Mark D. Hoover, PHD, CHP, CIH

304-285-6374

mhoover1@cdc.gov

National Institute for Occupational Safety and Health

Morgantown, West Virginia

The findings and conclusions in this presentation

are those of the author and do not necessarily

represent the views of the NCRP or the National

Institute for Occupational Safety and Health.

Mention of company names or products

does not constitute endorsement.

An Overview of National Council on Radiation Protection and Measurements

Report No. 176 on Radiation Safety Aspects of Nanotechnology

August 30, 2017 Webinar

Natural and Engineered Nanoparticles

2

Nano-enhanced materials and processes are raising issues in radiation-related operations.

How should radiation dosimetry be conducted for nanomaterials?

What are the sources

of radiation-related nanomaterials?

How can exposure be assessed

over life-cycle processes?

3

NCRP Report No. 176

4

Contents• Types and Sources of Nanomaterials

including Radioactive Nanoparticles

• Physicochemical Concerns

• Operational Health Physics Issues

• Issues for Radiation Dosimetry

• Dose Assessment and MedicalManagement for Individuals

• Appendices

• Radiolabeled Nanoparticle Examples

• Biokinetic Models

• Nanoparticle Properties and Behaviors

State of knowledge relevant to nanotechnology and radiation safety programs.

NCRP 2017

NCRP Committee SC 2-6

on Radiation Safety Aspects of Nanotechnology

Mark D. Hoover

Chair

David S. Myers

Vice-Chair

Raymond A. Guilmette Wolfgang G. Kreyling Rachel SmithLeigh J. Cash Gunter Oberdorster

Bruce B. Boecker

Staff Consultant

Michael P. Grissom

Staff Consultant 5

3-15-2010 DRAFT

NIOSH

Current Intelligence Bulletin

Occupational Exposure to

Carbon Nanotubes

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

NCRP Report No. 176 builds on Guidance such as these Documents from NIOSH.

6www.cdc.gov/niosh/topics/nanotech

Our IH Decision-making Framework and Process

Anticipate and Recognize Evaluate

Constant communication, continuous improvement

Control and ConfirmProtection

Risk Management

Use the Hierarchy of Controls

to apply “appropriate” controls and programsand confirm protection

Hazard AssessmentIdentify and define dose-response relationships and “Hazard Criteria”• Occupational Exposure Limits• Skin Notations, … • Hazard Bands

Exposure AssessmentCollect all “relevant and reliable”

exposure information for assessment against

and refinement of the “Hazard Criteria”

Risk Characterization

Characterize risks associated with “realistic” combinations

of hazards and exposures

Risk Assessment

hazard-informed

exposure-informed

7Adapted from AIHA 2015

A Strategy for Assessing and

Managing Occupational Exposures

Ubiquitous Natural Sources of Nanoparticles

8

Nanoparticles occur naturally in sources such as

• sea spray,

• volcanic emissions,

• smoke from forest fires,

• exhausts from vehicle engines, and

• radon decay products.

Diesel Exhaust Aerosol:

Comparison of Particle Number and Mass

9

10

Nano-enabled products are everywhere

Eddie Bauer

Ruston Fit Nano-

Care khakis

Wilson Double

Core tennis balls

3M Adper Single

Bond Plus

dental adhesive

Hummer H2

Mercedes

CLS-class

Kodak EasyShare

LS633 camera

Laufen Gallery washbasin

with Wondergliss

Smith & Nephew Acticoat 7

antimicrobial wound dressing

NanoOpto subwavelength

polarizing beam splitter/combiner

Samsung Nano

SilverSeal Refrigerator

Wyeth Rapamune

immuno-suppressant

Gibbs, 2006

Example Applications of Nanomaterials

11

12

Nanotechnology Definition

• Definition includes all three of these features:

– Research and technology development at the

atomic, molecular, or macromolecular levels, in

the length scale of approximately 1-100 nm.

– Creating and using structures, devices, and

systems that have novel properties and

functions because of their small and/or

intermediate size.

