advancing risk analysis for nanomaterials and …risk analysis: advancing the science for...

Jo Anne Shatkin , Ph.D.

Managing DirectorCLF Ventures, Inc.

Boston, Massachusetts

November 19, 2008Society for Risk Analysis – New England

Harvard School of Public Health

Advancing Risk Analysis for Nanomaterials and Nanotechnologies

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Overview

• Framing the issues

– Nano challenges to risk assessment

• Society for Risk Analysis Expert Workshop Findings

• Adopting a life cycle approach in risk assessment

Risk Analysis:Advancing the Science for Nanomaterial Risk ManagementSept 10-11 2008, Wash.DC http://www.srananoworkshop.org

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What Is Nanotechnology?

“Nanotechnology is the understanding and control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications”

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What Is Nanotechnology?

• Current technology, novel engineered nanoscale raw materials (Feynmann, “There’s plenty of room at the bottom”)

• In the future, active applications, molecular manufacturing (Drexler)

• Attributes: – Manufactured– Surface area to size/mass– Unique behavior

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How small is a nanometer?

• Head of a pin = 20,000,000 nanometers

• Particulate Matter (PM10) = 10,000 nanometers

• Bacteria = 500 - 5000 nanometers

• Viruses = 20 - 400 nanometers

• DNA = 1-2 nanometers wide

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Categories of Nanoparticles

Natural Man-Made Engineered

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Categories of Nanomaterials

• Metals and metal oxides

– Titanium dioxide

– Quantum dots

– Metal nanotubes

• Carbon-based

– Fullerenes

– Carbon nanotubes

• Dendrimers

• Composites

Quantum dots

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Carbon at the Nanoscale

DIAMOND

GRAPHITE

CARBON NANOTUBE

FULLERENE

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Nanoscale Materials have More Particles and Surface Area per Unit Mass

Adapted from Oberdörster et al. 2005a

120.1535000

120153500

12,000153,000,0005

120,000153,000,000,0000.5

12,000,000153,000,000,000,000,0000.005

Particle surface area (μm2/cm3)

Particle concentration (#/cm3)

Particle diameter

(μm)

Table 1 Estimates of particle number and surface area per 10 μg/m3 of airborne particles

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Current Applications Using Nanotechnology

SOURCE: Woodrow Wilson International Center for Scholars Project on Emerging Technologies- ConsumeProduct Inventory nanotechproject.org

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Environmental APPLICATIONS of Nanotechnology

• Reducing Vehicle Emissions– Cerium Oxide in diesel fuel reduces

CO2, particulates, hydrocarbon emissions (Oxonica)

• Reducing Electric Consumption– Flexible solar batteries for personal

digital devices (Konarka)

• Making Solar Cells Affordable– Carbon nanotubes could help make

nanoparticle-based solar cells more efficient and practical using thinner coatings with improved transfer of energy.

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Issues for Risk Assessment

• Insufficient scientific information

• Physico-chemical changes of nanoparticles

• Translocation of nanoparticles

• Interactions with living matter

• Fate, distribution, and persistence

• Extrapolation of data from non-nano

Risk Analysis:Advancing the Science for Nanomaterial Risk Management

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Framing the Issues for Health/ Environmental Risk Assessment

Exposure Assessment

Risk Characterization

Hazard Characterization

Toxicity Assessment

(NRC 1983)

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Framing the Issues: Hazard characterization for nanotechnology

• How to define nanomaterials

– Distinguish engineered from other nanoparticles?

– Are agglomerated or aggregated particles nano?

– Is a composite material containing nanoparticles “nano”?

• Do we characterize the particle, or the product?

• What are the appropriate measurement units?

• How to characterize variability, uncertainty?

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Framing the Issues: Exposure Assessment for Nanotechnology

• Need new ways to characterize exposure– Mass may not be most useful measure

– Can mass be a surrogate? When?

– When does size trigger new measures?

• Limitations of available analytical techniques

• Methods require low detection limits

• Also need to characterize “background”exposures

• Limited data on transport and fate

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Framing the Issues: Dose Response for Nanotechnology

• Uncertainty in defining dose

• Different behavior of nanoparticles

• Difficulty in measuring responses- equivocal

• Absorption, distribution, metabolism, excretion

• Diversity of materials and characteristics

– When are particle distributions different?

– What are the tolerances?

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Framing the Issues:Characterizing Risks of Nanomaterials

• Current frameworks adequate and appropriate, but significant model and parameter uncertainty

• Still much research to be done to quantify risks• Need to address uncertainty and variability• Available studies are comparative, e.g.

– Brunner et al. (2006) (comparative in vitro toxicity)– Sayes et al. (2004) (cytotoxicity of variously substituted C60

fullerenes)– Robichaud et al. (2005) (comparative risks of nanomanufacturing– Warheit et al. (2007) (characterization of Nano-TiO2 toxicity)

• Do we need nano-safety factors?• New Metrics and Endpoints for Risk?

