitudes, and
the factors that affect exposures.
While hazard knowledge base is LARGE, exposure knowledge is small. This limits the ability to
complete a balanced CEA and risk assessment.
Reducing Chances of Unintended Consequences
Identifying populations of interest and key exposure routes can help identify appropriate
management and control measures.
This will help minimize exposures and thus, health impacts.
3,2,2.3 Presentation Motes
Presenter: Participant W
Exposure is on the left-hand column of the CEA framework, but we couldn't find it in the boxes.
It is perhaps implicit in the arrows, but it should be explicit.
We created a box for exposure.
Start with sources, pathways, various compartments and media, exposure routes,
populations and susceptible groups within those populations, the effects.
Exposure metrics - challenges
What are the appropriate metrics?
How to do personal sampling?
What biomarkers are relevant?
Key research areas
Exposure distributions, frequency, magnitude in occupational and nonoccupational and
susceptible groups
Relevant matrices
Effects of physiological characteristics
Effects of physical/chemical properties on magnitude of exposure
Modeling is essential part of exposure/susceptibility assessment
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Many human populations will be exposed to nano-Ag throughout their life and lifecycle of the
materials.
There are few studies of compliance and noncompliance, so we know little about exposure and
exposure distribution.
There is about a 5:1 ratio of hazard to exposure research.
To balance CEA, we need to correct above imbalance.
To reduce the chances of unintended consequences, we must identify the populations of
interest and the key exposure routes. We can then identify appropriate ways to minimize
exposure and impacts.
3,2,2.4 Questions and Answers
Participant L: We want to emphasize that we did not consider nonhuman populations.
Participant G: For exposure, is it best to focus on the 1- to 100-nm size range?
Participant W: No, I don't think so, personally. Particles can agglomerate to form larger
entities, but they might still retain some nano-sized features. Or they can be inhaled in
agglomerated form and they could disaggregate. I think we should also look at larger
particles up to a few nanometers.
Participant N: This is sort of a chicken/egg question. If there is a suspicion that there are
nanomaterials, what size are people exposed to? We do not even know the size of the
particles in the product. We couldn't say whether to concentrate on 1-100 until we look
and see what is actually in the product.
Observer 1: Looking at women of childbearing age - are they more exposed or are you thinking
of it from an effects standpoint?
Answer: These products are designed to be used in the home, so we thought their exposure
patterns might be different from a working adult.
Participant L: One member felt susceptibility could not be teased out from exposure.
Observer 2: You focused on humans - is it an intentional prioritization that it was more
important to focus on humans or just based on the people in your group?
Participant L: It was definitional. Exposure is a term you use for humans, whereas you use
concentration for other organisms, so I could not rebut that from a technical standpoint.
Participant N: There was some controversy. I think nonhuman exposures are important and
I don't see human exposures as separate from those in the environment. It was somewhat
an issue of time, so we decided that exposure to humans via fish and biota would be
covered in our pathways.
Participant W: It was definitional - the way the discussion had progressed up to that point.
When we come to human populations, we are talking exposure. When we talk about biota
we are talking about concentrations in them (tissue concentrations), and we felt that would
be covered in ecotox.
Participant M: That really is naive - exposure is used all across the ecotox arena. It is true there
are tissue concentrations, but how do they get there?
3-18
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Participant A: I agree it is not just humans. I think you missed a susceptible population -
immunocompromised individuals. They might use these products more often and use them in
the home.
Participant W: I think we will add that-that is a great point.
Participant W: One more point on exposure to biota. One group member used to be editor
of Exposure Science Journal, and that is all human, not eco.
Participant A: I did not see much on dosimetry. One of the big issues is what is our dose metric?
Traditionally we look as mass, which is not appropriate for nano. For immunocompromised
individuals, it might be particle numbers that affect them - based on mass, there is a huge
difference in particle number and surface area.
Participant W: We talked about exposure metrics, which include those issues. It was more
in the modeling part - modeling metrics - and no one has specifically talked about doses of
nanomaterials in humans - it is a modeled entity. That will be captured in biomarkers
where we will be monitoring something.
Participant Q: Assessing exactly what people will be coming in contact with - FDA did a survey
on 300 products on the market. We contacted suppliers and asked what the form of silver in
the product was. About 75% of the companies said it is a powder and looks like dust. I don't
think the suppliers of applications going to consumers even know what they are using. We will
need to go to source of the suppliers and then make sure the suppliers are using the materials in
the way it is intended.
Participant W: Access to parent material or product is a challenge - social challenge.
3,2,3. Physical and Chemical Toxicity
Group Members: Participants F, P, and Q
3.2.3,1 Group Summary
Short Description of Priority Theme:
These areas focus on linkages between specific physicochemical properties and toxicological effects.
This theme represents a cross-section among different disciplines seeking to integrate different levels of
theory into a comprehensive environmental assessment. Physicochemical properties (e.g., surface
coatings, surface charge, size, shape, chemical composition) of nano-Ag (and other nanoparticles) can be
used to predict toxicity to humans and biota. This theme also captures specific endpoints in which
nanoparticle characterization is important before, during, and after toxicity experiments.
Why is this research theme of high importance?
Physicochemical characterization:
Allows for an interdisciplinary and multidisciplinary approach
Requires competencies in biology, chemistry, physics, ecology, geochemistry, and toxicology
Represents a transitional and influential field. It is similar to the principles that govern
technology transfer.
Improves particle biocompatibility through an iterative material design process
3-19
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Demonstrates details in the interactions (e.g., effects, uptake, transport) between particles
and biological systems, representing opportunities to optimize particle design for novel
application
Provides an opportunity to improve on past research and development
Compels the environmental and toxicology communities to deal with solid-phase chemistry
Encourages chemists and physicists to consider the impact of engineered materials and
products
Where does this research theme fit within the CEA process?
The CEA should reflect the chemical and physical properties of the particles at every stage lifecycle. The
CEA should capture the physical and chemical properties of the particle at each stage of the lifecycle and
should correlate with the route of exposure and dosing concentration. The CEA should link the physical
and chemical properties of the particle to each potential toxic effect at the sub-individual, individual,
population, and ecosystem levels.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
Using models to predict toxicity:
Knowledge Gap: Marry fundamental physical/chemical models with the empirical toxicology
models and decision-based sciences.
Expected Results: The resultant model or models must ultimately talk to, feed, and relate to
each other.
Effects of Surface Coating:
Knowledge Gap: Surface coating represents a modification of the behavior of the pristine
particle and might represent a further modification of the properties and a potentially different
particle in CEA.
Expected Results: Potential surface modification of nanoparticles can have an effect on the
physiological and biochemical responses to the particle.
Effects of Other Particle Properties:
Knowledge Gap: There is a need to tease out the weighted contributions of each feature, e.g.,
size, shape, chemical composition, and surface charge, to their biological response and the
integration of these properties.
Expected Result: Effect = A(size)+B(shape)+C(chemical composition)+D(surface charge).
Characterization and re-characterization in the experiment design:
Knowledge Gap: Some of the best published papers that focus on the fate of a particle are
when the researchers track the nanoparticle throughout the toxicity study and map the results
in terms of accumulation and speciation.
Expected Result: Inclusion of particle characterization before and after the toxicity study will
enhance the accuracy within the assessment.
3-20
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For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
For all four research questions, physicochemical characterization is necessary to specific applications of
nano-Ag, all applications of nano-Ag, and all applications of nanomaterials in general.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Technical challenge: separating the dissolved silver from particle silver and what the effects of the
different species are.
Policy challenge: at the different stages of experimentation, complete chemical/physical
characterization is prohibitively expensive.
Social challenge: explaining how the different methods and instrumentation work and the information
they provide.
How are the research questions under this theme related to other top priority themes or questions?
Physical/chemical characterization provides a fundamental understanding of the nanomaterial. A
fundamental understanding of the nanomaterial is necessary for all of these other top priority themes:
Test methods development for human and mammalian systems
Test methods development for ecological systems
Test methods development for analytical methods
Surface characteristics
Ecological toxicity
Fate and transport
Mechanisms
Biological Effects
Is nano unique
Kinetics I
Kinetics II
Exposure/Dose
Exposure/Susceptibility
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Physicochemical characterization strengthens the nanomaterial iterative design process that represents
an inherent proactive approach designed to reduce the chance of unintended consequences through
guided, environmentally sustainable nanotechnologies. Coupling physical/chemical properties with
ecotoxicological and human health effects provides specific information to developers with respect to
needed modifications of the materials.
3-21
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3.2,3,2 Group Presentation Slides
Short Description of Priority Theme:
These areas focus on linkages between specific physicochemical properties and toxicological
effects.
This theme represents a cross-section among different disciplines seeking to integrate different
levels of theory into a comprehensive environmental assessment.
Physicochemical properties (e.g., surface coatings, surface charge, size, shape, chemical
composition) of nano-Ag (and other nanoparticles) can be used to predict toxicity to humans
and biota.
This theme also captures specific endpoints in which nanoparticle characterization is important
before, during, and after toxicity experiments.
Why is this research theme of high importance?
Physicochemical Characterization
Allows for an interdisciplinary and multidisciplinary approach
Requires competencies in biology, chemistry, physics, ecology, geochemistry, and toxicology
Represents a transitional and influential field. It is similar to the principles that govern
technology transfer
Improves particle biocompatibility through an iterative material design process
Demonstrates details in the interactions (e.g., effects, uptake, transport) between particles
and biological systems, representing opportunities to optimize particle design for novel
application
Provides an opportunity to improve upon past research and development
Compels the environmental and toxicology communities to deal with solid-phase chemistry
Encourages chemists and physicists to consider the impact of engineered materials and
products
Using Models to Predict Toxicity
Knowledge Gap: Marry fundamental physical/chemical models with the empirical toxicology
models and decision-based sciences.
Expected Results: The resultant model or models must ultimately talk to, feed, and relate to
each other.
Effects of Surface Coating:
Knowledge Gap: Surface coating represents a modification of the behavior of the pristine
particle and might represent a further modification of the properties and a potentially different
particle in CEA.
Expected Results: Potential surface modification of nanoparticles can have an effect on the
physiological and biochemical response to the particle.
Effects of Other Particle Properties:
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Knowledge Gap: There is a need to tease out the weighted contributions of each feature, e.g.,
size, shape, chemical composition, and surface charge, to their biological response and the
integration of these properties.
Expected Result: Effect = A(size)+B(shape)+C(chemical composition)+D(surface charge).
Characterization and Re-characterization in the Experiment Design:
Knowledge Gap: Some of the best published papers that focus on the fate of a particle are
when the researchers track the nanoparticle throughout the toxicity study and map the results
in terms of accumulation and speciation.
Expected Result: Inclusion of particle characterization before and after the toxicity study will
enhance the accuracy within the assessment.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Physicochemical characterization strengthens the nanomaterial iterative design process that
represents an inherent proactive approach designed to reduce the chance of unintended
consequences through guided environmentally sustainable nanotechnologies.
Coupling physical/chemical properties with ecotoxicological and human health effects provides
specific information to developers with respect to needed modifications of the materials.
3.2.3.3 Presentation Motes
Presenter: Participant F
I wonder if we can predict potential toxicities by measuring physical/chemical properties and
using them in modeling.
Focus on the link between physical/chemical properties and biological effects.
This has been an issue since the beginning.
It is a cross-section among several disciplines, integrating several levels of theory.
Let us characterize nanomaterials and let us characterize the cells before exposure, during
exposure, and after exposure. Can we move toward recapturing the nanomaterials?
Physical/chemical properties are the key in toxicological research, allowing for a
multidisciplinary approach.
It is a transitional field, an iterative process.
It forces the environmental scientist and toxicologist to learn solid-state physics and engineers
to consider impacts.
Using models - mathematical or experimental - to predict toxicity: We would expect results of
the models to "talk" to each other. There are existing models, but the research opportunity is in
integrating models from different disciplines. How can some model data influence upstream or
downstream models?
Effects of surface coating - modification of behavior of particle and possible modification of
properties: This might make it a different particle in terms of the CEA - ions, particle, or
composite material?
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Other particle properties - weighted contributions of physical/chemical properties, properties
from what we know from the literature: Weight size heavily if it is more important, but don't
exclude other properties because some of it is synergy.
Characterization and re-characterization are issues.
We can reduce unintended consequences through guided technologies.
3,2,3.4 Questions and Answers
Participant G: Your list of properties did not include surface area.
Participant F: For what we were talking about, we might be most used to looking at
particles in a suspension or a complex matrix, and it is difficult for us to measure surface
area - we can calculate it - but I rely on other properties that I can measure.
Participant P: We normalize surface charge by surface area, called specific surface charge.
3,2.4. Kinetics and Dissolution
Group Members: Participants G, I, T, and U
3,2.4.1 Group Summary
Short Description of Priority Theme:
The research questions are the following:
What is the half-life of nano-Ag in the environment?
What are the rates of dissolution of nano-Ag in the environment?
Do nanoparticles react with other materials (e.g., organic matter, other metals polymers) and
alter properties such as redox potential or leached metal ion rates?
What information exists on the temporal changes in the release of ionic silver by nano-Ag in
relation to particle physicochemical and environmental characteristics?
Does the particle size, source, or agglomeration state affect the rate of release of silver ions in
environmental compartments?
Why is this research theme of high importance?
The question we must answer is: What is the persistence of nano-Ag in the environment?
Environmental persistence is a function of the physical and chemical characteristics of nano-Ag. In this
research area, we must consider all the possible mechanisms of transformation in soil, water, and air:
Dissolutions - Redox chemistry
Passivation
Coagulation
Growth
Binding to humic substances in soils and water
Deposition onto surfaces
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Secondary effects of nano-Ag reactivity.
The speciation that occurs on these physical and chemical transformations establishes relevant test
materials, exposure, toxicology, and measurement methods.
Where does this research theme fit within the CEA process?
This theme fits within the environmental pathways and fate and transport. The pollutant is partitioned
to the environmental compartments and is affected by external factors. This, in turn, affects its physical
and chemical transformations and ultimately its toxicological and ecological effects.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
For this CEA, we need to accurately predict concentrations of nano-Ag and its reaction products. Failure
to accurately identify relevant silver species in the environment will result in unproductive research
activities in exposure, toxicology, development of test methods, and risk assessment.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
Knowledge of the chemical and physical transformation mechanisms of nanomaterials is key for
understanding the exposure, dose, and toxicity of all engineered nanomaterials in the environment.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
One of the most important technical challenges is measurement technology to measure nano-Ag as it is
transformed. Although a mass spectrometric method has been developed for air studies and
microscopy has been utilized for condensed-phase studies, better methodologies might be needed to
accurately measure chemical and physical transformations.
A resulting policy challenge is the emphasis from federal agencies to prioritize chemical and physical
transformations of nano-Ag and other nanomaterials. Of particular concern is the timing of the research
programs. Because the relevancy of other programs depends on the results of this and the
measurements research, positioning the research is a particular challenge.
Again, because the other research questions of exposure, dose, toxicology, and effect depend on testing
the correct materials in the proper physicochemical form, it is imperative that the chemistry community
communicate these results to the researchers undertaking these endeavors. What is more, EPA should
be proactive in their call for research as to what is known about the physicochemical properties of nano-
Ag and its products as they exist in the environment.
How are the research questions under this theme related to other top priority themes or questions?
Analytical methods - Analytical methods need to be developed for proper identification of
nano-Ag and its transformation products.
Exposure and susceptibility - The kinetics determine what the exposure concentration of all
nano-Ag species will be.
The physical and chemical properties on toxicity - The kinetics determine what the physical and
chemical properties of nano-Ag species will be.
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Surface characteristics - The kinetics determine what the physical and chemical properties of
nanomaterials and the daughter species will be.
Sources and release - Oxidation and dissolution are sources of active silver species in
environment compartments.
Biological Effects, Ecological Toxicity, and Mechanisms of Toxicity-The kinetics determine the
oxidation state of the silver which can then act as a toxicant.
Human and Ecology Test Methodologies - Researchers should be aware of the transformations
of nano-Ag to design proper test methodologies.
Is new nano unique? - Data and risk assessments for existing and historical "colloidal" silver can
inform our understanding of chemical and physical transformations of nano-Ag.
Communication - Researchers in other fields should have an appreciation of the time factor
between sources and exposure.
Fate and Transport - A feedback needs to be established between modelers and
experimentalists on the chemical and physical transformations of nanomaterials.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Answering these research questions will inform proper experimental conditions for exposure and
toxicity studies. There are connections between the persistence of nano-Ag and the type of coating of
these particles. Thus, lifetimes of nano-Ag might be extended from seconds or minutes to months or
years.
3.2.4.2 Group Presentation Slides
Short Description of Priority Theme:
Knowledge of the physical and chemical transformations of nano-Ag is crucial for productive
research activities in exposure, toxicology, development of test methods, and risk assessment.
Why is this research theme of high importance?
What is the persistence of nano-Ag in the environment?
Environmental persistence is a function of the physical and chemical characteristics of nano-Ag.
We must consider the possible mechanisms of transformation
Dissolutions - Redox chemistry
Passivation
Coagulation
Growth
Binding to humic substances in soils and water
Deposition onto surfaces
Secondary effects of nano-Ag reactivity
In air, water, and soil:
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The speciation that occurs as a result of these physical and chemical transformations establishes
relevant test materials, exposure, toxicology, and measurement methods.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
For this CEA, we need to accurately predict concentrations of nano-Ag and its reaction products.
Failure to accurately identify relevant silver species in the environment will result in
unproductive research activities in exposure, toxicology, development of test methods, and risk
assessment.
3.2.4,3 Presentation Motes
Presenter: Participant U
Nanomaterials are designed to be more reactive - quantum effect, increased surface defects,
etc.
When released to atmosphere, water, or soil, they will react.
Knowledge of reaction pathways is crucial for productive research activities.
Exposure, tox, test methods, and risk assessment - all need a kinetics base.
Persistence
Size, surface coatings, and physical/chemical properties are important.
Need to consider all reaction pathways in all compartments.
Dissolution - Take silverO and put it in water, it will be a long time before it dissolves. If you
have nano-Ag in water with some ionic strength, some material will be adsorbed onto the
surface of the nano-Ag and will take an electron away in a redox reaction. One question
was: Does size make a difference for dissolution chemistry? Yes. As they get smaller,
atoms are mostly on the surface.
Complication - if you start with 20-nm nano-Ag, it starts to dissolve; now you have more
atoms on the surface and the reaction or dissolution rate will increase.
There are many different pathways in which it can react - it can form silver sulfide, can
grow, can bind to humic substances (making it more bioavailable), deposit onto surfaces,
etc.
We need to know what happens between sources and exposure.
Plot: y-axis is nano-Ag concentration and x-axis is time. Over time, nano-Ag starts to react
away. Over time, reaction products increase. This is just reaction time independent of when a
system is exposed. On a short time scale, you want to measure the properties of one mixture,
and at the other, you want to measure the properties of another mixture.
It is crucial to understand what happens between sources and receptors.
Failure to assess kinetics will result in unproductive research.
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3.2,4,4 Questions and Answers
Participant F: Playing the Devil's advocate - for risk assessments of things we feel comfortable
understanding, these molecules change over time. So certainly established risk assessment
methods are used to look at, say, PFOA. The effects of time and transformation have been
considered to the extent that they have already occurred. If these established risk assessments
are not taking this transformation into consideration already, then we have a bigger problem
than nano.
For risk assessors, they run these pollution models to understand how these chemicals change
over time and how people will be exposed, based on thousands of kinetics studies.
Participant I: In my opinion, that perspective is right. In ordinary assessment of chemicals,
the daughter products should be considered.
Participant A: It is true for many pesticides; they do include metabolites, so that is considered
for many compounds going into the human body. This is not considered as a must for
environment, but it is taken into account for some chemicals. If it goes into food, you look at
compounds and metabolites. It might mostly be an issue for environmental effects.
Participant U: You look at metabolites, but the rates are not there, so that is important.
3,2.5. Surface Characteristics
Group Members: Participants C, G, S, and V
3.2.5.1 Group Summary
Short Description of Theme:
How does the surface coating affect the physicochemical properties of nano-Ag?
What effect, if any, do surface composition and surface treatments of nano-Ag particles have on
a) human exposures and uptake, b) biopersistence, c) bioaccumulation, d) biomagnification, and
e) other biological and environmental processes?
Why is this research theme of high importance?
Surface characteristics, for example, composition, coatings, treatments, passivation,
morphology, surface charge, surface area, can affect the behavior of nano-Ag as it moves away
from the source towards some receptor.
