UNCLASSIFIED FOUO

Evaluation of the Potential Medical

Effects of Engineered Nanomaterials in

Army Systems

Mark W. Widder

US Army Center for Environmental Health Research

Fort Detrick, MD

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Army ENM Objectives

• Identify engineered nanomaterials (ENMs) to be

incorporated into Army materiel

• Conduct initial risk ranking of identified materiel

• Identify research gaps and data needs

• Conduct research to address high priority requirements

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Approach

• Data call through ASA(ALT) to identify

Army materiel incorporating

nanomaterials

• Extramural contract (RTI) to provide

a database and risk ranking system for

Army nanomaterials associated

applications

• Partner with NIOSH to evaluate PHC

risk/health effects assessment

methods

• Identify changes to existing

approaches used for chemicals

• Where necessary, develop new

toxicity tests and other

assessment approaches for

nanomaterials

IDENTIFY ENMs

RISK RANKING

SYSEM

HEALTH EFFECTS

ASSESSMENT

NEW

TESTS

NEW

METHODS

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Army Nanomaterials Database

TEARR (Tool for ENM Application pair Risk Ranking)

Grieger et al, Environment Systems & Decisions 2014. (DOI 10.1007/s10669-014-9531)

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Army ENMs

Category No. ENM (Abbreviation in TEARR)

Carbon-based

1 Boron Carbide (B4C)

2 Carbon Nanoparticles (Carbon)

3 Carbon Aluminum Composite (CarbAl)

4 Clays (Clays)

5 Carbon Nanotubes (CNT)

6 Fullerene (Fullerene)

7 Graphene (Graphene)

8 Graphite (Graphite)

9 Misc (Misc)

10 Multi-walled Carbon Nanotubes (MWCNT)

11 Nylon (Nylon)

12 Polymer (Polymer)

13 Silica-coated Nanotubes (SiCNT)

Metals

14 Silver Nanoparticles (Ag)

15 Aluminum Nanoparticles (Al)

16 Gold Nanoparticles (Au)

17 Brass Nanoparticles (Brass)

18 Cobalt Nanoparticles (Co)

19 Copper Nanoparticles (Cu)

20 Iron Nanoparticles (Fe)

21 Germanium Nanoparticles (Ge)

22 Lithium Aluminum Silicate Glass (LiAlSi)

23 Nickel Nanoparticles (Ni)

24 Palladium Nanoparticles (Pd)

25 Platinum Nanoparticles (Pt)

26 Silicon Nanoparticles (Si)

27 Titanium Nanoparticles (Ti)

Metal Oxides

28 Alumina (Al2O3)

29 Barium Titanate (BaTiO3)

30 Cuprous Oxide (Cu2O)

31 Cupric Oxide (CuO)

32 Misc (Misc)

33 Silica (SiO2)

34 Titanium Dioxide (TiO2)

35 Zinc Oxide (ZnO)

36 Zirconia (ZrO2)

Inorganic 37 Tungsten Nanoparticles (W)

38 Tungsten Disulfide (WS2)

39 Ceramics (Ceramics)

Quantum Dots

40 Cadmium Sulfide Quantum Dots (CdS)

41 Cadmium Selenide Quantum Dots (CdSe)

42 Cadmium Telluride (CdTe)

43 Lead Sulfide Quantum Dots (PbS)

44 Lead Selenide Quantum Dots (PdSe)

Unknown 45 Unknown

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Army Materiel Category No. Army Materiel (Additional Descriptors in TEARR)

Chemicals

1 Coatings and Paints (Flame retardants; Paint; Fabric decontaminators; Topcoat

system; Corrosion controls; Camouflage)

2 Compounds (Powders; Emulsions)

3 Coolants (Coolants)

4 Dispersants (Dispersants)

5 Greases (Greases; Additives)

6 Lubricants (Engine oil; Paste; Gear oil)

Equipment

7 Air filtration and purification (Filters; Suits; Barriers)

8 Energetics (Warheads)

9 Protection (Armor; Anti-armor; Optical laser protection; Body armor; Chemical

biological protection; Flame retardants; Ballistic protection; Eyewear; Transparent

armor)