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Framing the Issues: Uncertainty Analysis Haven’t we been here before?

• Cellular phones and non-ionizing radiation• Foodborne vs. Nosocomial antimicrobial resistance• Chemical mixtures• Climate change impacts• Fish consumption advisories

• Nano is not new, but does raise some novel challenges

• Risk Analysis is a robust approach for assessing and managing uncertain hazards and risks

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Risk Analysis:

Advancing the Science for Nanomaterial Risk Management Sept 2008, Washington DC

• Public expert workshop organized by the Society for Risk Analysis Emerging Nanoscale Materials Specialty Group

• Brought together risk analysts with nano-experts in to advance our understanding and build new networks

• A deliberative workshop to address: – What is “nano” about risk assessment for nanoscale materials?

– What tools in the field of risk analysis can be used for managing nanomaterials?

– What are the needs for communicating about risks?

– How to consider the benefits of nanotechnology for risk reduction?

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Workshop Co-SponsorsRisk Analysis:Advancing the Science for Nanomaterial Risk Management

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Main Topics for Workshop Papers

• Uncertainty Analysis– Model and parameter uncertainty pervades material

characterization and hazard assessment • Exposure Assessment

– When and how best to get beyond mass-based assessments, can other dimensions be simplified?

• Dose-response Assessment– Dosing regimes must be tied to real world exposure

• Risk Characterization– Not ready for quantitative assessments – adopt life cycle

approach, can we also consider benefits?• Risk Communication

– Difficult to communicate about uncertain topics. Nano as an enabling technology complicates this message


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Repeated themes

• Considerable uncertainty in understanding of nano-specific attributes and relevance to biological and environmental effects

• Size matters, but its not clear there is a bright line, e.g. at 100 nm

• Regulatory approaches are likely to be case-by-case in the near term

• Perceptions outside of industry and the government are critical, and proactive measures to communicate with the public are critical to ensuring the development of nano-products


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Key Issues Identified

• Many previously identified concerns are not specific to nanomaterials or nanotechnologies

• Can address some concerns “by design”

– Engage risk analysts to work with product designers

• Need for a long term plan/framework to answer questions with pending data

• Conduct case-by-case evaluations to elicit key concerns

• Also conduct expert workshops more broadly to raise overarching issues

• Test/compare adaptive approaches to risk analysis that incorporate the product life cycle


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Units of Material Characterization

• It’s possible that once we get the units right, there will be no nano-specific issues in risk assessment

• However nanoparticles are dynamic – this drives decisions about units for a breadth of contexts

• May need more than one set of units, but it may also be possible to build relationships across units to unify them

• There may be a role for applying a nano-specific uncertainty factor in some situations.


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Size tolerances and “purity”

100% within range 50% within range50% impurity?

10% within range90% impurity?

What does 99% pure mean for a nanomaterial?

size size size

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When are populations different for extrapolation purposes?

impuritiesimpurities

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Risk Characterization must be Context-specific

• It is important to consider the context for the material application – different applications and decision context might be best served by different levels of uncertainty evaluation or sensitivity analysis.

• In the case-by-case approach, consider models and data from other substances to inform data gaps


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Is nano risk communication different?

• Overall, no. – It is similar to that for emerging technologies

• But, definitional problems exist:– Have not defined what we are communicating about– Are agglomerates (>100 nm) considered nano?

• As in other areas, diagram needed to demonstrate parties: who is involved and how


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Using expert judgment

• There is a lot of expertise, and this could be tapped for understanding some of the uncertainties– Almost don’t need to state, must be informed by data

• Qualitative approaches are more appropriate in the short term. Strive to be in a position to make quantitative assessments of uncertainty – By developing models and frameworks now

– Build structures and test uncertainty

Take aways


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Work toward a 10 year plan

• To have an overarching frame for the data that are developed

• To investigate the relationships between the mode of action and properties to allow extrapolation

• Encourage interaction between risk analysts and product developers to bring about risk-informed product design

• Build adaptive approaches


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Workshop Outcomes

• Publication of white papers• Presentations on www.srananoworkshop.org• Symposium at SRA Annual Meeting December 8-10• Identified next steps

– Follow on conference to discuss role and development of “top down/bottom up” frameworks

– Built new networks of experts networks across continents– Potential collaboration with Organization for Economic

Cooperation and Development (OECD)– Research agendas to address key uncertainties about size,

nano-specific outcomes– Test and compare risk frameworks that incorporate product

life cycle


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Consider Adaptive Life Cycle Approaches to Risk Assessment and Risk Management

• Provide a framework for assessing biological and environmental exposure- a significant advance

• How to implement these approaches – not part of the current risk management paradigm