Surface characteristics can affect uptake and biological response.
Where does this research theme fit within the CEA process?
Surface characteristics can modulate the distribution, transport, and fate of nano-Ag as it moves
through the lifecycle stages.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
A better understanding of the surface characteristics of nanomaterials will reduce the uncertainty in
establishing the relationship of how the nano-Ag product will affect or be affected by the various
processes associated with the CEA.
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For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
Research questions regarding surface characteristics are relevant to nanomaterials in general.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Surface characterization of nanoparticles in their native state is a challenge because of current
instrumental limitations with respect to spatial resolution, sensitivity, detection limits, etc., and a lack of
standardized methods for sample preparation and characterization.
How are the research questions under this theme related to other top priority themes or questions?
Top 7 Priorities: Analytical Methods, Exposure and Susceptibility, Chem-Phys-Tox, Kinetics,
Biological Mechanisms.
Second 7 Priorities: Is New Nano Unique, Biological Effects, Fate and Transport.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Products having poorly understood surface characteristics can lead to exposures that were
unanticipated with consequential unintended effects on ecosystems. A better understanding of surface
characteristics can force reconsideration of how nano-Ag is applied in a product.
3.2.5.2 Group Presentation Slides
Short Description of Priority Theme:
How does the surface coating affect the physicochemical properties of nano-Ag?
What effect, if any, do surface composition and surface treatments of nano-Ag particles have on
a) human exposures and uptake, b) biopersistence, c) bioaccumulation, d) biomagnification, and
e) other biological and environmental processes?
Why is this research theme of high importance?
Surface characteristics, for example, composition, coatings, treatments, passivation,
morphology, surface charge, surface area, can affect the behavior of nano-Ag as it moves away
from the source towards some receptor.
Surface characteristics can affect uptake and biological response.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Products having poorly understood surface characteristics can lead to exposures that were
unanticipated with consequential unintended effects on ecosystems. A better understanding of
surface characteristics can force reconsideration of how nano-Ag is applied in a product.
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3.2,5,3 Presentation Motes
Presenter: Participant C
X-ray photoelectron spectroscopy is of utmost importance.
Surface is where particles will interact with things in the environment and anything else they
come into contact with.
Surface properties will affect many things in CEA.
Surface properties are determined with analytical techniques. Twenty years ago, there were
over 100 techniques to do this. Some measure different depths - "surface" is subjective.
Many techniques don't have high spatial resolution, but there has been a lot of improvement.
There are tabletop scanning electron microscopes, and you can get great images at great
resolution to get elemental information, but surface chemistry analytical techniques need a lot
of development.
Most techniques still limited to aggregates of other accumulations.
3.2.5,4 Questions and Answers
Participant P: Surfaces are so hard to deal with. We crank up the energy to hit them with high-
flux X-rays, but then they permeate the surface and you pick up signals from the bulk. This
highlights the challenge of doing surface spectroscopy. The more technology we throw at it, the
more it increases curve balls.
Participant S: There is difficulty in characterizing the native surface; the preparation
techniques required to allow us to look at the surface affect the surface. Particles in
suspensions - are there things available to look at surfaces?
3.2.6, Sources and Releases
Group Members: Participants A, E, and J
3.2,6.1 Group Summary
Short Description of Priority Theme:
Characterize the release rates of nano-Ag into the environment, including manufacturing and
research workplaces, for all sources where relevant.
Identify the associated feedstocks and by-products of nano-Ag spray disinfectants. Of these
feedstocks and by-products, characterize those that could be released, in what quantities, and
via which pathways.
Identify, characterize, and where possible, quantify potential exposure vectors by which nano-
Ag or nano-Ag by-products could be released to the environment at all lifecycle stages, including
nano-Ag "life after death," e.g., use of sludges for agriculture and gardening.
Characterize the effectiveness of nano-Ag removal from sewage and industrial process water by
waste-waste treatment technology.
Characterize and quantify amounts and sizes of Ag in the sludge.
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All stages of the lifecycle have potential intended and unintended releases. Lifecycle stages of nano-Ag
products are not well understood. Limited data have been identified on specific points of release or the
quantity of nano-Ag released as a result of the manufacturing, including feedstocks.
Validation of current information and additional information about specific points of release and the
quantities of the releases are needed for the CEA. At this time, focusing on the potential releases from
feedstocks and manufacturing processes would be important to characterize before commercial
production increases.
Why is this research theme of high importance?
Without the basic information about sources and releases during all stages of the lifecycle, especially for
the early stages of feedstocks and manufacturing process, the CEA cannot be completed. We need to
know where is it and how much. This information is critical.
Where does this research theme fit within the CEA process?
This theme fits into the entire spectrum of life-cycle stages, including feedstocks, manufacturing,
distribution, storage, use, disposal, and "life after death."
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
Finding answers to this research question will lay a solid foundation for the nano-Ag spray CEA, as well
for all other nano-material CEAs.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
Characterize the release rates of nano-Ag into the environment, including manufacturing and
research workplaces, for all sources where relevant.
All three
Identify the associated feedstocks and by-products of nano-Ag spray disinfectants. Of these
feedstocks and by-products, characterize those that could be released, in what quantities and
via which pathways.
All three
Identify, characterize, and where possible, quantify potential exposure vectors by which nano-
Ag or nano-Ag by-products could be released to the environment at all lifecycle stages, including
nano-Ag "life after death," e.g., use of sludges for agriculture and gardening.
All three
Characterize the effectiveness of nano-Ag removal from sewage and industrial process water by
waste-waste treatment technology.
Characterize and quantify amounts and sizes of Ag in the sludge.
Relevant to 1. For 2, relevant to "free" nano-Ag, such as hand sanitizers, cosmetics, or food
contact substances.
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What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Requiring this information to be collected as it is unlikely to be voluntarily offered.
Collecting "proprietary" information on feedstocks and manufacturing processes, geographical
information, and quantities. Who is producing what and where?
Lack of readily available, robust, field-tested detection and monitoring devices and technologies.
Wide variety of complex matrices that could contain nano-Ag will pose significant
challenges.
Lack of labeling requirements will make identifying products containing nano-Ag difficult;
therefore we cannot identify products to track releases that could result in consumer exposures.
How are the research questions under this theme related to other top priority themes or questions?
Analytical methods
2.10 - Do adequate analytical methods exist to detect and characterize nano-Ag in
environmental compartments and biota?
2.12 - Do adequate analytical methods exist to detect and characterize exposure to nano-Ag
via soil, water, and air?
Lifecycle Stages
3.3 - What are realistic strategies for collecting data on production quantities and product
characteristics given that much of this information is proprietary?
3.6 - What changes occur to the physicochemical properties of nano-Ag throughout the
materials lifecycle stages, either as a function of process and product engineering or as a
function of incidental encounters with other substances and the environment? May be
particularly applicable to the nano-Ag sludge issue.
Fate and Transport
4.11 - To what extent does nano-Ag bind to wastewater sludge and settle out or remain
with treated water and enter downstream aquatic environments?
4.14 - Leaching and runoff are two terms mentioned frequently as a means for introducing
nano-Ag to the natural environment.
Exposure
Sources and releases are critical to exposure.
5.1 and 5.20 - Are available methods adequate to characterize nano-Ag concentrations and
associated exposure via relevant matrices such as air, water, food, surface dust?
5.7Ecologically, is nano-Ag a point source or regional exposure problem? If it is a regional
distribution issue, what are the exposure concentrations and concentration gradients in key
media (e.g., air water, soil)?
Surface characteristics
5.3 - What effect if any does surface treatment of nano-Ag particles have on uptake,
biopersistence, bioaccumulation, or biomagnification?
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How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
For ecological and human health, potential disruption of microflora and fauna populations
through biological actions of the nano-Ag.
Examples: Disruption of wastewater treatment organisms; human dermal or gut organisms
Widespread use of nano-Ag sprays will select for microbial adaptation and resistance.
If the research questions are answered and the sources and releases of nano-Ag spray are
known, the focus can be on high-release geographic sites and the potential consequences of
dispersing nano-Ag-containing sludge (via agriculture or gardening) can be reduced.
From the limited data available, a holistic approach to nano-Ag spray production is needed, as
other potentially hazardous and toxic materials are involved in the processes or product. These
other ingredients within the disinfectant spray could also have impacts on the environment and
human health.
3,2,6.2 Group Presentation Slides
Short Description of Priority Theme:
Characterize the release rates of nano-Ag into the environment, including manufacturing and
research workplaces, for all sources where relevant.
Identify the associated feedstocks and by-products of nano-Ag spray disinfectants. Of these
feedstocks and by-products, characterize those that could be released, in what quantities, and
via which pathways.
Identify, characterize, and where possible, quantify potential exposure vectors by which nano-
Ag or nano-Ag by-products could be released to the environment at all lifecycle stages, including
nano-Ag "life after death," for example, use of sludges for agriculture and gardening.
Characterize the effectiveness of nano-Ag removal from sewage and industrial process water by
waste-waste treatment technology.
Characterize and quantify amounts and sizes of Ag in the sludge.
Why is this research theme of high importance?
Without the basic information about sources and releases during all stages of the lifecycle,
especially for the early stages of feedstocks and the manufacturing process, the CEA cannot be
completed.
We need to know where is it and how much. This information is critical.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
For ecological and human health, potential disruption of microflora and fauna populations
through biological actions of the nano-Ag.
Examples: Disruption of wastewater treatment organisms; human dermal or gut organisms
Widespread use of nano-Ag sprays will select for microbial adaptation and resistance.
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If the research questions are answered and the sources and releases of nano-Ag spray are
known, the focus can be on high-release geographic sites and the potential consequences of
dispersing nano-Ag containing sludge (via agriculture or gardening) can be reduced.
From the limited data available, a holistic approach to nano-Ag spray production is needed, as
other potentially hazardous and toxic materials are involved in the processes or product. These
other ingredients within the disinfectant spray could also have impacts on the environment and
human health.
3.2.6.3 Presentation Motes
Presenter: Participant A
Need to look at feedstocks and by-products, and need to characterize quantities and pathways.
Missing from CEA - issue of life after death for these products. For nano-Ag in other products, if
they get into wastewater, and then onto sludges that get used agriculturally, etc. Some of these
sources could be regional and high
All stages of life cycle have intended and unintended releases.
Points and quantities of release are not well understood.
Often we don't even know where the releasing facilities are located.
Without basic information about where it comes from and how much is released through the
lifecycle, specifically for feedstocks and by-products, you can't do a CEA.
Earlier stages will result in larger exposures, but more they are limited in geographical space.
Once you go down to the product level, exposures might be lower, but be more widespread.
Because nano-Ag is antimicrobial, there might be disruption of wastewater treatment bacteria
or human gut or skin microflora.
A lot is confidential business information. This should not be proprietary. We need the
information so we can focus on high-release areas and dispersing nano-Ag sludges.
Exposure through local wastewater treatment plants could be high and might be used locally.
WE need to know that so we can take action to reduce impact. People are often using these in
their gardens and they are labeled as organic.
We need a holistic approach to spray production because there are potentially other hazardous
materials involved in the production and incorporated into the spray. This issue needs to be
looked at collectively.
3.2.6.4 Questions and Answers
None.
3,2.7, Mechanisms of Nanoscale Silver Toxicity
Group Members: Participants D, O, and R
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3.2,7.1 Group Summary
Short Description of Theme:
A wealth of information exists on the mechanisms of toxicity of silver ions (Ag+). However, little is
known about the mechanisms by which nano-Ag induces toxicity in living organisms. This is of great
importance due to the increase in the commercial and industrial use of nano-Ag in various products and
the potential for increased exposure risks. Based on the current state of knowledge, there is a need for
studies that address the following research topics related to mechanisms of toxicity of nano-Ag:
Role of Ag+ on nano-Ag toxicity
Are the effects observed for exposure to nano-Ag due to Ag+ desorbed from the
nanoparticles or the nanoparticles themselves?
Can nano-Ag generate Ag+ in vivo?
Are the mechanisms of toxicity similar among conventional Ag, Ag+, and nano-Ag?
Role of physicochemical properties of nano-Ag on toxicity
How do different physicochemical properties (size, surface coating, surface area, etc.) affect
the mechanisms of toxicity of nano-Ag at the cell, organ, and whole-animal levels?
Why is this research theme of high importance?
The need to understand the mechanisms and factors governing the toxicity of nano-Ag is of prime
importance for assessing risk, decreasing the impact to non-target species, and proposing remedial
actions when required.
Where does this research theme fit within the CEA process?
Mechanisms of toxicity of nano-Ag should be an integral component of any CEA framework process. For
instance, during the lifecycle stages, the mechanism of action of the particles will impact how the
product is manufactured to minimize adverse human exposure an environmental effects. Mechanisms
of toxicity will also be impacted by external factors, such as water chemistry and presence of other
contaminants. Finally, knowing the mechanism of toxicity of nano-Ag will help us understand the
biological effects from the subcellular organism to the population levels.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
Conducting research on the mechanisms of toxicity of nano-Ag will help develop new and improved
laboratory assays that could be applied to other types of metal-based nanoparticles. It will also help
determine key issues related to toxicity that should be considered when testing other types of
nanoparticles.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
Role of Ag+ in Ag-nanoparticle toxicity: Bullets 1 and 2 apply. And Bullet 3 applies only to
metallic-based nanomaterials.
Role of physicochemical properties of nano-Ag in toxicity: Bullets 1, 2, and 3 apply.
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What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
The major challenge is the current inability to quantify the total amount of Ag+ absorbed to the particles
in nano-Ag products or formulations and in biological/environmental matrices. Another challenge is the
inability to quantify the amount of nano-Ag that gets oxidized to Ag+ inside the cell.
How are the research questions under this theme related to other top priority themes or questions?
Our research questions are related to the following themes: analytical methods, test methods,
exposure and susceptibility, physicochemical toxicity, kinetics, surface characterization, sources and
release, comparison between conventional and nanoscale silver, biological effects, ecotoxicity,
communication, and fate and transport.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
If the mechanism of toxicity is primarily due to absorption of Ag+ during the production phase,
this could be addressed through changes/modifications to the manufacturing process.
If the physicochemical properties of nano-Ag are found to affect the mechanisms of toxicity,
without influencing the efficacy of the spray disinfectants, then steps could be taken to ensure
that a safer nano-Ag product is generated.
An understanding of the mechanisms of toxicity could lead to the development of
manufacturing standards and exposure limits.
3.2.7.2 Group Presentation Slides
Short Description of Priority Theme:
Based on the current state of knowledge, studies are needed to address the following research topics
related to mechanisms of toxicity of nano-Ag:
Role of Ag+ on nano-Ag toxicity
Are the effects observed for exposure to nano-Ag due to Ag+ desorbed from the
nanoparticles or the nanoparticles themselves?
Can nano-Ag generate Ag+ in vivo?
Are the mechanisms of toxicity similar among conventional Ag, Ag+, and nano-Ag?
Role of physicochemical properties of nano-Ag on toxicity
How do different physicochemical properties (size, surface coating, surface area, etc.) affect
the mechanisms of toxicity of nano-Ag at the cell, organ, and whole-animal levels?
Why is this research theme of high importance?
The need to understand the mechanisms and factors governing the toxicity of nano-Ag is of prime
importance for:
Assessing risk
Identifying critical components related to the CEA framework
Concentrate on most sensitive populations for exposure
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Minimizing the potential impact to non-target species
Eliminating unintentional effects to consumers and product users
Assuring product effectiveness
Proposing remedial actions when required
Changes in manufacturing protocols
Worker protection guidelines
Recommendations for consumer use
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
If the mechanism of toxicity is primarily due to absorption of Ag+ during the production phase,
this could be addressed through changes/modifications to the manufacturing process.
If the physicochemical properties of nano-Ag are found to affect the mechanisms of toxicity,
without influencing the efficacy of the spray disinfectants, then steps could be taken to ensure
that a safer nano-Ag product is generated.
An understanding of the mechanisms of toxicity could lead to the development of
manufacturing standards and exposure limits.
3.2.7.3 Presentation Motes
Presenter: Participant D
Role of silver ions on nano-Ag toxicity (e.g., toxicity of nano-Ag may be largely due to release of
silver ions)
Concerned at cell versus organ versus whole animal levels
Had broad discussion incorporating both human and eco
Intended to be toxic to bacteria, but what are off-target effects?
Mechanism would affect worker guidelines, etc.
Mechanism of toxicity - if due to silver ions during production phase, that would impact
manufacturing process
3.2.7.4 Questions and Answers
Participant F: Did your group talk about dosimetry at all? Is there a different MOA at
lower/higher concentrations?
Participant R: This is not captured here, but it is discussed in the biological effects
questions.
3,2.8. Ecotoxiclty Test Methods
Group Members: Participants H, K, and M
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3.2,8.1 Group Summary
Short Description of Priority Theme:
2
We considered questions 6.16 and 6.6.
Are the current tests for evaluating ecological receptors scientifically relevant and acceptable for
regulation of nano-Ag substances/products? (6.16)
What assays should be incorporated into a harmonized test battery for determining ecological
effects of nano-Ag? (6.6)
Why is this research theme of high importance?
Releases of nano-Ag to the environment have occurred historically, are occurring, and are expected to
increase as production expands.
There are novel properties of nano-Ag products, notwithstanding century-old use of nano-Ag, and these
pose unknowns with respect to impacts to ecological receptors. Early studies reveal toxic responses
following exposure to aquatic and terrestrial receptors. However, the methods have been challenged
because they were designed for testing bulk substances and might not capture the unique behaviors of
nano-Ag.
The critical physical-chemical properties that must be considered in toxicity tests methods include those
pertaining to kinetics of dissolution, bioavailability, etc. Perhaps the most unique feature is the
possibility that the nano-particle might function as a proximal delivery source of free ions at the surface
of or in the cell, and not just as a concentration of free ions distributed in the test matrix.
There are gaps in conventional standardized test methods that can be picked up for nanomaterials. In
particular, there are opportunities to move to population-, community-, and system-level methods.
Candidates include mesocosms to explore secondary or cascade effects, multigeneration tests to
explore transition to F1 and F2 generations, and system processes (e.g., nutrient cycling).
Where does this research theme fit within the CEA process?
Toxicity testing is used to measure the capacity of a test substance to have an adverse effect on
organisms. It is used to obtain a hazard classification. The most important function pertaining to the
CEA matrix is that surrogate organisms (the test subjects) integrate the exposure parameters to test
substances (i.e., bio-accessibility, bioavailability) and effects. These data are the basis for completing
the finals stages in assessing risk.
Contemporary toxicity test methods are typically limited to organism-level effects. The emergent
properties of populations, communities, and ecological systems are not captured in the current tests.
2 Question 2.8 was in this initial group, but the Breakout Group elected to delete it as it was functionally
equivalent to the other two questions; the aspect of F1 impacts offered to 6.16 was incorporated in the response
to question 1; N1 pertaining to climate change was also addressed in the response to Question 1.
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How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
Test methods will be required for any substance and therefore will be useful for all future CEA efforts.
The details of any test will likely require modifications that consider unique behaviors of test substances,
not unlike what is needed in conventional testing of volatiles, semi-volatiles, organics, and metals.
Having consensus-based test methods improves the confidence end users will have and generates
acceptance of the results among affected stakeholders.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
The basic methods will be applicable to all nanomaterials. Nevertheless, the specific modifications
needed for characterization of particles before, during, and after the exposure period in the test will
likely differ for each class of nanomaterial. Importantly, guidance can be developed as to which
parameters should be modified to maintain the integrity of test protocols.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
There are several major challenges in the design of test methods for nanomaterials. These include:
Selecting the test volume required for nominal performance of test organisms (conventional
test procedures might be prohibitively expensive because of the cost of the test substance);
Selecting the appropriate test concentrations that capture both biological response and realistic,
possible environmental concentrations;
Maintaining a homogeneous distribution of the test substance for the duration of the test;
Characterizing the relevant physical and chemical parameters of the test substance;
Choosing the most relevant response endpoints (e.g., are the conventional endpoints of growth,
survival, reproduction sufficient to capture relevant impacts from nanomaterials); and
Ensuring safety of laboratory technicians and others coming into contact with the test
substances.
One emerging theme of responses seen in toxicity tests is the "bathtub" response surface. As the
concentration of the test substance increases, aggregation/agglomeration effectively removes the test
substance from the test matrix. This means that traditional range-finding approaches that test high
concentrations are prone to giving false negative results. This also introduces challenges for chronic
exposures as the aggregated/agglomerated material can subsequently revert to behaving merely as bulk
material or be retrained into the media as nanomaterial at some future time.