Electronics

10 Communication (Power devices)

11 Computers (Transmitters)

12 Energy (Photonic detectors; EDLC; Thermal management; Solar cells;

Electrochemical electrodes; Batteries; Heat pumps)

13 Detection (Signal processing)

14 Imaging (SERS spectroscopy; CBE detection; NIR detection; SWIR detection

15 Luminescence (LEDs; TTL; Bolometrics)

16 Sensors (Molecular sensors; Electrodes; Batteries; Filters; Suits; Barriers; Sensor

membranes)

17 Thermal interface (Thermal interface)

Munitions

18 Energetics (Warheads)

19 Explosives (Explosives)

20 Kinetic penetrators (Ballistics)

21 Projectiles (Projectiles)

22 Smokes and Obscurants (Obscurant grenades; Bispectral grenades)

Support

23 Batteries (Electrodes; Batteries; Thermal anodes;)

24 Food packaging (Pouches)

25 Rations (Absorption enhancers)

26 Research and development (Research)

Structural

Materiel

27 Components (Ink; Antennas; Ceramics)

28 Sensors (Molecular sensors; Electrodes; Batteries; Filters; Suits; Barriers; Sensor

membranes)

29 Shielding (EMI shielding)

30 Vehicles (GCV)

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Army Materiel Characteristics

7

Characteristics Used in Scoring

Amount

The amount (%) of ENM incorporated into the materiel (relates to release potential,

exposure potential) (e.g. a materiel containing a very small % of ENM would be less likely

to release the ENM and would result in a smaller exposure concentration)

Number of End

Items

The total number of individual final (produced) items for a particular ENM-application pair

(relates to exposure potential) (e.g. if 5,000 end items are produced, the likelihood of

exposure is greater than a materiel with currently only 2 end items)

Number of People

Exposed

The total number of current individuals with the potential for exposure to the ENM-

containing materiel (relates to exposure potential)) (e.g. if 3 people have the potential for

exposure due to current use, rather than thousands, then exposure potential is considered

low)

Acquisition Phase

The current status of the ENM-containing materiel based on life cycle stage, from concept

design production and deployment (relates to exposure potential) (e.g., a materiel that is

still in the concept design phase (e.g. planning only) would have no exposure potential,

whereas a materiel that has been deployed for use could potentially have a large exposure

potential)

Use Patterns

A descriptor for who will primarily be using the ENM-containing materiel in its current stage

and in what setting (relates to release, exposure potential, and toxicity potential) (e.g., an

ENM used in an obscurant would theoretically have a higher release, exposure, and toxicity

potential than an ENM used in body armor)

Incompatibility A list of substances that may be incompatible with the ENM-containing materiel

Method of

Incorporation

(Method of Incorporation): A descriptor for how the ENM is incorporated into the materiel

(i.e., on the surface, in a polymer matrix, in a powder, etc.) relates to release, exposure,

and toxicity potential (e.g., if the ENM is present in a polymer matrix, then the likelihood of

release and subsequent exposure/toxicity would be diminished)

Characteristics Provided for Informational Purposes Only

Toxicity Clearance Yes/No answer on whether or not a toxicity clearance has been performed for the materiel

application containing ENMs

MSDS Yes/No answer representing the presence/absence of a material safety data sheet for the

ENM used in the application

Health Hazard

Assessment

Yes/No answer on whether or not a health hazard assessment has been performed on the

materiel application containing the ENMs

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Nanomaterial Characteristics

8

Chemistry Solubility

Aggregation

Surface Chemistry

Fate Dispersability

Carbon Affinity

Water Affinity

Persistence

Bioaccumulation

Degradation Potential

Half-life

Pair-specific Form

Shape

Reactivity Surface reactivity

Toxicity

Radical Formation

Catalytic Reaction

Flammability

Explosivity

Surface Charge/Zeta

Potential

Structural Particle Size

Density

Composition

Surface Area

Molecular Structure

Porosity

Crystallinity

Dustiness

Significant Data Gaps:

• 85% of database incomplete

• Size, shape, composition ENM <50%

Significant Army Assessment Gaps:

• Performed health assessment, 69%

• Presence of MSDS, 62%

• Toxicity clearance performed, 71%

Significant Usage/Exposure Data

Gaps:

• 58% of database incomplete

• Method of synthesis, 12%

• Acquisition phase, 35%

• Amount of ENM, 92%

• Number of end items, 69%

• Number of people exposed, 71%

• Use patterns, 38%

• Incompatibility, 100%

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Progress/Deliverables

• Deliverables to date • Database and risk ranking system

for Army engineered nanomaterials

and applications

• Risk ranking report

(133 ENM/application pairs)

• Progress • Interagency agreement with NIOSH

• Awaiting delivery of revised draft report

• Planned deliverables • NIOSH report with recommendations for

improvements to the Army health risk

assessment process for nanomaterials (FY15)

• Development and validation of in silico and

tiered testing procedures for predicting health

effects of Army ENMs

NIOSH

REPORT

TEARR: Tool for ENM-Application Pair Risk Ranking

FY15

FY13

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Army Nanomaterials and Predictive Toxicology

Problem: Significant scientific gaps in our understanding of the toxicology of nano-based materials that:

– Are already contained in commercial & military products not intended for human exposure

– Could contaminate the environment while also not intended for human exposure

– Are intended for biomedical application such as drug delivery, imaging, and sensing

• This lack of knowledge regarding the relationship among ENM properties, exposure, and toxicological endpoints renders most (if not all) currently available risk models incapable of providing reliable estimates of risk (Grieger et al., 2010; Johnston et al., 2011). – The USAPHC lacks in silico tools that predict toxicity of ENMs.

– The USAPHC lacks significant amounts of data on the ADME parameters of ENMs.

– Commanders lack tools to assess risks from ENMs.

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Solutions

• Develop a comprehensive, and ideally, predictive knowledge of the

effects of ENM on the environment, animals and humans

– Test and evaluate predictive knowledge of high priority-ENM

exposure scenarios

– Transition in silico tools and experimental knowledge of high priority-

ENM to USAPHC

• Develop an experimental approach to facilitate tiered testing for new ENM

– Identify changes to existing approaches used for chemicals

– Where necessary, develop new toxicity tests and other assessment

approaches for nanomaterials (eg. Zebrafish embryo assay)

– Develop end-points that provide prioritization schemes for testing

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Text

Extraction &

Network

Analysis

Text Mining

Predictive

Modeling Pilot

Study

Improve user

flexibility and

option in

TEARR

TEARR

133 ENMs

Objective 1

TEARR-2.0

Objective 2

In silico model

based on

extracted data

Test exemplar

ENMs for

health effects

in Zebrafish &

refine model

Objective 3A

Test ENMs in

Zebrafish

Embryo

Nanomaterial

characterization

TEARR-3.0

Identify key

biomarkers

and pathways

anchored to

toxicity

indicators

Objective 3B

Test ENMs

with known

toxicity in

adult

Zebrafish

Integrate

NIOSH health

hazard bands

with toxicity in

Zebrafish

1. New in silico model for ENMs

2. New Rapid Screening Tool

3. Improved Health Risk Database

Buys: USACEHR

NIOSH/RTI

BHSAI

OSU

ERDC

NCI NCL

Army Collaborative Framework

UNCLASSIFIED Mark W. Widder (301-619-7665) Mark.W.Widder.civ@mail.mil

Acknowledgements

13

Dr. Khara Grieger (RTI)

Dr. Eric Money (North Carolina State, formerly RTI)

Stephen Beaulieu (formerly RTI)

Jennifer Redmon (RTI)

Megan Tulloch (RTI)

Dr. Christie Sayes (RTI)

Dr. Martin Philbert (University of Michigan)

MAJ Jonathan Stallings (USACEHR)

Dr. William van der Schalie (USACEHR, retired)

Christopher Carroll (PHC, retired)

Mike McDevitt (PHC)

Dr. Mark Johnson (PHC)

Dr. Charles Geraci (NIOSH)

Dr. Eileen Keumple (NIOSH)

Dr. Jenny Roberts (NIOSH)

Dr. Aleksandr Stefaniak (NIOSH)

Dr. Mary Schubauer-Berigan

Ralph Zumwalde

Laura Hodson

Dr. Jeff Stevens (ERDC)

Dr. Alan Kennedy (ERDC)

Jessica Coleman (ERDC)