– Ability to control or manipulate on the

atomic scale.

www.nano.gov

We have some mixed-experience

case studies with actual

exposures to nanomaterials

13

• The Magic Nano™ event

• The Chinese event

• A nickel sensitization case

• The polymer and metal fume experience

The Magic Nano™ event

• In March 2006, the household cleaning spray Magic Nano™

was associated with severe health effects in more than 100

customers.

– Symptoms included coughing, headaches, sleep disruption and

vomiting.

• The German Federal Institute for Risk Assessment (BfR)

investigated the event thoroughly but could not find any NP in

the product.

• The manufacturer subsequently claimed no content of NP

since the product name was selected from the fact that the

spray would form a very thin protective film on glass or

ceramics.

• The BfR associated the health effects with the liquid

constituents of the spray solution (BFR, 2006).

14“nano” was not involved in this event.

The Chinese event

• In 2009, the European Respiratory Journal published a report

on the death of several workers for which the authors

claimed the causal effects were from NP (Song et al., 2009).

• Yet, international interrogations concluded that there was no

formal proof that NP exposure at the workplace caused the

observed pulmonary disease and deaths of several workers

in a primitive workplace that lacked any safety measures but

had very high concentrations of gaseous and particulate

compounds in the air.

• Electron-microscope images remained inconclusive

regarding the presence of any NP.

• The authors had drawn conclusions by analogy which was

not scrutinized thoroughly enough by the editor and

reviewers of the journal (Brain et al., 2010; ERJ, 2010).

15

Good IH practices would have prevented this event.

“nano” may not have been involved in this event.

A nickel sensitization case• Journeay and Goldman (2014) reported a case of nickel

sensitization in a 26 y old chemist who worked in a laboratory that

typically formulated polymers and coatings using silver ink

particles.

• The powder materials used in the formulations were routinely

weighed out and handled on a laboratory bench with no protective

measures.

• When she later began working with a nickel nanoparticle powder,

the chemist developed throat irritation, nasal congestion, post-

nasal drip, facial flushing, and new skin reactions to her earrings

and belt buckle.

• Those symptoms are consistent with exposure to nickel. Dimitri et

al. (2015) have noted this case as an example of the fact that

failure to use basic industrial hygiene precautions when working

with any hazardous material in any form can have negative

consequences.

16Good IH practices would have prevented this event.

The polymer and metal fume experience

• Fumes generated by heating of polymers such as

polytetrafuoroethylene (PTFE) or metals such as zinc consist of

ultrafine particles.

• The terms polymer fume fever and metal fume fever have been

coined to characterize the fever chills, pneumonitis, and

pulmonary edema associated with exposure to such fumes.

• Animal studies have revealed the extremely high toxicity of

freshly generated PTFE fumes whereas a decrease in toxicity

of aged fumes was found.

• Ultrafine particles present in these fumes are believed to be

responsible for the fume toxicity and coagulation of these

ultrafine particles with increasing fume age may lead to less

reactive larger particles.

17

Inhalation hazards, exposures, and associated health

risks can be understood and managed.

18

Evidence for Potential Health Concerns

• Lung

– Lung cancer occurs rats exposed to ultrafine Ti02 particles

• Up to 50% of inhaled nanoparticles may deposit in gas exchange region of the lung

• Cardiovascular

– Detrimental effects occur in humans exposed to diesel exhaust in air pollution

• Inflammatory effects, platelet aggregation are observed in animals

• Central Nervous System

– Nose to brain is a route of exposure

• Metals are transported via olfactory pathways

• Graphite rods accumulate in olfactory lobe of brain

Major compartments of the ICRP

Human Respiratory Tract Model (HRTM)

19Adapted from ICRP Publication 66

20

Particle size-dependent deposition in the human respiratory tract

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0.001 0.01 0.1 1 10 100

Total

Head Airways

Tracheo-Bronchial

Alveolar

Particle Diameter (µm)

Dep

osit

ion

Fra

cti

on

Calculated from the ICRP 66 model for an adult male, light exercise, nose breathing.