How are the research questions under this theme related to other top priority themes or questions?
Prelude to understanding mechanisms of action
Relevance for and understanding of the importance of environmental concentrations
Biological effects that might occur in the environment (useful in risk assessment)
Communication and engagement - tied back to acceptance of standardized terminology
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Acquired/adaptive tolerance
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Relevant data will be developed through these tests. There will be more evidence to take regulatory
action. The development of population-, community-, and system-level test methods will make possible
answering the higher level policy concerns that occur at these levels of ecological organization (i.e., not
relying on inappropriate extrapolations from organism-level to systems impacts).
3.2.8.2 Group Presentation Slides
Short Description of Priority Theme:
Are the current tests for evaluating ecological receptors scientifically relevant and acceptable for
regulation of nano-Ag substances/products? (6.16)
What assays should be incorporated into a harmonized test battery for determining ecological
effects of nano-Ag? (6.6)
(2.8 deleted because it merely restates what is in 6.6 and 6.16; N1 Climate Change link
addressed in response to Question 1.)
Why is this research theme of high importance?
Releases of nano-Ag to the environment have occurred historically, are occurring, and are
expected to increase as production expands.
Early studies reveal toxic responses following exposure to aquatic and terrestrial receptors.
However, the methods have been challenged because they were designed for testing bulk
substances and might not capture the unique behaviors of nano-Ag.
There is a possibility that the nanoparticle might function as a proximal delivery source of free
ions at the surface of or in the cell, and not just as a concentration of free ions distributed in the
test matrix.
There are gaps in conventional standardized test methods that can be picked up for
nanomaterials. In particular, there are opportunities to move to population-, community-, and
system-level methods.
Candidates include mesocosms to explore secondary or cascade effects, multigeneration tests to
explore transition to F1 and F2 generations, and system processes (e.g., nutrient cycling).
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Relevant data will be developed through these tests.
There will be more evidence to take regulatory action.
The development of population-, community-, and system-level test methods will make possible
answering the higher level policy concerns that occur at these levels of ecological organization;
(i.e., not relying on inappropriate extrapolations from organism-level to systems impacts.
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3.2,8.3 Presentation Motes
Presenter: Participant M
Humans are another set of the ecosystem, so we create artificial silos by separating them.
Considering these questions is a lot of work. There was a workshop at Clemson last year, and
Rick Cannady led one group. They generated about a 40-page submission that should be out
soon.
There needs to be some focus on making sure there is an added level of ensuring clean
glassware and eliminating contaminants. Also consideration of different endpoints, including
'omics.
Current methods are being challenged because of inability to measure what is there and we
don't capture the unique behavior of nano-Ag.
Trojan Horse - it's possible that there is a mechanism that is unique to nano and possibly nano-
Ag.
A postulated additional function is that the nano-Ag gets out through the membrane or
internally and then becomes a concentrated source of free ions that would have a
disproportionate effect if one were to normalize concentration across the matrix.
Tox tests largely focused on individual organisms and because there are emergent properties of
communities and ecosystems, we make an error in assuming that we can multiply the number
of organisms and have a population.
With respect to animal systems, we are getting fewer numbers of test organisms, so the power
of tests is going down, making it increasingly difficult, especially for vertebrates.
There are some candidate methods - standardized mesocosm tests. But also there are some
problems - we don't always get same result, which is not surprising. That is the nature of an
ecological system. Also, they are expensive, and we often have to minimize effort and cost,
which minimizes results.
Also looking at 'omics - we should look at F1 and F2. Modifications can translate into second
and third generations.
One thing we are learning more about in nanotox - concentration on x-axis is response only. If
we challenge, we get a reduction in growth or survival, but once we get that response where
everything falls out biologically, it should get worse. But what we find with chemistry is that, at
a certain point, we get agglomeration/aggregation and settling out, and the response goes down
as concentration increases, that is, a bathtub curve.
Try to do a limit test. If you go to the far ends and test 0 and a high concentration, you will get a
false negative. If you look at lower concentrations, though, you will get a response.
The problem is: This relationship is not locked down. The nano-Ag that settles out or reacts to
become unavailable might become available again at some point, but in what form?
There is information to take regulatory action, but this would provide more evidence.
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3.2,8.4 Questions and Answers
Participant F: I like the representation of dose-response for nano. A traditional dose-response
doesn't happen all the time - it's sometimes an interesting curve. Some nanomaterials do
follow a linear or exponential curve, so we can't make assumptions.
Observer 3: I want to follow up on testing at environmentally relevant doses. There is also an
issue of extrapolating for human health and for stress at high levels. Did you think about low-
dose testing?
Participant M: Bioassays were developed because we could not measure in environmental
media, but we could elicit responses in the assay. Also without the bioassay, we don't know
what it means to have any particular concentration in the environment. The way we arrive
at reference values is to find a point that is biologically relevant, which is not necessarily
something you could detect. I think we can do a lot with nominal concentrations, but the
need for detection and characterization is also great, but we don't need to wait for it.
Observer 4: Dispersion - the way we prepare the test system has a big impact, but I have not
seen this issue addressed. We normally buy a powder and sonicate or stir, which can affect the
results.
Participant M: Excellent point, we should add it in.
Participant S: The levels we see it toxic at are down in the ppb range. We can detect it, but
only as silver, so we don't know much about the particle characteristics. For gold, we can
see that the nano aspects are preserved throughout the assays, but we are using much
higher doses.
Question: What kind of test methods do you use to look at algae? Population dynamics or
growth? Seems very broad.
Participant M: Standardized methods traditionally look at growth and cell size. In effect,
that is population, not like other things that are single organism. One can measure
chlorophyll content or effectiveness. There are five or six major groups of algae used in
standard tests.
3,2.9. Is New Nano Unique?
Group Members: Participants B, F, Q, and T
3.2.9.1 Group Summary
Short Description of Priority Theme:
This theme addresses the fundamental question of size, morphology, and surface. Are new
nanoparticles unique from bulk, ionic, and colloidal particles that have been commercially available for
some time? For some nanomaterials, we should recognize that there are differences, for others there
might not be. By using modern analytical tools and bioassays we can determine systematically which
nanomaterials might pose a new risk.
Why is this research theme of high importance?
The historical information about colloidal silver can be applied to developing the CEA of nano-Ag.
However, there is a need to resolve terminology issues. In addition, because there is already established
data and risk assessments, research priorities and available funding can be used in a more efficient way,
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while not minimizing efforts in validating or confirming results. This is a relatively financially inexpensive
and time saving way to relate historical data and risk assessments to nano-Ag. For example, materials
used in a previously conducted study that involved the avian toxicity effects could be characterized
today with modern techniques and instrumentation in an effort to bridge results to fill knowledge gaps.
Specific to the theme of this group, that is, is new nano-Ag unique, silver nanoparticles can be produced
into highly monodispersed suspensions, with unique surface coatings and treatments, and in different
morphologies and shapes.
Where does this research theme fit within the CEA process?
The CEA should capture the historical database. Although new investigations can and should be
initiated, it is important to identify specific experiments that address the question: Are we investigating
a new material that is fundamentally different or the same materials with unique properties?
A supplemental research question is: Are new nano-Ag applications unique? This fits into the CEA
lifecycle stages. New applications can be in a different form, format, or use pattern than historical
applications of colloidal silver.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
A cross comparison of already established CEAs of:
Similarly functioning material to the new nanomaterial
Colloidal particles to nanomaterials
Ions, including salts, to new nanomaterials
Bulk materials to the new nanomaterials
However, EPA acknowledges that there are no complete CEAs. There is an urgent need to complete a
comprehensive environmental assessment if EPA insists that this should be done for nanomaterials.
Otherwise, EPA should support the concept of simply requiring a more traditional risk assessment.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
For comparisons between other antimicrobial materials and new nano-Ag, it is specific to an
application of nano-Ag.
For comparisons between ionic silver and new nano-Ag, this is applicable to all soluble metal-
based nanomaterials.
For comparisons between bulk silver and new nano-Ag, this is applicable to all nanomaterials.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Technical challenge: Engagement of investigators to do a thorough literature review that
compares their new materials with existing materials in an effort to put into context what is
known and where the knowledge gaps are.
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Technical challenge: Overcoming terminology misconceptions. For example, the definition of
colloids is different to not only different scientific disciplines, it is often misconceived in
communication (i.e., between scientists and from science to general).
Technical challenge: Resolving the poor characterization of the historical data relative to the
better characterization of today's materials.
Social challenge: If new nano is unique, and we pursue nanotechnologies, it is important to
establish manufacturing methods and processes that are environmentally friendly.
Policy challenge: Because there is an outstanding question of whether new nano-Ag is unique
from other forms of silver, a debate in regulatory actions is ongoing.
Social challenge: How do scientists begin a conversation of cost-benefit analyses with the
public? For example, the health effects of salmonella vs. the health effects of nano-Ag.
How are the research questions under this theme related to other top priority themes or questions?
Test methods development for human and mammalian systems
Test methods development for ecological systems
Test methods development for analytical methods
Surface characteristics
Ecological toxicity
Fate and transport
Mechanisms
Biological Effects
Physicochemical & toxicity
Kinetics I
Kinetics II
Exposure/Dose
Exposure/Susceptibility.
The historical data and risk assessments do inform all of these other themes. However, emerging
surface coating technologies have the potential to influence these themes.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Emerging surface coating technologies can influence toxicity, mechanisms of action, persistence, fate
and transport, half-life, and lifecycle stages.
Another consequence that could be avoided is the misapplication of resources (e.g., funding, time,
reagents, efforts, animals).
3,2,9.2 Group Presentation Slides
Short description:
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This theme addresses the fundamental question of size, morphology, and surface. Are new
nanoparticles unique from bulk, ionic, and colloidal particles that have been commercially
available for some time? For some nanomaterials, we should recognize that there are
differences, for others there might not be. By using modern analytical tools and bioassays, we
can determine systematically which nanomaterials could pose a new risk.
Why is this research theme of high importance?
The historical information about colloidal silver can be applied to developing the CEA of nano-
Ag. However, there is a need to resolve terminology issues. In addition, because there is
already established data and risk assessments, research priorities and available funding can be
used in a more efficient way, while not minimizing efforts in validating or confirming results.
This is a relatively financially inexpensive and time saving way to relate historical data and risk
assessments to nano-Ag.
Specific to the theme of this group, that is, is new nano-Ag unique, silver nanoparticles can be
produced into highly monodispersed suspensions, with unique surface coatings and treatments,
and in different morphologies and shapes.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Emerging surface coating technologies have can influence toxicity, mechanisms of action,
persistence, fate and transport, half-life, and lifecycle stages.
Another consequence that could be avoided is the misapplication of resources (e.g., funding,
time, regents, efforts, animals).
3.2.9.3 Presentation Motes
Presenter: Participant T
I was not able to find any historical discussion in the Ti02 document.
This particular case offers a unique history that lets us ask this question.
As described, you need to pull away some of the definitional soup that exists when you look at
fields touching nano.
Focus on size, morphology, and surface.
Are new nanomaterials unique compared to colloidal, bulk, and ionic?
Colloidal definition here is very different for eco and material scientists.
There will be differences between historical and now - need to be well past using MSDS
(material safety data sheets) for graphite for carbon nanotubes.
Can't sideline relevant data that can inform research activities and priorities.
Need to establish if new materials pose new risk.
Historical data can be applied to CEA; however, there is a need to resolve terminology.
Get a better sense of size ranges of historical products - what was once called colloidal might
very well be nano.
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Strong database for silver -important with limited funds and resources to use it efficiently.
Need to tease out new things to apply new dollars.
Existence of historical materials does not substitute for current and future assessments. They
can augment and inform them, though.
Avian toxicity data - electron microscopy on test material, 7 to 10 nm, commercially available
for a long time.
Need to look at what is being commercialized.
What are the things that were understood and weren't unique. Citrate-capped particles have
been around for some time.
Availability of unique surface coatings can change properties where we've made advancements,
and we may not be able to draw from historical data to understand new morphologies.
What are emerging surface coatings? They might have highest probability of unintended
consequences.
Opportunity cost - if information is available, we can bridge historical data and populate box in
terms of what is known.
Animal testing - if we can go back and characterize what previous studies have been tested for,
we can bridge more easily and reduce costs.
3,2,9.4 Questions and Answers
Participant F: One thing this group was passionate about - apples to oranges comparison of
using historical data - there is no historical CEA to compare to new CEA.
Participant T: As you look at risk/benefit, it is difficult to compare two materials that have
had risks assessed in two different ways. For example, to compare Clorox to nano-Ag using
CEA, you couldn't because neither CEA exists. A traditional risk assessment with what we
know currently, even using high uncertainty factors and precautionary measures, could help
us do apples to apples comparisons.
Participant S: In working with nano, do you see greater antimicrobial properties relative to
other antimicrobials?
Answer: Everything is formulation dependent, but if you try to set them to be comparable,
we don't see heightened efficacy over ions, but you see a more durable effect. A primary
concern in hand sanitizers in medical community is lack of persistence. For someone who
develops those for that environment, there is an interest there. AgCI also has similar release
rates, but has photosensitivity issues. So heightened efficacy, no, but persistence, yes.
Observer 2: Is it an implication that you would place more emphasis on characterization and
relating older colloidal data over doing more effects studies?
Answer: I think these can affect effects data, but I'd hate to pick. I think you might prioritize
the data mining approach over a more expensive approach. Also, we don't want to plow
the same field twice when we can use data that already exist (e.g., photographic industry). I
think it has to be considered sooner rather than later, but I don't want to say to ignore more
effects work until historical data are mined.
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Question: Did you talk about how to characterize the historical data? There is so much
emphasis on characterization.
Answer: Great point - the literature sometimes gives particle size, but several materials
have been on market in continuum since the 1920s. Argyrol was used in millions of
households in the 1920s, and it predates FDA, and is still available in its original form. That
material is in a time capsule - can test now and relate back to epi studies. You have some
niche areas where you have some opportunity for this using the original products.
Participant A: Evidence for antimicrobial resistance to silver - some studies showing resistance
to AgN03. Have you looked at that, and what other microbes might have stable resistance?
People seem to think resistance doesn't happen.
Answer: Good question - I recommend bringing some of the FDA medical device
professionals who have been doing approvals on these medical products for years. They
distinguish between resistance in lab and clinical relevance where it could be stable and
relevant to public health.
Participant F: We recognize those themes of resistance and tolerance are important, and
we have captured these in the Word document along with the importance of appropriate
controls in efficacy, resistance, and toxicities.
Participant N: I like this data mining approach, and there is a lot to learn from this. Colloidal
silver includes nanosized particles. Those studies that are still being used for regulatory
purposes for silver were done in the 1930s and are called epi but are not really epi. We don't
know what they were exposed to even. Since these are still on the market, why don't we now
do epi studies with the current tools?
Answer: Could not agree more - we are on shaky ground using a constellation of various
animal studies to make assumptions about human health. We don't have some history, but
we have this embedded experiment with drinkers of colloidal silver, and many of them are
squarely within the 1- to 100-nm range and people drink them every day. I think this is a
walking epi study. I think there is little scientific support that it will do all these wonderful
things.
Participant N: Yes, it is hard to reach the people being exposed, and it is particularly challenging
given why people ingest silver. In my review of the historical data, there is no epi data and no
characterization, but you need to go to different literature in the medical case study literature.
Mining all of the literature could result in much relevant data.
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3,2,10, Biological Effects
Group Members: Participants A, H, and R
3.2.10.1 Group Summary
Short Description of Priority Theme:
The biological effects of nano-Ag are mostly unknown. These effects are concerned with all living
biological systems, including ecological and human. The following are the main research questions to
address:
What are the sensitive endpoints (e.g., subcellular, cellular, tissue, organism, or population
level) for nano-Ag exposure?
What are the relevant susceptibility factors (e.g., changes in genetic makeup)?
What are the short-term and long-term responses observed at current occupational and
consumer exposure levels?
Why is this research theme of high importance?
Data on biological effects are necessary to compile metrics to determine hazard identification as a first
step. Then, hazard identification can be combined with exposure data, where available, to facilitate risk
assessment. The biological effects data are important to be able to help set health benchmarks, such as
NOEL (no observed effect level), NOAEL (no observed adverse effect level), WHEL (worker health
exposure level) and MRL (maximum residue level), etc. Without this knowledge, an adequate risk
assessment cannot be performed.
Where does this research theme fit within the CEA process?
Assays incorporating sensitive endpoints, susceptibility factors and data covering the full range of levels
from subcellular to population are needed to be performed to obtain information on biological effects.
Compiling this information helps to understand the magnitude of the concern for nano-Ag exposure.
Biological effects data are necessary for completion of the CEA framework and set the groundwork for
guidelines, regulations, and policies.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
The biological effects data are a key step in completing future CEA frameworks of nanomaterials. The
information on biological responses is used to determine impact, the end of the theoretical spectrum of
the CEA framework.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
Each research question outlined above is relevant to 1, 2, and 3.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
It is important to know biological responses relative to nano-Ag, not conventional Ag. It is also
important to gather information on effects at the subcellular level up to the population level. Assays
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need to be developed and included in the regulatory regimen, which observes epigenetic and
generational effects.
It is necessary to gather information on sources and releases and exposure levels that can be compiled
with biological effects to determine risk. In addition, the whole ecosystem needs to be taken into
consideration because the most sensitive species might be affected but might not be the point where
the most biological effect occurs. A species farther downstream (i.e., keystone species) might be the
most appropriate due to its heightened response and the spread of this effect throughout the
ecosystem.
How are the research questions under this theme related to other top priority themes or questions?
Biological effects research questions go hand in hand with mechanisms. It also relates ultimately with
communication and education to be able to set guidelines for worker and consumer exposure as well as
setting recommendations for consumer use.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
By answering the questions really well, a better prediction of unintended consequences can be made.
For example, studies with sensitive endpoints at various biological levels can lead to a more
comprehensive picture of biological effects. Effects at the subcellular level might vary greatly from
effects on the tissue or organ level.
In addition, investigations into susceptibility factors, such as changes in genetic makeup among
individuals in the population, could provide a greater knowledge base to prepare guidelines for the
general population and define which individuals might be more sensitive.
3.2.10.2 Group Presentation Slides
Short description:
The following are the main research questions to address:
What are the sensitive endpoints (e.g., subcellular, cellular, tissue, organism, or population
level) for nano-Ag exposure?
What are the relevant susceptibility factors (e.g., changes in genetic makeup)?
What are the short-term and long-term responses observed at current occupational and
consumer exposure levels?
Why is this research theme of high importance?
Data on biological effects are necessary to compile metrics to determine hazard identification as
a first step. Then, hazard identification can be combined with exposure data, where available,
to facilitate risk assessment.
The biological effects data are important to be able to help set health benchmarks, such as NOEL
(no observed effect level), NOAEL (no observed adverse effect level), WHEL (worker health
exposure level) and MRL (maximum residue level), etc.
Without this knowledge, an adequate risk assessment cannot be performed.
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How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
By answering the questions really well, a better prediction of unintended consequences can be
made. For example, studies with sensitive endpoints at various biological levels can lead to a
more comprehensive picture of biological effects. Effects at the subcellular level might vary
greatly from effects on the tissue or organ level.
In addition, investigations into susceptibility factors, such as changes in genetic makeup among
individuals in the population, could provide a greater knowledge base to prepare guidelines for
the general population and define which individuals might be more sensitive.
3.2.10.3 Presentation Motes
No separation of effects on human and ecological populations (this was done consciously).
Focus was on "biological effects."
3.2.10.4 Questions and Answers
Observer 2: It always concerns me when I see a list of examples that includes a bunch of
endpoints. Which of those are the more important things to focus on or why?
Participant E: I think the answer you are looking for should be in test methods, and no one
signed up for that.
Participant F: I don't think it could be one in particular. Our research shows that it is
synergies of properties and endpoints. I don't think scientists can answer that question.
Observer 2: To pick a strategy, we need to focus. Where would you focus?
Participant S: The previous point was interesting . The myth of the most sensitive species
can be adapted to the myth of the most sensitive endpoint. Maybe it is not the most
sensitive endpoint that we are looking for, but what is most important to explore - like
effects on children, which we are not well equipped to do.