• A variety of frameworks exist/proposed

– Nano LCRA (Shatkin 2008. Nanotechnology Health and Environmental Risks CRC Press)

– Comprehensive Environmental Assessment (Davis 2007)

– Nano Risk Framework (EDF/DuPont 2007)

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NANO LCRAAdaptive Streamlined Life Cycle/ Risk Assessment Framework for NM (Shatkin 2008)

RAWMATERIALS Process USE/ REUSE/

DISPOSALPRODUCT Packaging

IDENTIFY ANDCHARACTERIZE

HAZARDSEVALUATE TOXICITY

ASSESS EXPOSURE

CHARACTERIZE RISK ASSESS CONFIDENCE

ITERATE

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Key Attributes of NANO LCRA Adaptive Risk Framework

• Initially, a streamlined analysis appropriate for early stage decisions

• Proactive approach for evaluating safety of novel materials

• Steps sequentially across processes through product lifecycle

• Applies to health and safety and environmental concerns

• Transparent decision framework

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Key Attributes of NANO LCRA Adaptive Risk Framework

• Identifies Potential for Hazard and Exposure at each step

• Focuses on exposure potential to streamline analysis

• Only evaluates toxicity and risk when exposure may occur

• Allows comparison of different NM products and processes

• Adaptive: easy to update when new information is available

• Focuses and prioritizes risk management on key concerns

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NANO LCRA framework

• Adaptive approach applies broadly to array of situations – not nano-specific

• Use as a screening tool to identify and prioritize health and environmental/ process issues

• Identifies key uncertainties

• Revisits early decisions with new information

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Hazard Identification•Release of silver during manufacturing •Improper disposal practices for NM wastesPackaging step allows release of particles

•Product contains unbound silver particles•Disposal may release silver to environment•Exposure Assessment•Worker exposure during production process•Packaging into final product poorly controlled•Final product includes human dermal contact exposure

•Recycling creates inadvertent exposure•Environmental pathways unknownToxicity Assessment•Potential dermal toxicity during use•Unknown ecological fate and toxicity

NANO LCRA Case Example

Nano Silver as Coating in Consumer Product

RecommendationsOccupational hazards• Install secondary containment in production area

• Develop disposal practices for NM wastes

• Contain packaging releases

Exposure Assessment•Test dermal uptake in bioassays•Conduct ecological fate evaluation

Toxicity Assessment• Material characterization• Assess toxicity of product

•?? Conduct ecological tox studies ??

SILVERRAW

MATERIALSProcess RECYCLE/

DISPOSALPRODUCT

PACKAGINGPRODUCT

USE

ID and CHARACTERIZE

HAZARDS

EVALUATE EXPOSURE

Analysis

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Comprehensive Environmental Assessment (CEA)

CEA ≈ LC + RA

LC = Product Life Cycle frameworkRA = Risk Assessment paradigm

See: Davis, J. M. “How to assess the risks of nanotechnology: learning from past experience”J. Nanosci. Nanotechnol. 7(2): 402-409, 2007

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Life Cycle Stages

Environmental Pathways

Fate & Transport Exposure Effects

Feedstocks

Manufacture

Distribution

Storage

Use

Disposal

Air

Water

Soil

Food chain

Biota

Human populations

Eco-systems

Human Health

Primary contaminants

Secondary contaminants

Comprehensive Environmental Assessment (CEA)

Source: adapted from Davis, J. M. and Thomas, V.M. Annals N.Y. Academy of Science 1076: 498-515, 2006

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Process

•Focus on specific case studies

•Include diverse technical & stakeholder perspectives

•Use expert judgment methods

•Identify strategic priorities

•Repeat periodically / adaptive management

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EPA’s Nanomaterial Case Studies

•Goals: –Identify & prioritize research needed for comprehensive

assessment of nanomaterials–Refine long-term research strategy for nanomaterials risk

assessment•Rationale: Focus on specific examples & scenarios•Selected applications of nano-titanium dioxide (TiO2):

–Case study 1: Water treatment (e.g., arsenic removal)–Case study 2: Sunscreen

•Organized around CEA approach (see next slide)•Note: Case studies are not completed assessments

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Summary• Risk assessment continues as a valid approach to managing

emerging substances • Broad agreement to adopt a life cycle approach in risk

assessment

– NANO LCRA Screening Level Risk Assessment is a useful tool for identifying and managing amidst uncertainty

– Comprehensive Environmental Assessment also an adaptive approach

• SRA Workshop concluded risk analysis can inform management of NM and NT– Top Down (frameworks) and Bottom Up (case by case) approaches– Risk Perceptions must be addressed by transparent and proactive

communication

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Thank You Very Much!

Jo Anne Shatkin, Ph.D.

CLF [email protected]

+1 617-850 1715

advancing risk analysis for nanomaterials and …risk analysis: advancing the science for...

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