5Occupationally

relevant default

21

Filtration is effective for nanoparticles.

n = 5; error bars represent standard deviations

Sodium Chloride (TSI 3160); Silver (custom-built)

Flow rate 85 L/min

0.0

0.5

1.0

1.5

2.0

2.5

3.0

1 10 100 1000

Particle Size (nm)

% P

en

etr

ati

on

Silver Sodium chloride

Filtration performance of NIOSH-approved N95

and P100 filtering facepiece respirators against

nanoparticles, [2008] S. Rengasamy, WP King,

B. Eimer and R. Shaffer, Journal of Occupational

and Environmental Hygiene, 5: 556-564.

Filtration performance of a typical NIOSH-approved N95 filtering facepiece respirator

Relationship between Particle Concentration

and Particle Agglomeration Time

22

Very high aerosol

number concentrations

are time-limited

by coagulation

23

Committed effective dose

per unit measured activity

in urine is higher for larger particles.

Thus, in this case, bioassay interpretation

based on the default particle size should be

protective.

Better characterization of particles will lead to better dosimetry.

23

An example of bioassay interpretation based on a

limited understanding of particle characteristics

Analyses suggest higher urinary excretion

of nano- 239Pu compared to the default

5-µm particle size.

AMAD = 5 μm

AMAD = 10 nm

AMAD = 5 μm

AMAD = 10 nm

Adapted from Cash 2014 and Cash et al. 2016

24

It makes sense to manage nanomaterials as a component of a traditional

Radiation or Chemical Hygiene Program.

• A written program with defined responsibilities

• Basic Rules and Procedures– Chemical Procurement, Distribution, and Storage

– Environmental Monitoring

– Housekeeping, Maintenance, and Inspections

– Medical Program

– Personal Protective Apparel and Equipment

– Records

– Signs and Labels

– Spills and Accidents

– Waste Disposal

• Training and Information

External Radiation Exposure Control

Table 5.1—Guidance for Implementation of Radiation

Safety Program Elements in Nanotechnology Settings

Dose Guidelines

Follow standard radiation protection guidance (e.g., NCRP, 1998)

Dose control Techniques

Follow standard radiation protection guidance (e.g., NCRP, 1998)

External radiationdosimetry

Follow standard radiation protection guidance (e.g., NCRP, 1998)

NCRP, 1998 is NCRP Report No. 127 Operational Radiation Safety 25

Specific Guidance from NCRP Report No. 176

Table 5.1—Guidance for Implementation of Radiation

Safety Program Elements in Nanotechnology Settings

Engineered Controls

Ventilation Follow standard radiation protection guidance (e.g., NCRP, 1998) and consider enhanced mobility of NP (Section 5.2.2 and Figure 5.1)

Filtration of exhaust

Follow standard radiation protection guidance (e.g., NCRP, 1998) and note the use of HEPA filters is appropriate for all materials, including nano-sized materials (see Section 5.2.2.3 for guidance).

26

Table 5.1—Guidance for Implementation of Radiation

Safety Program Elements in Nanotechnology Settings

Internal Radiation Exposure Control

Contaminationmonitoring

Follow standard radiation protection guidance (e.g. NCRP1998) monitoring when developing and implementing a monitoring plan consider enhanced mobility of NP (see Section 5.2.3.2 for guidance).