Sensitive future impacts that we have no way of seeing might be the most important
Participant R: in response to the question. If you have no idea what your test substance will
do, you start with well characterized systems. You can start with in vitro to get a better idea
to start with. Starting with in vivo would result in such a complex response, you wouldn't
even know what you were looking at. Can't really use single endpoint assays to understand
the total characterization - need multiplex. Avoid snapshot time or dose. Where we
started was the logical place to start.
Participant E: We are not even suggesting to do basic screening assays, just a mix of in vitro and
in vivo. As far as I could tell from the case study, the assays we use for screening aren't even
there - E. coli assays, cellular. What you have now is a potpourri across a huge list of materials.
Start with any nanomaterial of whatever size, and do some basic studies for a couple time
periods and concentrations and see what you get, because we haven't done that.
Participant Q: that is the goal of the OECD effort. Use the same particles in different labs
throughout the world looking at eco, mammalian, and in vitro systems. It is very slow - over a
year ongoing, and we still have a lot to do. At FDA, we are trying to incorporate our work into
that body by using the same particles. In total, we are doing many assays. Some are being
repeated in different countries. It will be a long time coming - it does not move fast.
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Observer 5: We've been testing nano-Ag and nano-Ti02, and we can see these cells with
nanoparticles going to the cells, and sometimes going in using dark-field microscopy. You can
use those images for risk assessment, but it is not widely used or accepted for some reason.
There is some capability here.
3.2.11. Ecological Effects Required for Risk Assessment
Group Members: Participants D, M, and O
3.2.11.1 Group Summary
Short Description of Priority Theme:
Examining the current state of knowledge related to responses of ecological receptors to nano-Ag in the
environment. The research questions under this theme are:
Are there sufficient data to conduct an Ecological Risk Assessment (ERA) on nano-Ag?
What information would improve the robustness and acceptance of the ERA related to
freshwater, marine, and terrestrial systems?
Why is this research theme of high importance?
Based on the information presented in the nano-Ag disinfectant spray case study that focused on the
CEA framework, we conclude that sufficient information already exists on Ag+ that would allow us to
perform an ERA on nano-Ag, though there would be large uncertainties. The greatest uncertainty
regarding nano-Ag is related to the "Trojan Horse" mechanism that has been postulated as a unique
aspect of this nanomaterial. However, there are other parameters for which the information could be
improved to minimize the uncertainties, increase our confidence level, and gain broader acceptance of
the risk characterization. Some of these parameters include developing:
Analytical methods needed to verify the occurrence and concentrations of nano-Ag in
environmental media
Toxicity test methods needed to assess the effects of nano-Ag on ecological receptors
Exposure scenarios
A better understanding of the uniqueness of nano-Ag with respect to bulk and Ag+
Communication, engagement, and education programs related to nanomaterials.
These other sources of information are critical to address ecological effects. In particular, the next steps
are to construct relevant conceptual models that depict routes of exposure, select the assessment
species, the assessment endpoints, and translate these to data quality objectives and sampling and
analysis plans.
Where does this research theme fit within the CEA process?
The ERA framework should drive the CEA framework. Currently, the CEA appears to assemble large
quantities of data that might not be used for an ERA. The nano-Ag case study using the CEA framework
focuses on collating data on the effects on generic representatives of sub-individual and individual
organisms, and many other parameters. A formal ERA requires expansion to include exposure and
effects assessments.
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How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
If done first, the steps of problem formulation of an ERA would streamline the CEA framework by
identifying parameters that will be needed for a regulatory determination based on ERA. This would
avoid the unnecessary generation and gathering of extraneous data.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
RQ1: Are there sufficient data to conduct an Ecological Risk Assessment (ERA) on nano-Ag?
Yes, this is relevant to all metal-based nanoparticles.
RQ2: What information would improve the robustness and acceptance of the ERA related to
freshwater, marine, and terrestrial systems?
Yes, this is relevant to all nanomaterials.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
The stakeholder engagement is the most frequently skipped part of problem formulation. Eliciting the
values of affected stakeholders is not only the most difficult, but the most crucial for getting the
questions of the ERA articulated. Without getting the right values, ERAs tend to miss what the public
cares about. The role of the science and technical practitioners is to ensure that the stakeholders' needs
and concerns are addressed. Often this requires a dialog between scientists and the other stakeholders
regarding what is technically feasible and economically practical.
Another major challenge is encountered in translating organism-level toxicity information to population,
community, or systems levels. This is because there are emerging properties of these higher levels of
organization that cannot be inferred from lower level information.
How are the research questions under this theme related to other top priority themes or questions?
The research questions for ecological effects are related to
Analytical methods
Exposure and susceptibility (including fate and transport, kinetics, etc.)
Biological effects (including humans)
Nano uniqueness
Communication, engagement, and education.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
If an integrated holistic approach is used in performing the problem formulation stage, unintended
ecological consequences would be minimized. This systems-based approach explicitly considers
alternative scenarios, the results of which can be used in active adaptive management.
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3.2.11.2 Group Presentation Slides
Short description:
Examining the current state of knowledge related to responses of ecological receptors to nano-
Ag in the environment. The research questions under this theme are
Are there sufficient data to conduct an Ecological Risk Assessment (ERA) on nano-Ag?
What information would improve the robustness and acceptance of the ERA related to
freshwater, marine, and terrestrial systems?
Why is this research theme of high importance?
Sufficient information already exists on Ag+ that would allow us to perform an ERA on nano-Ag,
although there would be large uncertainties.
The greatest uncertainty regarding nano-Ag is related to the "Trojan Horse" mechanism.
Other parameters could be improved to minimize the uncertainties, increase our confidence
level, and gain broader acceptance of the risk characterization (on next slide).
Why is this research theme of high importance?
Some of these parameters include the development of
Analytical methods for verification of the occurrence and concentrations of nano- Ag in
environmental media
Toxicity test methods needed to assess the effects of nano-Ag on ecological receptors
Exposure scenarios
Understanding the uniqueness of nano-Ag with respect to bulk and Ag+
Communication, engagement, and education related to nanomaterials.
This other information is critical to construct relevant conceptual models that depict routes of exposure,
select the assessment species, and the assessment endpoints and to translate these to data quality
objectives and sampling and analysis plans.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
If an integrated holistic approach is used in performing the problem formulation stage, unintended
ecological consequences would be minimized
This systems-based approach explicitly considers alternative scenarios, the results of which can be used
in active adaptive management.
3.2.11.3 Presentation Motes
Yes, there is sufficient data to conduct an ecological assessment for nano-Ag.
If you use silver ion data, you can conduct a nano-Ag risk assessment.
Several members were wondering why a risk assessment was not conducted as a continuation
of the CEA document.
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By and large for aquatic, terrestrial, and human health, the existing information suggests risks
are low.
Exceptions are water quality impairment in certain places.
Will have more dispersed exposure scenario in different places.
Because of the Trojan Horse phenomenon, it would lend some uncertainty.
There is enough information to begin to move forward.
Uncertainty means "we don't know what we are talking about," but there are a lot of things that
we know about silver - sulfide, for example, probably trumps many of the consequences.
Need an integrated, holistic approach to help break down artificial barriers (human, eco, etc.),
and make it a systems approach. If one starts with existing eco risk framework, it works through
iteratively, the development of a conceptual model. The model helps in engagement and dialog
with other stakeholders about what people care about and what we can do as scientists.
It gets at Mike's question of what endpoint would be most useful.
Tells us about precision, numbers of needed samples, relevant endpoints, relevant species, and
from there the risk assessment is reduced to easy math.
This procedure needs to be looked at the front end of the CEA. There are so many boxes that
need to be filled, it can be paralyzing. Rather than using it as a way to paralyze the process,
move forward rapidly and conduct a risk assessment identifying what we know and don't know.
Begin with what is reasonable, based on what you know. Don't use lack of knowledge as an
excuse not to move forward.
3,2,11,4 Questions and Answers
Observer 2: What we want to do here is engage a broader array of perspectives that we
typically don't get in a regulatory setting. How is what you are proposing different from what
we are doing here? Also, we are struggling with how to define these questions. Typically in a
regulatory approach, we ask clients what questions they want us to answer. This, on the other
hand, is not paralysis by analysis at all, we just want to raise some to the top and make sure
some don't drop off the table a priori. We want the whole array of questions we should
consider and which should be high priority.
Participant M: This is useful in one context, but the flip side is that people run out and
gather data. A lot of parameters in the CEA boxes are requesting data to fill them without
having done the scenario analysis to decide what information one needs before running out
to get the data. We ask the questions of what we need to make the decision and what we
need to get that data. This can be a living, iterative process.
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3,2,12, Communication, Engagement, and Education
Group Members: Participants E, J, K, L, and N
3.2.12.1 Group Summary
Short Description of Priority Theme:
A research strategy should be developed to engage or involve consumers, workers, researchers
and trainees in discussions to gather information about the uses, benefits, and risks of nano-Ag
sprays. Such a strategy should be informed by the principles of community-based participatory
research.
A research strategy should develop methods (with metrics where appropriate) that improve the
collaboration, information exchange, and communication among multiple disciplines.
A research strategy should be developed to effectively communicate risk/benefit information
for nano-Ag to the general public for the purposes of improving the quality of the information
exchange
Why is this research theme of high importance?
Comprehensive Environmental Assessment cannot be considered comprehensive if relevant information
about real-world industrial and consumer uses from relevant populations is not adequately considered.
This information is gathered by active engagement with consumers, workers, and others about their
interactions with silver nanomaterials and the products in which they are incorporated.
Building on recommendations from the National Academies in the area of Science and Decisions:
Advancing Risk Assessment (NRC 2009), which calls for formal provisions for external and internal
stakeholder involvement at all stages of risk assessment, this research theme should be considered to
be an integral part of CEA.
Where does this research theme fit within the CEA process?
Currently it is not explicit within the CEA Framework. However, it could be incorporated into Figure 1.1
as a cross-cutting input to each stage of the CEA analogous to the cross-cutting role of analytical
methods development and application. There is precedent for this in the NRC recommendations to EPA
in the document, Science and Decisions.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
It would improve the quality of the information inputs, such as the intended and unintended consumer
products usage and real-world workplace contexts, as well as the transparency, credibility, and
efficiency of the CEA process.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
Each research question is relevant to nanomaterials in general.
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What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Changing the CEA process to include greater stakeholder participation.
Traditionally, stakeholders have been separated from the decision making of the technical
community, resulting in an undervaluation of stakeholder knowledge that is highly relevant to
the CEA process.
CEA is a complex process requiring specialized knowledge. Engaging non-technical communities
is time-consuming, expensive, and complex.
Mindsets of the technical community and non-technical communities are vastly different.
Establishing common ground for discussions is a challenge and there are very few formally
trained practitioners who can facilitate these processes.
There are few to no incentives and encouragement to the technical community to engage with
stakeholders.
It is difficult to motivate stakeholders to be involved.
There is often lack of trust between stakeholders and technical communities that impedes
meaningful engagement.
The Technical community is encouraged only to publish adverse results. As a consequence,
unbalanced data are the only kinds available for CEA.
How are the research questions under this theme related to other top priority themes or questions?
Exposure and Susceptibility: Inadequate stakeholder engagement could result in incomplete
understanding of exposures and susceptibility.
Sources and Release: Better understanding of stakeholder use of nano-Ag products could provide useful
information about potential sources and releases into the environment.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
More complete information about actual uses of and interactions with nano-Ag spray products would
reduce the potential for unintended health impacts by
Providing information for interventions by public health agencies
Supporting the development of better consumer information, including product labeling by
product manufacturers
Enabling the development of better worker training tools and exposure controls
Creating more informed environmental and public health policies to prevent harmful consumer
exposures and environmental releases.
3.2.12.2 Group Presentation Slides
Short description:
A research strategy should be developed to engage or involve consumers, workers, researchers
and trainees in discussions to gather information about the uses, benefits, and risks of nano-Ag
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sprays. Such a strategy should be informed by the principles of community-based participatory
research.
A research strategy should develop methods (with metrics where appropriate) that improve the
collaboration, information exchange, and communication among multiple disciplines.
A research strategy should be developed to effectively communicate risk/benefit information
for nano-Ag to the general public for the purposes of improving the quality of the information
exchange.
Why is this research theme of high importance?
Comprehensive Environmental Assessment cannot be considered comprehensive if relevant
information about real-world industrial and consumer uses from relevant populations is not
adequately considered. This information is gathered by active engagement with consumers,
workers, and others about their interactions with silver nanomaterials and the products in which
they are incorporated.
Building on recommendations from the National Academies in the area of Science and Decisions:
Advancing Risk Assessment (NRC 2009), which calls for formal provisions for external and
internal stakeholder involvement at all stages of risk assessment, this research theme should be
considered to be an integral part of CEA.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
More complete information about actual uses of and interactions with nano-Ag spray products
would reduce the potential for unintended health impacts by
Providing information for interventions by public health agencies
Supporting the development of better consumer information, including product labeling by
product manufacturers
Enabling the development of better worker training tools and exposure controls
Creating more informed environmental and public health policies to prevent potentially
harmful exposures to humans and environmental organisms.
3.2.12.3 Presentation Motes
Education has dropped out of it.
We thought we were making a radical statement.
We've tried to say that more communication and engagement needs to be associated with the
CEA process. Need to ask researchers how this can happen.
This tried to address the silos and that for something as complex as nano, need to cross-cut
disciplines.
If you are only talking about risks and not benefits, you are not getting to the level where people
are making a conscious decision.
At all levels of the CEA, there should be more engagement with stakeholders.
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Resistance of the technical community to have a dialog with the community in their area was
immense.
It is hard to do - time consuming and complex, and the mindsets are vastly different.
Establishing common ground is difficult, and there is a lack of experienced facilitators.
It might help in focusing research design.
Difficult to motivate stakeholders to be involved.
Often a lack of trust between stakeholders and technical communities.
Technical community only encouraged to publish adverse results.
If we could implement almost any part of this, it would help a lot.
3,2,12,4 Questions and Answers
Participant N: We didn't purposefully drop education. It was sort of lumped into engagement
because education is inherent in engagement.
Participant L: Quality of information exchange - want better input from external and
internal stakeholders. All part of the process of understanding why you want information,
why you think it is important, and how you will use it. A two-way communication.
Participant F: Academic community - publish or perish. What is easiest to get published is
hazard. All of us have the negative results that should be published as well, and we get grants
based on publication record. In this particular thing, it is just important to publish the stuff that
gives us no toxic effects and no exposure, etc.
Participant L: I have seen negative results get into the literature as controls or comparative
studies. They are not the part of the paper that is emphasized. This is a communication issue -
a lot of the negative results are in the literature, just not emphasized.
3,2,13, Fate and Transport of Nano-Ag
Group Members: Participants I, P, U, and W
3,2.13,1 Group Summary
Short Description of Priority Theme:
Knowing the fate and transport is essential to understanding how nano-Ag gets to the point of release to
its receptors, the different paths it takes, and the rates at which it moves through those different paths.
By that, we mean it ultimately leads to prediction of exposure concentrations at the organism (both
media concentration and target organisms), which is essential for ecological and human risk assessment.
Why is this research theme of high importance?
It would be desirable to have tools that are predictive of the kinetics of nanomaterial interactions in a
wide variety of environments. Given the fact that every experimental or theoretical environmentally
relevant scenario cannot be performed, we need to use models to breach these knowledge gaps. In
particular, we need to be able to distinguish properties, and other aspects, that are specific to
nanomaterials, and how these might be distinctive from classical models of contaminants.
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Where does this research theme fit within the CEA process?
Identifying pathways of relevance/importance to human exposure and ecological receptors. Fate and
transport fits under fate and transport in the CEA. External factors represent sensitivity factors for each
of the models. By performing sensitivity analysis on the external factors, we can determine controlling
mechanisms governing transformations, etc.
Oxidation, subsequent dissolution, and binding are an important part of fate and transport. Dispersion
characteristics drive fate and transport. This builds on the fundamental chemistry and expands to
relevant properties in the appropriate environmental compartments.
There is a feedback between the models and experiments.
How would answering the research questions under this theme directly support or relate to a future
CEA of nanomaterials?
If we are to predict nano-Ag behavior, we need to know its properties, and interaction in the
environment; otherwise, we will not have accurate or relevant exposures, assessments, or effects of
different control strategies.
For each of the research questions under this theme, indicate whether it is relevant to (1) a specific
application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in general (not only nano-
Ag).
All - having a model that predicts nano-Ag fate is applicable to nanomaterials in general; even if the
constants are different, the concepts are useful. Nano-Ag and its particular properties can be very
useful for modeling other nanomaterials, given the inherent complexity of dispersion and dissolution
processes. This model could be useful for other nanomaterials that are known to exhibit more simplistic
behaviors.
What challenges might arise in answering the research questions under this theme (e.g., from a
technical, policy, or social perspective)?
Technical: Centered around difficulties of making measurements. Hard to find, very dilute in the
environment, making validation of models very difficult. Also, to arrive experimentally at half-lives that
are relevant for input into the models.
Policy: Because half-lives are tied in with so many aspects of the CEA, its implications are obvious. Fate
and transport will represent the endpoints on which regulations will be crafted.
Social: Fate and transport are complementary to the source information, but important for
communicating risk to the public. This information, however, is not communicated separately to the
public, but lumped into the overall assessment.
How are the research questions under this theme related to other top priority themes or questions?
These questions are related to many of these themes. Kinetics needs to be run for the models, and vice
versa. Surface characteristics help to provide basic tenets for physical modeling. They are related to
exposure in identifying which routes are relevant, as well as material species, etc. Also, they are related
to analytical methods as they provide an anchor for the models. Models can dictate the kind of
measurements that need to be made.
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How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
They can be used as a predictive tool for policymakers, risk assessors, control strategists, material
developers, etc. If we did not do this, we could easily miss an important pathway or route to exposure.
The questions can help determine the relevant toxicological models and species that can be employed,
such as benthic vs. aquatic. The questions can also help assess the efficacy of different control
strategies.
3.2.13.2 Group Presentation Slides
Short description:
Essential to understanding how nano-Ag gets
from the point of release to its receptors
the different paths it takes
the rates at which it moves through those different paths.
Leads to prediction of exposure concentrations at the organism (both media concentration and
target organisms), which is key for ecological and human risk assessment.
Why is this research theme of high importance?
Desire to have tools that are predictive of the kinetics of nanomaterial interactions in a wide
variety of environments.
Given the fact that every experimental or theoretical environmentally relevant scenario cannot
be performed, need to use models to breach these knowledge gaps.
In particular, need to be able to distinguish properties, etc., that are specific to nanomaterials,
and how these might be distinct from models for classical contaminants.
How might answering the research questions under this theme reduce the chances of unintended
ecological, human health, or other consequences?
Can be used as a predictive tool for policymakers, risk assessors, control strategists, material
developers, etc. If we did not do this, could easily miss out on an important pathway or route to
exposure.
Can help determine the relevant toxicological models and species that can be employed, such as
benthic vs. aquatic.
Can help assess efficacy of different control strategies.
3.2.13.3 Presentation Motes
Different pathways - soils, aerosols
Fate and transport leads to exposure concentrations and species to which organisms are
exposed
Highly integrative
Ability to develop particular tools - cannot experiment and develop experimental scenarios that
are applicable to everything in the environment, so we need to generalize
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Use models with lots of constants and then we plug those into other models, which is how we
get around having to chase a nanomaterial through compartments
Helps comprehend data we have for other disciplines
For people that deploy the technology, we can develop a predictive model for them to utilize,
and they can add in some site-specific data and tailored kinetic data
Good geochemical speciation models and surface complexation models exist, and these can be
applied to tox models
3,2.13,4 Questions and Answers
Where are we with fate and transport modeling?
Participant I: We are well off for conventional materials, but we need to think about how to
apply them to nano. I am pessimistic about applying existing models to nano, but if we are
smart enough and if we collect all the possible mechanistic data and calculate a rate
constant for removal of parent material, I think we could do it, but it would require the
additional step of developing a rate constant.
Participant S: The prevailing models that are being looked at for stability of particles in water
generally show us that ionic composition and pH will do things to the particles to make them
settle out, etc., but we don't know the lifetime of the process and if they will become
resuspended.
Participant P: Basic models deal with shifting of solutes between solid and solute phase, but
we have two behaviors to track - particulate and dissolution behavior. Once they diverge,
they interact in different ways. The colloid chemistry is probably the first approach, but we
need more sophisticated and accurate colloid theory. Also, mathematics on colloid theory is
terrible, and you need to know how to translate into the field, and then how to deal with
the ionic factor. It is a substantial challenge.
Participant U: I was thinking about gas phase, and the models that exist now for organic
materials can be adapted to nano if we know rate constants.
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4. Other Workshop Documents
4.1. Workshop Agenda
All events in EPA conference room C111B/C unless otherwise specified.
11:30 AM
Shuttle from Hilton to EPA
3:30-4:00 PM
Registration / Check In - outside of EPA conference room C111B/C
4:00-4:45 PM
Introductions
4:00-4:15 PM
Purpose of workshop
4:15-4:30 PM
Review agenda and establish ground rules
4:30-4:45 PM
Brief participant introductions
4:45 -5:00 PM
Presentation of Pre-Workshop Ranking Results
5:00 -5:30 PM
Introduction of Nominal Group Technique (NGT)
5:30 PM
End of Day 1
6:30 PM
Optional Group Dinner at Tyler's Tap Room - meet in hotel lobby
7:30 AM
7:45 AM
Shuttles from Hilton to EPA
8:00-8:30 AM
Participant and Observer Check In
8:30-8:35 AM
Welcome Back
8:35-10:00 AM
NGT Round Robin Discussions - Round 1
10:00 -10:30 AM
Break
10:30 -12:00 PM
NGT Round Robin Discussions - Rounds 2 and 3
12:00-1:00 PM
Lunch - EPA Lakeside Cafe (on your own)
1:00-3:30 PM
NGT - Consolidation and Multi-Vote
3:30-4:00 PM
Break
4:00-4:30 PM
Discuss Vote Results
4:30-5:00 PM
Breakout Group Assignments
5:00-5:30 PM
Breakout Groups Meet (Topic 1) - Rooms C111B, C111C, and C113
5:30 PM
End of Day 2
6:30 PM
Optional Group Dinner at Pop's Trattoria - meet in hotel lobby
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Day 3 - Thursday, January 6, 2011
7:30 AM
7:45 AM
Shuttles from Hilton to EPA
8:00-8:30 AM
Participant Check In
8:30-12:00 PM
Breakout Groups Meet (Topic 1) - Rooms C111B, C111C, and C113
Groups take 30 minute break at their discretion.
12:00-1:00 PM
Lunch - EPA Lakeside Cafe (on your own)
1:00-1:30 PM
Breakout Group Assignments (Topic 2) - Room C111C
1:30-5:30 PM
Breakout Groups Meet (Topic 2) - Rooms C111B, C111C, and C113
Groups take 30 minute break at their discretion.
5:30 PM
End of Day 3
6:30 PM
Optional Group Dinner at Nantucket Grill - meet in hotel lobby
7:30 AM
7:45 AM
Shuttles from Hilton to EPA
8:00-8:30 AM
Participant and Observer Check In
8:30-8:35 AM
Welcome Back
8:35-10:30 AM
Breakout Group Presentations (Topic 1)
10:30 -10:45 AM
Break
10:45 -12:45 PM
Presentation of Breakout Group Results (Topic 2)
12:45 -1:00 PM
Conclusion and Closing Remarks
1:00 PM
Workshop Adjourns
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4,2. Workshop Participants and Observers
4.2.1. Participants
Mary Boudreau
Mary Boudreau is a Research Toxicologist in the Division of Biochemical Toxicology at the FDA
National Center for Toxicological Research (NCTR). The Division conducts fundamental and
applied research designed specifically to define the biological mechanisms of action underlying
the toxicity of products regulated by, or of interest to, the FDA. Dr. Boudreau received a Ph.D.
in Veterinary Medical Sciences with a major in toxicology from Louisiana State University and
completed a post-doctoral program at the Pennington Biomedical Research Center. She was
recruited by the NCTR in 2000 and has served as the principal investigator on three National
Toxicology Program (NTP) studies, including the cosmetic ingredients aloe vera and retinyl
palmitate, and the dietary supplement aloe vera. She has served as co-investigator on
photococarcinogenicity studies of tattoo pigments and nanoscale titanium dioxide and zinc
oxide. At present, she is the principal investigator on the NTP study of nano-Ag that is designed
to evaluate the effects of particle size on the bioavailability, distribution, and toxicity in rats.
She is manager of the FDA/NTP/NCTR Phototoxicology Laboratory Facility, a member of the
NCTR Nanotechnology Working Group, reviewer for the Office of Women's Health, and has 24
years of research experience in applied biochemistry and nutritional toxicology.
Mark Chappell
Dr. Mark Chappell is a Research Physical Scientist and leader of the Soil and Sediment
Geochemistry Team in the Environmental Laboratory, U.S. Army Engineer Research and
Development Center (ERDC) in Vicksburg, MS. Dr. Chappell earned a Ph.D. in Soil Science from
Iowa State University in 2004. He served as an Oak Ridge Institute Science and Education
Postdoctoral Fellow with the U.S. Environmental Protection Agency before joining ERDC in
2007. One of Dr. Chappell's main research interests involves understanding the impact of
humic materials on the dispersion stability of natural colloids. With respect to nanomaterials,
he serves as a Co-Technical Lead for ERDC's research program into the ecological risk associated
with these materials. Within that effort, Dr. Chappell heads up the investigations on the
environmental fate of nanomaterials, leading studies into their dispersion stability and
dissolution potential in natural aqueous systems.
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Hongda Chen
Dr. Hongda Chen is the National Program Leader for Bioprocess Engineering and
Nanotechnology in National Institute of Food and Agriculture (NIFA) of U.S. Department of
Agriculture (USDA). He has represented USDA on the National Science and Technology Council
(NSTC) subcommittee on Nanoscale Science, Engineering, and Technology (NSET) since 2001.
Currently, he is a co-chair of the National Nanotechnology Initiative (NNI) Strategic Planning
Task Force. He provides national leadership to develop, coordinate, and manage research,
education, and extension programs in the areas of value-added novel products for food and
nonfood applications. He has spoken frequently on nanotechnology for agriculture and foods
at professional conferences, symposia, and strategic planning meetings both in the U.S. and
internationally. He received his Ph.D. in engineering from University of California-Davis and
served as professor of food engineering at the University of Vermont for more than 10 years
before joining USDA/CSREES in December 2000.
Mary Jane Cunningham
Dr. Mary Jane Cunningham is the President and Founder of Nanomics Biosciences, Inc., a
Delaware incorporated nanobiotechnology company in Cary, North Carolina. Nanomics
Biosciences offers global screening services in genomics and proteomics for manufacturers and
developers of a variety of substances, including nanomaterials. Dr. Cunningham received her
B.A. degree with double majors in biology and chemistry from Case Western Reserve University
and her Ph.D. in Physiological Chemistry from The Ohio State University. She completed
postdoctoral fellowships in genetic toxicology at Haskell Laboratory of E.I. du Pont de Nemours
& Co., Inc. and in prostate cancer and molecular biology at Stanford University. Dr.
Cunningham worked in several biotech start ups in Northern California and was one of the first
investigators to apply gene expression microarrays and proteomics to study the adverse effects
of chemical compounds. She is an inventor on several gene expression patents and has
presented and published on the use of OMICs technologies in toxicology. For the last seven
years, Dr. Cunningham's research focus has been in applying OMICs technologies to predict the
efficacy and safety of nanomaterials.
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James Delattre
Dr. James Delattre is Vice President of NanoHorizons Inc., a spin-out of Penn State University
and manufacturer of nanoscale materials based in Bellefonte, Pennsylvania. He received his
bachelors with honors from Penn State University, where he studied inorganic chemistry. After
working in electronic materials research at Novellus Systems, Inc. in Santa Clara, California, he
earned his Ph.D. in Chemistry from the University of California-Berkeley with a focus on
processes for reducing greenhouse gas emissions from semiconductor manufacturing and the
development of new synthetic techniques for the solid state. Following postdoctoral work
investigating the plasma treatment of polymers at the Consiglio Nazionale delle Ricerche at the
University of Bari, Italy, Dr. Delattre joined the research team at NanoHorizons as Product
Development Manager in 2005. He has presented at many international conferences and is the
author of numerous peer-reviewed scientific and trade magazine articles. As a representative
of NanoHorizons, he is active in the Silver Nanotechnology Working Group, a program of the
Silver Institute, and the U.S. Silver Task Force.
David Ensor
Dr. David Ensor is a Distinguished Fellow at RTI International. He has a Ph.D. in engineering and
an M.S. in chemical engineering from the University of Washington and a B.S. in chemical
engineering from Washington State University. He has over 40 years experience in the field of
aerosol science. His current research is in the area of nanofiber applications and nanomaterial
characterization. Dr. Ensor is a member of the Homeland Security Subcommittee of U. S. EPA
Science Advisory Board. He is Convener of the International Organization of Standards (ISO)
technical committee (TC) 209 "Cleanrooms and associated controlled environments" working
group (WG) 7 Separative devices and WG10 Nanotechnology. As a U.S. Delegate and Expert to
ISO/TC 229 "Nanotechnologies" since the initial meeting in 2005, Dr. Ensor is active on WG1
Terminology, WG2 Metrology, WG3 Health, safety and environment, and WG4 Material
specifications. He was President of the American Association for Aerosol Research (1988-1990)
and is a Founding Editor of Aerosol Science and Technology. Dr. Ensor is an Adjunct Professor of
Environmental Engineering at the University of North Carolina at Chapel Hill. He has over 85
peer reviewed publications, 7 patents, and over 200 presentations.
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Michael Hansen
Dr. Michael Hansen, a Senior Staff Scientist with Consumers Union (CU), publisher of Consumer
Reports, currently works primarily on food safety issues. He has been largely responsible for
developing CU positions on safety, testing and labeling of genetically engineered food and "mad
cow" disease. Since 2003, he has worked on a multi-state effort to ban the use of food crops to
produce pharmaceutical drugs and industrial chemicals. He also represents Consumers
International, a federation of more than 250 organizations in 110 countries, at Codex
Alimentarius and other international fora on issues. Dr. Hansen speaks on CU's concerns on
mad cow disease, GMOs, pest management, and antibiotics in animal feed, at meetings and
conferences throughout the world. Dr. Hansen served on the USDA Advisory Committee on
Agricultural Biotechnology from 1998-2002, and on the California Department of Food and
Agriculture Food Biotechnology Advisory Committee, from 2001-2002. Dr. Hansen received his
undergraduate degree from Northwestern University and his doctorate in ecology and
evolutionary biology from the University of Michigan.
Carol Henry
Dr. Carol Henry is a Professorial Lecturer at the George Washington University School of Public
Health and Health Services and a consultant to Society of Automotive Engineers (SAE)
International. She advises organizations on issues in toxicology, risk assessment, public and
environmental health, and sustainable green chemistry and engineering practices. She retired
as Vice President, Industry Performance Programs at the American Chemistry Council in
November 2007. Previously, Dr. Henry served as Director of the Health and Environmental
Sciences Department of the American Petroleum Institute; Associate Deputy Assistant
Secretary for Science and Risk Policy at the U.S. Department of Energy; Director of the Office of
Environmental Health Hazard Assessment (OEHHA) at the California Environmental Protection
Agency. She is Chair of the Federal Advisory Committee for the National Children's Study, Co-
Chair of the Montgomery Country Maryland Water Quality Advisory Group, and President of
the Chemical Society of Washington of the American Chemical Society. Dr. Henry received her
undergraduate degree in chemistry from the University of Minnesota and doctorate in
microbiology from the University of Pittsburgh. She is a diplomate of the American Board of
Toxicology, certified in general toxicology.
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Matthew Hull
Matthew Hull is President of NanoSafe, Inc., a provider of nanotechnology environmental
health and safety services founded in 2007 and headquartered in Blacksburg, VA. In 2009, Hull
co-edited the book Nanotechnology Environmental Health and Safety: Risks, Regulation, and
Management. In 2008, Hull developed NanoSafe Inc.'s NanoSafe Tested program and
companion Nanotech Register , which provides independent verification of nanomaterials and
nanotechnology products. Hull also holds an NSF IGERT fellowship in Civil and Environmental
Engineering at Virginia Tech, where his doctoral research is focused on understanding the
factors influencing partitioning of engineered nanomaterials in the environment. Previously,
Hull served as Senior Research Scientist at Luna Innovations Incorporated, where in 2003 he
developed the concept for the NanoSafe frameworkan integrated approach for addressing
nanotechnology environment, health, and safety issues in nanotechnology facilities. That
framework has gone on to spin-off programs focused on web-enabled nanotechnology EHS
management systems, nanotechnology waste recovery and recycling processes, and life-cycle
ecotoxicological studies of nanomanufacturing. Hull has an M.S. in Biology from Virginia Tech
and a B.S. in Environmental Science from Ferrum College in Virginia.
Ian llluminato
Ian llluminato is the Health and Environment Campaigner at Friends of the Earth U.S. and serves
on the Executive Committee of Friends of the Earth International. At the international level he
helps direct the work of more than one thousand employees and five thousand volunteers
throughout the world as they foster solidarity and human/environmental justice in some of the
planet's most vulnerable places, lan's mandate at Friends of the Earth U.S. is to encourage the
safe and precautionary management of nanotechnology. He has worked for Greenpeace Italy,
Greenpeace International, and the United Nations Environmental Program in Italy and has
extensive experience monitoring the impact of technological change on the environment. At
Greenpeace he helped lead an international movement against genetically engineered crops in
Europe and the Middle East. He persuaded Europe's largest rice company to stop importing
American rice to keep its stock GM-free. He also works closely with the Campaign for Safe
Cosmetics to remove toxins from beauty products. He has authored reports including, "Nano
and biocidal silver: extreme germ killers present a growing threat to public health" and
"Nanotechnology, climate and energy: over-heated promises and hot air?" His writing has
appeared in publications including the Journal of Nanoparticle Research and the European
Journal of Oncology. He has also appeared in numerous media outlets including the New York
Times, Scientific American, Business Week, and Reuters. Ian has a Bachelor's of Arts degree in
Human Ecology from the College of the Atlantic in Bar Harbor, Maine.
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Larry Kapustka
Larry Kapustka (LK Consultancy) has been a leader in the field of environmental risk assessment
since the late 1980s. He has held positions in academia, government and the private sector.
Currently, he chairs the ASTM-I E47 Committee on Biological Effects and Environmental Fate,
which is examining the efficacy of existing toxicity test methods to evaluate nanoscale products.
He also serves as the Assistant Chair of the Society of Environmental Toxicology and Chemistry
(SETAC) Nanotechnology Advisory Group. He has extensive publications in the fields of ecology,
risk assessment, toxicology, and environmental management including a framework for
addressing emerging issues in nanotechnology.
Bojeong Kim
Dr. Bojeong Kim is a postdoctoral associate in the Department of Geosciences at Virginia Tech.
Her recent work has focused on the fate, transport, and transformation of engineered
nanoparticles in the environment. Her latest research article "Discovery and Characterization
of Silver Sulfide Nanoparticles in Final Sewage Sludge Products" published in Environmental
Science and Technology (2010) has received much media coverage, including articles in
Chemical & Engineering News, Environmental Health Perspectives, and a perspective paper in
Science. She was also named as a 2010 Trendsetter by Public Works Magazine for her
exceptional research on the environmental impact of silver nanoparticles. She holds a B.S. in
chemistry from Sungkyunkwan University, an M.S. in chemistry from Seoul National University
and a Ph.D. in environmental toxicology from Cornell University, where she studied long-term
environmental perturbations in terrestrial ecosystems by anthropogenic activities.
Kristen Kulinowski
Dr. Kristen Kulinowski is a Faculty Fellow in the Department of Chemistry at Rice University and
Director for External Affairs for the Center for Biological and Environmental Nanotechnology
(CBEN). She currently serves as the Director of the International Council on Nanotechnology
(ICON), an international, multi-stakeholder organization whose mission is to develop and
communicate information regarding potential environmental and health risks of
nanotechnology thereby fostering risk reduction while maximizing societal benefit. She has
experience as a chemical researcher, educator, curriculum developer, administrator, outreach
coordinator, and policy fellow. Since 2004, Dr. Kulinowski has been actively engaged in
developing and promoting the International Council on Nanotechnology (ICON) which provides
a neutral forum in which experts from academia, governments, industry and nonprofit
organizations can explore questions of nanotechnology's impact on environment, health, and
safety (EHS). She directed an effort that resulted in the web publication of the first publicly
available database of citations to peer-reviewed papers on nano EHS. Other activities of ICON
include a survey of best practices for nanomaterial handling in the workplace and a public
portal of information on nanotechnology EHS. Dr. Kulinowski earned a B.S. in chemistry at
Canisius College and her M.S. and Ph.D. in chemistry at the University of Rochester.
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Debbie Lander
Dr. Debbie Lander received a B.S. in chemistry from McGill University and obtained a Ph.D. in
physical chemistry from Rice University. She has served as a plant chemist for Exxon Chemical
Company, and later worked in contamination control technologies at W.L. Gore. She used her
field experience of analytical chemistry and process engineering to work as Chief Scientist at
the chemical weapons neutralization facility in Maryland, maximizing safety of workers and
preventing any chemical release into the environment. This led her to begin estimating
exposures of chemical weapons to workers and the environment in order to enable the safe
destruction of the facility and restoration of the environment. Afterwards, she joined DuPont
as a risk assessor and became involved in exposure assessments for REACH. Over the last three
years at DuPont, she has focused on exposure assessments for industrial chemicals. This
requires an understanding of the use scenarios of workers, professionals, and consumers, in
order to define potential routes of exposure to humans and the environment. She uses
available data and modeling tools to estimate exposures and characterize risk by comparing
exposure estimates to the developed health or environmental benchmarks.
Paul Lioy
Dr. Paul Lioy is a Professor and Vice Chair of the Department of Environmental and
Occupational Medicine at UMDNJ-Robert Wood Johnson Medical School (RWJMS), Piscataway,
N.J. He is Deputy Director for Government Relations at the Environmental and Occupational
Health Sciences Institute (EOHSI) of Rutgers University and RWJMS, and Director of the
Exposure Science Division. He is a member of EPA's Science Advisory Board was a member of
the National Academy of Sciences Board of Toxicology and Environmental Studies, and was the
Chair of the National Research Council's first committee on Exposure Assessment. Now Dr. Lioy
is Vice Chair of the NRC Committee on Exposure Science in the 21st Century. He was a founder
of International Society for Exposure Analysis (Science) and President from 1993-94. Dr. Lioy
has published 255 scientific papers, and is identified by the Information Science Institute as a
highly cited scientist in Environment/Ecology, and published the book Dust: the Inside Story of
its role in the September 11th Aftermath. He is an Associate editor for Environmental Health
Perspectives, and the Journal of Exposure Science and Environmental Epidemiology.
Brian O'Connor
Dr. Brian O'Connor obtained his Ph.D. in organic chemistry from McGill University, Canada in
1987 and started his career at FPInnovations (a Forest Products Research Institute) in 1988. He
is currently Program Manager in charge of the Environment Research Program which covers a
variety of issues of concern to the pulp and paper industry such as environmental assessment
of new products, environmental impact in receiving waters, effluent treatment, and energy and
resource recovery from solid residues. One new product that is being examined is
nanocrystalline cellulose (NCC), a renewable nanomaterial that is formed from kraft cellulose
pulp. An environmental assessment of NCC is currently being conducted in order to ensure its
safe use in products for sale in Canada and the United States.
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Maria Powell
Dr. Maria Powell is a community-based participatory researcher and community organizer with
the Nanotechnology Citizen Engagement Organization and the Midwest Environmental Justice
Organization (MEJO) in Madison, Wisconsin. She has a B.A. in biology from the University of
California and M.S. and Ph.D. from the University of Wisconsin, Madison, both in environmental
studies. From 2004-2009 she was a postdoctoral researcher with the University of Wisconsin's
Nanoscale Science and Engineering Center and co-leader of the center's societal group. Her
research focused on outlining factors that shape uncertainties about risks of nanotechnologies
and in developing meaningful ways for citizens to engage with scientists and policymakers in
decision-making on these issues. She has published numerous peer-reviewed papers on citizen
engagement, nanotechnology risk assessment and policy, and environmental justice. She co-
created the Madison Nano Cafes, which developed into NanoCEO. She also led a
multidisciplinary team of local and state government scientists who collaboratively outlined
potential environmental health risks of emerging nanotechnologies and developed strategies to
proactively address them in the context of their agencies. Nanosilver became a priority issue
for this team and in collaboration with NanoCEO they are currently analyzing levels and forms
of silver/nanosilver released from several consumer products on the market.