Internal dosimetry

See Section 6 for discussion of internal dosimetry for radioactive nanomaterials. See Section 5.2.3.4 for guidance on nanomaterial characterization requirements for internal dosimetry

27

Characterization Methods

• Particle number

• Mass concentration

• Size distribution

(by count or mass)

• Surface area

• Qualitative

– Morphology

– Extent of agglomeration

– Complexity

• Confirmation

– e.g. TEM with elemental analysis

28

Condensation Particle Counter (CPC)

TSI 3007:

particle size range 10 nm to greater than 1.0 µm

concentration range 0 to 100,000 particles/cm3

Optical Particle

Counter/Sizer (OPC)

1 nm 10 nm 100 nm 300 nm 1 um 10 um

OPC

CPC

ART Instruments (ARTI):

0.3 to >10 um in six sizes simultaneously

29

Physical Form

Task

Du

rati

on

Qu

anti

ty

milligrams

kilograms

15 minutes

8 hours

slurry or suspension

highly dispersible

powder

agglomerated

A graded approach to control options

Engineered Local Exhaust Ventilation

Closed Systems

Occupational Health Hazardmild /

reversible

severe / irreversible

30

General Ventilation

Laboratory Hoods

GloveboxEnclosures

Adapted from Heidel, in Approaches to Safe Nanotechnology 2009

Exposure assessmentstrategy is a work in progress

• The graded approach is promising

• Routine monitoring examples are lacking

• Relevant metrics are needed for specific nanomaterials and nanotechnology tasks

• Differentiation between materials of interest and background is problematic

• Partnering opportunities are welcomed

31Hoover 2011

The Lawrence Berkeley National Laboratory Unbound Nanoparticle (UNP) Study

http://www.lbl.gov/ehs/ 32

Pilot Study Design for Unbound Engineered Nanoparticles (UNP) at LBNL

• Phase 1: Understand research through interviews,

demonstrations, analysis of raw materials

• Phase 2: Develop preliminary control bands

– List of potential hazards and ways to control them

• Phase 3: Validate and modify control bands

Sampling and Analysis, Personal exposure,

Environmental release, Finalize Control Bands

• Phase 4: Develop ongoing monitoring plan

33

Worker and Environmental Assessment of Potential Unbound

Engineered Nanoparticle Releases, Phase I Final Report, G.

Casuccio and R. Ogle, RJ Lee Group, Inc., L. Wahl and R. Pauer,

Lawrence Berkeley National Laboratory, September 2009.

LBNL Pilot Study Step 1: Survey

• Assess potential for exposure of nanoparticles to the worker and the environment

• Objective:

– Survey labs

– Interviewed researchers

– Evaluate existing controls/programs

– Obtain source material

Worker and Environmental Assessment of Potential Unbound

Engineered Nanoparticle Releases, Phase I Final Report, G.

Casuccio and R. Ogle, RJ Lee Group, Inc., L. Wahl and R. Pauer,

Lawrence Berkeley National Laboratory, September 2009.

34

Step 2: Characterize (Establish Source Signature)

35RJ Lee Group

Step 3: Risk assessment

• Control Banding Approach used to provide guidance on risk management of UNP at LBNL– Qualitative method for summarizing risks and controls

– Useful when there is incomplete information on hazard and exposure

– Utilizes basic characteristics of a process and materials to determine generalized risk level

NIOSH Publication No. 2009-152: Qualitative Risk Characterization and Management of Occupational Hazards: Control Banding (CB), Published August 17, 2009.

Zalk, D.M. and Nelson, D.I., “History and Evolution of Control Banding: A Review,” J. Occupational and Environmental Hygiene, 5:5, 330-346, 2008.

Maynard, A.D., “Nanotechnology: The Next Big Thing, or Much Ado about Nothing??”, Annals of Occupational Hygiene, 51:1, 1-2, 2007.

36

Step 3: Risk assessment (continued)

Worker and Environmental Assessment of Potential Unbound

Engineered Nanoparticle Releases, Phase I Final Report, G. Casuccio

and R. Ogle, RJ Lee Group, Inc., L. Wahl and R. Pauer, Lawrence

Berkeley National Laboratory, September 2009.

37

Step 4: Process and worker exposure sampling

• Direct Reading

– Source

– Lab Background

• Filter-based Sampling

– Source

– Worker Breathing Zone

– Lab Background

38

Key Dosimetry Considerations

• Route of intake of the radioactive nanoparticles (RNp)

(i.e., inhalation, ingestion, wound, dermal)

• Biokinetic behavior in the intake tissues and organs

(as well as the systemic organs) after reaching the

blood

• The selection and description of target organs and

tissues for calculating doses.