Gurumurthy Ramachandran
Dr. Gurumurthy Ramachandran is a Professor of Industrial Hygiene in the Division of
Environmental and Occupational Health in the School of Public Health at the University of
Minnesota-Minneapolis. He conducts research in various areas relating to human exposure
assessment in occupational and non-occupational settings. His recent research includes
occupational exposure assessment for nanoparticles including the development of robust
strategies and analyzing measurement data and the use of expert judgment in risk assessment
for nanomaterials. Additional areas of expertise include retrospective exposure assessment
using Bayesian methods for silica, asbestos fibers, and a variety of gases and vapors;
occupational hygiene decision-making; and developing mathematical methods for exposure
modeling and analyzing occupational measurements. The focus of these interests is the
development of more effective and accurate methods to assess health-related human
exposure. He has a Bachelor's degree in electrical engineering, a Master's degree in
environmental engineering, and a Ph. D. in environmental sciences and engineering from the
University of North Carolina.
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Christie Sayes
Dr. Christie Sayes is a tenure-track Assistant Professor at Texas A&M University where she is
principal investigator of the Nanomaterials, Bioavailable Metals, & Toxicology Research
Laboratory in the Department of Physiology & Pharmacology and the Department of
Biomedical Engineering. She completed a post-doctoral fellowship at the DuPont Global
Centers Haskell Laboratory for Health and Environmental Sciences and is actively studying the
health effects of various nanomaterials in in vitro and in vivo systems. She has made
correlations between physicochemical properties and toxicological effects. Dr. Sayes has a
Ph.D. in chemistry, specializing in nanoscience, from Rice University. She pioneered many
cytotoxicity studies, including biocompatibility investigations with carbon, metal, and oxide
nanomaterials to various in vitro systems. She is on the Executive Committees of Texas A&M
Toxicology Program and Texas A&M Biotechnology Professional program. She is also a member
of the Intercollegiate Faculty of Material Science and Engineering. She is a member of Society
of Toxicology, Society of Environmental Toxicology & Chemistry, and American Chemical
Society.
Maria Sepulveda
Dr. Marisol Sepulveda received a Doctorate in Veterinary Medicine in 1991. Between 1993 and
2000, she obtained a M.S. in wildlife ecology and a Ph.D. in veterinary sciences from the
University of Florida. Her Masters was focused on evaluating the impact of mercury in great
egrets from the Everglades. Her dissertation was centered around the effects of paper mill
effluents on fish reproduction. She then joined the USGS Florida Integrated Science Center as a
post-doctoral researcher where she studied the influence of chlorinated pesticides in growth
and development of fish-eating birds and alligators. In 2004, she joined the Department of
Forestry and Natural Resources at Purdue University as an Assistant Professor of Ecotoxicology
and Aquatic Animal Health and was promoted to Associate Professor in 2009. Her laboratory
conducts research evaluating the sublethal effects of a wide-range of environmental
contaminants on the physiology of different species of aquatic animals. One major research
area consists of developing molecular biomarkers of exposure and effects to pollutants. For
that purpose, her laboratory utilizes "omic" approaches, including transcriptomics, proteomics,
and metabolomics. In relation to nanotoxicology, her laboratory is working with nano-Ag and
its effects on fish and aquatic invertebrates.
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Brian Strohmeier
Dr. Brian Strohmeier has over 30 years experience in applied surface science. Brian holds a
Ph.D. in analytical chemistry from the University of Pittsburgh and an M.A. in business
leadership from Duquesne University. He is currently Manager of the Surface Analysis
Laboratory at RJ Lee Group, Inc., an analytical services and consulting firm located in
Monroeville, PA. Brian's interests involve applications of surface analytical and microscopic
techniques for industrial problem solving, product/process development, and the
characterization of complex materials. His expertise includes: X-ray photoelectron
spectroscopy (XPS), Auger electron spectroscopy (AES), secondary ion mass spectrometry
(SIMS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and
various other analytical techniques. His technical experience includes the study of adhesion,
corrosion, oxidation, and wetting phenomena; chemical and plasma modification of material
surfaces; and the surface and microscopic characterization of asbestos and associated minerals,
catalysts, ceramics, glass and fiberglass, metals, oxides, paints and coatings, polymers,
semiconductors, and vacuum-deposited thin films. Dr. Strohmeier is the co-inventor of one
patent and the author/co-author of 51 publications and 74 technical presentations (30 invited).
Michael Tolocka
Dr. Michael Tolocka received a Ph.D. in physical chemistry from George Washington University
after earning a B.S. in chemistry from Fairleigh Dickinson University in Madison, New Jersey. He
is an expert in spectroscopy, separation methods, and mass spectrometry techniques. Until
2001 he worked as a Physical Scientist for U.S. EPA comparing chemical composition of ambient
aerosols in the Eastern and Southwestern United States. From 2001 to 2006 he conducted
postdoctoral research at the University of Delaware as well as the University of North Carolina
at Chapel Hill, where he was recently hired to develop an aerosol ion trap mass spectrometer
for use in indoor air quality studies.
Dik van de Meent
Dr. Dik van de Meent is a senior scientist with the National Institute of Public Health and the
Environment (RIVM) in Bilthoven, The Netherlands, where he has worked since 1982. He is
leading expert in modeling of fate and ecological effects of toxic substances in the environment.
He has contributed to this field by developing the multimedia fate model SimpleBox, which has
become one of the pillars of the European Union System for Evaluation of Substances (EUSES).
He is currently involved in research aimed at making EU exposure and risk assessment models
suitable for predicting environmental fate of nanomaterials. Dr. Van de Meent obtained an
Engineering degree in chemistry and a Ph.D. in environmental science, both from Delft
University of Technology. He has taught Environmental Quality at Radboud University
Nijmegen since 2004. He serves as an editorial board member for several scientific journals.
He actively contributes to various professional organizations as a board member or meeting
organizer. Dr. Van de Meent has adopted as his scientific mission to quantify the impact of
toxic emissions on biodiversity and indicate how these impacts can best be controlled.
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4,2.2. Observers
Observer Affiliation
Lauren Barton
Duke
Jed Costanza
EPA/OCSPP/OPP/AD
Genya Dana
EPA National Center for Environmental Assessment
J. Michael Davis
EPA National Center for Environmental Assessment
Patricia Gillespie
EPA National Center for Environmental Assessment
Maureen Gwinn
EPA National Center for Environmental Assessment
Jaydee Hanson
International Center for Technology Assessment
Murray Height
HeiQ
Christine Hendren
EPA National Center for Environmental Assessment
Ross Highsmith
EPA National Exposure Research Laboratory
Michael Hughes
EPA
William Jordan
EPA Office of Pesticide Programs
Kirk Kitchin
EPA National Health and Environmental Effects Research Laboratory
Tom Long
EPA National Center for Environmental Assessment
Tara Lyons-Darden
NiPERA, Inc.
Jennifer McClain
EPA Office of Pesticide Programs
Dotti Miller
EPA Office of Research and Development
Eric Money
Duke
Christy Powers
Duke University
Alan Rae
NanoMech Inc.
Jo Anne Shatkin
CLF Ventures
Julian Taurozzi
National Institute of Standards & Technology
Mathieu Therezien
Duke
David Thomas
EPA
Thabet Tolaymat
EPA Office of Research and Development
John Vandenberg
EPA National Center for Environmental Assessment
Rosalind Volpe
Silver Nanotechnology Working Group
Debra Walsh
EPA National Center for Environmental Assessment
Ron White
Johns Hopkins Bloomberg School of Public Health
Robert Zucker
EPA National Health and Environmental Effects Research Laboratory
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4,3. Pre-Workshop Charge to Workshop Participants
IMPORTANT: Please read this entire charge and the accompanying instructions before starting your review.
Introduction and Objectives
We request that you complete five tasks prior to the Nanomaterial Case Study Workshop:
1) Review Nanomaterial Case Study: Nanoscale Silver in Disinfectant Spray
2) Comment on the case study document
3) Rank potential research or information gap questions listed in the case study document
4) Add new questions or modifications of existing ones (optional)
5) Provide a biosketch
The Nanomaterial Case Study: Nanoscale Silver in Disinfectant Spray document is one step in the
development of a research strategy for the comprehensive environmental assessment of nanomaterials
such as nanoscale silver (nano-Ag). It serves as a starting point for the Nanomaterial Case Study
Workshop. Prior to the workshop (by December 15th), please submit review comments and ranking of
research questions (information gaps), as explained below. The preliminary ranking results will be
provided at the workshop. Any new questions submitted by reviewers by December 15th will be
distributed to workshop participants prior to the workshop via email and at the workshop.
The case study attempts to take a holistic view of a selected use of nano-Ag and the potential ecological
and health implications of nano-Ag products across their life cycle. Although the case study report
presents a great deal of information, many questions remain to be answered. Many of these questions,
which can also be thought of as information or research needs, are listed throughout the case study
report.
The document is meant to stimulate thinking about potential release scenarios and implications,
both direct and indirect. The case study is a starting point for your thinking, not an end in itself.
A key aspect of the review is to identify and rank the research or information that is most needed to
conduct a comprehensive environmental assessment of nano-Ag used in disinfectant sprays.
Separate instructions for the ranking process are provided below and should be read before
reviewing the document.
Instructions for Completing Pre-Workshop Tasks
Instructions are provided below for accessing the case study draft report, preparing comments on the
draft report, preparing a brief biosketch, ranking research/information needs, and submitting all of your
materials prior to the workshop. A checklist is provided at the end of this Charge to assist you.
Thank you for your thoughtful review and participation in this endeavor.
Accessing the Draft Case Study
You can download an Adobe PDF version of the document at the following Web URL:
http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=226723
If you prefer to have a hardcopy version, you can email a request to NanoWorkshop@icfi.com. ICF will
send it to you by FedEx within three days of receipt of your email.
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Reviewing the Draft Case Study
You are asked to read the entire document, not just your own areas of expertise or interest. We want
reviewers to take a "big picture" view and not focus exclusively on a particular chapter or section. As
you review the document, please consider this overarching question:
"What research or information is most needed to conduct a comprehensive
environmental assessment of nano-Ag used in disinfectant spray?"
Preparing Comments on the Draft Case Study
In your review comments, please indicate:
1) Is the information presented in the document accurate, objective, and logical? Are statements
properly supported by references? Note that we have by necessity had to rely on gray literature
and personal communications at times. If you have better sources to cite for such information,
please provide them.
2) Is information clearly and concisely presented? If not, please suggest alternative wording.
3) Is the information complete? Have any important points been omitted? Do you know of other
information that bears directly or indirectly on the case study? Can you provide a source (e.g., a
document, Web site, person) for additional information?
For comments on specific text in the document:
1) Please "triage" your comments for us by noting your 5 most important substantive comments.
2) Please indicate the specific document page and line number. For comments about the
questions that are listed at the ends of chapters, please indicate the question number in your
comment (e.g., 2.1, 5.10)
Email your review comments to NanoWorkshop@icfi.com by December 15, 2010.
Submitting Pre-Workshop Rankings
The research/information needs for conducting a comprehensive environmental assessment of nano-Ag
in disinfectant spray are posed as questions at the end of chapters 2-6 in the draft case study.
You will need to identify what you perceive as the highest- and lowest-priority needs through the
ranking system described below. You will record your rankings in an Excel workbook provided by ICF.
(Please read the detailed ranking instructions embedded in the first tab of the workbook.)
Within the Excel workbook, you will be asked to:
1) Rank the top 10 needs: Identify and rank the top 10 priorities by assigning a score of 10 to the
question you believe is the most important of all identified, a score of 9 to the question you
think is the second most important, a score of 8 for the third most important, and so on. In the
workbook, select "Top ten, [priority number]" from the options in the dropdown list (e.g., "Top
ten, 9; Top ten, 4).
2) Identify 15 unranked high-priority needs: Select an additional 15 questions you believe are
among your 25 most important. (Your top 10 priorities selected in the previous step will
automatically be included in this group.) In the workbook, select "High (unranked)" for these 15
questions.
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3) Identify the 10 lowest or "zero" priority needs: Identify up to 10 questions that you believe are
not important or are the lowest priority of all of the questions listed in the document. In the
workbook, select "Low (unranked)" for these 10 questions.
Email your completed Excel workbook to NanoWorkshop(5)icfi.com by December 15, 2010.
Adding New Questions and Modifying Existing Questions
You also may submit new questions and revisions of existing questions. Any new research/information
needs should be significantly and directly relevant to a comprehensive environmental assessment of
nano-Ag. (Many interesting questions could be asked, for example, about uses of nanomaterials or
about policies or regulations that could be applied to them, but these types of questions are outside the
intended purview of this exercise.)
Please add only questions that you would consider among your top-ranked issues. New questions
will not be ranked in the pre-workshop rankings, but all new questions will be distributed in advance
to the workshop participants, and participants will have an opportunity to discuss their highest
priority issues (including new questions) during the workshop.
You will need to type (or copy and paste) any new questions in the spaces provided on the third tab
of the Excel workbook. You should identify the case study report chapter to which each question
belongs (provided in a drop-down menu in the Excel worksheet).
If you are modifying an existing question, please indicate the number of the original question, and
enter the revised wording (otherwise select if it is a new question). Please limit
modifications to questions that are among your top 25. You should rank the original question if it is
among your top 10.
The Excel workbook can accommodate submittal of up to 10 new/revised questions, each with a
maximum of 250 characters. If you have more than 10 new questions, please email your entire list
to NanoWorkshop@icfi.com.
Preparing a Brief Biosketch
Please prepare a brief biosketch of up to 200 words. This information will be shared with the other
workshop participants and will facilitate introductions and interactions.
Email your biosketch to NanoWorkshop@icfi.com by December 15, 2010.
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Check List for Pre-Workshop Activities
Bv December 15:
Provide review comments on the draft case study report
Rank the questions (research/information needs) in the ICF Excel workbook
Top 10 highest-priority needs
Additional 15 high-priority needs
Lowest 10 priority needs
(Optional) Add new or modified questions
Provide a 200-word biosketch
Email all materials (completed Excel workbook, review comments, and biosketch) to
NanoWorkshop(5)icfi.com.
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4,4, Research Questions
Questions about Physicochemical Properties and Analytical Methods
2.1.
What information could be provided about the nano-Ag contained in spray
disinfectants to enable adequate characterization of exposure routes and toxic
effects?
2.2.
How can engineered nano-Ag particles be distinguished from incidental, background,
or naturally occurring nano-Ag particles?
2.3.
Which physicochemical properties of conventional silver can be applied to nano-Ag?
2.4.
Does the morphology of nano-Ag determine the efficacy of use in spray
disinfectants?
2.5.
How does surface coating affect:
a. the physicochemical properties of nano-Ag?
b. toxicity to humans or biota?
2.5.a.
How does surface coating affect the physicochemical properties of nano-Ag?
2.5.b.
How does surface coating affect toxicity to humans or biota?
2.6.
What physicochemical properties of nano-Ag can be used to:
a. predict fate and transport in environmental media?
b. predict toxicity to humans or biota?
2.6.a.
What physicochemical properties of nano-Ag can be used to predict fate and
transport in environmental media?
2.6.b.
What physicochemical properties of nano-Ag can be used to predict toxicity to
humans or biota?
2.7.
Which physicochemical properties of nano-Ag are most essential to characterize
before and during toxicity experiments?
2.8.
What standardized test methods or characterization protocols are necessary to
ensure that research results generated in multiple laboratories are consistent,
reproducible, and reliable?
2.9.
Are there standard nano-Ag reference materials that can be used in exposure and
effects testing to aid in comparison of results among investigators?
2.10.
Do adequate analytical methods exist to detect and characterize nano-Ag in
environmental compartments and in biota?
2.11.
What analytical methods are available to disaggregate nano-Ag particles in preparing
environmental samples for analysis?
2.12.
Do adequate analytical methods exist to detect and characterize exposure to nano-
Ag via soil, water, and air?
2.13.
What new analytical methods would enhance characterization of nano-Ag particles?
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2.14.
For the purpose of assessing potential risk, what metrics are most informative for
quantifying dose of nano-Ag?
New Questions about Physicochemical Properties and Analytical Methods
2.15.
What are the particle sizes of silver products currently registered under FIFRA?
2.16.
Does nano-Ag react with materials (i.e. organic matter, other metals, polymers) and
alter properties such as REDOX potential or leached metal ion rates?
2.17.
How can engineered nano-Ag particles be routinely, inexpensively detected,
monitored, or distinguished from incidental, background, or naturally occurring
nano-Ag particles?
2.18.
Can electron microscopy or other imaging methods be used to QUANTITAVELY
measure nano-Ag in tissues?
2.19.
Do any methods exist that can accurately measure ABSORBED DOSE of nano-Ag and
distinguish total amount of silver in tissues from conventional silver?
2.20.
What would constitute good reference positive and negative controls for nano-Ag
experiments?
2.21.
For the purpose of assessing potential risk, what metrics are most informative for
quantifying exposure and dose of nano-Ag?
Questions about Life-Cycle Stages
3.1.
What is a reliable estimate of worldwide and domestic nano-Ag production?
3.2.
What data regarding the physicochemical properties, concentrations, and
formulations in nano-Ag spray disinfectants are appropriate for assessing their
behaviors in and impacts on the environment?
3.3.
What are realistic strategies for collecting data on production quantities and product
characteristics given that much of this information is proprietary?
3.4.
What properties of engineered nano-Ag particles that are incorporated in spray
disinfectants are different from known properties of colloidal silver?
3.5.
Which manufacturing methods for nano-Ag and spray disinfectants containing nano-
Ag are most common at the industrial scale?
3.5.a.
What are the associated feedstocks and by-products; of these feedstocks and by-
products, which might be released, in what quantities, and via which pathways?
3.5.b.
Does the choice of manufacturing method for nano-Ag or spray disinfectant
containing nano-Ag affect the release rate of silver ions?
3.6.
What changes occur to the physicochemical properties of nano-Ag throughout the
material life cycle stages, either as a function of process and product engineering or
as a function of incidental encounters with other substances and the environment?
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3.6.a.
Do the changes that occur as a function of process and product engineering (e.g., the
incorporation of nano-Ag into disinfectant sprays) affect the release rate of silver
ions such that the rate might differ throughout the life cycle stages?
3.7.
What are the potential exposure vectors by which nano-Ag or nano-Ag by-products
could be released to the environment at the various life-cycle stages?
3.7.a.
What information is most relevant (e.g., product handling throughout different life
cycle phases, product use patterns, and nanoparticle release rates from products) for
determining which of these potential exposure vectors represent the most significant
pathway(s) for environmental release?
3.7.b.
What are the prevailing release pathways expected to be for nano-Ag and
disinfectant sprays containing nano-Ag into the environment?
3.7.C.
What are the frequencies and durations of releases of nano-Ag during various life-
cycle stages?
New Questions about Life-Cycle Stages
3.8.
Is there any experimental evidence that indicates that nano-Ag disposed down the
drain would not rapidly react with sulfides, thiols, chlorides or other ions entrained
in the sewer system?
3.9.
Do explosion risks exist for dried nano-Ag powders or nano-Ag powders modified
with certain types of surface coatings?
3.10.
How persistent are the antibacterial activity or otherwise toxic characteristics of
nano-Ag?
3.11.
What other examples of widespread use of toxic metals in consumer products can
we look to for information on nano-Ag in disinfectant sprays? In general, how have
those applications faired?
3.12.
Can we start measuring silver/nanosilver right now using available, existing methods
to see where it is concentrated and begin to at least get general baseline data and
track changes over time?
3.13.
What are the mechanisms during the application of disinfectant spray that affect
availability of nanoscale silver?
Questions about Fate and Transport in Environmental Media
4.1.
Do the properties of nano-Ag that differ from those of well-characterized colloidal
silver, if any, cause them to behave differently in aquatic, terrestrial, and atmospheric
environmental compartments?
a. If they do differ, how do they differ?
b. Can information about how colloidal silver behaves in these environments be
used to understand how nano-Ag behaves?
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4.1.a.
Do the properties of nano-Ag that differ from those of well-characterized colloidal
silver, if any, cause them to behave differently in aquatic, terrestrial, and atmospheric
environmental compartments? If they do differ, how do they differ?
4.1.b.
Do the properties of nano-Ag that differ from those of well-characterized colloidal
silver, if any, cause them to behave differently in aquatic, terrestrial, and atmospheric
environmental compartments? Can information about how colloidal silver behaves in
these environments be used to understand how nano-Ag behaves?
4.2.
Does particle size of nano-Ag affect the rate of release of silver ions in environmental
compartments?
4.3.