39

Fate of Nanoparticles in the Human Body

40

Generic Biokinetic Model for Dosimetry

41Adapted from ICRP 1993

ICRP Human Alimentary Tract Model

42

Illustration of the Possible Clearance and

Translocation of Inhaled, Poorly Soluble RNp

43

Proposed Human Respiratory Tract Clearance

Model to account for Intact RNp Translocation

44

NCRP Report No. 156 Wound Biokinetic Model

45

Specific Research Needs

• New transport pathways and rates for nanoparticle

translocation across the air-blood barrier need to be

considered for inclusion in a new human respiratory

tract model.

• Accumulation of nanoparticles in secondary organs

needs to be considered in an updated human

respiratory tract model.

46

Specific Research Needs

(continued)

• Modeling of the systemic biokinetic behavior of RNp

reaching the blood should be treated discretely from

solubilized radionuclides in blood because the

uptake, distribution and retention of particulate and

soluble radionuclides systemically are often very

different.

• For chronic exposure conditions that involve

nanoparticles, the potential for the accumulation of

poorly soluble nanoparticles in secondary organs

should be addressed.

47

Specific Research Needs

(continued)

• In future dosimetric models, chemical and particulate

dosimetric quantities and factors may need to be

evaluated in addition to the more traditional

radiological dosimetric quantities for nanomaterials.

• In addition, the possibility that biological effects may

occur as a result of combined insults from the

radiological, chemical and particulate properties of

RNp should be investigated.

48

A Vision for Information Sharing to Move Us Ahead

Safety, Health,

Well-being, and

Productivity

New Technologies

Risk Management

*

49

Focus on theConvergence = Focus on Success.

Context of

NCRP

Report No.

176

50

For worker protection

practitioners who want to

understand and harness

“informatics” to get the

right things done right.

For what audience are we creating this initiative?

For “informaticians” who

want to understand and

meet the needs of the

worker protection

community.

For anyone wanting to understand and respond to the

growing impact of worker safety, health, well-being, and

productivity on their daily activities and interests.

Worker Protection InformaticsConfirming worker safety, health, well-being, and productivity

A draft concept for Information Sharing

Draft for discussion

A concept of BIG DATA for Worker Protection InformaticsIf we begin by grouping the amount and complexity of the IH data we encounter,

we may be able to define and develop a graded informatics approach

to managing big data for worker protection.

51

Co

mp

lex

ity

of

Da

ta

Amount of Data

Small amount

needing

complex

assessment

Large amount

needing

complex

assessment

Vast amount

needing

complex

assessment

Small amount

needing

detailed

modeling

Large amount

needing

detailed

modeling

Vast amount

needing

detailed

modeling

Small amount

with obvious

implication

Large amount

with obvious

implication

Vast amount

with obvious

implication

What IH situations fit in which categories?

Our Working Definition

of Worker Protection Informatics• The science and practice of determining which

information is relevant to protecting worker safety, health, well-being, and productivity,

• and then developing and implementing effective mechanisms

• to collect, validate, store, share, analyze, model, and apply the information, and then to confirm achievement of the intended outcome from use of that information,

• and then conveying experience to the broader community, contributing to generalized knowledge, and updating standards and training.

52Adapted from http://www.internano.org/nanoinformatics/and Hoover et al. 2015

How we view our informatics roles and responsibilities

Set

Mis

sio

nO

bje

ctiv

es

Det

erm

ine

R

ele

van

ce

Co

llect

Val

idat

e

Sto

re

Shar

e

An

alyz

e

and

Mo

de

l

Ap

ply

Co

nfi

rmEf

fect

ive

ne

ss

Co

nve

y Ex

pe

rie

nce

Ge

ne

raliz

e

Up

dat

e

Gu

idan

ce

Customers X X X X X X X

Creators X X X X X

Curators X X X X X X

Analysts X X X X X X

Sensor and Data

Customers

1 5 6

2

4

3

Sensor and Data Creators

Sensor and Data Curators

Sensor and Data Analysts

Communication and understanding are essential at all steps. 53

54

Engage the community

We are Following Four Steps for Community Actionto build and sustain leaders, cultures, and systems

for safety, health, well-being, and productivity.

Thank you for partnering with us for success.

Hoover et al. (2015) Application of an informatics-based decision-making

framework and process to the assessment of radiation safety in nanotechnology,

Health Phys. 108(2): 179-194, 2015.

Some cited references

55

BFR (2006). Bundesinstitut für Risikobewertung. “Nanopartikel waren nicht die

ursache für gesundheitsprobleme durch versiegelungssprays!” (in German)

http://www.bfr.bund.de/de/presseinformation/2006/12/nanopartikel_waren_ni

cht_die_ursache_fuer_gesundheitsprobleme_durch_versiegelungssprays_-

7839.html (accessed February 14, 2015) (German Federal Institute for Risk

Assessment, Germany).

Brain, J.D., Kreyling, W. and Gehr, P. (2010). “To the editors: Express concern

about the recent paper by Song et al.,” European Resp. J. 35(1; DOI:

10.1183/09031936.00159909), 226-227.

Dimitri, J., Shepard, M.N., Webb, P.J. and Baker, J. (2015). “Nanomaterials:

The next wave of nanotechnology and the 21st century workplace,” The

Synergist 26(2), 28-31.

ERJ (2010). The European Respiratory Journal Editors. “From the editors,”

European Resp. J. 35(1; DOE 10.1183/09031936.00169809), 227.

Hoover, M.D., T. Armstrong, T. Blodgett, A.K. Fleeger, P.W. Logan, B.

McArthur, and P.J. Middendorf: Confirming Our IH Decision-Making

Framework, The Synergist, 22(1): 10, 2011.

Some cited references (continued)

56

Hoover, M.D., L.J. Cash, S.M. Mathews, I.L. Feitshans, J. Iskander, and S.L.

Harper: ‘Toxic’ and ‘Nontoxic’: Confirming Critical Terminology Concepts

and Context for Clear Communication, in Encyclopedia of Toxicology,3rd

edition (P. Wexler, ed), Elsevier, Oxford, 2014.

Hoover, M.D., D.S. Myers, L.J. Cash, R.A. Guilmette, W.G. Kreyling, G.

Oberdȍrster, R. Smith, J.R. Cassata, B.B. Boecker, and M.P. Grissom.

Application of an informatics-based decision-making framework and process

to the assessment of radiation safety in nanotechnology, Health Phys J.,

108(2): 179-194, 2015.

Journeay, W.S. and Goldman, R.H. (2014). “Occupational handling of nickel

nanoparticles: A case report,” Amer. J. Indust. Med. 57(9), 1073-1076.

Maiello, M.L., and M.D. Hoover (editors), Radioactive Air Sampling Methods,

CRC Press, Boca Raton, FL, 2011.

Song, Y., Li, X. and Du, X. (2009). “Exposure to nanoparticles is related to

pleural effusion, pulmonary fibrosis and granuloma,” European Resp. J.

34(3; DOI: 10.1183/09031936.00178308), 559-567.

57

Mark D. Hoover, PhD, CHP, CIH

Respiratory Health Division

and NIOSH Nanotechnology Research Center

Co-Director – NIOSH Center for Direct Reading

and Sensor Technologies

National Institute for Occupational Safety and Health

Centers for Disease Control and Prevention

1095 Willowdale Road

Morgantown, West Virginia 26505-2888

Phone: 304-285-6374

Email: mhoover1@cdc.gov

Questions ?

With extensive acknowledgments to everyone who has so graciously shared their

experiences and helped with the creation and advancement of this body of work.