Does the aggregation state, aggregate size, or aggregate density of nano-Ag affect the
rate of release of silver ions in environmental compartments?
4.4.
Which physicochemical properties of nano-Ag and nano-Ag coatings can best be used
to predict its fate and transport in different environmental media?
4.5.
Is nano-Ag as environmentally persistent as conventional silver?
4.6.
Does nano-Ag form the same strong complexes with anions as conventional silver, and
if so, is it also effectively immobilized in aquatic environments?
4.7.
How does nano-Ag partition among soil, water, sediment, and air, and what are the
key parameters determining this partitioning behavior?
4.8.
Which environmental factors significantly affect the behavior of nano-Ag in aquatic
and terrestrial ecosystems, and by what mechanisms do they impart these effects?
4.9.
What are the characteristics of nano-Ag surface coatings that affect the transport
behavior of nano-Ag within and between environmental compartments, and how is
the transport affected?
4.10.
How effectively is nano-Ag removed from sewage and industrial process water by
wastewater treatment technology, and can information on the removal of
conventional silver be applied to nano-Ag removal?
4.11.
To what extent does nano-Ag bind to wastewater sludge and settle out or remain with
treated water and enter the downstream aquatic environment?
4.12.
How could existing models applicable to conventional silver be used to adequately
predict the transport and fate of nano-Ag through environmental compartments, or
how could they be modified to do so?
4.13.
What role, if any, does temperature play in the behavior of nanoparticles?
New Questions about Fate and Transport in Environmental Media
4.14.
Leaching and run-off are two terms mentioned frequently as means for introducing
nano-Ag to the natural environment. How applicable are these fate and transport
processes to nano-Ag disinfectant sprays?
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4.15.
Surface properties factor prominently into nano-Ag toxicity, fate and transport; yet
surface attributes are poorly characterized in most published nano-Ag studies. How
can we improve understanding of nano-Ag surface properties, and what tools can
enhance our understanding of nanoscale surface features?
4.16.
How does the path of nanoscale silver affect its persistence and fate in the
environment? For example, if the material is oxidized or agglomerated with inert,
sorptive materials, its impact may be greatly reduced.
Questions about Exposure, Uptake, and Dose
5.1.
Are available methods adequate to characterize nano-Ag concentrations and
associated exposure via relevant matrices such as:
a. air?
b. water?
c. food?
5.1.a.
Are available methods adequate to characterize nano-Ag concentrations and
associated exposure via relevant matrices such as air?
5.1.b.
Are available methods adequate to characterize nano-Ag concentrations and
associated exposure via relevant matrices such as water?
5.I.e.
Are available methods adequate to characterize nano-Ag concentrations and
associated exposure via relevant matrices such as food?
5.2.
To what extent is information on conventional silver applicable to nano-Ag,
particularly regarding:
a. uptake?
b. biopersistence?
c. bioaccumulation?
d. biomagnification?
5.2.a.
To what extent is information on conventional silver applicable to nano-Ag,
particularly regarding uptake?
5.2.b.
To what extent is information on conventional silver applicable to nano-Ag,
particularly regarding biopersistence?
5.2.C.
To what extent is information on conventional silver applicable to nano-Ag,
particularly regarding bioaccumulation?
5.2.d.
To what extent is information on conventional silver applicable to nano-Ag,
particularly regarding biomagnification?
5.3.
What effect, if any, do surface treatments of nano-Ag particles have on:
a. uptake?
b. biopersistence?
c. bioaccumulation?
4-22
-------
d. biomagnification?
5.3.a.
What effect, if any, do surface treatments of nano-Ag particles have on uptake?
5.3.b.
What effect, if any, do surface treatments of nano-Ag particles have on
biopersistence?
5.3.C.
What effect, if any, do surface treatments of nano-Ag particles have on
bioaccumulation?
5.3.d.
What effect, if any, do surface treatments of nano-Ag particles have on
biomagnification?
5.4.
Which sources, pathways, and routes offer the greatest exposure potential to nano-Ag
for humans and biota?
5.5.
Do particular species of biota and particular human populations have greater potential
for exposure to nano-Ag?
5.6.
By region and environmental segment (e.g., air, water, soil), what are the background
concentrations and characteristics of nano-Ag in air, water, and soil due to natural
(non-anthropogenic) processes?
5.7.
Ecologically, is nano-Ag a point-source or regional exposure problem? If a regional
distribution issue, what are the exposure concentrations and concentration gradients
in key media (e.g., air, water, soil)?
5.8.
What is the potential for uncoated nano-Ag particles to interact with or form
complexes with constituents in water, and what impact do these interactions have on
particle bioavailability and release of silver ions?
5.9.
What is the impact of environmental characteristics such as water chemistry (e.g., pH,
ionic strength), the presence of suspended solids, and the concentration of sulfides
and other dissolved ligands on:
a. the potential for uptake of nano-Ag from the environment?
b. tissue distribution and dose of nano-Ag and silver ions?
5.9.a.
What is the impact of environmental characteristics such as water chemistry (e.g., pH,
ionic strength), the presence of suspended solids, and the concentration of sulfides
and other dissolved ligands on the potential for uptake of nano-Ag from the
environment?
5.9.b.
What is the impact of environmental characteristics such as water chemistry (e.g., pH,
ionic strength), the presence of suspended solids, and the concentration of sulfides
and other dissolved ligands on tissue distribution and dose of nano-Ag and silver ions?
5.10.
To what extent does nano-Ag facilitate the uptake of other contaminants in the
environment?
5.11.
What is the impact of organism characteristics such as physiology (e.g., cell membrane
structure for single-celled organisms; respiratory physiology for multicellular
organisms), behavior (e.g., filter feeding, habitat), and lifestage on:
4-23
-------
a. the potential for uptake of nano-Ag from the environment?
b. tissue distribution and dose of nano-Ag and silver ions?
5.11.a.
What is the impact of organism characteristics such as physiology (e.g., cell membrane
structure for single-celled organisms; respiratory physiology for multicellular
organisms), behavior (e.g., filter feeding, habitat), and lifestage on the potential for
uptake of nano-Ag from the environment?
5.11.b.
What is the impact of organism characteristics such as physiology (e.g., cell membrane
structure for single-celled organisms; respiratory physiology for multicellular
organisms), behavior (e.g., filter feeding, habitat), and lifestage on tissue distribution
and dose of nano-Ag and silver ions?
5.12.
What is the relative bioavailability of nano-Ag and silver ions in aquatic environments,
and how might the presence of nano-Ag alter the bioavailability of silver ions in
sediments, water, and biota?
New Questions about Exposure, Uptake, and Dose
5.13.
Can estimates of the historical number of exposures to nano-Ag in wound care,
medicinal, algaecidal, and disinfection be used to estimate a frequency for adverse
effects?
5.14.
Many effects of emerging substances are not known until many years after their
introduction and use in commerce. What are the chronic and subchronic effects of
nano-Ag, and how can we accelerate our understanding of them?
5.15.
What benefits do nano-Ag disinfectant sprays offer over conventional sprays? Do
these benefits warrant the risks already identified for nano-Ag disinfectant sprays?
5.16.
What effect, if any, do surface treatments of nano-Ag particles have on human
exposures and uptake?
5.17.
How should dose and exposure be characterized for human exposures and how do the
following parameters affect it: (1) physiological characteristics, (2) behavior, (3)
lifestage, (4) susceptibility factors?
5.18.
What is the distribution of exposure intensities and frequencies of such exposures
among homemakers, children, and maintenance personal, and are these of concern
for acute and or chronic health effects?
5.19.
Is the form of the nano-sliver released in from the source the most important factor in
affecting human exposure or does the final form after agglomeration deposition on
surfaces have a greater influence on human exposure?
5.20.
Are available methods adequate to characterize nano-Ag concentrations and
associated exposure via relevant matrices such as:
a. air?
b. water?
4-24
-------
c. food?
d. surface dust?
5.21.
What information exists on the temporal changes in the release of ionic silver by
nano-Ag in relation to particle physicochemical and environmental characteristics?
5.22.
Which sources, pathways, and routes offer the greatest exposure potential to nano-Ag
for humans?
5.23.
Which sources, pathways, and routes offer the greatest exposure potential to nano-Ag
for biota?
Questions about Ecological and Human Health Effects
6.1.
To what extent do particle properties (e.g., size, shape, chemical composition, surface
treatments) determine biological responses to nano-Ag?
6.2.
Are there physicochemical properties of nano-Ag that could change significantly
between the initiation and termination of toxicity studies, thereby affecting biological
responses?
6.3.
Are the effects observed for exposure to nano-Ag due to silver ion release or the
presence of nanoparticles? Can this be distinguished?
6.4.
Do nano-Ag particle size and phase partitioning (i.e., nano-Ag particle, nano-Ag
clustering, dissolved silver ions from nano-Ag) affect organ distribution and biological
effects?
6.5.
Is the available ecological effects evidence adequate to support ecological risk
assessment for nano-Ag? If no, what research is needed to make an assessment
possible?
6.6.
At a minimum, what assays could be considered in a harmonized test guideline for
determination of the ecological effects of nano-Ag?
6.7.
How do abiotic factors in the environment affect nano-Ag effects in biota? These
include but are not limited to:
a. UV light;
b. Water quality; and
c. Other chemicals.
6.7.a.
How do abiotic factors in the environment affect nano-Ag effects in biota? These
include but are not limited to UV light.
6.7.b.
How do abiotic factors in the environment affect nano-Ag effects in biota? These
include but are not limited to water quality.
6.7.C.
How do abiotic factors in the environment affect nano-Ag effects in biota? These
include but are not limited to other chemicals.
4-25
-------
6.8.
What are the most sensitive ecological endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to determine how sensitive specific endpoints
and organisms are to nano-Ag exposure, including:
a. Benthic invertebrates;
b. Marine invertebrates; and
c. Freshwater invertebrates?
6.8.a.
What are the most sensitive ecological endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to determine how sensitive specific endpoints
and organisms are to nano-Ag exposure, including benthic invertebrates?
6.8.b.
What are the most sensitive ecological endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to determine how sensitive specific endpoints
and organisms are to nano-Ag exposure, including marine invertebrates?
6.8.C.
What are the most sensitive ecological endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to determine how sensitive specific endpoints
and organisms are to nano-Ag exposure, including freshwater invertebrates?
6.9.
Are there secondary human health effects resulting from the ecological impacts of
nano-Ag exposure? For example, exposure of terrestrial biota to sewage sludge
contaminated with nano-Ag?
6.10.
At a minimum, what assays could be considered in a harmonized test guideline for
determination of the human health effects of nano-Ag?
6.11.
Is there sufficient information available to determine appropriate standard reference
materials for use in analysis of nano-Ag ecological and human health effects?
6.12.
What is the primary mechanism of action for nano-Ag in different species?
6.13.
What are the fundamental biological responses to and associated mechanisms of
nano-Ag exposure at the cell, organ, and whole-animal levels?
6.14.
What are the biological responses observed at current nano-Ag occupational exposure
levels?
6.15.
Do current publications describing the health effects of nano-Ag particles and
laboratory-generated nano-Ag particles accurately depict the toxicity of commercially
available nano-Ag materials?
New Questions about Ecological and Human Health Effects
6.16.
Are the current tests for regulatory acceptance relevant to nano-Ag?
6.17.
What relevance do acute, subchronic and chronic toxicity tests have in the prediction
of adverse effects for nano-Ag?
6.18.
Are the results from regulatory tests for colloidal Ag sufficient to apply to nano-Ag?
6.19.
What route of exposure in in vivo preclinical testing is the most relevant?
4-26
-------
6.20.
In several regulatory tests, a metabolic system is added to help with full metabolism of
the test substance. Is this relevant to nano-Ag itself? Is this relevant to surface-
modified or surface-coated nano-Ag? Is it relevant to functionalized nano-Ag because
of the added functionalized groups?
6.21.
Can differences in toxicity observed between nano-Ag and silver nitrate in in vitro
testing be extrapolated to human health toxicity?
6.22.
What rapid screening tests are available to identify relevant eco-endpoints for nano-
Ag?
6.23.
What rapid screening tests are available to identify relevant human health endpoints
for nano-Ag?
6.24.
What rational steps can be taken to assure that risks to sensitive populations,
particularly children are minimized?
6.25.
In the absence of rigorously defined threshold limit values (TLVs) or water quality
criteria-and with the understanding that development of such values may still be
years away-can a rational and conservative approach be devised to establish and
implement interim compliance standards for working with nano-Ag?
6.26.
Is there evidence of adaptive tolerance developing in microorganisms to Ag and to
nano-Ag that would render the products useless, especially as the products gain
widespread use?
6.27.
Are there sufficient data to develop concentration- or dose-response relationships
instead of the current emphasis on point estimates or narratives of relative effects?
6.28.
Are there any parallels between health effects of conventional silver and those in
emerging studies on nanosilver?
6.29.
What have the long-term effects (including sub-clinical) been to people who
chronically ingested or applied conventional and colloidal silver-which includes
nanoparticulate? Are there any studies on this?
6.30.
Given what is already known about conventional silver and nanosilver, what might the
long term human and ecological effects of the increasing levels of silver (in a variety of
forms) be?
6.31.
Can we predict the long-term effects to ecosystems of the disturbance to microbial
communities caused by increasing levels of nanosilver in the environment?
6.32.
Can we predict the potential effects on human and ecological systems over the long-
term from microbial resistance that may develop as a result of all this silver/nanosilver
use?
6.33.
Can we predict whether widespread resistance to silver ions may develop and if so,
are silver and/or nanosilver likely to be useful antimicrobials in the future?
4-27
-------
6.34.
What are the epidemiological hypotheses that have to be investigated among the
potential populations at risk due to nano-silver exposures in residential setting and
maintenance work locations?
6.35.
The majority of toxicity studies with conventional silver were conducted over a decade
ago. Are more studies needed that utilize state-of-the-art technology for comparing
its mode of toxicity to that of nano-Ag? In other words, can we accurately say that
nano-Ag and conventional silver have different modes of toxicity if most of the studies
available for conventional silver were not conducted using current methods?
New Questions Corresponding to Multiple Topics
0.1.
Safety factors have historically been used to group of bulk silver, colloidal silver and
silver compounds with vastly differing physiochemical properties and toxicity for risk
assessment purposes. Is there any evidence that nano-Ag is not adequately covered
by these safety factors?
0.2.
Could historical colloidal silver products with 100% of particles in the 1-100 nm range
be categorized as nano-Ag for risk assessment purposes? 99%? 90%?
0.3.
Colloidal silver algaecides for swimming pools with reported 7.5 nm particles have
been registered under FIFRA and commercially available in continuum since 1954. Has
incidents data, or the lack thereof, been considered for environment fate and human
health risk assessment?
0.4.
Has the database and risk assessment methodology used by FDA during approval of
nano-Ag medical devices been integrated with EPA's database and risk assessment
processes?
0.5.
Are there sufficient commonalities in nanomaterials reactivity, toxicology, and
environmental fate to warrant grouping nanomaterials for risk assessment purposes?
0.6.
Have adverse incidents, or the lack thereof, recorded in EPA's OPP Incident Database
System (IDS) for FIFRA registered nano-Ag products be considered for risk assessment
purposes?
4-28
-------
4.5. Pre-Workshop Ranking Results
The following steps describe the methodology used to analyze the pre-workshop question
rankings based on the rankings received from the participants.
1. Added 6 placeholder questions so there are a total of 100 questions.
2. For the top 10 ranked questions, converted the score of 10 to 100, score of 9 to 99,
score of 8 to 98, etc.
3. For the unranked high questions, assigned a random value between 76 and 90. Not all
participants selected unranked high questions, so for those participants, skipped this
step.
4. For the unranked low questions, assigned a random value between 1 and 10. Again, this
range of random numbers may be smaller or larger than 10, depending on how many
low questions the participant submitted. This range always began at 1. Not all
participants selected unranked low questions.
5. For the ones that were not ranked or selected as high or low (left blank in the ranking
spreadsheet), assigned a random value between 11 and 75. The placeholder questions
were included in this group. This range of random numbers varied from participant to
participant based on how many ranked, low, and high questions were submitted by that
participant.
6. Calculated total points, mean score, and standard deviation for each question.
7. Ran a Monte Carlo simulation 500 times, storing the total points, mean score, and
standard deviation for each run. Only the randomly assigned numbers changed from
run to run - the ranked questions always kept the same order and points from 100
down to 91.
8. Averaged the results of all Monte Carlo simulations to get the final results shown in the
charts and tables below.
Ranking Results (1-10)
Shown in ranked order beginning with the question awarded the most total points (Question 5.3.).
Number of Participants Selecting Question
0 4 8 12 16
5.3.
6.1.
3.6.
5.1.
S 3'7'
<5 2.6.
2.5.
3.2.
2.7.
4.7.
4-29
-------
Ranking Results (11-40)
Shown in ranked order beginning with the question awarded the most total
points (Question 4.1.).
Number of Participants Selecting Question
4 8 12
16
4.1.
2.12.
2.10.
4.4.
6.3.
6.13.
5.4.
6.14.
2.8.
2.1.
4.12.
6.7.
4.2.
2.14.
a
o
4.3.
-------
Ranking Results (41-70)
Shown in ranked order beginning with the question awarded the most total
points (Question 6.10.).
Number of Participants Selecting Question
4 8 12
16
6.10.
5.8.
4.8.
2.2.
5.5.
3.4.
4.1.b.
2.9.
6.6.
5.11.
6.12.
6.15.
3.6.a.
3.3.
a
o
2.6.b.
-------
Ranking Results (71-100)
Shown in ranked order beginning with the question awarded the most total
points (Question 5.10.).
0
u
5.3.c.
BLANK
5.I.e.
6.8.c.
BLANK
5.3.d.
BLANK
6.7.b.
BLANK
BLANK
5.3.b.
3.5.b.
6.7.a.
6.8.a.
6.8.b.
4.6.
2.5.a.
2.4.
5.7.
5.6.
3.1.
6.9.
4.13.
2.11.
5.10.
5
6.7.C.
0
4.1.a.
1 2 H 2
BLANK
0
5.2.b.
0
5.12.
2 2
Number of Participants Selecting Question
4 8 12
I I
16
Ranked
4-32
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
1
5.3.
What effect, if any, do surface treatments of
nano-Ag particles have on:
a. uptake?
b. biopersistence?
c. bioaccumulation?
d. biomagnification?
6
8
1
1486
71%
70.76
28.21
2
6.1.
To what extent do particle properties (e.g.,
size, shape, chemical composition, surface
treatments) determine biological responses to
nano-Ag?
5
8
0
1482
71%
70.55
25.84
3
3.6.
What changes occur to the physicochemical
properties of nano-Ag throughout the
material life cycle stages, either as a function
of process and product engineering or as a
function of incidental encounters with other
substances and the environment?
6
7
1
1464
70%
69.69
28.69
4
5.1.
Are available methods adequate to
characterize nano-Ag concentrations and
associated exposure via relevant matrices
such as:
a. air?
b. water?
c. food?
4
8
0
1427
68%
67.95
26.03
5
3.7.
What are the potential exposure vectors by
which nano-Ag or nano-Ag by-products could
be released to the environment at the various
life-cycle stages?
7
4
1
1404
67%
66.87
30.70
6
2.6.
What physicochemical properties of nano-Ag
can be used to:
a. predict fate and transport in
environmental media?
b. predict toxicity to humans or biota?
4
7
0
1396
66%
66.48
27.51
7
2.5.
How does surface coating affect:
a. the physicochemical properties of nano-
Ag?
b. toxicity to humans or biota?
4
8
1
1390
66%
66.17
28.78
4-33
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
8
3.2.
What data regarding the physicochemical
properties, concentrations, and formulations
in nano-Ag spray disinfectants are appropriate
for assessing their behaviors in and impacts
on the environment?
3
8
0
1389
66%
66.14
26.74
9
2.7.
Which physicochemical properties of nano-Ag
are most essential to characterize before and
during toxicity experiments?
5
5
0
1383
66%
65.86
28.46
10
4.7.
How does nano-Ag partition among soil,
water, sediment, and air, and what are the
key parameters determining this partitioning
behavior?
3
8
0
1383
66%
65.86
26.07
11
4.1.
Do the properties of nano-Ag that differ from
those of well-characterized colloidal silver, if
any, cause them to behave differently in
aquatic, terrestrial, and atmospheric
environmental compartments?
a. If they do differ, how do they differ?
b. Can information about how colloidal
silver behaves in these environments be
used to understand how nano-Ag
behaves?
6
4
1
1346
64%
64.09
30.79
12
2.12.
Do adequate analytical methods exist to
detect and characterize exposure to nano-Ag
via soil, water, and air?
6
4
1
1327
63%
63.18
30.47
13
2.10.
Do adequate analytical methods exist to
detect and characterize nano-Ag in
environmental compartments and in biota?
6
3
1
1317
63%
62.72
31.61
14
4.4.
Which physicochemical properties of nano-Ag
and nano-Ag coatings can best be used to
predict its fate and transport in different
environmental media?
6
3
1
1301
62%
61.97
30.72
15
6.3.
Are the effects observed for exposure to
nano-Ag due to silver ion release or the
presence of nanoparticles? Can this be
distinguished?
5
4
1
1301
62%
61.93
30.98
4-34
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
16
6.13.
What are the fundamental biological
responses to and associated mechanisms of
nano-Ag exposure at the cell, organ, and
whole-animal levels?
5
3
0
1281
61%
61.02
28.95
17
5.4.
Which sources, pathways, and routes offer
the greatest exposure potential to nano-Ag
for humans and biota?
4
6
2
1276
61%
60.77
31.38
18
6.14.
What are the biological responses observed at
current nano-Ag occupational exposure
levels?
4
4
0
1276
61%
60.76
28.35
19
2.8.
What standardized test methods or
characterization protocols are necessary to
ensure that research results generated in
multiple laboratories are consistent,
reproducible, and reliable?
3
6
1
1269
60%
60.44
29.22
20
2.1.
What information could be provided about
the nano-Ag contained in spray disinfectants
to enable adequate characterization of
exposure routes and toxic effects?
4
5
1
1267
60%
60.35
30.16
21
4.12.
How could existing models applicable to
conventional silver be used to adequately
predict the transport and fate of nano-Ag
through environmental compartments, or
how could they be modified to do so?
6
3
2
1262
60%
60.11
33.21
22
6.7.
How do abiotic factors in the environment
affect nano-Ag effects in biota? These include
but are not limited to:
a. UV light
b. Water quality
c. Other chemicals
3
6
1
1256
60%
59.82
28.85
23
4.2.
Does particle size of nano-Ag affect the rate of
release of silver ions in environmental
compartments?
5
3
1
1240
59%
59.06
30.17
24
2.14.
For the purpose of assessing potential risk,
what metrics are most informative for
quantifying dose of nano-Ag?
4
5
2
1231
59%
58.60
31.91
4-35
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
25
4.3.
Does the aggregation state, aggregate size, or
aggregate density of nano-Ag affect the rate
of release of silver ions in environmental
compartments?
2
5
0
1217
58%
57.94
26.36
26
3.5.a.
What are the associated feedstocks and by-
products; of these feedstocks and by-
products, which might be released, in what
quantities, and via which pathways?
1
6
0
1186
56%
56.49
25.84
27
2.13.
What new analytical methods would enhance
characterization of nano-Ag particles?
3
6
3
1182
56%
56.28
32.47
28
6.8.
What are the most sensitive ecological
endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to
determine how sensitive specific endpoints
and organisms are to nano-Ag exposure,
including:
a. Benthic invertebrates
b. Marine invertebrates
c. Freshwater invertebrates
6
1
2
1181
56%
56.23
32.34
29
4.11.
To what extent does nano-Ag bind to
wastewater sludge and settle out or remain
with treated water and enter the downstream
aquatic environment?
2
6
2
1175
56%
55.94
30.24
30
5.9.a.
What is the impact of environmental
characteristics such as water chemistry (e.g.,
pH, ionic strength), the presence of
suspended solids, and the concentration of
sulfides and other dissolved ligands on: the
potential for uptake of nano-Ag from the
environment?
3
3
0
1172
56%
55.80
26.83
31
4.10.
How effectively is nano-Ag removed from
sewage and industrial process water by
wastewater treatment technology, and can
information on the removal of conventional
silver be applied to nano-Ag removal?
5
4
4
1170
56%
55.72
35.22
4-36
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
32
6.2.
Are there physicochemical properties of nano-
Ag that could change significantly between
the initiation and termination of toxicity
studies, thereby affecting biological
responses?
1
7
2
1166
56%
55.51
30.11
33
3.7.C.
What are the frequencies and durations of
releases of nano-Ag during various life-cycle
stages?
0
7
1
1145
55%
54.52
27.06
34
4.9.
What are the characteristics of nano-Ag
surface coatings that affect the transport
behavior of nano-Ag within and between
environmental compartments, and how is the
transport affected?
0
7
1
1144
54%
54.49
26.90
35
3.7.a.
What information is most relevant (e.g.,
product handling throughout different life
cycle phases, product use patterns, and
nanoparticle release rates from products) for
determining which of these potential
exposure vectors represent the most
significant pathway(s) for environmental
release?
3
3
1
1138
54%
54.20
29.24
36
4.5.
Is nano-Ag as environmentally persistent as
conventional silver?
5
3
5
1090
52%
51.90
36.50
37
6.5.
Is the available ecological effects evidence
adequate to support ecological risk
assessment for nano-Ag? If no, what research
is needed to make an assessment possible?
4
3
4
1083
52%
51.58
34.58
38
3.7.b.
What are the prevailing release pathways
expected to be for nano-Ag and disinfectant
sprays containing nano-Ag into the
environment?
1
4
1
1073
51%
51.12
27.02
4-37
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
39
5.9.
What is the impact of environmental
characteristics such as water chemistry (e.g.,
pH, ionic strength), the presence of
suspended solids, and the concentration of
sulfides and other dissolved ligands on:
a. the potential for uptake of nano-Ag
from the environment?
b. tissue distribution and dose of nano-Ag
and silver ions?
1
4
1
1073
51%
51.09
26.93
40
5.2.
To what extent is information on conventional
silver applicable to nano-Ag, particularly
regarding:
a. uptake?
b. biopersistence?
c. bioaccumulation?
d. biomagnification?
4
2
3
1073
51%
51.08
32.25
41
6.10.
At a minimum, what assays could be
considered in a harmonized test guideline for
determination of the human health effects of
nano-Ag?
3
3
3
1072
51%
51.06
32.18
42
5.8.
What is the potential for uncoated nano-Ag
particles to interact with or form complexes
with constituents in water, and what impact
do these interactions have on particle
bioavailability and release of silver ions?
0
5
1
1065
51%
50.72
26.09
43
4.8.
Which environmental factors significantly
affect the behavior of nano-Ag in aquatic and
terrestrial ecosystems, and by what
mechanisms do they impart these effects?
2
5
4
1063
51%
50.63
33.08
44
2.2.
How can engineered nano-Ag particles be
distinguished from incidental, background, or
naturally occurring nano-Ag particles?
4
3
5
1055
50%
50.25
36.17
45
5.5.
Do particular species of biota and particular
human populations have greater potential for
exposure to nano-Ag?
2
3
2
1053
50%
50.16
29.53
4-38
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
46
3.4.
What properties of engineered nano-Ag
particles that are incorporated in spray
disinfectants are different from known
properties of colloidal silver?
2
4
3
1052
50%
50.11
30.89
47
4.1.b.
Do the properties of nano-Ag that differ from
those of well-characterized colloidal silver, if
any, cause them to behave differently in
aquatic, terrestrial, and atmospheric
environmental compartments? Can
information about how colloidal silver
behaves in these environments be used to
understand how nano-Ag behaves?
2
2
1
1049
50%
49.97
26.92
48
2.9.
Are there standard nano-Ag reference
materials that can be used in exposure and
effects testing to aid in comparison of results
among investigators?
5
2
5
1047
50%
49.86
35.97
49
6.6.
At a minimum, what assays could be
considered in a harmonized test guideline for
determination of the ecological effects of
nano-Ag?
1
4
2
1038
49%
49.43
28.58
50
5.11.
What is the impact of organism characteristics
such as physiology (e.g., cell membrane
structure for single-celled organisms;
respiratory physiology for multicellular
organisms), behavior (e.g., filter feeding,
habitat), and lifestage on:
a. the potential for uptake of nano-Ag from
the environment?
b. tissue distribution and dose of nano-Ag
and silver ions?
1
5
3
1036
49%
49.35
30.18
51
6.12.
What is the primary mechanism of action for
nano-Ag in different species?
2
4
4
1021
49%
48.60
32.10
52
6.15.
Do current publications describing the health
effects of nano-Ag particles and laboratory-
generated nano-Ag particles accurately depict
the toxicity of commercially available nano-Ag
materials?
2
3
3
1019
49%
48.53
30.68
4-39
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
53
3.6.a.
Do the changes that occur as a function of
process and product engineering (e.g., the
incorporation of nano-Ag into disinfectant
sprays) affect the release rate of silver ions
such that the rate might differ throughout the
life cycle stages?
2
2
2
1017
48%
48.44
28.79
54
3.3.
What are realistic strategies for collecting
data on production quantities and product
characteristics given that much of this
information is proprietary?
4
2
5
1010
48%
48.08
35.51
55
2.6.b.
What physicochemical properties of nano-Ag
can be used to: predict toxicity to humans or
biota?
2
0
0
1003
48%
47.75
24.62
56
5.9.b.
What is the impact of environmental
characteristics such as water chemistry (e.g.,
pH, ionic strength), the presence of
suspended solids, and the concentration of
sulfides and other dissolved ligands on: tissue
distribution and dose of nano-Ag and silver
ions?
1
1
0
997
47%
47.50
23.07
57
5.1.a.
Are available methods adequate to
characterize nano-Ag concentrations and
associated exposure via relevant matrices
such as: air?
1
1
0
992
47%
47.22
22.58
58
6.4.
Do nano-Ag particle size and phase
partitioning (i.e., nano-Ag particle, nano-Ag
clustering, dissolved silver ions from nano-Ag)
affect organ distribution and biological
effects?
0
5
3
988
47%
47.06
28.88
59
3.5.
Which manufacturing methods for nano-Ag
and spray disinfectants containing nano-Ag
are most common at the industrial scale?
2
5
6
985
47%
46.93
35.36
60
2.3.
Which physicochemical properties of
conventional silver can be applied to nano-
Ag?
2
4
5
983
47%
46.81
33.76
4-40
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
61
5.1.b.
Are available methods adequate to
characterize nano-Ag concentrations and
associated exposure via relevant matrices
such as: water?
0
2
0
976
46%
46.48
22.18
62
2.6.a.
What physicochemical properties of nano-Ag
can be used to: predict fate and transport in
environmental media?
2
0
1
972
46%
46.28
26.41
63
5.2.a.
To what extent is information on conventional
silver applicable to nano-Ag, particularly
regarding: uptake?
1
1
1
950
45%
45.26
24.81
64
2.5.b.
How does surface coating affect: toxicity to
humans or biota?
1
1
1
947
45%
45.10
24.23
65
5.11.b.
What is the impact of organism characteristics
such as physiology (e.g., cell membrane
structure for single-celled organisms;
respiratory physiology for multicellular
organisms), behavior (e.g., filter feeding,
habitat), and lifestage on: tissue distribution
and dose of nano-Ag and silver ions?
0
1
0
944
45%
44.94
20.96
66
5.2.d.
To what extent is information on conventional
silver applicable to nano-Ag, particularly
regarding: biomagnification?
0
1
0
943
45%
44.88
20.76
67
5.2.C.
To what extent is information on conventional
silver applicable to nano-Ag, particularly
regarding: bioaccumulation?
0
1
0
940
45%
44.77
20.90
68
5.3.a.
What effect, if any, do surface treatments of
nano-Ag particles have on: uptake?
0
1
0
939
45%
44.71
20.71
69
5.11.a.
What is the impact of organism characteristics
such as physiology (e.g., cell membrane
structure for single-celled organisms;
respiratory physiology for multicellular
organisms), behavior (e.g., filter feeding,
habitat), and lifestage on: the potential for
uptake of nano-Ag from the environment?
0
1
0
937
45%
44.60
20.68
4-41
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
70
6.11.
Is there sufficient information available to
determine appropriate standard reference
materials for use in analysis of nano-Ag
ecological and human health effects?
2
1
3
933
44%
44.45
29.25
71
5.10.
To what extent does nano-Ag facilitate the
uptake of other contaminants in the
environment?
0
5
5
914
44%
43.50
31.01
72
6.7.C.
How do abiotic factors in the environment
affect nano-Ag effects in biota? These include
but are not limited to: Other chemicals
0
0
0
910
43%
43.31
19.04
73
4.1.a.
Do the properties of nano-Ag that differ from
those of well-characterized colloidal silver, if
any, cause them to behave differently in
aquatic, terrestrial, and atmospheric
environmental compartments? If they do
differ, how do they differ?
0
2
2
909
43%
43.28
24.76
74
BLANK
Used for statistical analysis purposes only
0
0
0
909
43%
43.26
19.40
75
5.2.b.
To what extent is information on conventional
silver applicable to nano-Ag, particularly
regarding: biopersistence?
0
0
0
908
43%
43.23
19.19
76
5.12.
What is the relative bioavailability of nano-Ag
and silver ions in aquatic environments, and
how might the presence of nano-Ag alter the
bioavailability of silver ions in sediments,
water, and biota?
0
2
2
906
43%
43.15
24.68
77
5.3.C.
What effect, if any, do surface treatments of
nano-Ag particles have on: bioaccumulation?
0
0
0
906
43%
43.13
19.23
78
BLANK
Used for statistical analysis purposes only
0
0
0
906
43%
43.12
19.26
79
5.I.e.
Are available methods adequate to
characterize nano-Ag concentrations and
associated exposure via relevant matrices
such as: food?
0
1
1
905
43%
43.10
22.14
4-42
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
80
6.8.C.
What are the most sensitive ecological
endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to
determine how sensitive specific endpoints
and organisms are to nano-Ag exposure,
including: Freshwater invertebrates
0
0
0
903
43%
42.99
19.27
81
BLANK
Used for statistical analysis purposes only
0
0
0
902
43%
42.97
19.30
82
5.3.d.
What effect, if any, do surface treatments of
nano-Ag particles have on: biomagnification?
0
0
0
902
43%
42.96
19.22
83
BLANK
Used for statistical analysis purposes only
0
0
0
902
43%
42.93
19.11
84
6.7.b.
How do abiotic factors in the environment
affect nano-Ag effects in biota? These include
but are not limited to: Water quality
0
0
0
901
43%
42.89
19.30
85
BLANK
Used for statistical analysis purposes only
0
0
0
900
43%
42.84
19.20
86
BLANK
Used for statistical analysis purposes only
0
0
0
897
43%
42.72
19.20
87
5.3.b.
What effect, if any, do surface treatments of
nano-Ag particles have on: biopersistence?
0
0
0
895
43%
42.61
19.15
88
3.5.b.
Does the choice of manufacturing method for
nano-Ag or spray disinfectant containing
nano-Ag affect the release rate of silver ions?
1
2
4
881
42%
41.93
28.98
89
6.7.a.
How do abiotic factors in the environment
affect nano-Ag effects in biota? These include
but are not limited to: UV light
0
0
1
866
41%
41.23
20.40
90
6.8.a.
What are the most sensitive ecological
endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to
determine how sensitive specific endpoints
and organisms are to nano-Ag exposure,
including: Benthic invertebrates
0
0
1
866
41%
41.21
20.45
91
6.8.b.
What are the most sensitive ecological
endpoints to nano-Ag exposure? Are there
sufficient data/analytical techniques to
determine how sensitive specific endpoints
and organisms are to nano-Ag exposure,
including: Marine invertebrates
0
0
1
857
41%
40.82
20.57
4-43
-------
Question
Number of
Participants Who
Selected the
Question
O <0
o d,
ฃ ง
00
92
4.6.
Does nano-Ag form the same strong
complexes with anions as conventional silver,
and if so, is it also effectively immobilized in
aquatic environments?
1
1
4
841
40%
40.07
27.40
93
2.5.a.
How does surface coating affect: the
physicochemical properties of nano-Ag?
0
1
3
827
39%
39.37
24.21
94
2.4.
Does the morphology of nano-Ag determine
the efficacy of use in spray disinfectants?
1
2
6
814
39%
38.78
30.69
95
5.7.
Ecologically, is nano-Ag a point-source or
regional exposure problem? If a regional
distribution issue, what are the exposure
concentrations and concentration gradients in
key media (e.g., air, water, soil)?
1
2
6
804
38%
38.27
30.49
96
5.6.
By region and environmental segment (e.g.,
air, water, soil), what are the background
concentrations and characteristics of nano-Ag
in air, water, and soil due to natural (non-
anthropogenic) processes?
0
3
6
797
38%
37.94
29.26
97
3.1.
What is a reliable estimate of worldwide and
domestic nano-Ag production?
1
2
7
779
37%
37.08
31.23
98
6.9.
Are there secondary human health effects
resulting from the ecological impacts of nano-
Ag exposure? For example, exposure of
terrestrial biota to sewage sludge
contaminated with nano-Ag?
2
1
8
740
35%
35.24
31.67
99
4.13.
What role, if any, does temperature play in
the behavior of nanoparticles?
1
0
10
580
28%
27.60
27.79
100
2.11.
What analytical methods are available to
disaggregate nano-Ag particles in preparing
environmental samples for analysis?
1
2
12
577
27%
27.47
31.61
4-44
-------
4,6. Template and Instructions for Breakout Group Reports
4.6.1. Group Summary
Nanomaterial Case Study WorkshopReport from
Breakout Group [insert name of group]
Breakout group members: [insert group member names]
Short Description:
[Prepare a short paragraph, individual sentences, or bullet statements referring to specific
questions subsumed under this priority area. Synthesis of questions is encouraged. ]
1. Why is this research theme of high importance?
2. Where does this research theme fit within the CEA process?
3. How would answering the research questions under this theme directly support or relate to a
future CEA of nanomaterials?
4. For each of the research questions under this theme, indicate whether it is relevant to (1) a
specific application of nano-Ag, (2) all applications of nano-Ag, or (3) nanomaterials in
general (not only nano-Ag).
5. What challenges might arise in answering the research questions under this theme (e.g., from
a technical, policy, or social perspective)?
6. How are the research questions under this theme related to other top priority themes or
questions?
7. How might answering the research questions under this theme reduce the chances of
unintended ecological, human health, or other consequences?
4-45
-------
4.6.2. Group Presentation Slides
Nanomaterial Case Study Workshop
Developing a Comprehensive Environmental Assessment Research Strategy for Nanoscale Silver
Breakout Group [insert number of group] Summary
Title of priority theme:
Group members: [insert group member names]
Short description:
[Insert one to two sentences or bullet statements describing questions under this
theme; synthesis of questions is encouraged.]
Nanomaterial Case Study Workshop
Developing a Comprehensive Environmental Assessment Research Strategy for Nanoscale Silver
Why is this research theme of high importance?
[Insert one to two sentences or bullet statements describing why this research
theme is of high importance.]
4-46
-------
Nanomaterial Case Study Workshop
Developing a Comprehensive Environmental Assessment Research Strategy for Nanoscale Silver
How might answering the research questions under this theme
reduce the chances of unintended ecological, human health,
or other consequences?
[Insert one to two sentences or bullet statements describing why this research
theme is of high importance.]
4-47
-------
5, References
U.S. EPA (U.S. Environmental Protection Agency). (2007). Nanotechnology white paper. (EPA 100/B-
07/001). Washington, DC: Science Policy Council, Nanotechnology Workgroup, U.S.
Environmental Protection Agency, http://www.epa.gov/osa/pdfs/nanotech/epa-
nanotechnology-whitepaper-0207.pdf.
U.S. EPA (U.S. Environmental Protection Agency). (2010a). Nanomaterial case studies: Nanoscale
titanium dioxide in water treatment and topical sunscreen (final). (EPA/600/R-09/057F).
Research Triangle Park, NC. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=230972.
U.S. EPA (U.S. Environmental Protection Agency). (2010b). Nanoscale silver in disinfectant spray
(external review draft). (EPA/600/R-10/081). Washington, DC.
U.S. EPA (U.S. Environmental Protection Agency). (2010c). Workshop summary for the EPA Board of
Scientific Counselors. (EPA/600/R-10/042). Research Triangle Park, NC: National Center for
Environmental Assessment, Office of Research and Development, U.S. Environmental Protection
Agency.
Van de Ven. AH: Delbecq. AL. (1972). The nominal group as a research instrument for exploratory health
studies. Am J Public Health 62: 337-342. http://dx.doi.Org/10.2105/AJPH.62.3.337.
5-1
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